Arboviruses & Zoonotic RNA Viruses
Microbiology · Virology · lean revision notes
Arboviruses & Zoonotic RNA Viruses
Arboviruses (arthropod-borne) are RNA viruses transmitted by haematophagous vectors (mosquitoes, ticks), while zoonotic RNA viruses such as rabies and Ebola jump from an animal reservoir to humans. For NEET PG, the highest-yield material is the vector–reservoir–diagnostic test triad: who transmits, where the virus hides between epidemics, and which test clinches the diagnosis at a given point in the illness.
Classification & overview
Arboviruses span three classical families. Knowing the family fixes genome structure and a clutch of MCQ facts.
| Family | Key genus | Genome | Important members | Vector |
|---|---|---|---|---|
| Flaviviridae | Flavivirus | (+) ssRNA, enveloped | Dengue, Japanese encephalitis (JE), Yellow fever, West Nile, Zika, Kyasanur Forest Disease | Aedes, Culex, ticks |
| Togaviridae | Alphavirus | (+) ssRNA, enveloped | Chikungunya, Eastern/Western/Venezuelan equine encephalitis | Aedes |
| Bunyavirales (Peribunyaviridae, Phenuiviridae, Nairoviridae, Hantaviridae) | multiple | (−) ssRNA, 3 segments (L, M, S), enveloped | Crimean–Congo HF, Rift Valley fever, Sandfly fever, Hantavirus, severe fever with thrombocytopenia syndrome | ticks, sandflies, mosquitoes, rodents |
The two zoonotic RNA viruses that complete this topic are:
- Rabies — Rhabdoviridae, genus Lyssavirus, (−) ssRNA, bullet-shaped, transmitted by infected animal bite (not arthropod-borne).
- Ebola/Marburg — Filoviridae, (−) ssRNA, filamentous/thread-like, zoonotic with fruit-bat reservoir.
High-yield: Flaviviruses and togaviruses (alphaviruses) are positive-sense, so their genome is directly infectious; bunyaviruses, rhabdoviruses and filoviruses are negative-sense and carry their own RNA-dependent RNA polymerase.
Dengue
Etiology & pathophysiology
Dengue virus (DENV) is a flavivirus with four serotypes (DENV 1–4). Vector is Aedes aegypti (also Aedes albopictus), a daytime biter that breeds in clean stagnant water. Infection with one serotype confers lifelong homotypic immunity but only transient heterotypic immunity.
The cornerstone concept is Antibody-Dependent Enhancement (ADE): pre-existing non-neutralising heterotypic antibodies from a prior infection bind a new serotype and ferry it into Fc-receptor-bearing macrophages, amplifying viraemia. This explains why second infection with a different serotype carries the highest risk of severe dengue (DHF/DSS). The pathological hallmark is plasma leakage from increased vascular permeability (cytokine storm, complement activation), producing haemoconcentration, effusions and shock.
Clinical features & WHO classification
Phases: Febrile → Critical (defervescence, days 3–7, when leakage and shock occur) → Recovery.
| Category | Defining features |
|---|---|
| Dengue without warning signs | Fever + 2 of: nausea/vomiting, rash, aches, leucopenia, positive tourniquet test |
| Dengue with warning signs | Abdominal pain, persistent vomiting, mucosal bleed, lethargy, liver >2 cm, rising HCT with falling platelets |
| Severe dengue | Severe plasma leakage (shock/DSS, respiratory distress), severe bleeding, severe organ involvement (AST/ALT ≥1000, myocarditis, encephalitis) |
DHF (older classification) requires all 4: fever, thrombocytopenia (<1,00,000), haemorrhagic tendency (positive tourniquet test or spontaneous bleed), and plasma leakage (HCT rise ≥20%, effusion, hypoproteinaemia). DSS = DHF + circulatory failure.
High-yield: The tourniquet (Hess) test is positive when ≥10–20 petechiae appear in a 2.5 cm × 2.5 cm (1 inch square) area after inflating the BP cuff to midway between systolic and diastolic for 5 minutes.
