infectious disease case study examples

Earn HPCSA and SACNASP CPD Points
I have spots and my skin burns
A case of a 10 year old boy with a 3 week history of diarrhoea, vomiting and cough
A case of fever and general malaise
A case of persistant hectic fever
A case of sudden rapid neurological deterioration in an HIV positive 27 year old female
A case of swollen hands
An unusual cause of fulminant hepatitis
Case of a right axillary swelling
Case of giant wart
Case of recurrent meningitis
Case of repeated apnoea and infections in a premature infant
Case of sudden onset of fever, rash and neck pain
Doctor, my sister is confused
Eight month old boy with recurrent infections
Enlarged Testicles
Failure to thrive despite appropriate treatment
Right Axillary Swelling
Severe anaemia in HIV positive child
The case of a floppy infant
Two year old with spiking fevers and depressed level of consciousness
17 year old male with fever and decreased level of consciousness
3 TB Vignettes
A 10 year old girl with a hard palate defect
A case of decreased joint function, fever and rash
Keep up while the storm is raging
Fireworks of autoimmunity from birth
My eyes cross at twilight
A case of a 3 month old infant with bloody urine and stools
A case of scaly annular plaques
Case of eye injury and decreased vision
My head hurts and I cannot speak?
TB or not TB: a confusing case
A 7 year old with severe muscle weakness and difficulty walking
Why can I not walk today?
14 year old with severe hip pain
A 9 year old girl presents with body swelling, shortness of breath and backache
A sudden turn of events after successful therapy
Declining CD4 count, despite viral suppression?
Defaulted treatment
25 year old female presents with persistent flu-like symptoms
A case of persistent bloody diarrhoea
I’ve been coughing for so long
A case of acute fever, rash and vomiting
Adverse event following routine vaccination
A case of cough, wasting and lymphadenopathy
A case of lymphadenopathy and night sweats
Case of enlarged hard tongue
A high risk pregnancy
A four year old with immunodeficiency
Young girl with recurrent history of mycobacterial disease
Immunodeficiency and failure to thrive
Case of recurrent infections
An 8 year old boy with recurrent respiratory infections
4 year old boy with recurrent bacterial infections
Is this treatment failure or malnutrition
1. A Snapshot of the Immune System
2. Ontogeny of the Immune System
3. The Innate Immune System
4. MHC & Antigen Presentation
5. Overview of T Cell Subsets
6. Thymic T Cell Development
7. gamma/delta T Cells
8. B Cell Activation and Plasma Cell Differentiation
9. Antibody Structure and Classes
10. Central and Peripheral Tolerance
Immuno-Mexico 2024 Introduction
Modulation of Peripheral Tolerance
Metabolic Adaptation to Pathologic Milieu
T Cell Exhaustion
Suppression in the Context of Disease
Redirecting Cytotoxicity
Novel Therapeutic Strategies
ImmunoInformatics
Grant Writing
Introduction to Immuno-Chile 2023
Core Modules
Gut Mucosal Immunity
The Microbiome
Gut Inflammation
Viral Infections and Mucosal Immunity
Colorectal Cancer
Inflammatory Bowel Disease
Equity, Diversity, Inclusion in Academia
Immuno-India 2023 Introduction
Principles of Epigenetic Regulation
Epigenetics Research in Systems Immunology
Epigenetic (De)regulation in Non-Malignant Diseases
Epigenetic (De)regulation in Immunodeficiency and Malignant Diseases
Immunometabolism and Therapeutic Applications of Epigenetic Modifiers
Immuno-Morocco 2023 Introduction
Cancer Cellular Therapies
Cancer Antibody Therapies
Cancer Vaccines
Immunobiology of Leukemia & Therapies
Immune Landscape of the Tumour
Targeting the Tumour Microenvironment
Flow Cytometry
Immuno-Zambia 2022 Introduction
Immunity to Viral Infections
Immunity to SARS-CoV2
Basic Immunology of HIV
Immunity to Tuberculosis
Immunity to Malaria
Immunity to Schistosomiasis
Immunity to Helminths
Equity, Diversity and Inclusion in Academia
Immuno-Argentina 2022 Introduction
Dendritic Cells
Trained Innate Immunity
Gamma-Delta T cells
Natural Killer Cell Memory
Innate Immunity in Viral Infections
Lectures – Innate Immunity
T cells and Beyond
Lectures – Cellular Immunity
Strategies for Vaccine Design
Lectures – Humoral Immunity
Lectures – Vaccine development
Lectures – Panel and Posters
Immuno-Cuba 2022 Introduction
Poster and Abstract Examples
Immuno-Tunisia 2021 Introduction
Basics of Anti-infectious Immunity
Inborn Errors of Immunity and Infections
Infection and Auto-Immunity
Pathogen-Induced Immune Dysregulation & Cancer
Understanding of Host-Pathogen Interaction & Applications (SARS-CoV-2)
Day 1 – Basics of Anti-infectious Immunity
Day 2 – Inborn Errors of Immunity and Infections
Day 3 – Infection and Auto-immunity
Day 4 – Pathogen-induced Immune Dysregulation and Cancer
Day 5 – Understanding of Host-Pathogen Interaction and Applications
Student Presentations
Roundtable Discussions
Orientation Meeting
Poster Information
Immuno-Colombia Introduction
Core Modules Meeting
Overview of Immunotherapy
Check-Points Blockade Based Therapies
Cancer Immunotherapy with γδ T cells
CAR-T, armored CARs and CAR-NK therapies
Anti-cytokines Therapies
Tumor-infiltrating Lymphocytes (TIL)
MDSC Promote Tumor Growth and Escape
Immunological lab methods for patient’s follow-up
Student Orientation Meeting
Lectures – Week 1
Lectures – Week 2
Research Project
Closing and Social
Introduction to Immuno-Algeria 2020
Hypersensitivity Reactions
Immuno-Algeria Programme
Online Lectures – Week 1
Online Lectures – Week 2
Student Presentations – Week 1
Student Presentations – Week 2
Introduction to Immuno-Ethiopia 2020
Neutrophils
Leishmaniasis – Transmission and Epidemiology
Leishmaniasis – Immune Responses
Leishmaniasis – Treatment and Vaccines
Immunity to Helminth Infections
Helminth immunomodulation on co-infections
Malaria Vaccine Progress
Immunity to Fungal Infections
How to be successful scientist
How to prepare a good academic CV
Introduction to Immuno-Benin
Immune Regulation in Pregnancy
Immunity in infants and consequence of preeclampsia
Schistosome infections and impact on Pregnancy
Infant Immunity and Vaccines
Regulation of Immunity & the Microbiome
TGF-beta superfamily in infections and diseases
Infectious Diseases in the Global Health era
Immunity to Toxoplasma gondii
A. melegueta inhibits inflammatory responses during Helminth Infections
Host immune modulation by Helminth-induced products
Immunity to HIV
Immunity to Ebola
Immunity to TB
Genetic susceptibility in Tuberculosis
Plant Extract Treatment for Diabetes
Introduction to Immuno-South Africa 2019
Models for Testing Vaccines
Immune Responses to Vaccination
IDA 2019 Quiz
Introduction to Immuno-Jaipur
Inflammation and autoinflammation
Central and Peripheral Tolerance
Autoimmunity and Chronic Inflammatory Diseases
Autoimmunity & Dysregulation
Novel Therapeutic strategies for Autoimmune Diseases
Strategies to apply gamma/delta T cells for Immunotherapy
Immune Responses to Cancer
Tumour Microenvironment
Cancer Immunotherapy
Origin and perspectives of CAR T cells
Metabolic checkpoints regulating immune responses
Transplantation
Primary Immunodeficiencies
Growing up with Herpes virus
Introduction to IUIS-ALAI-Mexico-ImmunoInformatics
Introduction to Immunization Strategies
Introduction to Immunoinformatics
Omics Technologies
Computational Modeling
Machine Learning Methods
Introduction to Immuno-Kenya
Viruses hijacking host immune responses
IFNs as 1st responders to virus infections
HBV/HCV & Hepatocellular Carcinoma
Cytokines as biomarkers for HCV
HTLV & T cell Leukemia
HCMV and Cancers
HPV and Cancers
EBV-induced Oncogenesis
Adenoviruses
KSHV and HIV
Ethics in Cancer Research
Sex and gender in Immunity
Introduction to Immuno-Iran
Immunity to Leishmaniasis
Breaking Tolerance: Autoimmunity & Dysregulation
Introduction to Immuno-Morocco
Cancer Epidemiology and Aetiology
Pathogens and Cancer
Immunodeficiency and Cancer
Introduction to Immuno-Brazil
1. Systems Vaccinology
2. Vaccine Development
3. Adjuvants
4. DNA Vaccines
5. Mucosal Vaccines
6. Vaccines for Neurodegenerative Diseases
Introduction to Immuno-Gambia
Immuno-Gambia Photos
1. Infant Immunity and Vaccines
2. Dendritic Cells
3. Conventional T Cells
4. gamma/delta T Cells
5. Immunity to Viral Infections
6. Immunity to Helminth Infections
7. Immunity to TB
8. Immunity to Malaria
9. Flow Cytometry
Introduction to Immuno-South Africa
1. Introduction to Immunization Strategies
2. Immune Responses to Vaccination
3. Models for Testing Vaccines
4. Immune Escape
5. Grant Writing
Introduction to Immuno-Ethiopia
1. Neutrophils
3. Exosomes
5. Immunity to Leishmania
6. Immunity to HIV
7. Immunity to Helminth Infections
8. Immunity to TB
9. Grant Writing
Introduction to ONCOIMMUNOLOGY-MEXICO
ONCOIMMUNOLOGY-MEXICO Photos
1. Cancer Epidemiology and Etiology
2. T lymphocyte mediated immunity
3. Immune Responses to Cancer
4. Cancer Stem Cells and Tumor-initiating cells.
5. Tumor Microenvironment
6. Pathogens and Cancer
7. Cancer Immunotherapy
8. Flow cytometry approaches in cancer
Introduction to the Immunology Course
Immuno-Tunisia Photo
1. Overview of the Immune System
2. Role of cytokines in Immunity
3. Tolerance and autoimmunity
4. Genetics, Epigenetics and immunoregulation
5. Microbes and immunoregulation
6. Inflammation and autoinflammation
7. T cell mediated autoimmune diseases
8. Antibody-mediated autoimmune diseases
Introduction to the Immunology Symposium
Immuno-South Africa Photo
1. Antibody Generation by B cells
2. Mucosal Immunity
3. Immunity to TB
4. Immunity to Malaria
5. Immunity to HIV
6. Defining a Biomarker
7. Grant Writing Exercise
Immuno-Colombia Photo
1. Overview of Complement
2. Transplantation
3. Immune Regulation in Pregnancy
4. Breaking Tolerance: Autoimmunity & Dysregulation
5. Mucosal Immunity & Immunopathology
6. Regulation of Immunity & the Microbiome
7. Epigenetics & Modulation of Immunity
8. Primary Immunodeficiencies
9. Anti-tumour Immunity
10. Cancer Immunotherapy
Introduction
Immune Cells
NCDs and Multimorbidity
Mosquito Vector Biology
Vaccines and Other Interventions
Autoimmunity
Career Development
SUN Honours Introduction
A Snapshot of the Immune System
Ontogeny of the Immune System
The Innate Immune System
MHC & Antigen Presentation
Overview of T Cell Subsets
B Cell Activation and Plasma Cell Differentiation
Antibody Structure and Classes
Cellular Immunity and Immunological Memory
Infectious Diseases Immunology
Vaccinology
Mucosal Immunity & Immunopathology
Central & Peripheral Tolerance
Epigenetics & Modulation of Immunity
T cell and Ab-mediated autoimmune diseases
Immunology of COVID-19 Vaccines
11th IDA 2022 Introduction
Immunity to COVID-19
Fundamentals of Immunology
Fundamentals of Infection
Integrating Immunology & Infection
Infectious Diseases Symposium
EULAR Symposium
Thymic T Cell Development
Immune Escape
Genetics, Epigenetics and immunoregulation
AfriBop 2021 Introduction
Adaptive Immunity
Fundamentals of Infection 2
Fundamentals of Infection 3
Host pathogen Interaction 1
Host pathogen Interaction 2
Student 3 minute Presentations
10th IDA 2021 Introduction
Day 1 – Lectures
Day 2 – Lectures
Day 3 – Lectures
Day 4 – Lectures
Afribop 2020 Introduction
WT PhD School Lectures 1
EULAR symposium
WT PhD School Lectures 2
Host pathogen interaction 1
Host pathogen interaction 2
Bioinformatics
Introduction to VACFA Vaccinology 2020
Overview of Vaccinology
Basic Principles of Immunity
Adverse Events Following Immunization
Targeted Immunization
Challenges Facing Vaccination
Vaccine Stakeholders
Vaccination Questions Answered
Malaria Vaccines
IDA 2018 Introduction
Vaccine Development
Immune Escape by Pathogens
Immunity to Viral Infections Introduction
Flu, Ebola & SARS
Antiretroviral Drug Treatments
Responsible Conduct in Research
Methods for Enhancing Reproducibility
6. B Cell Activation and Plasma Cell Differentiation
7. Antibody Structure and Classes
CD Nomenclature
1. Transplantation
2. Central & Peripheral Tolerance
8. Inflammation and autoinflammation
9. T cell mediated autoimmune diseases
10. Antibody-mediated autoimmune diseases
1. Primary Immunodeficiencies
Cancer Stem Cells and Tumour-initiating Cells
6. Tolerance and Autoimmunity
Discovery of the Thymus as a central immunological organ
History of Immune Response
History of Immunoglobulin molecules
History of MHC – 1901 – 1970
History of MHC – 1971 – 2011
SAIS/Immunopaedia Webinars 2022
Metabolic control of T cell differentiation during immune responses to cancer
Microbiome control of host immunity
Shaping of anti-tumor immunity in the tumor microenvironment
The unusual COVID-19 pandemic: the African story
Immune responses to SARS-CoV-2
Adaptive Immunity and Immune Memory to SARS-CoV-2 after COVID-19
HIV prevention- antibodies and vaccine development (part 2)
HIV prevention- antibodies and vaccine development (part 1)
Immunopathology of COVID 19 lessons from pregnancy and from ageing
Clinical representation of hyperinflammation
In-depth characterisation of immune cells in Ebola virus
Getting to the “bottom” of arthritis
Immunoregulation and the tumor microenvironment
Harnessing innate immunity from cancer therapy to COVID-19
Flynn Webinar: Immune features associated natural infection
Flynn Webinar: What immune cells play a role in protection against M.tb re-infection?
JoAnne Flynn: BCG IV vaccination induces sterilising M.tb immunity
IUIS-Immunopaedia-Frontiers Webinar on Immunology taught by P. falciparum
COVID-19 Cytokine Storm & Paediatric COVID-19
Immunothrombosis & COVID-19
Severe vs mild COVID-19 immunity and Nicotinamide pathway
BCG & COVID-19
COVID-19 Vaccines
Antibody responses and serology testing
Flow Cytometry Part 1
Flow Cytometry Part 2
Flow Cytometry Part 3
Lateral Flow
Diagnostic Tools
Diagnostic Tests
HIV Life Cycle
ARV Drug Information
ARV Mode of Action
ARV Drug Resistance
Declining CD4 count
Ambassador of the Month – 2024
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Ambassador of the Month – 2023
Ambassador of the Month – 2022
The Day of Immunology 2022
AMBASSADOR SCI-TALKS
The Day of Immunology 2021
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Ambassador of the Month-2020
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Case report

Case reports submitted to BMC Infectious Diseases should make a contribution to medical knowledge and must have educational value or highlight the need for a change in clinical practice or diagnostic/prognostic approaches. We will not consider reports on topics that have already been well characterized or where other, similar, cases have already been published.

BMC Infectious Diseases will not consider case reports describing preventive or therapeutic interventions, as these generally require stronger evidence.

BMC Infectious Diseases will not consider case reports whose main message is the clinical use of Next Generation Sequencing (NGS) for the identification of a pathogen if it has been already previously reported in the literature.

BMC Infectious Diseases welcomes well-described reports of cases that include the following: • Unreported or unusual side effects or adverse interactions involving medications. • Unexpected or unusual presentations of a disease. • New associations or variations in disease processes. • Presentations, diagnoses and/or management of new and emerging diseases. • An unexpected association between diseases or symptoms. • An unexpected event in the course of observing or treating a patient. • Findings that shed new light on the possible pathogenesis of a disease or an adverse effect.

Authors must describe how the case report is rare or unusual as well as its educational and/or scientific merits in the covering letter that will accompany the submission of the manuscript. Case report submissions will be assessed by the Editors and will be sent for peer review if considered appropriate for the journal.

Case reports must include relevant positive and negative findings from history, examination and investigation, and can include clinical photographs, provided these are accompanied by a statement that written consent to publish was obtained from the patient(s). Case reports should include an up-to-date review of all previous cases in the field. Authors should follow the CARE guidelines and the CARE checklist should be provided as an additional file.

Authors should seek written and signed consent to publish the information from the patient(s) or their guardian(s) prior to submission. The submitted manuscript must include a statement that this consent was obtained in the consent to publish section as detailed in our editorial policies .

Professionally produced Visual Abstracts BMC Infectious Diseases will consider visual abstracts. As an author submitting to the journal, you may wish to make use of services provided at Springer Nature for high quality and affordable visual abstracts where you are entitled to a 20% discount. Click here to find out more about the service, and your discount will be automatically be applied when using this link .

Preparing your manuscript

The information below details the section headings that you should include in your manuscript and what information should be within each section.

Please note that your manuscript must include a 'Declarations' section including all of the subheadings (please see below for more information).

