research proposal on sexually transmitted disease

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Research Article

Prevalence of sexually transmitted infections among young people in South Africa: A nested survey in a health and demographic surveillance site

Roles Conceptualization, Funding acquisition, Investigation, Project administration, Supervision, Writing – original draft

* E-mail: [email protected]

Affiliation MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom

Roles Data curation, Formal analysis, Writing – review & editing

Affiliation Africa Health Research Institute, KwaZulu-Natal, South Africa

Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing

Affiliations MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom, Africa Health Research Institute, KwaZulu-Natal, South Africa

Roles Investigation, Project administration, Supervision, Writing – review & editing

Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Writing – review & editing

Affiliations Africa Health Research Institute, KwaZulu-Natal, South Africa, Centre for Maternal, Adolescent, Reproductive, and Child Health, London School of Hygiene & Tropical Medicine, London, United Kingdom

Roles Investigation, Project administration, Supervision, Validation, Writing – review & editing

Roles Conceptualization, Methodology, Resources, Writing – review & editing

Affiliation HIV/STI Reference Laboratory, Institute of Tropical Medicine, Antwerp, Belgium

Roles Data curation, Project administration, Resources, Software, Supervision, Writing – review & editing

Roles Conceptualization, Project administration, Resources, Supervision, Writing – review & editing

Roles Conceptualization, Methodology, Project administration, Resources, Supervision, Writing – review & editing

Affiliations Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, United Kingdom, Africa Health Research Institute, School of Nursing & Public Health, University of KwaZulu-Natal, KwaZulu-Natal, South Africa

Roles Conceptualization, Funding acquisition, Investigation, Resources, Supervision, Writing – review & editing

Affiliations Africa Health Research Institute, KwaZulu-Natal, South Africa, Division of Infection and Immunity, University College London, London, United Kingdom

Roles Conceptualization, Investigation, Methodology, Supervision, Writing – review & editing

¶ ‡ These authors are joint senior authors on this work.

Affiliations Africa Health Research Institute, School of Nursing & Public Health, University of KwaZulu-Natal, KwaZulu-Natal, South Africa, Academic Unit of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom, Department of Social Statistics and Demography, University of Southampton, Southampton, United Kingdom, Research Department of Epidemiology & Public Health, University College London, London, United Kingdom

Roles Conceptualization, Investigation, Methodology, Resources, Supervision, Writing – review & editing

Affiliations Africa Health Research Institute, KwaZulu-Natal, South Africa, Institute for Global Health, University College London, London, United Kingdom

• Suzanna C. Francis, 
• T. Nondumiso Mthiyane, 
• Kathy Baisley, 
• S. Lerato Mchunu, 
• Jane B. Ferguson, 
• Theresa Smit, 
• Tania Crucitti, 
• Dickman Gareta, 
• Siphephelo Dlamini, 

• Published: February 27, 2018
• https://doi.org/10.1371/journal.pmed.1002512
• Reader Comments

Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15–24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa.

Methods and findings

A total of 1,342 young people, stratified by age (15–19 and 20–24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home.

Conclusions

A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes.

Author summary

Why was this study done.

• Adolescents and young adults are particularly vulnerable to sexually transmitted infections (STIs).
• The first strategic direction of the WHO Global Health Sector Strategy on Sexually Transmitted Infections 2016–2021 is to collect information on STI prevalence and incidence across representative populations.
• There is evidence that bacterial vaginosis (BV) is a risk factor for poor birth outcomes and STIs including HIV. The collection of BV prevalence may therefore also be important.
• Developing new cohorts for dedicated STI/BV prevalence studies may not be realistic, particularly in sub-Saharan Africa, where the impact of STIs/BV and their consequences may be greatest.
• Nesting STI/BV surveys within networks of health and demographic surveillance sites (HDSSs) would be an efficient way of providing data to better understand STI epidemiology among adolescents and young people in high HIV prevalence settings.

What did the researchers do and find?

• We carried out a nested STI/BV survey among 1,342 adolescent and young people in an HDSS in KwaZulu-Natal, South Africa, between October 2016 and January 2017.
• Potential participants were contacted at home and invited to participate.
• Participants were interviewed, and samples were collected for STI/BV testing.
• We showed that this study was feasible within the 3.5-month time period: 1,171/1,342 (87%) individuals had ≥1 attempted home visit, of whom 790 (67%) were successfully contacted.
• The study was acceptable: among those contacted and eligible, 447/645 (69%) enrolled. Both men and women reported few problems with sample collection.
• We report a high burden of STIs/BV in this population, particularly of chlamydia (5% in men and 11% in women), herpes simplex virus type 2 (17% in men and 29% in women), and BV (42% in women).

What do these findings mean?

• Nested STI/BV surveys in HDSSs can be feasible and acceptable; however, more survey time is needed to ensure that all potential participants are visited and contacted.
• These studies should be carried out in conjunction with studies to measure STI/BV prevalence in high-risk populations (e.g., female sex workers) to provide robust prevalence estimates.
• These data are essential to advocate, fund, plan, implement, and evaluate interventions for STI prevention and control among adolescents and young people.
• Strategies for the prevention and control of chlamydia, herpes simplex virus type 2, and BV are needed in this population.

Citation: Francis SC, Mthiyane TN, Baisley K, Mchunu SL, Ferguson JB, Smit T, et al. (2018) Prevalence of sexually transmitted infections among young people in South Africa: A nested survey in a health and demographic surveillance site. PLoS Med 15(2): e1002512. https://doi.org/10.1371/journal.pmed.1002512

Academic Editor: Nicola Low, University of Bern, SWITZERLAND

Received: August 22, 2017; Accepted: January 19, 2018; Published: February 27, 2018

Copyright: © 2018 Francis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The dataset relating to these findings is the INDEPTH Data Repository, https://doi.org/10.7796/iGUGU.MAIN.STUDY.DATA.PLOS.MEDICINE.v1

Funding: Financial support for this research was provided by ViiV Healthcare's Positive Action for Adolescents Programme; the Wellcome Trust with core funding for AHRI (082384/Z/07/Z) and NM receiving support (WT083495MA); the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme FP7/2007-2013 under REA grant agreement MS receiving support (612216); and joint funding under the UK Medical Research Council (MRC)/ UK Department for International Development (DFID) Concordat agreement which is supported by the European Union under the EDCTP2 programme (reference MR/K012126/1) with SCF and KB receiving support (G0700837). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: AHRI, Africa Health Research Institute; BV, bacterial vaginosis; HDSS, health and demographic surveillance site; HPV, human papillomavirus; HSV-2, herpes simplex virus type 2; INDEPTH Network, International Network for the Demographic Evaluation of Populations and their Health; LMICs, low- and middle-income countries; OR, odds ratio; STI, sexually transmitted infection; TPHA, Treponema pallidum haemagglutination; VDRL, Venereal Disease Research Laboratory

Introduction

In 2012, 286 million people aged 12–24 years lived in Africa, accounting for 18% of the global youth population. By 2040, the number of young people in Africa is projected to increase by 60% to 466 million [ 1 ]. Health interventions targeted at this age group are important for current and future adult health and for the health of the next generation. This is particularly true for sexually transmitted infections (STIs), which, when acquired in adolescence, can jeopardise sexual and reproductive health later in life and, for women, the health of their babies. In low- and middle-income countries (LMICs), symptomatic STIs are treated by syndromic management (presumptive treatment for symptomatic people without the use of laboratory tests) [ 2 ], but most STIs are asymptomatic and go unnoticed and untreated. Both symptomatic and asymptomatic STIs can cause serious morbidity, including pregnancy complications, cancer, infertility, and enhanced HIV transmission. Many of these sequelae are preventable if STI testing and treatment is implemented. Moreover, there is growing evidence that the common reproductive tract condition bacterial vaginosis (BV) is an independent risk factor for HIV [ 3 , 4 ], and BV-associated microbiota may decrease the efficacy of topical microbicides [ 5 ].

High STI prevalence among young people has been observed worldwide and highlights the critical need for global efforts to improve sexual and reproductive health in this population. In an individual participant data meta-analysis of 18 HIV prevention studies among women in sub-Saharan Africa, STI prevalence was higher among young women aged 15–24 years than among older women for all STIs except herpes simplex virus type 2 (HSV-2) [ 6 ]; in this age group, the estimated range of prevalence of STIs in South Africa among clinic/community populations was 8.0% to 20.6% for chlamydia, 1.4% to 8.9% for gonorrhoea, 3.1% to 20.0% for trichomoniasis, 31.9% to 53.7% for HSV-2, and 35.8% to 52.4% for BV. In addition, viral STIs such as HSV-2 and human papillomavirus (HPV) infection are often acquired soon after sexual debut, which usually occurs in adolescence, and both are common among young people in sub-Saharan Africa [ 7 – 10 ]. However, many of the studies yielding these results are conducted in urban areas and/or clinical cohorts of adolescents and young adults known to be at high risk of infection. To date, there have been few population estimates of the burden of STIs among adolescent girls and young women and no studies among men [ 6 ].

The WHO Global Health Sector Strategy on Sexually Transmitted Infections 2016–2021 has outlined the goals and targets for global STI prevention and control. The first strategic direction is to collect information on STI prevalence and incidence across representative populations [ 11 ]. Understanding regional and national STI epidemics is essential to advocate, fund, plan, and implement interventions for STI prevention and control. The strategy also urges LMICs to move from syndromic to aetiologic surveillance of STIs, and to conduct routine surveillance in key populations most at risk for STIs including adolescents. Yet, in resource-limited settings, developing new cohorts for dedicated STI prevalence studies may not be realistic, particularly in sub-Saharan Africa, where the impact of STIs and their consequences may be greatest.

Networks of health and demographic surveillance sites (HDSSs) conducting longitudinal population-based research such as the International Network for the Demographic Evaluation of Populations and their Health (INDEPTH Network) may provide opportunities to obtain representative STI/BV prevalence estimates for adolescents and young people and facilitate community entry and engagement with sensitive topics such as sexual health [ 12 ]. However, population-based surveys can be challenging to conduct. Key requirements include the acceptability of being approached at home and home sampling, the feasibility of finding young people at home and a parent available to consent, the receipt of results while maintaining confidentiality, and establishing clinical pathways for the treatment of cases. We conducted a study in the Africa Health Research Institute (AHRI; formerly the Africa Centre for Health and Population Studies) HDSS, a member of the INDEPTH Network, to investigate the acceptability and feasibility of home-based sampling of STIs/BV among young people aged 15–24 years, and to measure prevalence and factors associated with STIs/BV. The background 2011 HIV prevalence in women aged 15–19 years and 20–24 years was 14.7% and 26.5%, respectively, and in men aged 15–19 years and 20–24 years was 7.0% and 10.2%, respectively [ 13 ].

This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines ( S1 STROBE Checklist ) [ 14 ].

Setting and sampling

The AHRI HDSS is located in the rural uMkhanyakude district of KwaZulu-Natal, covering an area of 438 km 2 , with a 2016 population of approximately 100,000 people who are members of 12,000 households [ 15 ]. Since 2000, annual household-based surveys have been used to collect information on births, deaths, and migration patterns from all household members, including non-residents. In addition, resident household members aged ≥15 years are invited to participate in an annual HIV serosurvey, and to complete a questionnaire on general health and sexual behaviour.

For the STI survey, young men and women who were resident in the HDSS, based on the data collected in the routine household surveillance, and aged 15–24 years as of 19 July 2016 were eligible for inclusion. A random sample of 1,342 young people was selected to obtain a target sample size of 800, allowing for 40% non-contact/refusals. This sample size would have provided acceptable precision for estimating the prevalence of an STI with a prevalence as low as 1.5%. Sampling was stratified by age group (15–19 years and 20–24 years) and sex. The HDSS is divided into 14 subareas; within each stratum, a fixed proportion was sampled from each subarea to reflect the population distribution across the HDSS.

Ethics, informed consent, and community engagement

The University of KwaZulu-Natal Biomedical Research Ethics Committee, the London School of Hygiene & Tropical Medicine Research Ethics Committee, the Southampton General Hospital Faculty of Medicine Ethics Committee, Hlabisa District Hospital, and the AHRI Somkhele Community Advisory Board approved the study protocol. The STI survey was called Ukuvikela impilo yetho yokuzalana eyigugu , isiZulu for ‘protecting our precious reproductive health’. The AHRI Community Engagement Team disseminated information about the study in community dialogues and road shows. Potential participants were contacted at home and invited to participate. Written parental consent was required for participants <18 years old, with participant written assent. Participants aged 18 years or older proved written consent. Participants consented separately for each sample type (vaginal swab [women only], urine [men only], and blood); participants who did not consent for a sample could still enrol in the study. Participants were asked for permission to link their STI survey data with the data collected in the annual routine household and individual surveillance.

Study procedures

The study team consisted of 2 field workers (1 male and 1 female), 2 female licensed practical nurses, 1 male licensed practical nurse, and 1 male registered nurse team leader, with an intention to match a same-sex nurse to participants whenever possible. The field work was conducted Tuesday to Saturday from 11 AM to 7 PM to maximise the chances of finding participants at home.

After informed consent/assent, the participant had a short computer-assisted personal interview by the study nurse [ 16 ]. The interview obtained data on demographics, substance use, sexual behaviour, violence, circumcision (men only), family planning (women only), genital hygiene, and genital symptoms. For questions about sexual behaviour and violence, the participant was asked to self-interview using a tablet device; however, the study nurse was available to support the participant if needed. If a participant reported genital complaints, they were referred to our study nurse in a local primary health clinic for syndromic management as per 2015 South African STI management guidelines [ 17 ].

All participants had 8.5 ml of blood drawn for syphilis and HSV-2 testing. For women, the research nurse explained the procedure to self-collect a total of 5 vaginal swabs for testing for chlamydia, gonorrhoea, trichomoniasis, and BV (an additional swab was collected for storage). Swab collection took place in a private setting identified by the participant. Men collected a urine sample for testing for chlamydia, gonorrhoea, and trichomoniasis.

After the sample collection, participants were asked to rate their agreement with 10 statements using a visual analogue scale (VAS) ranging from 0 (easy/agree) to 100 (difficult/disagree) to assess the ease of understanding of consent for the study, the instructions for collecting the sample, and the participant’s experience of participation.

All participants were asked to provide contact information for test results, including their preferred mode of contact for both positive and negative results (e.g., telephone call, SMS message, or WhatsApp message), and ideal hours for contact. We attempted to contact all participants with the results for laboratory-diagnosed curable STIs (chlamydia, gonorrhoea, trichomoniasis, and syphilis). All participants with mobile phones were given 5 South African rand (US$0.37) of air time to contact the study nurses with questions if needed. Participants who had a positive test for a curable STI were referred for free treatment; reimbursement for travel was provided. We traced all cases who were not contactable or did not come to clinic for treatment. We used British Association for Sexual Health and HIV guidelines for the treatment of laboratory-diagnosed chlamydia, gonorrhoea, and trichomoniasis [ 18 – 20 ], and South African STI management guidelines for the treatment of syphilis [ 17 ].

Laboratory methods

Laboratory testing was performed according to manufacturers’ instructions and standard operating procedures in the central AHRI laboratory and Global Clinical and Viral Laboratory in Durban, South Africa. Serum samples were used to test for IgG antibodies for HSV-2 by a type-specific ELISA (Kalon Biological, Guildford, UK). Syphilis infection was determined by the Determine Syphilis TP rapid test (Alere, Waltham, MA, US) in the central AHRI laboratory. All positives were confirmed at the Global Clinical and Viral Laboratory with Treponema pallidum haemagglutination (TPHA) (Randox Laboratories, Crumlin, UK) and tested with the Venereal Disease Research Laboratory (VDRL) test (Omega Diagnostics, Alva, UK) using a reverse algorithm as per South African STI management guidelines [ 17 ] due to the young age of participants (i.e., unlikely to have treated past infections). Syphilis infection was defined as follows: negative, TPHA−/VDRL−; early or previously treated infection, TPHA+/VDRL−; and active syphilis, TPHA+/VDRL+ low titre [<1:8] or TPHA+/VDRL+ high titre [≥1:8].

Vaginal swabs were used to prepare a slide at the home and air dried. Slides were transported to the central AHRI laboratory, methanol-affixed, Gram stained, and examined for BV using the Nugent score [ 21 ]. A Nugent score of 0–3 indicated normal microbiota, 4–6 indicated intermediate microbiota, and 7–10 indicated BV. Vaginal swabs (women) and urine (men) were sent to Global Clinical and Viral Laboratory for testing by real-time PCR for Neisseria gonorrhoeae , Chlamydia trachomatis , and Trichomonas vaginalis . Detection was carried out using the Lightmix Kit Neisseria gonorrhoeae , the Lightmix Kit Chlamydia trachomatis , and the Lightmix Kit Trichomonas vaginalis (TIB MOLBIOL, Berlin, Germany) following the manufacturer’s instructions. All positive tests for N . gonorrhoeae were confirmed using GeneXpert (Cepheid, Sunnyvale, CA, US). The confirmation test should have a higher specificity than the first test; the GeneXpert N . gonorrhoeae detection probe has 2 primer sets that increase the specificity needed for the N . gonorrhoeae confirmation [ 22 , 23 ]. External quality controls were carried out quarterly for real-time PCR with the College of American Pathologists.

Data management and statistical methods

Data were captured electronically using REDCap software [ 24 ]. Range and consistency checks were done automatically during data capture; further data cleaning and analysis was done using Stata 14 (College Station, TX, US). All questions required a response to minimise missing data, although participants could reply ‘don’t know’ or ‘prefer not to say’.

The statistical analysis plan was prepared prior to the statistical analysis ( S1 Analysis ). Changes in response to peer review of this paper included the inclusion of other STIs in the BV risk factor analysis, and the inclusion of transactional sex in each risk factor analysis. Continuous variables were summarised using means and standard deviations or medians and interquartile ranges; categorical data were summarised using frequency counts and percentages. Missing data were not imputed.

The acceptability and feasibility of our survey were measured by the following outcomes: proportion of participants who were selected and contactable, the proportion of those contacted who agreed to participate, the proportion who agreed to each sample collection (e.g., blood, vaginal swabs, and urine), median and interquartile range of responses to a VAS measuring acceptability post-sampling, and proportion of cases who presented for treatment. We also estimated STI/BV prevalence and explored factors associated with any curable STI (chlamydia, gonorrhoea, syphilis, and trichomoniasis), HSV-2, and BV.

The number of individuals who were successfully contacted and who consented to participate were tabulated by sex, age group, residence location (urban/peri-urban/rural), household socioeconomic status, education level, and HIV status using linked data from the HDSS. Characteristics of individuals who participated and the remainder in the eligibility list were compared using chi-squared tests.

The prevalence estimate of each STI or BV, and its 95% confidence interval, was calculated overall and by sex; prevalence estimates were weighted to account for the stratified sample design and non-response, calculated as the inverse probability of study participation in strata defined by age group, sex, and residence location (urban/peri-urban/rural). We compared these results to unweighted prevalence and prevalence weighted for the stratified sample design only.

Logistic regression was used to estimate odds ratios and 95% CIs for factors associated with the presence of any curable STI (chlamydia, gonorrhoea, syphilis, or trichomoniasis), of HSV-2, and of BV; separate models were developed for each outcome. Potential factors associated with curable STIs, HSV-2, and BV were examined using a conceptual framework with 3 levels: sociodemographic factors, modifiable behavioural factors (including genital hygiene), and sexual behaviour and violence. For each outcome, age and sex (except for BV, which was in women only) were considered a priori confounders and were included in all models. Sociodemographic factors whose age- and sex-adjusted associations with the outcome were significant at P < 0.10 were included in a multivariable model; those remaining associated at P < 0.10 were retained in a core model. Behavioural factors were then added to this core model one by one; those that were associated with the outcome at P < 0.10, after adjusting for sociodemographic factors, were included in a multivariable model and retained if they remained associated at P < 0.10. Associations with sexual behavioural and violence factors were subsequently determined in a similar way. Many of the questions about sexual relationships were asked only if participants reported having ever had sex, so analyses of these variables were restricted to that subgroup.

