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INFECTIOUS AGENT

Viral hemorrhagic fevers (VHFs) are caused by several families of enveloped RNA viruses: filoviruses (Ebola and Marburg viruses), arenaviruses (Lassa fever, Lujo, Guanarito, Machupo, Junin, Sabia, and Chapare viruses), bunyaviruses (Rift Valley fever [RVF], Crimean-Congo hemorrhagic fever [CCHF], and hantaviruses), and flaviviruses (dengue, yellow fever, Omsk hemorrhagic fever, Kyasanur Forest disease, and Alkhurma viruses).

TRANSMISSION

Some VHFs are spread person to person through direct contact with symptomatic patients, body fluids, or cadavers or through inadequate infection control in a hospital setting (filoviruses, arenaviruses, CCHF virus). Zoonotic spread may occur from contact with the following:

* Livestock via slaughter or consumption of raw meat from infected animals and, potentially, unpasteurized milk (CCHF, RVF, Alkhurma viruses) * Bushmeat, likely via slaughter or consumption of infected animals (Ebola, Marburg viruses) * Rodents via inhalation of or contact with materials contaminated with rodent excreta (arenaviruses, hantaviruses) * Other reservoir species, such as bats (Ebola, Marburg viruses)

Vectorborne transmission also occurs via mosquito (RVF virus) or tick (CCHF, Omsk, Kyasanur Forest disease, Alkhurma viruses) bites or by crushing infected ticks.

EPIDEMIOLOGY

The viruses that cause VHFs are distributed over much of the globe. Each virus is associated with ?1 nonhuman host or vector species, restricting the virus and the initial contamination to the areas inhabited by these species. The diseases caused by these viruses are seen in people living in or having visited these areas. Humans are incidental hosts for these enzootic diseases; however, person-to-person transmission of some viruses can result in large human outbreaks. Specific viruses are addressed below. Ebola and Marburg: Filoviral Diseases

Ebola and Marburg viruses cause hemorrhagic fever in humans and nonhuman primates. Five species of Ebola virus have been identified: Côte d’Ivoire, Sudan, Zaire, Bundibugyo, and Reston. Countries with confirmed human cases of Ebola hemorrhagic fever include Republic of the Congo, Côte d’Ivoire, Democratic Republic of the Congo, Gabon, Sudan, and Uganda. Ebola-Reston virus is believed to be endemic in the Philippines and potentially in neighboring countries but has not been shown to cause human disease. Countries with confirmed human cases of Marburg hemorrhagic fever include Angola, Democratic Republic of the Congo, Kenya, Uganda, and possibly Zimbabwe.

Growing evidence indicates that fruit bats are the natural reservoir for filoviruses. Outbreaks occur when a person becomes infected after exposure to the reservoir species or a secondarily infected nonhuman primate and then transmits the virus to other people in the community. Four cases of Marburg hemorrhagic fever have occurred in travelers visiting caves harboring bats, including Kitum cave in Kenya and a python cave in Maramagambo Forest, Uganda. Miners have also acquired Marburg infection from working in underground mines harboring bats in the Democratic Republic of the Congo and Uganda. Lassa Fever and Other Arenaviral Diseases

Arenaviruses are transmitted from rodents to humans, except Tacaribe virus, which was found in bats. Most infections are mild, but some result in hemorrhagic fever with high death rates. Old World (Eastern Hemisphere) and New World (Western Hemisphere) viruses cause the following diseases:

* Old World viruses: Lassa virus (Lassa fever) lymphocytic choriomeningitis virus (meningitis, encephalitis, and congenital fetal infection in normal hosts, hemorrhagic fever in organ transplant recipients). Lassa fever occurs in rural West Africa, with hyperendemic areas in Guinea, Liberia, Nigeria, and Sierra Leone. Lujo virus has been recently described in Zambia and the Republic of South Africa during a health care–associated outbreak. * New World viruses: Junin (Argentine hemorrhagic fever), Machupo (Bolivian hemorrhagic fever), Guanarito (Venezuelan hemorrhagic fever), Sabia (Brazilian hemorrhagic fever), and the recently discovered Chapare virus (a single case in Bolivia).

Reservoir host species are Old World rats and mice (family Muridae, subfamily Murinae) and New World rats and mice (family Muridae, subfamily Sigmodontinae). These rodent types are found worldwide, including Europe, Asia, Africa, and the Americas. Virus is transmitted through inhalation of aerosols from rodent urine, ingestion of rodent-contaminated food, or direct contact of broken skin or mucosa with rodent excreta. Risk of Lassa virus infection is associated with peridomestic rodent exposure. Inappropriate food storage increases the risk for exposure. Health care–associated transmission of Lassa, Lujo, and Machupo viruses has occurred through droplet and contact. One anecdotal report of possible airborne transmission exists. Several cases of Lassa fever have been confirmed in international travelers staying in traditional dwellings in the countryside.

Rift Valley Fever and Other Bunyaviral Diseases

RVF causes fever, hemorrhage, encephalitis, and retinitis in humans, but primarily affects livestock. RVF is endemic to sub-Saharan Africa. Sporadic outbreaks have occurred in humans in Egypt, Madagascar, and Mauritania. Large epidemics occurred in Kenya, Somalia, and Tanzania in 1997–1998 and 2006–2007; Saudi Arabia and Yemen in 2000; Madagascar in 2008; and South Africa, Botswana, Namibia, and Mauritania in 2010. RVF virus is transmitted by mosquito, percutaneous inoculation, and slaughter or consumption of infected animals.

CCHF is endemic where ticks of the genus Hyalomma are found in Africa and Eurasia, including South Africa, the Balkans, the Middle East, Russia, and western China, and is highly endemic in Afghanistan, Iran, Pakistan, and Turkey. CCHF virus is transmitted to humans by infected ticks or direct handling and preparation of fresh carcasses of infected animals, usually domestic livestock. Health care–associated transmission often occurs.

Hantaviruses cause hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). The viruses that cause HPS are present in the New World; those that cause HFRS occur worldwide. The viruses that cause both HPS and HFRS are transmitted to humans through contact with urine, feces, or saliva of infected rodents. Travelers staying in rodent-infested dwellings are at risk for HPS and HFRS. Human-to-human transmission has been reported only with Andes virus in Chile and Argentina.