Title page

The title page should:

"A versus B in the treatment of C: a randomized controlled trial", "X is a risk factor for Y: a case control study", "What is the impact of factor X on subject Y: A systematic review, A case report etc."
or, for non-clinical or non-research studies: a description of what the article reports
if a collaboration group should be listed as an author, please list the Group name as an author. If you would like the names of the individual members of the Group to be searchable through their individual PubMed records, please include this information in the “Acknowledgements” section in accordance with the instructions below
Large Language Models (LLMs), such as ChatGPT , do not currently satisfy our authorship criteria . Notably an attribution of authorship carries with it accountability for the work, which cannot be effectively applied to LLMs. Use of an LLM should be properly documented in the Methods section (and if a Methods section is not available, in a suitable alternative part) of the manuscript
indicate the corresponding author

The Abstract should not exceed 350 words. Please minimize the use of abbreviations and do not cite references in the abstract. The abstract must include the following separate sections:

Background: why the case should be reported and its novelty
Case presentation: a brief description of the patient’s clinical and demographic details, the diagnosis, any interventions and the outcomes
Conclusions: a brief summary of the clinical impact or potential implications of the case report

Keywords

Three to ten keywords representing the main content of the article.

The Background section should explain the background to the case report or study, its aims, a summary of the existing literature.

Case presentation

This section should include a description of the patient’s relevant demographic details, medical history, symptoms and signs, treatment or intervention, outcomes and any other significant details.

Discussion and Conclusions

This should discuss the relevant existing literature and should state clearly the main conclusions, including an explanation of their relevance or importance to the field.

List of abbreviations

If abbreviations are used in the text they should be defined in the text at first use, and a list of abbreviations should be provided.

Declarations

All manuscripts must contain the following sections under the heading 'Declarations':

Ethics approval and consent to participate

Consent for publication, availability of data and materials, competing interests, authors' contributions, acknowledgements.

Authors' information (optional)

Please see below for details on the information to be included in these sections.

If any of the sections are not relevant to your manuscript, please include the heading and write 'Not applicable' for that section.

Manuscripts reporting studies involving human participants, human data or human tissue must:

include a statement on ethics approval and consent (even where the need for approval was waived)
include the name of the ethics committee that approved the study and the committee’s reference number if appropriate

Studies involving animals must include a statement on ethics approval and for experimental studies involving client-owned animals, authors must also include a statement on informed consent from the client or owner.

See our editorial policies for more information.

If your manuscript does not report on or involve the use of any animal or human data or tissue, please state “Not applicable” in this section.

If your manuscript contains any individual person’s data in any form (including any individual details, images or videos), consent for publication must be obtained from that person, or in the case of children, their parent or legal guardian. All presentations of case reports must have consent for publication.

You can use your institutional consent form or our consent form if you prefer. You should not send the form to us on submission, but we may request to see a copy at any stage (including after publication).

See our editorial policies for more information on consent for publication.

If your manuscript does not contain data from any individual person, please state “Not applicable” in this section.

All manuscripts must include an ‘Availability of data and materials’ statement. Data availability statements should include information on where data supporting the results reported in the article can be found including, where applicable, hyperlinks to publicly archived datasets analysed or generated during the study. By data we mean the minimal dataset that would be necessary to interpret, replicate and build upon the findings reported in the article. We recognise it is not always possible to share research data publicly, for instance when individual privacy could be compromised, and in such instances data availability should still be stated in the manuscript along with any conditions for access.

Authors are also encouraged to preserve search strings on searchRxiv https://searchrxiv.org/ , an archive to support researchers to report, store and share their searches consistently and to enable them to review and re-use existing searches. searchRxiv enables researchers to obtain a digital object identifier (DOI) for their search, allowing it to be cited.

Data availability statements can take one of the following forms (or a combination of more than one if required for multiple datasets):

The datasets generated and/or analysed during the current study are available in the [NAME] repository, [PERSISTENT WEB LINK TO DATASETS]
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
All data generated or analysed during this study are included in this published article [and its supplementary information files].
The datasets generated and/or analysed during the current study are not publicly available due [REASON WHY DATA ARE NOT PUBLIC] but are available from the corresponding author on reasonable request.
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.
The data that support the findings of this study are available from [third party name] but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of [third party name].
Not applicable. If your manuscript does not contain any data, please state 'Not applicable' in this section.

More examples of template data availability statements, which include examples of openly available and restricted access datasets, are available here .

BioMed Central strongly encourages the citation of any publicly available data on which the conclusions of the paper rely in the manuscript. Data citations should include a persistent identifier (such as a DOI) and should ideally be included in the reference list. Citations of datasets, when they appear in the reference list, should include the minimum information recommended by DataCite and follow journal style. Dataset identifiers including DOIs should be expressed as full URLs. For example:

Hao Z, AghaKouchak A, Nakhjiri N, Farahmand A. Global integrated drought monitoring and prediction system (GIDMaPS) data sets. figshare. 2014. http://dx.doi.org/10.6084/m9.figshare.853801

With the corresponding text in the Availability of data and materials statement:

The datasets generated during and/or analysed during the current study are available in the [NAME] repository, [PERSISTENT WEB LINK TO DATASETS]. [Reference number]

If you wish to co-submit a data note describing your data to be published in BMC Research Notes , you can do so by visiting our submission portal . Data notes support open data and help authors to comply with funder policies on data sharing. Co-published data notes will be linked to the research article the data support ( example ).

All financial and non-financial competing interests must be declared in this section.

See our editorial policies for a full explanation of competing interests. If you are unsure whether you or any of your co-authors have a competing interest please contact the editorial office.

Please use the authors initials to refer to each authors' competing interests in this section.

If you do not have any competing interests, please state "The authors declare that they have no competing interests" in this section.

All sources of funding for the research reported should be declared. If the funder has a specific role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript, this should be declared.

The individual contributions of authors to the manuscript should be specified in this section. Guidance and criteria for authorship can be found in our editorial policies .

Please use initials to refer to each author's contribution in this section, for example: "FC analyzed and interpreted the patient data regarding the hematological disease and the transplant. RH performed the histological examination of the kidney, and was a major contributor in writing the manuscript. All authors read and approved the final manuscript."

Please acknowledge anyone who contributed towards the article who does not meet the criteria for authorship including anyone who provided professional writing services or materials.

Authors should obtain permission to acknowledge from all those mentioned in the Acknowledgements section.

See our editorial policies for a full explanation of acknowledgements and authorship criteria.

If you do not have anyone to acknowledge, please write "Not applicable" in this section.

Group authorship (for manuscripts involving a collaboration group): if you would like the names of the individual members of a collaboration Group to be searchable through their individual PubMed records, please ensure that the title of the collaboration Group is included on the title page and in the submission system and also include collaborating author names as the last paragraph of the “Acknowledgements” section. Please add authors in the format First Name, Middle initial(s) (optional), Last Name. You can add institution or country information for each author if you wish, but this should be consistent across all authors.

Please note that individual names may not be present in the PubMed record at the time a published article is initially included in PubMed as it takes PubMed additional time to code this information.

Authors' information

This section is optional.

You may choose to use this section to include any relevant information about the author(s) that may aid the reader's interpretation of the article, and understand the standpoint of the author(s). This may include details about the authors' qualifications, current positions they hold at institutions or societies, or any other relevant background information. Please refer to authors using their initials. Note this section should not be used to describe any competing interests.

Footnotes can be used to give additional information, which may include the citation of a reference included in the reference list. They should not consist solely of a reference citation, and they should never include the bibliographic details of a reference. They should also not contain any figures or tables.

Footnotes to the text are numbered consecutively; those to tables should be indicated by superscript lower-case letters (or asterisks for significance values and other statistical data). Footnotes to the title or the authors of the article are not given reference symbols.

Always use footnotes instead of endnotes.

Examples of the Vancouver reference style are shown below.

See our editorial policies for author guidance on good citation practice

Web links and URLs: All web links and URLs, including links to the authors' own websites, should be given a reference number and included in the reference list rather than within the text of the manuscript. They should be provided in full, including both the title of the site and the URL, as well as the date the site was accessed, in the following format: The Mouse Tumor Biology Database. http://tumor.informatics.jax.org/mtbwi/index.do . Accessed 20 May 2013. If an author or group of authors can clearly be associated with a web link, such as for weblogs, then they should be included in the reference.

Example reference style:

Article within a journal

Smith JJ. The world of science. Am J Sci. 1999;36:234-5.

Article within a journal (no page numbers)

Rohrmann S, Overvad K, Bueno-de-Mesquita HB, Jakobsen MU, Egeberg R, Tjønneland A, et al. Meat consumption and mortality - results from the European Prospective Investigation into Cancer and Nutrition. BMC Medicine. 2013;11:63.

Article within a journal by DOI

Slifka MK, Whitton JL. Clinical implications of dysregulated cytokine production. Dig J Mol Med. 2000; doi:10.1007/s801090000086.

Article within a journal supplement

Frumin AM, Nussbaum J, Esposito M. Functional asplenia: demonstration of splenic activity by bone marrow scan. Blood 1979;59 Suppl 1:26-32.

Book chapter, or an article within a book

Wyllie AH, Kerr JFR, Currie AR. Cell death: the significance of apoptosis. In: Bourne GH, Danielli JF, Jeon KW, editors. International review of cytology. London: Academic; 1980. p. 251-306.

OnlineFirst chapter in a series (without a volume designation but with a DOI)

Saito Y, Hyuga H. Rate equation approaches to amplification of enantiomeric excess and chiral symmetry breaking. Top Curr Chem. 2007. doi:10.1007/128_2006_108.

Complete book, authored

Blenkinsopp A, Paxton P. Symptoms in the pharmacy: a guide to the management of common illness. 3rd ed. Oxford: Blackwell Science; 1998.

Online document

Doe J. Title of subordinate document. In: The dictionary of substances and their effects. Royal Society of Chemistry. 1999. http://www.rsc.org/dose/title of subordinate document. Accessed 15 Jan 1999.

Online database

Healthwise Knowledgebase. US Pharmacopeia, Rockville. 1998. http://www.healthwise.org. Accessed 21 Sept 1998.

Supplementary material/private homepage

Doe J. Title of supplementary material. 2000. http://www.privatehomepage.com. Accessed 22 Feb 2000.

University site

Doe, J: Title of preprint. http://www.uni-heidelberg.de/mydata.html (1999). Accessed 25 Dec 1999.

Doe, J: Trivial HTTP, RFC2169. ftp://ftp.isi.edu/in-notes/rfc2169.txt (1999). Accessed 12 Nov 1999.

Organization site

ISSN International Centre: The ISSN register. http://www.issn.org (2006). Accessed 20 Feb 2007.

Dataset with persistent identifier

Zheng L-Y, Guo X-S, He B, Sun L-J, Peng Y, Dong S-S, et al. Genome data from sweet and grain sorghum (Sorghum bicolor). GigaScience Database. 2011. http://dx.doi.org/10.5524/100012 .

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BMC Infectious Diseases

ISSN: 1471-2334

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Volume 16, Number 1—January 2010

Books and Media

Case studies in infectious disease.

Cite This Article

The authors have assembled a collection of case studies about the 40 infectious diseases that cause the most illness and death worldwide. Each chapter begins with a brief case presentation. This example is followed by a section on microbiologic aspects of the organism, including the pathophysiology of infection. The host response is then described, followed by a discussion of clinical manifestations, diagnostic methods, and treatment options, including prevention. A summary highlights salient points of each section. References, suggestions for further reading, and websites for additional information are all provided. Chapters conclude with a series of questions (answers are given at the end of the book).

The book is meant for use by medical students in a microbiology course, but it can also be used by any clinician who wants a concise review of the pathogens that cause infectious diseases. The case presentations are short and not presented as conditions having an unknown cause, but they rather serve as a clinical starting point to open discussion. The microbiology sections are geared more toward the student in a microbiology course and tend to have more details than are needed by a practicing clinician. The sections on patient symptoms are generally quite good and are inclusive. The varied clinical manifestations, particularly of the tropical diseases, are presented in an easy-to-understand format. The level of detail given provides a thorough yet succinct picture of each disease. The sections on diagnosis are generally inclusive, although a few did not mention some available diagnostic options used in the United States; this may have been due to differences in the availability of some tests in the United Kingdom, where many of the authors are based. The treatment sections tend to be abbreviated and frequently do not include the length of therapy and some other details that a practicing clinician would want to know. For those needing specific therapy guidelines, another source will be necessary.

The summary sections are quite good and are an excellent quick reference source if one wants just the highlights and a brief summary about the pathogen and disease. The questions at the end tend to be multiple choice with several possible correct answers for each one; they are not structured to prepare for testing purposes (such as for a board review). The websites are helpful sources for downloadable slides as well as for further information if more details are wanted.

The only chapter that was confusing was that on coxsackie viruses. The authors kept referring to other enteroviruses. The chapter could benefit from either fewer references to other enteroviruses or renaming it to be a section on enteroviruses in general.

Case Studies in Infectious Diseases is a valuable compilation of information on the most common diseases that cause illness and death worldwide. The presentation format with distinct sections makes it readable and well suited for either students just learning about the pathogens causing infectious disease or clinicians who need an update. The level of detail is well thought out and gives the reader a useful summary of each pathogen and disease state. The condensed presentations make it a good reference source for those with insufficient time to read through more detailed textbooks.

DOI: 10.3201/eid1601.091254

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Emerg Infect Dis
v.16(1); 2010 Jan

Case Studies in Infectious Disease

Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward Garland Science, New York, NY, USA, 2010 ISBN: 978-0-8153-4142-0 Pages: 608; Price: US $50.00.

Suggested citation for this article : Brachman PS Jr. Case studies in infectious disease [book review]. Emerg Infect Dis [serial on the Internet] 2010 Jan [ date cited ]. Available from http://www.cdc.gov/EID/content/16/1/172a.htm

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Infectious Diseases: A Case Study Approach

4: Pharyngitis

Frank S. Yu; Jonathan C. Cho

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Patient presentation.

Full Chapter
Supplementary Content

Chief Complaint

“Mommy, my throat is on fire!”

History of Present Illness

JT is a 7-year-old Chinese American female, accompanied by her mother, who presents to the community pharmacy with complaints of sore throat and fever, looking for medications to take to relieve her symptoms. She is fussy and describes the pain when she swallows as feeling if her throat is “on fire.” Her symptoms began yesterday morning, and she has only tried drinking a pei pa koa syrup containing medicinal herbs (main active herb is elm bark) and honey to relieve the sore throat. This provided some relief but the pain has been getting worse. She did not have a temperature taken, but her forehead was hot to the touch. She was not given any medications to relieve the fever. She was dressed with additional clothing and blankets to “sweat the fever out,” but the fever still persisted. She reports that there may have been other sick classmates. She denies a prior history of sore throat.

Past Medical History

Attention-deficit disorder, recurrent otitis media (resolved)

Surgical History

Family history.

Non-contributory

Social History

Ear tubes at age 2

Amoxicillin (throat swelling, difficulty breathing)

Home Medications

Methylphenidate ER 18 mg PO daily

Physical Examination

Vital signs.

Temp 101.9°F (oral), Ht 4′4″, Wt 29.55 kg

Appears uncomfortable, tired, grimacing when swallowing

Anterior cervical lymph nodes enlarged and tender; tonsils moist, red, with white exudates

Point-of-Care GAS Rapid Antigen Detection Test

1. What is the most common pathogen responsible for acute bacterial pharyngitis in children?

A. Corynebacterium diphtheriae

B. Neisseria gonorrhoeae

C. Group C streptococcus

D. Group A streptococcus

2. What signs and symptoms in this patient definitely discriminate between GAS pharyngitis rather than viral pharyngitis?

A. Tonsils with white exudates

B. Temperature 101.9°F

C. Pain on swallowing

D. All of the above

3. If GAS is suspected, what age range is typically excluded for testing for GAS?

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Case Studies

Case study 1: what is this mysterious disease.

This case study examines the earliest reports of what we now know were AIDS cases. The medical community was perplexed and the public was scared because the cause of this disease and mode of transmission were not understood. Students will use the data provided to think about how scientists can look for meaningful patterns in data and how they practice formulating a scientific question — that is, one that can be answered through experiment or observation.

Many unresolved questions remain at the end of the lesson, illustrating the iterative nature of science and how science is not a list of facts to memorize but a process of discovery. The concepts presented here align well with those presented in ID Unit 1 .

Download Case Study 1 here .

Case Study 2 — Do bacteria cause stomach ulcers? Applying Koch’s postulates

This study grapples with the problem of arriving at causation from correlation with respect to infectious disease. First, students will discuss their stomach ulcer homework, and they will compare their predictions to real life excess-acid experiments in people. This is a key point because the results support the hypothesis; however, they do not prove causation. Next, students will design experiments that predict results for experiments to test the hypothesis that stomach ulcers are caused by an infectious agent. Students will then consider the implications of not being able to fulfill all of Koch’s postulates with Helicobacter pylori.

Download Case Study 2 here .

Case Study 3 — Where did HIV come from? Tracing the origin of disease

Prior to 1980, there were no reports of AIDS in the medical literature, but by 1987 the World Health Organization reported that an estimated 5-10 million people were living with HIV worldwide. The rapid emergence of this disease was indication that it might have “jumped” from an animal host. This is similar to flu viruses that are thought to have originated in birds. Most human viral diseases do originate in animals. In this case study, students develop a hypothesis and make predictions. Throughout the lesson, students will analyze and interpret a variety of data. The accumulation of results helps to support the hypothesis that HIV originated from a chimp virus.

Download Case Study 3 here .