Acceptability and feasibility

The field work took place from 4 October 2016 to 31 January 2017. Due to unexpected time limitations, only 1 visit attempt per selected individual was carried out from November to January to attempt coverage in subareas (a total of 14 subareas), but not all selected young people were visited. Among the 1,342 individuals selected, 1,171 (87%) had ≥1 attempted home visit, of whom 781 (67%) were successfully contacted ( Fig 1 ). Of those who were contacted, 645 (83%) were still eligible. Among those contacted and eligible, 447 (69%) enrolled. Individuals aged 20–24 years were less likely to be contacted than those aged 15–19 years (63% versus 70% of those with an attempted visit, P = 0.01) and less likely to be eligible after contact was made (mostly due to migration). Men were less likely to be contacted than women (58% versus 75%, P < 0.001). Overall, there was strong evidence that individuals who were sampled but did not enrol were more likely to be older, male, and from rural or urban areas, and to have completed secondary education or above, compared with those who enrolled ( S1 Table ).

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1 Not visited: no visit was made to the household because the study ended. 2 Not contacted: at least 1 visit was made to the household, but either a parent (if selected individual <18 years) or the individual was unavailable. 3 Ineligible: individuals who were found to have out-migrated from the health and demographic surveillance site ( N = 73 women and 53 men) or who were not capable of providing consent ( N = 6 women and 4 men). 4 Individuals who were interested in the study, but could not enrol because study ended.

https://doi.org/10.1371/journal.pmed.1002512.g001

Of those enrolled, 96% of women provided all vaginal swabs and 93% provided blood samples; all men provided urine samples and 98% provided blood samples. Both men and women reported that it was easy to understand how to collect urine and vaginal swabs, respectively ( Fig 2A ). Participants agreed they felt comfortable, in control, relaxed, and confident of their ability to collect the sample correctly ( Fig 2B ). Participants disagreed that sampling was painful. Most men disagreed that they felt anxious or embarrassed, and over half of women disagreed that they were anxious or embarrassed ( Fig 2C ).

The vertical line within the box indicates the median, the boundaries of the box indicate the interquartile range (25th and 75th percentiles), and the whiskers indicate values that are within 1.5 times the interquartile range above the 75th percentile, or 1.5 times the interquartile range below the 25th percentile. Values outside that range are plotted as individual points, e.g., the medians for (A) equal 0. (A) Ease of understanding the study and instructions, and the ease of sample collection. (B) Experience of self-collecting urine (males) or vaginal swabs (women)—positive items. (C) Experience of self-collecting urine (males) or vaginal swabs (women)—negative items.

https://doi.org/10.1371/journal.pmed.1002512.g002

Of those who provided samples, 206/245 (84%) of individuals aged 15–19 years and 184/192 (96%) of individuals aged 20–24 years enrolled had access to a telephone to receive results. Of those, the majority preferred a telephone call for both positive and negative results (59% and 57%, respectively), followed by an SMS message (37% and 39%, respectively). Few chose to receive their results (positive or negative) by WhatsApp message (4% and 4%, respectively). These results were similar by sex and age, although a higher proportion of males than females preferred to receive their results by telephone ( S2 Table ).

Fifty-five participants had ≥1 curable STI and were invited to the clinic for management: 52 (95%) came on their own, and 3 had to be traced.

Results of behavioural questionnaire

Most participants were currently enrolled in school ( Table 1 ). Few participants were working (11% of men and 5% of women). Proportionally, more men aged 20–24 years reported having ever smoked a cigarette compared to women of the same age (17% versus 8%, respectively). Conversely, proportionally fewer men compared to women reported having ever had at least 1 drink of alcohol (23% versus 51%, respectively). A small proportion of participants reported cannabis use: 8% among men aged 20–24 years and 4% among women of the same age. Few participants reported using other drugs (1%).

https://doi.org/10.1371/journal.pmed.1002512.t001

In all, 51% of men reported circumcision: younger men were more likely to be circumcised ( Table 1 ). Sixteen percent of women reported using intravaginal cleansing; older women were more likely to report intravaginal cleansing. In all, 23% of women aged 15–19 years and 50% of women aged 20–24 years reported use of any type of contraception.

In all, 61 (33%) men and 155 (63%) women reported having had sexual intercourse; of these, the median (IQR) number of lifetime partners was 4 (2–6) for men and 3 (2–3) for women. A larger proportion of men than women reported having used a condom at last intercourse (58% versus 41%, respectively). A smaller proportion of men than women reported knowing their last partner’s HIV status (37% versus 55%, respectively), and a smaller proportion of men than women reported discussing their own HIV status with their last partner (48% of men versus 63% of women).

More women aged 20–24 years reported providing (32%) or receiving oral sex (46%) than men of the same age group (12% and 13%, respectively). Few participants reported ever having anal sex, and fewer men than women (1% versus 5%). Among men who participated in the 2016 HIV serosurvey, the prevalence of laboratory-diagnosed HIV among those aged 15–19 years was 4% and among those aged 20–24 years was 19%. Among women, the prevalence of laboratory-diagnosed HIV among those aged 15–19 years was 9% and among those aged 20–24 years was 30%.

Prevalence of STIs/BV

Weighted prevalence from Table 2 shows a high prevalence of chlamydia in men aged 20–24 years (12.6%; 95% CI 6.4%–23.3%) and women in both age groups (15–19 years: 11.7%; 95% CI 6.8%–19.3%; 20–24 years: 10.2%; 95% CI 6.0%–16.9%). The prevalence of gonorrhoea was low, from 0 cases among men aged 20–24 years to 3.2% (95% CI 1.2%–8.2%) in women of the same age group. There was 1 case of active syphilis—the overall prevalence of active syphilis was 0.1%. There were 5 TPHA−/VDRL+ samples. The prevalence of trichomoniasis was lower in men compared with women (0.6% [95% CI 0.1%–4.0%] versus 4.6% [95% CI 2.6%–7.9%]); the highest prevalence was among women aged 20–24 years. In all, 14% of individuals had a curable STI (chlamydia, gonorrhoea, syphilis, or trichomoniasis). Of these, 75% reported no symptoms. The prevalence of HSV-2 was lower in men compared with women (16.8% [95% CI 11.3%–24.1%] versus 28.7% [95% CI 23.3%–34.7%]), with the highest prevalence among women aged 20–24 years. The prevalence of BV was 41.1% (95% CI 32.3%–50.5%) among women aged 15–19 years and 44.2% (95% CI 35.5%–53.2%) among women aged 20–24 years. Prevalence weighted for sampling and non-response ( Table 2 ) was similar to unweighted prevalence and prevalence using sampling weights only ( S3 Table ).

https://doi.org/10.1371/journal.pmed.1002512.t002

Factors associated with STIs/BV

In the adjusted analysis of factors associated with curable STIs (chlamydia, gonorrhoea, syphilis, and trichomoniasis), participants aged 20–24 years and women had more than twice the odds of having a curable STI compared to participants aged 15–19 years and men, respectively ( Table 3 ). Having a higher number of lifetime sexual partners was associated with having a curable STI ( P = 0.038). Reporting having had sexual intercourse was strongly associated with having a curable STI.

https://doi.org/10.1371/journal.pmed.1002512.t003

In the adjusted analysis of factors associated with HSV-2, participants aged 20–24 years and women had twice the odds of HSV-2 infection compared to participants aged 15–19 years and men, respectively ( Table 4 ). Participants currently enrolled in school or working had less than half the odds of HSV-2 infection compared to those who were neither in school nor working.

https://doi.org/10.1371/journal.pmed.1002512.t004

In the adjusted analysis of factors associated with BV, there was weak evidence that being currently enrolled in school or working was associated with a diagnosis of BV ( Table 5 ). Those having ever drunk alcohol had twice the odds of a diagnosis of BV, and there was weak evidence that having ever smoked a cigarette was associated with a diagnosis of BV. Independently, those reporting genital touching and having ever had sex had twice the odds of a diagnosis of BV. Participants who were HSV-2 seropositive had 4 times the odds of a diagnosis of BV.

https://doi.org/10.1371/journal.pmed.1002512.t005

In the subgroup analysis among participants who reported having had sex, there was some evidence that discussing the last partner’s HIV status was associated with not having a curable STI (adjusted OR 0.48; 95% CI 0.23–1.00; S4 Table ). There was no evidence that factors included in this subgroup analysis were associated with either HSV-2 infection or diagnosis of BV ( S5 and S6 Tables).

We conducted a nested STI survey among young people aged 15 to 24 years in a rural HDSS in KwaZulu-Natal, and found it to be feasible and acceptable. The HDSS provided infrastructure and a sampling frame to carry out a population-based cross-sectional study of STI/BV prevalence. There was a high burden of STIs/BV in this high HIV prevalence setting. Most of the infections were asymptomatic and would not have been identified or treated using national syndromic management guidelines.

This study is a proof of concept that STI surveys can be successfully conducted within HDSS networks such as the INDEPTH Network [ 12 ], the Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network) [ 25 ], the Department of Science and Technology (DST), and the South African Medical Research Council (SAMRC) South African Population Research Infrastructure Network (SAPRIN) [ 26 ] ( Fig 3 ). STI surveys can be conducted within the infrastructure of HDSSs with 2 important advantages. First, STI surveys can be carried out in LMICs intermittently to contribute to estimates of the global burden of STIs and to evaluate local implementation of global STI control programmes at a population level. Second, STI surveys can be carried out more frequently in settings with high HIV/STI prevalence to monitor and evaluate enhanced STI/HIV control programmes. HDSS networks could provide a strategic platform to strengthen STI surveillance and control in LMICs, especially in sub-Saharan Africa, where HIV and STI/BV prevalence are high. Importantly, while population-based data are crucial for an effective STI prevention and control programme, these data must be complemented by robust data from high-risk groups (e.g., female sex workers) to account for STI transmission dynamics that depend on high rates of partner change [ 27 ].

(A) International Network for the Demographic Evaluation of Populations and their Health (INDEPTH Network), a network of 48 members and 7 associate members in 21 low- and middle-income countries in Africa, Asia, and Oceania conducting population-based surveillance of the health status of communities (modified from http://www.indepth-network.org/member-centres ). (B) Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA Network), a network of 10 centres in sub-Saharan Africa conducting population-based HIV surveillance (modified from http://alpha.lshtm.ac.uk/partner-study-institutions/ ). (C) South African Population Research Infrastructure Network (SAPRIN), an expanding network of HDSSs in South Africa (modified from http://saprin.mrc.ac.za/nodes.html ). AHRI, Africa Health Research Institute; KZN, KwaZulu-Natal.

https://doi.org/10.1371/journal.pmed.1002512.g003

The prevalence of chlamydia was high in this STI survey among women of both age groups and among men aged 20–24 years. Several studies report high prevalence of chlamydia in South Africa [ 6 , 28 – 31 ]; both Microbicide Trials Unit (MTN)–003 (VOICE) and HIV Prevention Trials Network (HPTN) 055 showed higher baseline chlamydia prevalence and incidence among women in South Africa compared with other sites in the multi-site studies. Sub-regional or national differences in STI epidemics among young people could be further elucidated in STI surveys in a network of HDSSs. Aetiological diagnosis of STIs is unaffordable and inaccessible for most LMICs. Rapid, accurate, and affordable point-of-care tests might bridge this gap in future [ 32 ]. The development of tools such as these must be carried out in parallel with population-based STI surveys and analyses of risk factors.

Although HSV-2 and BV are not curable STIs, better control tools are needed for them, and we recommend continued integration of HSV-2 and BV in STI prevalence surveys. The prevalence of HSV-2 in our study was almost twice as high for young women as for young men, and almost 50% in women aged 20–24 years. Rapid acquisition of HSV-2 after sexual debut has been reported in several studies [ 8 , 10 ], suggesting that HSV-2 seropositivity could be used as a biological proxy for sexual activity. Over 40% of women in this study had BV, consistent with other studies in sub-Saharan Africa [ 32 ]. Factors associated with BV in our study (sexual debut, currently having more than 1 sex partner, and HSV-2 infection) are consistent with the literature [ 32 ]. Despite BV not being considered a traditional STI, there is an accumulating body of evidence suggesting that sexual transmission is an integral part of its pathogenesis [ 32 ]. In addition, BV is associated with serious sequelae, including preterm delivery and increased risk of STI and HIV acquisition and transmission of HIV [ 3 , 33 – 37 ].

Population-based demographic and behavioural data are also important for planning and evaluating STI prevention and control programmes [ 38 ]. In this HIV hyperendemic setting, it is reassuring that there was a higher prevalence of self-reported circumcision among the younger men than among the older men—suggesting the population impact of male medical circumcision programmes. However, the extremely low self-reported condom use at last sex is a tremendous concern. In addition, few participants knew their last partner’s HIV status. In this STI survey, current enrolment in school or working was protective for HSV-2 and BV. These data mirror findings from the AHRI HDSS, which showed that out-of-school youth reported earlier sexual debut and more high-risk sex than in-school youth [ 39 ], suggesting that interventions to keep adolescents in school may be just as relevant for other STIs as they are for HIV [ 40 , 41 ].

Strengths of this study include a high rate of acceptability for participation and sample collection, the success in treating those with a curable STI, and the use of a population-based platform as a sampling frame. There are several challenges for carrying out home-based studies, including contacting young people during school hours and the provision of confidential results to participants; however, we maximised contact by modifying the field work hours from 11:00 to 19:00 from Tuesday to Saturday, and provided participants with a choice of mode for receiving results. Once contacted, enrolment into a population-based study of STI/BV testing was acceptable among young people, as was the home-based collection of samples, including the self-collection of genital samples. An additional strength of this study is that it was conducted in an area with persistently high HIV incidence and prevalence. Results of this study could help to inform co‐strategies to address both HIV and STIs that synergise the transmission of HIV.

This study was not without limitations. The sample collection period was limited to 3.5 months by the start of the next HDSS surveillance round, and we did not reach our target of 800 young people. The smaller sample size of 447 provided less precision for prevalence estimates and less power to investigate factors associated with STIs/BV. In addition, the overall coverage in the survey was low, increasing the potential for selection bias. It was challenging to find young men aged 20–24 years at home. HPTN 017 (PopART), a cluster-randomised controlled trial offering home-based HIV counselling and testing in South Africa and Zambia, also reported that young men (32.7%) more often than young women (20.2%) were not at home at the time of visits [ 42 ]. Furthermore, many young people were not at home due to migration. The AHRI individual surveys of residents aged 17–49 years indicate that approximately one-fifth of men and women in any survey round have migrated at least once in the last 2 years, and persons with a recent migration history have a higher risk of HIV infection [ 43 ]; thus, those with a recent migration history are likely to have a different risk profile. The AHRI HDSS was established in a highly mobile population with a severe HIV epidemic, in which characterisation of migration and mobility was central to its conceptual and data model [ 44 ]. Indeed, nesting STI surveys in HDSSs may offer another advantage over one-off de novo STI prevalence surveys: the HDSS sampling frame has information about those who are not enrolled into the study. Additionally, while a one-time survey will miss some of those who have migrated; annual repeat cross-sectional surveys ensure that most age-eligible household members contribute data over time. Reassuringly, STI/BV prevalence weighted for both sampling and non-response data was very similar to the unweighted prevalence or prevalence weighted for sampling only.

Another limitation was that there was evidence of underreporting of sexual behaviours: 6% of participants with a curable STI and 15% of participants with HSV-2 reported never having had sex. Underreporting of sexual behaviour is common, especially among adolescents [ 45 ]. We used a computer-assisted survey instrument, study nurses were sex-matched, and interviews were conducted in a private location to improve the completeness and accuracy of self-reported sexual behaviour [ 16 , 46 ], but underreporting was still a challenge. Further research is needed to assess factors affecting the validity of self-reported behaviours among adolescents [ 47 , 48 ]. Importantly, underreporting of sexual behaviour highlights the need to have more robust biological measures of sexual risk, such as STI prevalence.

Finally, this survey is limited to the STIs we tested for—future surveys should consider surveillance of Mycoplasma genitalium infection and N . gonorrhoeae resistance in this population. In addition, surveillance of HPV infection and receipt of vaccination may be important to evaluate implementation of HPV vaccination programmes.

In conclusion, the global population of adolescents and young people is increasing, particularly in sub-Saharan Africa. STIs, including incident HIV, cluster in this population, especially among women. The principles of ‘epidemiology synergy’ between STIs and HIV strongly suggest that STI control must be addressed if HIV is to be brought under effective control [ 49 ]. Population-based, representative prevalence estimates of STIs should be complemented by robust prevalence estimates in key populations to gain a full understanding of the burden of STIs and the impact of interventions. Without robust prevalence estimates, moving an international STI agenda forward will continue to be a challenge. Nesting STI prevalence surveys in HDSSs could provide an efficient strategy for obtaining these data.

Supporting information

S1 strobe checklist. strobe statement—checklist of items that should be included in reports of cross-sectional studies..

https://doi.org/10.1371/journal.pmed.1002512.s001

S1 Analysis. Statistical analysis plan for protocol: A study to pilot the surveillance of reproductive tract infections among young people aged 15 to 24 years in the Africa Centre demographic surveillance area.

https://doi.org/10.1371/journal.pmed.1002512.s002

S1 Table. Comparison of selected characteristics of those who enrolled versus those who did not enrol in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal.

https://doi.org/10.1371/journal.pmed.1002512.s003

S2 Table. Contact preferences for results by age and sex in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal among participants who had access to a telephone.

https://doi.org/10.1371/journal.pmed.1002512.s004

S3 Table. Prevalence of STIs in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal: Unweighted prevalence and prevalence with sampling weights only.

https://doi.org/10.1371/journal.pmed.1002512.s005

S4 Table. Factors associated with gonorrhoea, chlamydia, syphilis, and trichomoniasis in a subgroup analysis among individuals who reported having had sex in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal.

https://doi.org/10.1371/journal.pmed.1002512.s006

S5 Table. Factors associated with herpes simplex virus type 2 in a subgroup analysis among individuals who reported having had sex in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal.

https://doi.org/10.1371/journal.pmed.1002512.s007

S6 Table. Factors associated with bacterial vaginosis in a subgroup analysis among women who reported having had sex in a population-based STI survey among young people aged 15–24 years in rural KwaZulu-Natal.

https://doi.org/10.1371/journal.pmed.1002512.s008

Acknowledgments

We thank the community for their continued support and participation in AHRI HDSS, and AHRI staff. We especially thank the young people who took part in the STI survey, and the STI survey team, including Nsika Sithole, Mbuso Mdletshe, Zandile Nkwanyana, Sithembile Msane, and Njabulo Dayi (data management). We thank Ayaykumar Sewnarain and Greg Ording (laboratory data management) and Sureshnee Pillay, Zizile Sikhosana, Shyamala Padayachi, Siva Danaviah, and Xoli Mpofana for processing and testing samples in the AHRI laboratory. We also thank Global Clinical and Virology Laboratory in Durban for testing services provided. We thank Philippa Matthews for reading and commenting on the protocol and informed consent forms, and Richard Hayes for reading and providing comments on a draft of this paper.

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• Open access
• Published: 08 November 2019

Prevalence of sexually transmitted infections and associated factors among the University of Gondar students, Northwest Ethiopia: a cross-sectional study

• Belayneh Ayanaw Kassie 1 ,
• Hedja Yenus 2 ,
• Resom Berhe 3 &
• Eskeziaw Abebe Kassahun 4  

Reproductive Health volume  16 , Article number:  163 ( 2019 ) Cite this article

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Introduction

Globally, sexually transmitted infections (STIs) remain a major public health problem. University students tend to practices sex which predisposes them to sexually transmitted infections, unwanted pregnancies, and unsafe abortions due to their freedom from families. Therefore, the study aimed to assess the prevalence of sexually transmitted infections and associated factors among the University of Gondar students, northwest Ethiopia.

