Marburg virus disease: Emerging threat, pathogenesis, and global public health strategies

Abstract

The Marburg virus (MARV) is a dangerous infection that causes a deadly sickness known as MARV disease. This severe hemorrhagic fever is a major concern for people all over the world. Since the initial identification in 1967 during simultaneous outbreaks in Germany and Serbia, MARV has caused recurrent epidemics predominantly in sub-Saharan Africa with fatality rates ranging from 24% to 90% as a result of differences in virus strains, healthcare infrastructure, and the quality of patient treatment. Like Ebola virus, MARV causes a viral hemorrhagic fever identified in some of the same principles of clinical and epidemiological concern. However, MARV has unique biologic characteristics that require specialized research and response by public health and among researchers. Diagnosis relies on molecular tools such as real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, as well as clinical and epidemiological assessments. Despite advancements in understanding MARV biology, no vaccines or antiviral therapies have been approved, with treatment limited to supportive care. Experimental therapeutics, monoclonal antibodies, RNA-based drugs, and adenovirus-based vaccines, show promise but require further validation. Current efforts in outbreak containment include surveillance, rapid diagnostics, case isolation, and safe burial practices. However, gaps in understanding MARV pathogenesis, limited diagnostic tools, and the absence of regulatory-approved vaccines underscore the urgent need for global collaboration and investment in research. Bridging these gaps is critical to mitigating the public health impact of MARV, ensuring effective response strategies for future outbreaks.

Key Words: Marburg virus; Hemorrhagic fever; Zoonotic transmission; Enzyme-linked immunosorbent assay; Real-time reverse transcriptase-polymerase chain reaction; Outbreak control

Core Tip: Marburg virus disease (MVD) is a highly fatal haemorrhagic fever with no approved vaccines or antiviral treatments. This review highlights the epidemiology, transmission, pathogenesis, and current diagnostic challenges of MVD. Recent advancements in molecular diagnostics, experimental therapeutics, and vaccine candidates such as cAd3-Marburg and Mvabea (MVA-BN-Filo) are discussed, emphasizing the urgent need for clinical validation. Strengthening global surveillance, rapid outbreak response, and international collaboration is critical to mitigating future epidemics. This review underscores the necessity for increased research investment to develop effective prevention and treatment strategies for this deadly virus.

INTRODUCTION

Marburg virus (MARV), a member of the Filoviridae family, is the causative agent of MARV disease (MVD), a severe hemorrhagic fever with a high fatality rate. First identified in 1967 during simultaneous outbreaks in Marburg and Frankfurt, Germany, and Belgrade, Serbia, the virus was linked to laboratory exposure from infected African green monkeys (Cercopithecus aethiops) imported from Uganda. Since then, recurrent outbreaks have primarily occurred in sub-Saharan Africa, with fatality rates varying between 24% and 90%, depending on the virus strain, healthcare response, and available treatment options[1].

Like Ebola virus (EBOV), MARV spreads through direct contact with bodily fluids of infected individuals or animals, including its natural reservoir, the Egyptian fruit bat (Rousettus aegyptiacus). It leads to severe vascular damage, immune dysfunction, and multi-organ failure, making early detection and intervention critical. The clinical presentation ranges from flu-like symptoms in the early phase to hemorrhagic manifestations and organ failure in severe cases[2].

Despite significant advancements in diagnostic techniques, including real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), no licensed vaccines or antiviral treatments are currently available. Ongoing research on monoclonal antibodies, RNA-based drugs, and viral vector vaccines shows promise but requires further validation. Outbreak containment measures focus on surveillance, rapid diagnostics, case isolation, contact tracing, and safe burial practices[3].

This review provides a comprehensive analysis of MVD, covering its epidemiology, pathogenesis, transmission, clinical presentation, diagnosis, and treatment approaches. It also highlights prevention strategies, ongoing research efforts, and future directions to enhance global preparedness against MARV outbreaks. Strengthened international collaboration and investment in research are essential to mitigate the public health impact of this deadly virus[4].

This underlines the need for strong vigilance and rapid outbreak containment in Guinea and Ghana in West Africa, in addition to one ongoing in Equatorial Guinea. MARV shares clinical and epidemiological characteristics with the EBOV, also in the Filoviridae family. Both viruses cause viral hemorrhagic fever (VHF), characterized by severe illness with high mortality potential[5]. Despite differences in specific viral structure and outbreak patterns, MARV and EBOV share similar mechanisms of pathogenesis and transmission, making their differentiation essential for targeted diagnostics, research, and public health interventions represented in the Table 1. VHFs are a group of illnesses caused by viruses that damage your blood vessels and can cause severe bleeding[6].

Table 1 Comparative overview of Marburg virus and Ebola virus.