Case Study 4 — Antibiotic resistance

In this study, students synthesize information from different studies to arrive at a model to explain how human antibiotic resistant infections may be linked to antibiotic use on farms. Importantly, the evidence does not prove causation, but conveys to students how an accumulation of evidence compels us to adopt a particular model. The concept of selective pressure is reviewed.

Download Case Study 4 here .

Case Study 5 — How would you know if you were infected with HIV?

The Centers for Disease Control (CDC) estimates that 1 in 4 new HIV infections is among youth ages 13-24, yet most do not know they are infected. In this case study, students engage in data analysis and interpretation to demonstrate that symptoms of initial HIV infection can go unrecognized for years. Classical symptoms of AIDS may only become apparent years after the initial HIV infection. Meanwhile, the infected individual could be infecting others. Students learn what behaviors are associated with high risk of infection and the importance of getting tested if they engage in these high-risk behaviors.

Download Case Study 5 here .

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56-year-old Korean immigrant sought medical attention for non-specific abdominal pain and mild, intermittent diarrhea.

A 42-year-old State Park employee sought medical care due to fatigue, insomnia, intermittent bloating, and mild anemia.

A 45-year-old male who recently returned from a trip overseas to Korea presented to his primary care clinic for an annual checkup at a clinic in the United States.

During a field study in Cambodia, stool ova and parasite (O&P) examinations were performed on participants in rural villages. Unusual eggs were found in the formalin-ethyl acetate concentrated stool specimen of one middle-aged woman.

A 53-year-old woman from Florida presented to a dermatology clinic with a raised, itchy, red rash on her torso that persisted over the past six months and did not respond to topical treatments.

A 25-year-old man with fever and myalgia presented to an urgent care clinic in Pennsylvania, and no travel history was obtained at that time.

As part of a refugee screening program, a young child had a fecal ova and parasite (O & P) examination which included a formalin-ethyl acetate (FEA) fecal concentration.

At a regional diagnostic laboratory, where specimens from the southeastern United States are evaluated, the objects shown in Figures A and B were observed on a wet mount preparation from a fecal formalin-ethyl acetate (FEA) concentrate.

In Singapore, a 54-year-old man with an extensive travel history to Vietnam, Thailand, and France presented to a clinic with prolonged fever, urticarial rash, and muscle aches.

A 67-year-old male from Houston, TX sought medical evaluation following 3 days of abdominal pain, diarrhea, and fatigue after returning from a two-week summer vacation in Nairobi, Kenya.

An 18-year-old male living in India presented with recurrent periumbilical abdominal pain for one week. Other symptoms included mild anemia and eosinophilic leukocytosis.

A 24-year-old man from Thailand presented to his healthcare provider with complaints of gastrointestinal pain and weight loss. He also reported seeing thin worms in his stool on rare occasion.

A group of college students traveled to Brazil on a rafting and camping trip for two weeks. Malaria prophylaxis was highly recommended however one student declined.

A 58 year-old-man from Peru visiting relatives in the United States was killed in a traffic accident. An autopsy revealed cysts in his liver of which a few were excised and sent to pathology for identification.

A 4-year-old boy went for a routine medical examination with his parents after they returned from a one-year sabbatical, studying primates in their natural habitat in central Africa.

A 24-year-old female exchange student from Guinea reported to the clinic with headaches, itchy skin, and enlarged lymph nodes.

A 60-year-old non-smoking male patient presented to his primary care physician with a chronic cough and shortness of breath. He reported no recent travel outside of the Southern United States.

A 29-year-old female patient presented to her primary care physician reporting a 15-day history of whitish, vaginal discharge associated with itching.

A 3-year-old boy was seen by a pediatrician for gastrointestinal pain and watery diarrhea. His parents conveyed that he has a propensity for putting insects in his mouth and sometimes eating them.

A 29-year-old man sought medical attention with his health care provider with a complaint of itchy maculopapular rash on several areas of his body.

A 63-year-old man returned from visiting with family in Nigeria. He developed fever, chills and a mild headache three days before presenting to the clinic.

A 69-year-old male patient from a rural town in Georgia experiencing symptoms of productive cough with blood, hematochezia (rectal bleeding) and chest pain sought medical attention at the county health clinic.

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Science teacher resources from baylor college of medicine.

Infectious Disease Case Study

Download Lesson and Student Pages
Print Materials List
Length: 60 Minutes

Students use evidence to determine whether a patient has a cold, flu or strep infection, and they also learn the differences between bacterial and viral infections.

This activity is from The Science of Microbes Teacher's Guide , and is most appropriate for use with students in grades 6-8. Lessons from the guide may be used with other grade levels as deemed appropriate.

The guide is available in print format.

This work was developed in partnership with the Baylor-UT Houston Center for AIDS Research, an NIH-funded program.

Teacher Background

Objectives and standards, materials and setup, procedure and extensions, handouts and downloads.

Many different microorganisms can infect the human respiratory system, causing symptoms such as fever, runny nose or sore throat. Even the common cold, which may range from mild to serious, can be caused by any of more than 200 viruses! Colds are among the leading causes of visits to physicians in the United States, and the Centers for Disease Control and Prevention (CDC) report that 22 million school days are lost in the U.S. each year due to the common cold. Usually, cold symptoms appear within two to three days of infection and include: mucus buildup in the nose, swelling of sinuses, cough, headache, sore throat, sneezing and mild fever (particularly in infants and young children). The body’s immune system, which protects against disease-causing microbes, almost always is able to eliminate the viruses responsible for a cold.

Flu (or influenza) often is more serious than the common cold. Caused by one of three types of closely related viruses, flu can come on quickly, with chills, fatigue, headache and body aches. A high fever and severe cough may develop. Flu may be prevented in some cases through a vaccine. However, since the viruses that cause flu change slightly from year to year, a new vaccine is required each flu season. Influenza was responsible for three pandemics (worldwide spread of disease) in the 20th Century alone.

Antibiotics do not kill viruses, and therefore, are not helpful in fighting the common cold or flu. But these diseases can make a person more susceptible to bacterial infections, such as strep throat, a common infection by a Streptococcus bacterium . Symptoms of “strep” infections include sore throat, high fever, coughing, and swollen lymph nodes and tonsils. Diagnosis should be based on the results of a throat swab, which is cultured, and/or a rapid antigen test, which detects foreign substances, known as antigens, in the throat. Strep infections usually can be treated effectively with antibiotics. Without treatment, strep throat can lead to other serious illnesses, such as scarlet fever and rheumatic fever.

Symptoms similar to those of a cold can be caused by allergens in the air. Health experts estimate that 35 million Americans suffer from respiratory allergies, such as hay fever (pollen allergy). An allergy is a reaction of an individual’s disease defense system (immune system) to a substance that does not bother most people. Allergies are not contagious.

Develop descriptions, explanations, predictions and models using evidence.

Think critically and logically to make the relationships between evidence and explanations.

Recognize and analyze alternative explanations and predictions.

Life Science

Disease is a breakdown in structures or functions of an organism. Some diseases are the result of infection by other organisms.

Teacher Materials (see Setup)

90 letter-size plain envelopes

6 sheets of white, self-stick folder labels, 3-7/16 in. x 2/3 in., 30 labels per sheet (Avery™ #5366, 5378 or 8366)

Overhead projector

Overhead transparency of the "Disorders and Symptoms" student sheet

Materials per Group of Students

Set of prepared envelopes (15 envelopes per set)

Copy of "What is Wrong with Allison?" and "Disorders and Symptoms" student sheets (see Lesson pdf)

Group concept map (ongoing)

Photocopy the "What is Wrong with Allison?" and "Disorders and Symptoms" student sheets (one copy of each per student), to be distributed in order (see Procedure).

Photocopy the label template sheet onto six sheets of white, self-stick labels, such as Avery™ #5366, 5378 or 8366, which contain 30 labels per sheet.

Use one page of photocopied labels to create each set of envelopes. Place a "Question" label on the outside of one envelope and stick the corresponding "Clue" label on the inside flap of the same envelope. Close the flap, but do not seal the envelope. Make six sets of 15 envelopes (one set per group).

Make an overhead transparency of the "Disorders and Symptoms" sheet. Have students work in groups of four.

Optional: Instead of using self-stick labels, copy the label template page onto plain paper and cut out each question and clue. Tape one question to the outside of an envelope and the corresponding clue to the inside flap of the envelope.

Begin a class discussion of disease by asking questions such as, How do you know when you are sick? What are some common diseases? Are all diseases alike? Are all diseases caused by a kind of microbe? Do some diseases have similar symptoms?

Tell your students that in this class session, they will be acting as medical personnel trying to diagnose a patient. Give each group a copy of the "What is Wrong with Allison?" sheet. Have one student read the case to the group, and then have groups discuss it. The reporter should record each group’s ideas about what might be wrong with Allison.

Have each student group list four possible questions that a doctor might ask a patient like Allison. Write these questions on the board and discuss with the class.

Have groups identify three possible diseases that Allison may have, based on the story, class discussion and their own experiences.

Give each student a copy of the "Disorders and Symptoms" sheet and briefly introduce the four illnesses to the entire class. Compare these illnesses to the ones that students suggested. Ask, Are there any similarities? Have students follow the instructions on the sheet to complete the exercise.

Give each group of students a set of envelopes. Warn students not to open the envelopes until they are instructed to do so. Tell students that each envelope contains information that a medical doctor might need about a patient. All information is important to the diagnosis, but only certain information will help to distinguish among the four possible respiratory disorders. Instruct students that their task is to decide which envelopes contain information that will help them determine Allison’s illness. Once a group has agreed on question choices, it may open as many envelopes—one at a time—as needed. The challenge is to use as few envelopes as possible to diagnose Allison’s illness. Each group should keep a tally of the number of envelopes opened. Remind students that in real life, a physician would conduct a complete examination and gather all possible information before making a diagnosis.

Allow time for groups to work. Provide assistance to students who may not understand the information contained in the envelopes. If the medicine and body temperature envelopes have been opened, make sure students understand that some medications, like Tylenol™, will mask the presence of mild fevers.

Have each group present its diagnosis and the reasoning used to arrive at its decision. (Allison’s disease is a common cold. If students have arrived at other conclusions, discuss the evidence they used. Mention the challenges of diagnosing respiratory diseases.)

Expand the discussion to address the importance of not taking antibiotics for viral diseases. Ask, Since Allison has a cold, should her doctor prescribe antibiotics? Would it be okay to take leftover antibiotics? Help students understand that antibiotics are effective for bacterial infections, but do not help against viral infections like colds. Also, mention that if antibiotics are prescribed for a bacterial infection, it is important to follow the doctor’s instructions and to take all the medication, even if symptoms start to improve before the medicine is gone. Otherwise, the disease may reoccur. Taking antibiotics incorrectly, or using them inappropriately (such as taking leftover medicine without a doctor’s guidance) can contribute to the development of antibiotic resistant forms of bacteria, which cannot be killed by existing antibiotics.

Have student groups add information to their concept maps.

X-Times: Career Options

Student magazine: Special issue featuring healthcare professionals who discuss why each chose his or her career, educational requirements needed to obtain the job, and day-to-day responsibilities.

X-Times: Microbes

Student magazine: articles focusing on microbes, both helpful and harmful. Includes a special report, "HIV/AIDS: The Virus and the Epidemic."

Science Education Partnership Award, NIH

MicroMatters Grant Number: 5R25RR018605

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Case Studies: Diseases

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Aging (including Alzheimer's disease)

C Rundel, Genes, aging, and the future of longevity. Engineering & Science LXV #4, 12/02, p 36. A delightful essay on some issues of aging, written by a Caltech undergraduate as part of a science writing class -- and then published in the Caltech magazine. The article is available online at http://eands.caltech.edu/articles/LXV4/longevity.html . The article discusses some genes that are known to affect aging in simple model organisms, and even a drug which seems to extend the life of fruit flies.

An intriguing result has recently been published: A team at Scripps Research Institute (La Jolla, California) has engineered mice to have a slightly lower core body temperature (by about 0.5 degree Celsius). These mice lived longer (by about 15%) than the "normal" mice. How did they lower the body temperature? By engineering the mice to make a heat-producing protein (uncoupling protein) in the hypothalamus -- where the body senses and regulates its temperature. The cooler mice ate and exercised normally, had somewhat higher weight (since they were producing less heat from the same food) -- and lived longer. Interestingly, one effect of severe caloric restriction, which is known to increase lifespan, is lowering the body temperature. So this work may give us one more piece of a complex puzzle. Its practical significance for now is purely speculative: there is no known way to reduce human body temperature, and of course we know nothing about what the side effects might be. The paper is B Conti et al, Transgenic mice with a reduced core body temperature have an increased life span. Science 314:825, 11/3/06. The paper is accompanied by a "perspective" article: C B Saper, Biomedicine: Life, the universe, and body temperature. Science 314:773, 11/3/06. These are online at http://www.sciencemag.org/content/314/5800/773.summary (perspective, probably the best place to start) and http://www.sciencemag.org/content/314/5800/825.abstract (article).

SAGE KE, the Science of Aging Knowledge Environment Archive Site, from Science magazine. "From October 2001 to June 2006, Science's SAGE KE provided news, reviews, commentaries, disease case studies, databases, and other resources pertaining to aging-related research. Although SAGE KE has now ceased publication, we invite you to search and browse the article content on this archive site." http://sageke.sciencemag.org/ .

Nature web focus sites on aging:

http://www.nature.com/nm/focus/alzheimer/index.html . Alzheimer's disease. (June 2006)
http://www.nature.com/nature/focus/s...nce/index.html . Senescence: Cells, ageing and cancer. (August 2005)
http://www.nature.com/nature/focus/l...pan/index.html . Determining lifespan. (September 2003)

Book. Stephen S Hall, Merchants of Immortality - Chasing the dream of human life extension. Houghton Mifflin, 2003. ISBN 0-618-09524-1. Available in Berkeley Public Library. For more about this book, see the listing of it under Cloning and stem cells . The "aging" parts of the book largely deal with telomerase, a fascinating scientific topic which probably is not a key limiting factor in human aging. In fact, much of the book deals with the hype surrounding telomerase -- and attempts to commercialize telomerase technologies.

Book. Lenny Guarente, Ageless Quest - One scientist's search for genes that prolong youth. Cold Spring Harbor Lab Press, 2003. ISBN 0-87969-652-4. Available in UC Berkeley Library. Guarente is a biologist at MIT. In this short book, he talks about finding a gene that extends the life of simple yeast -- and of worms. The question, then, is whether it is relevant to aging in higher organisms, including humans. He discusses evidence that it may be, though conclusive evidence is not yet available. This story is a good testimonial to the importance of basic research -- how studying simple model systems leads to insights that guide work in more complex systems. It is also a good story of how scientists develop and pursue leads -- some of which work out and some of which do not; that is how science works. It is an optimistic book -- perhaps too optimistic, since the gap between what has been shown and what is needed is still quite large. Enjoy the story, and Guarante's enthusiasm. But be careful to distinguish what turns out to work from the exciting discussions of what might be.

Anthrax vaccine immunization program. One place where the anthrax vaccine is actually used with high frequency is in the US military. This is their site about the vaccine and the program. Be alert for bias (as with any source!), but there is actually a lot of good info here. www.anthrax.osd.mil.

Researchers, including a group from UC Berkeley, have explored the tricks that the anthrax bacteria use to get the iron they need for growth. They found that these bacteria make two chemicals designed to steal iron from their host; such chemicals are generically called siderophores. One of these is attacked by the human immune system; however, the other -- the more novel one -- evades it, and actually succeeds in supplying iron to the bacteria. They suggest that this novel siderophore might be a good target for anti-anthrax drugs, or simply a marker for detection of this pathogen. The work was featured in the student newspaper, December 8, 2006: Researchers Find Possible Way to Block Anthrax, http://archive.dailycal.org/article/22576/_i_science_technology_i_br_researchers_find_possib . It was also discussed in a nice article in the student publication BSR: N Keith, Double Trouble - Anthrax has two tricks for stealing iron. Berkeley Science Review, Issue 12, p 15, Spring 2007. BSR is free online; this item is at sciencereview.berkeley.edu/ar...ticle=briefs_5. The work was published as R J Abergel et al, Anthrax pathogen evades the mammalian immune system through stealth siderophore production. PNAS 103:18499, 12/5/06. Online at http://www.pnas.org/content/103/49/18499.abstract . This work is also briefly noted on my Intro Chem Internet Resources page under solutions .

Book. For some interesting history, see the listing for Thomas D Brock, Robert Koch - A Life in Medicine and Bacteriology (1988) on my page Books: Suggestions for general reading . One major story is the first clear elucidation of the life cycle of a pathogenic bacterium -- anthrax. Those interested in bacteria, especially as agents of disease, will enjoy this fascinating tale of the origins of modern medical microbiology.

Antibiotics

Bacterial 'battle for survival' leads to new antibiotic -- Holds promise for treating stomach ulcers. A press release from MIT, Feb 2008, on a new approach for discovering new antibiotics. Briefly, they force bacteria not known to make antibiotics to compete with other bacteria. One possible response is for them to develop the ability to make antibiotics. This should be considered interesting lab work at this point. The potential of the new antibiotics is unknown. web.mit.edu/newsoffice/2008/a...tics-0226.html.

Alliance for the Prudent Use of Antibiotics. www.tufts.edu/med/apua/. This site has "an agenda" -- trying to reduce "inappropriate" use of antibiotics. A particular concern is the use of vast amounts of antibiotics with farm animals, sometimes with minimal justification. The site also contains a lot of general information about antibiotics, aimed at the consumer and at doctors.

