Dengue, Chikungunya, Japanese Encephalitis and Kyasanur Forest Disease — Vectors, Clinical Course and Diagnosis

Arboviruses are arthropod-borne viruses. Four dominate Indian medical examinations because all four circulate in India and each has a distinctive vector, host and clinical hook: dengue, chikungunya, Japanese encephalitis (JE) and Kyasanur Forest disease (KFD). Examiners rarely ask for mechanisms in isolation; they ask you to match the vector, the classic feature and the preferred test or vaccine.

Dengue virus (DENV) is a single-stranded positive-sense RNA virus of the genus Flavivirus with four antigenically distinct serotypes (DENV-1 to DENV-4). It is transmitted by the bite of infected female Aedes mosquitoes, most importantly Aedes aegypti, which thrive in urban and peri-urban settings. The incubation period is 4 to 10 days. Rare routes include perinatal transmission, blood transfusion and organ transplantation.

Infection with one serotype gives long-lasting immunity to that serotype only. A later infection with a different serotype (secondary heterologous infection) carries a higher risk of severe disease because sub-neutralising antibodies can enhance viral entry into Fc-receptor-bearing cells — antibody-dependent enhancement (ADE).

The hallmark of severe dengue is transient but profound plasma leakage from increased capillary permeability — functional endothelial dysfunction rather than direct endothelial destruction. The secreted viral NS1 protein damages the endothelial glycocalyx, activates Toll-like receptor 4 and promotes complement-mediated injury. Leakage peaks in the critical phase, which coincides with defervescence and falling viraemia.

Dengue follows a triphasic course: a febrile phase (abrupt high fever, headache, myalgia, arthralgia, rash, leukopenia, thrombocytopenia), a critical phase (plasma leakage) and a recovery phase (reabsorption of leaked fluid). Severity is graded by the WHO 2009 classification.

• Tourniquet test is positive when there are 10 or more petechiae per 2.5 cm (1 inch) square after 5 minutes at a cuff pressure midway between systolic and diastolic.
• Plasma leakage shows as haemoconcentration (raised haematocrit), pleural effusion, ascites and gallbladder-wall oedema on ultrasound.
• Most dengue infections are mild or asymptomatic; roughly 2 to 5% of symptomatic cases progress to severe dengue.

Test choice depends on day of illness. In the first week, RT-PCR (typically positive in the first 5 days) or NS1 antigen (detectable from day 1, up to about day 5 to 9) is used; NS1 sensitivity is above 90% in primary infection but about 60 to 80% in secondary infection. IgM can be detected from about day 4, and IgM seroconversion between paired samples confirms infection. Serology after day 5 to 6 is more informative but cross-reacts with other flaviviruses.

There is no specific antiviral. Management is supportive and centres on judicious fluid therapy: oral rehydration for mild leakage, and isotonic crystalloid (normal saline or Ringer's lactate) when there is established volume depletion or the patient cannot drink. Hypotonic fluids are avoided. Haematocrit and platelet trends guide therapy, but haematocrit must be read in context — dehydration raises it and bleeding lowers it.

• Fever and myalgia: paracetamol (acetaminophen); avoid aspirin and NSAIDs because of bleeding risk.
• Prophylactic platelet transfusion is not recommended in the absence of significant bleeding, even with profound thrombocytopenia.
• Significant bleeding with shock and an inappropriately low haematocrit may need blood transfusion.
• Discharge only when well, beyond the critical period, haemodynamically stable and generally afebrile for at least 24 hours with a stable haematocrit.

Chikungunya virus (CHIKV) is an RNA virus of the alphavirus genus, family *Togaviridae*. It was first identified in Tanzania in 1952; urban outbreaks were recorded in India in the 1970s. The name derives from a Kimakonde word meaning 'that which bends up', describing the stooped posture of patients with severe joint pain. It is carried by the same Aedes aegypti and Aedes albopictus mosquitoes, which bite mainly in daylight.

Onset is typically 4 to 8 days (range 2 to 12) after the bite, with abrupt fever and severe joint pain that is often debilitating and may last weeks, months or even years. Other features are joint swelling, myalgia, headache, nausea, fatigue and rash. Eye, heart and neurological complications are occasionally reported, and newborns infected at delivery and older people with comorbidities are at higher risk of severe disease.