Feature	MARV	Ebola virus
Virus family	Filoviridae	Filoviridae
First identified outbreak	1967: Marburg and Frankfurt, Germany, and Belgrade, Serbia	1976: Yambuku, Democratic Republic of the Congo, and Nzara, Sudan
Origin of outbreaks	African green monkeys imported from Uganda	Suspected zoonotic transmission, with bats as reservoirs and transmission to humans or other primates
Reservoir hosts	Egyptian fruit bat (Rousettus aegyptiacus) suspected	Fruit bats (Pteropodidae family), particularly Eidolon helvum
Case fatality rate (%)	24%-90%, depending on outbreak and case management	25%-90%, depending on outbreak and case management
Geographic distribution	Primarily sub-Saharan Africa	Primarily sub-Saharan Africa
Symptoms	Hemorrhagic fever, severe malaise, high fever, vomiting, diarrhea, organ dysfunction	Similarto MARV: Hemorrhagic fever, malaise, vomiting, diarrhea, multi-organ failure
Transmission	Direct contact with bodily fluids (e.g., blood, saliva, urine) of infected persons or animals	Direct contact with bodily fluids of infected persons or animals, contaminated surfaces
Laboratory diagnosis	PCR, ELISA, virus isolation	PCR, ELISA, virus isolation
Vaccines	No approved vaccine (research ongoing)	Approved vaccines available (e.g., rVSV-ZEBOV for Zaire strain)
Notable outbreaks	Angola (2004-2005), Democratic Republic of the Congo (1998-2000)	West Africa (2014-2016), Democratic Republic of the Congo (multiple outbreaks)

ELISA: Enzyme-linked immunosorbent assay; MARV: Marburg virus; PCR: Polymerase chain reaction.

We have included a "literature search strategy" section, outlining the research strategy employed to source relevant literature. This review was conducted by systematically searching multiple databases, including PubMed, Scopus, and Web of Science, using relevant keywords such as "Marburg virus", "Hemorrhagic fever", "Zoonotic transmission", "Diagnostics", and "Outbreak control". The search was restricted to peer-reviewed articles, guidelines from global health organizations [e.g., World Health Organization (WHO), Centers for Disease Control and Prevention (CDC)], and recent advancements published in the last two decades. Additionally, reference lists of key studies were screened to identify supplementary relevant literature.

EPIDEMIOLOGY

MVD has caused many outbreaks since its first recorded case in 1967 (Table 2). These epidemics mostly impact sub-Saharan African countries, although imported cases might infrequently reach North America and Europe. The death toll from this virus has varied greatly, from 23% to 88%, depending on the severity of the epidemic and the availability of healthcare in the affected areas[7]. While MVD has been the subject of large-scale epidemics in places like Angola and the Democratic Republic of the Congo, its persistence and zoonotic transmission potential have been brought to light by isolated occurrences in places like South Africa, Kenya, and Uganda. The need for close observation and quick action to contain the virus has been highlighted by recent outbreaks in Tanzania and West Africa[8]. With information on the areas hit, number of cases, number of deaths, and other pertinent details, the following Table 3 offers a historical perspective of major MVD outbreaks[6].

Table 2 Timeline of significant epidemics caused by the Marburg virus.

Year	Location	Cases	Deaths	Case fatality rate (%)	Notable features
1967	Marburg and Frankfurt, Germany; Belgrade, Serbia	29	7	24%	First recognized outbreak due to laboratory exposure
1967	Yugoslavia	2	0	0%	-
1975	South Africa	3	1	33%	-
1980	Kenya	2	1	50%	-
1987	Kenya	1	1	100%	-
1998-2000	Durba, Democratic Republic of the Congo	154	128	83%	Outbreak among gold miners
2004-2005	Uige Province, Angola	374	329	88%	Largest recorded outbreak
2007	Uganda	4	2	50%	-
2008	Netherland, United States of America	2	1	50%	-
2012	Ibanda, Uganda, and neighboring districts	15	4	27%	Spread across multiple districts
2014	Uganda	1	1	100%	-
2017	Kween District, Uganda	3	3	100%	Family cluster of cases
2021	Gueckedou, Guinea	1	1	100%	First reported case in West Africa
2022	Ashanti Region, Ghana	3	2	67%	Limited outbreak in West Africa
2023	Equatorial Guinea Equatorial Guinea	40	35	88%	Ongoing, affecting multiple provinces
2023	Kagera Region, Tanzania	9	6	67%	First Marburg virus disease outbreak in Tanzania

Table 3 Different types of viral haemorrhagic fevers and causative agents.