Diagnosis — test by timing
The single most-tested dengue concept is which test for which day.
Day 1–5 (viraemia): NS1 antigen (also RT-PCR, virus isolation) → Day 5 onward: IgM (MAC-ELISA) → Later/secondary: IgG.
| Test | Window | Note |
|---|---|---|
| NS1 antigen ELISA | Day 1–5 | Detectable even before antibodies; best early marker |
| RT-PCR / isolation | Day 1–5 | Confirmatory, viraemic phase |
| IgM MAC-ELISA | Day 5–10 onward | Indicates acute/recent infection |
| IgG | Rises late | High early IgG with low IgM = secondary infection |
High-yield: NS1 antigen is the investigation of choice in the first 5 days; IgM becomes the test of choice after day 5.
Management
Supportive — no specific antiviral. Careful fluid management is everything: isotonic crystalloids (Ringer lactate / normal saline) titrated to haematocrit and urine output. Avoid aspirin and NSAIDs (bleeding risk); use paracetamol for fever. Platelet transfusion only for active bleeding or platelets <10,000. A licensed tetravalent vaccine (Dengvaxia/CYD-TDV) is recommended only for seropositive individuals because of ADE risk in seronegatives.
Chikungunya
A togavirus (alphavirus), again transmitted by Aedes aegypti/albopictus. "Chikungunya" (Makonde) means "that which bends up" — referring to the stooped posture from arthralgia.
- Clinical triad: abrupt high fever + severe symmetrical polyarthralgia (small joints) + maculopapular rash. Arthralgia is the dominant, distinguishing feature and may persist for months (chronic arthritis).
- Thrombocytopenia is uncommon and shock is rare — useful to distinguish from dengue, which it mimics in co-endemic regions.
- Diagnosis: RT-PCR in first week (viraemia), then IgM ELISA.
- Management: symptomatic; paracetamol/NSAIDs for arthralgia (NSAIDs acceptable once dengue is excluded).
High-yield: Persistent, debilitating, symmetrical small-joint arthralgia points to chikungunya rather than dengue.
Japanese Encephalitis (JE)
The leading cause of vaccine-preventable viral encephalitis in Asia and a recurring NEET PG favourite.
- Agent: JE virus (flavivirus).
- Vector: Culex mosquito (Culex tritaeniorhynchus) — a night biter, breeds in rice paddy fields.
- Amplifying host: pigs (and ardeid wading birds such as herons/egrets). Humans and horses are dead-end hosts (insufficient viraemia to re-infect mosquitoes).
- Clinical: mostly subclinical; symptomatic cases → encephalitis with seizures, altered sensorium, extrapyramidal/parkinsonian features (basal ganglia and thalamic involvement). MRI shows bilateral thalamic lesions.
- Diagnosis: IgM-capture ELISA in CSF (or serum) is the test of choice.
- Prevention: vaccination (live attenuated SA-14-14-2), vector control, pig–human spatial separation.
High-yield: JE → Culex vector, pig amplifier, dead-end host = human, bilateral thalamic MRI lesions, CSF IgM ELISA for diagnosis.
Mnemonic — "JE PiCks the Paddy at Night": Pig amplifier, Culex vector, Paddy field breeding, Night biter.
Rabies
A nearly 100% fatal zoonotic encephalitis once symptomatic — and a guaranteed exam topic.
Virus & pathology
- Rhabdovirus, genus Lyssavirus, bullet-shaped, (−) ssRNA, single serotype.
- Five proteins: G (glycoprotein, surface spikes → neutralising antibody, neurovirulence), N (nucleoprotein → complement-fixing antibody, group-specific), L, P, M.
