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  • More than 20 RNA viruses within four families (Flaviviridae, Arenaviridae, Filoviridae, and Bunyaviridae) cause viral hemorrhagic fevers (VHFs).

  • The prevalent VHFs are dengue HF, yellow fever (YF), Lassa fever (LF), Rift Valley fever (RVF), and hemorrhagic fever with renal syndrome (HFRS).

  • Emerging VHFs include Chapare, Lujo, Alkhurma, severe fever with thrombocytopenia syndrome (SFTS), and novel hantaviruses.

  • Hantaviruses cause HFRS in the Old World and hantavirus cardiopulmonary syndrome (HCPS) in the New World. HCPS manifests as low-pressure pulmonary edema, pleural effusions, and cardiogenic shock, but not VHF.

  • Mosquitoes are the vector of dengue, YF, and RVF.

  • Ticks are the vector of Crimean-Congo HF (CCHF), Omsk HF (OHF), Kyasanur forest disease (KFD), Alkhurma HF, and SFTS.

  • Arenaviruses and hantaviruses are rodent-borne zoonoses.

  • Exposure to domestic animals is a major mode of infection in RVF and CCHF.

  • RVF causes simultaneous epizootics in animals and large epidemics in humans.

  • Dengue and Seoul hantavirus are urban infections. YF is endemic in jungles and African savannas, but also causes urban epidemics. The other VHFs are rural infections because of the distribution of ticks and rodent or bat reservoirs.

  • Nosocomial infections are a feature of CCHF, filoviruses, arenaviruses, Andes hantavirus, and SFTS bunyavirus. This risk is high when standard precautions for blood-borne pathogens are not followed. Attempting viral isolation requires high biosafety level precautions (BSL 3 or 4 for most VHF pathogens).

  • The incubation period usually is shorter than 2 weeks, but longer with hantaviruses. The onset of illness usually is sudden, but insidious with arenaviruses.

  • Clues to dengue fever are urban acquisition, break-bone fever, rash, hemoconcentration, and thrombocytopenia. Danger signs for dengue HF include abdominal pain, persistent vomiting, effusions, mucosal bleed, lethargy, restlessness, liver enlargement, hemoconcentration, and severe thrombocytopenia.

  • YF vaccine–associated viscerotropic disease (YEL-AVD) is encountered only rarely in recipients who are older or have abnormal thymus function.

  • Clues to LF are insidious onset, sore throat, chest pain, cervicofacial edema, high maternal mortality and fetal loss during pregnancy, and irreversible deafness.

  • Clues to filovirus (Marburg and Ebola) infections are a rash around the fifth day, severe bleeding, jaundice, person-to-person transmission in community outbreaks and nosocomial settings, and a very high mortality rate.

  • A delayed-onset rash is characteristic of dengue, filoviruses, and LF.

  • Jaundice and liver failure are typical of YF, CCHF, RVF, and filovirus HF.

  • Bleeding is often severe with CCHF, filoviruses, South American VHFs, and Hantaan virus–associated HFRS, but only rarely so in dengue and LF.

  • Neurological complications are seen in South American HF, KFD, Alkhurma HF, and a small minority of RVF virus infection.

  • Acute kidney injury is typical in HFRS and YF, and also seen in HCPS.

  • Ribavirin is proven effective in Lassa fever and HFRS, and may be effective in South American HF and CCHF.


Viral hemorrhagic fever (VHF) starts with a nonspecific febrile prodrome associated with protean manifestations, followed by widespread endovascular insult, viral immunosuppression, multiorgan damage, hemorrhagic complications, and shock. The ...

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