Vaccine-enhanced disease: case studies and ethical implications for research and public health

Euzebiusz Jamrozik Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing George Heriot Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Susan Bull Roles: Conceptualization, Funding Acquisition, Investigation, Supervision, Writing – Review & Editing Michael Parker Roles: Formal Analysis, Funding Acquisition, Project Administration, Supervision, Writing – Review & Editing

case study on human health and disease

This article is included in the Global Infectious Disease Ethics Collaborative (GLIDE) gateway.

case study on human health and disease

This article is included in the Epidemic Ethics: Global issues in ethics and COVID-19 collection.

Vaccine, ethics, uncertainty, risk, respiratory syncytial virus, measles, dengue, Staphylococcus aureus.

The views expressed in this article are those of the authors. Publication in Wellcome Open Research does not imply endorsement by Wellcome.

Introduction

Vaccination is one of the greatest achievements of public health and infectious disease research. Standard licensed vaccines are generally extremely safe, and typically the direct individual benefits of vaccination significantly outweigh any risks or side effects. In addition, the immunity of vaccinated individuals provides further public health benefits by indirect protection of others, collectively creating population (herd) immunity. Nevertheless, rare serious adverse effects do occur with experimental vaccines, sometimes halting vaccine development, and have also occurred with licensed vaccines, in exceptional cases leading to restriction or withdrawal of public health use.

Vaccine-enhanced disease (VED) is a distinct type of infection-related adverse event that occurs when disease severity is increased following exposure to the relevant pathogen after vaccination 1 . A key difference between VED and other adverse events is that it is contingent on post-vaccination infection with the relevant pathogen, whereas other types of adverse events are caused by the vaccine itself (including in rare cases where the microbes in live-attenuated vaccines themselves cause disease) or direct immune responses to the vaccine. Other authors have provided guidance for the detection of a correlation between vaccination and increased disease severity and the confirmation of likely VED with additional evidence supporting a causal link between vaccination and enhanced disease 1 .

Significant VED has occurred for at least four human vaccines, although the terminology used to describe disease enhancement has been different in each case ( Table 1 ). This article reviews these four case studies of VED in humans over the last six decades and explores the ethical implications for vaccine research and public health policy. The phenomenon of VED has recently received greater public attention because of concerns that COVID-19 vaccines might cause VED, due to disease enhancement observed in animal studies of experimental vaccines for other human coronaviruses 2 , 3 .

Table 1. Cases of vaccine-enhanced disease and relevant outcomes.

Reference for mechanisms of measles, RSV, dengue enhancement 7 .

RSV, respiratory syncytial virus; VED, vaccine-enhanced disease.

The ethical implications of VED for research and public policy require careful consideration because, although rare, VED can cause serious harm (including death) and has the potential to undermine public trust in vaccines 4 , 5 . Previous cases of VED have led to changes in research and public health practice 5 , 6 , yet the topic has not been widely discussed from an ethical perspective. We argue for careful and transparent evaluation of, and communication regarding, the risks and uncertainties regarding VED for novel vaccines. Where residual risks and uncertainties remain, these should be weighed against potential benefits and monitored during follow-up of recipients of novel vaccines.

Case studies

The four case studies below highlight the issues and challenges that arose in VED associated with measles virus, respiratory syncytial virus (RSV), Staphylococcus aureus , and dengue virus. Many of the points raised may also be relevant to vaccine development for other pathogens, and to some related types of adverse effects 7 , 8 . Some experimental vaccines, for example, have been associated with increased (as opposed to decreased) risks of infection without enhancement of disease (i.e., infection after vaccination is more likely, but the clinical severity of the resulting infection is not more severe than average). At least one human influenza vaccine has been associated with an increased rate of influenza diagnosis but no increased risk of hospitalisation 9 , 10 . Similarly, one experimental HIV vaccine was associated with an increased risk of infection, with no evidence that the natural history of the resulting HIV infections and/or disease outcomes were otherwise altered 11 . In animal studies, VED has also been noted with veterinary vaccines (e.g., for animal coronaviruses) and animal models intended for human vaccine development (e.g., for human coronaviruses, influenza, and West Nile virus) 7 . This paper focuses only on cases where there is convincing evidence that vaccines have led to disease enhancement in humans, as opposed to evidence of an association between vaccination and more severe disease without confirmatory evidence of a causal relationship, or evidence of an increased frequency of infection but not increased severity of disease, (e.g., the influenza and HIV vaccines described above). Following these case studies, and against the background of the understanding they provide of VED, we then analyse the ethical issues presented by the development and use of vaccines.

Case study one: Measles virus

Measles is a highly transmissible virus that is particularly harmful to infants or in those who are first infected in adulthood, as well as to those with comorbidities. Although modern live measles vaccines are highly safe and effective, measles still causes around 100,000 deaths per year, primarily in low-income communities where access to vaccination is poor. Despite the safety of current vaccines, outbreaks of measles have increased in some countries due to reduced vaccination rates partly attributable to vaccine hesitancy 12 .

From 1961–1967, a licensed measles vaccine created with formalin-inactivated (killed) virus, was associated with a type of VED referred to as ‘atypical measles’ 13 , 14 . Vaccinated individuals with atypical measles develop a severe clinical syndrome with rash and fever and a higher rate of lung involvement (pneumonitis) than usual cases of measles and, in some cases, liver dysfunction and abdominal pain 13 , 14 . By the time the enhanced disease syndrome was characterised, over 1.8 million people, mostly children, had received the vaccine 13 . The vaccine was withdrawn from public health use due to VED in 1967 14 . To our knowledge, there are no estimates of the total number of atypical measles cases due to the vaccine, although sporadic cases are still being reported 15 . To reduce subsequent risk of atypical measles, individuals who had received the withdrawn vaccine were re-vaccinated with an alternative (live-attenuated) vaccine 13 .

The initial phase III trial of the formalin-inactivated measles vaccine demonstrated 81% efficacy at 0–3 months after vaccination; however, vaccine efficacy waned over time. At 13 months, efficacy had reduced to 65% 16 . In addition to waning of immunity, interpretation of vaccine efficacy was complicated by changing patterns of community measles transmission. In some cases, vaccinated children experienced apparently normal measles disease post-vaccination (i.e., neither attenuated nor enhanced, likely due to vaccine failure). In others, it was hypothesised that “asymptomatic infections with wild measles viruses may have served to boost some with low and borderline [antibody] titers” 16 (i.e., post-vaccination infection with the wild-type virus was attenuated as a result of vaccination, and the combination of vaccine-derived and post-infection immunity could provide augmented and/or durable protection against subsequent infection) 16 . Early aggregate vaccine efficacy estimates in the study population may have obscured some short-term cases of VED and the short duration of the initial phase III trial meant that longer-term risks of VED due to waning of post-vaccination immunity over time were not detected until public health use of the vaccine, well after trial completion and vaccine approval 13 .

Case study two: Respiratory syncytial virus

Respiratory syncytial virus (RSV) is a ubiquitous virus and a major cause of hospitalisation of young children worldwide, causing up to around 200,000 deaths in children under five per year, primarily in low-income communities 17 . The first infection with RSV is usually the most severe, typically causing the clinical syndrome of bronchiolitis (lung inflammation and congestion). In more severe cases, RSV causes respiratory failure and death. Naturally acquired immunity to RSV wanes over time, and individuals are commonly re-infected many times throughout their lives despite prior infection. It is increasingly recognised that RSV results in significant mortality among older adults, despite numerous prior infections and some degree of immunity 18 .

There is currently no licensed vaccine for RSV (although at least one is in phase III clinical trials) in part because RSV vaccine research was impeded by the occurrence of a high-profile case of VED. In 1966, an experimental RSV vaccine studied in toddlers resulted in many severe cases of what was termed ‘enhanced respiratory disease’ (i.e., more severe lung inflammation and respiratory failure) among child participants subsequently exposed to wild-type RSV, including the death of two toddlers. This led to extreme caution regarding further RSV vaccine research 19 .

Thorough investigation of human cases and preservation of stocks of the 1966 vaccine informed the development of an animal model that closely replicates RSV VED 20 . This has provided opportunities for research on the pathogenesis of RSV VED as well as the prospective testing of future RSV vaccines against the model to ensure that they do not cause similar pathology. Although animal models have identified VED in vaccines which, as a result, did not proceed to human trials 8 , earlier animal models (before RSV VED was identified) had failed to detect this risk. This highlights the limitations of animal models in eliminating the risk of VED (among other adverse effects).

Case study three: Staphylococcus aureus

Staphylococcus aureus is a common species of bacteria found on the skin and upper respiratory tract. Around 30% of the world’s population carries S. aureus , usually without symptoms, yet it causes up to 600 total infections and 30–40 invasive infections, (i.e., with septicaemia, abscess, or vital organ involvement) per 100,000 person-years 21 – 23 , with a particularly high incidence noted among hospitalised patients, resulting in significant morbidity and mortality 24 , 25 . Early reinfection is common after one episode of clinical S. aureus disease (particularly in patients with risk factors for invasion) 26 and immunity to S. aureus is incompletely understood as antibodies to the bacteria are both ubiquitous and insufficient to prevent reinfection 27 . Moreover, the prevalence of resistant S. aureus is increasing worldwide, and WHO has identified methicillin-resistant S. aureus as a high priority resistant pathogen for which better control methods are urgently needed.

Of the 15 antigenic targets for a S. aureus vaccine identified in pre-clinical studies, none have resulted in effective human vaccine targets, despite three candidate vaccines reaching phase IIB/III trials 28 – 31 . One of these candidates (non-adjuvated IsdB) was associated with a five-fold increase in the mortality of patients with S. aureus infection occurring after cardiothoracic surgery (from 4% to 26%). This apparent VED was not seen in pre-clinical mouse challenge studies of the IsdB vaccine or phase I/II trials of healthy volunteers 32 , 33 . Post-hoc analyses of the trial subjects experiencing S. aureus infection suggested that individuals with particular pre-vaccination cytokine signatures (low serum IL-2 and/or IL17a) experienced high infection-related mortality after vaccination (but not after placebo administration), but the mechanisms of this case of VED remain poorly understood.

A subsequent large phase III trial of another candidate vaccine aimed at enhancing opsonophagocytic killing of S. aureus was not associated with VED in high-risk patients, despite very similar preclinical observations and lack of overall efficacy 29 , 34 . This serves to underscore the unpredictability of VED in late-stage trials, especially for pathogens with complicated and incomplete human immunity.

Case study 4: Dengue virus

Dengue is a vector-borne arboviral disease caused by four related strains of dengue virus. Dengue causes millions of cases per year in endemic areas, and increasing numbers of people are at risk 35 . A key feature of dengue is that while first infection is often mild or asymptomatic, second infection (with a different strain to the first infection) is the most likely to be severe, especially if the antibody response to first infection has waned to a certain level, potentiating antibody-dependent disease enhancement 36 . Severe dengue occurs in approximately 2–5% of secondary infections and sometimes results in death 37 . Third and subsequent infections (with any strain) are typically mild or asymptomatic.

A 2015 study of an experimental tetravalent dengue vaccine (known as CYD-TDV) which enrolled children in endemic areas revealed that the vaccine was, overall, associated with a 60% reduction in symptomatic dengue. However, in some younger children, the vaccine was associated with increased risks; for example, vaccinated children aged 2–5 in the Asia-Pacific arm of the trial were 7.45 times more likely to be hospitalized with severe dengue than those in the control group 38 . At the time, it was thought that the most likely reason for higher risks in some children was that the live vaccine primed the immune system in a similar way to a first dengue infection among those who had never been infected (seronegative children). When these individuals then had a naturally-acquired wild-type infection after being vaccinated, this resulted in ‘secondary-like’ VED (i.e., more likely to be severe). Not every person in an endemic area is exposed to dengue every year, and it can take several years before children are infected for the first time, i.e., before ‘seronegative’ individuals become ‘seropositive’. In older age groups in endemic areas, the majority are seropositive – and seropositive people (particularly those who have only been infected once before) appear to benefit from CYD-TDV vaccination.

In contrast to the cases discussed above, there is therefore good reason to think that CYD-TDV could provide net public health benefits, either by vaccinating only seropositive individuals or by vaccinating highly seropositive populations (although this strategy exposes a minority of individuals to a risk of VED). Public health modelling suggested that widespread use of CYD-TDV in populations with high proportion of seropositive individuals could reduce the burden of dengue disease by 10–40% over 10 years 1 . The vaccine was approved by WHO’s Strategic Advisory Group of Experts (SAGE) for use in children over the age of nine in endemic areas where the proportion of seropositive individuals was greater than 70%. The vaccine was initially rolled out without routine pre-vaccination serological testing (due to economic and technical constraints 6 ) but with a plan to seek further data regarding the elevated risk in seronegative individuals 6 .

In contrast to the hypothesis that dengue VED was merely akin to secondary dengue infection, researchers not involved in the development of the vaccine estimated that CYD-TDV VED was up to 3.5 times more (likely to be) severe than usual secondary dengue infection 39 . These authors recommended in 2016 that CYD-TDV vaccination be restricted to seropositive individuals “regardless of inconvenience or cost.” 39 , 40 . Later, controversy ensued because after vaccination campaigns had begun, results confirming the risk of VED among seronegative individuals were published. In the Philippines, where over 800,000 children had been vaccinated, the controversy resulted in political uproar and a decline in confidence regarding vaccines in general 4 , 41 .

Subsequently, SAGE convened a working group including an ethicist. The group proposed a change of policy to restrict the use of CYD-TDV to seropositive individuals, in whom there was clear evidence that the vaccine was safe and effective 6 . However, this resulted in significantly less public health use of the vaccine, because there is still no cost-effective serology testing strategy that could be used routinely to guide dengue vaccination strategies in endemic areas. It is likely that many thousands of seronegative individuals in endemic areas were vaccinated with CYD-TDV prior to the revised policy, and these individuals face a risk of VED if infected after vaccination. The true burden of CYD-TDV VED is difficult to estimate because seronegative individuals were not identified at the time of vaccination and because although it is known that the risk of VED persists for several years, the longer-term risks are poorly characterised.

Ethical implications

Although rare, VED has been associated with significant harms and has often been difficult to predict with a high degree of certainty. There is, therefore, a strong ethical rationale for measures to minimise risk and uncertainty regarding VED for novel vaccines, as well as for transparent communication regarding any residual risks and uncertainties. This is important not only to protect participants in vaccine trials and early recipients of newly approved vaccines, but also to promote public trust in vaccines. In some cases public trust has been undermined by the occurrence of VED and/or a lack of transparent public communication regarding such risks 41 , 42 . Below, we discuss relevant aspects of risk and uncertainty in more detail, including in the context of COVID-19 vaccine research and human challenge studies, before highlighting ethical implications for policymaking related to the public health implementation of vaccines.

Risk and uncertainty

Consensus standards in research ethics require, among other things, that risks to participants are carefully evaluated, minimised, and that residual risks are justified by the social value of the research. This requires comprehensive, rigorous, and systematic evaluation of the anticipated risks, burdens, and benefits of proposed research. Risks are sometimes distinguished from uncertainties by defining risks as harmful outcomes with a known magnitude and probability and uncertainties as potential outcomes with unknown probabilities and/or magnitudes. This sharp distinction between known and unknown outcomes obscures the frequent occurrence of situations in which estimates of the probability or magnitude of an outcome are more or less certain (reflected, for example, by narrower or wider confidence intervals around a risk estimate), ranging from zero certainty (strict uncertainty) to high certainty. In some cases, researchers may be aware of the possibility of particular outcomes without being able to characterise the probability of these outcomes with any certainty. In other cases, even the possibility of a particular outcome is unknown (or not considered) prior to its occurrence (situations of ignorance or so-called ‘unknown unknowns’) 43 . All such situations are captured by various uses of the term ‘uncertainty’. Early phase and first-in-human clinical research inevitably involves significant uncertainty with respect to both benefits and harms, meaning that both good and bad outcomes are sometimes poorly matched to those expected based on prior data 44 .

The case studies above feature both risks and uncertainties. For example, at the time of licensure of the CYD dengue vaccine, there were risks because a phase III trial had demonstrated a harm signal and the potential mechanism was well-described. There were also uncertainties regarding the probability and magnitude of the risk of VED in certain individuals and groups. In other cases where no risks are identified in earlier (animal or human) studies, the potential for VED during vaccine development and after licensure is highly uncertain. For example, in the other cases above, VED was not expected to occur during the phase III S. aureus vaccine trial in surgical patients who would face significant harms from such an enhanced disease, nor among children given the experimental RSV vaccine, nor during public health use of the measles vaccine.

The primary role of vaccine development processes, which involve gathering more data on safety, immunology, and efficacy, is to reduce or resolve uncertainties. Although safety is a key focus of preclinical and early clinical research, most measures of safety become more certain in later-phase research. However, because VED does not occur until a person is exposed to a subsequent infection, which might occur only in late phase research and/or after a considerable time has passed since vaccination. VED can therefore remain a safety concern and area of uncertainty during phase III (efficacy) testing, which necessarily involves participants being exposed to infection with the pathogen in question 45 . Safety concerns about VED may also remain relevant (or be first identified) in post-licensure surveillance, as demonstrated in the case studies of measles and dengue.

Minimising risks to vaccine trial participants necessarily involves trade-offs between the interests of trial participants and considerations related to scientific validity and/or efficiency, both of which are ethically salient to producing public health benefits associated with novel vaccines 44 . A key focus of risk minimisation is the reduction of the probability of serious or irreversible harms – which are a potential consequence of VED. Phase III trials may seek to recruit individuals who face a high probability of the infection in question, because this may optimise scientific validity/generalisability, produce results more rapidly, and because individuals at risk may be independently motivated to participate. In some cases, however, VED may be particularly harmful in groups where the outcome of enhanced disease would be particularly severe (e.g., thoracic surgical patients in the S. aureus case above). It may also be infeasible to reduce the risk of VED in remaining participants after it is observed (in some participants) during the trial – although the measles case illustrates that where other safe vaccines are available, re-vaccination with an alternative vaccine for the same pathogen may mitigate future VED risks.

Both for reasons of continued uncertainty and high magnitude of potential harm, phase III research should arguably involve particularly vigilant monitoring for VED. Where there is concern regarding potential VED, optimal risk minimisation may include particularly careful participant selection criteria and the exclusion of children where feasible. For example, because individuals are reinfected with RSV many times in a lifetime, it has been feasible to exclude children in the initial trials of novel RSV vaccines conducted since the case of VED described above, followed by cautious inclusion of children in subsequent studies once safety is demonstrated in adults.

Follow-up of all novel vaccine trial participants should arguably be of a long duration to detect rare late adverse effects including the potential for late VED. Exposure to infection may occur many months or years after the end of a trial and in some cases the risk of VED may increase with delayed infection (e.g., where the waning of post-vaccination immune response alters the risk of VED) 36 . Waning immunity may explain why the inactivated measles vaccine showed overall population protection during initial trials but was eventually shown to be associated with a significant risk of VED during public health implementation in the general community. Similarly, variations in the local incidence of infection during and after a phase III trial may alter the ability to detect VED. The incidence of dengue was highly variable during and after the initial multi-country CYD-TDV phase III study 46 , which may have contributed to variable efficacy findings in later years of the trial, including the harm signal suggestive of VED.

Implications for COVID-19 vaccines

Experimental vaccines for SARS-CoV and MERS-CoV have been associated with evidence of VED in animal models, which raised concerns regarding the potential for VED with COVID-19 vaccines 8 . A March 2020 expert meeting regarding the potential for COVID-19 VED proposed several measures to reduce the risks of VED including (i) vigilant investigation of vaccine immune responses for those previously associated with VED; (ii) the use of animal challenge models that adequately mimic human disease, ideally including adequate time delay between the vaccination of animals and infection challenge; (iii) consideration of antibody transfer from phase I/II vaccine trial human participants to animal challenge study subjects to test for VED; and (iv) longer follow-up of trial participants (to monitor for the increased disease severity upon exposure to the infection in question) 8 . Even with these resource-intensive measures in place, it is not possible to exclude the risk of VED altogether – in other words there will often be residual uncertainty – and trials of COVID-19 vaccines have involved informing volunteers regarding the risks and uncertainties related to VED 47 . Fortunately, no cases of COVID-19 VED have been documented in phase I-III trial participants 1 , yet this does not exclude the possibility of delayed disease enhancement in the context of waning immune responses. Clinicians and public health agencies should therefore thoroughly investigate any unusually severe cases of COVID-19 in vaccine recipients, ideally using recently proposed standardized criteria for the detection and confirmation of VED 1 .

Risks of vaccine-enhanced disease in human challenge studies versus standard vaccine trials

Human challenge studies involve exposing research participants to infection under controlled conditions and are often used to estimate the efficacy of experimental vaccines before proceeding to larger trials 48 . Phase III vaccine challenge trials typically involve around 100 rigorously screened young healthy adults, whereas standard phase III trials involve tens of thousands of individuals and often a wider age range of participants. Challenge trials permit especially close monitoring of participants for the duration of their infection. On the one hand, challenge studies are ethically sensitive partly because they involve the intentional exposure of participants to risk of infection, potentially including VED (although VED has not occurred in challenge studies to date). Since challenge studies are of short duration, they might detect short-term VED (such as those occurring with RSV and S. aureus above) but not delayed VED events (such as those that might occur during waning immunity). On the other hand, were VED to occur in a challenge study, far fewer participants would be exposed to such harms than if it were to occur in a standard phase III trial, participants would be more likely to have immediate access to treatment for any enhanced disease and the evidence of VED would prevent much larger numbers of people being exposed to that vaccine in a standard phase III trial. These competing considerations mean that there may be difficult ethical judgements to be made as to whether challenge studies or field trials are the optimal first method of testing vaccines for diseases where VED is a concern. However, because standard trials involve exposing many thousands more individuals to an experimental vaccine than challenge studies, cumulative risks of VED may be far higher in standard trials 48 , 49 . In particular, where there are many vaccine candidates, prioritising these candidates in challenge studies before proceeding to larger standard trials with only the most promising vaccines may reduce overall aggregate risks (including those related to VED) 49 , 50 .

Public health implementation

Vaccines typically provide both individual benefit (i.e., net risk reduction) as well as population level benefits (the sum of individual direct benefits plus indirect protection of others, with the combined effect of the latter constituting population ‘herd’ immunity). The occurrence of VED may alter the balance of risks and benefits of vaccine implementation in at least two ways. First, a particular sub-population may face a net risk from vaccination due to VED (despite overall population benefits). Importantly, in such cases, aggregate statistics from a phase III study may demonstrate that a vaccine is efficacious (i.e., beneficial) at the population level because the majority of individuals are protected even if a minority experience VED (see dengue and measles cases above). Researchers should therefore take care to investigate whether overall efficacy estimates conceal cases of VED as well as how benefits and harms associated with vaccination are distributed in the population. Where a vaccine is licensed despite a risk of VED in a minority of vaccine recipients, relevant public health implementation policies should be considered with the utmost care – and public health agencies should engage with sub-populations who might be placed at greater risk. Such engagement and policymaking should include transparent disclosure of relevant risks and uncertainties, the development of fair procedures for the identification of higher risk individuals (if possible), attention to how risks can be minimised, and provision for compensation for serious harms if these occur.

Where the sub-population at risk of VED due to a licensed vaccine is readily identifiable, it is important to consider whether they should be excluded from mass vaccination, although this may undermine the overall efficiency and/or cost-effectiveness of vaccine programs, especially if identifying higher risk individuals requires testing (e.g., of serostatus in the case of dengue) 6 . In addition to making policy based on the overall balance of potential health benefits and risks at the population level, the distribution of risk should also be considered – for example, it may be ethically problematic to impose risks on already marginalised sub-populations or those who cannot provide consent (e.g., children).

Where a sub-population is not readily identifiable, it may sometimes be more appropriate to make a vaccine that offers both significant potential benefits and significant risks (e.g., of VED) a matter of informed consent based on individual doctor-patient discussion of risks and benefits rather than as part of a mass vaccination strategy where the default is to be vaccinated. This informed consent approach is often employed for pre-travel use of the relatively risky but protective vaccines for Japanese encephalitis and yellow fever, for example.

Second, VED can alter the balance of risks and potential benefits of vaccination over time, whether it affects a sub-population or all vaccine recipients. For example, this might occur where a vaccine provides some degree of individual protection against disease in the short-term, but those who are exposed after a longer period of time experience not only less protection but also a higher risk of VED (which is one potential explanation for the epidemiology of atypical measles). In the case of dengue, mass CYD-TDV vaccination of high seroprevalence populations might provide overall population health benefits in the short-to-medium term despite exposing a minority to the risks of VED, but in the long term continued mass vaccination and reduced incidence of dengue might result in increasingly large numbers of seronegative people experiencing VED if/when dengue epidemics recur 51 .

Maintaining public confidence in vaccines

It is widely acknowledged that trust in licensed vaccines, vaccine research, and public health agencies is essential for the ethical acceptability and long-term success of public health programs – and vaccine hesitancy is considered a ‘top 10’ threat to global health 50 . Since VED and other rare but serious harms from vaccination have been associated with declines in public trust, policymakers should prepare for such outcomes. Public health agencies have a responsibility to develop evidence-based approaches to engage with target populations about the benefits, risks, and uncertainties of vaccine programmes (including VED where relevant) and to respond to their perspectives, concerns, and expectations. Engagement with relevant populations regarding vaccination should include careful transparent disclosure of the potential for VED where this is reasonable concern 5 , 6 , 42 . Other policies that might help to promote trust include commitments to undertake vigilant surveillance for vaccine side-effects, especially those that involve significant harm, and to provide appropriate compensation if any vaccine-related harms occur. Where a vaccine is planned for global use, it may also be appropriate for high-income countries or vaccine development sponsors to fund compensation programmes for people in low-income countries who may not otherwise have access to such remediation, especially where global vaccination programs seek to achieve collective aims such as disease eradication 52 .