- Spread: centripetal — virus travels from wound along peripheral nerves to the CNS (retrograde axonal transport), then centrifugally to salivary glands, cornea, skin.
| Feature | Street virus | Fixed virus |
|---|---|---|
| Source | Wild/natural isolate | Serially passaged in rabbit brain (Pasteur) |
| Incubation | Long, variable (weeks–months) | Short, fixed (~4–6 days) |
| Negri bodies | Present | Absent (or scarce) |
| Salivary gland involvement | Yes | No |
| Use | — | Vaccine production |
High-yield: Negri bodies are eosinophilic cytoplasmic inclusions, best seen in hippocampus (Ammon's horn) and Purkinje cells of cerebellum. Babes nodules = microglial proliferation in brainstem. Pathognomonic but seen in only ~70% of cases.
Clinical features
Incubation 1–3 months (depends on bite proximity to brain — bites on the face/head have the shortest incubation). Prodrome: pain/paraesthesia at the healed bite site. Two forms:
- Furious (encephalitic) rabies (~80%): hydrophobia, aerophobia, hyperexcitability, autonomic instability, pharyngeal spasms on attempting to drink.
- Paralytic (dumb) rabies (~20%): ascending flaccid paralysis, mimics Guillain–Barré.
Diagnosis
- Antemortem: RT-PCR (saliva), direct fluorescent antibody (DFA) on skin biopsy from nape of neck (hair follicle nerves), corneal impression smear, CSF/serum antibodies.
- Postmortem (gold standard): DFA on brain tissue for rabies antigen — most sensitive/specific; demonstration of Negri bodies (Seller's stain) is supportive but less sensitive.
Post-exposure prophylaxis (PEP)
The flow every aspirant must know:
- Wash the wound immediately with soap and running water for ≥15 minutes → virucidal (most important first step).
- Apply povidone-iodine/alcohol; do not suture immediately.
- Risk categorise:
- Category I (touching/feeding, intact skin) → no PEP, wash only.
- Category II (minor scratch, no bleeding) → wound care + vaccine.
- Category III (transdermal bite, mucosal contamination, bat exposure) → wound care + vaccine + Rabies Immunoglobulin (RIG).
Vaccine schedules: Essen IM (days 0,3,7,14,28) or updated 4-dose; intradermal Updated Thai Red Cross. RIG: human RIG 20 IU/kg or equine RIG 40 IU/kg, infiltrated into and around the wound.
High-yield: Rabies vaccine is the classic example where post-exposure vaccination works because of the long incubation period. Modern cell-culture vaccines (HDCV, PCEC, PVRV) have replaced the old nervous-tissue Semple vaccine (which caused neuroparalytic complications).
Pasteur developed the first rabies vaccine (1885, Joseph Meister) using dried infected rabbit spinal cord — the origin of the "fixed virus" concept.
Ebola virus disease (EVD)
- Family Filoviridae (with Marburg); (−) ssRNA, filamentous "shepherd's crook" morphology on EM.
- Species: Zaire ebolavirus (most lethal, up to 90% mortality) and Sudan ebolavirus are the major human pathogens; also Bundibugyo, Taï Forest, Reston (non-pathogenic to humans).
- Reservoir: fruit bats (Pteropodidae); spillover via primates/bush meat. Human-to-human spread by direct contact with body fluids (blood, vomit, diarrhoea) — a major nosocomial/burial hazard.
- Clinical: viral haemorrhagic fever — fever, severe GI fluid losses, coagulopathy, multi-organ failure; the maculopapular rash around day 5 is characteristic.
- Diagnosis: RT-PCR (antigen-detection ELISA) under BSL-4 containment.
- Management: aggressive fluid/electrolyte support; monoclonal antibodies (Inmazeb [atoltivimab/maftivimab/odesivimab], Ebanga [ansuvimab]); rVSV-ZEBOV (Ervebo) vaccine for Zaire strain.
High-yield: Ebola is a BSL-4 agent; Zaire strain is the deadliest; reservoir is fruit bats; diagnosis by RT-PCR.