A local angle. The July 24, 2003, issue of the Berkeleyan (a campus newspaper for staff) published part of an interview with science writer and UCB journalism professor Michael Pollan on the subject of antibiotics in beef farming, with a focus on McDonald's announcement of favoring suppliers that use less antibiotics. The article title is Prof has a beef with McDonald's antibiotics announcement. The entire interview is online at http://www.berkeley.edu/news/media/releases/2003/07/01_pollan.shtml . Very readable, with a useful general overview of why antibiotics are used in commercial production of animals. Pollan also expresses reservations about how significant the policy announcement will be.

The DNA double helix has become a popular icon, known well beyond the circles of those who know anything about biology. And of course, some artists are attracted to social issues. Thus it should not be surprising that DNA and genes and genomes and related issues have become the subject of artistic efforts.

John Sulston was the head of the British lab working on the human genome. Provocatively and/or appropriately, artist Marc Quinn did a "portrait" of Sulston -- using his DNA. For a news article on this, which includes the "portrait", see http://www.guardian.co.uk/culture/2001/sep/22/art . If you have access to Nature, see Martin Kemp's article about the portrait in the October 25, 2001, issue (413:778). (The printed article and the online PDF file contain the "portrait"; however the online HTML file does not.) This article is part of Nature's regular series, Science and Culture; art historian Kemp is a regular contributor.

Sulston shared the 2002 Nobel prize for his work on development in the worm Caenorhabditis elegans. In the course of that work, he played a key role in discovering the phenomenon of programmed cell death, now called apoptosis. http://www.nobelprize.org/nobel_priz...aureates/2002/ .

England issued a coin to commemorate the 50th anniversary of the DNA structure (which was developed at Cambridge Univ in England); it shows a DNA double helix on one side. (The other side shows the Queen, who coincidentally is celebrating her 50th anniversary as monarch.) For pictures of the coin, plus some information: http://www.taxfreegold.co.uk/2003two...dsdnagold.html .

Also see L Gamwell, Science in culture: Art after DNA. Nature 422:817, 4/24/03. http://www.nature.com/nature/journal...l/422817a.html . The subtitle notes "The double helix has inspired scientists and artists alike."

Bio-inspiration (biomimetics)

Book. Peter Forbes, The Gecko's Foot - Bio-inspiration: Engineering new materials from nature. Norton, 2005. The lotus leaf is easily rinsed clean; the gecko can climb a glass wall. Why? And, can we make use of the principles that Nature has used to achieve these remarkable accomplishments? Those are just two of the topics in this delightful book -- one of which is reflected in its title. The theme is bio-inspiration (sometimes called biomimetics), in which we look to Nature for an idea about how to do something. The hook-and-loop fastener, popularly known by the tradename Velcro, is an example of old, but the field has now taken on an identity that reflects a more focused effort to discover and exploit what Nature has already learned. Forbes emphasizes work at the "nano" level, where recent advances in instrumentation, such as the scanning electron microscope (SEM), helped us unlock Nature's secrets. Commercial importance? Well, products based on the self-cleaning lotus leaf and the sticky gecko foot are on the market. They are not yet big successes; perhaps that will take time, or perhaps there is less here of commercial importance than we would like to believe. In any case, the book is delightful biology, delightfully presented. It is suited for the scientific novice, but even biologists are likely to find it rewarding. This book is listed on my Book suggestions page, and as further reading for Intro Chem Ch 15, re intermolecular forces, and for Organic/Biochem Ch 15, re spider silk. In fact, it was reading this book that prompted me to start this BITN section.

From the University of Reading:

Centre for Biomimetics. www.reading.ac.uk/biomim/home.htm.
BIONIS: The Biomimetics Network for Industrial Sustainability. www.reading.ac.uk/bionis/.

From University of California, Berkeley

Biomimetic Millisystems Lab. "The goal of the Biomimetic Millisystems Lab is to harness features of animal manipulation, locomotion, sensing, actuation, mechanics, dynamics, and control strategies to radically improve millirobot capabilities. Research in the lab ranges from fundamental understanding of mechanical principles to novel fabrication techniques to system integration of autonomous millirobots. The lab works closely with biologists to develop models of function which can be tested on engineered and natural systems. The lab's current research is centered on fly-size flapping flight, and all-terrain crawling using nanostructured adhesives." The "Current Research Projects" listed in January 2008 include: Micromechanical Flying Insect, Biologically Inspired Synthetic Gecko Adhesives, Millirobot Rapid Prototyping, Micro-Robots and Microassembly. http://robotics.eecs.berkeley.edu/~ronf/Biomimetics.html . This page is from Ronald Fearing, in EECS (Electrical engineering and computer science). However, a glance at the people shows that this is a collaboration that also includes the Departments of Integrative Biology and Chemical Engineering.
CIBER. The Center for Interdisciplinary Bio-inspiration in Education & Research. A new center at Berkeley, headed by Dr Robert Full, of Integrative Biology. http://ciber.berkeley.edu . From "Objectives": CIBER "will innovate methods to extract principles in biology that inspire novel design in engineering and train the next generation of scientists and engineers to collaborate in mutually beneficial relationships. ... Biologists working with engineers, computer scientists and mathematicians are discovering general principles of nature from the level of molecules to behavior at an ever-increasing pace. Now more than ever before, nature can instruct us on how to best use new materials and manufacturing processes discovered by engineers, because these human technologies have more of the characteristics of life. This effort will require unprecedented integration among disciplines that include biology, psychology, engineering, physics, chemistry, computer science and mathematics." Choose Publications & Journals for good information on the work going on.

* Robot Flea Circus - Berkeley engineers build bionic bugs, by Tracy Powell. Berkeley Science Review, Fall 2007, p 22. Studying insect locomotion leads to ideas for designing robots. sciencereview.berkeley.edu/ar...cle=bionicbugs. * News story in the Daily Cal, the student newspaper, February 12, 2008. Mimicking the geckos' ability to defy gravity - From geckos to humans to robots: new adhesive tape makes the vertical horizontal. http://archive.dailycal.org/article/100353/mimicking_the_geckos_ability_to_defy_gravity . * News release: Engineers create gecko-inspired high-friction micro-fibers, August 2006. http://www.berkeley.edu/news/media/releases/2006/08/22_microfiber.shtml . As you read the item, note that they are not making synthetic gecko feet, but rather using some of what they learned about gecko feet to help them design a new material.

'Gecko foot' band-aids could promote healing. A news story in New Scientist, February 19, 2008, about the development of a new type of adhesive tape, which may be suitable for not only band-aids but also sutures. It is based in part on the structure of the gecko foot. Importantly, the work does not simply mimic the gecko foot, but builds on it, to develop a material suitable for the intended use. The story is online at http://www.newscientist.com/article/dn13347 . The work referred to is published as: A Mahdavi et al, A biodegradable and biocompatible gecko-inspired tissue adhesive. PNAS 105:2307, 2/19/08. There is a link to the article at the end of the news story.

Posts on my Musings pages on biomimetics include... * New, April 18, 2011. Why don't woodpeckers get headaches? Designing better shock absorbers (April 18, 2011) . * New, February 27, 2011. Robots should learn to crawl first, then walk (February 27, 2011) . * Added December 15, 2010. Armor (February 5, 2010) .

Brain (autism, schizophrenia)

There is evidence to suggest that infection of the mother during pregnancy may increase the chances of some brain diseases, including autism and schizophrenia. The effects seem to be due not to the infectious agent per se, but to the host response. Now, work with a mouse model system points to one specific component, the cytokine IL-6, as promoting the brain mis-development. Remember, this is with mice; the work generates some leads that must be followed up to see if they are relevant to humans. A press release about this work: "Researchers discover link between schizophrenia, autism and maternal flu", Oct 1, 2007: media.caltech.edu/press_releases/13039. The paper is: S E P Smith et al, Maternal immune activation alters fetal brain development through interleukin-6. Journal of Neuroscience, 27:10695-10702, 10/3/07.

Some general educational resources...

New, November 29, 2010. Inside Cancer. Educational materials, for the general public. Sections include: hallmarks, causes and prevention, diagnosis and treatment, pathways. Some materials are specifically for teachers. www.insidecancer.org. This is from the Dolan DNA Learning Center, Cold Spring Harbor Laboratory: http://www.dnalc.org/websites/ . Other parts of the Dolan DNA Learning Center are referred to under BITN Resources: DNA and the genome and Molecular Biology Internet Resources: Methods .

Understanding Cancer. A series of informational web pages for the general public, from the National Cancer Institute. www.cancer.gov/cancertopics/U...standingCancer. Also in Spanish.

Cancer Quest, a broad informational resource, largely organized as a tutorial, from G Orloff, Emory Univ. Topics range from the basic underlying biology to clinical issues. Special pages offer guidance to patients, educators, students, and health professionals. http://www.cancerquest.org . Also available in Chinese, Italian, Russian, Spanish.

Personalized cancer vaccine made in plants. This work deals with a cancer of the immune system, called follicular B cell lymphoma. An important characteristic of this cancer is that each case expresses a unique antigen, reflecting its development from a single immune system cell. The goal is to make a vaccine that targets this particular antigen. Here, they show that they can do this in a plant system -- which is both faster and cheaper than animal systems previously tried. The resulting vaccines do elicit an immune response in [most of] the patients, though no therapeutic benefit was seen in this small early study. The work is of note both for the special approach of making a personalized vaccine, and for the broader issue of making vaccines in plants. News story, from Stanford: Plants can be factories making vaccine to treat cancer, July 23, 2008. http://news.stanford.edu/news/2008/july23/med-plants-072308.html . The paper: A A McCormick et al, Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: Safety and immunogenicity in a phase I clinical study. PNAS 105:10131, 7/22/08. Free online: http://www.pnas.org/content/105/29/10131 .

Drug targeting. A group from UC Berkeley and San Francisco reported making a new drug delivery system. The active drug is attached to a large molecule called a dendrimer. Because the blood system in tumors tends to be leaky, the large drug complex is taken up by the tumor selectively, and then hydrolyzed. They report promising results in a mouse model system. Both the article and the story about it discuss some of the logic of the system. There is a good news story about the work in BSR, a student publication: N Parghi, Right on target - Reducing chemotherapy's collateral damage. Berkeley Science Review, issue 12, p 12, Spring 2007. Free online: sciencereview.berkeley.edu/ar...ticle=briefs_3. The paper: C C Lee et al, A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. PNAS 103:16649, 11/7/06. Free online: http://www.pnas.org/content/103/45/16649 .

Irreversible electroporation. UC Berkeley scientists, led by B Rubinsky, are working on a new approach to treating solid tumors. A new paper is on the use of the method with pigs, the first large animal tests. The method is a variation of the common electroporation used in laboratory work to make transient membrane pores that can allow uptake of drugs or even DNA. The key difference is that the conditions are chosen so that the pores do not quickly reseal; thus the cells "leak to death". In this method, the electrical pulse is delivered directly to tumor cells, in a surgical procedure. News story, "A breakthrough treatment for tumors? New medical technique uses electrical pulses to punch holes in target cell membrane." February 14, 2007. Online: http://www.berkeley.edu/news/berkele...reatment.shtml .

The Carcinogenic Potency Database (CPDB). A database of carcinogens, based on testing in animals. From Lois Swirsky Gold, Bruce Ames, and colleagues at UC Berkeley. potency.berkeley.edu/.

Book. J Michael Bishop, How to win the Nobel prize - An unexpected life in science. Harvard Univ Press, 2003. ISBN 0-674-00880-4. Bishop is a local story -- long time scientist at UCSF, now Chancellor there. Bishop's work on cellular genes that become cancer genes earned the Nobel Prize for him and his UCSF colleague Harold Varmus. (And a few days after the Nobel announcement he was at Candlestick Park for the World Series game that did not happen.) The book is based on a series of lectures, and has the informal breezy style of talks for a general audience. It is more generally about the nature of science, and about baseball, music and the human Michael Bishop, than about cancer in particular. One chapter does indeed give a good, not-too-technical introduction to the nature of cancer -- and his own contributions. The final chapter is about the future of science, and its role in society. All-in-all, a fairly light but interesting read.

J Diamond, The double puzzle of diabetes. Nature 423:599, 6/5/03. Feature. Nature's blurb for this article: "Why is the prevalence of type 2 diabetes now exploding in most populations, but not in Europeans? The genetic and evolutionary consequences of geographical differences in food history may provide the answer." The article gives an overview of the types of diabetes, and their incidence. The main purpose is to propose an explanation of why diabetes is not rampant among Europeans. As you read this, remember that he is proposing a hypothesis -- and some tests of it; be careful about remembering his "answer" as if it were true. Reading the article for its background information can be good. Online at http://www.nature.com/nature/journal...l/423599a.html .

Ebola and Marburg

Ebola and Marburg are related viruses. Ebola has been observed to emerge "from the jungle" from time to time. A major -- and important -- mystery is where is it "hiding". That is, what is the "reservoir" (likely an animal) from which the virus emerges? Now there is evidence that bats may be the culprit.; the bats carrying the virus show no symptoms. It is important to emphasize that this is a new finding, subject to further work. Even if correct, it only shows that the bats are a part of the story; there may be more to it. The article is: E M Leroy et al, Fruit bats as reservoirs of Ebola virus. Nature 438:575, 12/1/05. The abstract is at http://www.nature.com/nature/journal...s/438575a.html . Here are two news stories on this finding: http://www.innovations-report.com/ht...ort-53574.html and http://news.bbc.co.uk/2/hi/health/4484494.stm .

Now there is a report of Marburg virus being detected in bats. The work is published: J S Towner et al, Marburg virus infection detected in a common African bat. PLoS ONE 2(8):e764, 8/22/07. There is a news story, August 2007: Scientists detect presence of Marburg virus in African fruit bats, at: http://www.eurekalert.org/pub_releas...-sdp082107.php . This has a link to the article, which is freely available.

Progress with efforts to control Ebola, Marburg viruses. Microbe 1:217, 5/06. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=42381. Discusses both vaccines and drugs.

Emerging diseases (general)

In the Spring of 2003, as I started to put together a BITN web site, one dominant news story was a new illness, called SARS (severe acute respiratory syndrome). Our fears of SARS are enhanced by our ignorance. And that is not just the ignorance of the general public, but also the ignorance of the medical and scientific communities. SARS is a new disease. At least at the start, we do not know what causes it, how it is transmitted, how to contain or treat it -- even how to diagnose or define it, or what its risks are. Of course, over time, answers to some of these questions are developed. It is actually quite amazing how fast some of the answers come in. On the other hand, not all the answers we hear are correct. (For example, three different organisms were quickly "identified" as the cause of SARS. Obviously, two of those were likely to be incorrect.)

By mid-summer, we may have the disease under control. Yet, we still have little idea how the disease started -- and if/when it may return.

SARS is an example of an emerging disease -- a new disease. Other diseases that have emerged over the last 30 years include Legionnaire's diseases, AIDS , toxic shock syndrome, Ebola , West Nile Virus -- and perhaps a new strain of Influenza each year. Both SARS and the broader topic raise lots of questions about how we deal with a disease that has emerged, and how we might predict or prevent new emerging diseases.

M E J Woolhouse, Where Do Emerging Pathogens Come from? Microbe 1:511, 11/06. microbemagazine.org/index.php...gens-come-from. A discussion of the factors involved in the emergence of new diseases.

J L Fox, Cats with MRSA, elephants with TB are parts of a "microbial storm". Microbe 3:451, 10/08. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at microbemagazine.org/images/st...1008000448.pdf (scroll down to page 4 of the file for this item -- or just look for the elephants). "Emerging diseases" is a two-way street. Diseases may pass from humans to other animals, too. This news story discusses some examples and concerns.

The following sites track emerging diseases

Center for Infectious Disease Research and Policy (Univ Minnesota). http://www.cidrap.umn.edu . I list specific CIDRAP sections on my pages for Influenza (Bird flu) and Prions (BSE, CJD, etc) . Other topic areas here include: Bioterrorism, Biosecurity (e.g., food), Food safety (foodborne illnesses, irradiation), and a miscellaneous section that includes SARS, West Nile, Monkeypox, Chemical Terrorism. Useful for the general audience.
Healthmap, a "Global disease alert map", presents disease reports by country. You can click on a map or chose from a list of countries. http://www.healthmap.org/ . From J Brownstein, Harvard Medical School. Also in Arabic, Chinese, French, Portuguese, Russian, Spanish. Caution: loads very slowly.
ProMED-mail is aimed at medical professionals, informing them about emerging diseases; it is one of the major primary sources underlying the sites listed above. Includes announcements and maps of outbreaks, as well as general information. From the International Society for Infectious Diseases. http://www.promedmail.org . Parts of the site are also available in Chinese, Japanese, Portuguese, Russian, Spanish.
US government sites with information on emerging diseases:
CDC. www.cdc.gov/ncidod/diseases/e...ease_sites.htm.
NIH. http://www.niaid.nih.gov/topics/emerging/ .
Book. See the listing for Dorothy H Crawford, Deadly Companions - How microbes shaped our history (2007) on my page Books: Suggestions for general reading . This book is about the relationship between microbes and man. It starts with a discussion of SARS, and discusses many emergences of the past. Good perspective.
Added April 9, 2011. One health (November 15, 2010) .
Added March 12, 2011. Both ways (November 18, 2008) . ge

Ethical and social issues

As noted in the introductory materials, I intend the main emphasis here to be the scientific issues. Of course, other issues are important parts of the overall story. Some of the topic-specific resources listed include ethical and social issues. But occasionally, I may want to list a site that focuses on these matters.

Bloodlines: Technology Hits Home. The web site http://www.pbs.org/bloodlines/ was written to accompany a PBS show. It broadly deals with issues arising from reproductive and genetic technologies, and includes interactive questions which you can try to evaluate for yourself.