Conclusions

Vaccination is a cornerstone of global public health, and novel vaccines are developed in order to produce additional health benefits. Although rare, the potential for disease enhancement during vaccine research or public health use of novel vaccines remains a key source of uncertainty and potential risk, and cases of VED have resulted in serious harm as well as declining public trust in vaccines. Vaccine development and implementation should therefore involve measures to reduce risks and uncertainty during vaccine research, transparent communication regarding residual risks and uncertainties, and compensation for any research-related harms, including VED. At the level of public health policy, it should be acknowledged that novel vaccines sometimes produce unexpected harm, including VED, and ongoing public engagement programs should be carefully designed to maintain and promote public trust in vaccination, especially where there are any concerns regarding potential disease enhancement.

Data availability

No data are associated with this article.

1 Ferguson, N. Summary of modelling

https://www.who.int/immunization/sage/meetings/2016/april/3_Ferguson_Comparative_Dengue_Modelling_SAGE.pdf?ua=1

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  • 30.   Fowler VG, Allen KB, Moreira ED, et al. : Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial. JAMA. 2013; 309 (13): 1368–78. PubMed Abstract | Publisher Full Text
  • 31.   Pfizer Inc: Independent data monitoring committee recommends discontinuation of the phase 2B STRIVE clinical trial of Staphylococcus aureus vaccine following planned interim analysis. 2018. Reference Source
  • 32.   Kim HK, DeDent A, Cheng AG, et al. : IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine. 2010; 28 (38): 6382–92. PubMed Abstract | Publisher Full Text | Free Full Text
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Comments on this article Comments (0)

Open peer review.

Is the rationale for the Open Letter provided in sufficient detail?

Does the article adequately reference differing views and opinions?

Are all factual statements correct, and are statements and arguments made adequately supported by citations?

Is the Open Letter written in accessible language?

Where applicable, are recommendations and next steps explained clearly for others to follow?

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Infectious diseases , epidemiology, microbiology and Infection control and Prevention

  • Respond or Comment
  • COMMENT ON THIS REPORT

Reviewer Expertise: Bioethics

  • “In other cases where no risks are identified in earlier (animal or human) studies, the potential for VED during vaccine development and after licensure is highly uncertain. For example, in the other cases above, VED was not expected to occur during the phase III S. aureus vaccine trial in surgical patients who would face significant harms from such an enhanced disease, nor among children given the experimental RSV vaccine, nor during public health use of the measles vaccine.” I wonder whether ‘highly uncertain’ correlates with ‘not expected’- I would think that highly uncertain means that its effects were simply unknown, while not expected means that based on available knowledge risk was determined to be minimal. In this case, the latter seems to be what the authors want to say.  
  • “Follow-up of all novel vaccine trial participants should arguably be of a long duration to detect rare late adverse effects including the potential for late VED” I wonder how feasible this is? What is long enough? Otherwise put, what is the threshold for enough certainty in order to license a vaccine? And who determines the threshold? The obvious player may be the WHO, but what about individual communities? Maybe certain communities would prefer higher stakes for potentially higher gains or vice versa?  
  • It might be worthwhile to sound a warning about uncertainty delaying scientific progress.   After all, people are dying from infectious diseases, and the more we wait for certainty, the more will die, perhaps unnecessarily.  
  • “but in the long term continued mass vaccination and reduced incidence of dengue might result in increasingly large numbers of seronegative people experiencing VED if/when dengue epidemics recur” The article is extremely nuanced, but I wonder whether this consideration may be too nuanced. Worrying about what might happen if we achieve herd immunity against Dengue in terms of VED is like worrying about our planet and its subsistence when we consider developing a cure for cancer. Sure, it’s something to think about, the solution may exist or appear in the future and in any case, this is a tangential consideration in the current context. In other words, it is OK to leave some tangential considerations aside.  
  • “Public health agencies have a responsibility to develop evidence-based approaches to engage with target popuations about the benefits, risks, and uncertainties of vaccine programmes (including VED where relevant) and to respond to their perspectives, concerns, and expectations. Engagement with relevant populations regarding vaccination should include careful transparent disclosure of the potential for VED where this is reasonable concern” this sounds wonderful, but you know human psychology makes things much more complex. The manner in which data will be presented (and by whom) or views are gained will affect the outcome of the so-called engagement. If Covid-19 has shown us anything, it is that many folks tend to be conservative, opting to take their chances with a pathogen rather than uncertainty or some rare side effects. I have no solution to this and am not sure how the authors could address this issue, or if in fact, they should in this article.

Reviewer Expertise: public health ethics, infectious disease ethics, One Health ethics.

Reviewer Status

Alongside their report, reviewers assign a status to the article:

Reviewer Reports

  • Zohar Lederman , Rambam Medical Campus, Haifa, Israel
  • Mirko Ancillotti , Uppsala University, Uppsala, Sweden
  • Peter Collignon , Australian National University, Canberra, Australia

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Library Home

Health Case Studies

(29 reviews)

case study on human health and disease

Glynda Rees, British Columbia Institute of Technology

Rob Kruger, British Columbia Institute of Technology

Janet Morrison, British Columbia Institute of Technology

Copyright Year: 2017

Publisher: BCcampus

Language: English

Formats Available

Conditions of use.

Attribution-ShareAlike

Learn more about reviews.

Reviewed by Jessica Sellars, Medical assistant office instructor, Blue Mountain Community College on 10/11/23

This is a book of compiled and very well organized patient case studies. The author has broken it up by disease patient was experiencing and even the healthcare roles that took place in this patients care. There is a well thought out direction and... read more

Comprehensiveness rating: 5 see less

This is a book of compiled and very well organized patient case studies. The author has broken it up by disease patient was experiencing and even the healthcare roles that took place in this patients care. There is a well thought out direction and plan. There is an appendix to refer to as well if you are needing to find something specific quickly. I have been looking for something like this to help my students have a base to do their project on. This is the most comprehensive version I have found on the subject.

Content Accuracy rating: 5

This is a book compiled of medical case studies. It is very accurate and can be used to learn from great care and mistakes.

Relevance/Longevity rating: 5

This material is very relevant in this context. It also has plenty of individual case studies to utilize in many ways in all sorts of medical courses. This is a very useful textbook and it will continue to be useful for a very long time as you can still learn from each study even if medicine changes through out the years.

Clarity rating: 5

The author put a lot of thought into the ease of accessibility and reading level of the target audience. There is even a "how to use this resource" section which could be extremely useful to students.

Consistency rating: 5

The text follows a very consistent format throughout the book.

Modularity rating: 5

Each case study is individual broken up and in a group of similar case studies. This makes it extremely easy to utilize.

Organization/Structure/Flow rating: 5

The book is very organized and the appendix is through. It flows seamlessly through each case study.

Interface rating: 5

I had no issues navigating this book, It was clearly labeled and very easy to move around in.

Grammatical Errors rating: 5

I did not catch any grammar errors as I was going through the book

Cultural Relevance rating: 5

This is a challenging question for any medical textbook. It is very culturally relevant to those in medical or medical office degrees.

I have been looking for something like this for years. I am so happy to have finally found it.

Reviewed by Cindy Sun, Assistant Professor, Marshall University on 1/7/23

Interestingly, this is not a case of ‘you get what you pay for’. Instead, not only are the case studies organized in a fashion for ease of use through a detailed table of contents, the authors have included more support for both faculty and... read more

Interestingly, this is not a case of ‘you get what you pay for’. Instead, not only are the case studies organized in a fashion for ease of use through a detailed table of contents, the authors have included more support for both faculty and students. For faculty, the introduction section titled ‘How to use this resource’ and individual notes to educators before each case study contain application tips. An appendix overview lists key elements as issues / concepts, scenario context, and healthcare roles for each case study. For students, learning objectives are presented at the beginning of each case study to provide a framework of expectations.

The content is presented accurately and realistic.

The case studies read similar to ‘A Day In the Life of…’ with detailed intraprofessional communications similar to what would be overheard in patient care areas. The authors present not only the view of the patient care nurse, but also weave interprofessional vantage points through each case study by including patient interaction with individual professionals such as radiology, physician, etc.

In addition to objective assessment findings, the authors integrate standard orders for each diagnosis including medications, treatments, and tests allowing the student to incorporate pathophysiology components to their assessments.

Each case study is arranged in the same framework for consistency and ease of use.

This compilation of eight healthcare case studies focusing on new onset and exacerbation of prevalent diagnoses, such as heart failure, deep vein thrombosis, cancer, and chronic obstructive pulmonary disease advancing to pneumonia.

Each case study has a photo of the ‘patient’. Simple as this may seem, it gives an immediate mental image for the student to focus.

Interface rating: 4

As noted by previous reviewers, most of the links do not connect active web pages. This may be due to the multiple options for accessing this resource (pdf download, pdf electronic, web view, etc.).

Grammatical Errors rating: 4

A minor weakness that faculty will probably need to address prior to use is regarding specific term usages differences between Commonwealth countries and United States, such as lung sound descriptors as ‘quiet’ in place of ‘diminished’ and ‘puffers’ in place of ‘inhalers’.

The authors have provided a multicultural, multigenerational approach in selection of patient characteristics representing a snapshot of today’s patient population. Additionally, one case study focusing on heart failure is about a middle-aged adult, contrasting to the average aged patient the students would normally see during clinical rotations. This option provides opportunities for students to expand their knowledge on risk factors extending beyond age.

This resource is applicable to nursing students learning to care for patients with the specific disease processes presented in each case study or for the leadership students focusing on intraprofessional communication. Educators can assign as a supplement to clinical experiences or as an in-class application of knowledge.

Reviewed by Stephanie Sideras, Assistant Professor, University of Portland on 8/15/22

The eight case studies included in this text addressed high frequency health alterations that all nurses need to be able to manage competently. While diabetes was not highlighted directly, it was included as a potential comorbidity. The five... read more

The eight case studies included in this text addressed high frequency health alterations that all nurses need to be able to manage competently. While diabetes was not highlighted directly, it was included as a potential comorbidity. The five overarching learning objectives pulled from the Institute of Medicine core competencies will clearly resonate with any faculty familiar with Quality and Safety Education for Nurses curriculum.

The presentation of symptoms, treatments and management of the health alterations was accurate. Dialogue between the the interprofessional team was realistic. At times the formatting of lab results was confusing as they reflected reference ranges specific to the Canadian healthcare system but these occurrences were minimal and could be easily adapted.

The focus for learning from these case studies was communication - patient centered communication and interprofessional team communication. Specific details, such as drug dosing, was minimized, which increases longevity and allows for easy individualization of the case data.

While some vocabulary was specific to the Canadian healthcare system, overall the narrative was extremely engaging and easy to follow. Subjective case data from patient or provider were formatted in italics and identified as 'thoughts'. Objective and behavioral case data were smoothly integrated into the narrative.

The consistency of formatting across the eight cases was remarkable. Specific learning objectives are identified for each case and these remain consistent across the range of cases, varying only in the focus for the goals for each different health alterations. Each case begins with presentation of essential patient background and the progress across the trajectory of illness as the patient moves from location to location encountering different healthcare professionals. Many of the characters (the triage nurse in the Emergency Department, the phlebotomist) are consistent across the case situations. These consistencies facilitate both application of a variety of teaching methods and student engagement with the situated learning approach.

Case data is presented by location and begins with the patient's first encounter with the healthcare system. This allows for an examination of how specific trajectories of illness are manifested and how care management needs to be prioritized at different stages. This approach supports discussions of care transitions and the complexity of the associated interprofessional communication.

The text is well organized. The case that has two levels of complexity is clearly identified

The internal links between the table of contents and case specific locations work consistently. In the EPUB and the Digital PDF the external hyperlinks are inconsistently valid.

The grammatical errors were minimal and did not detract from readability

Cultural diversity is present across the cases in factors including race, ethnicity, socioeconomic status, family dynamics and sexual orientation.

The level of detail included in these cases supports a teaching approach to address all three spectrums of learning - knowledge, skills and attitudes - necessary for the development of competent practice. I also appreciate the inclusion of specific assessment instruments that would facilitate a discussion of evidence based practice. I will enjoy using these case to promote clinical reasoning discussions of data that is noticed and interpreted with the resulting prioritizes that are set followed by reflections that result from learner choices.

Reviewed by Chris Roman, Associate Professor, Butler University on 5/19/22

It would be extremely difficult for a book of clinical cases to comprehensively cover all of medicine, and this text does not try. Rather, it provides cases related to common medical problems and introduces them in a way that allows for various... read more

Comprehensiveness rating: 4 see less

It would be extremely difficult for a book of clinical cases to comprehensively cover all of medicine, and this text does not try. Rather, it provides cases related to common medical problems and introduces them in a way that allows for various learning strategies to be employed to leverage the cases for deeper student learning and application.

The narrative form of the cases is less subject to issues of accuracy than a more content-based book would be. That said, the cases are realistic and reasonable, avoiding being too mundane or too extreme.

These cases are narrative and do not include many specific mentions of drugs, dosages, or other aspects of clinical care that may grow/evolve as guidelines change. For this reason, the cases should be “evergreen” and can be modified to suit different types of learners.

Clarity rating: 4

The text is written in very accessible language and avoids heavy use of technical language. Depending on the level of learner, this might even be too simplistic and omit some details that would be needed for physicians, pharmacists, and others to make nuanced care decisions.

The format is very consistent with clear labeling at transition points.

The authors point out in the introductory materials that this text is designed to be used in a modular fashion. Further, they have built in opportunities to customize each cases, such as giving dates of birth at “19xx” to allow for adjustments based on instructional objectives, etc.

The organization is very easy to follow.

I did not identify any issues in navigating the text.

The text contains no grammatical errors, though the language is a little stiff/unrealistic in some cases.

Cases involve patients and members of the care team that are of varying ages, genders, and racial/ethnic backgrounds

Reviewed by Trina Larery, Assistant Professor, Pittsburg State University on 4/5/22

The book covers common scenarios, providing allied health students insight into common health issues. The information in the book is thorough and easily modified if needed to include other scenarios not listed. The material was easy to understand... read more

The book covers common scenarios, providing allied health students insight into common health issues. The information in the book is thorough and easily modified if needed to include other scenarios not listed. The material was easy to understand and apply to the classroom. The E-reader format included hyperlinks that bring the students to subsequent clinical studies.

Content Accuracy rating: 4

The treatments were explained and rationales were given, which can be very helpful to facilitate effective learning for a nursing student or novice nurse. The case studies were accurate in explanation. The DVT case study incorrectly identifies the location of the clot in the popliteal artery instead of in the vein.

The content is relevant to a variety of different types of health care providers and due to the general nature of the cases, will remain relevant over time. Updates should be made annually to the hyperlinks and to assure current standard of practice is still being met.

Clear, simple and easy to read.

Consistent with healthcare terminology and framework throughout all eight case studies.

The text is modular. Cases can be used individually within a unit on the given disease process or relevant sections of a case could be used to illustrate a specific point providing great flexibility. The appendix is helpful in locating content specific to a certain diagnosis or a certain type of health care provider.

The book is well organized, presenting in a logical clear fashion. The appendix allows the student to move about the case study without difficulty.

The interface is easy and simple to navigate. Some links to external sources might need to be updated regularly since those links are subject to change based on current guidelines. A few hyperlinks had "page not found".

Few grammatical errors were noted in text.

The case studies include people of different ethnicities, socioeconomic status, ages, and genders to make this a very useful book.

I enjoyed reading the text. It was interesting and relevant to today's nursing student. There are roughly 25 broken online links or "pages not found", care needs to be taken to update at least annually and assure links are valid and utilizing the most up to date information.

Reviewed by Benjamin Silverberg, Associate Professor/Clinician, West Virginia University on 3/24/22

The appendix reviews the "key roles" and medical venues found in all 8 cases, but is fairly spartan on medical content. The table of contents at the beginning only lists the cases and locations of care. It can be a little tricky to figure out what... read more

Comprehensiveness rating: 3 see less

The appendix reviews the "key roles" and medical venues found in all 8 cases, but is fairly spartan on medical content. The table of contents at the beginning only lists the cases and locations of care. It can be a little tricky to figure out what is going on where, especially since each case is largely conversation-based. Since this presents 8 cases (really 7 with one being expanded upon), there are many medical topics (and venues) that are not included. It's impossible to include every kind of situation, but I'd love to see inclusion of sexual health, renal pathology, substance abuse, etc.

Though there are differences in how care can be delivered based on personal style, changing guidelines, available supplies, etc, the medical accuracy seems to be high. I did not detect bias or industry influence.

Relevance/Longevity rating: 4

Medications are generally listed as generics, with at least current dosing recommendations. The text gives a picture of what care looks like currently, but will be a little challenging to update based on new guidelines (ie, it can be hard to find the exact page in which a medication is dosed/prescribed). Even if the text were to be a little out of date, an instructor can use that to point out what has changed (and why).

Clear text, usually with definitions of medical slang or higher-tier vocabulary. Minimal jargon and there are instances where the "characters" are sorting out the meaning as well, making it accessible for new learners, too.

Overall, the style is consistent between cases - largely broken up into scenes and driven by conversation rather than descriptions of what is happening.

There are 8 (well, again, 7) cases which can be reviewed in any order. Case #2 builds upon #1, which is intentional and a good idea, though personally I would have preferred one case to have different possible outcomes or even a recurrence of illness. Each scene within a case is reasonably short.

Organization/Structure/Flow rating: 4

These cases are modular and don't really build on concepts throughout. As previously stated, case #2 builds upon #1, but beyond that, there is no progression. (To be sure, the authors suggest using case #1 for newer learners and #2 for more advanced ones.) The text would benefit from thematic grouping, a longer introduction and debriefing for each case (there are learning objectives but no real context in medical education nor questions to reflect on what was just read), and progressively-increasing difficulty in medical complexity, ethics, etc.

I used the PDF version and had no interface issues. There are minimal photographs and charts. Some words are marked in blue but those did not seem to be hyperlinked anywhere.

No noticeable errors in grammar, spelling, or formatting were noted.

I appreciate that some diversity of age and ethnicity were offered, but this could be improved. There were Canadian Indian and First Nations patients, for example, as well as other characters with implied diversity, but there didn't seem to be any mention of gender diverse or non-heterosexual people, or disabilities. The cases tried to paint family scenes (the first patient's dog was fairly prominently mentioned) to humanize them. Including more cases would allow for more opportunities to include sex/gender minorities, (hidden) disabilities, etc.

The text (originally from 2017) could use an update. It could be used in conjunction with other Open Texts, as a compliment to other coursework, or purely by itself. The focus is meant to be on improving communication, but there are only 3 short pages at the beginning of the text considering those issues (which are really just learning objectives). In addition to adding more cases and further diversity, I personally would love to see more discussion before and after the case to guide readers (and/or instructors). I also wonder if some of the ambiguity could be improved by suggesting possible health outcomes - this kind of counterfactual comparison isn't possible in real life and could be really interesting in a text. Addition of comprehension/discussion questions would also be worthwhile.

Reviewed by Danielle Peterson, Assistant Professor, University of Saint Francis on 12/31/21

This text provides readers with 8 case studies which include both chronic and acute healthcare issues. Although not comprehensive in regard to types of healthcare conditions, it provides a thorough look at the communication between healthcare... read more

This text provides readers with 8 case studies which include both chronic and acute healthcare issues. Although not comprehensive in regard to types of healthcare conditions, it provides a thorough look at the communication between healthcare workers in acute hospital settings. The cases are primarily set in the inpatient hospital setting, so the bulk of the clinical information is basic emergency care and inpatient protocol: vitals, breathing, medication management, etc. The text provides a table of contents at opening of the text and a handy appendix at the conclusion of the text that outlines each case’s issue(s), scenario, and healthcare roles. No index or glossary present.

Although easy to update, it should be noted that the cases are taking place in a Canadian healthcare system. Terms may be unfamiliar to some students including “province,” “operating theatre,” “physio/physiotherapy,” and “porter.” Units of measurement used include Celsius and meters. Also, the issue of managed care, health insurance coverage, and length of stay is missing for American students. These are primary issues that dictate much of the healthcare system in the US and a primary job function of social workers, nurse case managers, and medical professionals in general. However, instructors that wish to add this to the case studies could do so easily.

The focus of this text is on healthcare communication which makes it less likely to become obsolete. Much of the clinical information is stable healthcare practice that has been standard of care for quite some time. Nevertheless, given the nature of text, updates would be easy to make. Hyperlinks should be updated to the most relevant and trustworthy sources and checked frequently for effectiveness.

The spacing that was used to note change of speaker made for ease of reading. Although unembellished and plain, I expect students to find this format easy to digest and interesting, especially since the script is appropriately balanced with ‘human’ qualities like the current TV shows and songs, the use of humor, and nonverbal cues.

A welcome characteristic of this text is its consistency. Each case is presented in a similar fashion and the roles of the healthcare team are ‘played’ by the same character in each of the scenarios. This allows students to see how healthcare providers prioritize cases and juggle the needs of multiple patients at once. Across scenarios, there was inconsistency in when clinical terms were hyperlinked.

The text is easily divisible into smaller reading sections. However, since the nature of the text is script-narrative format, if significant reorganization occurs, one will need to make sure that the communication of the script still makes sense.

The text is straightforward and presented in a consistent fashion: learning objectives, case history, a script of what happened before the patient enters the healthcare setting, and a script of what happens once the patient arrives at the healthcare setting. The authors use the term, “ideal interactions,” and I would agree that these cases are in large part, ‘best case scenarios.’ Due to this, the case studies are well organized, clear, logical, and predictable. However, depending on the level of student, instructors may want to introduce complications that are typical in the hospital setting.

The interface is pleasing and straightforward. With exception to the case summary and learning objectives, the cases are in narrative, script format. Each case study supplies a photo of the ‘patient’ and one of the case studies includes a link to a 3-minute video that introduces the reader to the patient/case. One of the highlights of this text is the use of hyperlinks to various clinical practices (ABG, vital signs, transfer of patient). Unfortunately, a majority of the links are broken. However, since this is an open text, instructors can update the links to their preference.

Although not free from grammatical errors, those that were noticed were minimal and did not detract from reading.

Cultural Relevance rating: 4

Cultural diversity is visible throughout the patients used in the case studies and includes factors such as age, race, socioeconomic status, family dynamics, and sexual orientation. A moderate level of diversity is noted in the healthcare team with some stereotypes: social workers being female, doctors primarily male.

As a social work instructor, I was grateful to find a text that incorporates this important healthcare role. I would have liked to have seen more content related to advance directives, mediating decision making between the patient and care team, emotional and practical support related to initial diagnosis and discharge planning, and provision of support to colleagues, all typical roles of a medical social worker. I also found it interesting that even though social work was included in multiple scenarios, the role was only introduced on the learning objectives page for the oncology case.

case study on human health and disease

Reviewed by Crystal Wynn, Associate Professor, Virginia State University on 7/21/21

The text covers a variety of chronic diseases within the cases; however, not all of the common disease states were included within the text. More chronic diseases need to be included such as diabetes, cancer, and renal failure. Not all allied... read more

The text covers a variety of chronic diseases within the cases; however, not all of the common disease states were included within the text. More chronic diseases need to be included such as diabetes, cancer, and renal failure. Not all allied health care team members are represented within the case study. Key terms appear throughout the case study textbook and readers are able to click on a hyperlink which directs them to the definition and an explanation of the key term.

Content is accurate, error-free and unbiased.

The content is up-to-date, but not in a way that will quickly make the text obsolete within a short period of time. The text is written and/or arranged in such a way that necessary updates will be relatively easy and straightforward to implement.

The text is written in lucid, accessible prose, and provides adequate context for any jargon/technical terminology used

The text is internally consistent in terms of terminology and framework.

The text is easily and readily divisible into smaller reading sections that can be assigned at different points within the course. Each case can be divided into a chronic disease state unit, which will allow the reader to focus on one section at a time.

Organization/Structure/Flow rating: 3

The topics in the text are presented in a logical manner. Each case provides an excessive amount of language that provides a description of the case. The cases in this text reads more like a novel versus a clinical textbook. The learning objectives listed within each case should be in the form of questions or activities that could be provided as resources for instructors and teachers.

Interface rating: 3

There are several hyperlinks embedded within the textbook that are not functional.

The text contains no grammatical errors.

Cultural Relevance rating: 3

The text is not culturally insensitive or offensive in any way. More examples of cultural inclusiveness is needed throughout the textbook. The cases should be indicative of individuals from a variety of races and ethnicities.

Reviewed by Rebecca Hillary, Biology Instructor, Portland Community College on 6/15/21

This textbook consists of a collection of clinical case studies that can be applicable to a wide range of learning environments from supplementing an undergraduate Anatomy and Physiology Course, to including as part of a Medical or other health... read more

This textbook consists of a collection of clinical case studies that can be applicable to a wide range of learning environments from supplementing an undergraduate Anatomy and Physiology Course, to including as part of a Medical or other health care program. I read the textbook in E-reader format and this includes hyperlinks that bring the students to subsequent clinical study if the book is being used in a clinical classroom. This book is significantly more comprehensive in its approach from other case studies I have read because it provides a bird’s eye view of the many clinicians, technicians, and hospital staff working with one patient. The book also provides real time measurements for patients that change as they travel throughout the hospital until time of discharge.

Each case gave an accurate sense of the chaos that would be present in an emergency situation and show how the conditions affect the practitioners as well as the patients. The reader gets an accurate big picture--a feel for each practitioner’s point of view as well as the point of view of the patient and the patient’s family as the clock ticks down and the patients are subjected to a number of procedures. The clinical information contained in this textbook is all in hyperlinks containing references to clinical skills open text sources or medical websites. I did find one broken link on an external medical resource.

