Other Viral Hemorrhagic Fevers

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Chapter 263 Other Viral Hemorrhagic Fevers

Scott B. Halstead

Viral hemorrhagic fevers are a loosely defined group of clinical syndromes in which hemorrhagic manifestations are either common or especially notable in severe illness. Both the etiologic agents and clinical features of the syndromes differ, but disseminated intravascular coagulopathy may be a common pathogenetic feature.

Etiology

Six of the viral hemorrhagic fevers are caused by arthropod-borne viruses (arboviruses) (Table 263-1). Four are togaviruses of the family Flaviviridae: Kyasanur Forest disease, Omsk, dengue (Chapter 261), and yellow fever (Chapter 262) viruses. Three are of the family Bunyaviridae: Congo, Hantaan, and Rift Valley fever (RVF) viruses. Four are of the family Arenaviridae: Junin, Machupo, Guanarito, and Lassa viruses. Two are of the family Filoviridae: Ebola and Marburg viruses. The Filoviridae are enveloped, filamentous RNA viruses that are sometimes branched, unlike any other known virus.

Table 263-1 VIRAL HEMORRHAGE FEVERS (HFs)

MODE OF TRANSMISSION	DISEASE	VIRUS
Tick-borne	Crimean-Congo HF*	Congo
	Kyasanur Forest disease	Kyasanur Forest disease
	Omsk HF	Omsk
Mosquito-borne^†	Dengue HF	Dengue (four types)
	Rift Valley fever	Rift Valley fever
	Yellow fever	Yellow fever
Infected animals or materials to humans	Argentine HF	Junin
	Bolivian HF	Machupo
	Lassa fever*	Lassa
	Marburg disease*	Marburg
	Ebola HF*	Ebola
	Hemorrhagic fever with renal syndrome	Hantaan

* Patients may be contagious; nosocomial infections are common.

^† Chikungunya virus is associated infrequently with petechiae and epistaxis. Severe hemorrhagic manifestations have been reported in some cases.

Epidemiology and Clinical Manifestations

With some exceptions, the viruses causing viral hemorrhagic fevers are transmitted to humans via a nonhuman entity. The specific ecosystem required for viral survival determines the geographic distribution of disease. Although it is commonly thought that all viral hemorrhagic fevers are arthropod borne, 7 may be contracted from environmental contamination caused by animals or animal cells or from infected humans (see Table 263-1). Laboratory and hospital infections have occurred with many of these agents. Lassa fever and Argentine and Bolivian hemorrhagic fevers are reportedly milder in children than in adults.

Crimean-Congo Hemorrhagic Fever

Sporadic human infection with Crimean-Congo hemorrhage fever in Africa provided the original virus isolation. Natural foci are recognized in Bulgaria, western Crimea, and the Rostov-on-Don and Astrakhan regions; a somewhat similar disease occurs in Kazakhstan and Uzbekistan. Index cases were followed by nosocomial transmission in Pakistan and Afghanistan in 1976, in the Arabian Peninsula in 1983, and in South Africa in 1984. Outbreaks have been reported from Pakistan, Oman, and southern Russia. In the Russian Federation, the vectors are Hyalomma marginatum and Hyalomma anatolicum, which, along with hares and birds, may serve as viral reservoirs. Disease occurs from June to September, largely among farmers and dairy workers.

Kyasanur Forest Disease

Human cases of Kyasanur Forest disease occur chiefly in adults in an area of Mysore State, India. The main vectors are 2 Ixodidae ticks, Haemaphysalis turturis and Haemaphysalis spinigera. Monkeys and forest rodents may be amplifying hosts. Laboratory infections are common.

Omsk Hemorrhagic Fever

Omsk hemorrhagic fever occurs throughout south-central Russia and northern Romania. Vectors may include Dermacentor pictus and Dermacentor marginatus, but direct transmission from moles and muskrats to humans seems well established. Human disease occurs in a spring-summer-autumn pattern, paralleling the activity of vectors. This infection occurs most frequently in persons with outdoor occupational exposure. Laboratory infections are common.

Rift Valley Fever

The virus causing RVF is responsible for epizootics involving sheep, cattle, buffalo, certain antelopes, and rodents in North, Central, East, and South Africa. The virus is transmitted to domestic animals by Culex theileri and several Aedes species. Mosquitoes may serve as reservoirs by transovarial transmission. An epizootic in Egypt in 1977-1978 was accompanied by thousands of human infections, principally among veterinarians, farmers, and farm laborers. Smaller outbreaks occurred in Senegal in 1987, Madagascar in 1990, and Saudi Arabia and Yemen in 2000-2001. Humans are most often infected during the slaughter or skinning of sick or dead animals. Laboratory infection is common.

Argentine Hemorrhagic Fever

Before introduction of vaccine, hundreds to thousands of cases of Argentine hemorrhage fever occurred annually from April through July in the maize-producing area northwest of Buenos Aires that reaches to the eastern margin of the Province of Cordoba. Junin virus has been isolated from the rodents Mus musculus, Akodon arenicola, and Calomys laucha laucha. It infects migrant laborers who harvest the maize and who inhabit rodent-contaminated shelters.

Bolivian Hemorrhagic Fever

The recognized endemic area of Bolivian hemorrhagic fever consists of the sparsely populated province of Beni in Amazonian Bolivia. Sporadic cases occur in farm families who raise maize, rice, yucca, and beans. In the town of San Joaquin, a disturbance in the domestic rodent ecosystem may have led to an outbreak of household infection caused by Machupo virus transmitted by chronically infected Calomys callosus, ordinarily a field rodent. Mortality rates are high in young children.

Venezuelan Hemorrhagic Fever

In 1989, an outbreak of hemorrhagic illness occurred in the farming community of Guanarito, Venezuela, 200 miles south of Caracas. Subsequently, in 1990-1991, there were 104 cases reported with 26 deaths due to Guanarito virus. Cotton rats (Sigmodon alstoni) and cane rats (Zygodontomys brevicauda) have been implicated as likely reservoirs of Venezuelan hemorrhage fever.

Lassa Fever

Lassa virus has an unusual potential for human-to-human spread, which has resulted in many small epidemics in Nigeria, Sierra Leone, and Liberia. Medical workers in Africa and the USA have also contracted the disease. Patients with acute Lassa fever have been transported by international aircraft, necessitating extensive surveillance among passengers and crews. The virus is probably maintained in nature in a species of African peridomestic rodent, Mastomys natalensis. Rodent-to-rodent transmission and infection of humans probably operate via mechanisms established for other arenaviruses.

Marburg Disease

Until recently, the world experience of Marburg disease had been limited to 26 primary and 5 secondary cases in Germany and Yugoslavia in 1967, and to small outbreaks in Zimbabwe in 1975, Kenya in 1980 and 1988, and South Africa in 1983. But, in 1999 a large outbreak occurred in Congo Republic and a still larger outbreak in Uige Province, Angola, with 351 cases and 312 deaths in 2005. In laboratory and clinical settings, transmission occurs by direct contact with tissues of the African green monkey or with infected human blood or semen. A reservoir in bats has been demonstrated. It appears that the virus is transmitted by close contact between fructivorous bats and from bats by aerosol to humans.

Ebola Hemorrhagic Fever

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