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Science.com

June 12, 2004



What is Crimean-Congo Haemorrhagic Fever?



By Dr Saleem Kharal & Dr Farrukh Abu Hazim


Crimean Congo Haemorrhagic Fever (CCHF), one of the most severe human viral diseases, has a death rate of up to 30 per cent. The highly pathogenic nature of the virus and rapidly fatal course of the disease require prompt and effective measures for the victim of the disease.

This haemorrhagic fever, known in Asia for a long time, came to international attention after a disease outbreak in the Crimean peninsula in 1944 and 1945. The causative agent was later recognized to be identical to the Congo virus, isolated in Zaire. Thus this was named as the Crimean-Congo Haemorrhagic Fever (CCHF).

This systemic name assigned by the CDC in 1997. Also known as Asian Haemorrhagic Fever, the CCHF is primarily a zoonosis affecting livestock and ground-feeding birds, such as ostriches. Surprisingly, sporadic cases and outbreaks of the CCHF affecting humans have also been found out . The disease is endemic in many countries in Africa, Europe and Asia, and during 2001, cases or outbreaks have been recorded in Kosovo, Albania, Iran, Pakistan, and South Africa.

The first confirmed occurrence of the disease in Pakistan was in 1978. Most of the cases were reported from Balochistan . While in 2001, two cases were reported from Karachi. The infection usually during spring to fall indicated that the tick was responsible for the transmission of this disease in drought.

The CCHF virus is a Nairovirus, a group of related viruses forming one of the five genera in the Bunyaviridae family of viruses. It is an enveloped spherical virus with two subgenomic single stranded RNAs.

Transmission
The CCHF virus is transmitted to humans and animals through ticks, which act both as reservoir and vector of the virus. All of the 32 members of the Nairovirus genus are transmitted by argasid or ixodid ticks, but only three have been implicated as causes of human disease: the Dugbe and Nairobi sheep viruses, and CCHF which is the most important pathogen amongst them to affect people. A number of tick genera, including Hyalomma, Dermanector, Amblyoma and Rhipicephalus, are capable of becoming infected with the CCHF virus, but the most efficient and common vectors for the CCHF appear to be members of the Hyalomma genus. The virus is introduced in ticks from infected small vertebrates on which immature Hyalomma ticks feed. Trans-ovarial (transmission of the virus from infected female ticks to offspring via eggs) and venereal transmission have been detected in some vector species. These important routes which may contribute to maintaining the circulation of the virus in nature. Once infected, the tick remains infected through its developmental stages, and the mature tick may transmit the infection to large vertebrates, such as livestock. Domestic ruminant animals, such as cattle, sheep and goats, are viraemic (virus circulating in the bloodstream) for around one week after becoming infected. Humans can acquire the virus from direct contact with blood or other infected tissues from livestock during this time.

Population at risk
The CCHF virus is transferred to humans in one of the three ways: from a single tick bite or through simply penetration of the skin to the blood system if a tick is crushed; through contact with blood from a butchered animal infected with the virus; or through bodily fluids — urine, saliva, tears and potentially even milk. The population at risk are those involved with the livestock industry such as agricultural workers, slaughterhouse workers and veterinarians, doctors, paramedical staff and close contacts of the patient.

A contact is defined as a person who has been exposed to an infected person or to an infected person’s secretions, excretions, or tissues within three weeks of the patient’s onset of illness.

Clinical features
Following the infection via tick bite, the incubation period is usually one to three days, with a maximum of nine days. The incubation period following contact with infected blood or tissues is usually five to six days, with a documented maximum of 13 days.

Symptoms start with the onset of fever with muscle pain , dizziness, neck stiffness, backache, headache, sore eyes and photophobia (sensitivity to light). There may be nausea, vomiting and sore throat, which may be accompanied by diarrhoea and generalized abdominal pain. Over the next few days, the patient may experience sharp mood swings, and may become confused and aggressive. After two to four days, the agitation may be replaced by sleepiness, depression and lassitude, and the abdominal pain may localize to the right upper quadrant, with detectable hepatomegaly (liver enlargement).

Other clinical signs which emerge include tachycardia (fast heart rate), enlarged lymph nodes, and bleeding tendency marked by a petechial rash ( bleeding under the skin ), melaena (bleeding from the upper bowel, passed as altered blood in the faeces), haematuria (blood in the urine), epistaxis (nosebleeds) and bleeding from the gums. There is usually evidence of hepatitis. The severely ill may develop hepatorenal (i.e., liver and kidney) and pulmonary failure after the fifth day of illness. The mortality rate from the CCHF is approximately 30 per cent, with death occurring in the second week of illness. In those patients who recover, improvement generally begins on the ninth or tenth day after the onset of illness.