The diseases presented are relevant and will remain so. Some of the links are directly related to the Canadian Medical system so they may not be applicable to those living in other regions. Clinical links may change over time but the text itself will remain relevant.

Each case study clearly presents clinical data as is it recorded in real time.

Each case study provides the point of view of several practitioners and the patient over several days. While each of the case studies covers different pathology they all follow this same format, several points of view and data points, over a number of days.

The case studies are divided by days and this was easy to navigate as a reader. It would be easy to assign one case study per body system in an Anatomy and Physiology course, or to divide them up into small segments for small in class teaching moments.

The topics are presented in an organized way showing clinical data over time and each case presents a large number of view points. For example, in the first case study, the patient is experiencing difficulty breathing. We follow her through several days from her entrance to the emergency room. We meet her X Ray Technicians, Doctor, Nurses, Medical Assistant, Porter, Physiotherapist, Respiratory therapist, and the Lab Technicians running her tests during her stay. Each practitioner paints the overall clinical picture to the reader.

I found the text easy to navigate. There were not any figures included in the text, only clinical data organized in charts. The figures were all accessible via hyperlink. Some figures within the textbook illustrating patient scans could have been helpful but I did not have trouble navigating the links to visualize the scans.

I did not see any grammatical errors in the text.

The patients in the text are a variety of ages and have a variety of family arrangements but there is not much diversity among the patients. Our seven patients in the eight case studies are mostly white and all cis gendered.

Some of the case studies, for example the heart failure study, show clinical data before and after drug treatments so the students can get a feel for mechanism in physiological action. I also liked that the case studies included diet and lifestyle advice for the patients rather than solely emphasizing these pharmacological interventions. Overall, I enjoyed reading through these case studies and I plan to utilize them in my Anatomy and Physiology courses.

Reviewed by Richard Tarpey, Assistant Professor, Middle Tennessee State University on 5/11/21

As a case study book, there is no index or glossary. However, medical and technical terms provide a useful link to definitions and explanations that will prove useful to students unfamiliar with the terms. The information provided is appropriate... read more

As a case study book, there is no index or glossary. However, medical and technical terms provide a useful link to definitions and explanations that will prove useful to students unfamiliar with the terms. The information provided is appropriate for entry-level health care students. The book includes important health problems, but I would like to see coverage of at least one more chronic/lifestyle issue such as diabetes. The book covers adult issues only.

Content is accurate without bias

The content of the book is relevant and up-to-date. It addresses conditions that are prevalent in today's population among adults. There are no pediatric cases, but this does not significantly detract from the usefulness of the text. The format of the book lends to easy updating of data or information.

The book is written with clarity and is easy to read. The writing style is accessible and technical terminology is explained with links to more information.

Consistency is present. Lack of consistency is typically a problem with case study texts, but this book is consistent with presentation, format, and terminology throughout each of the eight cases.

The book has high modularity. Each of the case studies can be used independently from the others providing flexibility. Additionally, each case study can be partitioned for specific learning objectives based on the learning objectives of the course or module.

The book is well organized, presenting students conceptually with differing patient flow patterns through a hospital. The patient information provided at the beginning of each case is a wonderful mechanism for providing personal context for the students as they consider the issues. Many case studies focus on the problem and the organization without students getting a patient's perspective. The patient perspective is well represented in these cases.

The navigation through the cases is good. There are some terminology and procedure hyperlinks within the cases that do not work when accessed. This is troubling if you intend to use the text for entry-level health care students since many of these links are critical for a full understanding of the case.

There are some non-US variants of spelling and a few grammatical errors, but these do not detract from the content of the messages of each case.

The book is inclusive of differing backgrounds and perspectives. No insensitive or offensive references were found.

I like this text for its application flexibility. The book is useful for non-clinical healthcare management students to introduce various healthcare-related concepts and terminology. The content is also helpful for the identification of healthcare administration managerial issues for students to consider. The book has many applications.

Reviewed by Paula Baldwin, Associate Professor/Communication Studies, Western Oregon University on 5/10/21

The different case studies fall on a range, from crisis care to chronic illness care. read more

The different case studies fall on a range, from crisis care to chronic illness care.

The contents seems to be written as they occurred to represent the most complete picture of each medical event's occurence.

These case studies are from the Canadian medical system, but that does not interfere with it's applicability.

It is written for a medical audience, so the terminology is mostly formal and technical.

Some cases are shorter than others and some go in more depth, but it is not problematic.

The eight separate case studies is the perfect size for a class in the quarter system. You could combine this with other texts, videos or learning modalities, or use it alone.

As this is a case studies book, there is not a need for a logical progression in presentation of topics.

No problems in terms of interface.

I have not seen any grammatical errors.

I did not see anything that was culturally insensitive.

I used this in a Health Communication class and it has been extraordinarily successful. My studies are analyzing the messaging for the good, the bad, and the questionable. The case studies are widely varied and it gives the class insights into hospital experiences, both front and back stage, that they would not normally be able to examine. I believe that because it is based real-life medical incidents, my students are finding the material highly engaging.

Reviewed by Marlena Isaac, Instructor, Aiken Technical College on 4/23/21

This text is great to walk through patient care with entry level healthcare students. The students are able to take in the information, digest it, then provide suggestions to how they would facilitate patient healing. Then when they are faced with... read more

This text is great to walk through patient care with entry level healthcare students. The students are able to take in the information, digest it, then provide suggestions to how they would facilitate patient healing. Then when they are faced with a situation in clinical they are not surprised and now how to move through it effectively.

The case studies provided accurate information that relates to the named disease.

It is relevant to health care studies and the development of critical thinking.

Cases are straightforward with great clinical information.

Clinical information is provided concisely.

Appropriate for clinical case study.

Presented to facilitate information gathering.

Takes a while to navigate in the browser.

Cultural Relevance rating: 1

Text lacks adequate representation of minorities.

Reviewed by Kim Garcia, Lecturer III, University of Texas Rio Grande Valley on 11/16/20

The book has 8 case studies, so obviously does not cover the whole of medicine, but the cases provided are descriptive and well developed. Cases are presented at different levels of difficulty, making the cases appropriate for students at... read more

The book has 8 case studies, so obviously does not cover the whole of medicine, but the cases provided are descriptive and well developed. Cases are presented at different levels of difficulty, making the cases appropriate for students at different levels of clinical knowledge. The human element of both patient and health care provider is well captured. The cases are presented with a focus on interprofessional interaction and collaboration, more so than teaching medical content.

Content is accurate and un-biased. No errors noted. Most diagnostic and treatment information is general so it will remain relevant over time. The content of these cases is more appropriate for teaching interprofessional collaboration and less so for teaching the medical care for each diagnosis.

The content is relevant to a variety of different types of health care providers (nurses, radiologic technicians, medical laboratory personnel, etc) and due to the general nature of the cases, will remain relevant over time.

Easy to read. Clear headings are provided for sections of each case study and these section headings clearly tell when time has passed or setting has changed. Enough description is provided to help set the scene for each part of the case. Much of the text is written in the form of dialogue involving patient, family and health care providers, making it easy to adapt for role play. Medical jargon is limited and links for medical terms are provided to other resources that expound on medical terms used.

The text is consistent in structure of each case. Learning objectives are provided. Cases generally start with the patient at home and move with the patient through admission, testing and treatment, using a variety of healthcare services and encountering a variety of personnel.

The text is modular. Cases could be used individually within a unit on the given disease process or relevant sections of a case could be used to illustrate a specific point. The appendix is helpful in locating content specific to a certain diagnosis or a certain type of health care provider.

Each case follows a patient in a logical, chronologic fashion. A clear table of contents and appendix are provided which allows the user to quickly locate desired content. It would be helpful if the items in the table of contents and appendix were linked to the corresponding section of the text.

The hyperlinks to content outside this book work, however using the back arrow on your browser returns you to the front page of the book instead of to the point at which you left the text. I would prefer it if the hyperlinks opened in a new window or tab so closing that window or tab would leave you back where you left the text.

No grammatical errors were noted.

The text is culturally inclusive and appropriate. Characters, both patients and care givers are of a variety of races, ethnicities, ages and backgrounds.

I enjoyed reading the cases and reviewing this text. I can think of several ways in which I will use this content.

Reviewed by Raihan Khan, Instructor/Assistant Professor, James Madison University on 11/3/20

The book contains several important health issues, however still missing some chronic health issues that the students should learn before they join the workforce, such as diabetes-related health issues suffered by the patients. read more

The book contains several important health issues, however still missing some chronic health issues that the students should learn before they join the workforce, such as diabetes-related health issues suffered by the patients.

The health information contained in the textbook is mostly accurate.

I think the book is written focusing on the current culture and health issues faced by the patients. To keep the book relevant in the future, the contexts especially the culture/lifestyle/health care modalities, etc. would need to be updated regularly.

The language is pretty simple, clear, and easy to read.

There is no complaint about consistency. One of the main issues of writing a book, consistency was well managed by the authors.

The book is easy to explore based on how easy the setup is. Students can browse to the specific section that they want to read without much hassle of finding the correct information.

The organization is simple but effective. The authors organized the book based on what can happen in a patient's life and what possible scenarios students should learn about the disease. From that perspective, the book does a good job.

The interface is easy and simple to navigate. Some links to external sources might need to be updated regularly since those links are subject to change that is beyond the author's control. It's frustrating for the reader when the external link shows no information.

The book is free of any major language and grammatical errors.

The book might do a little better in cultural competency. e.g. Last name Singh is mainly for Sikh people. In the text Harj and Priya Singh are Muslim. the authors can consult colleagues who are more familiar with those cultures and revise some cultural aspects of the cases mentioned in the book.

The book is a nice addition to the open textbook world. Hope to see more health issues covered by the book.

Reviewed by Ryan Sheryl, Assistant Professor, California State University, Dominguez Hills on 7/16/20

This text contains 8 medical case studies that reflect best practices at the time of publication. The text identifies 5 overarching learning objectives: interprofessional collaboration, client centered care, evidence-based practice, quality... read more

This text contains 8 medical case studies that reflect best practices at the time of publication. The text identifies 5 overarching learning objectives: interprofessional collaboration, client centered care, evidence-based practice, quality improvement, and informatics. While the case studies do not cover all medical conditions or bodily systems, the book is thorough in conveying details of various patients and medical team members in a hospital environment. Rather than an index or glossary at the end of the text, it contains links to outside websites for more information on medical tests and terms referenced in the cases.

The content provided is reflective of best practices in patient care, interdisciplinary collaboration, and communication at the time of publication. It is specifically accurate for the context of hospitals in Canada. The links provided throughout the text have the potential to supplement with up-to-date descriptions and definitions, however, many of them are broken (see notes in Interface section).

The content of the case studies reflects the increasingly complex landscape of healthcare, including a variety of conditions, ages, and personal situations of the clients and care providers. The text will require frequent updating due to the rapidly changing landscape of society and best practices in client care. For example, a future version may include inclusive practices with transgender clients, or address ways medical racism implicitly impacts client care (see notes in Cultural Relevance section).

The text is written clearly and presents thorough, realistic details about working and being treated in an acute hospital context.

The text is very straightforward. It is consistent in its structure and flow. It uses consistent terminology and follows a structured framework throughout.

Being a series of 8 separate case studies, this text is easily and readily divisible into smaller sections. The text was designed to be taken apart and used piece by piece in order to serve various learning contexts. The parts of each case study can also be used independently of each other to facilitate problem solving.

The topics in the case studies are presented clearly. The structure of each of the case studies proceeds in a similar fashion. All of the cases are set within the same hospital so the hospital personnel and service providers reappear across the cases, giving a textured portrayal of the experiences of the various service providers. The cases can be used individually, or one service provider can be studied across the various studies.

The text is very straightforward, without complex charts or images that could become distorted. Many of the embedded links are broken and require updating. The links that do work are a very useful way to define and expand upon medical terms used in the case studies.

Grammatical errors are minimal and do not distract from the flow of the text. In one instance the last name Singh is spelled Sing, and one patient named Fred in the text is referred to as Frank in the appendix.

The cases all show examples of health care personnel providing compassionate, client-centered care, and there is no overt discrimination portrayed. Two of the clients are in same-sex marriages and these are shown positively. It is notable, however, that the two cases presenting people of color contain more negative characteristics than the other six cases portraying Caucasian people. The people of color are the only two examples of clients who smoke regularly. In addition, the Indian client drinks and is overweight, while the First Nations client is the only one in the text to have a terminal diagnosis. The Indian client is identified as being Punjabi and attending a mosque, although there are only 2% Muslims in the Punjab province of India. Also, the last name Singh generally indicates a person who is a Hindu or Sikh, not Muslim.

Reviewed by Monica LeJeune, RN Instructor, LSUE on 4/24/20

Has comprehensive unfolding case studies that guide the reader to recognize and manage the scenario presented. Assists in critical thinking process. read more

Has comprehensive unfolding case studies that guide the reader to recognize and manage the scenario presented. Assists in critical thinking process.

Accurately presents health scenarios with real life assessment techniques and patient outcomes.

Relevant to nursing practice.

Clearly written and easily understood.

Consistent with healthcare terminology and framework

Has a good reading flow.

Topics presented in logical fashion

Easy to read.

No grammatical errors noted.

Text is not culturally insensitive or offensive.

Good book to have to teach nursing students.

Reviewed by april jarrell, associate professor, J. Sargeant Reynolds Community College on 1/7/20

The text is a great case study tool that is appropriate for nursing school instructors to use in aiding students to learn the nursing process. read more

The text is a great case study tool that is appropriate for nursing school instructors to use in aiding students to learn the nursing process.

The content is accurate and evidence based. There is no bias noted

The content in the text is relevant, up to date for nursing students. It will be easy to update content as needed because the framework allows for addition to the content.

The text is clear and easy to understand.

Framework and terminology is consistent throughout the text; the case study is a continual and takes the student on a journey with the patient. Great for learning!

The case studies can be easily divided into smaller sections to allow for discussions, and weekly studies.

The text and content progress in a logical, clear fashion allowing for progression of learning.

No interface issues noted with this text.

No grammatical errors noted in the text.

No racial or culture insensitivity were noted in the text.

I would recommend this text be used in nursing schools. The use of case studies are helpful for students to learn and practice the nursing process.

Reviewed by Lisa Underwood, Practical Nursing Instructor, NTCC on 12/3/19

The text provides eight comprehensive case studies that showcase the different viewpoints of the many roles involved in patient care. It encompasses the most common seen diagnoses seen across healthcare today. Each case study comes with its own... read more

The text provides eight comprehensive case studies that showcase the different viewpoints of the many roles involved in patient care. It encompasses the most common seen diagnoses seen across healthcare today. Each case study comes with its own set of learning objectives that can be tweaked to fit several allied health courses. Although the case studies are designed around the Canadian Healthcare System, they are quite easily adaptable to fit most any modern, developed healthcare system.

Content Accuracy rating: 3

Overall, the text is quite accurate. There is one significant error that needs to be addressed. It is located in the DVT case study. In the study, a popliteal artery clot is mislabeled as a DVT. DVTs are located in veins, not in arteries. That said, the case study on the whole is quite good. This case study could be used as a learning tool in the classroom for discussion purposes or as a way to test student understanding of DVTs, on example might be, "Can they spot the error?"

At this time, all of the case studies within the text are current. Healthcare is an ever evolving field that rests on the best evidence based practice. Keeping that in mind, educators can easily adapt the studies as the newest evidence emerges and changes practice in healthcare.

All of the case studies are well written and easy to understand. The text includes several hyperlinks and it also highlights certain medical terminology to prompt readers as a way to enhance their learning experience.

Across the text, the language, style, and format of the case studies are completely consistent.

The text is divided into eight separate case studies. Each case study may be used independently of the others. All case studies are further broken down as the focus patient passes through each aspect of their healthcare system. The text's modularity makes it possible to use a case study as individual work, group projects, class discussions, homework or in a simulation lab.

The case studies and the diagnoses that they cover are presented in such a way that educators and allied health students can easily follow and comprehend.

The book in itself is free of any image distortion and it prints nicely. The text is offered in a variety of digital formats. As noted in the above reviews, some of the hyperlinks have navigational issues. When the reader attempts to access them, a "page not found" message is received.

There were minimal grammatical errors. Some of which may be traced back to the differences in our spelling.

The text is culturally relevant in that it includes patients from many different backgrounds and ethnicities. This allows educators and students to explore cultural relevance and sensitivity needs across all areas in healthcare. I do not believe that the text was in any way insensitive or offensive to the reader.

By using the case studies, it may be possible to have an open dialogue about the differences noted in healthcare systems. Students will have the ability to compare and contrast the Canadian healthcare system with their own. I also firmly believe that by using these case studies, students can improve their critical thinking skills. These case studies help them to "put it all together".

Reviewed by Melanie McGrath, Associate Professor, TRAILS on 11/29/19

The text covered some of the most common conditions seen by healthcare providers in a hospital setting, which forms a solid general base for the discussions based on each case. read more

The text covered some of the most common conditions seen by healthcare providers in a hospital setting, which forms a solid general base for the discussions based on each case.

I saw no areas of inaccuracy

As in all healthcare texts, treatments and/or tests will change frequently. However, everything is currently up-to-date thus it should be a good reference for several years.

Each case is written so that any level of healthcare student would understand. Hyperlinks in the text is also very helpful.

All of the cases are written in a similar fashion.

Although not structured as a typical text, each case is easily assigned as a stand-alone.

Each case is organized clearly in an appropriate manner.

I did not see any issues.

I did not see any grammatical errors

The text seemed appropriately inclusive. There are no pediatric cases and no cases of intellectually-impaired patients, but those types of cases introduce more advanced problem-solving which perhaps exceed the scope of the text. May be a good addition to the text.

I found this text to be an excellent resource for healthcare students in a variety of fields. It would be best utilized in inter professional courses to help guide discussion.

Reviewed by Lynne Umbarger, Clinical Assistant Professor, Occupational Therapy, Emory and Henry College on 11/26/19

While the book does not cover every scenario, the ones in the book are quite common and troublesome for inexperienced allied health students. The information in the book is thorough enough, and I have found the cases easy to modify for educational... read more

While the book does not cover every scenario, the ones in the book are quite common and troublesome for inexperienced allied health students. The information in the book is thorough enough, and I have found the cases easy to modify for educational purposes. The material was easily understood by the students but challenging enough for classroom discussion. There are no mentions in the book about occupational therapy, but it is easy enough to add a couple words and make inclusion simple.

Very nice lab values are provided in the case study, making it more realistic for students.

These case studies focus on commonly encountered diagnoses for allied health and nursing students. They are comprehensive, realistic, and easily understood. The only difference is that the hospital in one case allows the patient's dog to visit in the room (highly unusual in US hospitals).

The material is easily understood by allied health students. The cases have links to additional learning materials for concepts that may be less familiar or should be explored further in a particular health field.

The language used in the book is consistent between cases. The framework is the same with each case which makes it easier to locate areas that would be of interest to a particular allied health profession.

The case studies are comprehensive but well-organized. They are short enough to be useful for class discussion or a full-blown assignment. The students seem to understand the material and have not expressed that any concepts or details were missing.

Each case is set up like the other cases. There are learning objectives at the beginning of each case to facilitate using the case, and it is easy enough to pull out material to develop useful activities and assignments.

There is a quick chart in the Appendix to allow the reader to determine the professions involved in each case as well as the pertinent settings and diagnoses for each case study. The contents are easy to access even while reading the book.

As a person who attends carefully to grammar, I found no errors in all of the material I read in this book.

There are a greater number of people of different ethnicities, socioeconomic status, ages, and genders to make this a very useful book. With each case, I could easily picture the person in the case. This book appears to be Canadian and more inclusive than most American books.

I was able to use this book the first time I accessed it to develop a classroom activity for first-year occupational therapy students and a more comprehensive activity for second-year students. I really appreciate the links to a multitude of terminology and medical lab values/issues for each case. I will keep using this book.

Reviewed by Cindy Krentz, Assistant Professor, Metropolitan State University of Denver on 6/15/19

The book covers eight case studies of common inpatient or emergency department scenarios. I appreciated that they had written out the learning objectives. I liked that the patient was described before the case was started, giving some... read more

The book covers eight case studies of common inpatient or emergency department scenarios. I appreciated that they had written out the learning objectives. I liked that the patient was described before the case was started, giving some understanding of the patient's background. I think it could benefit from having a glossary. I liked how the authors included the vital signs in an easily readable bar. I would have liked to see the labs also highlighted like this. I also felt that it would have been good written in a 'what would you do next?' type of case study.

The book is very accurate in language, what tests would be prudent to run and in the day in the life of the hospital in all cases. One inaccuracy is that the authors called a popliteal artery clot a DVT. The rest of the DVT case study was great, though, but the one mistake should be changed.

The book is up to date for now, but as tests become obsolete and new equipment is routinely used, the book ( like any other health textbook) will need to be updated. It would be easy to change, however. All that would have to happen is that the authors go in and change out the test to whatever newer, evidence-based test is being utilized.

The text is written clearly and easy to understand from a student's perspective. There is not too much technical jargon, and it is pretty universal when used- for example DVT for Deep Vein Thrombosis.

The book is consistent in language and how it is broken down into case studies. The same format is used for highlighting vital signs throughout the different case studies. It's great that the reader does not have to read the book in a linear fashion. Each case study can be read without needing to read the others.

The text is broken down into eight case studies, and within the case studies is broken down into days. It is consistent and shows how the patient can pass through the different hospital departments (from the ER to the unit, to surgery, to home) in a realistic manner. The instructor could use one or more of the case studies as (s)he sees fit.

The topics are eight different case studies- and are presented very clearly and organized well. Each one is broken down into how the patient goes through the system. The text is easy to follow and logical.

The interface has some problems with the highlighted blue links. Some of them did not work and I got a 'page not found' message. That can be frustrating for the reader. I'm wondering if a glossary could be utilized (instead of the links) to explain what some of these links are supposed to explain.

I found two or three typos, I don't think they were grammatical errors. In one case I think the Canadian spelling and the United States spelling of the word are just different.

This is a very culturally competent book. In today's world, however, one more type of background that would merit delving into is the trans-gender, GLBTQI person. I was glad that there were no stereotypes.

I enjoyed reading the text. It was interesting and relevant to today's nursing student. Since we are becoming more interprofessional, I liked that we saw what the phlebotomist and other ancillary personnel (mostly different technicians) did. I think that it could become even more interdisciplinary so colleges and universities could have more interprofessional education- courses or simulations- with the addition of the nurse using social work, nutrition, or other professional health care majors.

Reviewed by Catherine J. Grott, Interim Director, Health Administration Program, TRAILS on 5/5/19

The book is comprehensive but is specifically written for healthcare workers practicing in Canada. The title of the book should reflect this. read more

The book is comprehensive but is specifically written for healthcare workers practicing in Canada. The title of the book should reflect this.

The book is accurate, however it has numerous broken online links.

Relevance/Longevity rating: 3

The content is very relevant, but some links are out-dated. For example, WHO Guidelines for Safe Surgery 2009 (p. 186) should be updated.

The book is written in clear and concise language. The side stories about the healthcare workers make the text interesting.

The book is consistent in terms of terminology and framework. Some terms that are emphasized in one case study are not emphasized (with online links) in the other case studies. All of the case studies should have the same words linked to online definitions.

Modularity rating: 3

The book can easily be parsed out if necessary. However, the way the case studies have been written, it's evident that different authors contributed singularly to each case study.

The organization and flow are good.

Interface rating: 1

There are numerous broken online links and "pages not found."

The grammar and punctuation are correct. There are two errors detected: p. 120 a space between the word "heart" and the comma; also a period is needed after Dr (p. 113).

I'm not quite sure that the social worker (p. 119) should comment that the patient and partner are "very normal people."

There are roughly 25 broken online links or "pages not found." The BC & Canadian Guidelines (p. 198) could also include a link to US guidelines to make the text more universal . The basilar crackles (p. 166) is very good. Text could be used compare US and Canadian healthcare. Text could be enhanced to teach "soft skills" and interdepartmental communication skills in healthcare.

Reviewed by Lindsey Henry, Practical Nursing Instructor, Fletcher on 5/1/19

I really appreciated how in the introduction, five learning objectives were identified for students. These objectives are paramount in nursing care and they are each spelled out for the learner. Each Case study also has its own learning... read more

I really appreciated how in the introduction, five learning objectives were identified for students. These objectives are paramount in nursing care and they are each spelled out for the learner. Each Case study also has its own learning objectives, which were effectively met in the readings.

As a seasoned nurse, I believe that the content regarding pathophysiology and treatments used in the case studies were accurate. I really appreciated how many of the treatments were also explained and rationales were given, which can be very helpful to facilitate effective learning for a nursing student or novice nurse.

The case studies are up to date and correlate with the current time period. They are easily understood.

I really loved how several important medical terms, including specific treatments were highlighted to alert the reader. Many interventions performed were also explained further, which is great to enhance learning for the nursing student or novice nurse. Also, with each scenario, a background and history of the patient is depicted, as well as the perspectives of the patient, patients family member, and the primary nurse. This really helps to give the reader a full picture of the day in the life of a nurse or a patient, and also better facilitates the learning process of the reader.

These case studies are consistent. They begin with report, the patient background or updates on subsequent days, and follow the patients all the way through discharge. Once again, I really appreciate how this book describes most if not all aspects of patient care on a day to day basis.

Each case study is separated into days. While they can be divided to be assigned at different points within the course, they also build on each other. They show trends in vital signs, what happens when a patient deteriorates, what happens when they get better and go home. Showing the entire process from ER admit to discharge is really helpful to enhance the students learning experience.

The topics are all presented very similarly and very clearly. The way that the scenarios are explained could even be understood by a non-nursing student as well. The case studies are very clear and very thorough.

