Marburg Virus Disease (MVD) is a rare but highly severe illness that causes viral hemorrhagic fever in humans and non-human primates. The disease was first recognized simultaneously in 1967 following outbreaks in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia, among laboratory workers exposed to infected African green monkeys. Due to its potential for rapid spread and high fatality rates, which have historically ranged from 24% to 90% in some outbreaks, the Marburg virus is categorized as a high-priority pathogen by international health organizations. This classification underscores the need for a deeper understanding of the virus’s characteristics and effective control methods.
The Virus’s Blueprint
The Marburg virus (MARV) is classified within the Filoviridae family, a group of viruses that also includes the closely related Ebola virus. It belongs to the genus Marburgvirus, with the single species designated as Marburg marburgvirus. The virus is enveloped and contains a non-segmented, single-stranded RNA genome with a negative sense polarity.
The virions exhibit a distinctive, highly pleomorphic morphology. While often described as filamentous or thread-like, they commonly appear in U-shapes, circles, or the characteristic “shepherd’s crook” shape. The particle length is variable, typically between 800 and 1400 nanometers.
The virus structure incorporates seven structural proteins encoded by its approximately 19-kilobase genome. The outer lipid envelope is studded with glycoprotein (GP) spikes, which are necessary for attaching to and fusing with host cell membranes to initiate infection. Inside the envelope, the viral RNA is coiled into a helical ribonucleocapsid complex by the nucleoprotein (NP) and the polymerase cofactor VP35. The L protein serves as the RNA-dependent RNA polymerase, responsible for transcribing and replicating the viral genome once inside the host cell.
Disease Progression Within the Host
Following initial exposure, the Marburg virus undergoes an incubation period that can last anywhere from two to 21 days before symptoms begin abruptly. The virus initially targets and infects primary immune cells, specifically dendritic cells and macrophages, which are normally responsible for initiating the body’s immune response. Infection of these cells allows the virus to replicate rapidly and systemically disseminate throughout the body while simultaneously suppressing the host’s innate antiviral defenses.
The viral proteins, such as VP35 and VP40, actively block the host cell’s ability to produce and respond to interferon signaling. This immune evasion allows the virus to multiply unchecked, leading to a release of proinflammatory molecules, often described as a cytokine storm. This process contributes significantly to the systemic damage observed in Marburg virus disease.
As the infection progresses, the virus causes extensive damage to the vascular endothelium. This damage increases vascular permeability, leading to widespread leakage of fluid and blood plasma from the circulatory system into surrounding tissues. The virus also impairs the blood clotting mechanism, causing coagulopathy, marked by prolonged clotting times and a depletion of clotting factors.
These combined effects result in disseminated intravascular coagulation (DIC) and hemorrhaging, which define the hemorrhagic fever syndrome. Major organs, particularly the liver, spleen, and adrenal glands, become primary targets for viral replication and subsequent necrosis. Adrenal gland damage can impair the production of stress hormones, contributing to severe hypotension and hypovolemic shock, which ultimately drives the high fatality rate through multi-organ failure.
Reservoirs, Transmission, and Containment
The natural reservoir for the Marburg virus is the African fruit bat, Rousettus aegyptiacus, which harbors the virus without showing signs of disease. Spillover events from the bat reservoir to humans typically occur when people enter caves or mines colonized by these bats and are exposed to their feces or aerosols. The virus can also transmit through the handling of infected animals, particularly in areas where bats are consumed as bushmeat.
Once a human is infected, the virus can spread rapidly from person to person through direct contact with infectious body fluids, including blood, saliva, vomit, urine, breast milk, and semen from an individual who is sick or has died. Transmission can also occur indirectly through contact with surfaces or objects, called fomites, such as contaminated bedding, clothing, or medical equipment. Notably, the virus can persist in immunologically privileged sites, such as the eyes and semen, for many months in survivors, posing a continued risk of sexual transmission.
Containment Measures
Containing outbreaks relies on a rapid public health response focused on breaking the chain of human-to-human transmission. This response involves several key measures:
- Immediate isolation of suspected and confirmed cases in specialized treatment centers to prevent further spread.
- Implementation of strict infection prevention and control protocols, requiring healthcare workers to use extensive personal protective equipment (PPE) when caring for patients.
- Comprehensive contact tracing to monitor everyone who may have been exposed to the virus.
- Safe and dignified burial practices, as deceased individuals remain highly infectious.
Current Medical Countermeasures
Diagnosis of Marburg virus disease in the early stages can be challenging because the initial symptoms are non-specific and mimic other tropical diseases like malaria and typhoid. Definitive diagnosis relies on specialized laboratory testing, primarily using molecular methods such as real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to detect the presence of viral genetic material in blood or body fluid samples. Enzyme-linked immunosorbent assays (ELISA) can also be used to detect viral antigens or antibodies in the later stages of infection or for surveillance.
Currently, there are no fully licensed antiviral drugs or vaccines specifically approved for the treatment or prevention of MVD. Therefore, patient management is based on supportive care, which focuses on maintaining the patient’s physiological functions as the body fights the infection. This includes fluid and electrolyte management to counteract dehydration and shock caused by vascular leakage and vomiting.
Maintaining blood pressure and supporting blood coagulation through the administration of blood products are important components of care. Several experimental countermeasures are in various stages of development, including monoclonal antibody therapies and broad-spectrum antiviral drugs like Remdesivir. Vaccine candidates, often based on viral vectors like adenovirus (cAd3) or recombinant vesicular stomatitis virus (rVSV), have shown promise in non-human primate models and are undergoing clinical trials.