Download A4Medicine Mobile App
Empower Your RCGP AKT Journey: Master the MCQs with Us! 🚀
Key Facts:
VHFs = severe illnesses caused by RNA viruses from 4 families:
Arenaviridae (e.g. Lassa)
Bunyaviridae (e.g. CCHF, Rift Valley)
Filoviridae (e.g. Ebola, Marburg)
Flaviviridae (e.g. Dengue, Yellow fever, KFD)
Zoonotic origin: spread from rodents, bats, mosquitoes, ticks
Main features:
High fever
↑ vascular permeability → hypotension, shock
Bleeding diathesis (↑ bleeding risk)
Multi-organ dysfunction
Transmission:
Direct contact with infected animals, vectors, or bodily fluids
Epidemiology of Viral Haemorrhagic Fevers (VHFs)
| VHF Disease | Region | Annual Burden & Notes |
|---|---|---|
| Dengue | Asia, Americas, Africa | ~390 million infections (96 million symptomatic); hyperendemic in many urban areas (World Health Organization) |
| Lassa fever | West Africa | 300,000–500,000 infections/year, ~5,000 deaths; rodent-borne (Centers for Disease Control and Prevention) |
| Ebola / Marburg | Sub-Saharan Africa | High case fatality rates (CFR): Ebola up to ↑63%, Marburg ranges from 24–88% (World Health Organization) |
| Crimean-Congo Haemorrhagic Fever (CCHF) | Africa, Middle East, Asia, Europe | Tick-borne; wide geographic spread; nosocomial (hospital-acquired) outbreaks reported (European Centre for Disease Prevention and Control) |
| Rift Valley fever | Africa, Arabian Peninsula | Affects humans & livestock; outbreaks linked to ↑ rainfall |
| Yellow fever | Africa, South America | Preventable via vaccination; cyclical outbreaks persist |
| Hantavirus | Americas, Europe, Asia | Rodent-borne; causes pulmonary or renal syndrome |
🧪 Note: VHFs often occur in settings with ↓ diagnostic capacity and weak public health infrastructure, complicating containment and reporting.
| Disease | Region | Transmission | Key Features |
|---|---|---|---|
| Dengue / Dengue Haemorrhagic Fever (DHF) | Nationwide (especially urban) | 🦟 Aedes mosquitoes | Monsoon-linked outbreaks; leading cause of VHF in India |
| Kyasanur Forest Disease (KFD) | Karnataka, Goa, Maharashtra | 🕷️ Ticks (via monkeys/rodents) | Seasonal forest outbreaks; occupational hazard for forest workers |
| Crimean-Congo Haemorrhagic Fever (CCHF) | Gujarat, Rajasthan, Haryana | 🕷️ Ticks; contact with livestock | Zoonotic; nosocomial transmission possible |
| Hantavirus (sporadic) | Isolated reports | 🐀 Rodents | Renal and/or respiratory involvement |
| Nipah virus (imported) | Kerala | 🦇 Bats; human-to-human transmission | Rare but ↑ CFR; outbreaks in 2018 & 2021 |
Viral entry & replication: Infects endothelial cells, macrophages, and dendritic cells → systemic dissemination.
Immune dysregulation:
Excessive cytokine release (“cytokine storm”)
Leads to capillary leak, coagulopathy, shock
Endothelial damage:
↑ Vascular permeability → haemorrhage, hypovolaemia
Multisystem involvement:
Affects liver, kidneys, CNS
Can lead to encephalitis, renal failure, DIC (Disseminated Intravascular Coagulation)
Acute onset: Typically within 2–10 days post-exposure
Non-specific symptoms (mimic flu/malaria):
↑ Fever (universal)
Fatigue, malaise
Headache
Severe myalgia (muscle pain)
Arthralgia (joint pain)
🧩 Challenge: Hard to distinguish from common febrile illnesses early on
| System | Symptoms | Notes |
|---|---|---|
| Gastrointestinal | Nausea, vomiting, abdominal pain, diarrhoea | Common during the progression phase |
| Respiratory | Cough, dyspnoea | Variable; more prominent in hantavirus & arenavirus infections |
| Neurological | Confusion, lethargy, seizures | ↑ Incidence in severe filovirus infections (Ebola, Marburg) |
| Mucosal Bleeding | Epistaxis, gum bleeding, conjunctival haemorrhage | Classical feature of bleeding diathesis |
| Skin | Petechiae, purpura, ecchymoses | Suggests platelet dysfunction or capillary leak |
| GI Bleeding | Melena, haematemesis | ↑ Risk of hypovolaemic shock |
| Shock | ↓ BP, ↑ HCT, poor perfusion | Result of vascular leak and fluid loss |
| Multi-organ Dysfunction |
Liver: ↑ AST/ALT, jaundice Kidneys: ↓ urine output, AKI CNS: Encephalopathy, AMS |
Markers of severe disease; often fatal if unmanaged |
| Coagulopathy / DIC | ↑ PT/aPTT, ↓ platelets, spontaneous bleeding | Classical DIC profile; poor prognostic sign |
🔍 Note: Not all VHFs show bleeding.