Bioethics Web. "BioethicsWeb is a gateway to evaluated, high quality Internet resources relating to biomedical ethics, including ethical, social, legal and public policy questions arising from advances in medicine and biology, issues relating to the conduct of biomedical research and approaches to bioethics." Subtopics include: Biomedicine, Clinical practice, Environment/agriculture/foods, Ethics: theory and concepts, Research conduct, Society/policy/law, and more.

aidsinfo.nih.gov. A broad source of HIV information, from NIH. It includes a section on vaccine trials, as well as drug treatments and other research areas.

The 2008 Nobel prize in Physiology or Medicine was awarded to Harald zur Hausen, "for his discovery of human papilloma viruses causing cervical cancer" and Francoise Barre-Sinoussi and Luc Montagnier, "for their discovery of human immunodeficiency virus". See the Nobel site: http://www.nobelprize.org/nobel_priz...aureates/2008/ . This item is listed on this page for HIV and HPV .

Hormone replacement therapy

A major and continuing news story for 2002-3 was based on some long term studies of the use of replacement hormones by post-menopausal women. The results were not at all what had been commonly expected. One important general point from the story is the problem of knowing what long term effects of a treatment are, especially the smaller effects -- without doing long term studies with large numbers of patients. Lots of info, with regular updates, is available at the home page for the Women's Health Initiative: http://www.whi.org . "The Women's Health Initiative (WHI) is a long-term national health study that focuses on strategies for preventing heart disease, breast and colorectal cancer and fracture in postmenopausal women. This 15-year project involves over 161,000 women ages 50-79, and is one of the most definitive, far reaching programs of research on women's health ever undertaken in the U.S. The purpose of this site is to provide WHI participants [and] others interested in the WHI findings a way of obtaining information about research results directly from the study."

And now, after five more years of data, the advice changes again. It is more detailed, more nuanced. This is common, and emphasizes that we must be cautious about over-interpreting any data set. News story, June 21, 2007, from Brigham and Women's Hospital and Harvard Medical School: "Estrogen Therapy and Coronary Artery Calcification. Women aged 50-59 who took estrogen show a reduced risk of coronary plaque buildup." www.brighamandwomens.org/abou...b=0&PageID=272.

For an introduction to the use of testosterone supplements in men, see a page from the US National Institute on Aging: Frequently Asked Questions About Testosterone and the IOM Report, 11/12/03. www.nia.nih.gov/NewsAndEvents...eIOMReport.htm.

HPV (Human papillomavirus)

A new vaccine was announced recently. It is widely known by its trade name, Gardasil. It acts to prevent infection by some strains of the human papillomavirus, which cause cervical cancer and genital warts. The vaccine itself is indeed a product of modern biotechnology: it contains only viral proteins (produced in yeast), with no viral genome; thus it cannot grow at all. Here are some materials from the CDC about this vaccine: * "Questions and Answers about HPV Vaccine Safety". www.cdc.gov/vaccinesafety/Vac.../hpv_faqs.html * A more technical report: "Quadrivalent Human Papillomavirus Vaccine -- Recommendations of the Advisory Committee on Immunization Practices (ACIP)", by L E Markowitz et al, dated March 23, 2007. It provides background about the type of virus and its effects, and the nature of the vaccine. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm

Notes... There are many strains of HPV. Only some of them cause cancer or warts. The vaccine is effective against four of these strains. Data so far suggests that the vaccine is extremely effective against those four strains, but it is important to realize that strains other than those in the vaccine are responsible for some cancer. One might be confused by hearing that the virus is "100%" effective or "70%" effective. The former number refers to the apparent effectiveness against the strains included in the vaccine; the latter number refers to the overall effectiveness against cervical cancer, given that the current vaccine works against only some of the relevant strains. Long term issues about this new vaccine are, of course, not known. For example, how long is it effective?

The May 10, 2007, issue of the New England Journal of Medicine contains several articles on this new vaccine -- with more data and perspectives. I suggest that readers start with two editorials, with differing views. Both are freely available online.

L R Baden et al, Human papillomavirus vaccine - opportunity and challenge. N Engl J Med 356:1990, 5/10/07. http://www.nejm.org/doi/full/10.1056/NEJMe078088
G F Sawaya & K Smith-McCune, HPV vaccination - more answers, more questions. N Engl J Med 356:1991, 5/10/07. http://www.nejm.org/doi/full/10.1056/NEJMe078060

Here is another approach to making an HPV vaccine. This one seeks to treat a person who is infected; it is thus a therapeutic vaccine. It targets a protein that is part of the viral life cycle in an infected cell -- and which is actually responsible for causing and maintaining cancer. This vaccine is still in testing. News story: Experimental HPV Vaccine Helps in Treating Mice with Cervical Cancer, Microbe 3:318, 7/08. Free online: microbemagazine.org/images/st...0708000314.pdf. Scroll down to page 5 of the file for this item.

The main emphasis with HPV and cancer has been cervical cancer. However, there is increasing evidence that these viruses, probably the same strains, may cause other cancers. Here is one news story on this: HPV-Linked Oral Cancer In Men Increasing, Feb 4, 2008. http://www.medicalnewstoday.com/articles/96053.php .

The traditional method of screening for cervical cancer is the pap smear, which looks for abnormal cells; in poor countries, little or no screening may be done. A new study suggests that it might be better to screen for the virus that causes the cancer. Their extensive testing shows that the test for the viral DNA is more effective than the pap smear. They argue that it is also likely to become inexpensive enough to be practical -- and worthwhile -- in poorer countries. A news story on this work: DNA Test Outperforms Pap Smear; April 6, 2009. www.nytimes.com/2009/04/07/he...virus.html.The paper is: R Sankaranarayanan et al, HPV Screening for Cervical Cancer in Rural India. N Engl J Med 360:1385, April 2, 2009. Freely available at http://www.nejm.org/doi/full/10.1056/NEJMoa0808516 . The article is accompanied by an editorial: M Schiffman & S Wacholder, From India to the World - A Better Way to Prevent Cervical Cancer. N Engl J Med 360:1453, April 2, 2009. Freely available at http://www.nejm.org/doi/full/10.1056/NEJMe0901167 . The editorial is a good overview of many issues surrounding cervical cancer.

Malaria is one of the world's great killers. Recent years have seen the analysis of the genome of both the malaria parasite itself and its mosquito vector. Nature has posted a "web focus" on the diverse aspects of this disease, 2008. http://www.nature.com/nature/focus/malaria/index.html

A UC Berkeley group led by Jay Keasling is working on production of artemisinin, a new type of anti-malarial drug, in microbes (bacteria and yeast).

Here is a campus news story on the funding of this project by the Gates Foundation: "QB3 + Gates' millions = a cure? Helped by Microsoft's founder, Jay Keasling and his industry partners hope to create an inexpensive treatment for malaria". January 12, 2005. http://www.berkeley.edu/news/berkele...keasling.shtml .
A status report -- a news story, June 4, 2008. "Synthetic yeast to brew up vital malaria drug." http://www.newscientist.com/article/...aria-drug.html .
This group of items is also listed for Organic/Biochemistry Internet resources: Alkenes . It is also noted in the Synthetic biology section of this page.

Malaria Vaccine Initiative (MVI). http://malariavaccine.org/ . For a short news story on malaria vaccines, including the role of the MVI: Money, Technology, and Fresh Ideas Converge on Malaria. Microbe 3:9, 1/08. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=55316.

In some ways measles would seem to be a good target for eradication. It occurs only in humans, so there is no need to worry about animal reservoirs. A good vaccine is available. Yet measles remains a major killer. One key reason is that the virus is highly infectious, thus a very high level of population immunity is needed to block its transmission. The following article is a good readable discussion of the issues of measles, its vaccine, and the difficulty of eradicating this disease. D E Griffin & W J Moss, Can We Eradicate Measles? Microbe 1:409, 9/06. It is at microbemagazine.org/images/st...0906000409.pdf.

Whatever happened to polio?. A history site from the Smithsonian Institution, posted to coincide with the 50th anniversary of the first polio vaccine. http://americanhistory.si.edu/polio/ . Includes information on the current effort to eradicate polio.

A report from the Institute of Medicine (IOM)... K Stratton et al, Immunization safety review: SV40 Contamination of Polio Vaccine and Cancer, October 2002. http://www.nap.edu/catalog.php?record_id=10534 . Some early batches of the original polio vaccine (the Salk vaccine, with killed virus) were later found to be contaminated with the virus SV40 (which was not killed by the treatment used to kill the poliovirus). SV40 may be a cancer-causing virus. So, inadvertently, we have been running a big test on whether it causes cancer in humans. A long enough time has passed that it is rather clear there is no big problem. Some data has suggested increases in certain very rare cancers. This report analyzes what is known. One of the frustrations, inherent in an accidental test, is that the data is not kept very well. This is an interesting story, but I do suggest you read it for the message about how things should be done, and not try to make SV40 into a big problem.

Nature web focus: http://www.nature.com/nature/focus/polio/index.html . End of polio - the final assault. (September 2004)

Protein Folding -- and diseases

This topic was suggested by a student. It was stimulated in part by the Sept 8, 2003, issue of The Scientist, including a feature article by P Hunter, Protein Folding: Theory meets disease, p 24: http://classic.the-scientist.com/art...display/14060/ . It is also related to the topic Prions (BSE, CJD, etc.) .

There are several issues here. The general topic of how proteins fold has long fascinated -- and frustrated -- biologists. But the topic has taken on greater significance with the increasing recognition of how relevant the protein folding problem is to disease. In fact, a good place to start with the Hunter article, listed above, is the side-bar on p 25, "Miss a fold, prompt a disease." Many cases are now known where we realize that the main effect of a mutation that causes a disease is to interfere with protein folding. For example, the major mutation found in cystic fibrosis is of this type. Once/if the mutant protein manages to fold, it works fine, but the mutation greatly slows the folding process.

Another type of folding-disease connection is illustrated by the prions. Although our understanding of prions is still incomplete, it seems that the prion proteins have two stable forms. One is the normal form of the protein, in your cells, and the other form causes disease. See the Prions (BSE, CJD, etc.) page for more.

A classic experiment in the history of studying protein folding was done by Christian Anfinsen, around 1960. Anfinsen showed that a protein could fold up properly in vitro, without any external source of "information" on how to fold. This established the paradigm that the 3D shape of a protein follows from its amino acid sequence. Although there are some nuances, this still underlies our modern understanding of protein folding. Anfinsen shared the 1972 Nobel prize for Chemistry "for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation". See the Nobel site: http://www.nobelprize.org/nobel_priz...aureates/1972/ .

RNAi (RNA interference or silencing)

Natural small RNA molecules act as gene regulators. Similarly, synthetic small RNA molecules may be useful to biologists to probe gene function -- and may be useful as therapeutic agents. This is a new field. Particularly with regard to actual therapeutic use, there is much promise but little information. Two articles in the March 29, 2004, issue of The Scientist provide a good introduction and overview. The articles are A Adams, RNAi inches toward the clinic (p 32), and A Constans, Concocting a knock-out punch for HIV-1 (p 28). http://classic.the-scientist.com/art...display/14559/ & http://classic.the-scientist.com/art...display/14552/ .

The Scientist for Sept 13, 2004 (Vol 18 #17) has the feature topic of RNAi, with multiple articles: classic.the-scientist.com/2004/9/13/. Again, an excellent introduction and overview.

The idea of using an inhibitory RNA as a therapeutic is simple enough, but there are many technical hurdles. Here is a report of targeting an siRNA (small interfering RNA) to the brain -- by using a protein from rabies virus. Rabies infects the nervous system, and the scientists exploit one part of that virus to deliver the therapeutic RNA across the blood brain barrier. The therapeutic RNA attached to the rabies virus delivery system protects the mice from an experimental viral infection of the brain. Press release, from NIH, June 17, 2007: Blood-Brain Barrier Breached by New Therapeutic Strategy. http://www.niaid.nih.gov/news/newsre...inbarrier.aspx . The work was published: P Kumar et al, Transvascular delivery of small interfering RNA to the central nervous system . Nature 448:39, 7/5/07. Accompanying news story: E M Cantin & J J Rossi, Molecular medicine: Entry granted. Nature 448:33, 7/5/07.

The 2006 Nobel prize for physiology or medicine was awarded to Andrew Z Fire and Craig C Mello for their discovery of "RNA interference - gene silencing by double-stranded RNA". http://www.nobelprize.org/nobel_priz...aureates/2006/ .

See the BITN page Prions (BSE, CJD, etc): Treatment for a paper on the possible use of RNAi to treat a prion disease.

See the BITN page Agricultural biotechnology (GM foods): Recent items for a paper on the use of RNAi, targeted to the seeds, to reduce production of a toxic chemical in cotton seeds.

Nature has a web focus site on this topic. Of particular interest may be a set of animations of how the process works: www.nature.com/focus/rnai/ani...ons/index.html.

SARS (Severe acute respiratory syndrome)

See Emerging diseases section, above, for perspective.

The web site of the US Centers for Disease Control (CDC) is a good site to keep abreast of SARS -- and of course of other diseases. The CDC SARS page: www.cdc.gov/ncidod/sars/

The CDC site has links to all local and state public health departments, and also includes travel advisories.

Nature magazine's "web focus" on SARS: http://www.nature.com/nature/focus/sars/index.html . This set seems to be freely available.

In July, Nature published a "news feature" called "SARS - What have we learned?" It is in the form of a series of questions, with answers, about various aspects of the SARS story. Among the questions... Was the fuss overblown? Are we prepared for the next viral threat? Where did the SARS virus come from? What about a vaccine? Very readable overview and update. Nature 424:123, 7/10/03; also available at the top of their web focus page, listed above.

A free online SARS "textbook", maintained by B S Kamps & C Hoffmann: http://www.sarsreference.com . Also available in Chinese, French, Greek, Italian, Portuguese, Romanian, Spanish, Vietnamese.

www.bt.cdc.gov/agent/smallpox/index.asp. The site provides a wide range of information, including much history. Some materials are also available here in Spanish.

Sudden Oak Death

http://www.suddenoakdeath.org . A range of information, both for the consumer and the scientist. The site is from UC Berkeley.

Sudden larch death (SLD) is due to the same pathogen. Some information on the spread of SLD in Europe is included at this site. Just search on larch.

Synthetic biology

A nice overview of the field of synthetic biology. M Stone, Life redesigned to suit the engineering crowd. Microbe 1:566, 12/06. Microbe, the news magazine of the American Society for Microbiology, is free online; this item is at forms.asm.org/microbe/index.asp?bid=47155 (HTML) or forms.asm.org/ASM/files/ccLib...1206000566.pdf (PDF).

Craig Venter, of genome sequencing fame, plans to make new organisms. One key step along the way was to take a small bacterium, and determine how many of its -- already small -- gene set are really needed. This sets the stage for making artificial genomes -- and then for designing new organisms to do specific tasks. News has been coming fast and furious from the Venter lab; I list some of the news coverage and some of their own press releases below.

Good news stories: * Venter Institute team builds M. genitalium genome from scratch (Microbe magazine, April 2008). microbemagazine.org/images/st...0408000162.pdf. * Countdown to a synthetic lifeform (7/11/07). http://www.newscientist.com/article/mg19526114.000 . * Genetic engineers who don't just tinker (7/8/07). http://www.nytimes.com/2007/07/08/we...ew/08wade.html . * Tycoon's team finds fewest number of genes needed for life (6/8/07). http://www.guardian.co.uk/science/20...etics.research . Press releases from the J Craig Venter Institute: * First Self-Replicating Synthetic Bacterial Cell (5/20/10). www.jcvi.org/cms/press/press-...te-researcher/. Since the terms "synthetic" or "artificial" cells are ambiguous and subject to hype, we should be clear what is accomplished here. They made a synthetic genome; that is, they assembled a new genome without using any natural DNA. They then transplanted this into an existing cell, and the new genome "took over". In this case, the synthetic genome is (substantially) identical to a known genome. That is, this work is proof of principle that a new genome can be made and used. * Synthetic bacterial genome (1/24/08). www.jcvi.org/cms/research/pro...press-release/. * JCVI scientists publish first bacterial genome transplantation changing one species to another (6/28/07). www.jcvi.org/cms/press/press-...es-to-another/.

Jay Keasling's work, at UC Berkeley, to develop a cheaper way to make the anti-malarial drug artemisinin is noted in the Malaria section of this page. The work involves making major changes in the metabolic capabilities of the microbes, and is considered synthetic biology.

TGN1412: The clinical trial disaster

March 2006. The news media carried a story of a clinical trial gone terribly wrong. Within an hour or so of receiving a drug, all recipients were seriously ill. What happened? Was there some mix-up -- perhaps the wrong drug used? Was the trial not properly planned or executed? Or was this just "one of those things" -- showing why we start with a small test in humans? So far, the evidence suggests that the last possibility is correct. Everything seems to have been done properly. However, given the severe result in this case, people are questioning whether "properly" was good enough. Was there reason to have been more cautious in this case -- more cautious than just following standard procedure? Perhaps -- and people are debating this. The drug was of a new type, one about which we know little, and about which some are very concerned -- despite the good data from animal tests. It is clear that even a simple precaution, of giving the drug to one patient at a time, and watching them for an hour or two, would have been much better in this case.

As to the nature of the drug, it is hard to describe briefly. But a simple start would be that it was designed to stimulate the immune system -- and the problem is that it did so inappropriately in the human subjects.

The analysis of the incident is still in progress. However, some information is now appearing in the literature, so it seems appropriate to share that here. I do encourage people to be cautious in reaching conclusions at this point.