An institution based cross-sectional study was conducted on 845 the University of Gondar students selected using the multistage sampling technique from March 7–10, 2016. The data were collected using a structured, pre-tested self-administered questionnaire. Bivariate and multivariable logistic regression analyses were employed through SPSS version 20 to identify factors associated with sexually transmitted infections. Odds ratio with a 95% confidence interval was computed to determine the level of association. In the multivariable analysis, variables with p -value less than 5% were considered as statistically significant association between covariates and sexually transmitted infections.

Sexually transmitted infections among university students were found to be 18.20% (95%CI,15.40,20.80). Previous history of sexually transmitted infections (AOR = 2.1; 95%CI: 1.04, 4.38), multiple sexual partners in life (AOR = 2.7; 95%CI:1.70, 4.40), not use of condoms during sexual intercourses (AOR = 2.4; 95%CI:1.50,3.75) and poor knowledge of sexually transmitted infections (AOR = 3.3; 95%CI:1.09,5.32) were significantly associated with sexually transmitted infections.

The prevalence of STIs was high among university students. The previous history of sexually transmitted infections, multiple sexual partners, not using condoms during sexual intercourse and poor knowledge of sexually transmitted infections were found to be associated with the infections. Opening and strengthen reproductive health centers on the campuses, popularizing sexual, and reproductive health information and education, particularly on STI modes of transmission, prevention, and health-seeking behaviors, and providing information on accessing of condoms is recommended to reduce sexually transmitted infections.

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Plain English summary

Sexually transmitted infections (STIs) are a variety of clinical syndromes caused by pathogens that can be acquired and transmitted through sexual contact and remain a major public health problem. Sexually transmitted infections predispose to major health consequence such as infertility, certain cancers, and other chronic disease occurs year after the initial infection. The burden of STIs varies from area to area in the world particularly higher in low-income countries including Ethiopia. There has been limited information on the prevalence and associated factors of sexually transmitted infections among university students in Ethiopia including the study area. Therefore, this study aimed to assess the prevalence of sexually transmitted infections and its associated factors among the University of Gondar students.

A total of 803 students were included of which, 491(61.1%) of students ever practiced sex. Moreover, 18.2% of students were developed sexually transmitted infections. The previous history of sexually transmitted infections, multiple sexual partners in life, not the use of condoms during sexual intercourse and poor knowledge of sexually transmitted infections were significantly and independently associated with sexually transmitted infections. Therefore, improving student’s awareness of the risk factors and implications of sexually transmitted infection is crucial to overcome the burden.

Sexually transmitted infections (STIs) are a variety of clinical syndromes caused by pathogens that can be acquired and transmitted through sexual contact. There are over 30 bacterial, viral, and parasitic pathogens that have been identified to date to be transmitted sexually [ 1 ]. Sexually transmitted infections are a major public health problem worldwide that cause of acute illness, long-term complication, infertility, medical as well as psychological consequences and death [ 2 ]. Moreover, STIs facilitate the spread of the human immunodeficiency virus (HIV) [ 3 ]. In 2012, 498.9 and 92.6 million new cases of STIs occurred on the globe and in Africa, respectively. Thus, on average, about 1.4 million people are infected with STIs every day [ 4 ]. In Ethiopia, the highest reported rates of STIs are found among 15–24-year old, while about half of all of the people infected with HIV and 60% of all new HIV infections are also in that age group [ 5 ].

Because young people are at high risk for risky behaviors and low use of preventive mechanisms and/or services in developing nations, STIs were common sexual and reproductive health problems. Adolescents and young adults catch the highest rates of curable STIs, and 1 in 20 adolescents acquire new STIs each year [ 6 ]. Young people, especially those who are unlikely to have access to quality health care services, such as university students are at high risk of STIs [ 7 ]. About 80–90% of the global burden of STIs which found in the developing world where there is limited and/or no access to diagnostics of STIs [ 8 ].

Adolescents and the youth, in general, tend to experiment risky behavior due to their new freedom at boarding institutions, liberty from familiarized community, parents or guardians and teachers in secondary schools. University students are categorized under the most at-risk population segment (MARPS) due to their inclination to be engaged in risky sexual behavior and their poor sense of vulnerability [ 9 , 10 , 11 , 12 , 13 , 14 ]. Despite this, youth have not traditionally been considered a health priority since they have lower morbidity and mortality rates than older and younger age groups [ 15 ].

The national HIV/AIDS policy of Ethiopia identifies STIs prevention and control as one of the strategies to prevent and control HIV/AIDS [ 16 ]. Despite the large scale-up of health care investment for the prevention and treatment of STIs in Ethiopia [ 17 ], the prevalence among the Ethiopian youth rose from 1.15% in 2005 to 4% in 2011 [ 18 , 19 ]. This continued increase in the prevalence of STIs among the youth may have a significant impact on the next fate of the country since the youth constitute the bulk of the future workforce [ 20 ]. In spite of the continued increase in the prevalence of STIs in the country, relatively little epidemiological research has been carried out on the prevalence and associated risk factors of STIs [ 21 ]. Hence, quantifying the burden of these infections and identifying factors among students of higher institutions is important for designing an effective intervention and allocating resources. Therefore, this study aimed to assess the prevalence of STIs and its associated factors among the University of Gondar regular undergraduate students.

Study design and setting

An institution based cross-sectional study was conducted from March 7–18 / 2016 at the University of Gondar, located in Gondar town, 748 km from Addis Ababa, the capital of Ethiopia. There were 32,962 students enrolled in different programs. There are three student clinics and one teaching and referral hospital providing STI diagnosis and treatment services to students.

Sample size and sampling procedures

All students attended the University of Gondar in the regular undergraduate program during the study period were eligible for the study. The sample size was calculated using the single population proportion formula by considering the prevalence of STIs among university students as 19.5% [ 22 ], a 95% confidence interval (CI), and a 4% margin of error. By adding a 10% non-response rate and a design effect of 2, the final sample was 845 students. A multistage sampling technique was used to select participants. Considering 30% rule of thumb and simple random sampling technique with proportional allocation, 13 departments were selected. The final samples were selected from the specified departments using the systematic random sampling technique.

Data collection tool and procedures

Data was collected using a structured self-administered questionnaire prepared in English. To maintain the privacy of participants, seats were arranged far apart. The questionnaire was pre-tested on 42 Debre-Tabor University students outside the study area. Three days of intensive training was given to 10 data collectors selected from the University of Gondar, Institute of Public Health, before data collection. The data were collected on different variables such as age, sex, religion, marital status, ethnicity, religious involvement, year of study, family residence, monthly pocket money, age at first sexual initiation, number of sexual partners, unprotected sex, sex with commercial sex workers (CSWs) , knowledge on STIs, substance use, watch/read, pornography, peer pressure to had sex and previous history of STIs. A male student was considered as STIs positive if he reported one or more of the following syndromes: a history of Genital ulcer or sores, urethral discharge, scrotal swelling, inguinal bubo syndromes in the past 12 months prior to data collection. A female student was considered as STIs positive, if she reported one or more of the following syndromes: abnormal vaginal discharge, genital ulcer or sores, lower abdominal pain syndromes in the past 12 months prior to data collection. Knowledge of STIs was assessed using different questions which contained having information on STIs, prevention, ways of transmission, sign and symptoms and possible complications of STIs. Students who scored the mean and above in knowledge assessment questions were considered having good knowledge of STIs.

Data processing and analysis

Data were checked, coded, and entered into EpiData version 3.1 and exported to SPSS version 20 statistical software for further analysis. Descriptive statistics were used to characterize participants using different variables. Both bivariate and multivariable logistic regression analyses were done to identify factors associated with STIs. Variables with P- value ≤0.2 in the bivariate logistic regression were fitted into the multivariable logistic regression analysis. Prior to the multivariable analysis, multicollinearity diagnostic was performed, and there was no significant interaction between independent variables. Adjusted Odds Ratio (AOR) with a 95% Confidence Interval (CI) was calculated to determine the presence and strength of association. In the multivariable analysis, a variable with a p -value less than 0.05 was considered statistically significant.

Socio-demographic and family-related characteristics

A total of 803 university students participated in the study with a response rate of 95%. The median age of the participants was 21 years (IQR ± of 2 years). Of the participants, 52.9% were male,58.3% Orthodox Christian, and 87.9% were single. The majority (96.9%) of the students were boarding, and 87.3% received pocket money from families and relatives (Table 1 ).

Behavioral characteristics

About 60% of students drank alcohol, 11.6% chewed khat, 6.1% smoked shisha, and 75.5% seen or read pornography ( Table 2 ).

Sexual characteristics

About 61.1% of participants, had ever sex, of which 73.5% had sexual intercourse in the last 12 months. The mean age at first sexual intercourse was 18.8 (SD +  1.9) years. Furthermore, 42.8% of the students started a sexual activity after they joined the University. Of the sexually active respondents, 23.6% were initiated their first sex before the age of 18 years ( Table 3 ) .

Knowledge of sexually transmitted infections

Almost all students (98%) were ever heard about STIs. The majority of students (90.4%) reported that unprotected sex was the major mode of transmission for STIs. Moreover, more than half (55.3%) of students had good knowledge of STIs.

Prevalence of sexually transmitted infections

The overall prevalence of sexually transmitted infections at the University of Gondar was 18.2% (95% CI, 15.4, 20.8) in the past 12 months. About half (46.6%) female students were known to be infected ( Fig. 1 ). In the last 12 months, genital ulcer and vaginal discharge were the most prevalent syndromes reported by 43.6 and 55.9% of the male and female students who had signs and symptoms of STIs, respectively ( Fig. 2 ).

Prevalence of sexually transmitted infections among students in the last 12 months, the University of Gondar, northwest Ethiopia, 2016

Syndromes of sexually transmitted infections reported by students, the University of Gondar, northwest Ethiopia, 2016

Factors associated with sexually transmitted infections

Both bivariate and multivariable logistic regression analyses were done to see the effect of the selected characteristics on STIs. As presented in Table 4 , peer pressure, viewed or read pornographic materials, chewing khat, drinking alcohol, the previous history of STIs, multiple lifetime sexual partners, no use of condoms and poor knowledge of STIs were found to have an association with STIs in the bivariate analyses at p -value less than 0.2. In the multivariable analyses, previous history of STIs, multiple lifetime sexual partners, no use condoms and poor knowledge of STIs were significantly associated with developing sexually transmitted infections.

The odds of having STIs were two times higher among students who had the previous history of STIs (AOR = 2.1; 95% CI: 1.04,4.38) compare to no history of STIs. Students who didn’t use condoms had two times more chance of acquiring STIs than those students who had used (AOR = 2.4; 95% CI: 1.50:3.75). Likewise, the odds of developing STIs among students who had two or more sexual partners in life were 2.7 times (AOR = 2.7; 95% CI:1.70,4.40) higher as compared to those who had a single sexual partner. Moreover, students who had poor knowledge of STIs were about three times (AOR = 3.3; 95% CI: 1.09,5.32) higher odds of acquiring STIs as compared to the knowledgeable students ( Table 4 ) .

Identifying of sexually transmitted infections and providing relevant information, and offering the necessary health services is a highly effective intervention in the prevention and control of STIs. The prevalence of STIs among university students in the last 12 months was 18.2% (95% CI; 15.4, 20.8%). The finding is comparable with those of studies conducted on the University students in Wolaita Sodo (19.5%) [ 22 ] and Addis Ababa (15.74%) [ 23 ]. But, this finding was slightly lower than those of other studies conducted on Debre Birhan University students (28%) [ 24 ] and female youth at Mekelle (21.3%) [ 25 ]. The possible difference from Mekelle study might be due to the difference in the study area and study subjects were selected from the health facilities where there was a high probability of finding suspected cases. Furthermore, the possible difference might be due to the differences in the study subjects. This study included both male and female while Mekelle study included female only. Due to that female’s anatomy can place at higher risk of sexually transmitted infections than males [ 26 ].

The finding from this study was higher when compared with Ethiopian Demography and Health Survey (EDHS) 2011 report, among the youth (4%) [ 19 ], Bonga college students (13.9%) [ 27 ], Bahir Dar University students (6.4%) [ 28 ] and high school students in Gondar (10.7%) [ 29 ]. The possible difference from the EDHS report might be due to that EDHS survey was a population-based survey which included youth who are living with, and are under the control of the family. The data collection methods might also account for the variation. Likewise, in the Bonga and Gondar, the variation could be due to the differences in age and the student’s lifestyle. Residing and living with families and relatives helps the parent or relatives to monitor their children and improve decision-making capacity on risky health behaviors [ 13 , 14 ]. Besides, the Gondar and Bahir Dar research included only female students.

In this study, 61.1% of the study subjects reported to had sex, of these 54.2% have multiple sexual partners in their life. Of the sexually active study subjects in the previous year before the survey, 23.6% were initiated sex before the age of 18 years and 31.3% had sex under the influence of substance. The fact is that risky sexual behaviors such as having multiple sexual partners, having sex before 18 years old and sex under the influence of substance can expose individuals for the risk of contracting sexually transmitted infections (STIs) [ 30 ].

Large number (75%) of students were exposed for pornography. Exposing to pornographic materials could alter the normal sexual desire and care taking of exposing to sexually transmitted infections [ 31 , 32 ].

Having good knowledge of STIs is one of the protective factors for students to be aware of the modes of transmission, prevention methods and its complications which helps to take care of themselves from STIs. In this study, students with poor knowledge of STIs were more likely to develop STIs than students with good knowledge. This finding agrees with those of other studies conducted in Mekelle [ 25 ], Wolaita Sodo University [ 27 ], and Bahir Dar town [ 33 ].

Similarly, having multiple sexual partners is a known risk factor of sexual and reproductive health. Since university students come from different regions and towns with different cultures and values, they may be vulnerable to influences in their new environment as they live away from family or relatives with new friends and classmates. This may limit the student’s capability to defend themselves from peer pressure. Students could also be easily betrayed by monetary incentives from individuals [ 13 , 14 ]. In this study, students who had two or more sexual partners in life were more likely to acquiring STIs than a student who had only one sexual partner. This is consistent with the various studies conducted at Mada Wulabu university [ 34 ], on Malawian youth [ 35 ], and at Bahir Dar [ 33 ].

Condom use is one of the methods of preventing the transmission of STIs [ 36 ]. Individuals who had never used condoms were significantly associated with STIs. Accordingly, the higher odds of STIs were observed among students who had never used condoms during sexual intercourse. This finding is supported by the previous studies in Debre Berhan [ 24 ]. This could be because of individuals who used condoms might have more access, information, and experiences in its appropriate use.

Having the previous history of STIs had a positive association with the development of STIs, that is, students who previously had STIs were more likely to develop STIs than students with no such history. This finding was supported by researches conducted from the United States [ 37 ] and Mekelle [ 25 ]. This might be due to relapse, untreated sexual partner, poor compliance with treatment, inappropriate treatment, and antimicrobial drug resistance.

Since sexual behavior and practice is private, intimate and sensitive, respondents may feel mortified or ashamed to report syndromes (may be subject to social desirability bias). To minimize the problem, we used a self-administered questionnaire and clearly informed participants about the purpose of the study and the confidentiality of information. Sexually transmitted infections were assessed only through students reports which approach may miss asymptomatic students and may misdiagnose signs/symptoms due to other problems similar to STIs might be the possible limitation of the study.

In this study, the prevalence of self-reported STIs in the last 12 months among the University of Gondar regular undergraduate students was found to be high as compared to the national figure. Multiple sexual partners in life, previous history of STIs, not the use of condoms and poor knowledge of STIs were factors associated with STIs. Therefore, developing and strengthen reproductive health centers on the campuses, popularizing sexual and reproductive health information and education, particularly STI modes of transmission, prevention, health-seeking behaviors, and providing information and improving access to condom is recommended to reduce sexually transmitted infections.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Adjusted Odds Ratio

Confidence Interval

Crude Odds Ratio

Inter Quartile Range

Statistical Package for Social Sciences

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Acknowledgments

The authors would like to thank the University of Gondar for ethical approval. The authors have special gratitude for data collectors and supervisors for their dedicated work and for the study participants for their valuable information.

Ethical considerations

Ethical approval was obtained from the Ethical Review Board (IRB) of the Institute of Public Health, the University of Gondar. A letter of permission was obtained from the University of Gondar Dean of students, and subsequent permission was secured from the respective departments. The purpose, benefits, confidentiality of information, and the voluntary nature of participation in the study were explained and informed consent was obtained from participants. Any personal identifications were not collected from participants during data collection.

No specific fund was secured for this study.

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BAK and EAK developed the concept of the research, BAK acquired the research proposal, facilitated data collection, carried out statistical analysis and draft the manuscript. HY, RB, and EAK participated in the design of the study and proposal development, statistical analyses and critically reviewed the manuscript. All authors prepared, read and approved the manuscript.

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Kassie, B.A., Yenus, H., Berhe, R. et al. Prevalence of sexually transmitted infections and associated factors among the University of Gondar students, Northwest Ethiopia: a cross-sectional study. Reprod Health 16 , 163 (2019). https://doi.org/10.1186/s12978-019-0815-5

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Systematic review on effectiveness of prevention programs for sexually transmitted diseases (STD)

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• Hasanain Faisal Ghazi   ORCID: orcid.org/0000-0003-0367-3596 1 ,
• Taqi Mohammed Jwad Taher 2 &
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Sexually transmitted diseases (STD) are one of the most common infections worldwide. The current study aimed to determine what the current STD prevention programs are and their effectiveness.

Subject and methods

A systematic review of the literature was done for a period of 10 years (2009–2019) in two databases (PubMed and Cochrane) based on PICO strategy. Inclusion criteria were articles published in the English language only, involving clinical trials with control groups. In order to determine the quality of studies, two reviewers reviewed all qualifying papers independently. Twelve studies met our inclusion criteria.

Five of the studies were about tenofovir effectiveness, followed by three about community-based intervention, two regarding vaginal gel effectiveness and two about school-based intervention. The two studies on vaginal gel concluded no effectiveness.

As a conclusion, community-based prevention programs targeting adolescent and tenofovir gel showed promising results but more studies and at different locations in the world are needed so that some recommendations can be made in the future.

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Ghazi, H.F., Taher, T.M.J. & Hassan, M.R. Systematic review on effectiveness of prevention programs for sexually transmitted diseases (STD). J Public Health (Berl.) 30 , 2173–2180 (2022). https://doi.org/10.1007/s10389-021-01499-w

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Awareness and knowledge of sexually transmitted diseases (STDs) among school-going adolescents in Europe: a systematic review of published literature

• Florence N Samkange-Zeeb 1 ,
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Sexually transmitted diseases (STDs) are a major health problem affecting mostly young people, not only in developing, but also in developed countries.

We conducted this systematic review to determine awareness and knowledge of school-going male and female adolescents in Europe of STDs and if possible, how they perceive their own risk of contracting an STD. Results of this review can help point out areas where STD risk communication for adolescents needs to be improved.

Using various combinations of the terms "STD", "HIV", "HPV", "Chlamydia", "Syphilis", "Gonorrhoea", "herpes", "hepatitis B", "knowledge", "awareness", and "adolescents", we searched for literature published in the PubMed database from 01.01.1990 up to 31.12.2010. Studies were selected if they reported on the awareness and/or knowledge of one or more STD among school-attending adolescents in a European country and were published in English or German. Reference lists of selected publications were screened for further publications of interest. Information from included studies was systematically extracted and evaluated.

A total of 15 studies were included in the review. All were cross-sectional surveys conducted among school-attending adolescents aged 13 to 20 years. Generally, awareness and knowledge varied among the adolescents depending on gender.