🦟 Example: Dengue Haemorrhagic Fever presents more often with bleeding than Ebola or Marburg virus disease.
Diagnosis depends on:
Suspected virus
Stage of illness
Epidemiological exposure
Begin with detailed history:
Recent travel to endemic areas
Exposure to animals, arthropod vectors, or infected individuals.
| Category | Test | Use & Comments |
|---|---|---|
| Serological Tests | IgM / IgG ELISA (Enzyme-Linked Immunosorbent Assay) |
Detects virus-specific antibodies; used for dengue, KFD, CCHF, Lassa fever. Timing critical – early testing may yield false negatives (IgM usually positive after day 5). Can help identify recent (IgM) vs past infection (IgG). |
| Neutralization Tests |
Confirmatory test for Lassa and others; differentiates closely related viruses. Slower and more complex; used in reference labs. |
|
| Advanced Serology (Recombinant Antigen-based) |
In development; uses synthetic viral proteins to ↑ specificity. Potential to reduce cross-reactivity. |
|
| Molecular Techniques | RT-PCR (Reverse Transcription Polymerase Chain Reaction) |
Gold standard for early detection; detects viral RNA in blood/tissues. Useful in first 5–7 days; highly sensitive and specific. Requires cold chain, skilled handling. |
| Multiplex PCR Panels |
Detect multiple VHFs (e.g., dengue, Ebola, CCHF) simultaneously. Useful in outbreaks or syndromic diagnosis. |
|
| Metagenomic Sequencing |
Identifies known and unknown viruses; useful when conventional tests are inconclusive. Resource-intensive; emerging use in outbreak investigations. |
|
| Antigen Tests | NS1 Antigen (Dengue) |
Detectable from day 1–5 of illness; rapid and widely available. Good for early diagnosis before antibody formation. |
| Virology | Virus Isolation |
Gold standard but rarely used due to biosafety needs (BSL‑4 lab). Slow; requires high-level containment. |
🔍 Clinical Tip: Begin with high suspicion based on symptoms + travel/exposure history. Use RT-PCR early, and confirm with serology if needed.
🩺 Nonspecific Early Symptoms
VHFs often mimic malaria, typhoid, influenza, or leptospirosis
Symptoms like fever, myalgia, headache, and GI upset can delay recognition, especially in non-endemic areas
(Choi et al., 2018)
⏱️ Timing of Sample Collection
Diagnostic accuracy depends heavily on when samples are collected:
Too early: Serological tests (IgM/IgG) may be negative
Too late: RT-PCR may miss the viral RNA phase
Ideal testing windows vary by virus but are typically within first 5–7 days for molecular tests
(Iani et al., 2024)
⚕️ Limited Access to Advanced Diagnostics
RT-PCR and sequencing require specialist labs, often unavailable in rural or resource-limited settings
Transport delays can degrade sample integrity
🌐 Cross-reactivity in Serology
Serological tests may yield false positives due to overlapping antigens across VHF viruses
Confirmatory testing with neutralization assays or RT-PCR is essential.
Recognise key symptoms: sudden fever, myalgia, GI distress, bleeding
Take thorough exposure/travel history
Initiate prompt serology / RT-PCR testing
Hydration & electrolyte management
Antipyretics & analgesia for symptom relief
Transfusions in cases of bleeding or shock
Monitor for:
Capillary leak syndrome
Thrombocytopenia
Coagulopathy (↑ PT/aPTT, ↓ platelets)
Isolate suspected cases
Use PPE and barrier nursing
Train staff in standard & contact precautions
Notify public health authorities of suspected/confirmed cases
Contribute to outbreak tracking and early warning systems
Educate on vector control (e.g. ticks, mosquitoes)
Promote safe animal handling practices
Raise awareness of early symptom recognition
Stay updated with:
New diagnostic methods
Updated guidelines & research
Participate in CPD (continuing professional development) on emerging VHFs
Aydın, M., & Aydın, N. (2025). Crimean-Congo hemorrhagic fever with severe bradycardia treated with theophylline. Revista Da Sociedade Brasileira De Medicina Tropical, 58. https://doi.org/10.1590/0037-8682-0416-2024
Baize, S., et al. (2020). Clinical features and pathogenesis of the 2014 Ebola virus outbreak. New England Journal of Medicine.
Basler, C. (2017). Molecular pathogenesis of viral hemorrhagic fever. Seminars in Immunopathology, 39(5), 551–561. https://doi.org/10.1007/s00281-017-0637-x
Bausch, D.G., et al. (2023). Hemorrhagic fever viruses in the Central African Republic. Transactions of the Royal Society of Tropical Medicine and Hygiene.
Choi, M., Worku, S., Knust, B., Vang, A., Lynfield, R., Mount, M., … & DeVries, A. (2018). A case of Lassa fever diagnosed at a community hospital—Minnesota 2014. Open Forum Infectious Diseases, 5(7). https://doi.org/10.1093/ofid/ofy131
Connolly, A., Whitaker, H., Klingström, J., & Ahlm, C. (2017). Risk of venous thromboembolism following hemorrhagic fever with renal syndrome: a self-controlled case series study. Clinical Infectious Diseases, 66(2), 268–273. https://doi.org/10.1093/cid/cix777
Dell'Acqua, F., et al. (2022). Multi-organ dysfunction in Ebola virus disease: a systematic review. Critical Care.