The New England Journal of Medicine published three articles in the September 7 issue on this topic. In the order listed below: one is a perspective (an overview discussion of the topic), one is the main scientific report, and one is a commentary. All are freely available online. For most people, the first item listed below -- the perspective -- may be the best place to start. * A H Sharpe & A K Abbas, Perspective: T-Cell Costimulation � Biology, Therapeutic Potential, and Challenges. New England Journal of Medicine 355:973, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMp068087 . * G Suntharalingam et al, Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412. New England Journal of Medicine 355:1018, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMoa063842 . * J M Drazen, Commentary: Volunteers at Risk. New England Journal of Medicine 355:1060, 9/7/06. http://www.nejm.org/doi/full/10.1056/NEJMe068175 .

There is also a government report on the incident. I might cynically comment that it reads like a government report. Nevertheless, browsing it may be useful, at least as a guide to the questions that get raised. The final report (December 2006) is at www.dh.gov.uk/en/Publications...ance/DH_063117. (The link to the preliminary version of the report at the end of the Drazen article listed above is now a dead link.)

Vaccines (general)

A general comment and caution... Vaccines seem to be the subject of many controversies. But be particularly careful with any arguments that appear to make criticism of vaccines in general. The diseases against which we have vaccines are diverse, and the vaccines are diverse. Most real vaccine issues are specific to a particular vaccine or type of vaccine. This section is mainly for sources about vaccines in general, or sources with info about many vaccines. Also see sections for individual diseases for info about specific vaccines. For example, the sections on Anthrax , Ebola , HIV (AIDS) , HPV (Human papillomavirus) , Malaria , Measles , Polio , Smallpox , and West Nile Virus contain info on vaccines for those diseases. An item listed under Cancer deals with making personalized vaccines in plants.

Added September 21, 2011. VIOLIN -- the Vaccine Investigation and Online Information Network. A broad-based vaccine resource, from the University of Michigan Medical School... http://www.violinet.org .

Added September 8, 2011. A report from the Institute of Medicine (IOM)... Adverse Effects of Vaccines: Evidence and Causality, August 25, 2011. www.iom.edu/Reports/2011/Adve...Causality.aspx. The report addresses numerous possible side effects of vaccines, and tries to analyze whether evidence supports a causal relationship between vaccine and effect. You can download a pdf file of a "Report Brief", or read the report online.

Making a wimpy virus. One approach to making vaccines is to use an attenuated strain of the infectious agent -- one that can induce an immune response, but not cause disease. Scientists at Stony Brook have developed a new approach to making an attenuated virus for use in a vaccine. They re-code the virus so that it uses codons that are poorly translated. They made a few hundred changes in the poliovirus genome, each one making it harder for the genome to function. The result was a virus that seemed to work well as a vaccine strain in mouse tests. A nice feature of this approach is that it would seem to be of general applicability, though of course it needs to be tested in each case. Press release, summarizing the story: "SBU Team Designs Customized "Wimpy" Polioviruses, A Method That Could Be A New Path To Vaccines. Reported in Science, the 'Save' Computer-driven Method Creates a Weakened Synthetic Virus"; June 26, 2008. commcgi.cc.stonybrook.edu/am2...Vaccines.shtml. The paper is: J R Coleman et al, Virus attenuation by genome-scale changes in codon pair bias. Science 320:1784, 6/27/08.

Thimerosal in vaccines. Thimerosal is an organic mercury compound, used as a preservative -- including in vaccines. As with any mercury compound, it is toxic. Of course, the fact that it is toxic is why it is used as a preservative. The intent is that it is more toxic to bacteria and fungi than to humans. The available information suggests that the risks from exposure to mercury from thimerosal are quite small. (Exposures from eating fish and from coal-fired power plants are likely to be larger.) As a precaution -- in the US and Europe -- thimerosal is now rarely used in vaccines intended for children; the common Influenza vaccine is the one prominent exception. Note points of uncertainty, especially regarding children (which is why extra precautions are taken with children), but also note that there is really no data suggesting any problem with thimerosal as used in vaccines. * This FDA web page is a good overview of the use of thimerosal. It should serve as a good framework for further discussion. http://www.fda.gov/BiologicsBloodVac...fety/UCM096228 . * A new study shows that ethyl mercury, the form of mercury from thimerosal, is eliminated from the body much faster than methyl mercury. (Methyl mercury is a more common toxic form of mercury, and has been used as a frame of reference for discussing thimerosal in the absence of more direct information.) Children getting many vaccines containing thimerosal (in Argentina) do not show elevated blood level of mercury. A press release from the University of Rochester accompanying publication of this work: Babies Excrete Vaccine-Mercury Quicker than Originally Thought, January 30, 2008. http://www.urmc.rochester.edu/news/s...ex.cfm?id=1848 . The paper is M E Pichichero et al, Mercury Levels in Newborns and Infants After Receipt of Thimerosal-Containing Vaccines. Pediatrics 121:e208-e214, 2/08. It is freely available at http://pediatrics.aappublications.or.../e208.abstract . * I have posted a page showing the chemical structure of thimerosal and some related compounds, including aspirin: thimerosal . * This topic is also listed under Introductory Chemistry Internet Resources: Thimerosal and Introduction to Organic and Biochemistry Internet Resources: Alcohols, ethers, sulfur compounds .

Open access
Published: 11 April 2024

Diagnostic delay of sarcoidosis: an integrated systematic review

Tergel Namsrai 1 ,
Christine Phillips 4 ,
Anne Parkinson 1 ,
Dianne Gregory 1 , 2 ,
Elaine Kelly 1 , 2 ,
Matthew Cook 3 &
Jane Desborough ORCID: orcid.org/0000-0003-1406-4593 1

Orphanet Journal of Rare Diseases volume 19 , Article number: 156 ( 2024 ) Cite this article

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Sarcoidosis is a chronic inflammatory granulomatous disease of unknown cause. Delays in diagnosis can result in disease progression and poorer outcomes for patients. Our aim was to review the current literature to determine the overall diagnostic delay of sarcoidosis, factors associated with diagnostic delay, and the experiences of people with sarcoidosis of diagnostic delay.

Three databases (PubMed/Medline, Scopus, and ProQuest) and grey literature sources were searched. Random effects inverse variance meta-analysis was used to pool mean diagnostic delay in all types of sarcoidosis subgroup analysis. Diagnostic delay was defined as the time from reported onset of symptoms to diagnosis of sarcoidosis.

We identified 374 titles, of which 29 studies were included in the review, with an overall sample of 1531 (694 females, 837 males). The overall mean diagnostic delay in all types of sarcoidosis was 7.93 months (95% CI 1.21 to 14.64 months). Meta-aggregation of factors related to diagnostic delay in the included studies identified three categories: (1) the complex and rare features of sarcoidosis, (2) healthcare factors and (3) patient-centred factors. Meta-aggregation of outcomes reported in case studies revealed that the three most frequent outcomes associated with diagnostic delay were: (1) incorrect diagnosis, (2) incorrect treatment and (3) development of complications/disease progression. There was no significant difference in diagnostic delay between countries with gatekeeper health systems (where consumers are referred from a primary care clinician to specialist care) and countries with non-gatekeeper systems. No qualitative studies examining people’s experiences of diagnostic delay were identified.

The mean diagnostic delay for sarcoidosis is almost 8 months, which has objective consequences for patient management. On the other hand, there is a paucity of evidence about the experience of diagnostic delay in sarcoidosis and factors related to this. Gaining an understanding of people’s experiences while seeking a diagnosis of sarcoidosis is vital to gain insight into factors that may contribute to delays, and subsequently inform strategies, tools and training activities aimed at increasing clinician and public awareness about this rare condition.

Trial registration

PROSPERO Registration number: CRD42022307236.

Introduction

Sarcoidosis is a multisystem granulomatous inflammatory disease of unknown cause, which can affect any organ, but primarily affects the lungs. Sarcoidosis can present as acute or chronic disease - acute sarcoidosis, with joint pain, erythema nodosum and hilar adenopathy, that resolves spontaneously; or chronic sarcoidosis with insidious onset and slow progression that continues to invade multiple systems. In studies using national patient registers the incidence appears to be highest in northern Europe at 11.5 per 100,000 per year in Sweden [ 1 ] and 11.3–14.8 per 100,000 per year in Denmark [ 2 ], There are significant intra-country differences attributable to ethnicity in the USA where African Americans have significantly higher rates of disease [ 1 , 2 ], earlier peak age of onset [ 3 ] and higher mortality [ 4 ]. The patterns of organ involvement [ 5 , 6 , 7 ] and gender distribution [ 3 , 4 , 8 ] vary between countries and within countries.

The reported delay of diagnosis in sarcoidosis ranges from 6 months [ 2 ] to 24 months [ 9 ]. Its complex clinical features, acute or chronic presentation, spontaneous or treatment-induced remission in some cases, and the absence of a single simple diagnostic test all contribute to challenges in timely diagnosis. In many cases, diagnosis hinges on tissue diagnosis and therefore a firm diagnosis might be delayed even when the diagnosis is suspected. Some of the most consequential extrapulmonary manifestations of sarcoidosis – neurological, ophthalmic, and cardiac – are among the most difficult to diagnose [ 8 , 9 , 10 , 11 ]. Spontaneous remission occurs frequently in sarcoidosis [ 12 ]; some studies report remission in half of the cases [ 13 ]. Diagnostic delay can occur with both acute and chronic presentations of sarcoidosis, but particularly for chronic presentations marked by slow progression and complex features, mimicking other diseases. Failure to initiate treatment for progressive pulmonary sarcoidosis [ 14 ] and many extrapulmonary manifestations of sarcoidosis can result in permanent organ damage [ 11 , 15 , 16 ]. Since the pathogenesis of sarcoidosis remains unknown, it is a diagnosis of exclusion. The differential diagnosis includes other causes of granulomas, which encompass infections, including mycobacteria, fungi and bacteria, occupational exposures such as beryllium and silica, sterile granulomatous inflammation, and lymphoma.

There is a paucity of research examining the diagnostic delay of sarcoidosis, including factors associated with diagnostic delay and people’s experiences from the time of symptom onset to diagnosis. Our aim was to systematically review the current evidence regarding the diagnostic delay of sarcoidosis and people’s experiences of this. This evidence may help to inform the development of strategies to enhance awareness of rare manifestations of sarcoidosis, enabling timely intervention when warranted for chronic and progressive sarcoidosis.

This systematic review was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [ 17 ] and the Cochrane Handbook for Systematic Reviews [ 6 ]. It is registered with PROSPERO, an International prospective register of systematic reviews (registration number: CRD42022289830).

Literature search, study selection, and data extraction

A systematic electronic search of the literature was conducted using PubMed/Medline, Scopus, and ProQuest databases up to the 25th of May 2022, with no limitations. The search string was pre-developed and peer-reviewed using the PRESS checklist [ 18 ]. The final search string included “sarcoidosis” AND “delay in diagnosis” OR “diagnostic delay” OR “misdiagnosis” OR “time to diagnosis” OR “incorrect diagnosis” OR “missed diagnosis” OR “delayed diagnosis” without restrictions on study type, date, and language. A detailed search string and strategy are available in the published protocol [ 19 ]. Grey literature sources were searched up to the 25th of May 2022 in Open Access Theses and Dissertations ( https://oatd.org/ ), ProQuest thesis and dissertations, and the National Library of Australia. Manual reference searches were conducted on all review articles identified in the literature search.

There was no restriction on publication dates. All studies, both qualitative and quantitative, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of sarcoidosis in all age groups were included, except for review articles. Studies in languages other than English, German and Indonesian were excluded. Final search results were imported into a systematic review management software (Covidence) to facilitate reviewer collaboration [ 20 ].

Two authors conducted an independent screening of titles and abstracts followed by a full-text screening of articles using pre-developed PICOS eligibility criteria outlined in Table 1 . Articles that did not meet the eligibility criteria were excluded. Discrepancies were resolved in discussion with a third reviewer and through reaching a consensus. Included studies were quality appraised using the Mixed Methods Appraisal Tool (MMAT) [ 21 ]. A pre-developed and pre-piloted data extraction tool was used, and following further discussion after piloting, data describing the initial specialist and the presence/absence of gatekeeper health systems were also extracted.

Data analysis

General data preparation.

Diagnostic delay was defined in accordance with the included studies - from reported onset of symptoms to a diagnosis of sarcoidosis. In studies where mean diagnostic delay was presented in years or days, we converted it to months. For studies that did not report a standard deviation (SD) of mean diagnostic delay, we imputed the SD using the method recommended by Cochrane, which calculates SD using an upper limit, lower limit, and confidence interval [ 6 ]. In studies where the confidence interval was not reported, we calculated SD using the method improved by Wan and colleagues, incorporating the sample size or population [ 22 ].

Categorisation of studies was based on the location or organ involvement of sarcoidosis - pulmonary, extrapulmonary, and systemic. Where sarcoidosis involved only the lungs (defined as changes in hila, mediastina, and the lungs) the location was categorised as pulmonary; where sarcoidosis involved two or more organs the location was categorised as systemic. If only one organ other than the lungs was involved, the location was categorised as extrapulmonary. Health systems were categorised as either gatekeeper (where primary care physicians authorise access to specialist physicians) or non-gatekeeper health systems, based on the dominant health system in the country where the study was conducted. A country was classified as having a gatekeeper system if the system of health financing uniformly used primary care gatekeepers, without the option of self-funding to see specialists, or models of health funding that supported open access to specialists. In countries with diverse health insurance models which may include open access and gatekeepers, such as the USA, an assessment was made for each publication by two authors. Where we could not determine the gatekeeper system used by participants the paper was excluded. We calculated the missing mean age of the study sample when complete data of the study participants was available.

Analysis of diagnostic delay in sarcoidosis

We used an inverse variance weighted random effects model (Der-Simonian-Laird method) to pool mean diagnostic delay [ 6 ]. Sensitivity analyses between studies with estimated SDs and original SDs were conducted. Additionally, we conducted subgroup analyses based on healthcare system type and publication year to investigate possible group differences in diagnostic delay in sarcoidosis. We analysed quantitative data through a meta-synthesis. The alpha level was set at 0.05, and the heterogeneity of meta-analysis estimates was presented using the I 2 statistic. Funnel plots were used to assess the risk of publication bias.

We descriptively analysed and presented a narrative synthesis of the quantitative data from case reports that could not be pooled. Gender difference in diagnostic delay was calculated in case reports where data on sex and delay in diagnosis (months) was available. The distribution of delay in diagnosis in case reports was examined by density plot and Shapiro test ( p <.05), indicating non-normal distribution; thus, the Mann-Whitney-Wilcoxon test was used to analyse the group differences of delay in diagnosis by sex. All statistical analyses were performed using R version 4.6.2 [ 23 ] and the ‘meta’ package.

Analysis of symptoms, factors, outcomes and experiences associated with diagnostic delay

To investigate the factors associated with diagnostic delay, data on symptoms that changed the diagnosis, and factors related to and outcomes of diagnostic delay were extracted and synthesised using meta-aggregation, for which meanings from qualitative data are identified and aggregated into categories that can be synthesised and analysed [ 24 ]. The broader categorisation of the aggregated data was decided through peer discussion and referral back to the original papers when needed. Additionally, factors linked to pulmonary, extrapulmonary and systemic sarcoidosis were grouped and further analysed.

To our knowledge, none of the included studies reported data on experiences of diagnostic delay in sarcoidosis.

Out of 374 titles identified, we removed 100 duplicates, and screened 274 titles and abstracts. Of those, 67 articles were reviewed at full text and 29 studies were included in the review as shown in Fig. 1 .

Selection flow chart of studies included in the systematic review

Description of included studies

Included studies are summarised in Table 2 and a full data extraction table is presented in Supplementary Table 1 . The 29 included studies comprised 24 non-comparative descriptive studies (including 15 case reports [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], five case series [ 40 , 41 , 42 , 43 , 44 ], two surveys [ 45 , 46 ], and two descriptive cross-sectional studies [ 2 , 47 ]), and five comparative studies (all analytical cross-sectional studies) [ 9 , 48 , 49 , 50 , 51 ]. Twenty-eight of the included studies used non-patient-reported data including clinical reports and retrospective patient registry data, while one used patient-reported data [ 45 ]. In total, there were eleven studies from Europe [ 2 , 9 , 25 , 26 , 33 , 35 , 38 , 42 , 45 , 47 , 48 ], nine from the United States or Canada [ 27 , 29 , 30 , 32 , 34 , 37 , 43 , 44 , 49 ], three from West Asia [ 41 , 46 , 50 ], four from East Asia [ 28 , 31 , 39 , 40 ], one from sub-Saharan Africa [ 36 ], and one from South America [ 51 ]. Various organ involvement of sarcoidosis was reported, including eyes [ 9 ], nasal passages [ 42 ], kidney [ 26 , 27 ], skin [ 28 , 34 ], heart [ 40 , 48 ], nervous system [ 30 , 38 , 44 ], lungs [ 35 , 36 , 37 , 43 ], skeletal muscle [ 33 ], subcutaneous tissue [ 39 ], and systemic or mixed [ 2 , 25 , 29 , 31 , 32 , 41 , 45 , 46 , 49 , 50 , 51 ]. Based on the manual categorisation, thirteen studies examined extrapulmonary sarcoidosis [ 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 39 , 40 , 44 , 47 , 48 ], five examined systemic sarcoidosis [ 9 , 25 , 31 , 38 , 42 ], and four examined pulmonary sarcoidosis [ 35 , 36 , 37 , 43 ]. In seven studies it was not possible to differentiate between pulmonary and non-pulmonary sarcoidosis [ 2 , 41 , 45 , 46 , 49 , 50 , 51 ]. Of the 29 included studies, 18 were from countries with non-gatekeeper health systems (2, 25, 27–33, 3537, 39, 40, 43, 44, 47, 49) and 11 were from countries with gatekeeper health systems [ 9 , 26 , 34 , 38 , 41 , 42 , 45 , 46 , 48 , 50 , 51 ]. Twelve studies reported data on ethnicity or race [ 2 , 25 , 29 , 30 , 31 , 32 , 33 , 36 , 42 , 43 , 49 , 51 ].