Six STDs were focussed on in the studies included in the review, with awareness and knowledge being assessed in depth mainly for HIV/AIDS and HPV, and to some extent for chlamydia. For syphilis, gonorrhoea and herpes only awareness was assessed. Awareness was generally high for HIV/AIDS (above 90%) and low for HPV (range 5.4%-66%). Despite knowing that use of condoms helps protect against contracting an STD, some adolescents still regard condoms primarily as an interim method of contraception before using the pill.

In general, the studies reported low levels of awareness and knowledge of sexually transmitted diseases, with the exception of HIV/AIDS. Although, as shown by some of the findings on condom use, knowledge does not always translate into behaviour change, adolescents' sex education is important for STD prevention, and the school setting plays an important role. Beyond HIV/AIDS, attention should be paid to infections such as chlamydia, gonorrhoea and syphilis.

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Over the period 1985-1996, a general decrease of gonorrhoea, syphilis and chlamydia infections was noted in developed countries, both in the general population and among adolescents [ 1 ]. From the mid-1990s however, increases in the diagnoses of sexually transmitted diseases, in particular syphilis, gonorrhoea and chlamydia have been reported in several European countries, especially among teenagers 16-19 years old [ 2 – 7 ].

The problem with most STDs is that they can occur symptom-free and can thus be passed on unaware during unprotected sexual intercourse. On an individual level, complications can include pelvic inflammatory diseases and possibly lead to ectopic pregnancies and infertility [ 8 – 11 ]. Female adolescents are likely to have a higher risk of contracting an STD than their male counterparts as their partners are generally older and hence more likely to be infected [ 2 , 12 ].

The declining age of first sexual intercourse has been proffered as one possible explanation for the increase in numbers of STDs [ 7 ]. According to data from different European countries, the average age of first sexual intercourse has decreased over the last three decades, with increasing proportions of adolescents reporting sexual activity before the age of 16 years [ 13 – 18 ]. An early onset of sexual activity not only increases the probability of having various sexual partners, it also increases the chances of contracting a sexually transmitted infection [ 19 ]. The risk is higher for female adolescents as their cervical anatomic development is incomplete and especially vulnerable to infection by certain sexually transmitted pathogens [ 20 – 23 ].

The reluctance of adolescents to use condoms is another possible explanation for the increase in STDs. Some surveys of adolescents have reported that condoms were found to be difficult to use for sexually inexperienced, detract from sensual pleasure and also embarrassing to suggest [ 24 – 26 ]. Condoms have also been reported to be used primarily as a protection against pregnancy, not STD, with their use becoming irregular when other contraceptives are used [ 15 , 27 ]. Furthermore, many adolescents do not perceive themselves to be at risk of contracting an STD [ 27 ].

We conducted this systematic review in order to determine awareness and knowledge of school-going adolescents in Europe of sexually transmitted diseases, not only concerning HIV/AIDS, but also other STDs such as chlamydia, gonorrhoea, syphilis and human papillomavirus (HPV). Where possible we will identify differences in awareness and knowledge by key demographic variables such as age and gender, and how awareness has changed over time.

Although knowledge and awareness have been reported to have a limited effect on changing attitudes and behaviour, [ 16 , 28 – 30 ] they are important components of sex education which help promote informed, healthy choices [ 31 – 33 ]. As schooling in Europe is generally compulsory at least up to the age of 15 years [ 34 ] and sex education is part of the school curriculum in almost all European countries, school-going adolescents should be well informed on the health risks associated with sexual activity and on how to protect themselves and others. In view of the decreasing age of sexual debut and the reported increasing numbers of diagnosed STDs among young people, results of our review can help point out areas where STD risk communication for school-attending adolescents needs to be improved.

Search strategy

We performed literature searches in PubMed using various combinations of the search terms "STD", "HIV", "HPV", "chlamydia", "syphilis", "gonorrhoea", "herpes", "hepatitis B", "knowledge", "awareness", and "adolescents". The reference lists of selected publications were perused for further publications of interest. The search was done to include articles published from 01.01.1990 up to 31.12.2010. Inclusion and exclusion criteria were specified in advance and documented in a protocol (Additional File 1 ).

Inclusion criteria

Studies were selected if they reported on awareness and/or knowledge of one or more sexually transmitted disease(s) among school-attending adolescents in a European country, or in Europe as a whole, and were published in English or German.

Exclusion criteria

Case reports, reviews, editorials, letters to the editor, expert opinions, studies on sexual activity/behaviour only, studies evaluating intervention programmes and studies not specifically on school-attending adolescents were excluded.

Methodological assessment of reviewed studies

We used a modified version of the Critical Appraisal Form from the Stanford School of Medicine to assess the methodology of the studies included in the review [ 35 ]. The studies were classified according to whether or not they fulfilled given criteria such as 'Were the study outcomes to be measured clearly defined?', 'Was the study sample clearly defined?', or 'Is it clear how data were collected?' (Table 1 ). No points were allocated. Instead, the following categorisations could be selected for each assessment statement: 'Yes', 'Substandard', 'No', 'Not Clear', 'Not Reported', 'Partially Reported', 'Not Applicable', 'Not Possible to Assess', 'Partly'. The assessment was done independently by two of the authors (FSZ, LS) who then discussed their findings.

Definition of awareness and knowledge

For the purpose of this review studies were said to have assessed awareness if participants were merely required to identify an STD from a given list or name an STD in response to an open question. Knowledge assessment was when further questions such as on modes of transmission and protection were posed.

Overall, 465 titles and abstracts were obtained from the searches conducted. Three hundred and ninety-three articles were excluded as they did not report on studies conducted in Europe (Figure 1 ). A further 47 were excluded as they did not focus on knowledge and awareness of adolescents. Of the 25 identified articles dealing with knowledge on STDs among adolescents in Europe, 8 were excluded as they either did not specifically address the question of knowledge and/or awareness, or focused more on sexual behaviour/beliefs. A further seven articles were excluded because the study population was not clearly stated to be school-attending.

Flow diagram showing selection process of articles included in the review .

A review of the references listed in the 10 articles meeting inclusion criteria yielded four additional relevant articles. One article reported on two studies, hence a total of 15 studies published from 1990-2000 were included in the systematic review.

Six of the articles were published before the year 2000 [ 36 – 41 ], and nine after 2000 [ 42 – 49 ]. The studies report on surveys conducted from as early as 1986 to 2005 (Table 2 ).

The majority of the 15 studies specifically focused on HIV/AIDS only (7 studies) [ 36 , 39 , 41 , 43 , 44 , 49 ], four on STDs in general [ 37 , 38 , 40 , 42 ], one on STDs in general with focus on HPV [ 47 ], and three on HPV only [ 45 , 46 , 48 ]. All the HPV studies were published after the approval and market introduction of the HPV vaccine in 2006.

Generally the studies were conducted in particular regions/towns in different countries, with only one being conducted across three towns in three different countries (Russia, Georgia and the Ukraine) [ 43 ]. Six of the studies were conducted in Sweden [ 37 , 38 , 40 , 41 , 46 , 47 ] two in Russia [ 39 , 43 ] and one each in Ireland, [ 36 ] England, [ 42 ] Croatia, [ 44 ] Finland, [ 45 ] Italy [ 48 ] and Germany [ 49 ] (Table 2 ).

In the studies, generally both male and female adolescents varying in age from 13-20 years were surveyed. One study surveyed females only [ 40 ] and adolescents 11-12 years old were included in only one study [ 49 ] (Table 2 ). Whereas most of the studies included assessed awareness and knowledge among boys and girls separately, only one study [ 48 ] specifically assessed the association between age and awareness/knowledge.

Methodological summary of studies included in the review

All studies included in the review were cross-sectional in design. Apart from one study which recruited pupils by mailing the questionnaire to all households with adolescents in the 9 th grade, [ 45 ] pupils were recruited via schools. For 8 of the 15 studies it could not be deduced from the methods section how the participating schools were selected and in 4 studies it was not clear how the participating pupils were selected. The pupils completed questionnaires in school in 10 studies, and in two the questionnaires were completed at home [ 45 , 48 ]. Face-to-face interviews were used only in the surveys by Andersson-Ellström et al. [ 40 ] and by Goodwin et al. [ 43 ] (Table 2 ).

The study outcomes were clearly defined in all studies and the topics on which questions were posed were clearly described in all but one study. The majority of the studies also reported the individual questions posed to assess the given outcomes. In six studies the authors did not mention whether the instruments used for data collection had been pre-tested, validated, or whether the questions posed had been used in previous surveys (Table 1 ). Of the 9 studies which clearly reported participation rates, 7 had participation rates ranging from 79% to 100%. The remaining two studies had participation rates of 21.5% and 58% (Table 2 ).

Six STDs were focussed on in the studies included in the review, with awareness and knowledge being assessed in depth mainly for HIV/AIDS and HPV,[ 36 , 41 – 43 , 46 – 49 ] and to some extent for chlamydia [ 37 , 38 , 42 , 47 ]. For syphilis, gonorrhoea and herpes, only awareness was assessed in four studies [ 37 , 38 , 42 , 47 ].

Awareness and knowledge of HPV

The reported awareness of HPV among the surveyed adolescents was generally low (identification from given list), ranging from 5.4% in the study by Höglund et al. [ 47 ] to 66% in the study by Pelucchi et al. [ 48 ]. In the two studies which also reported results for females and males separately, awareness was observed to be statistically significantly higher among females than among males: 16.4% vs. 9.6% in the Swedish study by Gottvall et al. [ 46 ] and 71.6% vs. 51.2% in the Italian study by Pelucchi et al. [ 48 ]. In the study by Höglund et al., only one of the participating 459 adolescents mentioned HPV (in response to an open question on known STDs) [ 47 ].

Awareness of the HPV vaccine was also very low, with 5.8% and 1.1% of adolescents surveyed in the studies by Gottvall et al. and Höglund et al. respectively, reporting being aware of the vaccine [ 46 , 47 ]. Whereas only 2.9% and 9.2% of adolescents in these two Swedish studies were aware that HPV is sexually transmitted, the proportion was 60.6% in the Italian study [ 48 ]. A minority of adolescents knew that HPV is a risk factor for cervical cancer: 1.2% in the study by Höglund et al. [ 47 ] and 8.1% in the study by Gottvall et al. [ 46 ]. Among the adolescents who participated in the survey by Pelucchi et al., 48.6% were aware that the aim of the HPV vaccine is to prevent cervical cancer [ 48 ]. Among female adolescents who participated in the study by Gottvall et al., 11.8% did not believe they would be infected with HPV [ 46 ]. The proportion was 55% among female participants in the study by Pelucchi et al. [ 48 ]. The latter study surveyed pupils aged 14-20 years but did not report on age differences in awareness.

Three studies reported on awareness of condylomata, genital warts which are caused by the human papilloma virus. Two of the studies reported awareness of 35% [ 38 ] and 43% [ 37 ]. The third study mentioned that awareness of condylomata was lower than that for chlamydia without stating the corresponding figures [ 40 ].

Awareness and knowledge of HIV/AIDS

Knowledge and awareness was quite high in all studies reporting on HIV/AIDS, with more than 90% of adolescents being able to identify the disease as an STD from a given list or in response to the direct question "Have you ever heard of HIV/AIDS?" [ 36 , 38 , 42 ]. In one study where the open question "Which STDs do you know or have you heard of?" was used, 88% of respondents mentioned HIV/AIDS [ 47 ] (Table 3 ).

In the studies where this was asked, a large majority of the adolescents knew that HIV is caused by a virus, [ 36 , 41 ] is sexually transmitted,[ 36 , 41 , 43 , 47 , 49 ] and that sharing a needle with an infected person may lead to infection with the virus [ 36 , 41 , 43 , 49 ]. Statistically significant age specific differences in knowledge on mode of HIV-transmission were reported in the study conducted in Germany [ 49 ]. Compared to 13 and 15 year old pupils, a higher proportion of 14 year old pupils correctly identified the level of risk of HIV-transmission associated with bleeding wounds, intravenous drug use and sexual contact. For the latter mode of transmission, the lowest proportion of correct answers was observed among 16 year old pupils. Generally the proportion of respondents correctly reporting that use of condoms helps protect against contraction of HIV was above 90%. The only exception was in the Russian study conducted by Lunin et al. in 1993, in which only 42% of females and 60% of males were aware of this fact [ 39 ]. In the same study, only 15% of the adolescents perceived themselves 'not at risk' of contracting HIV (Table 3 ).

Only one study reported asking the adolescents if one can tell by looking at someone if they have HIV, to which 47% responded affirmatively [ 43 ].

Awareness and knowledge of chlamydia

The proportion of adolescents able to identify chlamydia as an STD from a list of diseases ranged from 34% in the study conducted in England by Garside et al. [ 42 ] to 96% in the Swedish study by Andersson-Ellström et al. [ 22 ]. In the Garside study, the proportion was higher among year 9 than among year 11 pupils (p < 0.05). In another Swedish study by Höglund et al. 86% of the surveyed adolescents mentioned chlamydia as one of the STDs known to them in response to an open question [ 47 ]. In the two studies which reported on awareness among boys and girls separately, girls were observed to have higher awareness proportions than boys [ 38 , 42 ]. While the observation was not statistically significant in one of the studies, [ 27 ] this was not reported on in the other study [ 38 ].

Not many adolescents knew that chlamydia can be symptom-free: 40% and 56% in the 1986 and 1988 surveys by Andersson-Ellström et al. [ 37 ] and 46% in the study by Höglund et al. [ 47 ]. In one Swedish study where the level of knowledge in the same study population was assessed at age 16 and 18, a statistically significant increase in knowledge was observed over time [ 40 ]. Only the Finish study reported on the subjective rating of risk of contracting chlamydia. 55% of the adolescents surveyed reported 'low perceived susceptibility' [ 45 ] (Table 3 ).

Awareness and knowledge of gonorrhoea

Gonorrhoea was identified as an STD from a given list by 84% of adolescents in the survey by Tyden et al.,[ 38 ] by 98% in the survey by Andersson-Ellström et al.,[ 37 ] and by 53% in the survey by Garside et al. [ 42 ]. In the latter, the difference between year 9 and year 11 pupils was more pronounced among boys: 53% among year 9 and 60% among year 11 (p > 0.05). A statistically significant increase in knowledge over time was observed in a group of girls surveyed at age 16 and 18 [ 40 ]. Only 50% of the adolescents surveyed in the study by Höglund et al. mentioned gonorrhoea in response to an open question on known STDs [ 47 ] (Table 3 ).

Awareness of syphilis and herpes

Awareness of syphilis was surveyed only in the study conducted in England where 45% of the participating adolescents correctly identified the disease from a given list as an STD. The proportion was slightly higher among year 11 compared to year 9 pupils and awareness was slightly higher among girls than among boys (p > 0.05) [ 42 ] (Table 3 ).

In the Tyden et al. study, [ 38 ] 56% of the surveyed adolescents identified herpes as an STD from a given list. The proportion was 90% in the survey by Andersson-Ellström et al. [ 37 ] and 59% in the Garside et al. study [ 42 ]. In the latter, considerable differences were observed between year 9 and year 11 pupils (p < 0.05), but not between girls and boys in the same school year. Herpes was mentioned as an STD by 64% of the adolescents surveyed in the study by Höglund et al. [ 47 ] (Table 3 ).

Awareness of STDs in general

Five of the studies reviewed assessed the knowledge of participating adolescents on STDs in general. In the England study, all in all 59.7% of the participants knew that STDs in general can be symptom-free [ 42 ]. Among girls, knowledge was higher among year 11 than year 9 pupils, while the opposite was true for boys. The proportion of boys in year 9 who knew this fact (64.2%) was considerably higher than that of year 9 girls (53.8%) (Table 3 ). In two Swedish studies by Tyden et al. and by Andersson-Ellström et al., all surveyed adolescents knew that the use of condoms can protect against the contraction of STDs in general [ 38 , 40 ]. In an earlier study by Andersson-Ellström et al., 20% of sexually active pupils surveyed in 1986 were aware that condoms protect against infection. The figure significantly went up to 43% in 1988, with boys having significantly higher awareness than girls in both years [ 22 ] (Table 3 ). In the same study, the proportion of girls who felt themselves to be at risk of contracting an STD in general went down from 32% in the 1986 survey to 24% in the 1988 survey. Among boys, the proportion increased from 16% in 1986 to 24% in 1988. These changes were not statistically significant [ 37 ]. In the Finish study, 55% of the surveyed adolescents perceived themselves to be at low risk of contracting an STD [ 45 ].

Reported use of condoms

Use of condoms by sexually active participants was assessed in three studies, all conducted in Sweden [ 38 , 46 , 47 ]. Reported use at sexual debut was lowest in the study published in 1991 (31%), [ 38 ] and higher in the other studies both published in 2009: 61% [ 47 ] and 65% [ 46 ] respectively (Table 3 ). In the earlier study, the proportion of girls reporting condom use was, at 50%, considerably higher than that of boys (40%) [ 38 ]. In the study by Gottvall et al., no difference in condom use was observed between girls and boys [ 46 ]. Condom use at recent coitus was reported on only in the earlier study [ 38 ]. It was observed that the decrease in the proportion of girls reporting using condoms was more pronounced than that of boys (26% vs. 40%) (Table 3 ).

The highest awareness and knowledge were reported for HIV/AIDS. This is certainly linked to the fact that since the mid 1980s, extensive awareness campaigns on this topic have been conducted globally. The lowest proportions were reported for HPV, with awareness as low as 5.4% in one study [ 47 ]. With only about 1 in 8 respondents knowing that HPV is an STD, awareness was still very low in one of the two studies conducted after the introduction of the HPV vaccine [ 46 ]. A higher awareness (66.6% of respondents aware), measured in a different population, was observed in the second recent study on HPV [ 48 ].

Two factors appeared to have influenced awareness. The first was of a methodological nature and related to the fact whether an open or closed question was posed. Of the studies included in the review which assessed awareness, all but one used closed-form questions only. The adolescents either had to identify sexually transmitted diseases from a given list of diseases, or the question was in a yes/no format. Initially, Höglund et al. asked participating adolescents to list all STDs known to them and then later on, if they had ever heard of HPV. Only one participant (0.2%) mentioned HPV as one of the STDs known to them, but later, 24 (5.4%) reported to have heard of HPV [ 47 ]. In comparison to open-form questions, closed questions are not only more practical and easier to respond to, but also easier to code and analyse. One of the arguments raised against closed questions, especially where a list of possible answers is given, is the risk of guesswork. It can not be ruled out that some participants, unable to answer the question, will select answers at random [ 50 , 51 ]. In the study by Garside et al. for example, among year 9 pupils, 14.5% incorrectly identified plasmodium, and 20.6% filariasis from a given list as STDs [ 42 ]. Open questions have been recommended for surveying participants with unknown or varying knowledge/awareness [ 50 ] as these questions provide a more valid picture of the state of knowledge [ 51 ].

To a lesser extent, gender also appears to have influenced knowledge and awareness, especially for HPV [ 46 , 48 ]. Significant gender differences were observed, with females having better awareness and knowledge than males. Although the data are limited as not all studies reported results separately for males and females, these findings, could be reflective of the way awareness campaigns, for example on HPV, have been targeted more at females than at males.

The studies on HIV included in our review generally reported high awareness of the protective effect of condoms among adolescents [ 36 , 41 , 43 , 47 , 49 ]. One study included in the review however observed that adolescents seem to regard condoms primarily as a method of contraception and not as a means of protection against sexually transmitted diseases (40). In this study, 19 out of 20 female adolescents who reported more than 4 sexual partners at the age of 18 reported intercourse without a condom in relationships of less than 6 months' duration. The majority of them were, however, convinced that they had neither acquired (96%) nor transmitted (93%) an STD at last unprotected intercourse [ 40 ]. Other studies also indicate that consistent condom use is generally low among adolescents [ 27 , 52 – 55 ].

