Marburg hemorrhagic fever

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The Marburg virus causes severe viral haemorrhagic fever in humans with a case fatality rates that have ranged from 24% to 88%. [1] Rousettus aegypti, fruit bats of the Pteropodidae family, are considered to be natural hosts of Marburg virus. The Marburg virus is transmitted to people from fruit bats and spreads among humans through human-to-human transmission. No specific antiviral treatment or vaccine is available.

Histoircal Perspective

Marburg haemorrhagic fever was initially detected in 1967 after simultaneous outbreaks in Marburg, from which the disease takes its name, and Frankfurt in Germany; and in Belgrade, Serbia.

Pathophysiology

Pathogen

Marburg virus is the causative agent of Marburg haemorrhagic fever (MHF). Marburg and Ebola viruses are the two members of the Filoviridae family (filovirus). Though caused by different viruses, the two diseases are clinically similar. The viral structure is typical of filoviruses, with long threadlike particles which have a consistent diameter but vary greatly in length from an average of 800 nanometers up to 14,000 nm, with peak infectious activity at about 790 nm. Virions (viral particles) contain seven known structural proteins. While nearly identical to Ebola virus in structure, Marburg virus is antigenically distinct from Ebola virus — in other words, it triggers different antibodies in infected organisms. It was the first filovirus to be identified. The Marburg virus was briefly described in the book written by Richard Preston entitled The Hot Zone.

Transmission

Originally, human infection results from prolonged exposure to mines or caves inhabited by Rousettus bats colonies.

Transmission is mainly human-to-human, resulting from close contact with the blood, secretions, organs or other bodily fluids of infected persons. Burial ceremonies where mourners have direct contact with the body of the deceased can play a significant role in the transmission of Marburg. Transmission via infected semen can occur up to seven weeks after clinical recovery.

Transmission to health-care workers has been reported while treating Marburg patients, through close contact without the use of correct infection control precautions. Transmission via contaminated injection equipment or through needle-stick injuries is associated with more severe disease, rapid deterioration, and, possibly, a higher fatality rate.

Differentiating Marburg Hemorrhagic Fever from other Diseases

The differential diagnoses usually include

  • The clinician must treat the most likely cause of the fever according to local epidemiology and the appropriate treatment guidelines.
  • If the fever continues after 3 days of recommended treatment, and if the patient has signs such as bleeding or shock, the clinician must consider a VHF.
  • It is important to review the patient’s history for any contact with someone who was ill with fever and bleeding or who died from an unexplained illness with fever and bleeding.
  • If no other cause is found for the patient’s signs and symptoms, the clinician must suspect a VHF.
  • Shown below is a table summarizing the typical findings of the differential diagnoses of MHF.
Disease Findings
Shigellosis & other bacterial enteric infections Presents with diarrhea, possibly bloody, accompanied by fever, nausea, and sometimes toxemia, vomiting, cramps, and tenesmus. Stools contain blood and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and blood smears, should be made. Presence of leucocytosis distinguishes bacterial infections.
Typhoid fever Presents with fever, headache, rash, gastrointestinal symptoms, with lymphadenopathy, relative bradycardia, cough and leucopenia and sometimes sore throat. Blood and stool culture can demonstrate causative bacteria.
Malaria Presents with acute fever, headache and sometime diarrhea (children). Blood smears must be examined for malaria parasites. Presence of parasites does not exclude concurrent viral infection. Antimalarial must be prescribed in an attempt at therapy.
Lassa fever Disease onset is usually gradual, with fever, sore throat, cough, pharyngitis, and facial edema in the later stages. Inflammation and exudation of the pharynx and conjunctiva are common.
Yellow fever and other Flaviviridae Present with hemorrhagic complications. Epidemiological investigation may reveal a pattern of disease transmission by an insect vector. Virus isolation and serological investigation serves to distinguish these virus. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Others Viral hepatitis, leptospirosis, rheumatic fever, typhus, and mononucleosis produce signs and symptoms that may be confused with Ebola in the early stages of infection.
Table adapted from WHO Guidelines For Epidemic Preparedness And Response: Ebola Haemorrhagic Fever [2]

Epidemiology and Demographics

Both Marburg and Ebola hemorrhagic fevers are rare and have the capacity to cause dramatic outbreaks with high fatality rates.

Two large outbreaks that occurred simultaneously in Marburg and Frankfurt in Germany, and in Belgrade, Serbia, in 1967, led to the initial recognition of the disease. The outbreak was associated with laboratory work using African green monkeys (Cercopithecus aethiops) imported from Uganda. Subsequently, outbreaks and sporadic cases have been reported in Angola, Democratic Republic of the Congo, Kenya, South Africa (in a person with recent travel history to Zimbabwe) and Uganda. In 2008, two independent cases were reported in travelers who visited a cave inhabited by Rousettus bat colonies in Uganda.

Natural History, Complications and Prognosis

Marburg haemorrhagic fever (MHF) has a case fatality ratio of up to 88%.


Diagnosis

Symptoms

Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases, such as malaria or typhoid, diagnosis of the disease can be difficult, especially if only a single case is involved.

The incubation period (interval from infection to onset of symptoms) varies from 2 to 21 days.