Flórez‐Álvarez, L., Souza, E., Botosso, V., Oliveira, D., Ho, P., Taborda, C., … & Durigon, E. (2022). Hemorrhagic fever viruses: pathogenesis, therapeutics, and emerging and re-emerging potential. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.1040093
Fukushi, S., Tani, H., Yoshikawa, T., Saijo, M., & Morikawa, S. (2012). Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers. Viruses, 4(10), 2097–2114. https://doi.org/10.3390/v4102097
Garrison, C., et al. (2021). Severe manifestations of dengue fever. The Journal of Infectious Diseases.
Ghazaei, C. (2023). The role of endothelial cell dysfunction in hemorrhagic fevers. International Journal of Basic Science in Medicine, 8(2), 84–91. https://doi.org/10.34172/ijbsm.29634
Hutin, Y.J.F., et al. (2023). Ebola virus disease: the importance of rapid diagnosis and case management. Transfusion Medicine Reviews.
Iani, F., Campos, G., Adelino, T., Silva, A., Kashima, S., Alcântara, L., … & Slavov, S. (2024). Metagenomic analysis for diagnosis of hemorrhagic fever in Minas Gerais, Brazil. Microorganisms, 12(4), 769. https://doi.org/10.3390/microorganisms12040769
Iannetta, M., Di, A., Nicastri, E., Vairo, F., Masanja, H., Kobinger, G., … & Ippolito, G. (2019). Viral hemorrhagic fevers other than Ebola and Lassa. Infectious Disease Clinics of North America, 33(4), 977–1002. https://doi.org/10.1016/j.idc.2019.08.003
Iba, T., Levy, J., & Levi, M. (2021). Viral-induced inflammatory coagulation disorders: preparing for another epidemic. Thrombosis and Haemostasis, 122(01), 008–019. https://doi.org/10.1055/a-1562-7599
Iba, T., et al. (2023). Pathophysiology of coagulopathy in viral hemorrhagic fevers. Critical Care.
Johnson, K.M., et al. (2014). Pathogenesis of viral hemorrhagic fevers. Annual Review of Microbiology.
Kanda, K., Kinoshita, N., Kutsuna, S., Nakamura, K., Okuhama, A., Shimomura, A., … & Ohmagari, N. (2021). Residual and late onset symptoms in severe fever with thrombocytopenia syndrome. Viruses, 13(4), 657. https://doi.org/10.3390/v13040657
Kared, H., et al. (2023). Viral hemorrhagic fevers: Overview of pathogenesis and clinical manifestations. Infectious Disease Clinics of North America.
Ksiazek, T.G., et al. (2005). Clinical features of viral hemorrhagic fevers. Emerging Infectious Diseases.
Lahariya, C., Goel, M., Kumar, A., Puri, M., & Sodhi, A. (2012). Emergence of viral hemorrhagic fevers. Journal of Postgraduate Medicine, 58(1), 39–46. https://doi.org/10.4103/0022-3859.93251
Mukhtar, A., et al. (2009). Hemorrhagic manifestations in Ebola and Marburg virus infections. Virology Journal.
Oestereich, L., et al. (2021). Laboratory diagnosis and monitoring of viral hemorrhagic fevers. Clinical Microbiology and Infection.
Paessler, S., & Walker, D. (2013). Pathogenesis of the viral hemorrhagic fevers. Annual Review of Pathology: Mechanisms of Disease, 8(1), 411–440. https://doi.org/10.1146/annurev-pathol-020712-164041
Peters, C.J., et al. (2021). Current perspectives on the zoonotic and viral hemorrhagic fevers. Clinical Microbiology Reviews.
Rugarabamu, S., & Neel, G. (2023). Global preparedness and response strategies for emerging viral hemorrhagic fevers: Lessons from past outbreaks. Epidemiology and Public Health, 1(1). https://doi.org/10.52768/epidemiolpublichealth/1010
Rugarabamu, S., Rumisha, S., Mwanyika, G., Sindato, C., Lim, H., Misinzo, G., … & Mboera, L. (2022). Viral haemorrhagic fevers and malaria co-infections among febrile patients in Tanzania. Infectious Diseases of Poverty, 11(1). https://doi.org/10.1186/s40249-022-00959-z
Schmid, S., et al. (2022). Clinical features and management of viral hemorrhagic fever. Current Opinion in Infectious Diseases.
Srivastav, Y., Kumar, A., Singh, J., Srivastav, A., & Ahmad, M. (2024). Management of viral hemorrhagic fever: Pathogenesis to treatment. Asian Journal of Research in Infectious Diseases, 15(3), 17–25. https://doi.org/10.9734/ajrid/2024/v15i3334
Zapata, J., Cox, D., & Salvato, M. (2014). The role of platelets in the pathogenesis of viral hemorrhagic fevers. PLOS Neglected Tropical Diseases, 8(6), e2858. https://doi.org/10.1371/journal.pntd.0002858