Where reported, participation rates were generally high, probably due to the fact that the adolescents were recruited in schools. In some instances however, the number of participants was low even though the participation rate was reported as high. In the study by Tyden et al. for example, the study sample consisted of 213 pupils, 12% of the 1830 students in the first form of upper secondary school in Uppsala [ 38 ]. The authors base the participation rate of their study (98%) on the 12%, without explaining how it came about that only 213 pupils were considered for participation. The one study which recruited participants per post had a very low participation rate of 21.5% [ 45 ]. Nevertheless, the study had more participants than others with comparatively higher participation rates. Bias related to selective participation is an issue that needs to be considered on a study by study basis, and reporting on response proportions should be considered essential for all studies.

Study strengths and limitations

To our knowledge no systematic reviews of published literature on knowledge and awareness of sexually transmitted diseases among school-attending adolescents in Europe have been conducted to date. The current review confirms that there are considerable gaps in knowledge and awareness on major STDs in European adolescents. Our results underline the importance of the objectives set for adolescents' sexual and reproductive health in Europe, the first of which foresees that adolescents be informed and educated on all aspects of sexuality and reproduction [ 31 ].

We could not identify many studies on knowledge and awareness of sexually transmitted diseases among school-attending adolescents in Europe. This could be due to the fact that knowledge has been shown to have little impact on behaviour change, and prevention interventions have generally moved away from a focus on knowledge and awareness as key mediators. Another possible reason is that schools are not always willing to participate in such studies due to competing demands of other school activities or because of the subject content [ 16 , 28 – 30 ].

One limitation of our review is that the 15 studies included did not all focus on the same sexually transmitted diseases. The four studies conducted in Eastern Europe were all on HIV/AIDS knowledge and awareness only, whereas Western European studies were on STDs in general or on HPV. Furthermore, the formulation of the questions used to assess awareness and knowledge varied between studies, making it difficult to directly compare the findings of individual studies. Another potential limiting factor is the age variation of participants in the studies included in the review, especially as all but one study did not clearly investigate the association between age and awareness or knowledge. Due to the afore-mentioned factors and the small number of studies available, it was not possible to perform a meta-analysis of the study findings.

The representativeness of study participants in some studies could not be assessed as it was not mentioned how the schools were selected [ 37 , 40 – 44 , 49 ]. Different socioeconomic environments of individual schools are likely to affect results, but there is currently not sufficient information to assess this.

The school setting offers an effective way to access adolescent populations universally, comprehensively and uniformly [ 56 ]. It plays an important role for sex education, especially for those adolescents with no other information sources. Furthermore, some parents are not comfortable discussing sexual issues with their children. It therefore comes as no surprise that many young people cite the school as an important source of information about sexually transmitted diseases [ 26 , 27 ]. Although sex education is part of the school curriculum in many European countries, there are differences in the issues focused on. In some countries sex education is integrated in life skills approach, whilst biological issues are predominant in others and at times the focus is on HIV/AIDS prevention [ 57 ]. Generally it seems that education schedules offer a range of opportunities to raise knowledge and awareness of STD among adolescents.

In general, the studies reported similar low levels of knowledge and awareness of sexually transmitted diseases, with the exception of HIV/AIDS. Although, as shown by some of the findings on condom use, knowledge does not always translate into behaviour change, adolescents' sex education is important for STD prevention, and the school setting plays an important role. Beyond HIV/AIDS, attention should be paid to infections such as chlamydia, gonorrhoea and syphilis.

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Florence N Samkange-Zeeb, Lena Spallek & Hajo Zeeb

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Authors' contributions

FSZ developed the concept for the study, conducted the literature search, assessed studies for inclusion in the review and extracted data. She also prepared drafts and undertook edits. LS was involved in the development of the study concept, conducted the literature search, assessed studies for inclusion in the review and extracted data. HZ was involved in the development of the study concept. All authors contributed to the editing of the drafts and have read and approved all versions of the manuscript.

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Samkange-Zeeb, F.N., Spallek, L. & Zeeb, H. Awareness and knowledge of sexually transmitted diseases (STDs) among school-going adolescents in Europe: a systematic review of published literature. BMC Public Health 11 , 727 (2011). https://doi.org/10.1186/1471-2458-11-727

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Antimicrobial treatment and resistance in sexually transmitted bacterial infections

• Jorgen S. Jensen   ORCID: orcid.org/0000-0002-7464-7435 1 &
• Magnus Unemo   ORCID: orcid.org/0000-0003-1710-2081 2 , 3  

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Sexually transmitted infections (STIs) have been part of human life since ancient times, and their symptoms affect quality of life, and sequelae are common. Socioeconomic and behavioural trends affect the prevalence of STIs, but the discovery of antimicrobials gave hope for treatment, control of the spread of infection and lower rates of sequelae. This has to some extent been achieved, but increasing antimicrobial resistance and increasing transmission in high-risk sexual networks threaten this progress. For Neisseria gonorrhoeae , the only remaining first-line treatment (with ceftriaxone) is at risk of becoming ineffective, and for Mycoplasma genitalium , for which fewer alternative antimicrobial classes are available, incurable infections have already been reported. For Chlamydia trachomatis , in vitro resistance to first-line tetracyclines and macrolides has never been confirmed despite decades of treatment of this highly prevalent STI. Similarly, Treponema pallidum , the cause of syphilis, has remained susceptible to first-line penicillin.

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Acknowledgements

The authors are very grateful to the WHO and the WHO Global Gonococcal Antimicrobial Surveillance Program (GASP), especially T. Wi, M. Escher and I. Maatouk, for sharing antimicrobial resistance data for N. gonorrhoeae .

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Magnus Unemo

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Research on Sexually Transmitted Diseases

Table of contents, in a nutshell.

• What is the problem? Hundreds of millions of people are infected with sexually transmitted diseases (STDs), and more than a hundred thousand die due to STDs other than HIV each year. The World Health Organization (WHO) and Global Burden of Disease (GBD) Study estimate that STDs other than HIV and HPV are responsible for approximately 9-13 million disability-adjusted life year s (DALYs) per year. Based on their impact and the availability of treatments and preventative measures, we chose three diseases to investigate in more detail: herpes simplex virus (HSV), syphilis, and human papillomavirus (HPV). The GBD estimated the burden of HSV at approximately 300k DALYs per year, but this estimate does not include the burden of some additional conditions caused by HSV. We briefly looked at the burden of these conditions and concluded that the true burden may be somewhat or substantially larger. HSV cannot be cured and there is no vaccine, although antivirals can be used to treat it. Syphilis is responsible for most of the direct burden of STDs (7-11 million DALYs per year, according to the WHO and GBD), and there is no vaccine, but it can be cured with antibiotics. HPV is a necessary cause of cervical cancer, which is estimated to cause approximately 7-9 million DALYs per year, and can contribute to the development of other cancers as well (the burden of HPV is not included in WHO and GBD assessments of the burden of STDs, but cervical cancer burden is included separately in these sources). There are vaccines that appear to confer immunity against some strains of HPV, and precancerous lesions can often be removed once detected, but HPV cannot be cured.
• Who else is working on it? It’s our impression that there is relatively little nonprofit involvement in and private funding for STD research and development. The NIH contributed approximately $250 million in funding to support STD research in 2015 (funding for HIV and HPV research and development categorized separately from the $250 million figure). Grantome searches suggest NIH and NSF funding of approximately $100 million, $150 million, and $20 million in funding for HSV, HPV, and syphilis research in 2013, respectively.

1. What is the problem?

Sexually transmitted diseases (STDs) are widespread. Hundreds of millions of people are infected with at least one STD, 1  and the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated that STDs other than HIV and HPV caused approximately 142,000 deaths in 2013, while HIV caused approximately 1,341,000 deaths in 2013. 2

We may conduct a separate investigation into HIV/AIDS at a later date, but did not include it in this investigation.

We believe it is widely accepted that mother-to-child STD transmission can result in stillbirths, infant mortality, and chronic health conditions. Stigma, fear, and avoidance of sexual intimacy associated with STDs may lower quality of life. Common STDs, including genital herpes, HPV, and syphilis, are associated with an increased risk of HIV transmission, but it appears that high-quality evidence of a causal relationship is scarce. (See  below  for our take on this.)

Vaccines are available to prevent HPV (although note that currently-available HPV vaccines do not protect against all strains of HPV 3 ) and hepatitis B. 4  Other STDs, including syphilis, chlamydia, and trichomoniasis, are treatable and generally curable with antibiotics, 5  although some STDs, especially gonorrhea, are developing resistance to antibiotics. 6

We formulated an initial list of STDs from several other lists of STDs that we found. 7  We declined to include infections such as Pelvic Inflammatory Disease (PID) that result from infection with other STDs. Of these, we initially decided to assess the impact of and funding for diseases that are predominantly sexually-transmitted other than HIV, and that are currently difficult or impossible to treat or cure because we thought it was more likely that additional scientific research would be beneficial for cases where reliable cures or treatments have not been found. We later decided to investigate predominantly sexually-transmitted diseases that had a reported impact of greater than five million  disability-adjusted life years  (DALYs) per year as well, regardless of whether treatments or cures for those are available. 8  Based on these processes, we decided to examine herpes simplex virus (HSV), syphilis, and human papillomavirus (HPV) in more detail.

1.1 Size of the problem

1.1.1 overall burden.

To get a sense of the impact of different STDs on public health, we looked at the most recent estimates of the global annual burden of major STDs (excluding HIV and HPV) in DALYs from the Global Burden of Disease Study (GBD) and the World Health Organization’s (WHO) Global Health Observatory (GHO). The results are below:

However, it’s our impression that these numbers are very uncertain (indeed, they are not in close agreement with one another). The estimates did not include the impacts of neonatal forms of some STDs, and may have missed other impacts as well. 10

Additionally, we note that there are major negative impacts of STDs that we do not quantitatively assess in this report, such as the psychological and sociological effects of the presence of STDs in a community (e.g. fear of transmission and stigmatization). In addition, there may be impacts we do not know of and that our brief investigation did not uncover.

1.1.2 STDs and HIV Transmission

There is evidence of a correlation between HIV and infection with other STDs, including HSV, HPV, and gonorrhea. 11  Some researchers also believe there are plausible mechanisms by which the presence of other STDs could increase the likelihood of HIV transmission, namely by 1) increasing the incidence of lesioned regions of flesh around the genitals, and 2) recruiting cells carrying CD4 receptors (which HIV uses to gain entry into host T-cells) to the area. 12  However, we believe the ability to definitively determine a causal relationship is complicated by confounding variables (for example, behavioral and health-status factors that contribute to the risk of contracting one STD may increase the risk of contracting another), and limitations on the types of experiments that can be performed without harming participants. We are not confident that attempts to fully control for confounding variables are able to do so.

We know of two small RCTs which concluded that HSV antivirals reduced HIV levels, either in the seminal fluids or in plasma and around the cervix. 13  However, according to @Mayer and Venkatesh 2011@, in a meta-analysis of randomized controlled trials (RCTs) on interventions to distribute antivirals for HSV and antibiotics for bacterial STDs, six out of seven RCTs they examined did not find a statistically-significant reduction in HIV transmission, nor have studies in subsequent reviews (note that there is overlap between the studies included in the different reviews). 14  Given that the majority of studies we encountered did not find an effect of STD treatment and prevention on HIV transmission, we chose not to include a quantitative estimate of the potential impact of STDs on HIV. However, we note that if STDs are in fact responsible for a substantial proportion of HIV transmission, that might make their overall impact substantially larger than our estimates below. 15

Some studies have detected an association between HIV and HPV. 16  Additionally, mechanisms by which HPV infection could increase HIV transmission have been proposed. 17  However, it is our impression that as of 2015, no RCTs have been conducted on the impact of HPV vaccination on HIV transmission. 18

We do not know if vaccines or improved treatments for STDs would reduce HIV transmission, or whether increased access to currently-available STD treatments would help prevent HIV.

1.1.3 Genital herpes

The herpes simplex virus (HSV) occurs in two forms, HSV-1 and HSV-2. 19  Hundreds of millions of people are infected with one or both types of HSV, although many show no symptoms. 20  Both types can be transmitted by sex. 21  There is no commercially-available HSV vaccine and HSV infections cannot be cured, but antiviral agents can reduce outbreaks. 22

Major sources of disease burden from HSV include:

Genital ulcers:  The Global Burden of Disease reports that genital HSV resulted in 311,600 years lived with disability (YLD) in 2013 due to genital ulcer disease. 23  We have not vetted this estimate, but did attempt to independently derive it by assigning what we felt was a plausible disability weight to genital ulcers and multiplying by its prevalence, and found that it was within the range of what we expected.

Neonatal deaths from HSV:  We found it difficult to come to an understanding the impact of neonatal HSV. This is because:

• We have major uncertainty about current global neonatal herpes incidence, although the data we found suggest that the overall incidence was likely more than 1/100,000 and less than 1/100 in the late 1990s and early 2000s. 24
• We are highly uncertain about the neonatal herpes mortality rate, and the sources we’ve found have not given us a strong sense of the likely true number because the estimates vary somewhat. We haven’t investigated their methodology, and we are unsure of how the mortality rate varies by country. 25  We don’t know if the difference in estimates of the mortality rates stem primarily from differences in incidence at the different study sites and times, differences in proportion of cases treated, differences in the quality of the treatment, other factors, or some combination of these. We think it require substantial additional work to understand neonatal HSV mortality rates somewhat better, but that even if we put in more time, we might not gain clarity on this.
• We did not look into the number of infants that sustain lifelong sources of disability from neonatal HSV.

Given the number of births/year, 26  it seems likely to us that thousands or tens of thousands of infants are infected with HSV every year, and it seems possible to us that more than 10% of those infants die. If that were true, the impact of neonatal HSV might represent a substantial fraction or the majority of the total burden of HSV. 27

Severe vision impairment from HSV:  One source suggests that 40,000 people per year may become profoundly visually impaired in one or both eyes due to HSV keratitis (an inflammation of the cornea). 28  We did not vet this estimate, and are not confident that these numbers reflect the true burden of severe vision impairment from HSV. We don’t know how many DALYs HSV keratitis is likely responsible for. It’s our impression that most cases of HSV keratitis occur late in life but may be more severe in children.  29

In many cases, HSV vision impairment may be the result of HSV-1 that was not directly sexually transmitted. Many researchers believe that HSV-1 can be and often is transmitted by non-sexual kissing (for example by family members) or by sharing items that touch the mouth such as eating utensils and toothbrushes.

Other impacts:  We did not investigate several other impacts of HSV, including:

• Sequelae in non-fatal cases of neonatal HSV
• Cases of mildly-moderately impaired vision from HSV
• Oral HSV ulcers
• A proposed connection between HSV-1 infection and the development of Alzheimer’s Disease 30
• Encephalitis and meningitis from herpes 31
• Herpes whitlow and gladiatorum 32

Overall burden:  The GBD estimated that genital herpes resulted in approximately 300k DALYs in 2013. Based on our research into conditions caused by HSV but not included in the GBD estimate (namely, the unquantified but possibly-substantial impact of HSV keratitis and neonatal HSV, the possible and (if real) plausibly substantial impact of HSV on HIV/AIDs transmission and Alzheimer’s Disease, and the likely small impact of the other conditions above) we would guess that the true impact of HSV is substantially larger, although we don’t know how much larger.

1.1.4 Human papillomavirus

HPV is a common infection; the WHO estimates that approximately 12% of women with normal cytological findings (which we believe to mean no cellular signs indicating cervical cancer or precancerous changes in the cervix, indicating that this number is likely an underestimate of the proportion of women with HPV) and 21% of men worldwide are infected at a given time. 33  There are many strains of HPV, most of which are asymptomatic but some of which increase cancer risk around the infected area (especially the cervix) or cause genital warts. 34

There is no treatment we know of for HPV, but there are vaccines that confer protection against some strains of the virus. 35  All the vaccines protect against strains 16 and 18, 36  which, according to the National Cancer Institute, are together responsible for 70% of cervical cancers. 37

There are also procedures that allow healthcare workers to identify and, if necessary, remove precancerous lesions on the cervix. 38  According to the WHO, HPV infections of healthy individuals often spontaneously resolve themselves within two years 39  and it usually takes approximately ten years for HPV infection to progress to an invasive cancer. 40

Major sources of disease burden from HPV include:

Cervical cancer:  In 2012 it was reported that there were 528,000 cases of cervical cancer and 266,000 deaths from cervical cancer, 41  all the result of some strain of HPV. 42  The DALY burden of cervical cancer was estimated at 6.9M in 2013 by the GBD, 43  and 9.2M by the WHO in 2012. 44

Cancers of the vulva, vagina, penis, anus, mouth, and oropharynx attributable to HPV:

There is evidence linking HPV to cancers of the vulva, vagina, penis, anus, mouth, and oropharynx. 45

One source indicated that in 2006, 87.8% of cancers from HPV were cervical cancers. 46  so we believe that the estimate of the burden of cervical cancer captures the majority of the known direct harm from HPV.

Other impacts:  There are other impacts of HPV which are not included in our calculation of the burden of HPV. These include:

• Respiratory papillomatosis 47
• A possible association between lung cancer and HPV. It’s our impression that a causal link has not been established, and we are uncertain about the quality of the evidence for the connection. 48
• Genital warts
• Common skin warts and rare skin conditions in immunocompromised individuals. 49  However, it is our understanding that these result from strains of HPV that are not predominantly sexually transmitted.

Some research suggests that HPV vaccination may increase the risk of becoming infected with the strains that the vaccine does not protect against. 50  We have not fully investigated this claim, and do not know how much it detracts from the public health benefit of HPV vaccines, if at all.

Overall burden:  In summary-

• The GBD estimates the burden of cervical cancer at 6.9M DALYs
• The WHO estimates the burden of cervical cancer at 9.2M DALYs
• HPV can cause other cancers as well, but these cancers probably contribute a small proportion of the total burden.
• There is evidence of an associated between HPV infection and HIV transmission, but we are unsure about the strength and cause of this association.
• We have not included other health consequences of HPV, which we believe to be small in comparison.

1.1.5 Syphilis

Syphilis is a bacterial infection caused by the bacterium  Treponema pallidum . 51  When left untreated, it can lead to sores, rashes, eye problems, neurological and heart problems, and death. 52  It can be treated and the infection cured with antibiotics. 53

Overall burden:  In 2013 the GBD estimated that there were 136,848 deaths due to syphilis, of which 120,537 were in children five years of age or under, 54  while the WHO GHO estimated that there were 78,910 deaths from syphilis in 2012, of which 67,489 were in children five years of age or under. 55  The DALY burden from syphilis (including neonatal syphilis) was estimated by the GBD at 11.3M DALYs and the WHO GHO at 7.0M DALYs. 56  Potential effects of syphilis on HIV transmission were not included in these assessments, 57  but we do not know of other direct impacts of syphilis that may have been excluded (despite a brief search).

2. Who else is working on this?

We do not have a comprehensive understanding of which organizations fund research on STDs, as opposed to raising awareness, offering services, or advocating on behalf of individuals that suffer from STDs. 58  However, it’s our understanding that philanthropic and nonprofit involvement in STD research is minimal. We are not aware of non-profit organizations specifically supporting HSV or syphilis research.