Family	Causative virus	Disease	Symptoms	Treatment
Arenaviridae	Lassa virus	Lassa fever	Fever, weakness, haemorrhage	Supportive care, ribavirin
Arenaviridae	Junin virus	Argentine haemorrhagic fever	Fever, malaise, haemorrhage	Supportive care
Arenaviridae	Chapare virus	Chapare hemorrhagic fever	fever, malaise, headache, vomiting and diarrhoea	Supportive care and early diagnosis
Arenaviridae	Guanarito virus	Venezuelan hemorrhagic fever	confusion, convulsions, coma, and bleeding from body orifices	No specific anti-viral treatment is available
Arenaviridae	Lujo virus	Lujo hemorrhagic fever	fever, headache, vomiting, diarrhea, arthralgia, myalgia	Supportive care
Arenaviridae	Lymphocytic choriomeningitis virus	Lymphocytic choriomeningitis	Fever (38.5 °C to 40 °C), malaise, myalgia, retro-orbital headache, photophobia, anorexia	Supportive care, ribavirin
Arenaviridae	Machupo virus	Bolivian hemorrhagic fever	Fever, malaise, fatigue headache, dizziness, myalgias, severe lower back pain	Supportive care
Arenaviridae	Sabia virus	Brazilian hemorrhagic fever	High fever, fatigue, maculopapular/petechial rash bleeding and haemorrhage	Supportive care, ribavirin antiviral drug
Bunyaviridae	Crimean-Congo haemorrhagic fever virus	Crimean-Congo haemorrhagic fever	Fever, myalgia, haemorrhage	Supportive care, ribavirin
Bunyaviridae	Hantan virus	Hantavirus pulmonary syndrome	Fever, muscle pain, pulmonary oedema	Supportive care
Bunyaviridae	Dobrava-Belgrade virus	Hemorrhagic fever with renal syndrome	Intense headache, back and abdominal pain, fever, chills, blurred vision	Supportive therapy, renal dialysis. Treatment with ribavirin
Bunyaviridae	Seoul virus	Hemorrhagic fever with renal syndrome	Intense headache, back and abdominal pain, fever, chills, blurred vision	Supportive therapy, renal dialysis. Treatment with ribavirin
Bunyaviridae	Puumalavirus	Hemorrhagic fever with renal syndrome	Intense headache, back and abdominal pain, fever, chills, blurred vision	Supportive therapy, renal dialysis. Treatment with ribavirin
Bunyaviridae	Rift Valley fever virus	Rift Valley fever	Transient fever, headache, severe muscle and joint pain, photophobia and anorexia	Drugs like Ibuprofen or Acetaminophen
Bunyaviridae	Saaremaa virus	Hemorrhagic fever with renal syndrome	Intense headache, back and abdominal pain, fever, chills, blurred vision	Supportive therapy, renal dialysis. Treatment with ribavirin
Bunyaviridae	Sin Nombre virus	Hantavirus pulmonary syndrome	Fever, muscle pain, pulmonary edema	Intubation and oxygen therapy, fluid replacement and use of medications to support blood pressure
Bunyaviridae	Severe fever and thrombocytopenia syndrome virus	Severe fever and thrombocytopenia syndrome	Fever, vomiting, diarrhoea, multiple organ failure, thrombocytopenia, leucopoenia elevated liver enzyme levels	Intravenous ribavirin
Bunyaviridae	Tula virus	Hemorrhagic fever with renal syndrome	Intense headache, back and abdominal pain, fever, chills, blurred vision	Supportive therapy, renal dialysis. Treatment with ribavirin
Filoviridae	Bundibugyo ebolavirus	EBOV disease	Fever, severe haemorrhage, organ failure	Supportive care, experimental treatments
Filoviridae	Marburg virus	Marburg haemorrhagic fever	Fever, severe haemorrhage, organ failure	Supportive care, experimental treatments
Filoviridae	Sudan ebolavirus	EBOV disease	Sudden onset of fever, fatigue, muscle pain, headaches, sore throat, vomiting, diarrhoea, rash, impaired kidney, liver functions	Monoclonal antibodies like Inmazeb, Ebanga
Filoviridae	Tai Forest ebolavirus	EBOV disease	Sudden onset of fever, fatigue, muscle pain, headaches, sore throat, vomiting, diarrhoea, rash, impaired kidney, liver	Monoclonal antibodies like Inmazeb, Ebanga
Filoviridae	EBOV	EBOV disease	Sudden onset of fever, fatigue, muscle pain, headaches, sore throat, vomiting, diarrhoea, rash, impaired kidney, liver functions	Monoclonal antibodies like Inmazeb, Ebanga
Flaviviridae	Dengue virus	Dengue fever	Fever, rash, haemorrhage	Supportive care, fluids
Flaviviridae	Kyasanur forest disease virus	Kyasanur forest disease	Sudden onset of chills, fever, and headache	Supportive treatment with maintenance of proper hydration and circulation by transfusion of IV fluids
Flaviviridae	Omsk hemorrhagic fever virus	Omsk hemorrhagic fever	Fever, headache, myalgia, cough, petechial rash or bruises	Supportive care
Flaviviridae	Yellow fever virus	Yellow fever	Fever, chills, headache, back pain, vomiting, fatigue	Rest, hydration and seek medical advice

EBOV: Ebola virus.

