Arboviruses, Rabies & Hemorrhagic Fever Viruses

Flaviviruses: dengue, yellow fever, West Nile, Zika

The family. "Arbovirus" names a route (arthropod-borne), not a family. Flaviviridae are enveloped, icosahedral viruses whose positive-sense ssRNA is translated directly into one polyprotein. Aedes carries dengue, yellow fever, and Zika; Culex carries West Nile and St. Louis encephalitis. Hepatitis C is a flavivirus spread by blood instead.

Dengue. Day-biting Aedes aegypti spreads four serotypes (DENV-1 to -4) in tropical cities. Expect abrupt high fever, retro-orbital headache, severe myalgia and arthralgia ("breakbone fever"), rash, leukopenia, and thrombocytopenia. The tourniquet test is positive with ≥10 petechiae per square inch after 5 minutes of cuff inflation. Use acetaminophen for fever; aspirin and NSAIDs worsen bleeding.

Severe dengue. Immunity is serotype-specific. With a second, different serotype, cross-reactive non-neutralizing IgG delivers virus into Fc receptor–bearing monocytes and macrophages (antibody-dependent enhancement), boosting viral load and cytokines. Around defervescence capillaries leak: rising hematocrit with falling platelets, effusions, ascites, bleeding, and shock. Care is supportive with careful fluids.

The same mechanism is why the first licensed dengue vaccine is reserved for people with proven past infection: in a seronegative recipient it acts as a "first infection."

Yellow fever. Tropical Africa and South America, with a monkey–forest mosquito jungle cycle and an Aedes urban cycle. Fever with relative bradycardia (Faget sign) may be followed, after a brief remission, by a toxic phase: jaundice, hematemesis ("black vomit"), bleeding, and AKI. The liver shows midzonal (zone 2) necrosis with Councilman bodies (eosinophilic apoptotic hepatocytes). One dose of the live, egg-grown 17D vaccine protects most people for life; avoid it under 6 months of age and in pregnancy, immunosuppression, thymus disease, or severe egg allergy.

West Nile virus. Culex mosquitoes and birds (dead crows are a clue) maintain the virus; humans and horses are dead-end hosts. It is the leading US arboviral encephalitis, peaking in late summer. About 80% of infections are silent and under 1% neuroinvasive — meningitis, encephalitis, or polio-like asymmetric flaccid paralysis (anterior horn cells) — mostly in older or immunosuppressed adults. Transfusion and transplant can transmit it; diagnose with IgM in CSF or serum.

Zika virus. Aedes-borne, but also sexual, vertical, and transfusion-transmitted; RNA persists in semen for months. Usually mild: low fever, pruritic maculopapular rash, nonpurulent conjunctivitis, arthralgia. Complications: Guillain-Barré syndrome and congenital Zika syndrome (severe microcephaly, subcortical calcifications, eye lesions, contractures).

Alphaviruses and rubella

Chikungunya. An Aedes-borne alphavirus (Togaviridae; enveloped, positive-sense ssRNA) that often co-circulates with dengue. Abrupt high fever brings severe, symmetric polyarthralgia of the hands, wrists, and ankles that can last months to years. Lymphopenia is common, while thrombocytopenia, bleeding, and shock are far less prominent than in dengue.

EEE and WEE. These alphaviruses cycle between birds and mosquitoes, with horses and humans as dead-end hosts, and cause summer encephalitis. EEE is the deadliest US arboviral encephalitis (about 30% fatal), and survivors often keep deficits.

Rubella. Formerly a togavirus, now in Matonaviridae; enveloped positive-sense RNA spread by droplets. It causes mild "3-day measles": low fever, tender postauricular, suboccipital, and posterior cervical nodes, and a fine pink rash moving from face to trunk and fading in about 3 days, sometimes with soft-palate petechiae (Forchheimer spots). Arthralgia or arthritis affects mainly adult women. Early-pregnancy infection causes congenital rubella (cataracts, sensorineural deafness, PDA); MMR is live, so vaccinate before pregnancy, never during.

Rash plus arthralgia in a young woman: postauricular and suboccipital nodes favor rubella over parvovirus B19.

Rodent-borne viruses: hantaviruses and arenaviruses

Hantavirus pulmonary syndrome. Hantaviruses (Bunyavirales; enveloped, segmented negative-sense RNA) are rodent-borne, not arthropod-borne. Sin Nombre virus is inhaled from deer mouse urine and feces, classically while sweeping out a closed cabin or shed in the US Southwest. A flu-like prodrome gives way abruptly to noncardiogenic pulmonary edema and shock. Lab triad: thrombocytopenia, hemoconcentration (rising hematocrit), and leukocytosis with immunoblasts. Care is supportive, sometimes with ECMO; over a third of patients die.

Hemorrhagic fever with renal syndrome. Old World hantaviruses — Hantaan (East Asia) and Puumala (Europe; the milder nephropathia epidemica), from field mice and voles — cause fever, petechiae, and hypotension, then AKI with proteinuria and oliguria, followed by polyuria.

Arenaviruses. Enveloped viruses with two ambisense RNA segments; host ribosomes give virions a sandy look (arena, "sand"). Lassa fever (West Africa) comes from Mastomys rat excreta and also spreads through body fluids, including in hospitals: fever, pharyngitis, facial edema, bleeding, shock, and deafness in survivors; early IV ribavirin helps. LCMV (house mice, pet hamsters) causes aseptic meningitis and, in pregnancy, fetal chorioretinitis and hydrocephalus.

Filoviruses: Ebola and Marburg

Spread and illness. Filamentous, enveloped negative-sense ssRNA viruses with a fruit-bat reservoir. After spillover they spread by contact with blood and body fluids of patients or corpses (caregivers, health workers, burials). After an incubation of 2–21 days come fever and myalgia, then profuse vomiting and diarrhea, bleeding, DIC, and shock; case fatality is about 25–90%. Strict contact and droplet precautions with full protective equipment are required.

Rabies

Virus and reservoirs. A bullet-shaped, enveloped negative-sense rhabdovirus. US human cases come mostly from bats (bites often unnoticed), plus raccoons, skunks, and foxes; worldwide, dogs cause nearly all deaths.

Pathogenesis. After replicating in muscle at the bite, the virus binds the nicotinic ACh receptor at the neuromuscular junction and rides retrograde, dynein-driven axonal transport to the CNS, then spreads outward to the salivary glands. Incubation (usually 1–3 months) is shorter for head and neck bites. Inside nerves the virus is hidden from antibody, so prophylaxis must precede symptoms.

Clinical course and pathology. Fever and pain or paresthesia at the healed bite precede furious encephalitis: agitation, hydrophobia and aerophobia (painful pharyngeal spasms), hypersalivation, and autonomic instability, then paralysis, coma, and death — nearly 100% fatal once symptomatic. About one-fifth have a paralytic form resembling Guillain-Barré. Negri bodies (eosinophilic cytoplasmic inclusions) sit in Purkinje and hippocampal neurons. Antemortem tests: nuchal skin biopsy, saliva RT-PCR, serum and CSF antibodies.

Who needs PEP. Any bite, scratch, or saliva contact with a wound or mucosa, and a bat found in the room of a sleeper, unattended child, or intoxicated adult unless the bat tests negative. A healthy biting dog, cat, or ferret can be observed for 10 days instead.

Immune globulin gives antibody at once while the killed vaccine needs 1–2 weeks to induce the patient's own; inject them at separate sites so the globulin does not blunt the vaccine.