Crimean-Congo hemorrhagic fever: A re-emerging, potentially deadly illness

Crimean-Congo hemorrhagic fever is one of the most widely distributed viral hemorrhagic fevers.

This disease occurs in much of Africa, the Middle East and Asia, as well as parts of Europe. Changes in climatic conditions could expand the range of its tick vectors, and increase the incidence of disease.

The Crimean-Congo hemorrhagic fever virus is also a potential bioterrorist agent; it has been listed in the United States as a CDC/NIAID Category C priority pathogen. A 22-year-old Army soldier, who died in September in a hospital in Germany after succumbing to CCHF, contracted the virus from a tick bite while serving in Afghanistan. This case has drawn the attention to current infection risks in servicemen in Afghanistan and Iraq.

Within the European arena, CCHF, known to be endemic in Bulgaria since the 1950s, emerged and/or re-emerged during the last decade in several Balkan countries, Turkey, southwestern regions of the Russian Federation and the Ukraine, with considerable high fatality rates. In Bulgaria, 1,568 CCHF lab-confirmed cases were recorded from 1953 to 2008, with an overall case fatality rate of 17%. In Turkey, where an epidemic commenced in 2002, more than 4,400 lab-confirmed cases have been recorded until 2009, with at least 279 fatalities. Between 2000 and 2009, more than 1,300 clinical cases were diagnosed in the Russian Federation with an overall fatality rate of 3.2% from 2002-2007.

Reasons for re-emergence of CCHF include climate and anthropogenic factors such as changes in land use, agricultural practices or hunting activities and movement of livestock that may influence host-tick-virus dynamics. The tick-vector has been identified recently, for the first time, in Germany and France. The EU has decided to undertake the identification of areas at risk for further CCHF expansion and to enhance human, vector and animal surveillance.

The disease

CCHF is a zoonotic viral disease that is asymptomatic in infected animals, but a serious threat to humans. It initially came to modern medical attention in 1944, when Soviet military personnel were infected while assisting peasants in war-devastated Crimea (Ukrainian SSR). Collaboration in 1968 between the Soviet and American experts M. P. Chumakov and Jordi Casals demonstrated the serologically identical properties of virus strains from human CCHF patients and corpses, lower mammals and ticks from Asian and European areas and from Bulgaria, Congo (Zaire), Nigeria and Pakistan. Human infections begin with nonspecific febrile symptoms, but progress to a serious hemorrhagic syndrome with a high case fatality rate. Although the causative virus is often transmitted by ticks, animal-to-human and human-to-human transmission also occur. This disease is a particular threat to farmers and other agricultural workers, veterinarians, laboratory workers and hospital staff.

Etiology

CCHF is caused by Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus in the family Bunyaviridae. It belongs to the CCHF serogroup.

Although early serological studies revealed very few differences between strains of CCHFV, nucleic acid sequence analysis has demonstrated extensive genetic diversity, particularly between viruses from different geographic regions.

Geographic distribution

CCHFV is widespread in Africa, the Middle East and Asia. It has also been found in parts of Europe, including southern portions of the former Union of Soviet Socialist Republics (Crimea, Astrakhan, Rostov, Uzbekistan, Kazakhstan, Tajikistan), Turkey, Bulgaria, Greece, Albania and Kosovo province of the former Yugoslavia. Limited serological evidence suggest that CCHFV might also occur in parts of Hungary, France and Portugal. The occurrence of this virus is correlated with the distribution of Hyalomma spp., the principal tick vectors.

Transmission and epidemiology

CCHFV circulates in an enzootic tick–vertebrate–tick cycle. There is no evidence that the virus causes disease in animals. It has been found in at least 31 species of ticks, including seven genera of the family Ixodidae (hard ticks). Members of the genus Hyalomma seem to be the principal vectors; transovarial, transstadial and venereal transmission occur in this genus. Hyalomma marginatum marginatum is particularly important as a vector in Europe, but CCHFV is also found in Hyalomma anatolicum anatolicum and other Hyalomma spp. Other ixodid ticks may also transmit the virus locally. Although CCHFV has been reported in other families of invertebrates, these species may not be biological vectors; the virus may have been ingested in a recent blood meal.