Since its first recorded outbreak in 1967, MVD has primarily affected sub-Saharan Africa, with occasional imported cases reported in Europe and North America. The initial outbreak occurred due to laboratory exposure to infected African green monkeys. Subsequent outbreaks have been linked to zoonotic transmission from Egyptian fruit bat (Rousettus aegyptiacus) and human-to-human transmission through direct contact with bodily fluids. Major outbreaks include the 1998–2000 epidemic in the Democratic Republic of the Congo, where gold miners were exposed to infected bats, and the 2004–2005 Angola outbreak, which had the highest case fatality rate (88%) due to delayed containment. More recent outbreaks in Guinea (2021), Ghana (2022), Equatorial Guinea, and Tanzania (2023) underscore the ongoing public health threat posed by MARV. Case fatality rates have varied from 23% to 88%, influenced by healthcare infrastructure and outbreak response measures. Strengthened surveillance, rapid diagnostics, and improved outbreak preparedness remain crucial in mitigating future outbreaks.

VIRUS STRUCTURE, GENOME AND GEOGRAPHICAL DISTRIBUTION

MARV is a filovirus with a single-stranded, negative-sense RNA genome (approximately 19 kb) that encodes seven structural proteins essential for replication and immune evasion. These include nucleoprotein (NP) for genome protection, viral matrix protein (VP) 35 for immune suppression, VP40 for viral assembly, glycoprotein (GP) for host cell entry, VP30 for transcription, VP24 for interferon (IFN) suppression, and L-polymerase for replication. Among EBOV proteins, NP, VP30, VP35, and L encapsidate the viral RNA into a nucleocapsid complex that is required for both genome protection and replication. Such a nucleocapsid is enclosed by a matrix protein, VP40, with a lipid envelope embedded with GP spikes. These GP spikes facilitate viral entry through host cells. GP also likely contributes to immune evasion by countering the IFN-stimulated protein tetherin that inhibits the spread of viruses. VP40 serves as a matrix protein and is an IFN antagonist, a virulence factor inhibiting the host innate immune response against infections, especially the IFN signalling[9]. Immune evasion is further facilitated by the minor matrix protein VP24 through disrupting cellular IFN responses. Finally, it is the responsibility of L-polymerase to perform replication of the genome and transcription, thus enabling efficient viral propagation[10]. These structural and functional adaptations enable MARV to evade host immune defences and cause severe, often fatal diseases in humans. The VP35 protein plays a crucial role in the virus’s replication and immune evasion (Figure 1)[11].

Figure 1 Structure of Marburg virus. NP: Nucleoprotein; VP: Viral matrix protein.

GEOGRAPHICAL DISTRIBUTION

MARV is primarily found in sub-Saharan Africa, where Egyptian fruit bat (Rousettus aegyptiacus) serve as its natural reservoir[12]. Outbreaks have been reported in: (1) Central Africa (DR Congo, Angola, Uganda); (2) West Africa (Guinea, Ghana); (3) East Africa (Kenya, Tanzania); and (4) Southern Africa (South Africa, Zimbabwe).

Imported cases in Europe (Germany, Serbia, Netherlands) and the United States through infected travelers or lab exposure.

Fatality and genotypic differences

There are two known variants of the virus: (1) MARV; and (2) Ravn virus (RAVV).

Both variants cause MVD, with fatality rates ranging from 23% to 90%, depending on outbreak response and healthcare access. Angola (2004-2005) outbreak had approximately 90% fatality, linked to a highly virulent MARV strain. RAVV cases, mainly in Kenya and Uganda, showed slightly lower fatality (approximately 50%-60%).

TRANSMISSION

The first step in the transmission of MVD to people is extended contact with places where Rousettus bat colonies are present, such as caves and mines. After infecting people, the MARV may transmit from person to person via physical contact. When one person's damaged skin or mucous membranes come into touch with another person's contaminated blood, secretions, organs, or other body fluids, this transmission happens[13]. Further factors that contribute to the transmission of viruses include surfaces and materials that have been in contact with infected body fluids, such as contaminated clothes or bedding. The lack of stringent enforcement of infection control safeguards puts health-care professionals at an increased risk. Another potential vector for infection is rituals associated with burials that include physical contact with the corpse. Until the virus is no longer detectable in their blood, infected individuals may spread the infection to others[14].

MARV reservoirs, like African fruit bat, may transmit the virus to other members of their own species via biting, sexual transmission, or direct contamination.