The book is very easy to navigate, prints well on paper, and is not distorted or confusing.

I did not see any grammatical errors.

Each case study involves a different type of patient. These differences include race, gender, sexual orientation and medical backgrounds. I do not feel the text was offensive to the reader.

I teach practical nursing students and after reading this book, I am looking forward to implementing it in my classroom. Great read for nursing students!

Reviewed by Leah Jolly, Instructor, Clinical Coordinator, Oregon Institute of Technology on 4/10/19

Good variety of cases and pathologies covered. read more

Good variety of cases and pathologies covered.

Content Accuracy rating: 2

Some examples and scenarios are not completely accurate. For example in the DVT case, the sonographer found thrombus in the "popliteal artery", which according to the book indicated presence of DVT. However in DVT, thrombus is located in the vein, not the artery. The patient would also have much different symptoms if located in the artery. Perhaps some of these inaccuracies are just typos, but in real-life situations this simple mistake can make a world of difference in the patient's course of treatment and outcomes.

Good examples of interprofessional collaboration. If only it worked this way on an every day basis!

Clear and easy to read for those with knowledge of medical terminology.

Good consistency overall.

Broken up well.

Topics are clear and logical.

Would be nice to simply click through to the next page, rather than going through the table of contents each time.

Minor typos/grammatical errors.

No offensive or insensitive materials observed.

Reviewed by Alex Sargsyan, Doctor of Nursing Practice/Assistant Professor , East Tennessee State University on 10/8/18

Because of the case study character of the book it does not have index or glossary. However it has summary for each health case study outlining key elements discussed in each case study. read more

Because of the case study character of the book it does not have index or glossary. However it has summary for each health case study outlining key elements discussed in each case study.

Overall the book is accurately depicting the clinical environment. There are numerous references to external sites. While most of them are correct, some of them are not working. For example Homan’s test link is not working "404 error"

Book is relevant in its current version and can be used in undergraduate and graduate classes. That said, the longevity of the book may be limited because of the character of the clinical education. Clinical guidelines change constantly and it may require a major update of the content.

Cases are written very clearly and have realistic description of an inpatient setting.

The book is easy to read and consistent in the language in all eight cases.

The cases are very well written. Each case is subdivided into logical segments. The segments reflect different setting where the patient is being seen. There is a flow and transition between the settings.

Book has eight distinct cases. This is a great format for a book that presents distinct clinical issues. This will allow the students to have immersive experiences and gain better understanding of the healthcare environment.

Book is offered in many different formats. Besides the issues with the links mentioned above, overall navigation of the book content is very smooth.

Book is very well written and has no grammatical errors.

Book is culturally relevant. Patients in the case studies come different cultures and represent diverse ethnicities.

Reviewed by Justin Berry, Physical Therapist Assistant Program Director, Northland Community and Technical College, East Grand Forks, MN on 8/2/18

This text provides eight patient case studies from a variety of diagnoses, which can be utilized by healthcare students from multiple disciplines. The cases are comprehensive and can be helpful for students to determine professional roles,... read more

This text provides eight patient case studies from a variety of diagnoses, which can be utilized by healthcare students from multiple disciplines. The cases are comprehensive and can be helpful for students to determine professional roles, interprofessional roles, when to initiate communication with other healthcare practitioners due to a change in patient status, and treatment ideas. Some additional patient information, such as lab values, would have been beneficial to include.

Case study information is accurate and unbiased.

Content is up to date. The case studies are written in a way so that they will not be obsolete soon, even with changes in healthcare.

The case studies are well written, and can be utilized for a variety of classroom assignments, discussions, and projects. Some additional lab value information for each patient would have been a nice addition.

The case studies are consistently organized to make it easy for the reader to determine the framework.

The text is broken up into eight different case studies for various patient diagnoses. This design makes it highly modular, and would be easy to assign at different points of a course.

The flow of the topics are presented consistently in a logical manner. Each case study follows a patient chronologically, making it easy to determine changes in patient status and treatment options.

The text is free of interface issues, with no distortion of images or charts.

The text is not culturally insensitive or offensive in any way. Patients are represented from a variety of races, ethnicities, and backgrounds

This book would be a good addition for many different health programs.

Reviewed by Ann Bell-Pfeifer, Instructor/Program Director, Minnesota State Community and Technical College on 5/21/18

The book gives a comprehensive overview of many types of cases for patient conditions. Emergency Room patients may arrive with COPD, heart failure, sepsis, pneumonia, or as motor vehicle accident victims. It is directed towards nurses, medical... read more

The book gives a comprehensive overview of many types of cases for patient conditions. Emergency Room patients may arrive with COPD, heart failure, sepsis, pneumonia, or as motor vehicle accident victims. It is directed towards nurses, medical laboratory technologists, medical radiology technologists, and respiratory therapists and their roles in caring for patients. Most of the overview is accurate. One suggestion is to provide an embedded radiologist interpretation of the exams which are performed which lead to the patients diagnosis.

Overall the book is accurate. Would like to see updates related to the addition of direct radiography technology which is commonly used in the hospital setting.

Many aspects of medicine will remain constant. The case studies seem fairly accurate and may be relevant for up to 3 years. Since technology changes so quickly in medicine, the CT and x-ray components may need minor updates within a few years.

The book clarity is excellent.

The case stories are consistent with each scenario. It is easy to follow the structure and learn from the content.

The book is quite modular. It is easy to break it up into cases and utilize them individually and sequentially.

The cases are listed by disease process and follow a logical flow through each condition. They are easy to follow as they have the same format from the beginning to the end of each case.

The interface seems seamless. Hyperlinks are inserted which provide descriptions and references to medical procedures and in depth definitions.

The book is free of most grammatical errors. There is a place where a few words do not fit the sentence structure and could be a typo.

The book included all types of relationships and ethnic backgrounds. One type which could be added is a transgender patient.

I think the book was quite useful for a variety of health care professionals. The authors did an excellent job of integrating patient cases which could be applied to the health care setting. The stories seemed real and relevant. This book could be used to teach health care professionals about integrated care within the emergency department.

Reviewed by Shelley Wolfe, Assistant Professor, Winona State University on 5/21/18

This text is comprised of comprehensive, detailed case studies that provide the reader with multiple character views throughout a patient’s encounter with the health care system. The Table of Contents accurately reflected the content. It should... read more

This text is comprised of comprehensive, detailed case studies that provide the reader with multiple character views throughout a patient’s encounter with the health care system. The Table of Contents accurately reflected the content. It should be noted that the authors include a statement that conveys that this text is not like traditional textbooks and is not meant to be read in a linear fashion. This allows the educator more flexibility to use the text as a supplement to enhance learning opportunities.

The content of the text appears accurate and unbiased. The “five overarching learning objectives” provide a clear aim of the text and the educator is able to glean how these objectives are captured into each of the case studies. While written for the Canadian healthcare system, this text is easily adaptable to the American healthcare system.

Overall, the content is up-to-date and the case studies provide a variety of uses that promote longevity of the text. However, not all of the blue font links (if using the digital PDF version) were still in working order. I encountered links that led to error pages or outdated “page not found” websites. While the links can be helpful, continued maintenance of these links could prove time-consuming.

I found the text easy to read and understand. I enjoyed that the viewpoints of all the different roles (patient, nurse, lab personnel, etc.) were articulated well and allowed the reader to connect and gain appreciation of the entire healthcare team. Medical jargon was noted to be appropriate for the intended audience of this text.

The terminology and organization of this text is consistent.

The text is divided into 8 case studies that follow a similar organizational structure. The case studies can further be divided to focus on individual learning objectives. For example, the case studies could be looked at as a whole for discussing communication or could be broken down into segments to focus on disease risk factors.

The case studies in this text follow a similar organizational structure and are consistent in their presentation. The flow of individual case studies is excellent and sets the reader on a clear path. As noted previously, this text is not meant to be read in a linear fashion.

This text is available in many different forms. I chose to review the text in the digital PDF version in order to use the embedded links. I did not encounter significant interface issues and did not find any images or features that would distract or confuse a reader.

No significant grammatical errors were noted.

The case studies in this text included patients and healthcare workers from a variety of backgrounds. Educators and students will benefit from expanding the case studies to include discussions and other learning opportunities to help develop culturally-sensitive healthcare providers.

I found the case studies to be very detailed, yet written in a way in which they could be used in various manners. The authors note a variety of ways in which the case studies could be employed with students; however, I feel the authors could also include that the case studies could be used as a basis for simulated clinical experiences. The case studies in this text would be an excellent tool for developing interprofessional communication and collaboration skills in a variety healthcare students.

Reviewed by Darline Foltz, Assistant Professor, University of Cincinnati - Clermont College on 3/27/18

This book covers all areas listed in the Table of Contents. In addition to the detailed patient case studies, there is a helpful section of "How to Use this Resource". I would like to note that this resource "aligns with the open textbooks... read more

This book covers all areas listed in the Table of Contents. In addition to the detailed patient case studies, there is a helpful section of "How to Use this Resource". I would like to note that this resource "aligns with the open textbooks Clinical Procedures for Safer Patient Care and Anatomy and Physiology: OpenStax" as noted by the authors.

The book appears to be accurate. Although one of the learning outcomes is as follows: "Demonstrate an understanding of the Canadian healthcare delivery system.", I did not find anything that is ONLY specific to the Canadian healthcare delivery system other than some of the terminology, i.e. "porter" instead of "transporter" and a few french words. I found this to make the book more interesting for students rather than deter from it. These are patient case studies that are relevant in any country.

The content is up-to-date. Changes in medical science may occur, i.e. a different test, to treat a diagnosis that is included in one or more of the case studies, however, it would be easy and straightforward to implement these changes.

This book is written in lucid, accessible prose. The technical/medical terminology that is used is appropriate for medical and allied health professionals. Something that would improve this text would to provide a glossary of terms for the terms in blue font.

This book is consistent with current medical terminology

This text is easily divided into each of the 6 case studies. The case studies can be used singly according to the body system being addressed or studied.

Because this text is a collection of case studies, flow doesn't pertain, however the organization and structure of the case studies are excellent as they are clear and easy to read.

There are no distractions in this text that would distract or confuse the reader.

I did not identify any grammatical errors.

This text is not culturally insensitive or offensive in any way and uses patients and healthcare workers that are of a variety of races, ethnicities and backgrounds.

I believe that this text would not only be useful to students enrolled in healthcare professions involved in direct patient care but would also be useful to students in supporting healthcare disciplines such as health information technology and management, medical billing and coding, etc.

Table of Contents

  • Introduction

Case Study #1: Chronic Obstructive Pulmonary Disease (COPD)

  • Learning Objectives
  • Patient: Erin Johns
  • Emergency Room

Case Study #2: Pneumonia

  • Day 0: Emergency Room
  • Day 1: Emergency Room
  • Day 1: Medical Ward
  • Day 2: Medical Ward
  • Day 3: Medical Ward
  • Day 4: Medical Ward

Case Study #3: Unstable Angina (UA)

  • Patient: Harj Singh

Case Study #4: Heart Failure (HF)

  • Patient: Meryl Smith
  • In the Supermarket
  • Day 0: Medical Ward

Case Study #5: Motor Vehicle Collision (MVC)

  • Patient: Aaron Knoll
  • Crash Scene
  • Operating Room
  • Post Anaesthesia Care Unit (PACU)
  • Surgical Ward

Case Study #6: Sepsis

  • Patient: George Thomas
  • Sleepy Hollow Care Facility

Case Study #7: Colon Cancer

  • Patient: Fred Johnson
  • Two Months Ago
  • Pre-Surgery Admission

Case Study #8: Deep Vein Thrombosis (DVT)

  • Patient: Jamie Douglas

Appendix: Overview About the Authors

Ancillary Material

About the book.

Health Case Studies is composed of eight separate health case studies. Each case study includes the patient narrative or story that models the best practice (at the time of publishing) in healthcare settings. Associated with each case is a set of specific learning objectives to support learning and facilitate educational strategies and evaluation.

The case studies can be used online in a learning management system, in a classroom discussion, in a printed course pack or as part of a textbook created by the instructor. This flexibility is intentional and allows the educator to choose how best to convey the concepts presented in each case to the learner.

Because these case studies were primarily developed for an electronic healthcare system, they are based predominantly in an acute healthcare setting. Educators can augment each case study to include primary healthcare settings, outpatient clinics, assisted living environments, and other contexts as relevant.

About the Contributors

Glynda Rees teaches at the British Columbia Institute of Technology (BCIT) in Vancouver, British Columbia. She completed her MSN at the University of British Columbia with a focus on education and health informatics, and her BSN at the University of Cape Town in South Africa. Glynda has many years of national and international clinical experience in critical care units in South Africa, the UK, and the USA. Her teaching background has focused on clinical education, problem-based learning, clinical techniques, and pharmacology.

Glynda‘s interests include the integration of health informatics in undergraduate education, open accessible education, and the impact of educational technologies on nursing students’ clinical judgment and decision making at the point of care to improve patient safety and quality of care.

Faculty member in the critical care nursing program at the British Columbia Institute of Technology (BCIT) since 2003, Rob has been a critical care nurse for over 25 years with 17 years practicing in a quaternary care intensive care unit. Rob is an experienced educator and supports student learning in the classroom, online, and in clinical areas. Rob’s Master of Education from Simon Fraser University is in educational technology and learning design. He is passionate about using technology to support learning for both faculty and students.

Part of Rob’s faculty position is dedicated to providing high fidelity simulation support for BCIT’s nursing specialties program along with championing innovative teaching and best practices for educational technology. He has championed the use of digital publishing and was the tech lead for Critical Care Nursing’s iPad Project which resulted in over 40 multi-touch interactive textbooks being created using Apple and other technologies.

Rob has successfully completed a number of specialist certifications in computer and network technologies. In 2015, he was awarded Apple Distinguished Educator for his innovation and passionate use of technology to support learning. In the past five years, he has presented and published abstracts on virtual simulation, high fidelity simulation, creating engaging classroom environments, and what the future holds for healthcare and education.

Janet Morrison is the Program Head of Occupational Health Nursing at the British Columbia Institute of Technology (BCIT) in Burnaby, British Columbia. She completed a PhD at Simon Fraser University, Faculty of Communication, Art and Technology, with a focus on health information technology. Her dissertation examined the effects of telehealth implementation in an occupational health nursing service. She has an MA in Adult Education from St. Francis Xavier University and an MA in Library and Information Studies from the University of British Columbia.

Janet’s research interests concern the intended and unintended impacts of health information technologies on healthcare students, faculty, and the healthcare workforce.

She is currently working with BCIT colleagues to study how an educational clinical information system can foster healthcare students’ perceptions of interprofessional roles.

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Review article, effects of water pollution on human health and disease heterogeneity: a review.

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  • 1 Research Center for Economy of Upper Reaches of the Yangtse River/School of Economics, Chongqing Technology and Business University, Chongqing, China
  • 2 School of Economics and Management, Huzhou University, Huzhou, China

Background: More than 80% of sewage generated by human activities is discharged into rivers and oceans without any treatment, which results in environmental pollution and more than 50 diseases. 80% of diseases and 50% of child deaths worldwide are related to poor water quality.

Methods: This paper selected 85 relevant papers finally based on the keywords of water pollution, water quality, health, cancer, and so on.

Results: The impact of water pollution on human health is significant, although there may be regional, age, gender, and other differences in degree. The most common disease caused by water pollution is diarrhea, which is mainly transmitted by enteroviruses in the aquatic environment.

Discussion: Governments should strengthen water intervention management and carry out intervention measures to improve water quality and reduce water pollution’s impact on human health.

Introduction

Water is an essential resource for human survival. According to the 2021 World Water Development Report released by UNESCO, the global use of freshwater has increased six-fold in the past 100 years and has been growing by about 1% per year since the 1980s. With the increase of water consumption, water quality is facing severe challenges. Industrialization, agricultural production, and urban life have resulted in the degradation and pollution of the environment, adversely affecting the water bodies (rivers and oceans) necessary for life, ultimately affecting human health and sustainable social development ( Xu et al., 2022a ). Globally, an estimated 80% of industrial and municipal wastewater is discharged into the environment without any prior treatment, with adverse effects on human health and ecosystems. This proportion is higher in the least developed countries, where sanitation and wastewater treatment facilities are severely lacking.

Sources of Water Pollution

Water pollution are mainly concentrated in industrialization, agricultural activities, natural factors, and insufficient water supply and sewage treatment facilities. First, industry is the main cause of water pollution, these industries include distillery industry, tannery industry, pulp and paper industry, textile industry, food industry, iron and steel industry, nuclear industry and so on. Various toxic chemicals, organic and inorganic substances, toxic solvents and volatile organic chemicals may be released in industrial production. If these wastes are released into aquatic ecosystems without adequate treatment, they will cause water pollution ( Chowdhary et al., 2020 ). Arsenic, cadmium, and chromium are vital pollutants discharged in wastewater, and the industrial sector is a significant contributor to harmful pollutants ( Chen et al., 2019 ). With the acceleration of urbanization, wastewater from industrial production has gradually increased. ( Wu et al., 2020 ). In addition, water pollution caused by industrialization is also greatly affected by foreign direct investment. Industrial water pollution in less developed countries is positively correlated with foreign direct investment ( Jorgenson, 2009 ). Second, water pollution is closely related to agriculture. Pesticides, nitrogen fertilizers and organic farm wastes from agriculture are significant causes of water pollution (RCEP, 1979). Agricultural activities will contaminate the water with nitrates, phosphorus, pesticides, soil sediments, salts and pathogens ( Parris, 2011 ). Furthermore, agriculture has severely damaged all freshwater systems in their pristine state ( Moss, 2008 ). Untreated or partially treated wastewater is widely used for irrigation in water-scarce regions of developing countries, including China and India, and the presence of pollutants in sewage poses risks to the environment and health. Taking China as an example, the imbalance in the quantity and quality of surface water resources has led to the long-term use of wastewater irrigation in some areas in developing countries to meet the water demand of agricultural production, resulting in serious agricultural land and food pollution, pesticide residues and heavy metal pollution threatening food safety and Human Health ( Lu et al., 2015 ). Pesticides have an adverse impact on health through drinking water. Comparing pesticide use with health life Expectancy Longitudinal Survey data, it was found that a 10% increase in pesticide use resulted in a 1% increase in the medical disability index over 65 years of age ( Lai, 2017 ). The case of the Musi River in India shows a higher incidence of morbidity in wastewater-irrigated villages than normal-water households. Third, water pollution is related to natural factors. Taking Child Loess Plateau as an example, the concentration of trace elements in water quality is higher than the average world level, and trace elements come from natural weathering and manufacture causes. Poor river water quality is associated with high sodium and salinity hazards ( Xiao et al., 2019 ). The most typical water pollution in the middle part of the loess Plateau is hexavalent chromium pollution, which is caused by the natural environment and human activities. Loess and mudstone are the main sources, and groundwater with high concentrations of hexavalent chromium is also an important factor in surface water pollution (He et al., 2020). Finally, water supply and sewage treatment facilities are also important factors affecting drinking water quality, especially in developing countries. In parallel with China rapid economic growth, industrialization and urbanization, underinvestment in basic water supply and treatment facilities has led to water pollution, increased incidence of infectious and parasitic diseases, and increased exposure to industrial chemicals, heavy metals and algal toxins ( Wu et al., 1999 ). An econometric model predicts the impact of water purification equipment on water quality and therefore human health. When the proportion of household water treated with water purification equipment is reduced from 100% to 90%, the expected health benefits are reduced by up to 96%.. When the risk of pretreatment water quality is high, the decline is even more significant ( Brown and Clasen, 2012 ).

To sum up, water pollution results from both human and natural factors. Various human activities will directly affect water quality, including urbanization, population growth, industrial production, climate change, and other factors ( Halder and Islam, 2015 ) and religious activities ( Dwivedi et al., 2018 ). Improper disposal of solid waste, sand, and gravel is also one reason for decreasing water quality ( Ustaoğlua et al., 2020 ).

Impact of Water Pollution on Human Health

Unsafe water has severe implications for human health. According to UNESCO 2021 World Water Development Report , about 829,000 people die each year from diarrhea caused by unsafe drinking water, sanitation, and hand hygiene, including nearly 300,000 children under the age of five, representing 5.3 percent of all deaths in this age group. Data from Palestine suggest that people who drink municipal water directly are more likely to suffer from diseases such as diarrhea than those who use desalinated and household-filtered drinking water ( Yassin et al., 2006 ). In a comparative study of tap water, purified water, and bottled water, tap water was an essential source of gastrointestinal disease ( Payment et al., 1997 ). Lack of water and sanitation services also increases the incidence of diseases such as cholera, trachoma, schistosomiasis, and helminthiasis. Data from studies in developing countries show a clear relationship between cholera and contaminated water, and household water treatment and storage can reduce cholera ( Gundry et al., 2004 ). In addition to disease, unsafe drinking water, and poor environmental hygiene can lead to gastrointestinal illness, inhibiting nutrient absorption and malnutrition. These effects are especially pronounced for children.

Purpose of This Paper

More than two million people worldwide die each year from diarrhoeal diseases, with poor sanitation and unsafe drinking water being the leading cause of nearly 90% of deaths and affecting children the most (United Nations, 2016). More than 50 kinds of diseases are caused by poor drinking water quality, and 80% of diseases and 50% of child deaths are related to poor drinking water quality in the world. However, water pollution causes diarrhea, skin diseases, malnutrition, and even cancer and other diseases related to water pollution. Therefore, it is necessary to study the impact of water pollution on human health, especially disease heterogeneity, and clarify the importance of clean drinking water, which has important theoretical and practical significance for realizing sustainable development goals. Unfortunately, although many kinds of literature focus on water pollution and a particular disease, there is still a lack of research results that systematically analyze the impact of water pollution on human health and the heterogeneity of diseases. Based on the above background and discussion, this paper focuses on the effect of water pollution on human health and its disease heterogeneity.

Materials and Methods

Search process.

This article uses keywords such as “water,” “water pollution,” “water quality,” “health,” “diarrhea,” “skin disease,” “cancer” and “children” to search Web of Science and Google Scholar include SCI and SSCI indexed papers, research reports, and works from 1990 to 2021.

Inclusion-Exclusion Criteria and Data Extraction Process

The existing literature shows that water pollution and human health are important research topics in health economics, and scholars have conducted in-depth research. As of 30 December 2021, 104 related literatures were searched, including research papers, reviews and conference papers. Then, according to the content relevancy, 19 papers were eliminated, and 85 papers remained. The purpose of this review is to summarize the impact of water pollution on human health and its disease heterogeneity and to explore how to improve human health by improving water pollution control measures.

Information extracted from all included papers included: author, publication date, sample country, study methodology, study purpose, and key findings. All analysis results will be analyzed according to the process in Figure 1 .

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FIGURE 1 . Data extraction process (PRISMA).

The relevant information of the paper is exported to the Excel database through Endnote, and the duplicates are deleted. The results were initially extracted by one researcher and then cross-checked by another researcher to ensure that all data had been filtered and reviewed. If two researchers have different opinions, the two researchers will review together until a final agreement is reached.

Quality Assessment of the Literature

The JBI Critical Appraisal Checklist was used to evaluate the quality of each paper. The JBI (Joanna Briggs Institute) key assessment tool was developed by the JBI Scientific Committee after extensive peer review and is designed for system review. All features of the study that meet the following eight criteria are included in the final summary:1) clear purpose; 2) Complete information of sample variables; 3) Data basis; 4) the validity of data sorting; 5) ethical norms; (6); 7) Effective results; 8) Apply appropriate quantitative methods and state the results clearly. Method quality is evaluated by the Yes/No questions listed in the JBI Key Assessment List. Each analysis paper received 6 out of 8.

The quality of drinking water is an essential factor affecting human health. Poor drinking water quality has led to the occurrence of water-borne diseases. According to the World Health Organization (WHO) survey, 80% of the world’s diseases and 50% of the world’s child deaths are related to poor drinking water quality, and there are more than 50 diseases caused by poor drinking water quality. The quality of drinking water in developing countries is worrying. The negative health effects of water pollution remain the leading cause of morbidity and mortality in developing countries. Different from the existing literature review, this paper mainly studies the impact of water pollution on human health according to the heterogeneity of diseases. We focuses on diarrhea, skin diseases, cancer, child health, etc., and sorts out the main effects of water pollution on human health ( Table 1 ).

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TABLE 1 . Major studies on the relationship between water pollution and health.

Water Pollution and Diarrhea

Diarrhea is a common symptom of gastrointestinal diseases and the most common disease caused by water pollution. Diarrhea is a leading cause of illness and death in young children in low-income countries. Diarrhoeal diseases account for 21% of annual deaths among children under 5 years of age in developing countries ( Waddington et al., 2009 ). Many infectious agents associated with diarrhea are directly related to contaminated water ( Ahmed and Ismail, 2018 ). Parasitic worms present in non-purifying drinking water when is consumed by human beings causes diseases ( Ansari and Akhmatov., 2020 ) . It was found that treated water from water treatment facilities was associated with a lower risk of diarrhea than untreated water for all ages ( Clasen et al., 2015 ). For example, in the southern region of Brazil, a study found that factors significantly associated with an increased risk of mortality from diarrhoea included lack of plumbed water, lack of flush toilets, poor housing conditions, and overcrowded households. Households without access to piped water had a 4.8 times higher risk of infant death from diarrhea than households with access to piped water ( Victora et al., 1988 )

Enteroviruses exist in the aquatic environment. More than 100 pathogenic viruses are excreted in human and animal excreta and spread in the environment through groundwater, estuarine water, seawater, rivers, sewage treatment plants, insufficiently treated water, drinking water, and private wells ( Fong and Lipp., 2005 ). A study in Pakistan showed that coliform contamination was found in some water sources. Improper disposal of sewage and solid waste, excessive use of pesticides and fertilizers, and deteriorating pipeline networks are the main causes of drinking water pollution. The main source of water-borne diseases such as gastroenteritis, dysentery, diarrhea, and viral hepatitis in this area is the water pollution of coliform bacteria ( Khan et al., 2013 ). Therefore, the most important role of water and sanitation health interventions is to hinder the transmission of diarrheal pathogens from the environment to humans ( Waddington et al., 2009 ).