In total, a population size of 1531 participants (694 females; 837 males) was included in the review. The mean age was 47.91 years (SD = 5.47), excluding case reports (see below). Overall, participant ages ranged from 9.3 years to 69 years (including case reports).

Results of the quality appraisal

Consensus on the quality appraisal of the included studies is shown in Supplementary Table 2 . After the double-quality appraisal, a consensus was reached by two authors regarding an overall low risk of bias for all studies; therefore, no study was excluded.

Case studies

Twenty case studies comprising 15 case reports (8 females; 7 males) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and five case series [ 40 , 41 , 42 , 43 , 44 ], with 29 participants (22 females, 7 males), were included. The mean age of participants in case report studies was 47.87 years (SD = 14.06 years), with individual age ranging between 26 years [ 25 ] and 69 years [ 27 ]. In the case series, mean age of individuals ranged from 9.3 years [ 41 ] to 44 years [ 42 ].

Of the 20 included case studies, 11 examined extrapulmonary sarcoidosis [ 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 39 , 40 , 44 ], and four each focused on pulmonary [ 35 , 36 , 37 , 43 ] and systemic sarcoidosis [ 25 , 31 , 38 , 42 ]. In the one remaining case study, it was not possible to determine the extent of organ involvement [ 41 ].

In the 15 included case reports, individual diagnostic delay ranged from 0.25 months (0.02 years) [ 39 ] to 96 months (8 years) [ 35 ] and the mean diagnostic delay was 21.73 months. In the five case series, the mean diagnostic delay ranged from 5 months [ 42 ] to 43.5 months [ 43 ].

There was no significant gender difference in delay in diagnosis in case reports ( n = 15, Mann-Whitney-Wilcoxon test: w = 21.5, p =.749).

Pooled diagnostic delay in sarcoidosis

The results of the pooled mean diagnostic delay of the five studies [ 2 , 9 , 23 , 41 , 42 ] with an overall sample size of 124 are presented in Fig. 2 . Individual study sample size of these studies ranged from 8 [ 41 , 42 ] to 67 [ 9 ], while the mean diagnostic delay ranged from 5 months [ 42 ] to 23 months [ 9 ]. The pooled diagnostic delay was 7.93 months (95% CI 1.21 to 14.64 months) ( Fig. 2 ) . A funnel plot of the pooled diagnostic delay is presented in Supplementary Fig. 1 . We conducted a sensitivity analysis on SD estimated studies and SD not estimated studies and found no significant difference (between groups difference = 1.06 months, P =.30) in mean diagnostic delay between the two groups as shown in Supplementary Fig. 2 .

Pooled mean diagnostic delay in sarcoidosis

We could not conduct a subgroup analysis between pulmonary, extrapulmonary and systemic sarcoidosis due to the small number of studies with complete data (mean delay, total number of participants and SD of mean delay) in each group. However, in the included studies, systemic sarcoidosis had the longest mean diagnostic delay at 23.0 months [ 9 ] compared with extrapulmonary sarcoidosis, which had the shortest mean diagnostic delay of 5.0 months [ 42 ].

A subgroup analysis comparing studies ( n = 5) with different healthcare systems is presented in Supplementary Fig. 3 . There was no significant difference in mean diagnostic delay in countries with gatekeeper healthcare systems when compared with those with non-gatekeeper systems (between groups difference = 0.34 months, P = .56).

We conducted an additional subgroup analysis examining publication year of studies, which showed a significant inter-study difference in diagnostic delay in studies conducted (between groups difference = 16.99 months, P =.002) (see Supplementary Fig. 4 ). Further analysis examining publication year of the studies (e.g., before 2000 and after 2000) was not feasible due to the small number of studies.

Initial symptoms

Twenty-one studies comprising 15 case reports [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], three case series [ 40 , 42 , 43 ], two cross-sectional studies [ 47 , 49 ] and one survey [ 46 ] reported initial symptoms. Initial symptoms included weight loss [ 29 , 36 , 37 , 41 , 43 ], fatigue or generalised weakness [ 29 , 37 , 40 , 43 ], dyspnoea [ 36 , 40 , 43 ], muscle pain/muscle cramps/general body pain [ 32 , 37 , 40 ], headache [ 38 ], palpitations [ 40 ], nasal obstruction [ 42 ] and a subcutaneous mass [ 39 ] (refer to Supplementary Table 3 ). When aggregated, these symptoms could be categorised as: (1) general symptoms (fever, fatigue, weight loss), (2) organ-specific extrapulmonary symptoms (neurological- nausea, headache, vomiting; cardiac- palpitations; skin - rash, ulcers), and (3) pulmonary symptoms (cough, dyspnoea). Of the initial symptoms, 31.25% (25/80) were general; 55% (44/80) were organ specific and related to extrapulmonary symptoms, while 13.75% (11/80) were pulmonary (see Supplementary Table 3 ).

Initial specialist and treatment/diagnostic centre

Five of the included studies reported the cadre of specialist first consulted, one study each reporting general practitioner [ 29 ], emergency specialist [ 31 ], gynaecologist [ 38 ], oncologist [ 39 ], and neurologist [ 32 ] as the first specialist consulted. Twenty-one studies reported visits to treatment or diagnostic centres including secondary or tertiary hospitals, research centres and university hospitals [ 2 , 9 , 25 , 26 , 27 , 31 , 32 , 33 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 44 , 47 , 48 , 49 , 50 , 51 ]. Nineteen of these 21 studies reported treatment or diagnosis at multidisciplinary centres [ 2 , 9 , 25 , 26 , 27 , 31 , 32 , 33 , 35 , 37 , 38 , 41 , 42 , 44 , 47 , 48 , 50 , 51 ], and one study each at an institute of oncology [ 39 ] and a research centre [ 49 ].

Symptoms that changed the diagnostic approach

Twelve case studies, containing a total of 13 cases/participants, reported 24 symptoms that changed the diagnostic approach [ 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 43 ]. These symptoms ranged from no response to treatment [ 31 , 36 , 43 ], persistent or increasing shortness of breath/dyspnoea [ 35 , 40 , 43 ], persistent cough [ 35 , 37 ] to worsening hypertension [ 27 ], renal function decline and hypercalcemia [ 27 ] (Supplementary Table 4 ). None of the cross-sectional studies and surveys reported symptoms that changed the diagnostic approach. When aggregated, symptoms that changed the diagnostic approach were categorised into: (1) persistent symptoms (7/24, 29.2%) [ 33 , 35 , 40 , 43 ], (2) new symptoms or signs (7/24, 29.2%) [ 31 , 32 , 38 ], (3) worsening of symptoms (6/24, 25%) [ 27 , 34 , 40 ] and (4) no response to treatment (4/24, 16.6%) [ 31 , 36 , 43 ], as shown in Supplementary Tables 4 and Supplementary Fig. 5 .

Factors related to diagnostic delay

Fifteen case reports [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], three case series [ 40 , 42 , 44 ], two analytical cross-sectional studies [ 9 , 48 ], one survey [ 45 ] and one descriptive cross-sectional study [ 47 ] reported factors that might influence diagnostic delay in sarcoidosis (see Supplementary Table 5 ). Two analytical cross-sectional studies examined association between several factors and diagnostic delay [ 49 , 51 ]. In one study, the presence of pulmonary symptoms was associated with a longer time to diagnosis, whereas the presence of skin symptoms was associated with a shorter time to diagnosis [ 49 ]. People assessed as being at a higher stage on the Scadding scale (radiological scale to measure lung changes; higher stage correlates to greater structural damage in lungs) had a longer time-to-diagnosis compared to people with lower stage features (stage IV vs. stage II, stage III vs. stage 0 or I on chest radiographs) [ 49 ]. One study in Brazil found that misdiagnosis of and treatment for tuberculosis was more likely to be reported among those with a time-to-diagnosis of more than 6 months [ 51 ].

The factors mentioned in the 22 studies were meta-aggregated and the results are shown in Fig. 3 . We categorised these factors into: (1) complex and rare features of sarcoidosis (27/35, 77.1%), (2) healthcare factors (7/35, 20%) and (3) patient-centred factors (1/35, 2.9%). Of these, 77.1% (27/35 factors) were related to complex and rare features of sarcoidosis (category 1), including broad clinical features and differential diagnosis [ 9 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 42 , 44 , 47 , 48 ], rare presentation [ 28 , 32 , 34 , 36 , 37 , 38 , 42 ], lack of awareness and rarity of sarcoidosis [ 29 , 30 , 32 , 33 , 40 ], and coexisting disease or comorbidities [ 35 , 38 ]. The 20% (7/35 factors) pertaining to healthcare factors (category 2) included exclusion diagnosis [ 39 ], lack of standard procedure to distinguish sarcoidosis [ 47 ], not using appropriate diagnostic techniques/ relying on chest x-ray [ 45 , 48 ], challenges with biopsy [ 9 , 40 ], and challenges with making a definitive diagnosis in sarcoidosis [ 32 ]. The remaining 2.9% of factors were patient-centred (category 3), which referred to refusal of biopsy (1/35 factors) [ 35 ].

Meta-aggregation results of factors related to diagnostic delay in sarcoidosis

We further analysed these factors by sarcoidosis type (Supplementary Table 6 ). Twenty-two studies reported types of sarcoidosis; of these, 21 studies [ 9 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 44 , 47 , 48 ] reported factors related to diagnostic delay. Three studies reported five factors of diagnostic delay in pulmonary sarcoidosis. Of these, 80% were categorised as complex and rare features of sarcoidosis (category 1), which included co-existing disease and comorbidities [ 35 ], rare presentations [ 36 , 37 ] and broad clinical features [ 37 ]. The remaining 20% were patient-centred factors, referring to patient’s refusal of a biopsy (category 3) [ 35 ]. Thirteen studies reported twenty factors related to diagnostic delay in extrapulmonary sarcoidosis [ 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 39 , 40 , 44 , 47 , 48 ]. Of these, 75% were linked to complex and rare features of sarcoidosis (category 1), including broad clinical features and differential diagnosis [ 26 , 27 , 28 , 40 , 44 , 47 , 48 ], rare presentation [ 28 , 32 , 34 ] and lack of awareness of sarcoidosis [ 29 , 30 , 32 , 33 , 40 ]. The remaining 25% were categorised as healthcare related (category 2), which included factors relating to healthcare providers [ 48 ] and challenges with diagnostic approach or tools [ 32 , 39 , 40 , 47 ]. Nine factors were mentioned to be linked to diagnostic delay in systemic sarcoidosis [ 9 , 25 , 31 , 38 , 42 ]; eight of these were linked to the complex and rare features of sarcoidosis (category 1); broad clinical features [ 25 , 31 , 38 , 42 ], rare presentation [ 9 , 38 , 42 ], and co-existing disease [ 38 ]. One factor was linked to healthcare (category 2): challenges with diagnostic approach and tool, described by the authors of the paper as limited number of patients amenable to lymph node biopsy [ 9 ].

Outcomes related to diagnostic delay

Sixteen studies described the outcomes of diagnostic delay, including 11 case reports [ 26 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], two case series [ 40 , 44 ], two analytical cross-sectional studies [ 48 , 51 ], and one survey [ 45 ]. The survey and analytical cross-sectional studies did not use statistical methods to examine the relationship between independent variables and diagnostic delay; however, they reported descriptive or comparative results of the outcomes of diagnostic delay. One study described incorrect diagnoses that were provided instead of sarcoidosis, including tuberculosis, lung cancer, rheumatic fever, Hodgkin’s lymphoma, pneumonia, and patients simulating the symptoms [ 45 ]. One study reported irreversible deterioration of cardiac function (6/10 cases) and high mortality (5/10 cases) in people with a late diagnosis of sarcoidosis [ 48 ], and another study reported poor lung function in people with a late diagnosis [ 51 ].

While case reports or case studies are not designed to assess the association between two variables, we analysed their data using meta-aggregation as shown in Supplementary Tables 7 and Fig. 4 . Thirteen case studies, including 11 case reports [ 26 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ] and two case series [ 40 , 44 ], described outcomes from 26 cases. We aggregated the outcomes into: (1) incorrect diagnosis, (2) incorrect treatment and (3) complications/progression of the condition. Incorrect diagnosis (category 1) was reported in 38.5% (10/26 cases), including xanthogranulomatous pyelonephritis [ 26 ], monoclonal gammopathy of undetermined significance [ 27 ], tuberculosis [ 31 , 36 ], deep tissue infection [ 34 ], bronchitis [ 35 ], respiratory infection [ 37 ], tachycardia and heart block [ 40 ], and multiple sclerosis [ 44 ]. Incorrect treatment (category 2) was reported in 34.6% (9/10 cases), consisting of nephrectomy [ 26 ], anti-tuberculosis agents [ 31 , 36 ], antibiotics [ 34 , 35 , 37 ] and excision of mass [ 39 ]. Complications/progression of symptoms or the condition (category 3) was reported in 26.9% (7/10 cases) of the cases. These included renal failure [ 27 ], seizure [ 32 ], weakness of the extremities [ 33 ], infection [ 34 ], dyspnoea and oxygen therapy [ 35 ], headache, vomiting and blurred vision [ 38 ], dyspnoea and haemoptysis [ 40 ].

Meta-aggregation of outcomes of diagnostic delay in case studies

People’s experiences related to diagnostic delay

We did not identify any studies, including qualitative, that examined people’s experiences of diagnostic delay in our systematic search.

Using data from the 29 studies included in this review, we were able to present a pooled analysis of diagnostic delay in all types of sarcoidosis to describe factors that are related to and associated with diagnostic delay, and the outcomes for people living with sarcoidosis. Pooled mean diagnostic delay for all types of sarcoidosis was 7.93 months (95% CI 1.21 to 14.64 months), a similar range to delays described for other chronic inflammatory diseases, including inflammatory bowel disease [ 52 ]. The overall sample pool of this study consisted of more males than females (54.7% vs. 45.3%). No difference in delay in diagnosis was found between males and females based on the analysis conducted on case reports. The high number of single-person case studies on misdiagnosis attests to the size of the diagnostic challenge for the clinician. Several factors may influence diagnostic delay of sarcoidosis, including the clinical characteristics of the condition, prevalence, different types/presentation of the condition, clinicians’ and patients’ awareness of the condition, and the availability of diagnostic tests.

The present review found complex and rare features of sarcoidosis, healthcare factors, and patient-centred factors may contribute to diagnostic delay in all types of sarcoidosis. In some studies included in the review, associations were found between pulmonary symptoms and higher Scadding scores, and prolonged diagnostic delay of sarcoidosis. The presence of pulmonary symptoms that may be attributable to various health conditions (common flu, pneumonia, bronchitis, asthma, emphysema, and lung cancer) create challenges for healthcare providers working to narrow down the health condition and differentiate between possible causes of pulmonary symptoms. In these cases, healthcare providers may first choose to investigate more common causes of pulmonary symptoms and pursue a diagnostic approach that excludes the most common causes through minimal testing, which is cost effective.

The review also revealed healthcare factors (exclusion diagnosis, challenges with obtaining a biopsy and lack of standard procedure to distinguish sarcoidosis) may lead to diagnostic delay. Difficulties with access to medical resources needed to conduct a biopsy (availability of clinicians and medical facilities) may cause delay in the definitive diagnosis of sarcoidosis through extending the time between suspicion and confirmation of diagnosis. Identifying the difference between suspicion and confirmation of diagnosis can provide further insights into the depth of the impact on diagnostic delay associated with healthcare factors.

Diagnostic delay due to misdiagnosis of tuberculosis was also identified in this review, highlighting the similarity of the two conditions and that differentiating between them is crucial for initiating the correct treatment, as treatment of sarcoidosis involves immunosuppression. In countries with a high prevalence of tuberculosis, it is understandable that clinicians may initially suspect tuberculosis. A misdiagnosis of tuberculosis has implications for the individual, their families and carers, and the use of medical resources, signalling the need for a careful and methodical approach in diagnosis. Once a clinician has made a diagnosis, it is natural to attribute the constellation of symptoms and signs of a rare disease to the identified cause (misdiagnosed condition), until clear evidence arises to disprove the current diagnosis.

Both acute and chronic presentation of sarcoidosis may influence the diagnostic delay. Acute sarcoidosis may follow acute onset with more typical features and radiological findings (hilar adenopathy in chest x-ray). Chronic sarcoidosis has insidious onset and may mimic other disorders (signs and symptoms from multiple systems); therefore, chronic sarcoidosis may present additional challenges for diagnosis of sarcoidosis. The present review did not study the difference in diagnostic delay between acute and chronic sarcoidosis due to limited data. Analyses of sarcoidosis location and factors related to diagnostic delay revealed similar findings, in which most reported factors were linked to complex and rare features, regardless of the location of sarcoidosis. Raising clinicians’ awareness of the complex clinical presentations of all types of sarcoidosis, including rare presentations, may assist in expediting diagnosis.

