Haemorrhagic Fever Viruses

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G. Haukenes

Haemorrhagic fever viruses are found within several families. They have natural transmission cycles among animals and are therefore geographically restricted to certain areas.

FLAVIVIRUSES (Lat. flavus = yellow)

Flaviviruses are enveloped positive-sense single-stranded RNA viruses, about 50 nm in diameter. Yellow fever and dengue haemorrhagic fever occur in the tropics and adjacent subtropics and are transmitted by mosquitoes (Aedes and Haemagogus). The host reservoirs of yellow fever virus are humans (urban form) and monkeys (jungle form). Kyasanur Forest (India) disease and Omsk (Western Siberia, Russia) haemorrhagic fever are transmitted by ticks, the reservoirs being different vertebrate animal species.

Common clinical features are fever, headache, haemorrhages in the skin and mucous membranes. Case fatality rate is particularly high in secondary attacks of dengue, apparently due to immunological mechanisms. Deafness, hair loss and psychomotor disturbances are frequently recorded sequelae in Omsk haemorrhagic fever.

There is one distinct type of the yellow fever virus and four types of dengue fever virus. The Kyasanur disease and Omsk fever viruses belong to the TBE complex (see Chapter 34).

Interferon treatment seems to reduce lethality in dengue. The live (17D) yellow fever vaccine is safe and effective. Inactivated vaccines seem to provide some protection against Omsk haemorrhagic fever and Kyasanur disease. Important preventive measures are insect control and protection against bites.

Virus may be isolated from the blood in the acute phase of the disease. Serological diagnosis is performed by CF and HI and by ELISA for demonstration of specific IgG and IgM, with due attention to cross-reactions between members of the flavivirus family.

TOGAVIRUSES (Lat. toga = gown, cloak)

Togaviruses are somewhat larger than flaviviruses (70 nm in diameter), but have the same gross morphological structure (for more virus details, see Chapter 15). Haemorrhagic fever is caused by Chickungunya (East Africa) virus belonging to the Alphavirus genus. The disease, which is milder than dengue haemorrhagic fever, is seen in Asia and Africa and is transmitted from man to man by Aedes aegypti and other mosquitoes.

Table 36.1 HAEMORRHAGIC FEVER VIRUSES: MODE OF TRANSMISSION AND CURRENTLY AVAILABLE PROPHYLAXIS AND THERAPY

Disease

Transmission

Immunoglobulin/vaccine

Antiviral

Yellow f.* } Dengue h.f. }

Mosquito bite

Live vaccine

Interferon

Omsk h.f. ]

Inactivated vaccine

Kyasanur Forest } disease J

Tick bite

Inactivated vaccine

Chickungunya f.

Mosquito bite

Rift Valley f.

Mosquito bite

Inactivated vaccine

Crimean-Congo h.f.

Tick bite

(Argentinian/ Bolivian h.f.)

Contact: rodents man

Immunoglobulin

Interferon Ribavirin

Marburg/ Ebola disease

Contact: rodents monkeys man

Convalescent plasma

Interferon Ribavirin

Haemorrhagic fevers with renal syndrome are discussed in Chapter 35.

Haemorrhagic fevers with renal syndrome are discussed in Chapter 35.

BUNYAVIRUSES (Bunyaamvera in Uganda)

Bunyaviruses are large, enveloped negative-sense single-stranded RNA viruses with a segmented genome. Haemorrhagic fever with renal syndrome (HFRS) is discussed in Chapter 35.

Rift Valley (East Africa) fever virus (genus Phlebovirus) is transmitted by mosquitoes (Culex and Aedes) from cattle to man, and occurs in Africa. Serious symptoms including encephalitis, blindness and haemorrhages are seen in some cases.

Crimean-Congo haemorrhagic fever virus (genus Nairovirus) is seen in Africa, Asia and Eastern Europe and is transmitted to man by ticks feeding on various wild and domestic animals. Man-to-man transmission also occurs.

An inactivated vaccine is available for Rift Valley fever. Otherwise prophylaxis consists of mosquito and tick control and protection against bites.

ARENAVIRUSES (Lat. arenosus = sandy)

Arenaviruses are pleomorphic enveloped single-stranded negative-sense RNA viruses with ribosome-like ('sandy') particles in the envelope. The natural host reservoir is in rodents which have acute or persistent infections.

Lassa fever is a severe haemorrhagic fever seen in rural West Africa. Similar fevers are Argentinian (Junin virus) and Bolivian (Machupo virus)

haemorrhagic fevers. Transmission occurs on contact with secretions from infected rodents. In addition, virus may be transmitted by contact with patients.

Handling of viruses and clinical material from patients with Lassa fever should be restricted to special laboratories (containment category 4) equipped for work with highly infectious agents. Some therapeutic effect is obtained by the use of specific immunoglobulins, interferons and ribavirin (see Chapter 4). Rodent control is an important preventive measure in endemic areas.

FILOVIRUSES (Lat. filo = thread-like)

These viruses are enveloped negative-sense single-stranded RNA viruses forming filamentous elements of varying lengths up to 1400 nm. They cause the severe haemorrhagic fevers termed Marburg (from an outbreak associated with monkeys imported to Europe) and Ebola (a river in the Democratic Republic of Congo, formerly Zaire) diseases. The transmission cycles of these viruses are elusive, but person-to-person transmission seems to be important in human outbreaks. Serological surveys from Central Africa indicate that filoviruses commonly cause subclinical infections in these areas. The natural host is unknown.

Work with filoviruses causing haemorrhagic fever is restricted to containment category 4 laboratories. Treatment with interferon, convalescent plasma and ribavirin (see Chapter 4) seems promising. There is no vaccine against filoviruses.

ENRAGING THE WORLD

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