Meta-analyses are the most commonly used method for water quality and diarrhea studies. It was found that improving water supply and sanitation reduced the overall incidence of diarrhea by 26%. Among Malaysian infants, having clean water and sanitation was associated with an 82% reduction in infant mortality, especially among infants who were not breastfed ( Esrey et al., 1991 ). All water quality and sanitation interventions significantly reduced the risk of diarrhoeal disease, and water quality interventions were found to be more effective than previously thought. Multiple interventions (including water, sanitation, and sanitation measures) were not more effective than single-focus interventions ( Fewtrell and Colford., 2005 ). Water quality interventions reduced the risk of diarrhoea in children and reduced the risk of E. coli contamination of stored water ( Arnold and Colford., 2007 ). Interventions to improve water quality are generally effective in preventing diarrhoea in children of all ages and under 5. However, some trials showed significant heterogeneity, which may be due to the research methods and their conditions ( Clasen et al., 2007 ).

Water Pollution and Skin Diseases

Contrary to common sense that swimming is good for health, studies as early as the 1950s found that the overall disease incidence in the swimming group was significantly higher than that in the non-swimming group. The survey shows that the incidence of the disease in people under the age of 10 is about 100% higher than that of people over 10 years old. Skin diseases account for a certain proportion ( Stevenson, 1953 ). A prospective epidemiological study of beach water pollution was conducted in Hong Kong in the summer of 1986–1987. The study found that swimmers on Hong Kong’s coastal beaches were more likely than non-swimmers to complain of systemic ailments such as skin and eyes. And swimming in more polluted beach waters has a much higher risk of contracting skin diseases and other diseases. Swimming-related disease symptom rates correlated with beach cleanliness ( Cheung et al., 1990 ).

A study of arsenic-affected villages in the southern Sindh province of Pakistan emphasized that skin diseases were caused by excessive water quality. By studying the relationship between excessive arsenic in drinking water caused by water pollution and skin diseases (mainly melanosis and keratosis), it was found that compared with people who consumed urban low-arsenic drinking water, the hair of people who consumed high-arsenic drinking water arsenic concentration increased significantly. The level of arsenic in drinking water directly affects the health of local residents, and skin disease is the most common clinical complication of arsenic poisoning. There is a correlation between arsenic concentrations in biological samples (hair and blood) from patients with skin diseases and intake of arsenic-contaminated drinking water ( Kazi et al., 2009 ). Another Bangladesh study showed that many people suffer from scabies due to river pollution ( Hanif et al., 2020 ). Not only that, but water pollution from industry can also cause skin cancer ( Arif et al., 2020 ).

Studies using meta-analysis have shown that exposure to polluted Marine recreational waters can have adverse consequences, including frequent skin discomfort (such as rash or itching). Skin diseases in swimmers may be caused by a variety of pathogenic microorganisms ( Yau et al., 2009 ). People (swimmers and non-swimmers) exposed to waters above threshold levels of bacteria had a higher relative risk of developing skin disease, and levels of bacteria in seawater were highly correlated with skin symptoms.

Studies have also suggested that swimmers are 3.5 times more likely to report skin diseases than non-swimmers. This difference may be a “risk perception bias” at work on swimmers, who are generally aware that such exposure may lead to health effects and are more likely to detect and report skin disorders. It is also possible that swimmers exaggerated their symptoms, reporting conditions that others would not classify as true skin disorders ( Fleisher and Kay. 2006 ).

Water Pollution and Cancer

According to WHO statistics, the number of cancer patients diagnosed in 2020 reached 19.3 million, while the number of deaths from cancer increased to 10 million. Currently, one-fifth of all global fevers will develop cancer during their lifetime. The types and amounts of carcinogens present in drinking water will vary depending on where they enter: contamination of the water source, water treatment processes, or when the water is delivered to users ( Morris, 1995 ).

From the perspective of water sources, arsenic, nitrate, chromium, etc. are highly associated with cancer. Ingestion of arsenic from drinking water can cause skin cancer and kidney and bladder cancer ( Marmot et al., 2007 ). The risk of cancer in the population from arsenic in the United States water supply may be comparable to the risk from tobacco smoke and radon in the home environment. However, individual susceptibility to the carcinogenic effects of arsenic varies ( Smith et al., 1992 ). A high association of arsenic in drinking water with lung cancer was demonstrated in a northern Chilean controlled study involving patients diagnosed with lung cancer and a frequency-matched hospital between 1994 and 1996. Studies have also shown a synergistic effect of smoking and arsenic intake in drinking water in causing lung cancer ( Ferreccio et al., 2000 ). Exposure to high arsenic levels in drinking water was also associated with the development of liver cancer, but this effect was not significant at exposure levels below 0.64 mg/L ( Lin et al., 2013 ).

Nitrates are a broader contaminant that is more closely associated with human cancers, especially colorectal cancer. A study in East Azerbaijan confirmed a significant association between colorectal cancer and nitrate in men, but not in women (Maleki et al., 2021). The carcinogenic risk of nitrates is concentration-dependent. The risk increases significantly when drinking water levels exceed 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Drinking water with nitrate concentrations lower than current drinking water standards also increases the risk of colorectal cancer ( Schullehner et al., 2018 ).

Drinking water with high chromium content will bring high carcinogenicity caused by hexavalent chromium to residents. Drinking water intake of hexavalent chromium experiments showed that hexavalent chromium has the potential to cause human respiratory cancer. ( Zhitkovich, 2011 ). A case from Changhua County, Taiwan also showed that high levels of chromium pollution were associated with gastric cancer incidence ( Tseng et al., 2018 ).

There is a correlation between trihalomethane (THM) levels in drinking water and cancer mortality. Bladder and brain cancers in both men and women and non-Hodgkin’s lymphoma and kidney cancer in men were positively correlated with THM levels, and bladder cancer mortality had the strongest and most consistent association with THM exposure index ( Cantor et al., 1978 ).

From the perspective of water treatment process, carcinogens may be introduced during chlorine treatment, and drinking water is associated with all cancers, urinary cancers and gastrointestinal cancers ( Page et al., 1976 ). Chlorinated byproducts from the use of chlorine in water treatment are associated with an increased risk of bladder and rectal cancer, with perhaps 5,000 cases of bladder and 8,000 cases of rectal cancer occurring each year in the United States (Morris, 1995).

The impact of drinking water pollutants on cancer is complex. Epidemiological studies have shown that drinking water contaminants, such as chlorinated by-products, nitrates, arsenic, and radionuclides, are associated with cancer in humans ( Cantor, 1997 ). Pb, U, F- and no3- are the main groundwater pollutants and one of the potential causes of cancer ( Kaur et al., 2021 ). In addition, many other water pollutants are also considered carcinogenic, including herbicides and pesticides, and fertilizers that contain and release nitrates ( Marmot et al., 2007 ). A case from Hebei, China showed that the contamination of nitrogen compounds in well water was closely related to the use of nitrogen fertilizers in agriculture, and the levels of three nitrogen compounds in well water were significantly positively correlated with esophageal cancer mortality ( Zhang et al., 2003 ).

In addition, due to the time-lag effect, the impact of watershed water pollution on cancer is spatially heterogeneous. The mortality rate of esophageal cancer caused by water pollution is significantly higher downstream than in other regions due to the impact of historical water pollution ( Xu et al., 2019 ). A study based on changes in water quality in the watershed showed that a grade 6 deterioration in water quality resulted in a 9.3% increase in deaths from digestive cancer. ( Ebenstein, 2012 ).

Water Pollution and Child Health

Diarrhea is a common disease in children. Diarrhoeal diseases (including cholera) kill 1.8 million people each year, 90 per cent of them children under the age of five, mostly in developing countries. 88% of diarrhoeal diseases are caused by inadequate water supply, sanitation and hygiene (Team, 2004). A large proportion of these are caused by exposure to microbially infected water and food, and diarrhea in infants and young children can lead to malnutrition and reduced immune resistance, thereby increasing the likelihood of prolonged and recurrent diarrhea ( Marino, 2007 ). Pollution exposure experienced by children during critical periods of development is associated with height loss in adulthood ( Zaveri et al., 2020 ). Diseases directly related to water and sanitation, combined with malnutrition, also lead to other causes of death, such as measles and pneumonia. Child malnutrition and stunting due to inadequate water and sanitation will continue to affect more than one-third of children in the world ( Bartlett, 2003 ). A study from rural India showed that children living in households with tap water had significantly lower disease prevalence and duration ( Jalan and Ravallion, 2003 ).

In conclusion, water pollution is a significant cause of childhood diseases. Air, water, and soil pollution together killed 940,000 children worldwide in 2016, two-thirds of whom were under the age of 5, and the vast majority occurred in low- and middle-income countries ( Landrigan et al., 2018 ). The intensity of industrial organic water pollution is positively correlated with infant mortality and child mortality in less developed countries, and industrial water pollution is an important cause of infant and child mortality in less developed countries ( Jorgenson, 2009 ). In addition, arsenic in drinking water is a potential carcinogenic risk in children (García-Rico et al., 2018). Nitrate contamination in drinking water may cause goiter in children ( Vladeva et al.., 2000 ).

Discussions

This paper reviews the environmental science, health, and medical literature, with a particular focus on epidemiological studies linking water quality, water pollution, and human disease, as well as studies on water-related disease morbidity and mortality. At the same time, special attention is paid to publications from the United Nations and the World Health Organization on water and sanitation health research. The purpose of this paper is to clarify the relationship between water pollution and human health, including: The relationship between water pollution and diarrhea, the mechanism of action, and the research situation of meta-analysis; The relationship between water pollution and skin diseases, pathogenic factors, and meta-analysis research; The relationship between water pollution and cancer, carcinogenic factors, and types of cancer; The relationship between water pollution and Child health, and the major childhood diseases caused.

A study of more than 100 literatures found that although factors such as country, region, age, and gender may have different influences, in general, water pollution has a huge impact on human health. Water pollution is the cause of many human diseases, mainly diarrhoea, skin diseases, cancer and various childhood diseases. The impact of water pollution on different diseases is mainly reflected in the following aspects. Firstly, diarrhea is the most easily caused disease by water pollution, mainly transmitted by enterovirus existing in the aquatic environment. The transmission environment of enterovirus depends on includes groundwater, river, seawater, sewage, drinking water, etc. Therefore, it is necessary to prevent the transmission of enterovirus from the environment to people through drinking water intervention. Secondly, exposure to or use of heavily polluted water is associated with a risk of skin diseases. Excessive bacteria in seawater and heavy metals in drinking water are the main pathogenic factors of skin diseases. Thirdly, water pollution can pose health risks to humans through any of the three links: the source of water, the treatment of water, and the delivery of water. Arsenic, nitrate, chromium, and trihalomethane are major carcinogens in water sources. Carcinogens may be introduced during chlorine treatment from water treatment. The effects of drinking water pollution on cancer are complex, including chlorinated by-products, heavy metals, radionuclides, herbicides and pesticides left in water, etc., Finally, water pollution is an important cause of children’s diseases. Contact with microbiologically infected water can cause diarrhoeal disease in children. Malnutrition and weakened immunity from diarrhoeal diseases can lead to other diseases.

This study systematically analyzed the impact of water pollution on human health and the heterogeneity of diseases from the perspective of different diseases, focusing on a detailed review of the relationship, mechanism and influencing factors of water pollution and diseases. From the point of view of limitations, this paper mainly focuses on the research of environmental science and environmental management, and the research on pathology is less involved. Based on this, future research can strengthen research at medical and pathological levels.

In response to the above research conclusions, countries, especially developing countries, need to adopt corresponding water management policies to reduce the harm caused by water pollution to human health. Firstly, there is a focus on water quality at the point of use, with interventions to improve water quality, including chlorination and safe storage ( Gundry et al., 2004 ), and provision of treated and clean water ( Khan et al., 2013 ). Secondly, in order to reduce the impact of water pollution on skin diseases, countries should conduct epidemiological studies on their own in order to formulate health-friendly bathing water quality standards suitable for their specific conditions ( Cheung et al., 1990 ). Thirdly, in order to reduce the cancer caused by water pollution, the whole-process supervision of water quality should be strengthened, that is, the purity of water sources, the scientific nature of water treatment and the effectiveness of drinking water monitoring. Fourthly, each society should prevent and control source pollution from production, consumption, and transportation ( Landrigan et al., 2018 ). Fifthly, health education is widely carried out. Introduce environmental education, educate residents on sanitary water through newspapers, magazines, television, Internet and other media, and enhance public health awareness. Train farmers to avoid overuse of agricultural chemicals that contaminate drinking water.

Author Contributions

Conceptualization, XX|; methodology, LL; data curation, HY; writing and editing, LL; project administration, XX|.

This article is a phased achievement of The National Social Science Fund of China: Research on the blocking mechanism of the critical poor households returning to poverty due to illness, No: 20BJY057.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Keywords: water pollution, human health, disease heterogeneity, water intervention, health cost

Citation: Lin L, Yang H and Xu X (2022) Effects of Water Pollution on Human Health and Disease Heterogeneity: A Review. Front. Environ. Sci. 10:880246. doi: 10.3389/fenvs.2022.880246

Received: 21 February 2022; Accepted: 09 June 2022; Published: 30 June 2022.

Reviewed by:

Copyright © 2022 Lin, Yang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Xiaocang Xu, [email protected]

This article is part of the Research Topic

Bioaerosol Emission Characteristics and the Epidemiological, Occupational, and Public Health Risk Assessment of Waste and Wastewater Management

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  • Published: 31 March 2021

Plant health and its effects on food safety and security in a One Health framework: four case studies

  • David M. Rizzo 1 ,
  • Maureen Lichtveld 2 ,
  • Jonna A. K. Mazet 3 ,
  • Eri Togami 3 &
  • Sally A. Miller   ORCID: orcid.org/0000-0001-9611-0535 4  

One Health Outlook volume  3 , Article number:  6 ( 2021 ) Cite this article

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Although healthy plants are vital to human and animal health, plant health is often overlooked in the One Health literature. Plants provide over 80% of the food consumed by humans and are the primary source of nutrition for livestock. However, plant diseases and pests often threaten the availability and safety of plants for human and animal consumption. Global yield losses of important staple crops can range up to 30% and hundreds of billions of dollars in lost food production. To demonstrate the complex interrelationships between plants and public health, we present four case studies on plant health issues directly tied to food safety and/or security, and how a One Health approach influences the perception and mitigation of these issues. Plant pathogens affect food availability and consequently food security through reductions in yield and plant mortality as shown through the first case study of banana Xanthomonas wilt in East and Central Africa. Case studies 2, 3 and 4 highlight ways in which the safety of plant-based foods can also be compromised. Case study 2 describes the role of mycotoxin-producing plant-colonizing fungi in human and animal disease and examines lessons learned from outbreaks of aflatoxicosis in Kenya. Plants may also serve as vectors of human pathogens as seen in case study 3, with an example of Escherichia coli (E. coli) contamination of lettuce in North America. Finally, case study 4 focuses on the use of pesticides in Suriname, a complex issue intimately tied to food security though protection of crops from diseases and pests, while also a food safety issue through misuse. These cases from around the world in low to high income countries point to the need for interdisciplinary teams to solve complex plant health problems. Through these case studies, we examine challenges and opportunities moving forward for mitigating negative public health consequences and ensuring health equity. Advances in surveillance technology and functional and streamlined workflow, from data collection, analyses, risk assessment, reporting, and information sharing are needed to improve the response to emergence and spread of plant-related pathogens and pests. Our case studies point to the importance of collaboration in responses to plant health issues that may become public health emergencies and the value of the One Health approach in ensuring food safety and food security for the global population.

Background: plant health as part of one health

Although plant health is currently part of the definition of One Health [ 1 ], plants have typically not been well integrated into discussions of One Health approaches [ 2 , 3 ]. However, plant health is vital to sustain human and animal health and a critical component of the complex interactions among the environment, humans, and animals. Recognizing the key role of plants in public health, the United Nations declared the year 2020 to be the International Year of Plant Health (IYPH) [ 4 , 5 ]. The overarching purpose of the IYPH was to raise awareness of plant health and its effects on society [ 4 ]. Maintaining plant health has important consequences for human and animal health as an important driver of food security and safety, as a source of livelihoods in plant-based agriculture, as a source of pharmaceuticals, and as part of healthy environments [ 3 , 6 , 7 , 8 , 9 ].

Plants provide over 80% of the food consumed by humans and are the primary source of nutrition for livestock [ 5 ]. Food security—the state of having reliable access to sufficient, safe, affordable, and nutritious food at all times—is necessary to have healthy and productive societies [ 7 , 10 ]. Food security is also a crucial aspect of One Health and is a pillar of the United Nations Sustainable Development Goals (SDGs) [ 11 , 12 ]. The UN definition of food security identified four key pillars: 1) availability, 2) access (both economic and socio-cultural), 3) utilization, including food preparation and safety, and 4) lastly the stability of these three pillars [ 13 ]. Food security thus reflects a complex value chain of production, food processing and distribution, and food access, beginning with plant health in the field. Employing a One Health approach to ensure the safety and continuity of this value chain will result in the protection and advancement of public health.

Plant diseases and pests influence the availability and safety of plants for human and animal consumption, reduce crop yield and detrimentally affect quality [ 9 , 14 ]. Measures to prevent or treat diseases, including application of pesticides, may adversely impact the health of agricultural workers and consumers, as well as drive the development of antimicrobial and antifungal resistance in pathogens [ 15 , 16 ]. In addition, food plants may serve as carriers of human pathogens and harmful microbial-based toxins. For example, foodborne illnesses pose a serious global burden on human health, reportedly affecting 600 million people or 33 million Disability Adjusted Life Years (DALYs) in a single year [ 17 ]. Although international food standards, such as the Codex Alimentarius, are implemented to protect consumers’ health and fair trade, foodborne illnesses continue to affect high-, middle-, and low-income countries around the world [ 17 , 18 ]. Plants are important origins of foodborne outbreaks, including fresh vegetables and fruits irrigated with, washed with, or exposed to water and soil contaminated with pathogens of animal or human origin. More than half (51%) of outbreak-associated illnesses in the US were traced to plant-foods over a 10-year period, higher than any other food commodity, such as meat, fish, and dairy products [ 19 ]. Additionally, antibiotic resistant bacteria and resistance genes originating from animal feces can also contaminate fresh produce and pose health risks for humans [ 20 ]. Therefore, a key aspect of food security is timely and effective management of plant pathogens and pests and other microbes associated with plants that can cause foodborne illnesses, often disproportionately impacting the most vulnerable and health disparate populations locally and globally.

The emergence of new variants of pathogens and pests, as well as the expansion of the geographic range of known ones, can cause significant disruption in food production and pose a burden on the global economy. Global yield losses of important staple crops to pathogens and pests can range up to 30% with estimated costs to the global economy due to lost food production in the hundreds of billions of dollars [ 7 ]. Effective pest and disease management approaches, including pesticide management strategies, are required to successfully prevent and mitigate these issues. Recognition of and action to address the need for quantification of crop losses and their impact on humans, plants, animals, and land use are critically important [ 2 , 10 , 21 ]. Traditional surveillance strategies are often expensive and associated with a delay in problem recognition and access to actionable data. The lack of time-sensitive responses to foodborne outbreaks negatively impacts public health and the food service industry.

To show the complex interrelationships between plants and public health, and to demonstrate the value of the One Health approach, we review four cases studies. One study shows the relationship between plant health and food security. Two case studies involving a naturally-occurring pathogen (one plant-based and one animal-based) show the relationship between plant food safety and human health. The final case study involving a man-made toxin represents a study of both food security and food safety. Through these case studies, we examine challenges and opportunities moving forward for mitigating negative public health consequences and ensuring health equity.

Case studies

Case study 1: plant pathogens and food availability: banana xanthomonas wilt in east and central africa, 2001-present (fig.  1 ; fig.  2 -1).

Based on currently available data, up to 30% of global staple food crops are lost annually due to plant pests, including diseases, insects, and weeds, but excluding abiotic factors such as drought, excessive water, or poor soils [ 7 ]. When diseases severely affect staple crops in low income or under-resourced regions of the world, food availability is threatened, potentially resulting in malnutrition and population-based famine in severe cases. In addition, loss of income from cash crops sold by small commercial farms can have a cascading effect, exacerbating poverty among populations who depend upon farmers to purchase goods and services from the rural non-farm sector.

figure 1

Rotting banana fruit caused by the bacterial phytopathogen Xanthomonas campestris pathovar musacearum in Uganda. The disease (banana Xanthomonas wilt) also causes wilting and death of banana plants and significant reductions in availability of this staple food in East and Central Africa (source S. Miller)

figure 2

Case studies and linkages to One Health as discussed in the text. The studies illustrate different examples of the interconnectedness of plant, animal and human health, and the negative consequences of plant health problems to public health

Bananas ( Musa spp.), including dessert banana, plantain, and cooking banana, comprise the eighth most important food crop in the world and the fourth most important in low- and middle-income countries in terms of gross production value [ 22 ]. Bananas are a staple crop and important source of protein, starch, vitamins, and minerals in East and Central Africa, ranging from 20% of household food consumption each day in Uganda to 80% in Rwanda [ 23 ]. Bananas historically had been among the least expensive of the staple crops to produce [ 24 ]. They have multiple uses in crop production systems, such as cycling carbon and soil nutrients, preventing soil erosion, and providing shade for understory crops [ 23 ]. Additionally, bananas are a source of food for livestock and used for the production of goods such as baskets, carpets, and shoes [ 23 ].

Banana Xanthomonas wilt (BXW) is an invasive bacterial disease first observed in Uganda in 2001, where it developed into a severe epidemic within 4 years of emergence and spread to the Democratic Republic of the Congo, Rwanda, Kenya, Tanzania, and later to Burundi [ 22 ]. BXW is caused by Xanthomonas campestris pathovar musacearum , a gram-negative rod-shaped bacterium that enters the plant through wounds or natural openings, colonizes the plant’s vascular system, and causes wilting, fruit rotting, and plant death [ 22 ]. The disease is spread by planting infected banana pseudostems, by various insects that visit the male flowers, by wind-driven rain, and by using contaminated cutting tools [ 22 ].

During the peak of the 2000–2010 epidemic in heavily affected areas of Tanzania, Burundi, and Rwanda, there were significant harmful effects on food production, availability, and subsequently, household consumption practices [ 25 ]. For example, the production of banana beer and juice declined approximately 60%, and the number of banana bunches sold and consumed declined 35 and 25% respectively, compared to pre-BXW levels. Importantly, the BXW epidemic greatly affected the availability of bananas, because the price of banana bunches increased by 46% compared to pre-BXW levels. As a result of reduced banana availability and higher prices, households coped by eating fewer meals than usual, eating smaller meals than needed, or substituting bananas with other available food items, such as maize, cassava, or sweet potatoes. Increased food prices have a disproportionate influence on low income households, often already struggling to meet basic needs. Loss of bananas from cropping systems may also result in damage to the environment (soil erosion) and reduced crop productivity (loss of shade) [ 26 ]. Long-term impacts of BXW epidemics on human nutrition and health, poverty, the environment and cultural practices in East and Central Africa have not yet been determined.

There are no effective antibiotics or other pharmaceutical treatments available for BXW. However, the disease can be managed by adoption of specific farming practices, including removing the male flower buds to reduce insect transmission of the pathogen, removing or burning affected plant pseudostems, decontaminating farm tools after each use, and using disease-free planting materials [ 26 ]. The cost and complexity of these disease management practices pose barriers to adoption by farmers [ 27 ]. Deployment of BXW-resistant varieties would be a significant step forward in managing this disease locally and reducing its spread. However, banana breeding is extremely slow and difficult, and sources of resistance to BXW have not been found in cultivated banana. Musa balbisiana is the only known source of resistance but is not preferred for breeding due to genome configuration differences [ 28 ]. Genetically engineered (GE) bananas resistant to BXW have been developed and tested extensively in field trials [ 22 , 29 ]. In Uganda, which has been particularly hard-hit by BXW, it has been estimated that adoption of GE bananas could benefit farmers by $15 million and consumers by $10 million annually and could result in 55,000 people escaping poverty each year. BXW-resistant GE banana varieties may be available for distribution by 2023, if an appropriate biosafety regulatory system is in place. However, for Uganda and other countries affected by BXW, political considerations based on public perceptions of GMO foods may delay or even stop the implementation of the necessary regulatory systems [ 30 ]. In the meantime, increased adoption of BXW cultural management practices can be better facilitated by effective training programs such as farmer field schools and refining disease management strategies into more feasible and easy-to-implement recommendations. These include limiting removal of BXW-affected plants to dry periods when the disease is least likely to spread, covering cut plant stems with soil and sterilizing tools in fire pits within banana fields [ 26 ]. Furthermore, leveraging advances in technology to track transmission patterns by using innovative citizen science strategies as well as collaboration between scientists and farmers to improve training, can accelerate progress toward prevention of BXW. Specifically, citizen science and information communication technologies can accelerate the identification of new outbreaks, information sharing can enable rapid decision making among farmers, and enhanced connectivity among stakeholders can create networks for collective action [ 31 ].