The disease is spread through bodily fluids, including blood, excrement, saliva, and vomit and a history of such contact should be solicited. Early symptoms are often non-specific, and usually include fever, headache and myalgia after an incubation period of 3-9 days. After five days, a macropapular rash is often present on the trunk. Later-stage Marburg infection is acute and can include jaundice, pancreatitis, weight loss, delirium and neuropsychiatric symptoms, hemorrhaging, hypovolemic shock and multi-organ dysfunction with liver failure most common. Accounts of external hemorrhaging from bodily orifices are pervasive in popular references to the disease but are in fact rare. The time course varies but symptoms usually last for one to three weeks until the disease either resolves or kills the infected host. The fatality rate is between 23-90% and more. [3] [4]

If a patient survives, recovery is usually prompt and complete, though it may be prolonged in some cases. These symptoms may include inflammation or secondary infection of various organs, including: orchitis (testicles), hepatitis (liver), transverse myelitis (spinal cord), uveitis (eyes), or parotitis (salivary glands).

Many patients develop severe haemorrhagic manifestations between 5 and 7 days, and fatal cases usually have some form of bleeding, often from multiple areas. Fresh blood in vomitus and faeces is often accompanied by bleeding from the nose, gums, and vagina. Spontaneous bleeding at venepuncture sites (where intravenous access is obtained to give fluids or obtain blood samples) can be particularly troublesome. During the severe phase of illness, patients have sustained high fever. Involvement of the central nervous system can result in confusion, irritability, and aggression. Orchitis has been reported occasionally in the late phase of disease (15 days).

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

Laboratory Studies

Marburg virus infections can be diagnosed definitively only in laboratories, by a number of different tests:

Enzyme-linked immunosorbent assay (ELISA); Antigen detection tests; serum neutralization test; Reverse-transcriptase polymerase chain reaction (RT-PCR) assay; and Virus isolation by cell culture.

Tests on clinical samples present an extreme biohazard risk and are conducted only under maximum biological containment conditions.

Treatment

Acute Medical Therapy

Severe cases require intensive supportive care, as patients are frequently in need of intravenous fluids or oral rehydration with solutions containing electrolytes.

Primary Prevention and Vaccines

No specific treatment or vaccine is yet available for MHF. Several vaccine candidates are being tested but it could be several years before any are available. New drug therapies have shown promising results in laboratory studies and are currently being evaluated.

Precautionary measures for pig farms in endemic zones

Precautionary measures are needed in pig farms in Africa to avoid pigs becoming infected through contact with fruit bats. Such infection could potentially amplify the virus and cause or contribute to MHF outbreaks.

Reducing the risk of infection in people

In the absence of effective treatment and human vaccine, raising awareness of the risk factors for Marburg infection and the protective measures individuals can take to reduce human exposure to the virus, are the only ways to reduce human infections and deaths.

During MHF outbreaks in Africa, public health educational messages for risk reduction should focus on:

Reducing the risk of bat-to-human transmission arising from prolonged exposure to mines or caves inhabited by fruit bats colonies. During work or research activities or tourist visits in mines or caves inhabited by fruit bat colonies, people should wear gloves and other appropriate protective clothing (including masks). Reducing the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their body fluids. Close physical contact with Marburg patients should be avoided. Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home. Regular hand washing should be performed after visiting sick relatives in hospital, as well as after taking care of ill patients at home. Communities affected by Marburg should make efforts to ensure that the population is well informed, both about the nature of the disease itself and about necessary outbreak containment measures, including burial of the dead. People who have died from Marburg should be promptly and safely buried.

Controlling infection in health-care settings

Human-to-human transmission of Marburg virus is primarily associated with direct contact with blood and body fluids, and Marburg virus transmission associated with provision of health care has been reported when appropriate infection control measures have not been observed.

Health-care workers caring for patients with suspected or confirmed Marburg virus should apply infection control precautions to avoid any exposure to blood and body fluids and to direct unprotected contact with possibly contaminated environment. Therefore, provision of health care for suspected or confirmed Marburg patients requires specific control measures and reinforcement of standard precautions, particularly hand hygiene, use of personal protective equipment (PPE), safe injection practices, and safe burial practices.

Laboratory workers are also at risk. Samples taken from suspected human and animal Marburg cases for diagnosis should be handled by trained staff and processed in suitably equipped laboratories.

WHO response

WHO has been involved in all past Marburg outbreaks by providing expertise and documentation to support disease investigation and control.

Recommendations for infection control while providing care to patients with suspected or confirmed Marburg haemorrhagic fever is provided in the: Interim infection control recommendations for care of patients with suspected or confirmed filovirus (Ebola, Marburg) Haemorrhagic Fever, March 2008.

WHO has created an aide–memoire for standard precautions in health care. Standard precautions are meant to reduce the risk of transmission of bloodborne and other pathogens. If universally applied, the precautions would help prevent most transmission through exposure to blood and body fluids. Standard precautions are recommended in the care and treatment of all patients regardless of their perceived or confirmed infectious status.

They include the basic level of infection control and include hand hygiene, use of personal protective equipment to avoid direct contact with blood and body fluids, prevention of injuries from needle sticks and from other sharp instruments, and a set of environmental controls.

References

Sources

WHO Fact sheet http://www.who.int/mediacentre/factsheets/fs_marburg/en/


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