Lab diagnosis
Diagnosis of the suspected CCHF cases is performed in specially-equipped and having high biosafety level laboratories. IgG and IgM antibodies may be detected in serum by enzyme-linked immunoassay (the `ELISA’ or `EIA’ methods) from about day six of illness. IgM remains detectable for up to four months, and IgG levels decline but remain detectable for up to five years. Before a detectable antibody level is reached, the only diagnostic tool is isolation of the virus. The virus may be isolated from blood or tissue specimens in the first five days of illness, and grown in cell culture. Viral antigens may sometimes be shown in tissue samples using immunofluorescence or EIA. The PCR ( the polymerase chain reaction ), a molecular method for detecting the viral genome, has been successfully applied in diagnosis. Associated findings are leucopenia and thrombocytopenia.

Treatment
Specific antiviral therapy with supportive therapy according to clinical condition of patient is advised. The antiviral drug Ribavirin has been found to be effective. Both oral and intravenous formulations are available.

Disinfection: The virus is killed by common disinfectants, solvents, and dry heat (56°C, 30 min.). The vectors (ticks of the genus Hyalomma) also need to be controlled with acaricides and possible animal reservoirs will need to be monitored. Suitable disinfectant solutions include 0.5 per cent sodium hypochlorite (10 per cent aqueous solution of household bleach), as well as fresh, correctly prepared solutions of glutaraldehyde (2 per cent or as recommended by the manufacturer) and phenolic disinfectants (0.5-3 per cent). Soaps and detergents can also inactivate these viruses and should be used liberally.

Laboratory personnel accidentally exposed to potentially-infected material (for example, through injections or cuts or abrasions on the hands) should immediately wash the infected part, apply a disinfectant solution such as hypochlorite solution, and notify the patient’s physician. The person should then be considered as a high-risk contact and placed under surveillance.

Accidental spills of potentially contaminated material should liberally be covered with disinfectant solution, left to soak for 30 minutes, and wiped up with absorbent material soaked in disinfectant.

Guidelines for control
Although an inactivated, mouse brain-derived vaccine against the CCHF has been developed and used on a small scale in Eastern Europe, there is no safe and effective vaccine widely available for human use. The tick vectors are numerous and widespread and tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well-managed livestock production facilities.

Persons living in endemic areas should use protective measures that include avoidance of areas where tick vectors are abundant, specially when they are active (during spring to fall); regular examination of clothing and skin for ticks, and their removal; and use of repellents.

People who work with livestock or other animals in the endemic areas can take practical measures to protect themselves. These include the use of repellents on the skin, for instance, DEET and clothing, for instance permethrin and wearing gloves or other protective clothing to prevent skin contact with infected tissues or blood.

When patients with the CCHF are admitted to hospital, there is a risk of nosocomial spread of infection. In the past, serious outbreaks have occurred in this way and it is imperative that adequate infection control measures be observed to prevent this disastrous outcome.

Patients with suspected or confirmed CCHF should be isolated and cared for using barrier nursing techniques. Specimens of blood or tissues taken for diagnostic purposes should be collected and handled using universal precautions. Sharps (needles and other penetrating surgical instruments) and body wastes should be safely disposed of using appropriate decontamination procedures.

Healthcare workers are at a risk of acquiring infection from injuries during surgical procedures and, in the past, infection has been transmitted to surgeons operating on patients to determine the cause of the abdominal symptoms in the early stages of (at that moment undiagnosed) infection. Healthcare workers who have had contact with tissues or blood from patients with suspected or confirmed CCHF should be followed up with daily temperature and symptom monitoring for at least 14 days after the putative exposure.

More info
— WHO factsheet No 208 , revised Nov 2001
— Viddya Medical News Service, Vol 2, Issue 43
— Aristotelian University of Thessaloniki , Greece and Chinese Academy of Preventive Medicine, Beijig , China.
— Fisher-Hoch SP , Simpson DIH. Dangerous pathogens. Br Med Bull 1985;41:391-5.
— CDC Viral hemorrhagic fever: initial management of suspected and confirmed cases. MMWR 1983, 32 (2S): 27S-39S.


Dr Saleem Kharal is an associate professor and heads the Department of Microbiology at BMSI, JPMC, Karachi, and Dr Farrukh Abu Hazim M.Phil student of Microbiology at JPMC, Karachi



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