Case study 2: food safety and mycotoxins: aflatoxicosis outbreak in Kenya, 2004–2005 (Fig. 2 -2)

Aflatoxin B 1 is a type of mycotoxin produced by Aspergillus flavus and A. parasiticus [ 32 ]. Mycotoxins, which are small molecular-weight fungal metabolites, are produced on a wide array of food plants and are toxic to animals and humans [ 33 ]. Aflatoxins can contaminate human foods such as cereals, roots, nuts, and pulses under favorable conditions such as high temperatures, high humidity, and drought stress, which lead to plant colonization by the A. flavus and A. parasiticus molds [ 32 ]. In 2004–2005, aflatoxin contamination of maize—a major staple food in Kenya—was found to be the cause of a severe outbreak of acute liver disease in eastern Kenya, resulting in 317 cases, including 125 deaths [ 33 ]. The primary risk factor for aflatoxicosis in this event was the consumption of homegrown maize, followed by storage of wet grain in the home [ 33 ]. Aflatoxin B 1 concentrations in stored maize in affected households were up to 50 times the limit prescribed for food in Kenya [ 33 ]. Chronic aflatoxin B 1 contamination is a risk factor for acute liver damage, which may lead to chronic illnesses including liver cancer and immune system suppression [ 32 ].

The toxicity, morbidity, and potentially lethal effects of aflatoxin, as observed in the Kenya outbreak, highlight the significance of aflatoxin as an important public health challenge. Humans are exposed to aflatoxins through contaminated food crops or by consuming products from animals that have been exposed to contaminated feed. Aflatoxin contamination threatens the health and wellbeing of already vulnerable populations, such as children and individuals with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections [ 32 ]. Children are especially susceptible to aflatoxins and can suffer short- and long-term effects such as malnutrition and stunting [ 32 ]. Additionally, chronic exposure to aflatoxins disproportionately affects low-resourced populations, with an estimated 5 billion people in low- and middle-income countries (LMICs) at risk of chronic exposure to aflatoxins [ 34 ].

Chronic exposure to aflatoxins has detrimental effects on animal health and can cause growth inhibition and immune suppression [ 32 ]. Consequently, health risks to animals and humans alike and compounding impacts on livelihoods result when aflatoxicosis is not prevented. Limited availability of food, lack of regulatory systems for monitoring and controlling aflatoxin, and environmental conditions that favor fungal development in crops are some of the common factors that increase the likelihood of aflatoxin poisoning [ 32 ]. Therefore, preventing and mitigating aflatoxin poisoning requires employing a One Health approach to protect human, plant, and animal health.

Ultimately, prevention and mitigation of aflatoxin contamination of food and feed, particularly in LMICs that often lack the expertise and infrastructure to effectively prevent and interdict aflatoxin contamination, require multi-pronged, economically-feasible, integrated approaches supported by private and public sector entities. For example, the appropriate and recommended use of irrigation and insecticides during the pre-harvest period and hand sorting of grains and effective rodent control during the post-harvest period could mitigate risks of aflatoxin contamination. Increasing awareness of the burden of aflatoxin exposure on public health is critical to encourage implementation of these strategies. In response to the deadly 2004–2005 outbreak in Kenya, Kenyan government agencies investigated the cause and established the National Food Safety Coordinating Committee in 2006, active at the policy level and coordinating mycotoxin testing in food and feed, inspection, enforcement, education, and program monitoring and evaluation [ 35 ]. A holistic, coordinated approach including plant, animal, and public health research and practice is necessary to address the gaps in knowledge, technology and education to prevent aflatoxicosis. These include insufficient documentation of human exposure, lack of measurements of economic impacts of aflatoxin contamination throughout various value chains and analyses of long-term impacts of aflatoxin mitigation approaches, inadequate sampling of grains on smallholder farms and storage facilities, lack of consumer awareness of the attributes associated with aflatoxin contamination and absence of economic incentives for the production and/or marketing of low-aflatoxin grain [ 35 , 36 ].

Case study 3: human pathogens associated with plants and food safety: E. coli O157:H7 outbreak caused by romaine lettuce in the United States and Canada, 2018–2019 (Fig. 2 -3)

Between October 2018 and January 2019, a foodborne outbreak of Shiga-toxin producing E.coli O157:H7 (STEC) resulted in 91 illnesses and 35 hospitalizations, including four cases of hemolytic uremic syndrome (HUS) but no deaths, in multiple areas of the United States (US) and Canada [ 37 , 38 ]. Fortunately, the outbreak was detected in its early stages by US and Canadian surveillance systems, including FoodNet and PulseNet, and on November 1, 2018 the US Food and Drug Administration (FDA), CDC, Canadian Food Inspection Agency (CFIA), and Public Health Agency of Canada initiated a multi-agency outbreak investigation. On November 20, FDA issued a public health advisory warning to consumers not to eat romaine lettuce until further notice, a bold and atypical advisory against a type of produce without identifying its farm of origin. In Canada, CFIA advised industry not to import, distribute, or sell romaine lettuce during the investigation. Ultimately, trace back of suspected food ingredients, field visits, and laboratory testing, including whole-genome sequencing, determined that the cause of the outbreak was in fact romaine lettuce produced on a farm in Santa Barbara, California, whose irrigation system was implicated as the contamination source for E. coli O157:H7. Genetic characterization of the pathogens revealed that the DNA footprints of the E. coli strains in this outbreak were genetically closely linked among cases, as well as related to a previous E. coli outbreak that affected the US and Canada in December 2017 [ 37 , 38 , 39 ]. By early January 2019, despite its extensive geographical spread, the outbreak was contained and declared over within 11 to 14 weeks since the recognition of illness in the initial cases in both the US and Canada.

By employing One Health approaches to food surveillance, public health, and animal health, and taking rapid actions as demonstrated during this outbreak, public health officials will be better able to understand the source of foodborne illnesses, rapidly enabling and informing prevention and mitigation measures for future outbreaks. It is important to consider that the intestinal tracts of healthy ruminant animals are reservoirs of E. coli O157:H7, and cattle feces are believed to be a major source for human illness [ 40 ]. Shedding of E. coli O157:H7 by cattle is influenced by seasonality, food production strategies, and life stage of cattle. In addition, the pathogen can persist in the environment, such as in water troughs, in animal feces that are not removed expeditiously, and on feedlots [ 41 ]. In this outbreak, there was no conclusive evidence that the water was contaminated from domestic ruminant feces. However, the final investigation highlighted that ruminant intestinal tracts are well-established reservoirs for E. coli O157:H7. Wildlife and humans can also be sources of bacterial contamination of the food supply, and investigators noted “evidence of extensive wild animal activity, including waterfowl, rodents, coyotes, etc., and animal burrows near the contaminated reservoir sediment,” likely warranting intensive exploration in future outbreaks, including water supplies. In California, this and other foodborne outbreaks have highlighted the importance of complying with, and accelerated the implementation of, local and national produce safety practices, such as the Produce Safety Rule under the Food Safety Modernization Act of the FDA which came into effect in 2016 [ 42 , 43 ]. Farmers are required to reduce the likelihood of direct or indirect contamination of produce with wildlife fecal material through soil, water, vehicles, and other means of transmission and have taken an active role in preventing foodborne illnesses as integral stakeholders for protecting public health.

The successful rapid containment of this large-scale STEC outbreak can be attributed to early detection of the event through robust surveillance systems, swift multi-agency coordination with an employment of the One Health approach, use of whole genome sequencing for E. coli characterization, and timely and appropriate issuance of a broad public health advisory. Plant, environmental, animal, and human health experts will likely continue to be challenged by the burden of foodborne illnesses, which should be addressed by continuing to coordinate multi-agency prevention, detection, response, and containment strategies; incorporating state-of-the art technologies to identify pathogens; and balancing the benefits of protecting the health of populations with the economic cost of issuing prompt public safety advisories.

Case study 4: pesticide use in plant-based agriculture and food security and safety in Suriname, 2010–2015 (Fig. 2 –4; Fig.  3 )

Suriname, a middle-income country located on the northeastern coast of South America, has one of the highest pesticide use rates per area crop land in the Caribbean (8.8 kg/ha). Pesticides are intended for preventing, destroying, repelling, or mitigating any pest [ 44 ]. They can be classified according to the target organism (most commonly: insecticides, herbicides, and fungicides), or molecular structure (such as insecticides categorized as organophosphates, carbamates, organochlorines, pyrethroids, and neonicotinoids). The term pesticide in this case study will refer to chemical pesticides that are used for agricultural purposes.

figure 3

Manual application of pesticides (center) with potential exposure of workers during manual crop maintenance operations in Southeast Asia (Source: S. Miller)

Agriculture is a developing sector in Suriname, which contributes approximately 9% to the Gross Domestic Product (GDP) and employs 17% of the population [ 45 , 46 ]. Screening data from the Dutch Food and Consumer Product Safety Authority (NVWA) from 2010 to 2015 consistently showed pesticide residues in crops imported from Suriname [ 47 ]. The Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) is examining the association of pesticide exposure to birth outcomes in 1000 mother/child dyads [ 48 ]. CCREOH’s preliminary environmental assessment showed pesticide residues in Surinamese produce, including the insecticides endosulfan and lindane in the leafy vegetable Xanthosoma brasiliense (tannia). According to an interviewer-assisted dietary survey, which was administered to assess dietary exposure to pesticides in Surinamese women (including 696 pregnant women), women living in non-urban districts and less educated women were more likely to have a higher tannia intake rate compared to those living in urban districts and women who received higher levels of education [ 47 ]. This disparity in exposure to tannia illustrates how pesticide use can have inequitable consequences for food safety based on region and education level.

Pesticides play an important role in food security by protecting crops from pests and diseases, leading to improved productivity. However, the misuse of pesticides may lead to residues in produce, potentially compromising food safety [ 49 ]. In addition, the use of banned pesticides continues to be a problem in low-income countries. Due to financial constraints and lack of policy and enforcement, less favorable (older, more toxic and environmentally persistent) pesticides are being used in these countries [ 50 ].

Chronic low-level pesticide exposures, such as through diet, are harmful to human health and have been associated with depression and neurodegenerative disease in adults [ 51 , 52 ]. Furthermore, exposure during gestation and the early postnatal period has been associated with a lower birth weight, decreased gestational age, and neuro-developmental toxicity that can lead to motor- and neurocognitive developmental delays in children [ 53 , 54 ]. In addition, the presence of pesticide residues in plants and the environment has been linked to the emergence of antimicrobial resistant organisms [ 15 ]. Recently, the use of triazole fungicides in certain horticultural systems in Europe has been linked to the emergence of azole-resistant environmental isolates of Aspergillus fumigatus and subsequent fatal human aspergillosis cases [ 55 ]. Especially in the case of Suriname, the greenest country in the world with biodiverse and unique flora and fauna, it is important to consider the possible negative consequences of pesticides on wildlife, such as loss of species and declines in diversity [ 56 , 57 , 58 ].

Appropriate use of pesticides is important for safeguarding food security, food safety, and health equity. While pesticide use is highly regulated in high income countries, there is an urgent need in LMICs to formulate policies on pesticide residues in plants and the environment, such as monitoring and reporting levels of pesticide residues. In Suriname, the development and implementation of national pesticide policies are limited, and the country does not monitor pesticide residues in crops. Although there is currently no policy on the emergence and spread of resistance in plant pathogens associated with pesticides, guidance exists for developing comprehensive action plans to address these potential threats.

Training farmers to use pesticides correctly and screening pesticide residues in crops are pivotal to reducing human risk of pesticide exposure. In addition, approaches to reduce the use of pesticides should be implemented. A well-known strategy is Integrated Pest Management (IPM), which prioritizes the use and integration of multiple cultural, biological, and host resistance strategies, while reducing pesticide use, to manage pests and diseases of plants and animals [ 59 ]. IPM is geared toward improving economic benefits of production systems and reducing human health risks and adverse environmental effects of pesticide use. Ultimately, implementation of IPM, development and enforcement of international recommendations and national policies, and equipping of farmers with the knowledge and means to use pesticides appropriately will minimize pesticide residues in food and the environment and enable economically sustainable food production while reducing adverse health effects in people.

Conclusions

Threats to plant health pose challenges to population health, productivity, and prosperity across the globe. Efforts to protect plants from emerging and endemic pathogens and pests help to not only increase food security and safety to ensure healthy lives, but also to alleviate poverty, promote equity, confront the impact of climate change, protect the environment, boost economic development, and strengthen global partnerships. Establishing a much closer partnership among advocates for One Health, including experts in sustainable agriculture, and public health practitioners will lead to promoting a safe, sustainable, and nutritious diet for families worldwide.

The case studies presented above demonstrate how management practices aimed at reducing crop losses and ensuring food safety would benefit from employment of a One Health approach. Outbreaks of emerging pathogens can be mitigated by mobilizing experts and resources from all arms of One Health to elevate integrated research and development in human, animal, and plant health. For example, protecting bananas from the harmful effects of banana Xanthomonas wilt and alleviating the shortage of food caused by the disease involves a framework that highlights the interaction and interdependence of physical and socio-cultural factors across all levels of a health problem [ 60 ]. This involves effective integrated training on individual and organizational levels; collaboration with plant, environmental, and animal health specialists on the interpersonal level; and implementation of feasible policies on the community and society levels. Similar approaches can be utilized in ensuring food safety, as evidenced in the cases of aflatoxicosis, E. coli , and pesticide use. The 2004 case of aflatoxicosis in Kenya resulted in an intervention on the societal and policy levels with positive effects observed by individuals, communities and organizations. Suriname’s case of pesticide use and safety concerns exhibits a need for societal policy interventions that lead to positive cascading effects on the economy and other parts of society.

The relationship between plant health and human health is especially important in public health and illustrates a need for research specifically focused on the direct and indirect effects of compromised plant health to human populations. Research and development that allows for inclusion of multiple potential causes for public health concern, including plant diseases and pests that endanger human and animal health and wellbeing, is vital for holistically preventing and mitigating the effects of public health threats. To successfully and effectively protect plant health and address food security, there will need to be a stronger regulatory framework, effective surveillance and monitoring systems, feasible disease management practices, and effective training of food production professionals in protecting plant, animal, environmental, and human health. Our case studies also point to the importance of interagency coordination in facilitating rapid responses to public health emergencies, benefits of technological advances that facilitate data sharing, and the value of the One Health approach in ensuring food safety and food security for the global population.

Availability of data and materials

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Abbreviations

Banana Xanthomonas wilt

Caribbean consortium for research in environmental and occupational health

Canadian Food Inspection Agency

Gross domestic product

Hepatitis C virus

Hemolytic uremic syndrome

Integrated pest management

International year of plant health

Low- and middle-income countries

Sustainable development goals

Shiga-toxin producing E. coli

United Nations

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Acknowledgements

We are thankful for the intellectual input from members and staff of the One Health Action Collaborative and the Forum on Microbial Threats of the National Academies of Sciences, Engineering, and Medicine. Special thanks to Chris Braden, Gail Hansen, James Hughes, Ayano Ogawa, Edith Amponsah, Mary Wilson, and Firoz Abdoel Wahid for their contributions to this paper. We also thank NASEM for financial support of this effort.

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DMR and SAM led the conceptualization of the manuscript. DMR wrote the introduction and conclusion sections, SAM wrote case studies 1 and 2, JM and ET wrote case study 3, and ML wrote case study 4. All authors contributed to manuscript editing and read and approved the final manuscript.

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Rizzo, D.M., Lichtveld, M., Mazet, J.A.K. et al. Plant health and its effects on food safety and security in a One Health framework: four case studies. One Health Outlook 3 , 6 (2021). https://doi.org/10.1186/s42522-021-00038-7

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Case Study Questions Class 12 Biology Human Health and Disease

Case study questions class 12 biology chapter 8 human health and disease.

CBSE Class 12 Case Study Questions Biology Human Health and Disease. Term 2 Important Case Study Questions for Class 12 Board Exam Students. Here we have arranged some Important Case Base Questions for students who are searching for Paragraph Based Questions Human Health and Disease.

At Case Study Questions there will given a Paragraph. In where some Important Questions will made on that respective Case Based Study. There will various types of marks will given 1 marks, 2 marks, 3 marks, 4 marks.

CBSE Case Study Questions Class 12 Biology Human Health and Disease

Case study 1:.

Our mind and mental state can affect our health. Of course, health is affected by- (i) genetic disorders – deficiencies with which a child is born and deficiencies/defects which the child inherits from parents from birth; (ii) infections and (iii) life style including food and water we take, rest and exercise we give to our bodies, habits that we have or lack etc. When the functioning of one or more organs or systems of the body is adversely affected, characterised by appearance of various signs and symptoms, we say that we are not healthy, i.e., we have a disease. Diseases can be broadly grouped into infectious and non-infectious.

Diseases which are easily transmitted from one person to another, are called infectious diseases. Infectious diseases are very common and every one of us suffers from these at some time or other. Some of the infectious diseases like AIDS are fatal. Among non-infectious diseases, cancer is the major cause of death. Drug and alcohol abuse also affect our health adversely.

Que. 1) Which of the following thing mainly affects health?

(a) Life style

(b) Education

(c) Genetic disorder

(d) Both (a) and (b)

Que. 2) When the child is born with some deficiencies then it is ……………………………………………………………………… .

(a) Heart disease

(b) Genetic disorder

(c) Obesity

(d) Infections

Que. 3) If a person’s organ or organ system is affected then the symptoms will appear. And the person can say ……………………………………………………………… .

(a) I am healthy.

(b) I am in good state.

(c) I am unhealthy.

(d) I am resting.

Que. 4) Define the term ‘Infectious disease’ and write an example.

Que. 5) Identify ‘B’

Que. 1) (d) Both (a) and (b)

Que. 2) (b) Genetic disorder

Que. 3) (c) I am unhealthy.

Que. 4) Answer: Transmission of the diseases from one person to another is called as Infectious diseases. AIDs is an example of infectious disease.

Case Study 2:

A wide range of organisms belonging to bacteria, viruses, fungi, protozoans, helminths, etc., could cause diseases in man. Such disease causing organisms are called pathogens. Most parasites are therefore pathogens as they cause harm to the host by living in (or on) them. The pathogens can enter our body by various means, multiply and interfere with normal vital activities, resulting in morphological and functional damage. Pathogens have to adapt to life within the environment of the host. For example, the pathogens that enter the gut must know a way of surviving in the stomach at low pH and resisting the various digestive enzymes. A few representative members from different groups of pathogenic organisms are discussed here along with the diseases caused by them. Preventive and control measures against these diseases in general, are also briefly described. Salmonella typhi is a pathogenic bacterium which causes typhoid fever in human beings. These pathogens generally enter the small intestine through food and water contaminated with them and migrate to other organs through blood. Sustained high fever (39° to 40°C), weakness, stomach pain, constipation, headache and loss of appetite are some of the common symptoms of this disease. Intestinal perforation and death may occur in severe cases.

Typhoid fever could be confirmed Widal test : A classic case in medicine, that of Mary Mallon nicknamed Typhoid Mary, is worth mentioning here. She was a cook by profession and was a typhoid carrier who continued to spread typhoid for several years through the food she prepared.

Que. 1) In a classic case, who was spreading typhoid by cooking?

(a) Mary Mallon

(b) Typhoid Cook

(c) Classic Mallon

(d) Mary Classic

Que. 2) Which of the following is a pathogenic bacterium?

(a) Plasmodium vivax

(b) Salmonella typhi

(c) Entamoeba histolytica

(d) Aedes Aegypti

Que. 3) The organisms like viruses, helminths, protozoa and bacteria which are responsible for causing disease in man are known as ……………………………………………………………………………………… .

(a) Non-Infectious

(b) Enzymes

(c) Typhoid

(d) Pathogens

Que. 4) Write the name of pathogenic bacteria that causes typhoid and its symptoms.

Que. 5) Why most of parasites are pathogens?

Que. 1)(a) Mary Mallon.

Que. 2) (b) Salmonella typhi .

Que. 3) (d) Pathogens.

Que. 4) Answer: A pathogenic bacterium that causes typhoid fever in humans is Salmonella typhi . Salmonella typhi causes typhoid by entering small intestine. The common symptoms of typhoid disease are weakness, high fever, and loss of appetite, constipation, and headache.

Que. 5) Parasites live in or on the host and causes harm to the host. Hence, most of parasites are pathogens.

Case Study 3:

Bacteria like Streptococcus pneumoniae and Haemophilus influenzae are responsible for the disease pneumonia in humans which infects the alveoli (air filled sacs) of the lungs. As a result of the infection, the alveoli get filled with fluid leading to severe problems in respiration. The symptoms of pneumonia include fever, chills, cough and headache. In severe cases, the lips and finger nails may turn gray to bluish in colour. A healthy person acquires the infection by inhaling the droplets/aerosols released by an infected person or even by sharing glasses and utensils with an infected person. Dysentery, plague, diphtheria, etc., are some of the other bacterial diseases in man. Many viruses also cause diseases in human beings. Rhino viruses represent one such group of viruses which cause one of the most infectious human ailments – the common cold. They infect the nose and respiratory passage but not the lungs.

The common cold is characterised by nasal congestion and discharge, sore throat, hoarseness, cough, headache, tiredness, etc., which usually last for 3-7 days. Droplets resulting from cough or sneezes of an infected person are either inhaled directly or transmitted through contaminated objects such as pens, books, cups, doorknobs, computer keyboard or mouse, etc., and cause infection in a healthy person.

Que. 1) Which organ in the humans get affected by pneumonia disease?

(a) Stomach

(d) Bladder

Que. 2) Rhino virus can infect ………………………………………………………………………… in the humans.

Que. 3) By which of the following reason, an healthy person can acquire pneumonia disease?

(a) By exhaling droplets of non-infected person.

(b) By headache or leg pain.

(c) By eating fast food.

(d) By inhaling droplets of infected person.

Que. 4) How long does common cold last?

Que. 5) Write any two symptoms of common cold and pneumonia.

Que. 1)(c) Lungs

Que. 2) (b) Nose

Que. 3) (d) By inhaling droplets of infected person.

Que. 4) Answer: Common cold usually last for three to Seven days.

Que. 5) Answer: Common cold manly infects respiratory passage and pneumonia mainly infects alveoli. Symptoms of common cold are sore throat, cough and headache etc., and symptoms of pneumonia are fever, cough and chills etc. Fingers and lips turn gray to bluish colour in severe cases.

Case Study 4:

Ascaris, the common round worm and Wuchereria, the filarial worm, are some of the helminths which are known to be pathogenic to man. Ascaris, an intestinal parasite causes ascariasis. Symptoms of these disease include internal bleeding, muscular pain, fever, anemia and blockage of the intestinal passage. The eggs of the parasite are excreted along with the faeces of infected persons which contaminate soil, water, plants, etc. A healthy person acquires this infection through contaminated water, vegetables, fruits, etc. Wuchereria (W. bancrofti and W. malayi), the filarial worms cause a slowly developing chronic inflammation of the organs in which they live for many years, usually the lymphatic vessels of the lower limbs and the disease is called elephantiasis or filariasis. The genital organs are also often affected, resulting in gross deformities. The pathogens are transmitted to a healthy person through the bite by the female mosquito vectors.

Many fungi belonging to the genera Microsporum, Trichophyton and Epidermophyton are responsible for ringworms which is one of the most common infectious diseases in man. Appearance of dry, scaly lesions on various parts of the body such as skin, nails and scalp are the main symptoms of the disease.

Que. 1) If a person is having dry and scaly lesions on various parts of the body, then the person is infected by …………………………………………………………………. Disease.

(a) Ringworm

(b) Roundworm

(c) Filarial worm

(d) Earthworm

Que. 2) A healthy person can have infection of Ascaris through ………………………………………………………………………………… .

(a) Moisture

(b) Mosquito

(d) Contaminated food and water

Que. 3) The disease filariasis can transmit to a healthy person through ……………………………………………………………………………… .

(a) Through fungi

(b) Through round worm

(c) Through female mosquito bite

(d) Through ringworms

Que. 4) Name any two genera of the fungi which are responsible for causing ringworms.

Que. 5) Give an example of filarial worm and round worm.

Que. 1)(a) Ringworm.

Que. 2) (d) Contaminated food and water

Que. 3) (c) Through female mosquito bite.

Que. 4) Answer: Epidermophyton and Microsporum are the two genera of fungi which are responsible for causing ringworms. 

Que. 5) Answer: Example of filarial worm is Wuchereria and an example of round worm is Ascaris.

Case Study 5:

Every day we are exposed to large number of infectious agents. However, only a few of these exposures result in disease. Why? This is due to the fact that the body is able to defend itself from most of these foreign agents. This overall ability of the host to fight the disease-causing organisms, conferred by the immune system is called immunity.

 Immunity is of two types: (i) Innate immunity and (ii) Acquired immunity. Innate Immunity Innate immunity is non-specific type of defence, that is present at the time of birth. This is accomplished by providing different types of barriers to the entry of the foreign agents into our body. Innate immunity consist of four types of barriers. These are — (i) Physical barriers: Skin on our body is the main barrier which prevents entry of the micro-organisms. Mucus coating of the epithelium lining the respiratory, gastrointestinal and urogenital tracts also help in trapping microbes entering our body. (ii) Physiological barriers: Acid in the stomach, saliva in the mouth, tears from eyes–all prevent microbial growth. (iii) Cellular barriers: Certain types of leukocytes (WBC) of our body like polymorpho-nuclear leukocytes (PMNL-neutrophils) and monocytes and natural killer (type of lymphocytes) in the blood as well as macrophages in tissues can phagocytose and destroy microbes. (iv)Cytokine barriers: Virus-infected cells secrete proteins called interferons which protect non-infected cells from further viral infection.

Que. 1) A skin barrier that protects our body from entering micro-organisms is a …………………………………………………………….. barrier.

(a) Cellular barrier

(b) Physical barrier

(c) Physiological barrier

(d) Both (a) and (c)

Que. 2) A non-specific type of defence is also known as ……………………………………………………………………………… .

