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Marburg haemorrhagic fever

Marburg haemorrhagic fever is a severe and highly fatal disease caused by a virus from the same family as the one that causes Ebola haemorrhagic fever. Viewed under electron microscopy, the viruses show particles shaped like elongated filaments, sometimes coiled into strange shapes, that give the Filoviridae family its name. These viruses are among the most virulent pathogens known to infect humans.

Though caused by different viruses, the two diseases are clinically almost indistinguishable. Both diseases are rare, but have a capacity to cause dramatic outbreaks with high fatality. Historically, outbreaks have tended to reach the attention of health authorities only after transmission has been amplified by inadequate infection control in health care settings.

Neither disease has a vaccine or specific treatment. Despite years of intensive investigation involving the testing of hundreds of animals, insects, and plants, no animal reservoir or other environmental source of either virus has been identified. Monkeys are susceptible to infection but are not considered viable reservoir hosts as virtually all infected animals die too rapidly to sustain survival of the virus. Humans are not considered part of the natural transmission cycle; their infection is accidental.

Natural history and clinical features

Causative agent. Marburgvirus of the Filoviridae family.

Geographical occurrence. Outbreaks and sporadic cases have been reported in Angola, Democratic Republic of Congo, Kenya, and South Africa (in a person with a recent travel history to Zimbabwe). The initial outbreaks, in Germany and the former Yugoslavia in 1967, have been linked to laboratory work using African green monkeys (Cercopithecus aethiops) imported from Uganda.

Transmission. Transmission of the virus from person to person requires extremely close contact with a patient. Infection results from contact with blood or other body fluids (faeces, vomitus, urine, saliva, and respiratory secretions) with high virus concentration, especially when these fluids contain blood. Transmission via infected semen can occur up to seven weeks after clinical recovery.

Infection through casual contact is thought to be exceedingly rare. The low rate of transmission to persons with casual contact suggests that aerosol transmission via the respiratory tract is not efficient, if it occurs at all. Transmission does not occur during the incubation period.

Patients appear to be most infectious during the phase of severe illness accompanied by haemorrhagic manifestations. Close contact with a severely ill patient, during care at home or in hospital, and certain burial practices are common routes of infection. Transmission via contaminated injection equipment or through needle-stick injuries is associated with more severe disease, rapid deterioration, and possibly higher fatality.

Incubation period. 3 to 9 days.

Susceptibility. All age groups are susceptible to infection, but most cases have occurred in adults. Prior to the present outbreak in Angola, paediatric cases were considered extremely rare. In the largest outbreak previously recorded, which occurred in the Democratic Republic of Congo from late 1998 to 2000, only 12 (8%) of the cases were under the age of 5 years.

Clinical features. Illness caused by Marburg virus begins abruptly, with severe headache and severe malaise. Muscle aches and pains are a common feature.

A high fever usually appears on the first day of illness, followed by progressive and rapid debilitation. A severe watery diarrhoea, abdominal pain and cramping, nausea, and vomiting begin about the third day. Diarrhoea can persist for a week. The appearance of patients at this phase has been described as showing “ghost-like” drawn features, deep-set eyes, expressionless faces, and extreme lethargy. In the 1967 European outbreak, a non-itchy rash was a feature noted in most patients between days 2 and 7 after symptom onset.

Many patients develop severe haemorrhagic manifestations between days 5 and 7, and fatal cases usually have some form of bleeding, often from multiple sites. Findings of fresh blood in vomitus and faeces are often accompanied by bleeding from the nose, gums, and vagina. Spontaneous bleeding at venipuncture sites can be particularly troublesome. During the severe phase of illness, patients have sustained high fevers. Involvement of the central nervous system can result in confusion, irritability, and aggression. Orchitis has been reported occasionally in the late phase of disease (day 15).

In fatal cases, death occurs most often between 8 and 9 days after symptom onset, usually preceded by severe blood loss and shock.

Natural reservoir of the virus. Unknown.

History of recorded outbreaks

1967: Germany and Yugoslavia. Marburg haemorrhagic fever was initially detected following simultaneous outbreaks in Marburg and Frankfurt, Germany and Belgrade, former Yugoslavia. The initial cases occurred in laboratory workers handling African green monkeys imported from Uganda. The outbreaks involved 25 primary infections, with 7 deaths, and 6 secondary cases, with no deaths. The primary infections were in laboratory staff exposed to Marburg virus while working with monkeys or their tissues. The secondary cases involved two doctors, a nurse, a post-mortem attendant, and the wife of a veterinarian. All secondary cases had direct contact, usually involving blood, with a primary case. Both doctors became infected through accidental skin pricks when drawing blood from patients.

1975: South Africa, possibly via Zimbabwe. In mid-February 1975, an acutely ill Australian man, aged 20 years, was admitted to a hospital in Johannesburg, South Africa. During early February, he and his 19-year-old female companion had travelled extensively through Zimbabwe, often sleeping outdoors. He died four days after hospital admission. All primary contacts of the case were placed in isolation and strict infection control was introduced. Infection nonetheless spread to his travelling companion and a 20-year-old female nurse, who attended both patients. Both women were given vigorous supportive treatment and eventually recovered.

1980: Kenya. On 8 January 1980, a 56-year-old Frenchman, employed in Western Province, developed a sudden febrile illness, followed by headache, diarrhoea and vomiting. His recent travel history included a visit to Kitum Cave in Kenya’s Mount Elgon National Park. Despite specialized care in Nairobi and aggressive resuscitation attempts, he died on 15 January. The doctor who attempted resuscitation developed symptoms 9 days later. He recovered.

1987: Kenya. On 13 August 1987, a 15-year old Danish male, who had been in Kenya for one month, was admitted to hospital with a three-day history of headache, malaise, fever, and vomiting. Nine days prior to symptom onset, he had visited Kitum Cave in Mount Elgon National Park. Despite aggressive supportive therapy, the patient died on the 11th day of illness. No further cases were detected.

1998–2000: Democratic Republic of Congo. The outbreak in DRC marked the first large outbreak of this disease under natural conditions. The outbreak, which occurred from late 1998 to 2000, involved 154 cases, of which 128 were fatal, representing a case fatality of 83%. The majority of cases occurred in young male workers at a gold mine in Durba, in the north-eastern part of the country, which proved to be the epicentre of the outbreak. Cases were subsequently detected in the neighbouring village of Watsa. Family members involved in the close care of patients accounted for some cases, but secondary transmission appeared to be rare. Subsequent virological investigation indicated that virus of several different strains was introduced to human populations, from some yet unknown environmental source, on more than seven separate occasions.

2004–2005 (ongoing): Angola. The outbreak is believed to have begun in Uige Province in October 2004. As of 2 April 2005, the Ministry of Health reported a cumulative total of 163 cases, of which 150 were fatal. Most cases detected in other provinces have been linked directly to the outbreak in Uige. At the request of the government, international assistance, coordinated by WHO, has been organized to help contain the outbreak.

Updated information on the evolution of this outbreak can be found at the WHO disease outbreak news site.

Sources: US Department of Health; The World Health Organization

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