Crimean-Congo hemorrhagic fever (CC-HF) is caused by a virus that is widely distributed in wild and domestic mammals, birds and ticks in many regions of Africa, Europe and Asia.¹ CCHF was first observed in the Crimea in 1944 by Russian scien-tists. The virus was first isolated in Africa from the blood of a febrile patient in Zaire in 1956.² In 1967, Simpson et al described 12 cases of a feverish illness with similar signs and symptoms of CCHF, of whom five were diagnosed as infection in the laboratory and the virus was isolated after inoculation of newborn mice with sera samples of infected patients. They were able to show that these viruses were serologically indistinguishable from the one isolated in 1956, and that this type of Congo virus was also similar to other virus strains from Central Asia, USSR and Bulgaria.³

The virus has been classified as a Nairovirus genus from the family of Bunyaviridae. The virus contains RNA and is inactivated by lipid solvents and detergents.^4,5 In Africa, the virus has been isolated from a variety of animals, including cattle, sheep, goats, and from a number of ticks that parasitize them, including Hyalomma spp, Hyalomma maginatum, Hyalomma anatolieum and Rhipicephalus spp.⁶ In Iran, Hyalomma spp probably plays the main role in transmitting the infection from animals to humans.⁷

The disease is usually transmitted to man following a tick bite, or through contact with the patient's blood or blood-contaminated specimens. Exposure to the blood of infected animals, especially cattle and sheep, has led to severe and often fatal infections. The incubation period for CCHF depends on the mode of transmission. It can extend from 2 to 7 days following a tick bite, or up to 10 to 14 days after blood transfusion or organ transplantation. The onset of the illness is sudden, with fever, chills, severe muscular pains, headache, vomiting, and pain in the epigastric and lumbar regions. A hemorrhagic state develops from the third to the fifth day and manifests with skin petechiae or purpura, and bleeding from the mucous membranes that manifests with epistaxis, hemoptysis, hematemesis, melena and hematuria. At this stage the conjunctiva is infected, face is flushed, tongue is dry, blood pressure decreases and heart sounds become weak. The liver is enlarged and tender, and there is tenderness over the epigastrium and splenic region. In patients who recover, the temperature decreases between the 10th and the 20th days and bleeding stops; however, convalescence can last up to 4 weeks or longer. In fatal cases, death from massive hemorrhage and cardiac arrest occurs 7 to 9 days after onset of the illness.^{8 – 10}

The diagnosis is based on epidemiologic studies and clinical presentation. The diagnosis may be confirmed in a reference laboratory by detection of a rise in specific IgG or IgM titers using ELISA.¹⁰

Meticulous patient care is the mainstay of treatment. Intensive monitoring and blood transfusion are mandatory in some cases. Prescription of antiviral medication such as ribavirin may show some benefit in established cases.^{7 – 10}

CCHF has been reported as a nosocomial infection among medical staff. Three cases are reported here.

A 26-year-old female medical student became ill in August 1999 at Shahrekurd (southcentral Iran) and presented with severe undulant fever, vomiting and diarrhea. Laboratory investigations revealed thrombocytopenia. After 2 weeks, the patient was transferred to a University Hospital in Tehran because of severe dizziness and a sudden onset of gastrointestinal bleeding. Three days later, she died of disseminated intravascular coagulation (DIC). A serum sample that was sent to South Africa showing a rise in CCHF IgG (> 0.2). These results confirmed the presence of CCHF virus.

Case 2

A 32-year-old male physician presented to a clinic in Isfahan (central Iran) with severe malaise, fever, vomiting, diarrhea, petechiae, epistaxis and oral bleeding. Based on these clinical findings, the patient was diagnosed with CCHF. There was no history of recent travel to suspicious regions or contact with domestic animals. Despite leukopenia, thrombocytopenia and a high titer of IgG (> 0.2), the patient recovered quickly. During hospitali-zation, antibiotics, steroids and intravenous immunoglobulin were administered. At the time of writing, the patient was well and without CCHF-associated sequelae.