(a) Innate immunity

(b) Acquired immunity

(c) Pathogen specific

Que. 3) When the host is able to fight against disease-casing organisms, then the ability is known as …………………………………………………………………………… .

(a) Microbial growth

(b) Immunity

(c) Barriers

(d) Interferons

Que. 4) What is meant by cellular barriers?

Que. 5) Which type of barrier include interferons that protects non-infected cells from further viral infection?

Que. 1)(b) Physical barrier.

Que. 2) (a) Innate immunity.

Que. 3) (b) Immunity.

Que. 4) Answer: An Innate immunity which has specific types of leukocytes (Like monocytes, polymorpho-nuclear leukocytes,and natural killer macrophages in tissue and in the blood) that can phagocytose and destroy microbes in our body, this is known as Cellular barriers.

Que. 5) Answer: Cytokine is a type of barrier which include interferons to protect non-infected cells from further viral infection.

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Case Study Questions for Class 12 Biology Chapter 8 Human Health and Diseases

Question 1:

In a study to test a new vaccine against a viral disease, mouse model testing is done. In this process, mice are vaccinated and their blood samples were tested. Mice developed mild disease symptom. After few days those mice were again infected with the virus. This time they do not show any disease symptoms. Their blood samples were tested. Two graphs show antibody concentration for the first and second infection in mice blood.

case study on human health and disease

Based on the above information, answer the following questions.

(i) P and Q in the given graphs indicate (a) IgM and IgG respectively (b) IgG and IgM respectively (c) IgG and IgE respectively (d) IgM and IgA respectively.

(ii) Which form of pathogen is used in vaccination?

(a) Activated and strong pathogenic antigens (b) Inactivated and weakened pathogenic antigens (c) Hyperactive and strong pathogen (d) Preformed antibodies

(iii) Which of the following is incorrect for P? (a) It is the most abundant class of Ig. (b) It is found in blood, lymph and intestine. (c) It is unable to cross the placental barrier. (d) It is a monomer.

(iv) How does vaccination work? (a) The immune system produces antibodies which stay in the blood. (b) Memory lymphocytes remain in the body to fight off any future infection with the same pathogen. (c) Antigenic proteins of pathogens generate primary immune response and the memory B and T cells. (d) All of these.

(v) Read the given statements and select the correct option. Statement A : Mice do not show any disease symptoms during second exposure to the pathogenic virus. Statement B : The antibody production is accelerated and more intense during secondary immune response. (a) Both statements A and B are true. (b) Statement A is false but statement B is true. (c) Statement A is true but statement B is false. (d) Both statements A and B are false.

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  • 13 March 2024

Massive public-health experiment sends vaccination rates soaring

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Vaccination team member Baison Salone (left) facilitates a vaccination clinic in Kafugumbah village, Karene district.

A vaccination clinic in Kafugumbah village, northwest Sierra Leone. Credit: Conor O'Donovan/Concern Worldwide

Deploying mobile COVID-19 vaccination clinics in rural areas of Sierra Leone increased vaccination rates sharply, according to an ambitious experiment involving 150 villages 1 . The effort is an outlier: many more studies examine vaccine hesitancy and misinformation than focus on vaccine access.

“The investigators made a great effort to bring vaccines to remote communities,” says Jean Nachega, an infectious-disease epidemiologist at the University of Pittsburgh in Pennsylvania, who has highlighted challenges in COVID-19 vaccine access in Africa 2 . The model could be transferred easily to other countries, he adds, calling the campaign “very laudable”.

The results, published on 13 March in Nature , highlight the importance of delivering vaccines, as well as other essential medical treatments and supplies, to rural, less affluent areas, says study co-author Ahmed Mushfiq Mobarak, an economist at Yale University in New Haven, Connecticut.

Vaccine disparity

By November 2023, more than 80% of people in high-income countries had received at least one dose of a COVID-19 vaccine, compared with roughly one-third of the population of Africa.

case study on human health and disease

COVID-19: talk of ‘vaccine hesitancy’ lets governments off the hook

In addition to vaccine supply issues , another possible reason for this disparity is that nearly 60% of people in sub-Saharan Africa live in rural areas, where medical care can be inaccessible. For example, when COVID-19 vaccines first became available, people in rural Sierra Leone, in western Africa, needed to make, on average, a seven-hour round trip to receive the jab, at a total cost that could exceed a week’s wages, Mobarak says.

To address this problem, Mobarak and his colleagues designed a system to make vaccines accessible to these rural communities. They selected 150 villages in Sierra Leone and randomly assigned 100 of them to host a two- or three-day vaccination clinic; the remaining 50 served as a control group. By the end of the clinics, 30% of people in the communities that had hosted one had been vaccinated against COVID-19, compared with about 6% of people in control villages.

Last-mile delivery

The researchers found that the clinics’ success varied by region; after the clinics were held, the vaccination rate was at least 65% in some communities and as low as 0% in others. Mobarak says that future research will need to identify the source of this variation, and the extent to which vaccine hesitancy might have played a part.

Hesitancy is important to understand, but it shouldn’t preclude vaccination campaigns or more research on vaccine supply and access, Mobarak says. “When you’re starting with a baseline vaccination rate of essentially zero, our research shows that the most cost-effective thing to do is just to show up,” he says.

The clinics cost about US$33 per person vaccinated. The researchers now plan to test the same strategy in other countries, and to deliver routine childhood vaccines and medical supplies, such as oral rehydration packets, that would further reduce costs per person treated.

doi: https://doi.org/10.1038/d41586-024-00730-4

Read the related News & Views, ‘ Mobile vaccine delivery is valuable in Sierra Leone ’

Meriggi, N. F. et al. Nature https://doi.org/10.1038/s41586-024-07158-w (2024).

Article   Google Scholar  

Nachega, J. B. et al. Lancet Glob. Health 9 , E746-E748 (2021).

Article   PubMed   Google Scholar  

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Case Study on Human Health And Diseases Class 12 Biology PDF

Better preparation of Case Study on Human Health And Diseases Class 12 Biology can help students score good marks in the CBSE Class 12 Board examination. Additionally, it helps build confidence and enables students to deepen their knowledge of Human Health And Diseases. Because case-based questions are equally important for learning and board exam preparation, our team has prepared Case Study on Human Health And Diseases Class 12 Biology in a PDF file for free distribution among students.

Links to download the PDF file of the Human Health And Diseases Case Study for Class 12 Biology free of cost are mentioned on this page.

Human Health And Diseases Case Study for Class 12 Biology with Solutions in PDF

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There are 4 solid tips to answer Class 12 Biology Human Health And Diseases Case Study questions that we are discussing in this section.

  • Read the Case Carefully: To start gathering insights from the given case-based questions, it is vital to read the Human Health And Diseases case carefully and identify the key facts, figures, and units of measurement. Pay attention to any diagrams or graphs related to Human Health And Diseases provided, as they may contain important information.
  • Identify the Problem: While reading the Human Health And Diseases case it is essential to consider the possible causes and effects. This will help you determine the appropriate approach to solving the problem in Class 12 Biology Human Health And Diseases.
  • Use Elimination Methods Too: Since case study questions of Class 12 Biology Human Health And Diseases, are often framed in Multiple choice questions, students should have the knowledge of elimination methods in MCQs to better answer the questions.
  • Before All, Master the Concept of Human Health And Diseases: If the above two methods are not working for you to answer Case Study on Human Health And Diseases Class 12 Biology then you need to revisit the lesson and master the concepts explained in the Human Health And Diseases Class 12 Biology.

What is the Benefit of Practising Class 12 Biology Human Health And Diseases Case Study Questions?

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  • Quick Conceptual Revision: Nothing is better for revision than solving relevant questions and therefore, those who involve in solving the Human Health And Diseases Case study questions before the Class 12 Biology exam are able to better revise their conceptual learnings from the lesson.
  • Better Board Exam Preparation: No doubt, the more you practise Human Health And Diseases case study questions the better your exam preparation will be so, solving Case-based questions prior to the board examination helps a lot in the preparation. It also enables the students to know what are the Human Health And Diseases questions which have the possibility to be asked in the board examination.
  • Confident in Using Analytical or Critical Thinking Skills: The Case-based questions on Human Health And Diseases are all about using analytical or critical thinking skills where students are required to solve problems based on the situations or data given. Thus, practising Case Study on Human Health And Diseases Class 12 Biology benefits students to feel confident and comfortable in using analytical skills.

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Class 12th Biology - Human Health and Disease Case Study Questions and Answers 2022 - 2023

By QB365 on 08 Sep, 2022

QB365 provides a detailed and simple solution for every Possible Case Study Questions in Class 12 Biology Subject - Human Health and Disease, CBSE. It will help Students to get more practice questions, Students can Practice these question papers in addition to score best marks.

QB365 - Question Bank Software

Human health and disease case study questions with answer key.

12th Standard CBSE

Final Semester - June 2015

Your classmate complains of cough and headache to the doctor. The doctor confirms that he is suffering from pneumonia and not just common cold. (a) How did the doctor arrive at this conclusion? (b) Write the binomials of the causative organisms of pneumonia. (c) What is common about the transmission of the two diseases, common cold and pneumonia?

case study on human health and disease

A youth in his twenties met with an accident and succumbed to the injuries. His parents agreed to donate his organs. Answer the following questions: (a) List any two essential clinical steps to be undertaken before any organ transplant. (b) Why is the organ transplant rejected sometimes? Name the kind of immunity responsible for this.

Following a road accident, four injured persons were brought to a nearby clinic. The doctor immediately injected them with tetanus antitoxin, (a) What is tetanus antitoxin? (b) Why were the injured immediately injected with this antitoxin? (c) Name the kind of immunity this injection provided.

case study on human health and disease

Prior to a sports event, blood and urine samples are collected for drug tests. (a) Name the drugs the authorities usually look for. (b) Write the scientific names of the plants from which these drugs are obtained. (c) Name two other plants which have hallucinogenic properties too.

When someone buys a packet of cigarette, he cannot miss the statutory warning given on the packing, which warns against smoking and tells it is injurious to health. Yet, smoking is very much prevalent in our society, both among youth and old. Mention six ill-effects of smoking to advise the adolescents to avoid smoking.

Read the following and answer any four questions from (i) to (v) given below : Riya studies in II standard in a government schooL She belongs to a backward family and her parents did not get her properly vaccinated according to immunisation programme. Once while playing in school playground she fell down due to weakness and developed high fever, headache and stiffness in her neck. Identify the illness she could be suffering from and answer the following questions. (i) The microbe responsible for Riyas illness could be

(ii) Which vaccine, if administered earlier, would have saved Riya from the illness she unfortunately contracted?

(iii) The disease that Riya has contracted spreads through

(iv) Riya can spread her illness to other children through

(v) Assertion: Polio produces inflammation of the nervous system. Reason: Stiffness of the neck, paralysis of particular skeletal muscle is an important symptom of polio.

Read the following and answer any four questions from (i) to (v) given below : X and Yare communicable diseases whereas Wand Z are non-communicable diseases. X is transmitted through vectors whereas Y is transmitted through droplet infection. W is caused due to a hormone deficiency whereas Z is a degenerative disease. Based on the above information, answer the following questions. (i) Identify W, X, Y and Z.

(ii) Select the correct statement.

(iii) If X and Y both are usual diseases then which of the following holds true?

 (iv) If X and Y both are bacterial diseases then select the correct match from the following.

(v) Assertion: Communicable diseases could be contagious or non-contagious. Reason: Diseases that spread through vectors are non-contagious disease.

Read the following and answer any four questions from (i) to (v) given below: Rajesh, Ravi and Rohit are roommates. They are doing their graduation. Few months back Ravi fell ill. It took him around 3 weeks to recover. Both his friends were absolutely healthy at that time. After sometime Rajesh also fell ill from some other disease. This time Ravi and Rohit both contracted the same illness. Based on the above information, answer the following questions. (i) Which of the following holds true for Ravi's illness?

(iii) Which could be correctly said for Rajesh's illness?

(iv) Which of the following may depicts Ravi's and Rajeshs illness?

(v) Assertion: Diabetes mellitus is a non-communicable disease which can be completely cured. Reason: Diabetes mellitus is caused by deficiency of aldosterone hormone.

case study on human health and disease

(ii) The given graph indicates that person Y is suffering from

(iii) Which of the following conditions are common in person Y?

(iv) A person suffering from diabetes mellitus becomes weak because

(v) Assertion: Type I diabetes involves failure of insulin to facilitate the movement of glucose into cells. Reason : Type II diabetes is caused by failure of beta cells to produce adequate amount of insulin due to beta cell depletion.

*****************************************

Human health and disease case study questions with answer key answer keys.

(a) In pneumonia, the lung alveoli become filled with a fluid leading to severe problems in breathing, whereas in common cold, only the nose and respiratory passage are affected, but not the lungs. (b) Pneumonia is caused by (i) Streptococcus pneumoniae (ii) Haemophilus influenzae. (c) Both common cold and pneumonia spread by the droplets/aerosols released by the infected person during coughing and sneezing.

(a) Since the antibodies are found in the blood, (humor - body fluid), they are said to show humoral immune response. (b) IgA, IgE, IgG and IgM are the four types of antibodies.

(a) Blood group matching and tissue matching are necessary before organ transplantation. (b) (i) The transplant is rejected sometimes because our immune system is able to differentiate between 'self and 'non-self cells. (ii) The cell-mediated immunity is responsible for this.

(i) Tetanus antitoxin is a preparation containing antibodies to the toxin. It is produced by tetanus bacteria Clostridium tetaní. (ii) Antitoxins neutralize the toxin produced by bacteria. Therefore, the injured persons are immediately injected with tetanus antitoxin for preventing any infection and septic. (iii) Tetanus antitoxin represents artificial passive immunisation where quick response is generated in the body.

(a) (i) Thymus (ii) Lymph nodes. (b) (i) Thymus (i) It provides the micro-environment for the maturation of immature T-Iymphocytes to mature into antigen-sensitive lymphocytes. (ii) Lymph nodes They trap the microbes or other antigens that have got into the lymph or tissue fluid; the trapped antigens activate the lymphocytes present there to develop an immune response .

(a) Macrophage. (b) RNA (Ribonucleic acid). (c) Reverse transcriptase.

(a) Morphine and heroin. (b) (i) Morphine is used as a sedative and painkiller. (ii) Heroin is a depressant and slows down body functions.

(a) It is morphine. (b) Papaver somniferum is its source plant. (c) Its receptors are present in the (i) cenqal nervous system. (ii) gastrointestinal tract.

(a) It is consumed by (i) inhalation and (ii) oral ingestion. (b) Marijuana, Hashish, Ganja, Charas.

(a) Cannabinoids and cocaine/coca alkaloids. (b) (i) Cannabinoids are obtained from Cannabis sativa. (ii) Cocaine is obtained from Erythroxylum coca. (c) Atropa bel/adona and Datura show hallucinogenic properties.

Smoking must be avoided as it causes the following ill-effects: (i) Tobacco contains a number of harmfu I chemicals, of which nicotine is an alkaloid, a stimulant and a poison. (ii) Nicotine stimulates the adrenal glands to secrete adrenaline and nor-adrenaline, both of which increase the blood pressure and the heart rate. (iii) It leads to cancer of throat, lungs and urinary bladder. (iv) Smoking also causes respiratory disorders like bronchitis and emphysema. (v) It causes oxygen deficiency in the body by increasing the carbon monoxide content in the blood and reducing the concentration of haembound oxygen. (vi) It causes gastric ulcers and increased risk of coronary heart diseases.

(i) (b) : Riya is suffering from polio that is caused by an Enterovirus, called Poliovirus. (ii) (a) (iii) (c) : Polio virus enters the body via alimentary canal (faecal oral route) (iv) (a): Riya has contracted polio which is transmitted through faecal oral route, as urine and faeces of the patient contain polio virus. (v) (b)

(i) (b) : X is a communicable disease that is transmitted through vectors. It could be malaria, chikungunya, etc. Y is communicable disease that is transmitted through droplet infection. It could be rhinitis, diphtheria, pertussis, etc. W is a non-communicable disease like diabetes that is caused by deficiency of insulin hormone. Z is a non-communicable degenerative disease like Alzheimer's disease. (ii) (c) : Sleeping sickness is caused by Trypanosoma. Diphtheria is caused by Corynebacterium diphtheriae. In myocardial infarction a large portion of heart muscle is deprived of blood due to coronary thrombosis and patient develops heart attack. (iii) (b) (iv) (a) : Leprosy is a bacterial infection that spreads through prolonged contact with the infected person. Whooping cough spreads through droplet infection. Botulism spreads through faecal oral route. (v) (b)

(i) (c) : Ravi must have suffered from a noncommunicable disease which cannot be spread from one person to another. Anaemia is caused by deficiency of iron and. lead to general weakness and associated problems. It can be corrected by proper diet and dietary supplements. Down's syndrome is also a non-communicable disease but it is not cured completely. It is a genetic disorder and is congenital. (ii) (d) : Non-communicable diseases are noncontagious. (iii) (d) (iv) (c) (v) (d) : Diabetes mellitus is a non communicable disease that has no cure. It is caused by deficiency of insulin hormone.

(i) (c) : Blood sugar level fluctuations in person X indicate that sugar level never exceed the normal limit and sufficient secretion of insulin at required times removes any extra sugar from blood and converts it into glycogen for future use. This implies that person X is normal and healthy. (ii) (a) : Elevated blood sugar levels in person Y indicate that he is suffering from diabetes mellitus. (iii) (d): (iv) (d): (v) (d) : Type I diabetes or insulin dependent diabetes mellitus or juvenile diabetes is an autoimmune disorder caused by failure of beta cells to produce adequate amount of insulin. Type II diabetes or non insulin dependent diabetes mellitus involves failure of insulin to facilitate the movement of glucose into body cells.

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Vaccine-enhanced disease: case studies and ethical implications for research and public health

Euzebiusz jamrozik.

1 The Ethox Centre & Wellcome Centre for Ethics and Humanities, University of Oxford, Oxford, UK

2 Monash Bioethics Centre, Monash University, Melbourne, Australia

3 Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

George Heriot

Michael parker, associated data.

No data are associated with this article.

Peer Review Summary

Vaccination is a cornerstone of global public health. Although licensed vaccines are generally extremely safe, both experimental and licensed vaccines are sometimes associated with rare serious adverse events. Vaccine-enhanced disease (VED) is a type of adverse event in which disease severity is increased when a person who has received the vaccine is later infected with the relevant pathogen. VED can occur during research with experimental vaccines and/or after vaccine licensure, sometimes months or years after a person receives a vaccine. Both research ethics and public health policy should therefore address the potential for disease enhancement. Significant VED has occurred in humans with vaccines for four pathogens: measles virus, respiratory syncytial virus, Staphylococcus aureus, and dengue virus; it has also occurred in veterinary research and in animal studies of human coronavirus vaccines. Some of the immunological mechanisms involved are now well-described, but VED overall remains difficult to predict with certainty, including during public health implementation of novel vaccines. This paper summarises the four known cases in humans and explores key ethical implications. Although rare, VED has important ethical implications because it can cause serious harm, including death, and such harms can undermine vaccine confidence more generally – leading to larger public health problems. The possibility of VED remains an important challenge for current and future vaccine development and deployment. We conclude this paper by summarising approaches to the reduction of risks and uncertainties related to VED, and the promotion of public trust in vaccines.

The views expressed in this article are those of the authors. Publication in Wellcome Open Research does not imply endorsement by Wellcome.

Introduction

Vaccination is one of the greatest achievements of public health and infectious disease research. Standard licensed vaccines are generally extremely safe, and typically the direct individual benefits of vaccination significantly outweigh any risks or side effects. In addition, the immunity of vaccinated individuals provides further public health benefits by indirect protection of others, collectively creating population (herd) immunity. Nevertheless, rare serious adverse effects do occur with experimental vaccines, sometimes halting vaccine development, and have also occurred with licensed vaccines, in exceptional cases leading to restriction or withdrawal of public health use.

Vaccine-enhanced disease (VED) is a distinct type of infection-related adverse event that occurs when disease severity is increased following exposure to the relevant pathogen after vaccination 1 . A key difference between VED and other adverse events is that it is contingent on post-vaccination infection with the relevant pathogen, whereas other types of adverse events are caused by the vaccine itself (including in rare cases where the microbes in live-attenuated vaccines themselves cause disease) or direct immune responses to the vaccine. Other authors have provided guidance for the detection of a correlation between vaccination and increased disease severity and the confirmation of likely VED with additional evidence supporting a causal link between vaccination and enhanced disease 1 .

Significant VED has occurred for at least four human vaccines, although the terminology used to describe disease enhancement has been different in each case ( Table 1 ). This article reviews these four case studies of VED in humans over the last six decades and explores the ethical implications for vaccine research and public health policy. The phenomenon of VED has recently received greater public attention because of concerns that COVID-19 vaccines might cause VED, due to disease enhancement observed in animal studies of experimental vaccines for other human coronaviruses 2 , 3 .

Reference for mechanisms of measles, RSV, dengue enhancement 7 .

RSV, respiratory syncytial virus; VED, vaccine-enhanced disease.

The ethical implications of VED for research and public policy require careful consideration because, although rare, VED can cause serious harm (including death) and has the potential to undermine public trust in vaccines 4 , 5 . Previous cases of VED have led to changes in research and public health practice 5 , 6 , yet the topic has not been widely discussed from an ethical perspective. We argue for careful and transparent evaluation of, and communication regarding, the risks and uncertainties regarding VED for novel vaccines. Where residual risks and uncertainties remain, these should be weighed against potential benefits and monitored during follow-up of recipients of novel vaccines.

Case studies

The four case studies below highlight the issues and challenges that arose in VED associated with measles virus, respiratory syncytial virus (RSV), Staphylococcus aureus , and dengue virus. Many of the points raised may also be relevant to vaccine development for other pathogens, and to some related types of adverse effects 7 , 8 . Some experimental vaccines, for example, have been associated with increased (as opposed to decreased) risks of infection without enhancement of disease (i.e., infection after vaccination is more likely, but the clinical severity of the resulting infection is not more severe than average). At least one human influenza vaccine has been associated with an increased rate of influenza diagnosis but no increased risk of hospitalisation 9 , 10 . Similarly, one experimental HIV vaccine was associated with an increased risk of infection, with no evidence that the natural history of the resulting HIV infections and/or disease outcomes were otherwise altered 11 . In animal studies, VED has also been noted with veterinary vaccines (e.g., for animal coronaviruses) and animal models intended for human vaccine development (e.g., for human coronaviruses, influenza, and West Nile virus) 7 . This paper focuses only on cases where there is convincing evidence that vaccines have led to disease enhancement in humans, as opposed to evidence of an association between vaccination and more severe disease without confirmatory evidence of a causal relationship, or evidence of an increased frequency of infection but not increased severity of disease, (e.g., the influenza and HIV vaccines described above). Following these case studies, and against the background of the understanding they provide of VED, we then analyse the ethical issues presented by the development and use of vaccines.

Case study one: Measles virus

Measles is a highly transmissible virus that is particularly harmful to infants or in those who are first infected in adulthood, as well as to those with comorbidities. Although modern live measles vaccines are highly safe and effective, measles still causes around 100,000 deaths per year, primarily in low-income communities where access to vaccination is poor. Despite the safety of current vaccines, outbreaks of measles have increased in some countries due to reduced vaccination rates partly attributable to vaccine hesitancy 12 .

From 1961–1967, a licensed measles vaccine created with formalin-inactivated (killed) virus, was associated with a type of VED referred to as ‘atypical measles’ 13 , 14 . Vaccinated individuals with atypical measles develop a severe clinical syndrome with rash and fever and a higher rate of lung involvement (pneumonitis) than usual cases of measles and, in some cases, liver dysfunction and abdominal pain 13 , 14 . By the time the enhanced disease syndrome was characterised, over 1.8 million people, mostly children, had received the vaccine 13 . The vaccine was withdrawn from public health use due to VED in 1967 14 . To our knowledge, there are no estimates of the total number of atypical measles cases due to the vaccine, although sporadic cases are still being reported 15 . To reduce subsequent risk of atypical measles, individuals who had received the withdrawn vaccine were re-vaccinated with an alternative (live-attenuated) vaccine 13 .

The initial phase III trial of the formalin-inactivated measles vaccine demonstrated 81% efficacy at 0–3 months after vaccination; however, vaccine efficacy waned over time. At 13 months, efficacy had reduced to 65% 16 . In addition to waning of immunity, interpretation of vaccine efficacy was complicated by changing patterns of community measles transmission. In some cases, vaccinated children experienced apparently normal measles disease post-vaccination (i.e., neither attenuated nor enhanced, likely due to vaccine failure). In others, it was hypothesised that “asymptomatic infections with wild measles viruses may have served to boost some with low and borderline [antibody] titers” 16 (i.e., post-vaccination infection with the wild-type virus was attenuated as a result of vaccination, and the combination of vaccine-derived and post-infection immunity could provide augmented and/or durable protection against subsequent infection) 16 . Early aggregate vaccine efficacy estimates in the study population may have obscured some short-term cases of VED and the short duration of the initial phase III trial meant that longer-term risks of VED due to waning of post-vaccination immunity over time were not detected until public health use of the vaccine, well after trial completion and vaccine approval 13 .

Case study two: Respiratory syncytial virus

Respiratory syncytial virus (RSV) is a ubiquitous virus and a major cause of hospitalisation of young children worldwide, causing up to around 200,000 deaths in children under five per year, primarily in low-income communities 17 . The first infection with RSV is usually the most severe, typically causing the clinical syndrome of bronchiolitis (lung inflammation and congestion). In more severe cases, RSV causes respiratory failure and death. Naturally acquired immunity to RSV wanes over time, and individuals are commonly re-infected many times throughout their lives despite prior infection. It is increasingly recognised that RSV results in significant mortality among older adults, despite numerous prior infections and some degree of immunity 18 .

