Crimean-Congo haemorrhagic fever

Crimean-Congo haemorrhagic fever

R SWANEPOEL AND F J BURT

Introduction

Crimean-Congo haemorrhagic fever (CCHF) is a zoonotic disease caused by a tick-borne virus of the genus Nairovirus of the family Bunyaviridae. The virus causes mild fever and viraemia in cattle, sheep and small mammals such as hares. Humans become infected by contact with infected blood or other tissues of livestock or human patients, or from a tick bite. The human disease is usually characterized by a febrile, influenza-like illness with a petechial rash, frequently followed by a haemorrhagic state and necrotic hepatitis. The mortality rate in humans is approximately 30 per cent.

A disease given the name Crimean haemorrhagic fever was first described in humans bitten by ticks while harvesting crops on the Crimean Peninsula in 1944. It was demonstrated in 1945, through the inoculation of filtered ticksuspensions and blood from patients into human subjects, that the disease was caused by a tick-transmitted virus, but the virus was only isolated in laboratory hosts, namely mice, in 1967.11 In 1969 it was shown that the agent of Crimean haemorrhagic fever was identical to a virus named Congo which had been isolated in 1956 from the blood of a febrile child in Stanleyville (now Kisangani) in what was then the Belgian Congo (now the Democratic Republic of Congo (DRC)), and since that time the two names have been used in combination.9, 11, 12, 57

Crimean-Congo haemorrhagic fever virus, or antibody to it, has been found in many countries of eastern Europe, Asia and Africa, mainly in the course of surveys. In some countries of eastern Europe and Asia, however, the presence of the virus first became evident in nosocomial outbreaks, or in epidemics which arose in circumstances where humans were exposed to ticks and livestock on a large scale, such as in major land reclamation or resettlement schemes in Bulgaria and parts of the former USSR.23, 24, 25, 42, 43, 58, 66

In February 1981, the first case of CCHF to be recognized in South Africa occurred in a child bitten by a Hyalomma tick in the North West Province. From 1981 to the middle of 2002 a total of 168 cases have been confirmed in southern Africa of which 40 were fatal infections.Of these 152 were indigenous cases in South Africa, two were imported cases from the DRC and Tanzania and 14 involved patients infected in Namibia.22, 32, 53, 59–64, 67 Thus it appears that the virus is present throughout the length of Africa, and that the disease which occurs here is no less severe than that which occurs in eastern Europe and Asia.

In southern Africa, antibody to CCHF was found to be widely distributed in the sera of livestock and wild vertebrates in South Africa, Zimbabwe and Namibia, including sera which had been in frozen storage since 1964.2, 52, 55, 59, 62, 64 This implies that the virus must have been in southern Africa long before its presence was recognized, and it is believed that the regular diagnosis of cases of CCHF in the subcontinent in recent years probably stems from the increased awareness among medical clinicians that resulted from wide publicity given to the disease. Hoogstraal24, 25 pointed out that mechanisms for the dissemination of ticks (and hence virus), which include the movement of birds that migrate annually on a north-south axis,26, 27 must have operated in Eurasia and Africa for millennia. In addition, ticks can be dispersed between continents by movement of livestock. Although there is evidence of CCHF outbreaks in the United Arab Emirates resulting from trade of livestock from Africa, long-established endemicity of CCHF in the region cannot be excluded. Despite the potential for dispersal of the virus between the continents, it appears from phylogenetic analyses of CCHF isolates that the circulation of the virus is largely compartmentalized within the two land masses of Africa and Eurasia.17, 35, 36, 39, 41, 47 The distribution of strains of the virus within the continents is probably related to the distribution and dispersal of the vectors of the virus.

The disease is the subject of a voluminous literature, much of which is in Russian and eastern European languages, but the information has been rendered available in a series of comprehensive reviews11, 24, 25, 68 which are cited in the following text in preference to original references located in inaccessible publications.

Aetiology

Crimean-Congo haemorrhagic fever virus (CCHFV) is classified as a member of the genus Nairovirus, of the family Bunyaviridae. 10, 14 The genus, consisting of 33 viruses, is divided into seven serogroups on the basis of antigenic relationships. Crimean-Congo haemorrhagic fever virus belongs to a serogroup of the same name and is the only member of the group that is known to cause human illness. The two other members of the serogroup are Hazara from Pakistan and Khasan from the former USSR. The classification of the nairoviruses was originally based on the results of serological investigations, but the groupings have subsequently been substantiated by comparison of morphological characteristics and molecular analyses.7

The nairoviruses are spherical, 90 to 120 nm in diameter, and have a host-cell-derived bilipid envelope incorporating virus-coded glycoproteins which form indistinct surface projections.15, 34 The single-stranded, negative-sense RNA genome has three segments with a total molecular...

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