A 29-year-old female staff member of the Blood Transfusion Center in Shahrekurd, Iran, presented with high fever, petechiae, epistaxis and oral bleeding. A diagnosis of CCHF virus was made. The patient had no history of recent travel or contact with domestic animals. Laboratory investigations showed no evidence of severe thrombocytopenia and there was no rise in IgG or IgM titers. Despite these results, the patient died as a result of DIC.

CCHF virus is most often transmitted to man following a tick bite (genus Hyalomma),¹¹ how-ever, an increasing number of cases have occurred among medical, laboratory and nursing staff in hospitals. In nosocomial cases, the infections have apparently been acquired by direct contact with patients’ blood or blood-contaminated specimens. There have been reports that exposure to the blood of infected animals, especially cattle and sheep, have led to severe and often fatal infections. The disease has recently been reported from several countries including China,⁴ Oman,¹² Senegal,^{11 – 14} Pakistan,¹⁵ United Arab Emirates,^16,17 Saudi Arabia,⁵ South Africa,⁶ Republic of Guinea,¹⁸ Central African Republic,¹⁹ Niger,²⁰ Sudan²¹ and Iran.²² The CCHF virus has been reported as a nosocomial infection from Iraq,²³ South Africa,^8,9,24,25 United Arab Emirates,²⁶ and Pakistan.²⁷ More than 144 cases of CCHF have been reported from Iran (between January 1st and October 1st 2002); however, few were identified as nosocomial infections.²⁸ This paper suggests that medical staff who works in hospitals or laboratories may acquire the infection directly from patients or contaminated human products. Other studies support these types of transmission.^{8,9,23 – 27}

It is of outmost importance to diagnose suspicious cases of CCHF in the early stages and initiate treatment as early as possible. Blood samples from suspected CCHF virus cases should be handled carefully, following stringent safety guidelines in the laboratory to prevent the transmission of CCHF among medical and laboratory staff.

1. Fisher-Hoch SP, McCormick JB, Swanepoel R, et al. Risk of human infections with Crimean-Congo hemorrhagic fever virus in a South African rural community. Am J Trop Med Hyg. 1992; 47: 337 – 45.

2. Gear JH, Thomson PD, Hopp M, et al. Crimean-Congo haemorrhagic fever in South Africa. Report of a fatal case in the Transvaal. S Afr Med J. 1982; 62: 576 – 80.

3. Simpson DI, Knight EM, Courtois G, et al. Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations – clinical notes. East Afr Med J. 1967; 44: 86 – 92.

4. Papa A, Ma B, Kouidou S, et al. Genetic characterization of the mRNA segment of Crimean-Congo hemorrhagic fever virus strains, China. Emerg Infect Dis. 2002; 8: 50 – 3.

5. El-Azazy OM, Scrimgeour EM. Crimean-Congo hemorrhagic fever virus infection in the western province of Saudi Arabia. Trans R Soc Trop Med Hyg. 1997; 91: 275 – 8.

6. Burt FJ, Spencer DC, Leman PA, et al. Investigation of tick-borne viruses as pathogens of humans in South Africa and evidence of Dugbe virus infection in a patient with prolonged thrombocytopenia. Epidemiol Infect. 1996; 116: 353 – 61.

7. Chinikar S. The specific serological investigation of suspected human and animals to have Crimean-Congo hemorrhagic fever in various parts of Iran using ELISA. Hakim. 2002; 4: 294 – 300.

8. Van Eeden PJ, Van Eeden SF, Joubert JR, et al. A nosocomial outbreak of Crimean-Congo hemorrhagic fever at Tygerberg Hospital. Part II. Management of patients. S Afr Med J. 1985; 68: 718 – 21.

9. Joubert JR, King JB, Rossouw DJ, et al. A nosocomial outbreak of Crimean-Congo hemorrhagic fever at Tygerberg Hospital. Part III. Clinical pathology and pathogenesis. S Afr Med J. 1985; 68: 722 – 8.

10. World Health Organization. Fact sheet No, 208. 2001. Avalable at: http:/www.who.int/inf-fs/en/fact208Htm/.

11. Faye O, Cornet JP, Camicas JL, et al. Experimental transmission of Crimean-Congo hemorrhagic fever virus: role of 3 vector species in the maintenance and trans-mission cycles in Senegal. Parasite. 1999; 6: 27 – 32.