NATURAL RESERVOIRS AND ANIMAL HOSTS

There is substantial evidence that bats of the Rousettus aegyptiacus species are the principal hosts for the MARV. These bats harbor the virus without apparent illness, enabling the virus to persist and spread within bat populations, particularly across regions where Rousettus bat are prevalent (Figure 2). In 1967, during the first Marburg outbreak, there was a potential case of sexual transmission, with the virus detectable in the semen of some patients up to 203 days post-infection. Pregnant women infected with MVD face heightened risks, including severe disease progression, spontaneous abortion, and stillbirth, possibly due to immune function changes or placental involvement. Filoviruses like Marburg may live for a long time in both water and dry materials. But gamma irradiation, heat (60–75 minutes at 60 °C or five minutes of boiling), lipid solvents, sodium hypochlorite, and other disinfectants may render them inactive[15]. Human illnesses during the original Marburg epidemic “were caused by African green monkeys (Cercopithecus aethiops) (Figure 3), which were brought from Uganda, in addition to bats”. Pigs may shed the virus and possibly play an amplifying role in MVD epidemics, according to experimental investigations. They are also vulnerable to other filoviruses. In MVD-prone locations, pigs and other domestic animals should be carefully regarded as possible amplifier hosts, even though no other domestic animals have been conclusively connected to filovirus outbreaks[16]. Precautionary measures, particularly on pig farms in Africa, are essential to prevent cross-species transmission from fruit bats to pigs, which could amplify and potentially drive MARV outbreaks (Figure 3)[17,18].

Figure 2 Marburg virus transmission and dissemination. Marburg virus reservoirs, like African fruit bat, may transmit the virus to other members of their own species via biting, sexual transmission, or direct contamination.

Figure 3 Rousettus aegyptiacus bat and Cercopithecus aethiops.

PATHOGENESIS

The MARV causes systemic immunological dysfunction by infecting cells via direct contact with their fluids or tissues, which in turn targets other cells (Figure 4). Upon entering the body, MARV infects dendritic cells, critical for immune activation, impairing their ability to present antigens and leading to poor stimulation of T-lymphocytes. This immune evasion results in widespread lymphocyte apoptosis and subsequent immunosuppression. Systemic inflammation and tissue damage are exacerbated when T-lymphocyte failure sets off a cytokine storm, which is defined as severe, uncontrolled immune response where the body releases a large amount of inflammatory cytokines, leading to systemic damage and often contributing significantly to the fatal complications of MVD; this occurs due to the virus's ability to dysregulate the immune system, causing an excessive inflammatory response. It triggers a cascade of immune responses, leading to the overproduction of pro-inflammatory cytokines like interleukin-6, tumor necrosis factor, and interferons, which can damage blood vessels and contribute to multi-organ failure[19]. Increased vascular permeability and breakdown of vascular integrity occur simultaneously when MARV-infected macrophages go through uncontrolled activation and release more cytokines that harm endothelial cells. Haemorrhages may be caused by Coagulopathy, disseminated intravascular coagulation, and systemic viral replication, all of which are influenced by this endothelial dysfunction[20].

Figure 4 Human model of Marburg virus hemorrhagic fever pathogenesis.

Lymphocyte apoptotic situation results from an infection of dendritic cells, which leads to inadequate T lymphocyte stimulation. As a result, the body's immune system is lowered and the amount of cytokines and chemokines increases, which may cause shock and harm several organs. Infection with macrophages or monocytes triggers the unchecked production of cytokines and chemokines, which in turn sustain the damage done to endothelial cells and T lymphocytes. When this infection spreads to endothelial cells, it may replicate throughout the body. Liver parenchymal cell infections may reduce coagulation factors, which in turn can lead to bleeding complications. Infection of the adrenal gland's adrenocortical cells by MARV may cause metabolic abnormalities, dysregulation of blood pressure, and, in advanced stages, haemorrhage. Lymph nodes and spleen infections are particularly dangerous because they cause tissue necrosis and impaired adaptive response when they infect lymphoid tissues.

MARV also targets hepatocytes, resulting in impaired liver function and decreased production of coagulation factors, which exacerbates bleeding. Infection of adrenal cortical cells disrupts hormone production, leading to metabolic disorders and blood pressure dysregulation. In the late phase of MARV infection, the most prominent organ failure is multi-organ failure where multiple organs like the liver, kidneys, and pancreas are severely damaged, leading to complications like shock, severe dehydration, and ultimately death due to systemic dysfunction; this typically occurs as a result of widespread inflammation, bleeding, and coagulopathy caused by the virus. Additionally, MARV affects lymphoid tissues, causing necrosis and impairing adaptive immune responses. The destruction of lymphoid tissues further compromises the immune system, leading to severe systemic damage. The combination of endothelial damage, immune suppression, coagulopathy, and metabolic dysfunction culminates in shock, multi-organ failure, and death in severe cases. These pathogenic mechanisms underscore the need for rapid diagnosis and supportive care to manage MVD effectively[21].

Symptoms

Symptoms similar to the flu, including a high temperature, a strong headache, and chills, are present during the first of three clinical stages of MVD, which lasts from days 1 to 4. Most patients quickly become incapacitated after experiencing gastrointestinal discomfort, which includes symptoms including nausea, vomiting, and diarrhoea. Hemorrhagic symptoms, including petechiae and mucosal bleeding, a maculopapular rash, and harm to vital organs such the kidneys and liver, intensify during the early organ phase (days 5–13). There are two potential outcomes in the last phase, the late organ phase: (1) Either recovery with supportive treatment; (2) Death from multiorgan failure, shock; and (3) Severe internal bleeding. Improving survival outcomes is greatly enhanced by early intervention and supportive care[22].

