Crimean-Congo haemorrhagic fever

Previous authors: R Swanepoel and FJ Burt

Current authors:
F J BURT - Professor, Medical Scientist, PhD, Division of Virology, Francois Retief Building, DF Malherbe Street, Bloemfontein, 9300, South Africa
D GOEDHALS - Division of Virology, Francois Retief Building, DF Malherbe Street, Bloemfontein, 9300, South Africa
R SWANEPOEL - Extraordinary Lecturer, BVSc, DTVM, PhD, Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, Gauteng, 0110, South Africa

GENERAL INTRODUCTION: BUNYAVIRIDAE

Introduction

Crimean-Congo haemorrhagic fever  (CCHF) is a tick-borne disease found in Africa, Asia, eastern Europe and the Balkans. The geographic distribution of the CCHF virus  (CCHFV) correlates with that of ticks belonging to the genus Hyalomma, which are considered to be the principal vectors. The virus causes benign infection with 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 tick bite. The human disease is usually characterized by a febrile illness with a petechial rash, often followed by a haemorrhagic state and necrotic hepatitis.

A disease given the name Crimean haemorrhagic fever was first described in people bitten by ticks while harvesting crops on the Crimean Peninsula in 1944. It was demonstrated in 1945, through the inoculation of filtered tick-suspensions 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 1967.²² 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 Democratic Republic of Congo, DRC), and since that time the two names have been used in combination.^{20, 22, 23, 93}

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 that 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.^{45, 51, 52, 80, 81, 94, 102} 

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 2019 just over 200 cases have been confirmed in southern Africa with a fatality rate of approximately 30 per cent.^{43, 59, 90, 95, 96, 98, 99, 100, 101, 105} The virus is likely present throughout  Africa, and causes disease that 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 that had been in frozen storage since 1964.^{16, 89, 91, 95, 99, 101} 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. Hoogstraal^{51, 52} 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,^{53, 54} 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.

The emergence and re-emergence of CCHFV in Balkan countries and south western regions of the Russian Federation, and more recently in southern regions of Europe, highlights the potential for this pathogen to spread to non-endemic regions where ticks belonging to the genus Hyalomma are present, although there is also the possibility of late recognition of the infection in areas where the virus has long been present.

Aetiology

Crimean-Congo haemorrhagic fever virus is classified as a member of the genus Orthonairovirus, order Bunyavirales,   family Nairoviridae, (formerly the genus Nairovirus of the family Bunyaviridae).^{21, 26} Species within the genus were originally grouped  on the basis of antigenic  affinities and recently revised using morphological and genetic relatedness.^{1, 18} Twelve orthonairovirus species are currently recognized: CCHF, Dera Ghazi Khan, Dugbe, Hughes, Qalyub, Sakhalin, Thiafora, Burana, Hazara, Kasokera, Keterah and Nairobi sheep disease.¹ Crimean-Congo haemorrhagic fever virus  is regarded as the only member of an eponymous group.

The orthonairoviruses are spherical, 90-120 nm in diameter, and have a host-cell-derived bilipid envelope incorporating virus-coded glycoproteins that form indistinct surface projections.^{29, 67} The single-stranded, negative-sense RNA genome has three segments with...