While none of the included studies used quantitative methods to examine outcomes of diagnostic delay, we used meta-aggregation to extract and examine outcomes described in case reports and case series which revealed incorrect diagnosis, incorrect treatment, and complications/progression of the condition as outcomes of diagnostic delay of sarcoidosis. This accords with findings from a recent review of diagnostic delay in myositis where outcomes including misdiagnoses, progression of symptoms, incorrect treatment, and early discharge were reported [ 53 ]. These outcomes align with people’s experiences of diagnostic delay recently described [ 54 ], signalling the need for improved awareness of sarcoidosis and a better understanding of its diagnosis and treatment.

As in our previous study examining diagnostic delay of myositis, where we did not find any studies examining people’s experiences of diagnostic delay [ 53 ], we did not find research examining experiences of diagnostic delay of sarcoidosis. We believe that further exploration of people’s experiences from symptom onset until diagnosis may assist in understanding these experiences and factors that may impact and influence diagnosis and its delay in sarcoidosis. This information may then be used to inform strategies aimed at reducing the undiagnosed period, including raising awareness and the development of clinical reasoning tools to distinguish when clinicians might consider re-evaluation of an existing diagnosis and the presence of a rare disease.

Despite the lack of studies examining people with sarcoidosis’ experiences of diagnostic delay, a recent commentary describes people with sarcoidosis’ experiences of misdiagnoses [ 54 ]. One person described frustration at ‘being dismissed’ and not listened to by their clinician, an experience that has also been described by people with multiple sclerosis seeking a diagnosis [ 55 ]. All of those interviewed for the article highlighted ongoing pain and discomfort from symptoms pre- and post-diagnosis as greatly impacting their lives, aligning with evidence of the negative impact that sarcoidosis has on people’s quality of life [ 56 ].

Diagnostic delay can create a sense of uncertainty and, in many cases, escalating symptoms, as found in research examining people’s experiences with multiple sclerosis [ 55 ], placing them in a stressful state of ‘not knowing”. Delayed diagnosis of childhood illnesses has consequences for both children and their families, including anxiety, frustration and stress, and fear of future reproduction due to ill-defined genetic risk [ 57 ]. Hospitalisation and surgical interventions related to rare diseases are more frequent among people who experience a delayed diagnosis [ 58 ]. Research examining experiences of hereditary angioedema found that inappropriate treatments were ineffective and at times, exacerbated the underlying condition [ 59 ]. For some patients, symptoms were attributed to psychological reasons and due to this, some stopped seeking medical care despite experiencing severe symptoms [ 59 ]. Attribution of rare disease symptoms to psychological or psychiatric reasons, and treatment in line with this is not uncommon; [ 57 , 58 , 59 ] however the impact of a rare disease on individuals’ mental health has important implications for the treatment and care of people with these health conditions [ 59 ].

Delay in diagnosis of sarcoidosis can cause impaired physical function, pain, reduced capacity to work, and strain on personal relationships, leading to a reduction in quality of life and the ability to engage in pleasurable activities, which in turn can have negative emotional consequences that impact wellbeing [ 60 ]. A survey of the treatment priorities of people with sarcoidosis found that they most valued quality of life and functionality and concluded that psychological support was key to their wellbeing [ 61 ]. Unfortunately, being able to discuss issues and concerns about sarcoidosis with clinician(s) cannot be realised until a diagnosis is received.

There is a paucity of evidence about the patient experience of diagnostic delay in sarcoidosis and factors related to this. Diagnosis of sarcoidosis can take a long time, during which the impacts on the lives of people living with sarcoidosis can be substantial, including receiving incorrect diagnoses and treatment, and suffering unfavourable outcomes. Further studies examining factors that contribute to diagnostic delay in sarcoidosis, and people’s experiences from symptom onset to diagnosis, are crucial in determining target areas for clinicians, policy-makers and consumer advocacy groups. With this further knowledge, we may develop strategies, training activities and awareness-raising programs that expedite diagnosis and improve outcomes for people living with sarcoidosis.

Strengths and limitation

The main strength of this review is inclusion of the current evidence of diagnostic delay in all types of studies (including qualitative and quantitative studies) which provided clear insight into the status of diagnostic delay, its factors, and consequences. This systematic review identified a lack of qualitative studies examining patients’ experience of diagnostic delay in sarcoidosis. The main limitation of the present systematic review is the low number of study samples used in pooling of the diagnostic delay ( n = 124 over 5 studies). The lack of available data on health specialists, clinics, acute or chronic presentation of sarcoidosis, and the period between suspected and confirmed diagnosis limited the possibility of analysing the difference in diagnostic delay in various settings. Lastly, the analysis of case reports may reflect features of chronic sarcoidosis with complex features due to publication bias- tendency to publish rare and interesting cases.

Data availability

All data relevant to the study is available in the supplementary materials. A detailed extracted data table can be accessed via figtree repository (via DOI: https://doi.org/10.6084/m9.figshare.24431275 ).

Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, et al. Sarcoidosis in America. Analysis based on Health Care Use. Ann Am Thorac Soc. 2016;13(8):1244–52.

Article PubMed Google Scholar

Leclerc S, Myers RP, Moussalli J, Herson S, Poynard T, Benveniste O. Sarcoidosis and interferon therapy: report of five cases and review of the literature. Eur J Intern Med. 2003;14(4):237–43.

Article CAS PubMed Google Scholar

Rybicki BA, Major M, Popovich J Jr., Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol. 1997;145(3):234–41.

Mirsaeidi M, Machado RF, Schraufnagel D, Sweiss NJ, Baughman RP. Racial difference in sarcoidosis mortality in the United States. Chest. 2015;147(2):438–49.

Perlman DM, Sudheendra MT, Furuya Y, Shenoy C, Kalra R, Roukoz H, et al. Clinical presentation and treatment of high-risk Sarcoidosis. Annals Am Thorac Soc. 2021;18(12):1935–47.

Article Google Scholar

Higgins JPTTJ, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane Handbook for Systematic Reviews of Interventions version 6.2 2021.

Pasadhika S, Rosenbaum JT. Ocular Sarcoidosis. Clin Chest Med. 2015;36(4):669–83.

Article PubMed PubMed Central Google Scholar

Kidd DP. Neurosarcoidosis: clinical manifestations, investigation and treatment. Pract Neurol. 2020;20(3):199–212.

Bolletta E, Mastrofilippo V, Invernizzi A, Aldigeri R, Spaggiari L, Besutti G et al. Clinical relevance of Subcentimetric Lymph Node Biopsy in the diagnosis of ocular sarcoidosis. Ocul Immunol Inflamm. 2020:1–4.

Kusano KF, Satomi K. Diagnosis and treatment of cardiac sarcoidosis. Heart. 2016;102(3):184–90.

Ungprasert P, Tooley AA, Crowson CS, Matteson EL, Smith WM. Clinical characteristics of ocular sarcoidosis: a Population-based study 1976–2013. Ocul Immunol Inflamm. 2019;27(3):389–95.

Johns CJ, Michele TM. The clinical management of sarcoidosis. A 50-year experience at the Johns Hopkins Hospital. Med (Baltim). 1999;78(2):65–111.

Article CAS Google Scholar

Hillerdal G, Nöu E, Osterman K, Schmekel B, Sarcoidosis. Epidemiology and prognosis. Am Rev Respir Dis. 1984;130(1):29–32.

CAS PubMed Google Scholar

Belperio JA, Shaikh F, Abtin FG, Fishbein MC, Weigt SS, Saggar R, et al. Diagnosis and treatment of pulmonary sarcoidosis: a review. JAMA. 2022;327(9):856–67.

Ungprasert P, Crowson CS, Matteson EL. Characteristics and long-term outcome of neurosarcoidosis: a Population-based study from 1976–2013. Neuroepidemiology. 2017;48(3–4):87–94.

Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(2):149–73.

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Reviews. 2015;4(1):1.

McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS peer review of electronic search strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;75:40–6.

Namsrai T, Phillips C, Desborough J, Gregory D, Kelly E, Cook M et al. December,. Diagnostic delay of sarcoidosis: protocol for an integrated systematic review. PLoS ONE Accepted on 7 2022.

Veritas Health Innovation. Covidence systematic review software Melbourne, Australia [Available from: Available at www.covidence.org.

Hong QN, Fàbregues S, Bartlett G, Boardman F, Cargo M, Dagenais P, et al. The mixed methods Appraisal Tool (MMAT) version 2018 for information professionals and researchers. Educ Inform. 2018;34:285–91.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.

RStudio Team. RStudio: Integrated Development for R. PBC, Boston MA. RStudio; 2020. http://www.rstudio.com/ .

Florczak KL. Meta-aggregation: just what is it? Nurs Sci Q. 2018;32(1):11.

Darugar A, Mathian A, Lehoang P, Bodaghi B. Acute posterior multifocal placoid pigment epitheliopathy as the initial manifestation of sarcoidosis. J Ophthalmic Vis Res. 2011;6(4):338–43.

PubMed PubMed Central Google Scholar

Froehner M, Meinhardt M, Parmentier S, Hugo C, Wirth MP. Renal Sarcoidosis Mimicking Xanthogranulomatous Pyelonephritis. Urology. 2016;97:e19–20.

Ghafoor A, Almakki A. Renal confined sarcoidosis: natural history and diagnostic challenge. Avicenna J Med. 2014;4(2):44–7.

Ghorpade A, Ramanan C. Cutaneous sarcoidosis. Indian J Dermatol Venereol Leprol. 1996;62(3):171–2.

Ho B, Choi KS, Ochoa W, Torralba KD, Sandhu VK, Pakbaz Z. Atypical manifestations of sarcoidosis in a hispanic male. J Community Hosp Intern Med Perspect. 2019;9(3):271–4.

Jaster JH, Dohan FC Jr., Bertorini TE, Bass JE, Mönkemüller KE, Handorf CR, et al. Solitary spinal cord sarcoidosis without other manifestations of systemic sarcoidosis. Clin Imaging. 1997;21(1):17–22.

Lee CH, Jung YS, Lee SH. Hydrocephalus as a presenting manifestation of neurosarcoidosis: easy to misdiagnose as tuberculosis. J Korean Neurosurg Soc. 2010;48(1):79–81.

Mehta A, Khan F, Wagner C, Hashemzadeh T, Stemer A, Sloan EA, et al. A case of Neurosarcoid presenting as multiple intraparenchymal hemorrhages. Neurohospitalist. 2022;12(1):162–6.

Meyer N, Sutter R, Schirp U, Gutzeit A. Extensive intramuscular manifestation of sarcoidosis with initially missed diagnosis and delayed therapy: a case report. J Med Case Rep. 2017;11(1):246.

Noiles K, Beleznay K, Crawford RI, Au S. Sarcoidosis can present with necrotizing granulomas histologically: two cases of ulcerated sarcoidosis and review of the literature. J Cutan Med Surg. 2013;17(6):377–83.

Papaetis GS, Pefanis A, Solomon S, Tsangarakis I, Orphanidou D, Achimastos A. Asymptomatic stage I sarcoidosis complicated by pulmonary tuberculosis: a case report. J Med Case Rep. 2008;2:226.

Plit ML, Miller GB. Cavitating pulmonary sarcoidosis. S Afr Med J. 1983;64(2):67–8.

Thomas PM, Mabrouk T, Li Y, Wallach SL. Delayed diagnosis in a Rare Case of Pulmonary Sarcoidosis presenting as unilateral Hilar Lymphadenopathy and Fever of unknown origin. Cureus. 2021;13(6):e15792.

van Rooijen JM, Mijnhout GS, Aalders TT, de Bondt RB. Hydrocephalus, a rare manifestation of sarcoidosis. Clin Pract. 2011;1(3):e66.

Viswanath L, Pallade S, Krishnamurthy B, Naveen T, Preethi BL, Pramod KP, et al. Darier-Roussy Sarcoidosis mimicking metastatic breast Cancer. Case Rep Oncol. 2009;2(3):251–4.

Guleria R, Sharma R, Mohan A, Das C. Cardiac sarcoidosis: an uncommon presentation of sarcoidosis in India. Indian J Chest Dis Allied Sci. 2006;48(2):133–7.

Al-Mayouf SM, Al-Sonbul A, Al Jumaah S, Al-Hemidan A. Sarcoidosis: a delayed or missed diagnosis in children. Ann Saudi Med. 2006;26(3):220–3.

Fergie N, Jones NS, Havlat MF. The nasal manifestations of sarcoidosis: a review and report of eight cases. J Laryngol Otol. 1999;113(10):893–8.

Judson MA, Vincent B, Huggins T, Silvestri GA, Sahn SA. Unusual presentations of pulmonary sarcoidosis: cases from the medical university of South Carolina. Semin Respir Crit Care Med. 2007;28(1):75–82.

Scott TF, Yandora K, Kunschner LJ, Schramke C. Neurosarcoidosis mimicry of multiple sclerosis: clinical, laboratory, and imaging characteristics. Neurologist. 2010;16(6):386–9.

Kirsten D. [Sarcoidosis in Germany. Analysis of a questionnaire survey in 1992 of patients of the German Sarcoidosis Group]. Pneumologie. 1995;49(6):378–82.

Okumus G, Musellim B, Cetinkaya E, Turker H, Uzaslan E, Yenturk E, et al. Extrapulmonary involvement in patients with sarcoidosis in Turkey. Respirology. 2011;16(3):446–50.

Send T, Tuleta I, Koppen T, Thiesler T, Eichhorn KW, Bertlich M, et al. Sarcoidosis of the paranasal sinuses. Eur Arch Otorhinolaryngol. 2019;276(7):1969–74.

Hoogendoorn JC, Ninaber MK, Piers SRD, de Riva M, Grauss RW, Bogun FM, et al. The harm of delayed diagnosis of arrhythmogenic cardiac sarcoidosis: a case series. Europace. 2020;22(9):1376–83.

Judson MA, Thompson BW, Rabin DL, Steimel J, Knattereud GL, Lackland DT, et al. The diagnostic pathway to sarcoidosis. Chest. 2003;123(2):406–12.

Kobak S, Yildiz F, Semiz H, Orman M. Elderly-onset sarcoidosis: a single center comparative study. Reumatol Clin (Engl Ed). 2020;16(3):235–8.

Rodrigues MM, Coletta EN, Ferreira RG, Pereira CA. Delayed diagnosis of sarcoidosis is common in Brazil. J Bras Pneumol. 2013;39(5):539–46.

Sulkanen E, Repo M, Huhtala H, Hiltunen P, Kurppa K. Impact of diagnostic delay to the clinical presentation and associated factors in pediatric inflammatory bowel disease: a retrospective study. BMC Gastroenterol. 2021;21(1).

Namsrai T, Parkinson A, Chalmers A, Lowe C, Cook M, Phillips C, et al. Diagnostic delay of myositis: an integrated systematic review. Orphanet J Rare Dis. 2022;17(1):420.

Morgan J. Misdiagnosis of sarcoidosis. Lancet Respir Med. 2021;9(7):696–8.

Desborough J, Brunoro C, Parkinson A, Chisholm K, Elisha M, Drew J, et al. It struck at the heart of who I thought I was’: a meta-synthesis of the qualitative literature examining the experiences of people with multiple sclerosis. Health Expect. 2020;23(5):1007–27.

Voortman M, Hendriks CMR, Lodder P, Drent M, De Vries J. Quality of life of couples living with Sarcoidosis. Respiration. 2019;98(5):373–82.

Zurynski Y, Deverell M, Dalkeith T et al. Australian children living with rare diseases: experiences of diagnosis and perceived consequences of diagnostic delays. Orphanet J Rare Dis. 2017/04/11 2017;12(1):68. https://doi.org/10.1186/s13023-017-0622-4 .

Benito-Lozano J, Arias-Merino G, Gómez-Martínez M, Ancochea-Díaz A, Aparicio-García A, de la Posada M et al. Diagnostic process in Rare diseases: determinants Associated with Diagnostic Delay. Int J Environ Res Public Health. 2022;19(11).

Isono M, Kokado M, Kato K. Why does it take so long for rare disease patients to get an accurate diagnosis?—A qualitative investigation of patient experiences of hereditary angioedema. PLoS ONE. 2022;17(3):e0265847.

Article CAS PubMed PubMed Central Google Scholar

Saketkoo LA, Russell AM, Jensen K, Mandizha J, Tavee J, Newton J et al. Health-Related Quality of Life (HRQoL) in Sarcoidosis: diagnosis, management, and Health outcomes. Diagnostics (Basel). 2021;11(6).

Baughman RP, Barriuso R, Beyer K, Boyd J, Hochreiter J, Knoet C, et al. Sarcoidosis: patient treatment priorities. ERJ Open Res. 2018;4(4):00141–2018.

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This work was supported by “Missed opportunities in clinical practice: Tools to enhance healthcare providers’ awareness and diagnosis of rare diseases in Australia” a project funded by the Commonwealth represented by Department of Health Australia [ID 4-G5ZN0T7]. Sponsors or funding officials were not involved in any part of the review including protocol development, data selection, synthesis, reporting and publishing of the results.

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AP, CP, JD, EK, DG, and MC conceptualised the study and supported the study methodology. TN, CP, AP, and JD conducted the data collection and analysis. TN drafted the original manuscript. JD, AP, CP, MC, DG, and EK reviewed and edited the manuscript.

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Namsrai, T., Phillips, C., Parkinson, A. et al. Diagnostic delay of sarcoidosis: an integrated systematic review. Orphanet J Rare Dis 19 , 156 (2024). https://doi.org/10.1186/s13023-024-03152-7

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Received : 23 March 2023

Accepted : 28 March 2024

Published : 11 April 2024

DOI : https://doi.org/10.1186/s13023-024-03152-7

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Sarcoidosis
Diagnostic delay
Misdiagnosis
Systematic review
Meta-analysis
Meta-aggregation
Rare disease

Orphanet Journal of Rare Diseases

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