2.1 How much funding is in this area?

The total NIH funding for sexually transmitted diseases/herpes (not including funding for HIV/AIDS, any hepatitis virus, or HPV/cervical cancer vaccines) was approximately $250M in 2015. 59  It was our impression of NIH STD funding that there is substantial funding for HPV vaccine trials, testing the effects of the HPV vaccine, and cervical cancer diagnostics. Even though HIV/AIDS had its own section, there seemed to be some funding allocated for HIV/AIDS research listed in the “sexually transmitted diseases/herpes” section, some funding for social science programs on sexual health and safety, and research on HSV and HSV vaccine candidates. We saw several funded projects on potential chlamydia and gonorrhea vaccine candidates. 60  In addition, we identified approximately $1.4M in funding for STDs from private foundations in 2012. 61

We searched  Grantome.com , a database of scientific research grants, for information about grants that included the words “sexually transmitted,” and found that in 2013 there was $188M in funding reported that met these search criteria. 62

We looked into the assets and funding from other sources, including smaller sources and those predominantly dedicated to STD advocacy, awareness-building, and service provision rather than research and development, but these numbers did not significantly affect our view of the crowdedness of this space. 63

The funding for research and development for each of our STDs of interest is below.

• Grantome, 2013, approximate: $104.3M 64
• NIH Project Reporter, 2015, approximate: $5.8-137.9M 65
• Grantome, 2013, approximate: $147.6M 66
• NIH, Estimates for Funding of Varion Research, Condition, and Disease Categories, 2015: $31M 67
• NIH Project Reporter, 2015, approximate: $35.2-204.3M 68
• Grantome, 2013, approximate: $17.3M 69
• NIH Project Reporter, 2015, approximate: : $2.2-22.9M 70

3. Our process

We initially decided to investigate this area because we thought STD research might be impactful and neglected due to associated stigma. We focused on quickly determining this, without investigating potential interventions in this space. The specific steps we took to investigate importance and neglectedness are as follows.

For investigating importance, we:

• Looked at global DALY burden from each STD in the  GBD 2013  and  WHO GHO 2012 data .
• Attempted to independently derive DALY estimates, where possible, from lives lost.
• Briefly researched the diseases we focused on, their sequelae, and treatments. We did this by reading fact sheets and Wikipedia articles about the diseases in question, scanning for highly-cited recent articles in Google Scholar about them, and investigating further points that seemed important.
• Looked for relevant Cochrane Library articles on HPV, HSV, syphilis, and STDs in general.

For investigating neglectedness, we:

• Looked at NIH  funding by disease  and the titles of all NIH grants larger than $500k from 2015 from the Sexually Transmitted Diseases/Herpes category. 71
• Looked at the  dataset  from our blogpost  “What Large-Scale Philanthropy Focuses on Today” .
• Searched the  Foundation Center’s 990 finder  for organizations working on STD research and development in general, or on our diseases of interest. 72
• Conducted Google searches 73
• Read through  grants.gov funding opportunities for STDs .
• Looked at the  NIH budget request .
• Searched  Guidestar.org  for organizations relevant to STD research (keywords: “sexually transmitted diseases”).

4. Questions for further investigation

Our investigation so far has focused almost exclusively on the burden of these diseases and how much attention they receive from funders of scientific research. If we were to do further research here, our primary focus would be on the tractability of potential research directions. Some questions we might aim to address include:

• What are the greatest barriers to STD diagnosis? Would improved diagnostics for STD infections lead to higher rates of treatment and cure?
• What are the greatest barriers to the development of new vaccines for STDs, including syphilis?
• Would it be practical to deliver a syphilis vaccine to the required population?
• How do HPV vaccines affect the prevalence and transmission of HPV strains against which they do not confer immunity? How is this likely to impact the future burden of HPV?
• To what extent do STDs increase HIV transmission? To what extent do STD treatments and vaccines reduce HIV transmission, if at all?
• What other research and development projects could potentially decrease the burden of STDs?

“More than 1 million STIs are acquired every day. Each year, there are estimated 357 million new infections with 1 of 4 STIs: chlamydia (131 million), gonorrhoea (78 million), syphilis (5.6 million) and trichomoniasis (143 million). More than 500 million people are living with genital HSV (herpes) infection. At any point in time, more than 290 million women have an HPV infection, one of the most common STIs.” @WHO STIs Fact Sheet@

2. See @Global Burden of Disease 2013: Mortality and Causes of Death@ Table 2

“Over 170 types of HPV have been identified, and they are designated by numbers. [11][12][13] Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals. [citation needed]  HPV types 6 and 11 can cause genital warts and respiratory papillomatosis. [2]  HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 are considered carcinogenic. [14] ” @Wikipedia: Human papillomavirus@

“Bivalent, quadrivalent, and 9-valent HPV vaccine all protect against HPV 16 and 18, the HPV types that cause about 66% of cervical cancers and the majority of other HPV-attributable cancers in the United States. 9-valent HPV vaccine targets five additional cancer-causing types, which account for about 15% of cervical cancers (12). Quadrivalent and 9-valent HPV vaccine also protect against HPV 6 and 11, the HPV types that cause anogenital warts.” @CDC: HPV Vaccine Information for Clinicians@

4. “Safe and highly effective vaccines are available for 2 STIs: hepatitis B and HPV. These vaccines have represented major advances in STI prevention. The vaccine against hepatitis B is included in infant immunization programmes in 93% of countries and has already prevented an estimated 1.3 million deaths from chronic liver disease and cancer.” @WHO STIs Fact Sheet@

“Three bacterial STIs (chlamydia, gonorrhoea and syphilis) and one parasitic STI (trichomoniasis) are generally curable with existing, effective single-dose regimens of antibiotics.” @WHO STIs Fact Sheet@

“Resistance of STIs—in particular gonorrhoea—to antibiotics has increased rapidly in recent years and has reduced treatment options. The emergence of decreased susceptibility of gonorrhoea to the “last line” treatment option (oral and injectable cephalosporins) together with antimicrobial resistance already shown to penicillins, sulphonamides, tetracyclines, quinolones and macrolides make gonorrhoea a multidrug-resistant organism. Antimicrobial resistance for other STIs, though less common, also exists, making prevention and prompt treatment critical.” @WHO STIs Fact Sheet@

@STD.gov List of All STDs and Their Symptoms@

@The STD Project’s List of All STDs@

@Wikipedia: Causes of sexually transmitted infections@

@Shrestha and Englund 2010@

8. We averaged the 2013 Global Burden of Disease Study (GBD) and the World Health Organization’s (WHO) Global Health Observatory (GHO) global DALY burden data to get our preliminary estimate of DALY impact size and determine which diseases that are not difficult or impossible to treat or cure met the 5m DALY bar.

9. We speculate that a reason this number is higher than the corresponding number in the GBD 2013 may be because “Other STDs” in the WHO report may include genital herpes, which was calculated separately in GBD 2013.

The spreadsheet @GBD 2013 International Classification of Diseases codes mapped to the Global Burden of Disease cause list@ cells B94-100 lists the ICD10 codes associated with the STDs for which the overall DALY burden was calculated in the 2013 GBD. We looked up these codes on  ICD10 data website  to find out what sequelae were included in the impact calculation in the table above. We corresponded with a GBD representative who confirmed that the ICD codes listed in the @GBD 2013 International Classification of Diseases codes mapped to the Global Burden of Disease cause list@ constituted the disease impacts included in the overall disease burden assessment. Note that in one case, we were unable to find the ICD code referenced in the GBD spreadsheet: cells B93, B94, B95 and B97 reference ICD code M73, but we were unable to find that code on the ICD10 website. The list of codes  from M70 to M79  does not seem to include M73. We do not know why we were unable to find the code.

We are uncertain about how the WHO GHO DALY burdens were calculated, and were unable to understand its process based on the information provided on the website (see @WHO GHO Data@). We reached out to a representative at the WHO GHO and have not received a response. Some information about the WHO GHO methodology and differences compared to the GBD 2010 approach are noted  here  (@WHO: Global Burden of Disease@).

We found that both sources included the impact of neonatal syphilis, the GBD did not include neonatal herpes, chlamydia, or gonorrhea (the DALY burden of each of these broken down by age group can be found at the @Global Burden of Disease Study 2013 (GBD 2013) Data Downloads – Full Results@ by selecting the diseases of interest as the ‘Causes’). The WHO GHO does not have a separate DALY estimate for herpes and very low estimates of the burden of chlamydia and gonorrhea in children under five (both diseases are listed as causing <30 DALYS per year in children under five, globally in the @WHO GHO DALYs by Cause@) to the extent that we doubt that this accurately captures the effects of the neonatal forms of these diseases.Below, we examine other effects of STDs which are not included in the assessments of the burdens given in the table above.

“Before the advent of highly active antiretroviral therapy (HAART), observational data demonstrated an association between non-ulcerative STDs, such as  N. gonorrhoeae  and  C. trachomatis , and the risk of HIV transmission.7 HIV-infected women who had intercurrent  N. gonorrhoeae ,  C. trachomatis , or  T. vaginalis  had increased rates of HIV detection in the cervix and vagina compared to HIV-infected women who did not have an STD, and HIV-infected men who had  N. gonorrhoeae  or  C. trachomatis  were more likely to have higher levels of HIV in the semen than mono-infected controls.8–11 For women, perturbations of the vaginal microflora associated with bacterial vaginosis have also been associated with increased HIV expression in the genital tract.12 In addition, HIV-infected individuals who experienced reactivations of HSV-2 can have high levels of HIV virus recovered from their genital tract ulcers. 13 ” @Mayer and Venkatesh 2011@

“Two further cohort studies provide evidence for the possible role of human papillomavirus (HPV) in the sexual transmission of HIV. Auvert and colleagues used data from a male circumcision trial in South Africa to look at the association between HPV and HIV incidence. [24**]After controlling for other factors, there was no association between low-risk HPV and HIV, but there was a 4-fold increased risk in men with high-risk HPV, and the incidence increased with the number of high-risk HPV genotypes detected. A similar finding was reported among MSM in the USA, where increasing numbers of anal HPV types increased HIV risk. [25]” @Ward and Rönn 2010@

“With regard to enhanced susceptibility, ulcerative STDs, such as syphilis,  Herpes simplex type 2  (HSV-2), and chancroid, result in lesions that cause a breakdown in mucosal integrity and recruit activated target cells containing an enriched population of cells carrying CD4 cell receptors… STDs may also increase the expression of HIV binding ligands which can facilitate HIV acquisition and transmission.” @Mayer and Venkatesh 2011@

“A randomized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy (valacyclovir, 500 mg twice daily, or placebo for 8 weeks, a 2-week washout period, then the alternative therapy for 8 weeks) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) who were not on antiretroviral therapy. Plasma samples (obtained weekly) and endocervical swab specimens (obtained thrice weekly) were collected for HIV-1 RNA polymerase chain reaction. Plasma HIV-1 level was significantly lower during the valacyclovir arm, compared with the placebo arm (−0.26 log10copies/mL, a 45% decrease [ P <.001]), as was cervical HIV-1 level (−0.35 log10 copies/swab, a 55% decrease [ P <001]).” @Baeten et al. 2008@ (Abstract)

“HSV was detected from 29% and 4.4% of swabs on placebo and valacyclovir, respectively (P<0.001). Valacyclovir significantly reduced the proportion of days with detectable seminal HIV-1 (63% during valacyclovir vs. 78% during placebo, p=0.04). The quantity of HIV-1 in semen was 0.25 log10 copies/mL lower (95%CI −0.40 to −0.10, p=0.001) during the valacyclovir arm compared with placebo, a 44% reduction. CD4 count (p=0.32) and seminal cellular CMV quantity (p=0.68) did not predict seminal plasma HIV-1 level.” @Zuckerman et al. 2009@ (Abstract)

• @Mayer and Venkatesh 2011@
• “Over the last decade and a half, there have been several large, multi-center clinical trials conducted in sub-Saharan Africa to evaluate whether the treatment of bacterial STDs could result in decreasing the incidence of HIV transmission and acquisition (see  Table I ). 22  In the Mwanza trial, the only clearly successful STD intervention study, multiple communities in Tanzania were randomized to receive syndromic management of acute bacterial STDs with a regimen that was effective against  N. gonorrhoeae , syphilis, and  C. trachomatis . 23,24  The study was initiated in communities with an average HIV prevalence of 1%, and by the end of the study HIV prevalence was approximately 4% across the sites. By the end of the study, the syndromic management approach resulted in a 29% decrease in syphilis and a 49% reduction in incident urethritis. Although there were no changes in condom use or sexual risk behaviors, there was a statistically significant 38% reduction in HIV incidence. However, several subsequent large interventional STD trials conducted in East Africa were not successful in demonstrating that STD treatment could decrease HIV incidence. In the Rakai study conducted in rural Uganda, the investigators randomized communities to receive periodic mass treatment with a regimen that was effective against  N. gonorroheae ,  C. trachomatis ,  T. vaginalis , and bacterial vaginosis, as well as syphilis. 25  Intervention teams went into villages every 9–10 months to offer the mass treatment. The investigators were able to demonstrate a 20% reduction in syphilis and a 41% reduction in incident  T. vaginalis , both of which were statistically significant. However, there was no reduction in HIV incidence in the intervention communities. In contrast to the Mwanza study, the HIV epidemic was already much more well-established in this part of rural Uganda, with an HIV prevalence at the beginning of the study of over 16% in the male population. 26,27  Subsequent analyses by researchers in the Rakai group found that the two largest predictors of incident HIV infection among HIV discordant couples were the level of circulating plasma HIV RNA in the infected partner 28  and, independently, also the presence of prevalent and incident HSV-2 infection. 27  Similar to the Rakai trial, two other large scale clinical trials of STD interventions, one involving syndromic management of STDs as part of a community randomized trial in Masaka, Uganda, and one involving monthly antibiotic chemoprophylaxis conducted among Kenyan female sex workers, did not lead to a decrease in HIV incidence. 29,30 ” See also Table 1 for details on each study.
• “In 2008, a large randomized controlled trial conducted among HIV uninfected, HSV-2 antibody-positive African women to prevent HIV acquisition, comparing acyclovir to placebo, had no impact. 47  Later that year, another large multi-center study among high-risk North and South American MSM and African women who were HIV-uninfected, HSV-2 seropositive failed to show a benefit of acyclovir prophylaxis in decreasing HIV incidence, but unlike the earlier study, this study did show a 47% reduction in genital ulcers. 48  More recently, a study of HSV-2 suppressive therapy among HIV-infected and HSV-2 seropositive Africans who were in HIV discordant relationships did not demonstrate a decrease in HIV transmission to their uninfected partners, but did show a decrease in genital ulcers by 73% and plasma HIV viral load by 0.25 log 10 . 49,50  A reason for the failure of acyclovir to prevent HIV acquisition and transmission could be due to the relatively low dosage that was used (400 mg/twice daily), while in some settings a drug concentration several times higher may be used for optimal HSV-2 suppression, particularly in individuals who are already HIV co-infected. 51,52  Another reason for the lack of efficacy may be that although acyclovir decreases active clinical shedding of HIV, it may not be sufficiently potent to alter the inflammatory genital tract milieu, including micro-ulcerations, recruitment of cells that can bind or transmit HIV, or other mucosal changes that may potentiate HIV transmission. 53 ”
• “There were three randomized controlled trials that met our inclusion criteria recruited HIV-negative participants with chancroid (two trials with 143 participants) and primary syphilis (one trial with 30 participants). The syphilis study, carried out in the US between 1995 and 1997, randomized participants to receive a single 2.0 g oral dose of azithromycin (11 participants); two 2.0 g oral doses of azithromycin administered six to eight days apart (eight participants); or benzathine penicillin G administered as either 2.4 million units intramuscular injection once or twice seven days apart (11 participants). No participant in the trial seroconverted during 12 months of follow-up. The chancroid trials, conducted in Kenya by 1990, found no significant differences in HIV seroconversion rates during four to 12 weeks of follow-up between 400 and 200 mg single oral doses of fleroxacin (one trial, 45 participants; RR 3.00; 95% CI 0.29 to 30.69), or between 400 mg fleroxacin and 800 mg sulfamethoxazole plus 160 mg trimethoprim (one trial, 98 participants; RR 0.33; 95% CI 0.04 to 3.09). Adverse events reported were mild to moderate in severity, and included Jarisch-Herxheimer reactions and gastrointestinal symptoms. The differences between the treatment arms in the incidence of adverse events were not significant. The quality of this evidence on the effectiveness of genital ulcer disease treatment in reducing sexual acquisition of HIV, according to GRADE methodology, is of very low quality.” @Mutua, M’Imunya, and Wiysonge 2012@
• “In the mass treatment trial in rural southwestern Uganda, after three rounds of treatment of all community members for STIs, the adjusted rate ratio (aRR) of incident HIV infection was 0.97 (95% CI 0.81 – 1.2), indicating no effect of the intervention. The three STI management intervention studies were all conducted in rural parts of Africa. One study, in northern Tanzania, showed that the incidence of HIV infection in the intervention groups (strengthened syndromic management of STIs in primary care clinics) was 1.2% compared with 1.9% in the control groups (aRR = 0.58, 95% CI 0.42 – 0.79), corresponding to a 42% reduction (95% CI 21.0% – 58.0%) in HIV incidence in the intervention group. Another study, conducted in rural southwestern Uganda, showed that the aRR of behavioural intervention and STI management compared to control on HIV incidence was 1.00 (95% CI 0.63 – 1.58). In the third STI management trial, in eastern Zimbabwe, there was no effect of the intervention on HIV incidence (aRR = 1.3, 95% CI 0.92 – 1.8). These are consistent with data from the mass treatment trial showing no intervention effect. Overall, pooling the data of the four studies showed no significant effect of any intervention (rate ratio [RR] = 0.97, 95% CI 0.78 – 1.2).Combining the mass treatment trial and one of the STI management trials, we find that there is a significant 12.0% reduction in the prevalence of syphilis for those receiving a biomedical STI intervention (RR 0.88, 95% CI 0.80 – 0.96). For gonorrhoea, we find a statistically significant 51.0% reduction in its prevalence in those receiving any of these interventions (RR 0.49, 95% CI 0.31 – 0.77). Finally, for chlamydia, we found no significant difference between any biomedical intervention and control (RR 1.03, 95% CI 0.77 – 1.4).” @Ng et al. 2011@

Note that there is overlap between the studies examined in the reviews above.

15. For example, for HSV, the potential impact seems very large. This is because:

• In an observational study from 2002, researchers found that approximately 20% of cases of HIV at their study site appeared to be attributable to HSV-2 when 22% of the population was infected with HSV-2. [1]  We have a very limited understanding of the reliability or methodology of these studies.
• In several studies from the 1990s and 2000s, the percentage of the population infected with HSV-2 in various countries was within a factor of 2-4 of that the HSV-2 prevalence in the observational study. [2]  We do not know if genital HSV-1 has been linked to HIV transmission. We note that it seems possible that other factors (e.g. likelihood of engaging in sexual intercourse while experiencing an outbreak of genital herpes) could potentially drive differences in HSV-driven HIV transmission even in regions where HSV-2 infection prevalence rates are similar.
• The global burden of HIV is estimated to be approximately 80M DALYs. [3]  80M*0.2=16M DALYs that could potentially be attributable to HSV-driven HIV transmission. We don’t know whether HIV cases that are attributable to HSV are representative of HIV cases in general in terms of their DALY burden.

However, we note that if STDs increase HIV transmission, HSV may be responsible for a larger share of these transmission events than other STDs because it is highly prevalent. [4]

[1] “For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4–3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1–5.1), but the temporal sequence of the 2 infections cannot be documented.” @Wald and Link 2002@

[2]  *”HSV-2 infections are markedly less frequent than HSV-1 infections, with 15%–80% of people in various populations infected (Corey and Wald, 1999). The rates of infection vary with country as well as levels of sexual activity. In some countries, such as Spain and the Philippines, the HSV-2 prevalence hovers around 10%, increasing to 20%–30% range for most European countries and the United States (Varela et al., 2001; Smith et al., 2001; Enders et al., 1998; Malkin et al., 2002). Developing countries bear a much higher burden of HSV-2 infection, with many populations in Africa having >50% prevalence in the general population (Weiss et al., 2001).” @Wald and Corey 2007@ (although we did not vet those prevalence estimates, and note that that many are over a decade old).

