Crimean-Congo haemorrhagic fever

Definition

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne viral disease of humans, which occurs in Africa, Eastern Europe and Asia. The viral haemorrhagic fevers are characterised by a propensity for person to person spread, and high death rates from multi-organ failure and haemorrhage, properties which place the causative viruses in the highest biohazard category.

CCHF was independently documented in Russia as Crimean haemorrhagic fever in 1945, and in the Democratic Republic of Congo (formerly Zaire, formerly the Belgian Congo) as Congo virus infection in 1956. The similarity of the subsequently isolated causative agents was established in 1969, and the two diseases, jointly renamed Congo-Crimean haemorrhagic fever, were considered to be identical.

CCHF or Congo fever as it is more commonly referred to, is the commonest viral haemorrhagic fever occurring in South Africa with between five and 25 cases reported annually. From 1981 until the end of 2002, approximately 171 cases have been diagnosed in South Africa. The vast majority of cases were from the Karoo, the Western Free State, Northern Cape and North-West Province. Most of the cases were in farmers, farm labourers, hunters and abattoir workers. Examples of cases and outbreaks include the following: an outbreak at the ostrich abattoir in Oudsthoorn affecting 17 persons; an outbreak at a hospital in the Western Cape involving one doctor who died and five nurses who became ill but recovered, after contracting the disease from a patient admitted with a suspected gastric ulcer; a case in an abattoir worker in Johannesburg; and a case in a man who worked in a hide processing factory in the Free State who was bitten by a Hyalomma tick.

Transmission

Humans acquire infection from infected ticks or from contact with fresh, infected blood and tissues of livestock or humans.

The virus is transmitted mainly by Hyalomma ticks, which have distinctive brown and white bands on their legs and are known in South Africa as bont-legged ticks (Afrikaans: bontpootbosluise). Hyalomma ticks are widely distributed in South Africa, but tend to be most numerous in the drier, north-western parts of the country in the Karoo, western Free State, Northern Cape and North-West Province, generally in the rural areas.

The virus transiently infects animals such as rodents and other small mammals, large animals such as antelopes and livestock (mainly cattle, sheep and goats) as well as birds, including guinea fowl and ostriches. The virus will circulate in the blood of the animal or bird for a short period (less than a week), until the immune system kills the virus. Generally young animals become infected. The animals and birds remain well, and do not experience any illness.

Hyalomma ticks become infected by feeding on the blood of the animals during this phase. Immature Hyalomma ticks (nymphs and larvae) feed on small mammals and birds, and adults ticks on the larger mammals and livestock as well as ostriches. Infected ticks become carriers of the virus and can pass on the virus to the next generation of ticks, as well as to mammals, birds and humans, when the ticks seek a blood meal. Fortunately ticks prefer feeding on animals and birds rather than on humans.

A human can be infected in one of four ways:

• Through an infected tick bite.
• By squashing an infected tick, and the tick fluid getting into cuts and abrasions in the skin, or onto mucous membranes.
• By exposure to blood from infected animals through broken skin or mucous membranes during the short period that the animal is infectious (from day three after the animal is infected until day seven). Humans can be exposed to infected blood during slaughtering, dehorning, castration, vaccination, the cutting of identity notches in the ears, or the attachment of ear tags. Abattoir workers, farmers and their workers, veterinarians and game hunters are particularly at risk. Meat which has been hung according to proper slaughterhouse procedures is not infectious and cooking destroys the virus. Therefore meat poses no risk to domestic consumers.
• By contact with blood or blood tinged body fluids from infected humans through broken skin or mucous membranes, or through an accidental needle stick injury in the case of medical personnel.

Other people at risk of being bitten by ticks include:

• Those who live in the countryside
• Town dwellers who visit the countryside for occupational and recreational purposes including hunting and hiking. Occasionally, no direct evidence can be obtained to indicate that a patient with CCHF had contact with animal blood or with ticks, and the only evidence to suggest possible exposure to infection is the fact that the patient lived in or visited an environment where such contact was possible.

Symptoms and signs

The symptoms of disease present abruptly from one to a maximum of 13 days after exposure to the virus, generally from one to three days after a tick bite, and between five to six days after exposure to blood. The abrupt onset and short incubation period help to differentiate CCHF from tick bite fever.

The patient presents with flu -like symptoms, headache, fever, muscle pain, especially lower back pain, cold shivers and hot sweats. Nausea, vomiting, diarrhoea and abdominal pain may be noted. Generally the patient feels extremely unwell. He or she may appear delirious or confused. After a few days, a rash may be seen which is initially similar to that found in measles. The rash evolves into one that looks like fine needlepoints which are small areas of bleeding into the skin, called petechiae.