JE virus is a mosquito-borne flavivirus and an important cause of viral encephalitis in Asia. It is transmitted by Culex mosquitoes, mainly *Culex tritaeniorhynchus*, in a cycle that involves pigs and water (wading) birds as amplifying hosts. Humans are dead-end hosts: they do not develop enough viraemia to infect feeding mosquitoes. Disease is concentrated in rural and peri-urban areas near rice fields and pig farms, and mainly affects children; most adults in endemic areas have natural immunity.

• Incubation 4 to 14 days. Most infections are mild or silent; about 1 in 250 infections causes severe illness.
• Severe disease: rapid-onset high fever, headache, neck stiffness, disorientation, coma, seizures and spastic paralysis. Children may first have abdominal pain and vomiting; seizures are commoner in children, headache and meningism in adults.
• Movement disorders such as dystonia and choreoathetoid movements can develop.
• Imaging: MRI or CT may show bilateral thalamic oedema, lesions or haemorrhage.
• CSF: raised opening pressure and protein with normal glucose.
• Case fatality can be as high as about 30% among those with symptoms, and 20 to 30% of survivors have permanent cognitive, behavioural or neurological sequelae.

Diagnosis: WHO recommends testing for JEV-specific IgM antibody in a single CSF or serum sample using an IgM-capture ELISA; CSF is preferred because it reduces false positives from previous infection or vaccination. There is no antiviral — treatment is supportive. Vaccination is the control tool: India uses the live attenuated SA 14-14-2 vaccine, introduced in selected endemic districts from 2006, and reduced JE incidence in vaccinated districts.

Kyasanur Forest disease virus (KFDV) is a tick-borne flavivirus (Flaviviridae, genus Orthoflavivirus). The hard tick *Haemaphysalis spinigera* is the reservoir and the most important vector; the virus passes through generations of ticks trans-ovarially. Monkeys and small mammals such as rodents are hosts, and monkey deaths in the forest are the sentinel event. Humans become infected through tick bites or contact with a sick or recently dead monkey; no person-to-person transmission is described. People who enter the forest for firewood, farming or charcoal making are at risk.

• Geography: from 1957 to 2012 activity was limited to five Karnataka districts (Shimoga, Chikmagalur, Uttara Kannada, Dakshina Kannada, Udupi); later cases were reported from Tamil Nadu (Nilgiris), Kerala (Wayanad and neighbouring districts), Goa and Maharashtra — the Western Ghats. More cases occur in the drier months (November to June).
• Incubation 3 to 8 days. First phase: sudden fever, chills, headache, severe body pain (neck, back, limbs), conjunctival congestion, haemorrhagic manifestations from about day 3 to 4.
• Second (neurological) phase in up to about 20% of patients: recurrent fever for 12 to 14 days with drowsiness, disorientation, confusion and occasionally convulsions.
• Case fatality about 2 to 10%. Convalescence is prolonged.
• Laboratory: leucopenia and thrombocytopenia are common; diagnosis is by RT-PCR and IgM/IgG ELISA (cross-reactivity among flaviviruses must be remembered). Work with the live virus needs high biosafety containment.

There is no specific antiviral drug; treatment is supportive with hydration, and blood products as needed. Prevention relies on tick-bite avoidance (DEET, protective clothing), tick control, and a formalin-inactivated tissue-culture vaccine used in endemic areas of Karnataka since 1990 (two doses a month apart and a booster at 6 to 9 months). Its efficacy is modest — about 62% after two doses and about 83% with the booster — so repeated boosters are advised.

• Dengue is not an antiviral-responsive disease and platelet count alone does not decide transfusion.
• Chikungunya is rarely fatal; the exam hook is chronic arthralgia.
• JE's reservoir/amplifier question and the dead-end host concept are tested repeatedly.
• KFD is a tick-borne flavivirus, not a mosquito-borne disease — easy to miss in a vector-matching question.

• Vector matching — dengue/chikungunya with Aedes, JE with Culex, KFD with Haemaphysalis ticks.
• Phase and warning signs — which finding is a warning sign, and what the critical phase means for fluid therapy.
• Test by day of illness — NS1 or RT-PCR early, IgM later, and the paired-sample rule.
• Drug to avoid — aspirin and NSAIDs in suspected dengue.
• Reservoir and host — pig as the JE amplifier; monkey as the KFD sentinel host.
• Vaccines — Dengvaxia restricted to seropositive children aged 9 to 16 years; SA 14-14-2 for JE; formalin-inactivated KFD vaccine.