March 28, 2005
Marburg Hemorrhagic Fever Virus: Contagious, Fatal, and No Antiviral Rx.
An outbreak of Marburg hemorrhagic fever virus is ongoing in Uige Province, northern Angola, near the border with the Democratic Republic of the Congo. On March 23 the WHO reported that of the 102 cases identified retrospectively, 95 (93%) have been fatal, including some health care workers. About 75% of these patients have been children less than 5 years of age, although no reason was given. Marburg virus is an RNA virus closely related to Ebola virus in the filovirus family. There is no treatment and no vaccine against Marburg.
The animal reservoir for Marburg virus is uncertain, although the original outbreak and discovery of the virus in 1967 involved African Green monkeys imported from Uganda to Europe (including Marburg and Frankfurt, Germany and Belgrade, Serbia). In chapter 10 of his book “Biohazard” the former Soviet bioweaponeer, Dr. Ken Alibek, described how experiments to weaponize Marburg virus included work with rabbits and guinea pigs, and lead to the death in April 1988 of a scientist, Dr. Ustinov, who was injecting Marburg into animals, and a pathologist who performed the autopsy on Dr. Ustinov. Thus, several animal species may be susceptible to Marburg virus. The US CDC includes Marburg virus on its Category A bioterrorism agent list, however, there is no report of the current outbreak in Angola being linked with bioterrorism.
After 1967, cases of Marburg infection occurred in Africa including Zimbabwe, Kenya, and the Democratic Republic of the Congo (DRC). The DRC outbreak from 1998-2000 was the largest to date, with 123 deaths and 149 cases (83% case fatality rate). No cases of Marburg virus have been reported outside Africa, Europe and the former Soviet Union.
Infection of Health Care Workers (HCWs) has occurred in most of the outbreaks of Marburg as well as in family members and other persons having close contact with infected patients or infected monkeys. The precise mode of transmission from person-to-person is not fully understood, but both direct contact and respiratory spread are suspected. Thus, strict isolation and barrier nursing techniques as part of preventive contact and respiratory infection control measures for this highly fatal, untreatable, contagious disease are recommended by WHO (www.who.int), CDC Special Pathogens Branch, USAMRIID (Aug. 2004 5th edition of the “Blue Book”), and the 26-person Working Group on Civilian Biodefense consensus document (JAMA May 8, 2002;287:2391-2405).
Clinically, the incubation period after infection is usually 5-10 days (CDC), and then fever, headache, and myalgias start. Notably, a non-itchy “maculopapular rash (resembling the rash of measles)” (JAMA 2002; 287:p. 2397) Figure 1 caption) may appear along with hemorrhage and multi-organ damage including to the liver, pancreas, brain, intestine and lung. Patients may complain of chest pain, cough, nausea and vomiting. Common differential diagnoses early in the disease course include malaria and typhoid fever as well as rash-like diseases such as measles and meningococcemia.
There are no antiviral drugs known to be effective against Marburg. There is no vaccine against Marburg. Antiserum therapy has not been shown to be effective in humans or animals. Dr. Alibek mentions that an antiserum was available and tried, (several days after infection) in 1988 to treat Dr. Ustinov.
Regarding the current outbreak in Angola, reports over the past two days have increased the number of deaths from 95 to 114. At least six patients have been treated in Luanda, Angola, but apparently all were infected in the northern Uige Province and not in the city of Luanda. No reports of cases across the border from Angola in the Democratic Republic of the Congo (e.g., in the cities of Kinshasa or Kikwit) have appeared.
Daniel R. Lucey, MD, MPH