12. Williams RJ, Al-Busaidy S, Mehta FR, et al. Crimean-Congo hemorrhagic fever: a sero-epidemiological and tick survey in the Sultanate of Oman. Trop Med Int Health. 2000; 5: 99 – 106.

13. Zeller HG, Cornet JP, Diop A, et al. Crimean-Congo hemorrhagic fever in ticks (Acari: Ixodidae) and ruminants: field observations of an epizootic in Bandia, Senegal (1989 – 1992). J Med Entomol. 1997; 34: 511– 6.

14. Camicas JL, Cornet JP, Gonzalez JP, et al. Crimean-Congo hemorrhagic fever in Senegal. Latest data on the ecology of the CCHF virus [in French]. Bull Soc Pathol Exot. 1994; 87: 11– 6.

15. Altaf A, Luby S, Ahmed AJ, et al. Outbreak of Crimean-Congo hemorrhagic fever in Quetta, Pakistan: contact tracing and risk assessment. Trop Med Int Health. 1998; 3: 878 – 82.

16. Khan AS, Maupin GO, Rollin PE, et al. An outbreak of Crimean-Congo hemorrhagic fever in the United Arab Emirates, 1994–1995. Am J Trop Med Hyg. 1997; 57: 519 – 25.

17. Rodriguez LL, Maupin GO, Ksiazek TG, et al. Molecular investigation of a multisource outbreak of Crimean-Congo hemorrhagic fever in the United Arab Emirates. Am J Trop Med Hyg. 1997; 57: 512 – 8.

18. Butenko AM. Arbovirus circulation in the Republic of Guinea [in Russian]. Med Parazitol (Mosk). 1996; 2: 40 – 5.

19. Guilherme JM, Gonella-Legall C, Legall F, et al. Seroprevalence of five arboviruses in Zebu cattle in the Central African Republic. Trans R Soc Trop Med Hyg. 1996; 90: 31 – 3.

20. Mariner JC, Morrill J, Ksiazek TG. Antibodies to hemorrhagic fever viruses in domestic livestock in Niger: Rift Valley fever and Crimean-Congo hemorrhagic fever. Am J Trop Med Hyg. 1995; 53: 217 – 21.

21. Watts DM, El-Tigani A, Botros BA, et al. Arthropod-borne viral infections associated with a fever outbreak in the northern province of Sudan. J Trop Med Hyg. 1994; 97: 228 – 30.

22. Mardani M. 135 cases of CCHF in Iran. The Second National Congress of Preventive Medicine and Public Health of Iran, November 2001. Kermanshah District (Kermanshah Province).

23. Tantawi HH, Al-Moslih M, Al-Janabi NY, et al. Crimean-Congo hemorrhagic fever virus in Iraq: isolation, identification and electron microscopy. Acta Virol (Praha). 1980; 24: 464 – 7.

24. Van Eeden PJ, Joubert JR, Van de Wal BW, et al. A nosocomial outbreak of Crimean-Congo hemorrhagic fever at Tygerberg Hospital. Part I. Clinical features. S Afr Med J. 1985; 68: 711 – 7.

25. Van de Wal BW, Joubert JR, Van Eeden PJ, et al. A nosocomial outbreak of Crimean-Congo hemorrhagic fever at Tygerberg Hospital. Part IV. Preventive and prophylactic measures. S Afr Med J. 1985; 68: 729 – 32.

26. Suleiman MN, Muscat-Baron JM, Harries JR, et al. Crimean-Congo hemorrhagic fever in Dubai: an outbreak at the Rashid Hospital. Lancet. 1980; 2: 939 – 41.

27. Burney MI, Ghafoor A, Saleen M, et al. Nosocomial outbreak of viral hemorrhagic fever caused by Crimean hemorrhagic fever-Congo virus in Pakistan, January 1976. Am J Trop Med Hyg. 1980; 29: 941 – 7.

28. Mardani M. Nesolomial Crimean-Congo hemorrhagic fever in Iran (1999 – 2000). Clin Microbial Infect. 2002; 7(suppl 1): 2201 – 13.