*”The estimated total number of people aged 15–49 years who were living with HSV-2 worldwide in 2003 is 536 million (Table 1). More women than men were infected, with an estimated 315 million infected women compared to 221 million infected men. The number infected increased with age, most markedly in the younger ages, until it peaked in the age stratum 35–39 years of age, after which it declined slightly.” @Looker Garnett and Schmid 2008@

[3]  It was estimated to be 91,907,414 DALYs by the WHO in 2012 (see @WHO GHO DALYs by Cause@), and 69,363,400 DALYs by the GBD in 2013 (see @GBD 2013 DALYs from all causes@ cell C7). We used 80M as a rough average of the two estimates.

[4]  For example: “A cohort study of women in two African countries, Zimbabwe and Uganda, followed 4439 women every 3 months for up to two years. [20**]With the exception of syphilis, which was uncommon, all the reproductive tract infections were associated with HIV in at least one statistical model. After controlling for demographic and behavioural factors, the strongest risk was from gonorrhoea, which conferred a 7-fold increase in HIV incidence, but the highest population attributable risk percent (PAR%) was for sero-prevalent HSV-2 (50.4%), with incident HSV-2 contributing 7.9%, gonorrhoea 5.3%, and bacterial vaginosis 17.2%.” @Ward and Rönn 2010@

“Three studies provided sufficient data to allow calculation of the proportion of HIV infections attributable to prevalent HPV infection ( Table 3 ). 21 and 37% of HIV infections in women in studies in Zimbabwe[24] and South Africa[29] were attributable to infection with prevalent HPV of any genotype at the visit prior to HIV acquisition. 28% of HIV infections in Kenyan heterosexual men[30] were attributable to infection with HPV at baseline.” @Houlihan et al. 2012@

17. “It is biologically plausible that prevalent HPV may increase the risk of HIV acquisition. It has been demonstrated that the E7 protein of HPV type-16 down-regulates an epithelial adhesion molecule called E-Cadherin[39], potentially increasing permeability of the genital lining to HIV. The lining of the genital tract contains Langerhans’ cells (LC), which can internalise HIV, preventing onward infection[40]. In HPV-infected tissue, a reduced density and altered morphology of LCs has been demonstrated[41-43]. The host immune response to HPV is mediated by T-lymphocytes[44], and this response may increase HIV risk since T-lymphocytes are primary target cells for HIV. An increased presence of these cells has been seen in HPV-infected cervical tissue[45]. Further, HPV non-persistence, which is likely to be associated with a T-lymphocyte influx, was associated with HIV acquisition in 2 studies in this review[24, 26], when persistent infection was not. Elevated levels of cytokine IL-Iβ, which activates a promoter region in the HIV genome[46], have also been demonstrated in women with HPV-associated abnormal cervical cytology[47] and defensins and thrombospondins, anti-HIV proteins, are also lower in precancerous cervical lesions[48] (although in this review cytological abnormalities were not associated with HIV acquisition[23, 26]).”@Houlihan et al. 2012@

18. “There are currently two vaccines that provide near 100% protection against persistent infection with HPV-16 and 18, two highly prevalent genotypes that are responsible for 70% of invasive cervical cancer cases and a relatively smaller fraction of other HPV-associated cancers. This raises the question as to whether individuals who receive HPV vaccination will have the added benefit of lowering risk of HIV infection [5,21]. Since there are currently no data to directly estimate this, we used our observational data to examine risk of HIV acquisition among men infected with vaccine-preventable types 16/18, taking into account other concurrent HPV infections” @Rositch et al. 2014@

19. “Genital herpes is a sexually transmitted disease (STD) caused by the herpes simplex viruses type 1 (HSV-1) or type 2 (HSV-2).” @Genital Herpes – CDC Fact Sheet (Detailed)@

• “We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital. Findings We estimated that 3709 million people (range: 3440–3878 million) aged 0–49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67–212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific.” @Looker et al. 2015@

@Looker Garnett and Schmid 2008@

“The large majority of persons with genital herpes do not know they have the disease and infection and reactivation are typically “asymptomatic” although, with teaching, most persons with positive HSV-2 serology (46 of 53, in one study) recognize genital lesions.”

“The estimated total number of people aged 15–49 years who were living with HSV-2 worldwide in 2003 is 536 million (Table 1). More women than men were infected, with an estimated 315 million infected women compared to 221 million infected men. The number infected increased with age, most markedly in the younger ages, until it peaked in the age stratum 35–39 years of age, after which it declined slightly.”

21. “Nationwide, 15.5 % of persons aged 14 to 49 years have HSV-2 infection. 21 The overall prevalence of genital herpes is likely higher than 15.5% because an increasing number of genital herpes infections are caused by HSV-1.” @Genital Herpes – CDC Fact Sheet (Detailed)@

22. “There is no cure for herpes. Antiviral medications can, however, prevent or shorten outbreaks during the period of time the person takes the medication. In addition, daily suppressive therapy (i.e. daily use of antiviral medication) for herpes can reduce the likelihood of transmission to partners.

Several clinical trials have tested vaccines against genital herpes infection, but there is currently no commercially available vaccine that is protective against genital herpes infection. One vaccine trial showed efficacy among women whose partners were HSV-2 infected, but only among women who were not infected with HSV-1. No efficacy was observed among men whose partners were HSV-2 infected. A subsequent trial testing the same vaccine showed some protection from genital HSV-1 infection, but no protection from HSV-2 infection. 17” @Genital Herpes – CDC Fact Sheet (Detailed)@

23. “The updated Global Burden of Disease Study (GBD) estimates that genital HSV resulted in 311,600 years lived with disability (YLD) in 2013 (95% uncertainty interval 98,300–748,500) due to genital ulcer disease alone [18]. GBD 2013 likely underestimates the impact of genital HSV, as these YLD estimates do not include disability due to neonatal herpes nor the contribution of genital HSV to HIV susceptibility, which are the most devastating consequences of infection.” @Johnston, Gottlieb, and Wald 2016@

See also @GBD 2013 DALYs from all causes@, cell C80

The impacts of genital herpes included in this assessment can be found in the @GBD 2013 International Classification of Diseases codes mapped to the Global Burden of Disease cause list@ cell B99. See the ICD codes associated with the GBD genital herpes assessment  here  (@ICD 10 Data: Anogenital herpes@).

• “The frequency of neonatal herpes varies by region and is estimated to occur from 1 in 3200 to 1 in 15000 pregnancies (Sullivan-Bolyai  et al ., 1983a; Tookey and Peckham, 1996; Mindel  et al ., 2000; Brown  et al ., 2003; Gutierrez  et al .,1999)” @Wald and Corey 2007@. We do not know what regions are represented in this estimate, and whether the frequency has changed since it was made.
• “The HSV-2 epidemic is of concern in part because of its potential to cause neonatal herpes. 11,24,49,97  Through pooling of prevalence values by age and sex in a random-effect model, followed by the use of a constant-incidence model, the worldwide prevalence of HSV-2 among 15- to 49-year-olds is estimated to be 536 million (16%). 48  NHANES data from 1999–2002 showed that 63% of pregnant women in the United States were seropositive for HSV-1, 22% for HSV-2, and 13% for both. 96  The incidence of neonatal HSV was estimated to be 5.9 per 100,000 live births in a nationwide surveillance program in Canada and ranged from 5.8 to 11.5 per 100,000 live births in the United States.14 Various manifestations of ocular infection occur in an estimated 13–20% of neonates with HSV. 54,61 ” @Farooq and Shukla 2012@

We did not vet these estimates or investigate the methodologies used in these studies.

• “Untreated neonatal HSV infection is associated with only a 40% survival rate, and even with the early initiation of high-dose intravenous acyclovir therapy, it results in considerable disability among survivors.” @Corey and Wald 2009@, p. 1376.
• “The mortality rate [of neonatal HSV infection] is relatively high (24%), and long-term sequelae may occur.” @Clinuvel: Herpes Simplex Virus@. We are uncertain about how this document arrived at the 24% figure, and could not find an explanation or source.
• Another study found a mortality rate of 0.8/100,000 live births in California from 1995-2003: “The overall incidence of neonatal herpes was 12.1 per 100,000 live births per year, with no observable change from 1995 to 2003. Neonatal herpes-related mortality, which was estimated to be 0.8 deaths per 100,000 live births, also did not show significant change over time.” @Morris et al. 2008@ (Abstract), indicating an overall mortality rate 6.6% (0.8 death rate from neonatal HSV/12.1 incidence of neonatal HSV) of neonatal HSV cases.

We would guess that the mortality rate might be higher in the developing world, where HSV may be more common and access to antivirals and diagnostic tools may be more limited, but we don’t know if this is true, and if so, how much higher it might be.

26. There are approximately 135M births/year ( CIA World Factbook , 525600 minutes/year*256 births/minute=134,553,600 births/year).

27. For example if 10,000 people would have lived to 70 years of age but die in infancy due to neonatal HSV each year, the DALY impact would be 700K. Note that this estimate is excluding the burden on infants that don’t die but live with disability as a result of HSV, which we understand to be substantial. Also note that these years are not discounted because the 2013 Global Burden of Disease does not use a discount rate, and we felt that it was useful to make the numbers more comparable.

28. We use the following estimate of severe vision loss from HSV: “One way to estimate vision loss in HSV would be to determine the proportion of HSV keratitis cases that lead to blindness in the affected eye and extrapolate this to annual incidence rates. A Moor-fields Eye Hospital study found that of 152 patients with epithelial keratitis, only 3% had a final visual acuity less than 20/200. 93  Final visual acuity ranged from 20/60 to 20/200 in 24%, and 20/20 to 20/40 in 73%. Liesegang et al found a slightly lower incidence of vision impairment in ocular HSV (3 of 131 cases); impairment was defined as an acuity worse than 20/100, however, and the series included diseases other than keratitis. 47  Final visual acuity was 20/40 or better in 78% of eyes. A study at the Aravind Eye Hospital in India found that at least 2% had visual acuity worse than 20/1200, and 62% improved to better than 20/40. 31  Norn et al found nearly 6% of eyes were worse than 20/200, although some were treated with idoxuridine or steroids. 64  In one series 20% of HSV uveitis cases led to severe vision loss; this did not include cases of uveitis without keratitis, which would be considered additive. 55  Although blindness can occur via ocular HSV without corneal involvement (e.g., acute retinal necrosis), these cases are much rarer.

There were several factors that needed to be considered in projecting the rates of vision loss from HSV keratitis ( Table 6 ). Based on these issues, and adjusting the Moorfields data for the effect of long-term antiviral treatment (which reduces the rate of recurrence), we estimate that at least 1.5% of clinically significant HSV keratitis leads to vision worse than 20/200, the WHO definition of severe visual impairment in developed nations ( Table 6 ). This is based on the assumption that a reduction in recurrence rate leads to a proportional decrease in visual impairment. It is slightly lower than the rate of visual impairment in the Rochester study, where acyclovir was available for only a portion of the study period. In the developing world, including Africa and India, it may be 3% or higher as access to treatment is often severely limited, and other risk factors may play a role. We are unable to estimate the proportion of cases leading to monocular blindness (lower than 20/400). Longer study periods might reveal higher rates of vision loss as there would be more time for recurrences.

Using the available data on visual prognosis, therefore, our conservative estimate is that HSV keratitis is the cause of roughly 40,000 new cases of severe monocular visual impairment or blindness annually in the world ( Table 7 ).” @Farooq and Shukla 2012@. Table 7 includes data about HSV keratitis incidence. We have not vetted this estimate.

29. For example, we read that, “[m]ost HSV eye disease occurs in adults, developing many years after the primary infection (mean age of presentation, late fifth to early sixth decade of life). Herpetic keratitis in children commonly involves the corneal epithelium and stroma and is marked by a disproportionate risk of bilateral disease, high recurrence rate, and amblyopia.” @Wang and Ritterband: Herpes Simplex Keratitis Epidemiology@

30. “In the presence of a certain gene variation (APOE-epsilon4 allele carriers), a possible link between HSV-1 (i.e., the virus that causes cold sores or oral herpes) and Alzheimer’s disease was reported in 1979. [39]  HSV-1 appears to be particularly damaging to the nervous system and increases one’s risk of developing Alzheimer’s disease. The virus interacts with the components and receptors of lipoproteins, which may lead to the development of Alzheimer’s disease. [40]  This research identifies HSVs as the pathogen most clearly linked to the establishment of Alzheimer’s. [41]  According to a study done in 1997, without the presence of the gene allele, HSV-1 does not appear to cause any neurological damage or increase the risk of Alzheimer’s. [42]  However, a more recent prospective study published in 2008 with a cohort of 591 people showed a statistically significant difference between patients with antibodies indicating recent reactivation of HSV and those without these antibodies in the incidence of Alzheimer’s disease, without direct correlation to the APOE-epsilon4 allele. [43]  It should be noted that the trial had a small sample of patients who did not have the antibody at baseline, so the results should be viewed as highly uncertain. In 2011 Manchester University scientists showed that treating HSV1-infected cells with antiviral agents decreased the accumulation of β-amyloid and P-tau, and also decreased HSV-1 replication. [44] ” @Wikipedia: Herpes simplex virus@

• “A herpetic infection of the brain thought to be caused by the transmission of virus from a peripheral site on the face following HSV-1 reactivation, along the trigeminal nerve axon, to the brain. HSV is the most common cause of viral encephalitis. When infecting the brain, the virus shows a preference for the temporal lobe. [14]  HSV-2 is the most common cause of Mollaret’s meningitis, a type of recurrent viral meningitis.” @Wikipedia: Herpes simplex@
• “Benign recurrent aseptic meningitis is a rare disorder described by Mollaret in 1944. When initially described, this form of aseptic meningitis had no identifiable infecting agent. New sophisticated diagnostic tools have now identified herpes simplex type 2 virus as the most commonly isolated agent. Antiviral treatment has been used successfully for prophylaxis and treatment.” @Farazmand Woolley and Kinghorn 2011@ (Abstract)

We were unable to find quantitative information about the prevalence and impact of Mollaret’s meningitis, but our impression from our reading is that it is rare.

32. “Herpes whitlow is a painful infection that typically affects the fingers or thumbs. On occasion, infection occurs on the toes or on the nail cuticle. Individuals who participate in contact sports such as wrestling, rugby, and football(soccer), sometimes acquire a condition caused by HSV-1 known as herpes gladiatorum, scrumpox, wrestler’s herpes, or mat herpes, which presents as skin ulceration on the face, ears, and neck. Symptoms include fever, headache, sore throat, and swollen glands. It occasionally affects the eyes or eyelids.” @Wikipedia: Herpes simplex@

33. @Human papillomavirus vaccines: WHO position paper, October 2014@

“Based on a meta-analysis, the adjusted HPV prevalence worldwide among women with normal cytological findings was estimated to be 11.7% (95% confidence interval (CI): 11.6–11.7%). 2  The highest adjusted prevalence was found in sub-Saharan African regions (24%; 95% CI: 23.1–25.0%), Latin America and the Caribbean (16.1%; 95% CI: 15.8–16.4%), Eastern Europe (14.2%; 95% CI: 14.1–14.4%), and south-eastern Asia (14%; 95% CI: 13.0–15.0). However, country-specific adjusted HPV prevalence in cervical specimens ranged from 1.6% to 41.9% worldwide. Age-specific HPV prevalence peaked at younger ages (<25 years) with a prevalence of 21.8% (95% CI: 21.3–22.3%, crude) and 24.0% (95% CI: 23.5– 24.5%, adjusted), with a lower prevalence plateau at middle-ages.”

“HPV prevalence in men: A systematic review of genital HPV among men in sub-Saharan Africa found that the prevalence of any HPV type ranges between 19.1% and 100%. 5  The estimated pooled prevalence of any HPV was 78.2% (95% CI: 54.2–91.6%) among HIV-positive men and 49.4% (95% CI: 30.4–68.6%) among HIV-negative men (p=0.0632). No clear age trend was observed. The most common high-risk HPV types were HPV-16 and HPV-52, and HPV-6 was the most common low-risk HPV type in the general population.

A systematic review of genital HPV-DNA prevalence in men examined data generally limited to men >18 years of age from Europe and North America. 6  The estimated HPV prevalence in men peaked at slightly older ages than in women and remained constant or decreased slightly with increasing age. HPV prevalence was high in all regions but varied from 1% to 84% among low-risk men, and from 2% to 93% among high-risk men (e.g. sexually transmitted infection (STI) clinic attendees, HIV-positive males, and male partners of women with HPV infection or abnormal cytology). HIV-positive men who have sex with men showed the highest prevalence. Anal HPV infections are very common in men who have sex with men, and almost universal among those who are HIV-infected. 7

A multicentre clinical trial (conducted in 18 countries from Africa, Asia-Pacific, Europe, Latin America and North America) examined the baseline prevalence of penile, scrotal, and perineal/perianal HPV infection in heterosexual men. The prevalence of any HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. HPV was most prevalent in African men and least prevalent in men from the Asia-Pacific region. Age was not associated with risk of positivity for HPV types 6, 11, 16, 18, or any tested HPV types. Having at least 3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% CI: 2.1–4.9) for HPV types 6, 11, 16, and 18; and OR 4.5 (95% CI: 3.3–6.1) for all HPV types tested. 8 ”

34. “Human papillomavirus (HPV) is a very common virus that infects epithelial tissue. More than 120 HPV types have been identified. Most HPV types infect cutaneous epithelial cells and cause common warts, such as those that occur on the hands and feet. Approximately 40 HPV types infect mucosal epithelial cells on the genitals, and the mouth and throat. Although most HPV infections are asymptomatic and resolve spontaneously or become undetectable, some HPV infections can persist and lead to cancer. Persistent infections with high-risk (oncogenic) HPV types can cause cancers of the anus, cervix, penis, vulva, and vagina, as well as the oropharynx (defined as the back of the throat, including the base of the tongue and tonsils). The most common high-risk types are 16 and 18.

Infection with low-risk (non-oncogenic) HPV types can cause genital warts and rarely laryngeal papillomas. These types can also cause benign or low-grade cervical cell abnormalities. The most common low-risk HPV types are 6 and 11.” @CDC: HPV Vaccine Information for Clinicians@

35. “It is important to note that HPV vaccines are highly efficacious as a 3-dose schedule in women aged 18–26 years for prevention of CIN 3; data on efficacy for prevention of cervical cancer are pending.49” @Human papillomavirus vaccines: WHO position paper, October 2014@

We understand CIN 3 to refer to severely abnormal cervical intraepithelial neoplasia, a precursor to cervical cancer, based on  this definition  of CIN 3.

“Gardasil 9 is a vaccine approved for use in females ages 9 through 26 and males ages 9 through 15. It is approved for the prevention of cervical, vulvar, vaginal and anal cancers caused by HPV types 16, 18, 31, 33, 45, 52 and 58, and for the prevention of genital warts caused by HPV types 6 or 11. Gardasil 9 adds protection against five additional HPV types—31, 33, 45, 52 and 58— which cause approximately 20 percent of cervical cancers and are not covered by previously FDA-approved HPV vaccines.” @FDA News Release: Gardasil 9@

“Virtually all cases of cervical cancer are caused by HPV, and just two HPV types, 16 and 18, are responsible for about 70 percent of all cases (7,8).” @National Cancer Institute: HPV Vaccine Fact Sheet@

“HPV-16 and HPV-18 were the most common HPV types in invasive cervical cancer during the period 1940–2007 with no statistically significant variations in their adjusted-relative contributions from 1940–1959 to 2000–2007 (HPV-16 from 61.5 to 62.1%, and HPV18 from 6.9 to 7.2%). 12  HPV types 16, 18, 45, 31, 33, 52, and 58 account for approximately 90% of the squamous-cell carcinomas which are positive for HPV DNA. 11 ” @Human papillomavirus vaccines: WHO position paper, October 2014@

38. @Human papillomavirus vaccines: WHO position paper, October 2014@

“Cervical HPV infection can be diagnosed using tests based on HPV-DNA performed on cervical or vaginal swabs; HPV-induced changes in the cervical epithelium can be detected by cytology using a microscopic examination of exfoliated cells, known as the Papanicolaou (Pap) test. Testing for HPV DNA, cytology, and visual inspection with acetic acid are used for cervical cancer screening. In low-resource settings, visual inspection of the cervix with acetic acid is used to identify cervical lesions. 29, 30  Anogenital warts are diagnosed by visual inspection including anoscopy.”