DIAGNOSIS

Diagnosing MVD involves identifying the virus through clinical evaluation, laboratory testing, and epidemiological insights. Early symptoms are non-specific, making laboratory diagnostics essential for confirmation. The timeline below outlines key diagnostic methods at different stages of the disease, helping to guide effective outbreak control and patient care. Histopathological approaches, such as immunohistochemistry, have proven useful, particularly in post-mortem analyses[22]. Diagnosing MVD involves identifying the virus through clinical evaluation, laboratory testing, and epidemiological insights. Early symptoms are non-specific, making laboratory diagnostics essential for confirmation. The timeline below outlines key diagnostic methods at different stages of the disease, helping to guide effective outbreak control and patient care[23]. The isolation of the MARV serves as a crucial diagnostic method for MVD, with Vero and Vero E6 cell lines being commonly utilized for viral propagation. However, due to the necessity of handling the virus in Biosafety level-4 (BSL-4) laboratories, which are not widely accessible, this method is not routinely employed for clinical diagnosis. Instead, molecular diagnostic techniques, such as RT-PCR, nested RT-PCR, and quantitative RT-PCR, offer high sensitivity and specificity for detecting MVD by targeting viral genes, including NP, L, and GP[24,25]. Among these, the GP gene is particularly strain-specific, aiding in differentiation between viral strains, while VP40 and NP genes are more conserved[26,27]. However, variability in the performance of RT-PCR systems across laboratories may lead to false negatives due to limited strain coverage.

For early-stage detection, antigen-based assays like the ELISA provide a viable alternative, targeting viral proteins such as NP, VP40, and GP. Additionally, serological tests, including ELISA and indirect immunofluorescence assay, have been employed to detect MARV-specific immunoglobulin (Ig) M and IgG antibodies. IgM detection is indicative of recent infection, appearing within 2 days to 4 days post-symptom onset, whereas IgG antibodies may persist for up to two years, signifying past exposure[28].

Currently, only a limited number of commercial diagnostic tests exist for MARV. Clinical specimens from suspected cases must be processed under strict biosafety measures, with RT-PCR and ELISA on non-inactivated samples requiring BSL-3 containment and virus isolation necessitating BSL-4 facilities. In contrast, RT-PCR and ELISA conducted on inactivated samples can be safely performed within BSL-2 laboratories, making them more accessible for diagnostic use[29].

The diagnosis of MVD is challenging due to its initial non-specific symptoms, which resemble other tropical diseases such as malaria, typhoid fever, leptospirosis, and other VHFs. Early and accurate diagnosis is critical for outbreak control, patient management, and preventing further transmission.

EARLY DETECTION METHODS

Early detection of MVD primarily relies on clinical evaluation, epidemiological history, and laboratory confirmation. Patients with a history of travel to endemic regions, exposure to caves or mines inhabited by fruit bats (Rousettus aegyptiacus), or contact with infected individuals should be suspected of MVD. Key early symptoms include sudden onset of high fever, severe headache, chills, muscle aches, and gastrointestinal disturbances (Table 4). However, laboratory confirmation is essential to distinguish MVD from other diseases.

Table 4 Phases of Marburg virus with symptoms.

Incubation Period (5–10 days)
Phase	Duration	Key symptoms	Outcome	Treatment
Generalization phase	Days 1–4	Fever (39–40 °C), headache, chills, myalgia, anorexia. Gastrointestinal symptoms like nausea, vomiting, diarrhoea	Supportive care may prevent progression	Galidesivir (BCX4430)
Early organ phase	Days 5–13	Hemorrhagic symptoms (petechiae, mucosal bleeding), maculopapular rash, fatigue, organ damage (kidney, liver)	Escalation in disease severity	Favipiravir (T-705), Obeldesivir
Late organ phase/convalescence phase	Days 13+	Recovery: Gradual resolution of symptoms. Fatality: Multiorgan failure, shock, dehydration	Recovery or death within 8–16 days	Remdesivir (GS-5734), AVI-7288

Environmental and socioeconomic factors influencing Marburg virus transmission

Several environmental and socioeconomic factors contribute to the transmission of MARV, influencing its spread within communities and across regions[30]. MARV transmission is influenced by a range of environmental and socioeconomic factors that contribute to its spread within human populations. Understanding these factors is crucial for developing effective prevention and control measures[31].

Contact with infected animals: The primary reservoir of MARV is the Egyptian fruit bat (Rousettus aegyptiacus). Individuals who enter caves, mines, or other bat-inhabited areas risk exposure to the virus through bat droppings, saliva, or direct contact. Additionally, early outbreaks were linked to laboratory exposure to infected African green monkeys(Cercopithecus aethiops) imported from Uganda. Close interaction with infected animals, particularly fruit bats (Rousettus aegyptiacus), or their bodily fluids poses a primary risk for human infection.

