Dengue Fever and Viral Haemorrhagic Fever

VHF as a Category

Syndrome (fever+bleeding±shock±MOF), NOT single disease. Grouped by vector/reservoir:

• Arboviral: dengue, chikungunya, yellow fever, KFD
• Filoviral: Ebola, Marburg (direct contact, MOST LETHAL)
• Hantaviral/arenaviral: Hantavirus, Lassa fever (rodent-transmitted)

Dengue = most significant by case burden.

Dengue

Flavivirus, 4 serotypes (DENV-1-4). 1st infection = lifelong serotype-specific immunity + brief cross-protection. 2nd infection, DIFFERENT serotype = STRONGEST risk factor for severe dengue.

Transmission: Aedes aegypti (principal, day-biting, urban, clean-water containers), A. albopictus (secondary).

Pathogenesis: ADE (Antibody-Dependent Enhancement) — pre-existing non-neutralizing Ab (1st infection) binds new serotype without neutralizing → ↑uptake by Fc-receptor monocytes/macrophages → ↑viral replication (paradox) → cytokine storm → endothelial damage → PLASMA LEAKAGE.

Clinical: Classic dengue fever: high fever, severe headache, retro-orbital pain, myalgia/arthralgia (“breakbone fever”), maculopapular rash. Self-limited.

Severe dengue (DHF/DSS): CRITICAL PHASE at DEFERVESCENCE (day 3-7) — fever falls but plasma leakage/thrombocytopenia/hemorrhage (petechiae, mucosal bleed, +tourniquet test) appear/worsen. KEY POINT: danger period = fever RESOLVING, not peaking (misleads clinicians). Uncontrolled leakage → hypovolemic shock (DSS), ↑mortality without prompt fluids.

Laboratory Diagnosis

NS1 antigen: day 1-5/7, preferred EARLY test. IgM ELISA: positive ~day5+, weeks-months (recent infection). IgG ELISA: later rise, persists years. Secondary infection = EARLIER/SHARPER IgG rise, proportionally LOWER IgM (distinguishes 1° vs 2°). RT-PCR: direct RNA + serotyping, first few days. Supportive: thrombocytopenia + rising hematocrit (hemoconcentration = plasma leakage marker, serial tracking in critical phase).

Management

NO specific antiviral. Supportive: careful fluid management (avoid under- AND over-resuscitation), platelet transfusion ONLY for significant bleeding (not thrombocytopenia alone), close critical-phase monitoring. AVOID aspirin/NSAIDs (bleeding risk).

Prevention

Vector control (eliminate Aedes breeding — standing water). Vaccine (Dengvaxia): ONLY for confirmed PRIOR dengue infection — ADE mechanism means vaccinating dengue-naive person ↑severe dengue risk on subsequent infection.

Other VHF Agents (Brief)

Chikungunya: Aedes-transmitted, prolonged POLYARTHRALGIA (key distinguisher from dengue), rarely hemorrhagic/fatal.

Yellow fever: flavivirus, Aedes(urban)/forest mosquito(sylvatic, monkey reservoir). Africa+S.America (NOT Asia). Fever+jaundice+hemorrhage (severe form). Highly effective live-attenuated vaccine — REQUIRED for travel under IHR.

Kyasanur Forest Disease: tick-borne flavivirus, Karnataka India. Monkey die-off = early warning signal. Fever+hemorrhage±neuro involvement.

Ebola/Marburg (filoviruses): DIRECT CONTACT (blood/fluids/fomites, NOT insect vector). Reservoir: fruit bats. MOST SEVERE VHF, case-fatality 25-90%. Strict contact/droplet isolation. Ebola: effective vaccine (rVSV-ZEBOV) + monoclonal Ab therapy now available.

Lassa fever: arenavirus, West Africa. Rodent excreta (Mastomys rat) or person-to-person (body fluids). Typically MILDER than filoviral VHF, can be severe esp. pregnancy.

Hantavirus: inhaled aerosolized rodent excreta. HFRS (hemorrhagic fever+renal syndrome, Asia/Europe) OR Hantavirus pulmonary syndrome (Americas).

Viral Haemorrhagic Fever as a Category

Viral haemorrhagic fever (VHF) is not a single disease but a clinical syndrome — fever plus a bleeding tendency, sometimes progressing to shock and multi-organ failure — produced by several unrelated RNA virus families that share a tropism for vascular endothelium. Because the underlying viruses differ enormously in transmission route and lethality, VHF agents are grouped by vector/reservoir rather than taxonomy: arboviral (dengue, chikungunya, yellow fever, Kyasanur Forest disease — arthropod-transmitted), filoviral (Ebola, Marburg — direct contact-transmitted, the most lethal group), and hantaviral/arenaviral (Hantavirus, Lassa fever — rodent-transmitted). Dengue is by far the most globally significant of these by case burden, and is covered here in detail; the others are outlined more briefly.

Dengue

The Virus

Dengue virus is a flavivirus with four distinct serotypes (DENV-1 through DENV-4) — a fact with real clinical weight, since infection with one serotype gives lifelong immunity to that serotype but only brief cross-protection against the others, and a second infection with a different serotype is the single strongest known risk factor for severe dengue (see pathogenesis below).