“Although there is no virus-specific treatment for HPV infection, the HPV-related diseases can be treated by tissue destructive measures. In low-income countries, precancerous lesions of the cervix are most commonly treated by cryotherapy. 31  Surgical excision of the affected tissue is also effective (loop electrosurgical excision procedure) and necessary when the lesion is large. 29, 31  Excision by cone biopsy is reserved for more advanced or recurrent cases, especially those involving disease in the endocervical canal. Screening and treatment for preinvasive disease of the cervix is highly successful in preventing progression to cervical cancer. 29 ”

39. “The majority (70%–90%) of HPV infections with both high and low risk types are asymptomatic and resolve spontaneously within 1–2 years. In some instances, persistent infection with the high-risk types may ultimately progress to invasive carcinoma at the site of infection, mainly of the genital tract, if not detected and treated appropriately. Persistent HPV infection is a necessary cause of cervical cancer. 10 ” @Human papillomavirus vaccines: WHO position paper, October 2014@

40. “The interval between the acquisition of HPV infection and progression to invasive carcinoma is usually about 10 years or longer.” @Human papillomavirus vaccines: WHO position paper, October 2014@

41. “Cervical cancer is the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases in 2012. As with liver cancer, a large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers. High-risk regions, with estimated ASRs over 30 per 100,000, include Eastern Africa (42.7), Melanesia (33.3), Southern (31.5) and Middle (30.6) Africa. Rates are lowest in Australia/New Zealand (5.5) and Western Asia (4.4). Cervical cancer remains the most common cancer in women in Eastern and Middle Africa.

There were an estimated 266,000 deaths from cervical cancer worldwide in 2012, accounting for 7.5% of all female cancer deaths. Almost nine out of ten (87%) cervical cancer deaths occur in the less developed regions. Mortality varies 18-fold between the different regions of the world, with rates ranging from less than 2 per 100,000 in Western Asia, Western Europe and Australia/New Zealand to more than 20 per 100,000 in Melanesia (20.6), Middle (22.2) and Eastern (27.6) Africa.” @Globocan Cervical Cancer Fact Sheet@

42. “Persistent HPV infection is a necessary cause of cervical cancer. 10 ” @Human papillomavirus vaccines: WHO position paper, October 2014@

43. @GBD 2013 DALYs from all causes@ cell C101

The number of fatalities from cervical cancer and estimated DALY burden appear to be in agreement. 6,900,000 DALYs/528,000 cases of cervical cancer=13 DALYs/case of cervical cancer.

44. @WHO GHO DALYs by Cause@, “Cervix uteri cancer”

45. “Most anal squamous cell cancers (80%) are caused by HPV, usually HPV-16.18” @Human papillomavirus vaccines: WHO position paper, October 2014@

“IARC26 considers that there is convincing evidence that infection with HPV 16,18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 66 can lead to cervical cancer. For HPV 16, the evidence further supports a causal role in cancer of the vulva, vagina, penis, anus, oral cavity and oropharynx and a limited association with cancer of the larynx and periungual skin. HPV 18 also shows a limited association with cancer at most of these sites. Evidence for associations of HPV types of genus beta with squamous cell carcinoma of the skin is limited for the general population. There is some evidence that HPVs are involved in squamous cell carcinoma of the conjunctiva, but inadequate evidence for a role of HPVs in cancer of the esophagus, lung, colon, ovary, breast, prostate, urinary bladder and nasal and sinonasal cavities.

With respect to cancer of the cervix, oncogenic HPV may be detected by PCR in virtually all cases of cervix cancer, and it is generally accepted that the virus is necessary for development of cancer, and that all cases of this cancer can be ‘attributed’ to infection.10

With respect to squamous cell cancers of the vulva and vagina, carcinoma of the penis and anal cancer, published studies do not allow quantification of relative risk and infection prevalence, because they are generally small in size and usually do not include comparable measurement of prevalence of infection at these sites in normal subjects. To estimate AFs, approximate estimates of the proportion of cancer cases infected with HPV in various series are used.

The prevalence of HPV in vaginal cancer is about 60–65% in studies using PCR methodology.26, 27 About 20–50% of vulvar cancers contain oncogenic HPV DNA,28, 29 but only the basaloid and warty type that tends to be associated with vulvar intraepithelial neoplasia is caused by HPV infection (prevalence 75–100%), and only 2–23% of the keratinizing carcinomas harbour HPV.30 HPV-related vulvar cancer occurs in younger women than the typical keratinizing squamous histology related to chronic inflammatory precursors. Vulvar carcinomas are generally rather more frequent than cancers of the vagina; an overall HPV prevalence of about 40% in cancers of the lower genital tract in women is assumed. For anal cancer, in a large series of cases from Denmark and Sweden 95% and 83% of cancers involving the anal canal in women and men, respectively, were positive for oncogenic HPV31; the AF is taken to be 90% worldwide. For penile cancer, HPV DNA was found in 30% of 71 cases of penile cancer from Brazil32 and in 42% of 148 cases from the USA and Paraguay;33 the AF is assumed to be 40%.

HPV probably plays a role in the aetiology of a fraction of cancers of the oral cavity and pharynx,34 although the major risk factors are, of course, tobacco and alcohol. Several studies have investigated prevalence of HPV in cancers of the mouth and pharynx.35, 36 On average ˜40% of tumours were HPV-positive, but the prevalence varied widely with the population studied, subsites, type of specimen and detection method. HPV was detected most commonly in oropharynx and tonsil, but at every subsite, HPV 16 was the predominant type.37 The largest study so far is a multicentre case-control study in 9 countries, including more than 1,600 cases of cancers of the mouth and oropharynx and 1,700 controls.38 HPV DNA was detected in tumour specimens (cases) by PCR, and presence of antibodies against HPV 16 L1 and HPV 16 E6 and E7 was tested for by ELISA methods in cases and controls. HPV DNA was detected in 4 and 18% of cancers of the mouth and oropharynx, respectively (HPV 16 was found in 95% of the positive cases). As HPV DNA cannot be evaluated in controls, and there was a good correlation between HPV DNA in cancer biopsies and serum anti-E6/E7 antibodies, a comparison was made between HPV-positive cases who were positive for HPV DNA or E6/E7 antibody (6.4% mouth cancers, 15.3% oropharyngeal cancers), and HPV-positive control subjects positive for anti E6 or anti-E7 antibody (1.6%). The AFs, based on these figures, would be 5% for mouth cancers and 16% for cancers of the oropharynx. However, assessment of HPV DNA presence by PCR assay may lead to an overestimation of cases in which the virus is etiologically involved, as suggested by the lower proportion of cases with E6/E7 expression39––4.6% of oral cancers and 12% of oro-pharyngeal cancers in the IARC multinational study.38 The corresponding OR’s and AFs would be 2.9 and 3% for mouth cancers and 9.2 and 12% for oropharynx cancers. For the purpose of estimation, it is assumed that 3% of oral cavity cancers and 12% of cancers of the oropharynx are attributable to HPV.” @Parkin 2006@

46. See  Table III  of @Parkin 2006@. We divided the number of cases of cervical cancer by the total number of HPV-attributable cancers in Table III (492900/561200) and find that 87.8% of HPV-attributable cancers were cervical cancers in 2006. This implies that 12.2% of HPV-attributable cancers are not cervical cancers, but rather are cancers of the vulva, vagina, penis, anus, mouth, or oropharynx (as listed in the table).

We note that the relative proportions of HPV-attributable cancers may have changed since the publication of @Parkin 2006@, but we did not investigate this.

47. “HPV-6 and HPV-11 can also cause a rare condition known as recurrent respiratory papillomatosis (RRP), in which warts form on the larynx or other parts of the respiratory tract. RRP occurs mainly in children younger than 5 years (juvenile-onset RRP) 23  or in persons in the third decade of life (adult-onset RRP). 24  In rare cases, women with genital HPV infection may transmit the virus to an infant during childbirth. 25  Untreated RRP can become seriously debilitating due to airway obstruction.” @Human papillomavirus vaccines: WHO position paper, October 2014@

48. “It is still not apparent whether HPV is a causal factor of lung cancer or whether it is just an opportunistic pathogen in the lung cancer tissue and the exact molecular mechanisms behind it. Almost all of the signalling pathways having a role in lung cancer are found to be altered or blocked by human papilloma viral proteins initiating tumorigenesis. Further evidence is mandatory to substantiate beyond doubt the causative role of HPV in the lung tissue tumorigenesis. Moreover, the cofactors supplementing the HPV in the transformation processes are yet to be classified.” @Prabhu Jayalekshmi and Pillai 2012@

49. @Wikipedia: Human papillomavirus@

“Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin. … In one study, infection by HPV types 2, 27, and 57 were found in people with warts, while infection by HPV types 1, 2, 63, and 27 were found in people with clinically normal skin”

“In very rare cases, HPV may cause epidermodysplasia verruciformis in immunocompromised individuals. The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells, resulting in lesions resembling warts or cutaneous horns. [65] ”

50. “After controlling for past sexual behaviors, vaccinated women had a lower risk of testing positive for the 4 types included in the HPV vaccine (6, 11, 16, or 18; Table 1). This association became stronger when the number of recent sexual partners was controlled for. However, vaccinated women had a higher prevalence of nonvaccine high-risk types than unvaccinated women (61.5% vs 39.7%, prevalence ratio 1.55, 95% CI 1.22-1.98). After adjusting for the number of recent sexual partners, the difference in prevalence of high-risk nonvaccine types was reduced, but remained significant.” @Guo et al. 2015@

But see: “The bivalent vaccine induces strong neutralizing antibody responses (>50% seropositivity) to HPV-31, HPV- 33, HPV-45, and HPV-52. The quadrivalent vaccine induces neutralizing antibody responses to HPV-31, HPV- 33 and HPV-52. Serum-neutralizing antibody responses against non-vaccine HPV types have been reported to be broader and of a higher magnitude in the bivalent versus quadrivalent vaccine recipients. The clinical significance and longevity of this cross-protection are unclear. 77, 78, 79  The vaccines appear to differ in their degree of cross protection. 80 ” @Human papillomavirus vaccines: WHO position paper, October 2014@

51. “Syphilis is a sexually transmitted disease (STD) caused by the bacterium  Treponema pallidum .” @Syphilis – CDC Fact Sheet (Detailed)@

52. “The primary symptoms may include small sores, cuts or bumps on genitals or mouth. Body rash on palms, feet and other parts of the body may follow. When untreated for extensive period of time, syphilis can start destroying body functions and lead to mental, neurological problems, heart diseases, blindness and even death. Infected pregnant women can easily pass syphilis to their children.” @STD.gov List of All STDs and Their Symptoms@

53. @Syphilis – CDC Fact Sheet (Detailed)@

“There are no home remedies or over-the-counter drugs that will cure syphilis, but syphilis is easy to cure in its early stages. A single intramuscular injection of long acting Benzathine penicillin G (2.4 million units administered intramuscularly) will cure a person who has primary, secondary or early latent syphilis. Three doses of long acting Benzathine penicillin G (2.4 million units administered intramuscularly) at weekly intervals is recommended for individuals with late latent syphilis or latent syphilis of unknown duration. Treatment will kill the syphilis bacterium and prevent further damage, but it will not repair damage already done.”

“Although data to support the use of alternatives to penicillin is limited, options for non-pregnant patients who are allergic to penicillin may include doxycycline, tetracycline, and for neurosyphilis, potentially ceftriaxone. These therapies should be used only in conjunction with close clinical and laboratory follow-up to ensure appropriate serological response and cure.”

54. @GBD 2013 deaths from syphilis@ cells M397 and M19

55. See the @WHO GHO Deaths by Cause@

56. Cell M397 of IHME-Data-Syphilis-DALYs from @Global Burden of Disease Study 2013 (GBD 2013) Data Downloads – Full Results@ and @WHO GHO DALYs by Cause@

@GBD 2013 International Classification of Diseases codes mapped to the Global Burden of Disease cause list@ lists syphilis in row 95, as a subcategory of “Sexually transmitted diseases other than HIV”, and the corresponding ICD disease codes listed in cell B95 do not appear to include HIV among the sequelae of syphilis.

58. Some examples of current organizations we are aware of in this space include:

• The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention  (and its  Division of STD Prevention (DSTDP) ) of the CDC
• ProjectAccept
• Johns Hopkins Bloomberg School of Public Health Center for Sexually Transmitted Diseases
• American Sexual Health Association
• International Union against Sexually Transmitted Infections (IUSTI)
• American Public Health Association
• Infectious Diseases Society of America
• Family Health International
• UNAIDS / WHO Global HIV/AIDS & STD Surveillance
• The California Family Health Council

The  HPV and Anal Cancer Foundation  appears to be active (see @The HPV and Anal Cancer Foundation: Role and Impact@) and had in ~$760K in assets 2013 (see @990 Finder: HPV and Anal Cancer Foundation Form 990 2013@). We don’t know how much of that was for HPV R&D.

59. @NIH Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC)@ This does not appear to include HIV/AIDS. There is a separate line for “HPV and/or cervical cancer vaccines”

60. based on looking at @NIH Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC)@ and the titles of all NIH grants larger than $500k from 2015 from the @NIH 2015 STD/Herpes project listing@

61. See @Foundation giving based on Foundation Center data@ sheet “FDO categories” cell E256 for “public health, STDs”  our blog post  What Large-Scale Philanthropy Focuses on Today

62. @Grantome.com “sexually transmitted”@

63. Specifically, we read that:

The National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) of the CDC received ~$760M in funding in 2015 (@CDC Office of Financial Resources 2015 Annual Report@, pg 12) but it’s our impression that little or none of this was allocated the STD R&D.

The  National Coalition of STD Directors  had approximately $940k in assets in 2014: @990 Finder National Coalition of STD Directors Form 990 2013@ but it’s our impression that little or none of this was allocated the STD R&D.

The  American Sexually Transmitted Diseases Association  had approximately $883k in assets in 2014: @990 Finder American Sexually Transmitted Diseases Association Form 990 2014@

The Foundation for Research into Sexually Transmitted Diseases had $1.8M in 2014:@990 Finder The Foundation for Research into Sexually Transmitted Diseases Form 990 2013@

“[N]on–HIV STIs received GBP 139 million across 378 studies” in the period from 1997-2013, according to @Head et al. 2015@

64. @Grantome.com “herpes simplex”@

65. The first figure includes only grants in which “herpes simplex” was included in the project title, while the latter also includes grants in which “herpes simplex” was included in the project abstract or project terms. To access this data, we went to the @NIH Project Reporter@, and:

• In “Fiscal Year”, unselected “active projects” and selected “2015”
• In “Text Search” entered “herpes simplex”
• In “Limit Project search to” selected “Project Title”
• Clicked “Submit Query”
• Clicked “Data and Visualize”
• Repeated this process, instead selecting “Project Title” “Project Terms” and “Project Abstracts” rather than just “Project Title”

See @NIH Reporter- Herpes simplex funding, project titles only@ cell C7 and @NIH Reporter- Herpes simplex funding, project titles, terms, and abstracts@ cell C20

66. @Grantome.com “hpv”@

67. @NIH Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC)@ line for “HPV and/or cervical cancer vaccines”

68. The first figure includes only grants in which “hpv” was included in the project title, while the latter also includes grants in which “hpv” was included in the project abstract or project terms. To access this data, we went to the @NIH Project Reporter@, and:

• In “Text Search” entered “hpv”

See @NIH Reporter- HPV funding, project titles only@ cell C10 and @NIH Reporter- HPV funding, project titles, terms, and abstracts@ cell C27

69. @Grantome.com “syphilis”@

70. The first figure includes only grants in which “syphilis” was included in the project title, while the latter also includes grants in which “syphilis” was included in the project abstract or project terms. To access this data, we went to the @NIH Project Reporter@, and:

• In “Text Search” entered “syphilis”

See @NIH Reporter- Syphilis funding, project titles only@ cell C6 and @NIH Reporter- Syphilis funding, project titles, terms, and abstracts@ cell C15

71. From the @NIH 2015 STD/Herpes project listing@

72. We searched with keywords: “STD” “STI” “Sexually-transmitted” “Venereal” “HPV” “Herpes” and “Syphilis”

73. We searched for “std nonprofits” “sexually transmitted disease R&D” “center for std research” “std research” and “syphilis nonprofit”

Privacy Overview

Funding Opportunities Open to Applicants

This section provides information on locating and applying for current CDC STD prevention funding opportunities and grants. A funding opportunity defines the scope of a project and expected outcomes, applicant activities, and CDC activities. Please visit this page frequently to find updated information on STD prevention funding opportunities from CDC.

CDC has published a Notice of Funding Opportunity (NOFO) announcement, PS-24-0003 , that supports the Ending the HIV Epidemic in the U.S. (EHE) initiative by scaling up HIV prevention and care services in sexual health clinics, including STI specialty clinics. This NOFO builds on progress made scaling up HIV prevention services in STI clinics through Component C of CDC’s PS20-2010 cooperative agreement. PS-24-0003 will further strengthen the infrastructure of sexual health clinics and improve service delivery to address the syndemic of HIV & other STIs and foster additional strategic partnerships. Eligible applicants include public and nonprofit private entities that are providers of clinical sexual health services in the proposed service area, or plan to provide the majority of funds to provider(s) of clinical sexual health services in the proposed area.

Applicants are strongly encouraged to use the CDC-provided work plan template  in their application.

An informational webinar for applicants was held on November 6, 2023. Review the FAQs and access the applicant resources for more information.

Full details for this cooperative agreement are available at  grants.gov .

CDC has published a Notice of Funding Announcement (NOFO), Enhancing STI and Sexual Health Clinic Infrastructure (ESSHCI), to strengthen clinic infrastructure and expand access to comprehensive sexual health services in communities with high STI burden and unmet need for STI clinical services. Eligible applicants include public and nonprofit private entities that are providers of clinical services in the proposed service area, or plan to provide the majority of funds to provider(s) of clinical services in the proposed area.

An informational webinar was held April 24, 2023 for applicants. Review the FAQs or watch the webinar recording for more information.

Full details for this cooperative agreement are available at Grants.gov .

CDC has published a Notice of Funding Announcement (NOFO), Support Technical Assistance Opportunities for Program, Policy, & Communications to prevent STDs (STOP STDs), to fund organizations with national reach to provide technical assistance (TA) to state, local, and territorial, STD/HIV public health programs. The NOFO activities will provide TA to public health programs on systems, policy and communication, partnerships, special and emerging STD program projects, and leadership education and training to advance STD prevention objectives.

An informational webinar was held on February 24, 2023 for applicants. Review the FAQs for more information or watch the webinar recording for more information.

Related Content

• Projects & Initiatives – Ongoing projects funded by CDC’s Division of STD Prevention
• Funding Archive  – Funding announcements that have expired
• Applying to CDC Funding Opportunities – Fact sheet about the application
• Grants.Gov  – Official website to find and apply for federal grants
• Bacterial Vaginosis (BV)
• Genital Herpes
• HIV/AIDS & STDs
• Human Papillomavirus (HPV)
• Pelvic Inflammatory Disease (PID)
• STDs & Infertility
• STDs & Pregnancy
• Trichomoniasis

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