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CRIMEAN-CONGO HAEMORRHAGIC FEVER
Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever of the
Nairovirus group. Although primarily a zoonosis, sporadic cases and outbreaks of
CCHF affecting humans do occur. 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 disease was first described in the Crimea in 1944 and given the name Crimean
haemorrhagic fever. In 1969 it was recognized that the pathogen causing Crimean
haemorrhagic fever was the same as that responsible for an illness identified in
1956 in the Congo, and linkage of the 2 place names resulted in the current name
for the disease and the virus. CCHF is a severe disease in humans, with a high
mortality rate. Fortunately, human illness occurs infrequently, although animal
infection may be more common.
The geographical distribution of the virus, like that of its tick vector, is
widespread. Evidence of CCHF virus has been found in Africa, Asia, the Middle
East and Eastern Europe. Healthcare workers in endemic areas should be aware of
the illness and the correct infection control procedures to protect themselves
and their patients from the risk of nosocomial (hospital-acquired) infection.
CCHF Virus
The virus which causes CCHF is a Nairovirus, a group of related viruses forming
one of the five genera in the Bunyaviridae family of viruses. 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 human pathogen
amongst them.
CCHF Reservoirs and Vectors
The CCHF virus may infect a wide range of domestic and wild animals. Many birds
are resistant to infection, but ostriches are susceptible and may show a high
prevalence of infection in endemic areas. Animals become infected with CCHF from
the bite of infected ticks. A number of tick genera are capable of becoming
infected with CCHF virus, but the most efficient and common vectors for CCHF
appear to be members of the Hyalomma genus. Trans-ovarial (transmission of the
virus from infected female ticks to offspring via eggs) and venereal
transmission have been demonstrated amongst some vector species, indicating one
mechanism which may contribute to maintaining the circulation of the virus in
nature.
However, the most important source for acquisition of the virus by ticks is
believed to be infected small vertebrates on which immature Hyalomma ticks feed.
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 who become infected with CCHF acquire the virus from direct contact with
blood or other infected tissues from livestock during this time, or they may
become infected from a tick bite. The majority of cases have occurred in those
involved with the livestock industry, such as agricultural workers,
slaughterhouse workers and veterinarians.
Clinical Features
The length of the incubation period for the illness appears to depend on the
mode of acquisition of the virus. Following 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.
Onset of symptoms is sudden, with fever, myalgia (aching muscles), dizziness,
neck pain and stiffness, backache, headache, sore eyes and photophobia
(sensitivity to light). There may be nausea, vomiting and sore throat early on,
which may be accompanied by diarrhoea and generalised 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),
lymphadenopathy (enlarged lymph nodes), and a petechial rash (a rash caused by
bleeding into the skin), both on internal mucosal surfaces, such as in the mouth
and throat, and on the skin. The petechiae may give way to ecchymoses (like a
petechial rash, but covering larger areas) and other haemorrhagic phenomena such
as 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 CCHF is approximately 30%, 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.
Diagnosis
Diagnosis of suspected CCHF is performed in specially-equipped, 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.
Patients with fatal disease do not usually develop a measurable antibody
response and in these individuals, as well as in patients in the first few days
of illness, diagnosis is achieved by virus detection in blood or tissue samples.
There are several methods for doing this. 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.
More recently, the polymerase chain reaction (PCR), a molecular method for
detecting the viral genome, has been successfully applied in diagnosis.
Treatment
General supportive therapy is the mainstay of patient management in CCHF.
Intensive monitoring to guide volume and blood component replacement is
required.
The antiviral drug ribavirin has been used in treatment of established CCHF
infection with apparent benefit. Both oral and intravenous formulations seem to
be effective.
The value of immune plasma from recovered patients for therapeutic purposes has
not been demonstrated, although it has been employed on several occasions.
Prevention and Control
Although an inactivated, mouse brain-derived vaccine against 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 personal protective
measures that include avoidance of areas where tick vectors are abundant and
when they are active (Spring to Fall); regular examination of clothing and skin
for ticks, and their removal; and use of repellents.
Persons 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 (e.g. DEET) and clothing (e.g. permethrin) and wearing
gloves or other protective clothing to prevent skin contact with infected tissue
or blood.
When patients with 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 risk of acquiring infection from
sharps 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 tissue 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.
WHO
Fact Sheet No 208
Revised November 2001
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