Exposure to contaminated surfaces: Hygiene and disinfection procedures are crucial since the virus may spread by touch with contaminated surfaces, materials, or items.

Inadequate infection control: MARV spreads through direct contact with the bodily fluids (blood, saliva, vomit, urine, and feces) of infected individuals, as well as through contaminated surfaces, objects, and medical instruments. Healthcare workers are particularly vulnerable, especially in settings with inadequate infection control practices and limited access to personal protective equipment (PPE). Healthcare workers are at high risk of infection when proper infection prevention measures, such as wearing PPE, are not strictly implemented while caring for patients.

Traditional burial practices: Traditional burial rituals, which often involve direct handling of the deceased, contribute significantly to viral transmission. Family members and caregivers are at high risk when preparing bodies for funerals without adequate protective measures. Educating communities about safe burial protocols is critical in containing outbreaks. Direct physical contact with a deceased person's body during burial processes significantly increases the threat of viral transmission across communities.

Travel to endemic regions: MARV outbreaks can spread across regions through human travel and migration. Movement between rural and urban areas increases the risk of transmission, making early detection, quarantine measures, and contact tracing vital to containment efforts. People are more likely to get the virus if they visit endemic areas in Africa, go into caves or mines where fruit bats live, or do anything else that might expose them to infected animals.

Healthcare system challenges: Limited healthcare infrastructure in endemic regions exacerbates the spread of MARV. Delayed diagnosis, lack of medical resources, and insufficient isolation facilities contribute to higher case fatality rates. Strengthening disease surveillance, diagnostic capabilities, and healthcare worker training is essential for outbreak response.

Economic and social disruptions: Outbreaks of MARV lead to severe economic consequences, including trade restrictions, loss of workforce productivity, and declining tourism. Fear and stigma associated with the disease further isolate affected individuals and communities, hindering outbreak response efforts and discouraging healthcare-seeking behavior.

TREATMENT

Currently, no approved vaccines or antiviral therapies exist for MVD, but significant progress has been made in developing potential candidates. Supportive care, including rehydration and symptom management, remains the primary treatment approach (Table 5). The Table 5 below summarizes the latest advancements in clinical trials for MARV vaccines and therapeutics.

Table 5 Treatment and next steps.

Vaccine/treatment	Type	Trial phase	Key findings	Next steps
cAd3-Marburg	Chimpanzee adenovirus vector	Phase 1	95% immune response in participants	Phase 2 trials pending
Mvabea (MVA-BN-Filo)	Modified Vaccinia Ankara	Phase 1	Safe, good immune response	Phase 2/3 trials planned
Marburg virus DNA plasmid vaccine	DNA-based vaccine	Phase 1	Early immune activation observed	Further studies required
Galidesivir	RNA polymerase inhibitor	Preclinical	Effective in animal models	Human trials needed
Remdesivir	Antiviral drug	Preclinical	Shows potential in vitro	Further evaluation required

The EMA has authorized Ebola vaccines Zabdeno (Ad26.ZEBOV) provides active immunisation for prevention of disease caused by EBOV in individuals ≥ 1 year of age and Mvabea (MVA-BN-Filo) is to prevent EBOV disease in people who are at least one year old, which may offer cross-protection against MVD, though not yet proven in clinical trials[32-34].

The people with suspected or confirmed MVD should be hospitalized for early care and to prevent the spread of the disease.

Isolation

Patients should be isolated in a designated treatment center.

Early care

Early intensive care can improve survival.

Fluid resuscitation

Patients may need 5–10 liters or more of intravenous or oral fluids per day.

PREVENTION AND CONTROL

Effective prevention and control of MVD require a multi-pronged approach, including case management, surveillance, infection control, and community engagement[35]. The WHO aims to prevent Marburg outbreaks by maintaining surveillance and supporting preparedness plans in at-risk countries. Key strategies areas below (Table 6).

Table 6 Prevention and control.

Category	Key strategies
Case management	Early diagnosis, isolation of confirmed cases, and supportive care to reduce mortality
Surveillance and contact tracing	Identifying cases, monitoring close contacts for 21 days, and implementing quarantine if necessary
Infection control in healthcare settings	Strict hand hygiene, PPE usage, safe injection practices, and handling of biological specimens in high-containment labs
Community awareness and engagement	Educating populations on transmission risks, reducing stigma, and encouraging early healthcare-seeking behavior
Preventing Bat-to-human transmission	Avoiding caves/mines with fruit bat colonies, using protective gear for workers in high-risk areas
Preventing human-to-human transmission	Avoiding contact with bodily fluids of infected individuals, using protective measures for caregivers and healthcare workers
Safe burial practices	Implementing protocols for dignified but safe burials, avoiding direct contact with deceased bodies
Public health measures	Restricting travel to and from outbreak zones, ensuring preparedness plans, and maintaining emergency stockpiles of PPE and diagnostic kits

PPE: Personal protective equipment.

