Marburg Virus Disease6 min read
Marburg virus (MARV), a highly pathogenic RNA virus that belongs to the Filoviridae family, is the cause of Marburg virus disease (MVD), a rare but severe hemorrhagic fever with a high case-fatality rate making it one of the most deadly pathogens. First discovered in an outbreak in 1967, the source of Marburg virus disease was traced back to the importation of African green monkeys from Uganda. It was previously known as green monkey disease.
The animal reservoir was then discovered to be the Rousettus fruit bat through epidemiological linkage. Transmission via inhalation of contaminated excreta from bats or contact with bodily fluid from sick patients is the presumed route of introduction into the human population. Following the initial exposure, MARV enters the body, replicates, disseminates, and leads to a clinical syndrome composed of fever, malaise, myalgia, and blood coagulation disorders. These symptoms progress to shock, multiorgan failure, and death in many cases.
Only viruses in the Marburgvirus or Ebolavirus genera are known to cause disease in humans and are most well known because of their high case-fatality rates and dramatic clinical presentation. MARV is currently classified as a Group 4 pathogen by the World Health Organization (WHO), indicating high individual and community risk.
The animal reservoir of MVD is the Egyptian fruit bat (Rousettus aegyptiacus), which demonstrates little to no clinical disease. The virus replicates and sheds from bats without displaying overt signs of infection, allowing for maintenance and dissemination of the virus. The identification of the host was discovered through epidemiological linkage to outbreaks, with almost all primary infections being linked to humans entering caves that contain bats. For example, the large outbreak in the DRC was related to gold mining in Goroumbwa cave in Durba. Notably, this outbreak demonstrated multiple independent, distinct virus strains, and infections continued until the mine flooded.
It is unclear whether the Egyptian fruit bat is the only exclusive reservoir for MARV or if other bat species could also perpetuate the virus. The virus spreads from animal hosts, either from bats or another intermediate host such as non-human primates to humans, but the exact route and specific fluid involved is unknown. The transmission through person-to-person contact can occur through blood or other infected bodily fluids (e.g., saliva, sweat, urine, stool, breast milk, etc.).
Patients most at risk of exposure include those that have close contact with:
- Excrements of the fruit bats (for example, recent travel to endemic regions in Africa, or those who enter caves and mines inhabited by Rousettus aegyptiacus)
- People sick with the Marburg virus (for example, family members or hospital staff who care for infected patients)
- Non-human primates (NHP) infected with Marburg virus
Following exposure and infection with MARV, there is a 3 to 21 day incubation period. After incubation, the course is then broken down into three phases: the initial generalization phase, the early organ phase, and a late organ phase or convalescence phase. In the generalization phase, patients begin experiencing flu-like, non-specific symptoms such as high fever, chills, myalgias, joint pain, headache, and malaise. Some patients will additionally experience gastrointestinal symptoms. Intensity increases on days 5 to 7, and a maculopapular, erythematous, non-pruritic rash is a common feature.
The early organ phase involves conjunctivitis, swings between hyper- and hypo-pyrexia, and symptoms of hemorrhagic fever, including mucosal bleeding, hematemesis, hematochezia, petechiae, and bleeding from venipuncture sites. In later stages of the disease, patients develop neurological symptoms such as agitation, seizures, confusion, and coma. Past day 13, patients enter the late organ/convalescence phase and either succumb to the disease or have an extended period of recovery and rehabilitation.
As of now, there are no approved treatments for the Marburg virus. During outbreaks, supportive care has been the mainstay of treatment: the CDC and the WHO have developed a manual for infection control. Key infection control precautions include placing patients in an individual room with a closed door, using proper personal protective equipment (PPE), using disposable patient care equipment when possible, limiting the use of needles and sharps, avoiding aerosol-generating procedures, performing hand hygiene frequently, monitoring and managing potentially exposed personnel and preventing the entry of visitors into the patients’ rooms. Although there are no currently approved treatments, there are several pharmaceutical agents in development.
Antivirals that have been investigated include Galidesivir, synthetic nucleoside analog that inhibits viral RNA-dependent RNA polymerase, favipiravir, a synthetic guanidine nucleoside, and remdesivir, a prodrug of an adenosine analog.
Antibodies have been used in humans with Ebola virus disease and led to improved outcomes. Specifically, a three-antibody cocktail called ZMapp was tested during the West Africa outbreak and the recent Ebola outbreak in the DRC. It is possible to consider monoclonal antibodies in Marburg virus disease as well, given the similarities between the two diseases.
Multiple trials and efforts are underway to develop an effective filovirus vaccine. Many different vaccine modalities are undergoing investigation, including inactivated virus, replication-incompetent vaccines, virus-like replicon particles (VRPs), adenovirus vector, DNA, virus-like particles (VLPs), replication-competent vaccines, recombinant vesicular stomatitis virus, and mixed modality.
Clinical trials were accelerated following the 2013 Ebola virus epidemic as the need for effective vaccination grew. However, challenges and hindrances associated with vaccine design remain as more data is needed to determine the utility and efficacy of these vaccines.
Clinical diagnosis is difficult in the early phase of disease as symptoms are nonspecific and similar to a multitude of other infectious diseases. The differential diagnosis for Marburg fever may include, but is not limited to: Ebola virus disease, Lassa fever, Dengue, Malaria, Typhoid fever, Rickettsial illness, Shigellosis, Meningitis.
As there is no current approved treatment for the Marburg virus and only supportive care can be provided, the prognosis of the disease remains poor with a high case fatality rate. Optimal management needs to occur in specialized biocontainment units.
All personnel with direct patient contact must adhere to the correct usage of personal protective equipment (PPE), hand hygiene, and minimal use of needles and sharps to avoid occupational exposure. Control of future outbreaks remains a vital component in preventing further primary infections as well as secondary transmission. The variability in disease severity in the known outbreaks is thought to be due to availability of medical care, infectious dose, route of infection, the virulence of the strain, and population health in general.
Complications of Marburg virus disease include signs and symptoms of hemorrhagic fever, multi-system organ failure, shock, and ultimately death. Transmission to others remains a significant concern, and proper PPE and prophylactic measures are necessary while caring for infected patients and handling the deceased. Additionally, given the immunosuppression induced by Marburg virus infection, secondary infections should be considered and treated appropriately.
The management of a patient with Marburg virus disease or an outbreak of Marburg virus disease should involve the infectious diseases team, hospital medicine team, the intensive care team, and public health team. There should be early involvement of the CDC in the USA, the UKHSA in the UK, and similar bodies in other parts of the world.
Patients located in or traveling to endemic regions of Marburg virus disease must be properly educated on recognizing signs and symptoms of the disease, preventing infection, and avoiding contact with bats, which can harbor the disease. Quarantine instructions and isolation of sick personnel once the disease is contracted should be emphasized.
Like the Ebola virus, the Marburg virus remains a public health crisis as recurrent epidemics demonstrate a need to stay informed on the disease with continuous research for future treatment options. Supportive care remains the mainstay of treatment at this time to give patients the best opportunity for a good prognosis and outcome. As many treatment options are currently being investigated, healthcare providers must remain educated as new information becomes available. Care coordination includes adhering to proper PPE, containment of infected patients, and use of specialized biocontainment units when available [Level 4].
Hunter N, Rathish B. Marburg Fever. [Updated 2023 Feb 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.