There is currently no licensed vaccine for RSV (although at least one is in phase III clinical trials) in part because RSV vaccine research was impeded by the occurrence of a high-profile case of VED. In 1966, an experimental RSV vaccine studied in toddlers resulted in many severe cases of what was termed ‘enhanced respiratory disease’ (i.e., more severe lung inflammation and respiratory failure) among child participants subsequently exposed to wild-type RSV, including the death of two toddlers. This led to extreme caution regarding further RSV vaccine research 19 .

Thorough investigation of human cases and preservation of stocks of the 1966 vaccine informed the development of an animal model that closely replicates RSV VED 20 . This has provided opportunities for research on the pathogenesis of RSV VED as well as the prospective testing of future RSV vaccines against the model to ensure that they do not cause similar pathology. Although animal models have identified VED in vaccines which, as a result, did not proceed to human trials 8 , earlier animal models (before RSV VED was identified) had failed to detect this risk. This highlights the limitations of animal models in eliminating the risk of VED (among other adverse effects).

Case study three: Staphylococcus aureus

Staphylococcus aureus is a common species of bacteria found on the skin and upper respiratory tract. Around 30% of the world’s population carries S. aureus , usually without symptoms, yet it causes up to 600 total infections and 30–40 invasive infections, (i.e., with septicaemia, abscess, or vital organ involvement) per 100,000 person-years 21 – 23 , with a particularly high incidence noted among hospitalised patients, resulting in significant morbidity and mortality 24 , 25 . Early reinfection is common after one episode of clinical S. aureus disease (particularly in patients with risk factors for invasion) 26 and immunity to S. aureus is incompletely understood as antibodies to the bacteria are both ubiquitous and insufficient to prevent reinfection 27 . Moreover, the prevalence of resistant S. aureus is increasing worldwide, and WHO has identified methicillin-resistant S. aureus as a high priority resistant pathogen for which better control methods are urgently needed.

Of the 15 antigenic targets for a S. aureus vaccine identified in pre-clinical studies, none have resulted in effective human vaccine targets, despite three candidate vaccines reaching phase IIB/III trials 28 – 31 . One of these candidates (non-adjuvated IsdB) was associated with a five-fold increase in the mortality of patients with S. aureus infection occurring after cardiothoracic surgery (from 4% to 26%). This apparent VED was not seen in pre-clinical mouse challenge studies of the IsdB vaccine or phase I/II trials of healthy volunteers 32 , 33 . Post-hoc analyses of the trial subjects experiencing S. aureus infection suggested that individuals with particular pre-vaccination cytokine signatures (low serum IL-2 and/or IL17a) experienced high infection-related mortality after vaccination (but not after placebo administration), but the mechanisms of this case of VED remain poorly understood.

A subsequent large phase III trial of another candidate vaccine aimed at enhancing opsonophagocytic killing of S. aureus was not associated with VED in high-risk patients, despite very similar preclinical observations and lack of overall efficacy 29 , 34 . This serves to underscore the unpredictability of VED in late-stage trials, especially for pathogens with complicated and incomplete human immunity.

Case study 4: Dengue virus

Dengue is a vector-borne arboviral disease caused by four related strains of dengue virus. Dengue causes millions of cases per year in endemic areas, and increasing numbers of people are at risk 35 . A key feature of dengue is that while first infection is often mild or asymptomatic, second infection (with a different strain to the first infection) is the most likely to be severe, especially if the antibody response to first infection has waned to a certain level, potentiating antibody-dependent disease enhancement 36 . Severe dengue occurs in approximately 2–5% of secondary infections and sometimes results in death 37 . Third and subsequent infections (with any strain) are typically mild or asymptomatic.

A 2015 study of an experimental tetravalent dengue vaccine (known as CYD-TDV) which enrolled children in endemic areas revealed that the vaccine was, overall, associated with a 60% reduction in symptomatic dengue. However, in some younger children, the vaccine was associated with increased risks; for example, vaccinated children aged 2–5 in the Asia-Pacific arm of the trial were 7.45 times more likely to be hospitalized with severe dengue than those in the control group 38 . At the time, it was thought that the most likely reason for higher risks in some children was that the live vaccine primed the immune system in a similar way to a first dengue infection among those who had never been infected (seronegative children). When these individuals then had a naturally-acquired wild-type infection after being vaccinated, this resulted in ‘secondary-like’ VED (i.e., more likely to be severe). Not every person in an endemic area is exposed to dengue every year, and it can take several years before children are infected for the first time, i.e., before ‘seronegative’ individuals become ‘seropositive’. In older age groups in endemic areas, the majority are seropositive – and seropositive people (particularly those who have only been infected once before) appear to benefit from CYD-TDV vaccination.

In contrast to the cases discussed above, there is therefore good reason to think that CYD-TDV could provide net public health benefits, either by vaccinating only seropositive individuals or by vaccinating highly seropositive populations (although this strategy exposes a minority of individuals to a risk of VED). Public health modelling suggested that widespread use of CYD-TDV in populations with high proportion of seropositive individuals could reduce the burden of dengue disease by 10–40% over 10 years 1 . The vaccine was approved by WHO’s Strategic Advisory Group of Experts (SAGE) for use in children over the age of nine in endemic areas where the proportion of seropositive individuals was greater than 70%. The vaccine was initially rolled out without routine pre-vaccination serological testing (due to economic and technical constraints 6 ) but with a plan to seek further data regarding the elevated risk in seronegative individuals 6 .

In contrast to the hypothesis that dengue VED was merely akin to secondary dengue infection, researchers not involved in the development of the vaccine estimated that CYD-TDV VED was up to 3.5 times more (likely to be) severe than usual secondary dengue infection 39 . These authors recommended in 2016 that CYD-TDV vaccination be restricted to seropositive individuals “regardless of inconvenience or cost.” 39 , 40 . Later, controversy ensued because after vaccination campaigns had begun, results confirming the risk of VED among seronegative individuals were published. In the Philippines, where over 800,000 children had been vaccinated, the controversy resulted in political uproar and a decline in confidence regarding vaccines in general 4 , 41 .

Subsequently, SAGE convened a working group including an ethicist. The group proposed a change of policy to restrict the use of CYD-TDV to seropositive individuals, in whom there was clear evidence that the vaccine was safe and effective 6 . However, this resulted in significantly less public health use of the vaccine, because there is still no cost-effective serology testing strategy that could be used routinely to guide dengue vaccination strategies in endemic areas. It is likely that many thousands of seronegative individuals in endemic areas were vaccinated with CYD-TDV prior to the revised policy, and these individuals face a risk of VED if infected after vaccination. The true burden of CYD-TDV VED is difficult to estimate because seronegative individuals were not identified at the time of vaccination and because although it is known that the risk of VED persists for several years, the longer-term risks are poorly characterised.

Ethical implications

Although rare, VED has been associated with significant harms and has often been difficult to predict with a high degree of certainty. There is, therefore, a strong ethical rationale for measures to minimise risk and uncertainty regarding VED for novel vaccines, as well as for transparent communication regarding any residual risks and uncertainties. This is important not only to protect participants in vaccine trials and early recipients of newly approved vaccines, but also to promote public trust in vaccines. In some cases public trust has been undermined by the occurrence of VED and/or a lack of transparent public communication regarding such risks 41 , 42 . Below, we discuss relevant aspects of risk and uncertainty in more detail, including in the context of COVID-19 vaccine research and human challenge studies, before highlighting ethical implications for policymaking related to the public health implementation of vaccines.

Risk and uncertainty

Consensus standards in research ethics require, among other things, that risks to participants are carefully evaluated, minimised, and that residual risks are justified by the social value of the research. This requires comprehensive, rigorous, and systematic evaluation of the anticipated risks, burdens, and benefits of proposed research. Risks are sometimes distinguished from uncertainties by defining risks as harmful outcomes with a known magnitude and probability and uncertainties as potential outcomes with unknown probabilities and/or magnitudes. This sharp distinction between known and unknown outcomes obscures the frequent occurrence of situations in which estimates of the probability or magnitude of an outcome are more or less certain (reflected, for example, by narrower or wider confidence intervals around a risk estimate), ranging from zero certainty (strict uncertainty) to high certainty. In some cases, researchers may be aware of the possibility of particular outcomes without being able to characterise the probability of these outcomes with any certainty. In other cases, even the possibility of a particular outcome is unknown (or not considered) prior to its occurrence (situations of ignorance or so-called ‘unknown unknowns’) 43 . All such situations are captured by various uses of the term ‘uncertainty’. Early phase and first-in-human clinical research inevitably involves significant uncertainty with respect to both benefits and harms, meaning that both good and bad outcomes are sometimes poorly matched to those expected based on prior data 44 .

The case studies above feature both risks and uncertainties. For example, at the time of licensure of the CYD dengue vaccine, there were risks because a phase III trial had demonstrated a harm signal and the potential mechanism was well-described. There were also uncertainties regarding the probability and magnitude of the risk of VED in certain individuals and groups. In other cases where no risks are identified in earlier (animal or human) studies, the potential for VED during vaccine development and after licensure is highly uncertain. For example, in the other cases above, VED was not expected to occur during the phase III S. aureus vaccine trial in surgical patients who would face significant harms from such an enhanced disease, nor among children given the experimental RSV vaccine, nor during public health use of the measles vaccine.

The primary role of vaccine development processes, which involve gathering more data on safety, immunology, and efficacy, is to reduce or resolve uncertainties. Although safety is a key focus of preclinical and early clinical research, most measures of safety become more certain in later-phase research. However, because VED does not occur until a person is exposed to a subsequent infection, which might occur only in late phase research and/or after a considerable time has passed since vaccination. VED can therefore remain a safety concern and area of uncertainty during phase III (efficacy) testing, which necessarily involves participants being exposed to infection with the pathogen in question 45 . Safety concerns about VED may also remain relevant (or be first identified) in post-licensure surveillance, as demonstrated in the case studies of measles and dengue.

Minimising risks to vaccine trial participants necessarily involves trade-offs between the interests of trial participants and considerations related to scientific validity and/or efficiency, both of which are ethically salient to producing public health benefits associated with novel vaccines 44 . A key focus of risk minimisation is the reduction of the probability of serious or irreversible harms – which are a potential consequence of VED. Phase III trials may seek to recruit individuals who face a high probability of the infection in question, because this may optimise scientific validity/generalisability, produce results more rapidly, and because individuals at risk may be independently motivated to participate. In some cases, however, VED may be particularly harmful in groups where the outcome of enhanced disease would be particularly severe (e.g., thoracic surgical patients in the S. aureus case above). It may also be infeasible to reduce the risk of VED in remaining participants after it is observed (in some participants) during the trial – although the measles case illustrates that where other safe vaccines are available, re-vaccination with an alternative vaccine for the same pathogen may mitigate future VED risks.

Both for reasons of continued uncertainty and high magnitude of potential harm, phase III research should arguably involve particularly vigilant monitoring for VED. Where there is concern regarding potential VED, optimal risk minimisation may include particularly careful participant selection criteria and the exclusion of children where feasible. For example, because individuals are reinfected with RSV many times in a lifetime, it has been feasible to exclude children in the initial trials of novel RSV vaccines conducted since the case of VED described above, followed by cautious inclusion of children in subsequent studies once safety is demonstrated in adults.

Follow-up of all novel vaccine trial participants should arguably be of a long duration to detect rare late adverse effects including the potential for late VED. Exposure to infection may occur many months or years after the end of a trial and in some cases the risk of VED may increase with delayed infection (e.g., where the waning of post-vaccination immune response alters the risk of VED) 36 . Waning immunity may explain why the inactivated measles vaccine showed overall population protection during initial trials but was eventually shown to be associated with a significant risk of VED during public health implementation in the general community. Similarly, variations in the local incidence of infection during and after a phase III trial may alter the ability to detect VED. The incidence of dengue was highly variable during and after the initial multi-country CYD-TDV phase III study 46 , which may have contributed to variable efficacy findings in later years of the trial, including the harm signal suggestive of VED.

Implications for COVID-19 vaccines

Experimental vaccines for SARS-CoV and MERS-CoV have been associated with evidence of VED in animal models, which raised concerns regarding the potential for VED with COVID-19 vaccines 8 . A March 2020 expert meeting regarding the potential for COVID-19 VED proposed several measures to reduce the risks of VED including (i) vigilant investigation of vaccine immune responses for those previously associated with VED; (ii) the use of animal challenge models that adequately mimic human disease, ideally including adequate time delay between the vaccination of animals and infection challenge; (iii) consideration of antibody transfer from phase I/II vaccine trial human participants to animal challenge study subjects to test for VED; and (iv) longer follow-up of trial participants (to monitor for the increased disease severity upon exposure to the infection in question) 8 . Even with these resource-intensive measures in place, it is not possible to exclude the risk of VED altogether – in other words there will often be residual uncertainty – and trials of COVID-19 vaccines have involved informing volunteers regarding the risks and uncertainties related to VED 47 . Fortunately, no cases of COVID-19 VED have been documented in phase I-III trial participants 1 , yet this does not exclude the possibility of delayed disease enhancement in the context of waning immune responses. Clinicians and public health agencies should therefore thoroughly investigate any unusually severe cases of COVID-19 in vaccine recipients, ideally using recently proposed standardized criteria for the detection and confirmation of VED 1 .

Risks of vaccine-enhanced disease in human challenge studies versus standard vaccine trials

Human challenge studies involve exposing research participants to infection under controlled conditions and are often used to estimate the efficacy of experimental vaccines before proceeding to larger trials 48 . Phase III vaccine challenge trials typically involve around 100 rigorously screened young healthy adults, whereas standard phase III trials involve tens of thousands of individuals and often a wider age range of participants. Challenge trials permit especially close monitoring of participants for the duration of their infection. On the one hand, challenge studies are ethically sensitive partly because they involve the intentional exposure of participants to risk of infection, potentially including VED (although VED has not occurred in challenge studies to date). Since challenge studies are of short duration, they might detect short-term VED (such as those occurring with RSV and S. aureus above) but not delayed VED events (such as those that might occur during waning immunity). On the other hand, were VED to occur in a challenge study, far fewer participants would be exposed to such harms than if it were to occur in a standard phase III trial, participants would be more likely to have immediate access to treatment for any enhanced disease and the evidence of VED would prevent much larger numbers of people being exposed to that vaccine in a standard phase III trial. These competing considerations mean that there may be difficult ethical judgements to be made as to whether challenge studies or field trials are the optimal first method of testing vaccines for diseases where VED is a concern. However, because standard trials involve exposing many thousands more individuals to an experimental vaccine than challenge studies, cumulative risks of VED may be far higher in standard trials 48 , 49 . In particular, where there are many vaccine candidates, prioritising these candidates in challenge studies before proceeding to larger standard trials with only the most promising vaccines may reduce overall aggregate risks (including those related to VED) 49 , 50 .

Public health implementation

Vaccines typically provide both individual benefit (i.e., net risk reduction) as well as population level benefits (the sum of individual direct benefits plus indirect protection of others, with the combined effect of the latter constituting population ‘herd’ immunity). The occurrence of VED may alter the balance of risks and benefits of vaccine implementation in at least two ways. First, a particular sub-population may face a net risk from vaccination due to VED (despite overall population benefits). Importantly, in such cases, aggregate statistics from a phase III study may demonstrate that a vaccine is efficacious (i.e., beneficial) at the population level because the majority of individuals are protected even if a minority experience VED (see dengue and measles cases above). Researchers should therefore take care to investigate whether overall efficacy estimates conceal cases of VED as well as how benefits and harms associated with vaccination are distributed in the population. Where a vaccine is licensed despite a risk of VED in a minority of vaccine recipients, relevant public health implementation policies should be considered with the utmost care – and public health agencies should engage with sub-populations who might be placed at greater risk. Such engagement and policymaking should include transparent disclosure of relevant risks and uncertainties, the development of fair procedures for the identification of higher risk individuals (if possible), attention to how risks can be minimised, and provision for compensation for serious harms if these occur.

Where the sub-population at risk of VED due to a licensed vaccine is readily identifiable, it is important to consider whether they should be excluded from mass vaccination, although this may undermine the overall efficiency and/or cost-effectiveness of vaccine programs, especially if identifying higher risk individuals requires testing (e.g., of serostatus in the case of dengue) 6 . In addition to making policy based on the overall balance of potential health benefits and risks at the population level, the distribution of risk should also be considered – for example, it may be ethically problematic to impose risks on already marginalised sub-populations or those who cannot provide consent (e.g., children).

Where a sub-population is not readily identifiable, it may sometimes be more appropriate to make a vaccine that offers both significant potential benefits and significant risks (e.g., of VED) a matter of informed consent based on individual doctor-patient discussion of risks and benefits rather than as part of a mass vaccination strategy where the default is to be vaccinated. This informed consent approach is often employed for pre-travel use of the relatively risky but protective vaccines for Japanese encephalitis and yellow fever, for example.

Second, VED can alter the balance of risks and potential benefits of vaccination over time, whether it affects a sub-population or all vaccine recipients. For example, this might occur where a vaccine provides some degree of individual protection against disease in the short-term, but those who are exposed after a longer period of time experience not only less protection but also a higher risk of VED (which is one potential explanation for the epidemiology of atypical measles). In the case of dengue, mass CYD-TDV vaccination of high seroprevalence populations might provide overall population health benefits in the short-to-medium term despite exposing a minority to the risks of VED, but in the long term continued mass vaccination and reduced incidence of dengue might result in increasingly large numbers of seronegative people experiencing VED if/when dengue epidemics recur 51 .

Maintaining public confidence in vaccines

It is widely acknowledged that trust in licensed vaccines, vaccine research, and public health agencies is essential for the ethical acceptability and long-term success of public health programs – and vaccine hesitancy is considered a ‘top 10’ threat to global health 50 . Since VED and other rare but serious harms from vaccination have been associated with declines in public trust, policymakers should prepare for such outcomes. Public health agencies have a responsibility to develop evidence-based approaches to engage with target populations about the benefits, risks, and uncertainties of vaccine programmes (including VED where relevant) and to respond to their perspectives, concerns, and expectations. Engagement with relevant populations regarding vaccination should include careful transparent disclosure of the potential for VED where this is reasonable concern 5 , 6 , 42 . Other policies that might help to promote trust include commitments to undertake vigilant surveillance for vaccine side-effects, especially those that involve significant harm, and to provide appropriate compensation if any vaccine-related harms occur. Where a vaccine is planned for global use, it may also be appropriate for high-income countries or vaccine development sponsors to fund compensation programmes for people in low-income countries who may not otherwise have access to such remediation, especially where global vaccination programs seek to achieve collective aims such as disease eradication 52 .

Conclusions

Vaccination is a cornerstone of global public health, and novel vaccines are developed in order to produce additional health benefits. Although rare, the potential for disease enhancement during vaccine research or public health use of novel vaccines remains a key source of uncertainty and potential risk, and cases of VED have resulted in serious harm as well as declining public trust in vaccines. Vaccine development and implementation should therefore involve measures to reduce risks and uncertainty during vaccine research, transparent communication regarding residual risks and uncertainties, and compensation for any research-related harms, including VED. At the level of public health policy, it should be acknowledged that novel vaccines sometimes produce unexpected harm, including VED, and ongoing public engagement programs should be carefully designed to maintain and promote public trust in vaccination, especially where there are any concerns regarding potential disease enhancement.

Data availability

[version 1; peer review: 3 approved]

Funding Statement

This work was supported by the Wellcome Trust [203132]; the World Health Organization [HQ/SCI/RFH/HEG COVID-19 Sep] and the Oxford-Johns Hopkins Wellcome Grant [221719/Z/20/Z].

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

1 Ferguson, N. Summary of modelling

https://www.who.int/immunization/sage/meetings/2016/april/3_Ferguson_Comparative_Dengue_Modelling_SAGE.pdf?ua=1

Reviewer response for version 1

Peter collignon.

1 Medical School, Australian National University, Canberra, ACT, Australia

This is a well written and important paper for anyone to read when examining the issue of Vaccine safety. 

The conclusion gives a very good summary and maybe some more of it in part could be incorporated into the Abstract as often the abstract is all readers read.

The study by Fowler et al. should be separately referenced when they mention the increased mortality rates in the group receiving the Staph aureus vaccine, so the reader can more easily find the appropriate reference.

Does the article adequately reference differing views and opinions?

Are all factual statements correct, and are statements and arguments made adequately supported by citations?

Is the Open Letter written in accessible language?

Where applicable, are recommendations and next steps explained clearly for others to follow?

Is the rationale for the Open Letter provided in sufficient detail?

Reviewer Expertise:

Infectious diseases , epidemiology, microbiology and Infection control and Prevention

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Mirko Ancillotti

1 Department of Public Health and Caring Sciences, Centre for Research Ethics & Bioethics, Uppsala University, Uppsala, Sweden

This article explores the ethical implications of vaccine-enhanced disease (VDE). The article is clear and of sure interest. I have definitely appreciated the description and analysis of the four cases, which provide evidence-based grounds for the normative discussion. I recommend the publication of this article.

I have a few minor comments that I would like to share with the authors (not a condition for publication, however).

In the Introduction, p.3 of the pdf, it is written: “The ethical implications of VED for research and public policy require careful consideration because, although rare, VED can cause serious harm (including death) and has the potential to undermine public trust in vaccines”. My focus is on the public trust issue, which is repeated multiple times in the article. For instance, at p.8: “Since VED and other rare but serious harms from vaccination have been associated with declines in public trust, policymakers should prepare for such outcomes”.

It is claimed that VED may affect public trust. To my understanding reading the article, trust appears to be undermined by how VED risks/uncertainties translate into vaccination policy and how this is communicated. The authors may consider it obvious and/or implicit. Nonetheless, statements like “VED can cause serious harm (including death) and has the potential to undermine public trust in vaccines” may suggest that the problem is VED per se , in the sense that morbidity and mortality of VED are particularly high and can alter the overall risk/benefit proportion. And given that a continuous assessment of risks and benefits is necessary to strengthen the confidence in immunization programmes, then it would be the impact of VED per se that need to be monitored to ensure public trust. Of course, one does not necessarily exclude the other but the quoted statements (and others in the article) may suggest that VED per se is the problem that may undermine public trust.

On a minor note, the description of the outcome of dengue vaccine in the table is “Vaccine use restricted, uncertain number of deaths, public controversy, effects on vaccine confidence”. Thus, a set of very different outcomes is considered. While ‘Vaccine use restricted’ and ‘uncertain number of deaths’ are in line with the description of the outcomes offered for the other three cases — the decision about the vaccine license and deaths — ‘public controversy’ and ‘effects on vaccine confidence’ refer to a completely different type of outcomes (essentially, public trust). These trust issues emerged only in response to the dengue vaccine? If yes, the table does not need any modifications. If no, the authors may consider to cancel ‘public controversy’ and ‘uncertain number of deaths’ from the description of dengue vaccine outcome (or add the description of potential consequences on public trust to the others).

Zohar Lederman

1 Rambam Medical Campus, Haifa, Israel

This article discussed the ethical implications of vaccine-enhanced disease, or when vaccination augments the symptoms and signs of a communicable disease. It is clearly written, and it addresses a novel and pertinent issue in bioethics, with a coherent normative deliberation based on solid empirical ground. In light of these, it should be indexed.

Several minor comments for consideration (not necessary to address for acceptance):

I wonder whether ‘highly uncertain’ correlates with ‘not expected’- I would think that highly uncertain means that its effects were simply unknown, while not expected means that based on available knowledge risk was determined to be minimal. In this case, the latter seems to be what the authors want to say.

I wonder how feasible this is? What is long enough? Otherwise put, what is the threshold for enough certainty in order to license a vaccine? And who determines the threshold? The obvious player may be the WHO, but what about individual communities? Maybe certain communities would prefer higher stakes for potentially higher gains or vice versa?

  • It might be worthwhile to sound a warning about uncertainty delaying scientific progress.   After all, people are dying from infectious diseases, and the more we wait for certainty, the more will die, perhaps unnecessarily.
  • “but in the long term continued mass vaccination and reduced incidence of dengue might result in increasingly large numbers of seronegative people experiencing VED if/when dengue epidemics recur” The article is extremely nuanced, but I wonder whether this consideration may be too nuanced. Worrying about what might happen if we achieve herd immunity against Dengue in terms of VED is like worrying about our planet and its subsistence when we consider developing a cure for cancer. Sure, it’s something to think about, the solution may exist or appear in the future and in any case, this is a tangential consideration in the current context. In other words, it is OK to leave some tangential considerations aside.
  • “Public health agencies have a responsibility to develop evidence-based approaches to engage with target popuations about the benefits, risks, and uncertainties of vaccine programmes (including VED where relevant) and to respond to their perspectives, concerns, and expectations. Engagement with relevant populations regarding vaccination should include careful transparent disclosure of the potential for VED where this is reasonable concern” this sounds wonderful, but you know human psychology makes things much more complex. The manner in which data will be presented (and by whom) or views are gained will affect the outcome of the so-called engagement. If Covid-19 has shown us anything, it is that many folks tend to be conservative, opting to take their chances with a pathogen rather than uncertainty or some rare side effects. I have no solution to this and am not sure how the authors could address this issue, or if in fact, they should in this article.

 To conclude, I guess my greatest concern with this fine piece is the lack of local voices in the decision-making process and the psychology involved in the mainstreaming and application of the scientific and normative complexity addressed here. Simply ‘engaging’ with local communities may not be enough. Public health is at the end of the day political, and- whether we as ethicists want it or not- people will make decisions based on what appeals to them most, rather than what is just or scientifically justified. Again, I think the authors should be allowed not to enter this rabbit hole.

public health ethics, infectious disease ethics, One Health ethics.

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