The patient can bleed from any organ: from the bowel leading to the vomiting of blood (often confused with a stomach ulcer), or the passing of stools containing fresh or dark altered blood, bleeding from the nose (epistaxis) or gums, or bruising of skin, bleeding into muscles (haematomata), or oozing from injection sites.

The bleeding is due to an effect on the clotting mechanisms in the body, including a decrease in the platelets in the blood. Liver, kidney and lung failure may occur and the patient may become comatose. Up to 30% of patients may die from CCHF, generally five to 14 days after initial presentation, generally as a result of multi-organ failure and haemorrhage.

Patients who recover start to show improvement from day 10 of the illness onwards.

Diagnosis

It should be remembered that the vast majority of suspected cases prove not to be CCHF, and the doctor should consult physicians specifically charged with handling viral haemorrhagic fever patients.

The disease should be suspected in any person with the above signs and symptoms who has had exposure to ticks, who has handled potentially infected animals or birds, or who has had contact with the blood or body fluids of patients with CCHF (or those with signs and symptoms compatible with the disease, e.g. bleeding).

Blood tests showing a low number of platelets and generally a decrease in the white cells, and evidence of liver dysfunction are generally demonstrated at the time of presentation of the first symptoms.

There are a number of diseases that can present in a similar manner to CCHF.

These include:

• Tick Bite Fever - the bite site may be noted to have a black centre with surrounding inflammation and an enlarged, tender lymph node in the region. Symptoms develop seven to 10 days after a tick bite. Headache is very severe, and a rash that typically involves the palms and soles, develops three to five days after the initial symptoms. Some patients will develop complications of the disease, unless antibiotic treatment is administered (tetracycline is the preferred antibiotic).
• Bacterial infections of the blood may present with a similar picture to CCHF. The most important one would be meningococcal septicaemia/meningitis. This infection can progress very rapidly over a number of hours to death, and treatment with an antibiotic (penicillin) may be lifesaving. Typical symptoms include fever, headache, vomiting and a fine petechial rash that starts on the buttocks and rapidly progresses to severe bruising.
• Malaria must always be excluded and infections of the liver (hepatitis) also need to be considered.
• A number of other viral haemorrhagic fevers need to be considered if the person has travelled to other areas of Africa, or has been exposed to patients who have travelled and acquired disease. These include Ebola, Lassa and Marburg Fevers.
• Leukaemia, poisons and toxins from some snake bites may also present with bleeding.

The diagnosis of CCHF can be confirmed or excluded by carrying out specific blood tests. These are conducted in specialised laboratories with appropriate facilities and expertise. In South Africa, this laboratory is the Special Pathogens Unit at the National Institute for Communicable Diseases in Sandringham, Johannesburg (formerly the National Institute for Virology).

Tests performed would depend on the stage of the disease and may include the detection of antibodies in the patient’s blood, inoculation of blood into mice, and special cell cultures, and a new rapid tests, called Polymerase Chain Reaction (PCR), which is able to detect small amounts of the virus and is very useful in the acute stages of the disease.

Management

If a patient is suspected of having CCHF, or the diagnosis is confirmed, appropriate measures should be instituted to prevent spread of the disease to other persons, especially health care personnel. The patient should be isolated in a hospital ward, and anyone coming in to contact with the patient is required to wear protective clothing including gloves, special gowns, face masks and eye goggles or visors.

Contacts of the patient do not require isolation, but are placed under observation and monitored for fever and CCHF symptoms for 14 days after last contact with the patient. Direct contact with the blood and excreta of the patient must be avoided. Quarantine of farms is not indicated as infected ticks are in any event widely distributed in the area.

General supportive management of any failing organ is indicated, including intravenous fluids and oxygen where necessary, and more specifically replacement of blood and blood components that aid clotting.

The drug ribavirin has been used to treat patients on a trial basis, and the results are promising. While the oral preparation is available and can be used on patients who are not very ill, or who are recovering, the availability of the intravenous preparation for critically ill patients is problematic.

Up to 30% of patients who contract CCHF will die, but the prognosis is favourable in the remaining 70%.

Prevention

• There is no effective vaccine currently available
• Decrease the number of infected vectors and the infection of livestock by the use of tick dips
• Decrease tick bites of humans by treating clothing with appropriate insecticide formulations (e.g. Peripal)
• Use of protective clothing (impervious clothing and gloves) by abattoir and farm workers, hunters and veterinarians, when slaughtering, dehorning, or castrating animals
• Veterinary regulations promulgated require that ostriches should be treated with an appropriate acaricide (insecticide against ticks) and held in tick-free circumstances for 14 days before slaughter. Similar regulations would be impossible to implement for other livestock

Written by Dr Lucille Blumberg, National Institute for Communicable Diseases