Many species of mammals can transmit CCHFV to ticks when they are viremic. Small vertebrates such as hares and hedgehogs, which are infested by immature ticks, may be particularly important as amplifying hosts.

Antibodies against CCHFV have been detected in the sera of horses, donkeys, goats, cattle, sheep and pigs in various regions of Europe, Asia and Africa. It must be remembered that antibody studies, particularly if the prevalence is low, are not as meaningful as obtaining actual virus isolates. Domesticated ruminants including cattle, sheep and goats are viremic for one week after experimental infection. Most species of birds seem to be resistant to infection, but in ostriches, CCHFV can be found in blood for one to four days and in visceral organs for up to five days after experimental infection. Birds are, generally, refractory to infection but may act as mechanical vectors by transporting infected ticks. Migratory birds might spread the virus between distant geographic areas.

Humans become infected through the skin and by ingestion. Aerosol transmission was suspected in a few cases in Russia. Sources of exposure include being bitten by a tick, crushing an infected tick with bare skin, contacting animal blood or tissues and drinking unpasteurized milk. Human-to-human transmission occurs, particularly when skin or mucous membranes are exposed to blood during hemorrhages or tissues during surgery. Possible horizontal transmission has been reported from a mother to her child.

Epidemiologically, CCHF cases are distributed mainly among actively working age groups exposed to tick populations. The major at-risk group is farmers living in endemic areas; most of the affected cases deal with agriculture and/or animal husbandry. Almost 90% of the cases in a recent outbreak in Turkey were farmers. Although there is no evidence that the virus causes disease in animals, CCHFV-infected individuals were reported after skin contact with livestock and other animals. Veterinarians and abattoir workers who work with large domestic animals are also an at-risk group; acquisition of the virus usually takes place while slaughtering animals. Viremic blood from subclinically infected animals was the most likely source of infection, but exposure to ticks during these processes is also likely, at least in some of the cases. Meat itself is not a risk because the virus is inactivated by postslaughter acidification of the tissues and would not survive cooking in any case.

Hiking, camping, and other rural activities are also a risk factor for tick exposure. Gender distribution varies between countries, depending on the participation of women in agricultural work.

Several outbreaks in South Africa were related to slaughter of heavily tick-infested ostriches, either by contact with ostrich blood or inadvertently crushing infected ticks while skinning ostriches. Although no antibody was detected among birds during the outbreak, ostriches have been experimentally infected, and viremia was observed for one to four days after infection. As a public health measure, the study suggested that birds should be kept free of ticks for 14 days before slaughtering. Similar measures were recommended for slaughter procedures of cattle, sheep and goats in endemic areas.

Health care workers are the second most affected group; they are at serious risk of transmission of CCHF infection when caring for patients with haemorrhages from the nose, mouth, gums, vagina, and injection sites. The transmission of the CCHF infections and deaths among health-care workers has been reported in parallel with outbreaks in the general population.

Diagnostic tests

Crimean-Congo hemorrhagic fever can be diagnosed by isolating CCHFV from listed tissues, by real-time RT-PCR assay on blood samples, an by serology. Virus isolation must be carried out in maximum biocontainment laboratories (BSL-4).

Prevention

In endemic regions, prevention depends on avoiding bites from infected ticks and contact with infected blood or tissues. Exposure of slaughterhouse personnel can be prevented by use of modern pyrethroid acaricides, which are highly effective and leave no residues in tissues, together with holding the animals for a prescribed period prior to slaughter in a place/s secured by suitable fencing from penetration by other hosts of ticks.

An inactivated vaccine from mouse brains has been used in the former Soviet Union and Bulgaria. In most countries, no vaccine is available.

Since CCHFV does not affect domestic animals clinically, it is not regarded by animal breeders as of significance. No prevention measures in farmed animals have been, so far, applied or recommended, except for pre-slaughter and export purposes.

Arnon Shimshony, DVM, is Associate Professor at the Koret School of Veterinary Medicine Hebrew University of Jerusalem, Rehovot, and is the ProMED-mail Animal Diseases Zoonoses Moderator. Dr. Shimshony was Chief Veterinary Officer, State of Israel, from 1974 to 1999.

Maltezou HC. Crimean-Congo hemorrhagic fever in Europe: current situation calls for preparedness. Euro Surveill. 2010;15(10):pii=19504. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19504.