Due to the high fatality rate and potential for widespread outbreaks, immediate action is required from health professionals, policymakers, and global health organizations to prevent and control MVD. Governments must prioritize investment in healthcare infrastructure, surveillance systems, and rapid response teams to detect and contain outbreaks before they escalate.

Healthcare professionals play a critical role in implementing strict infection control protocols, ensuring early diagnosis, and providing adequate patient care. Training programs should be intensified to equip frontline workers with the necessary skills and PPE to handle cases safely.

Global health authorities, including WHO and CDC, must strengthen cross-border collaborations to improve disease monitoring, rapid diagnostic capabilities, and vaccine research. Urgent acceleration of clinical trials for vaccines and antiviral treatments is essential, along with increased funding for research into sustainable outbreak control measures.

Public health campaigns should actively engage communities in at-risk regions to educate individuals on personal protective measures, safe burial practices, and the risks of bat-to-human transmission. Governments must work with local leaders to ensure culturally sensitive public health messaging to prevent misinformation and stigma.

The WHO plays a pivotal role in coordinating global responses by supporting outbreak surveillance, laboratory diagnostics, risk communication, and emergency preparedness in high-risk regions. WHO provides technical guidance, deploys rapid response teams, and ensures effective case management through international collaboration. Strengthening healthcare systems in endemic regions, investing in vaccine and therapeutic research, and maintaining global vigilance are critical steps in preventing future outbreaks

WHO RESPONSE AND FUTURE DIRECTIONS

The WHO leads global efforts to detect, contain, and prevent MVD through surveillance, rapid response teams, laboratory support, and infection control measures. Strengthening healthcare infrastructure, training healthcare workers, and promoting safe burial practices remain key priorities[36].

The WHO plays a pivotal role in preventing, detecting, and responding to MARV outbreaks through global surveillance, rapid response, and coordinated outbreak management. WHO supports early detection via global monitoring systems and facilitates laboratory diagnostics, case management, and infection control in affected regions. It provides technical expertise, emergency response teams, and medical resources to enhance national outbreak preparedness. WHO also coordinates vaccine research, promotes community awareness, and enforces infection control measures, including safe burials and healthcare protocols. Through its International Health Regulations framework, WHO strengthens global preparedness strategies, ensuring effective containment and response to MARV outbreaks while fostering international collaboration and research advancements.

Given the increasing outbreaks, international collaboration is essential for developing rapid diagnostics, effective treatments, and vaccines. WHO emphasizes cross-border cooperation, real-time data sharing, and funding for vaccine trials to accelerate response efforts.

Future strategies should focus on enhancing public health preparedness, integrating digital health tools, and investing in genomic surveillance. A unified, multisectoral approach involving governments, research institutions, and the private sector is critical to prevent future outbreaks and reduce MVD’s global health impact.

The emergence of mRNA technology has opened new avenues for Marburg vaccine development. The vaccines include MARVAX consortium, cAd3-MARV. The novel Promising therapeutic strategies for MARV infection are Estradiol benzoate, INVEGA (Paliperidone), Tilorone, Quinacrine, Galidesivir, Favipiravir (T-705)[37].

Additionally, concerted efforts must focus on accelerating the development and regulatory approval of novel therapies and vaccines. Bridging these research gaps is crucial to enhance global preparedness and response to MARV outbreaks, ultimately mitigating its impact on public health.

CONCLUSION

In both endemic and non-endemic countries, MARV may cause severe hemorrhagic fever and high fatality rates, making it a major and increasing public health concern. Recent outbreaks have highlighted the virus's potential for widespread transmission, emphasizing the need for global vigilance, rapid diagnostic tools, and effective therapeutic interventions. Despite sharing similarities with EBOV, MARV has distinct biological and epidemiological characteristics that require targeted research and public health strategies. Current efforts in vaccine development, experimental therapeutics, and enhanced outbreak containment measures show promise but remain insufficient to fully mitigate its impact. Bridging gaps in understanding MARV pathogenesis, improving diagnostics, and accelerating the regulatory approval of vaccines and treatments are critical for future preparedness. Addressing the difficulties presented by MARV and safeguarding public health on an international scale requires strengthened global cooperation and continuous investments in research. To achieve this goal, we must work together to discover and develop novel antimicrobial agents, reduce antibiotic overuse, and implement stringent measures to prevent and control infections. Public awareness and international cooperation further emphasize the need to act on the growing threat of antibiotic resistance. Small molecule inhibitors, nucleic acid therapies, and immune modulators are wielding their weapons against the virus, disrupting its replication, and bolstering our defences.

ACKNOWLEDGEMENTS

I acknowledgement my sincere thanks to Maharajah’s College of Pharmacy, Vizianagaram for continuous support and cooperation for completion of this work.