Transmission

Dengue is transmitted by the bite of an infected female Aedes aegypti mosquito (the principal vector, a day-biting, urban/peri-urban species breeding in small clean-water containers), with Aedes albopictus as a secondary vector in some regions. Humans are the main amplifying host in the urban transmission cycle.

Pathogenesis

Primary infection typically causes classic dengue fever with lifelong serotype-specific immunity. The mechanism behind severe dengue on secondary heterotypic infection is antibody-dependent enhancement (ADE): pre-existing, non-neutralizing antibody from the first infection binds the new serotype without neutralizing it, and this antibody-virus complex is taken up more efficiently by Fc-receptor-bearing monocytes/macrophages, paradoxically increasing viral replication rather than blocking it. The resulting surge in viral load drives a cytokine storm that damages vascular endothelium, causing the plasma leakage that defines severe dengue.

Clinical Manifestations

Classic dengue fever presents with abrupt high fever, severe headache, retro-orbital pain, myalgia and arthralgia (historically “breakbone fever”), and a maculopapular rash — usually self-limited.

Severe dengue (dengue haemorrhagic fever/dengue shock syndrome) follows a critical phase timed around defervescence (typically days 3–7), when fever falls but plasma leakage, thrombocytopenia, and haemorrhagic manifestations (petechiae, mucosal bleeding, positive tourniquet test) can appear or worsen — a pattern worth remembering precisely, since the period of greatest danger is exactly when the fever is resolving, not when it peaks, which can mislead an unwary clinician into premature reassurance. Uncontrolled plasma leakage progresses to hypovolaemic shock (dengue shock syndrome), with case-fatality rising sharply without prompt fluid management.

Laboratory Diagnosis

Diagnostic strategy tracks illness day, since antigen and antibody appear at different points:

• NS1 antigen (a viral non-structural glycoprotein) is detectable from day 1, typically through day 5–7 of illness — the preferred early test.
• IgM ELISA becomes positive from about day 5 onward and stays positive for weeks to months (recent infection marker); IgG ELISA rises later and persists for years — the ratio and timing of IgM:IgG help distinguish primary from secondary infection (secondary infection shows an earlier, sharper IgG rise with proportionally lower IgM).
• RT-PCR detects viral RNA directly and can also serotype the infecting strain, most useful in the first few days of illness.
• Supportive findings: thrombocytopenia and a rising haematocrit (haemoconcentration from plasma leakage) — the haematocrit trend is itself a key bedside marker of plasma leakage severity, tracked serially during the critical phase.

Management

There is no specific antiviral treatment — management is entirely supportive, centred on careful fluid management (avoiding both under-resuscitation, which risks shock, and over-resuscitation, which risks fluid overload once capillary integrity is restored), platelet transfusion only for significant bleeding (not for thrombocytopenia alone), and close monitoring through the critical phase. Aspirin and NSAIDs are avoided given bleeding risk.

Prevention

Vector control (eliminating Aedes breeding sites — standing water in containers) is the mainstay. A dengue vaccine (Dengvaxia) exists but is recommended only for individuals with confirmed prior dengue infection, since — echoing the ADE mechanism above — vaccinating a dengue-naive person can itself increase the risk of severe dengue on a subsequent natural infection.

Other VHF Agents (Brief)

Chikungunya: also Aedes-transmitted, causing fever with severe, often prolonged polyarthralgia (the defining clinical feature distinguishing it from dengue), rarely haemorrhagic or fatal.

Yellow fever: a flavivirus transmitted by Aedes (urban cycle) or forest mosquitoes (sylvatic cycle, from monkey reservoirs), endemic to parts of Africa and South America (notably absent from Asia); causes fever, jaundice, and haemorrhage in its severe form; a highly effective live-attenuated vaccine exists and is required for travel to/from endemic zones under International Health Regulations.

Kyasanur Forest disease: a tick-borne flavivirus endemic to Karnataka, India, with a monkey-die-off often preceding human cases (a genuine early-warning signal), causing fever, haemorrhage, and sometimes neurological involvement.

Ebola and Marburg (filoviruses): transmitted by direct contact with infected blood/body fluids/fomites (not by insect vector), with fruit bats as the presumed natural reservoir; cause the most severe VHF syndromes, with case-fatality rates historically reaching 25–90% depending on strain and outbreak, requiring strict contact/droplet isolation precautions and, for Ebola specifically, now supported by an effective vaccine (rVSV-ZEBOV) and monoclonal antibody therapeutics.

Lassa fever: an arenavirus endemic to West Africa, transmitted via rodent excreta (the multimammate rat, Mastomys) contaminating food/household surfaces, or person-to-person via infected body fluids; typically milder than filoviral VHF but can be severe, notably in pregnancy.

Hantavirus: transmitted by inhaling aerosolized rodent excreta; presents either as haemorrhagic fever with renal syndrome (HFRS, more typical in Asia/Europe) or hantavirus pulmonary syndrome (more typical in the Americas).

Essays (4)

Long Essays (1)

Short Essays (2)

Short Notes (5)