Comparative & key differentials
The classic exam confusion is dengue vs chikungunya, and the encephalitis viruses.
| Feature | Dengue | Chikungunya | JE |
|---|---|---|---|
| Family | Flavivirus | Alphavirus (Togavirus) | Flavivirus |
| Vector | Aedes (day) | Aedes (day) | Culex (night) |
| Hallmark | Plasma leakage, thrombocytopenia, shock | Severe persistent arthralgia | Encephalitis, thalamic lesions |
| Bleeding/shock | Prominent | Rare | Absent |
| Early test | NS1 antigen | RT-PCR | CSF IgM ELISA |
Vector–reservoir quick map:
| Virus | Vector | Reservoir/amplifier |
|---|---|---|
| Dengue / Chikungunya / Zika | Aedes aegypti | Human (urban cycle) |
| Japanese encephalitis | Culex | Pig, ardeid birds |
| Yellow fever | Aedes / Haemagogus | Monkeys (jungle cycle) |
| Kyasanur Forest Disease | Haemaphysalis tick | Monkeys, rodents |
| Rabies | None (bite) | Dogs (India), bats |
| Ebola | None (contact) | Fruit bats |
High-yield: Kyasanur Forest Disease (KFD) — a flavivirus of Karnataka, tick-borne (Haemaphysalis spinigera), monkey die-offs precede human cases; presents as haemorrhagic fever with biphasic illness. A vaccine exists.
Recently asked / exam angle
- NS1 antigen is the earliest detectable marker of dengue (positive from day 1) — repeatedly tested vs IgM (day 5+).
- Tourniquet test cut-off: ≥10 (some texts ≥20) petechiae per square inch.
- ADE explaining severe dengue in secondary heterotypic infection; Dengvaxia only for seropositives.
- JE: Culex vector, pig amplifier, human = dead-end host, bilateral thalamic MRI lesions, CSF IgM diagnosis.
- Negri bodies location (hippocampus/Purkinje cells); Babes nodules = brainstem microglial nodules.
- Street vs fixed virus differences (incubation, Negri bodies, vaccine use).
- Rabies PEP: first step = copious soap-and-water wash; RIG dose 20 IU/kg (human), 40 IU/kg (equine), infiltrated around wound; Category III needs RIG + vaccine.
- Semple vaccine = nervous-tissue vaccine causing neuroparalytic reactions; replaced by cell-culture vaccines.
- Ebola: Filovirus, Zaire most lethal, fruit-bat reservoir, BSL-4, RT-PCR diagnosis, Ervebo vaccine.
- Genome polarity: flaviviruses/alphaviruses (+) sense; bunya/rhabdo/filo (−) sense with own polymerase.
Rapid revision
- Aedes = day biter (dengue, chikungunya, Zika, yellow fever); Culex = night biter, paddy fields (JE); both flavi & alphaviruses are (+) ssRNA.
- Dengue = 4 serotypes; secondary heterotypic infection → severe dengue via ADE.
- Dengue test: NS1 day 1–5 → IgM after day 5; avoid aspirin/NSAIDs, use paracetamol.
- DHF = fever + thrombocytopenia + haemorrhage + plasma leakage (≥20% HCT rise); DSS adds shock.
- Tourniquet test positive = ≥10–20 petechiae/square inch.
- Chikungunya = crippling, persistent symmetrical small-joint arthralgia; shock/bleeding rare.
- JE: Culex vector, pig amplifier, human dead-end host, bilateral thalamic lesions, CSF IgM diagnosis, SA-14-14-2 vaccine.
- Rabies: bullet-shaped rhabdovirus; Negri bodies in hippocampus & Purkinje cells; Babes nodules in brainstem.
- Street virus = long variable incubation + Negri bodies; fixed virus = short fixed incubation, used for vaccine (Pasteur).
- Rabies PEP: wash wound first, Category III → vaccine + RIG (human 20 IU/kg, equine 40 IU/kg) into the wound; cell-culture vaccines replaced Semple.
- Ebola: filovirus, thread-like, Zaire deadliest, fruit-bat reservoir, body-fluid spread, BSL-4, RT-PCR, Ervebo (rVSV-ZEBOV) vaccine.
- KFD = tick-borne (Haemaphysalis) flavivirus of Karnataka with monkey reservoir; postmortem DFA on brain is rabies gold standard.