Marburg virus outbreak: a global health threat, zoonotic risks, and the urgent need for international action.

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Learn more: PMC Disclaimer | PMC Copyright Notice Virusdisease . 2025 Sep 18;36(2):233–240. doi: 10.1007/s13337-025-00940-y Marburg virus outbreak: a global health threat, zoonotic risks, and the urgent need for international action Sayak Das 1 , Nagendra Thakur 2, ✉ , Arpita S Harnam 3, 6 , Janusz T Paweska 4, 6 , Ahmed S Abdel-Moneim 5, 6 , Shailendra K Saxena 3, 6, 7, ✉ Author information Article notes Copyright and License information 1 Department of Life Science and Bioinformatics, Har Gobind Khurana School of Life Sciences, Assam University, Silchar, Assam India 2 Department of Microbiology, School of Life Sciences, Sikkim University, 6th Mile, Samdur, Tadong, Gangtok, Sikkim India 3 Centre for Advanced Research (CFAR), Faculty of Medicine, King George’s Medical University (KGMU), Lucknow, 226003 India 4 Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham-Johannesburg, South Africa 5 Department of Virology, Beni-Suef University, Beni-Suef, Egypt 6 World Society for Virology (WSV), Northampton, MA USA 7 The Indian Virological Society (IVS), New Delhi, India ✉ Corresponding author. Received 2025 Jun 26; Accepted 2025 Aug 20; Issue date 2025 Jun. © The Author(s), under exclusive licence to Indian Virological Society 2025 PMC Copyright notice PMCID: PMC12474775  PMID: 41018218 Abstract Bats, the archaic natural reservoir hosting a plethora of viruses, are rather a “Pandora's Box” and that has been opened. The recent SARS-CoV-2 pandemic has demonstrated the importance of global data sharing and international cooperation for health research. Recent Marburg virus (MARV) outbreaks have put West Africa on alert, and this calls for immediate attention from all travelers and globetrotters, as the situation is alarming. MARV is an enveloped virus with unsegmented negative-sense RNA as its genome, which belongs to the family of Filoviridae in the order Mononegavirales. MARV is a virus of zoonotic origin that can transmit from its natural reservoir in bats to primarily infect other hosts such as C. aethiops or humans. Marburg virus disease (Marburg/MVD) was first noted on the African continent in Uganda beginning in 1967, and subsequently, hemorrhagic fever outbreaks occurred in Belgrade, Yugoslavia, Marburg, and Frankfurt laboratories in 1968. Several preclinical evaluations for the Marburg virus vaccine, including vesicular stomatitis virus or adenoviral vectors, DNA, virus-like replicons, inactivated viruses, and combinatorial modalities, are under trial. However, due to the absence of a vaccine, it is imperative for policymakers and medical professionals to collaborate on developing effective safety and prevention protocols to curb the spread of the Marburg virus and control the ongoing outbreak. This situation underscores the need for proactive measures, timely responses, and international coordination to prevent further health crises linked to zoonotic viruses. Keywords: Marburg virus, Filoviruses, Pandemic, Natural reservoir, Zoonotic Introduction Marburg strikes Rwanda with a fatal filovirus outbreak, demanding immediate global attention. Between 20 January and 11 March 2025, 108 suspected MVD cases were reported in Tanzania with 106 testing negative, 281 contacts identified (nine later classified as probable or confirmed cases), and after 42 days without new confirmed cases since the last death on 28 January, the outbreak was declared over on 13 March 2025 as per WHO recommendations [ 8 , 46 , 63 ]. Deep-end crisis of wars upfront engaging humanitarian rescue missions from Ukraine to the Middle-East is yet to grasp for a breath,however, Pandora seems to never fail to contemplate the world. Current global scenario of virus outbreaks on platter served are—India and Sweden sharing its own heightened security scare with positive cases of Mpox virus, Europe still juggling with variants of COVID-19 strains, South American nations glancing at Oropouche virus (OROV), bird flu variants infecting cattle/cows in USA and dengue across other nations (DONs, 2024). WHO is left baffled, and the present situation is very dismaying to all travelers and globe-trotting communities. Amongst all of these potential biological outbreaks, threats more pertinent to the Marburg virus may be our future pandemic concern. In 1967, concurrent outbreaks in the German cities of Marburg and Frankfurt led to the discovery of the Marburg virus (MARV), an RNA virus with a single-stranded genome that causes Marburg virus disease (MVD) in humans [ 6 ]. Given that MVD is once again on the rise, the situation in West Africa appears to be alarming. On August 9, 2021, Guinea reported the first-ever case of MARV [ 40 ]. And most recently, on July 20, 2022, Ghana reported the nation's first-ever case of MARV [ 28 ]. The Marburg virus has a filamentous structure, a shape like shephered’s crook, number six or spiral, and can occasionally branch. It is an enveloped virus with unsegmented negative-sense RNA [ 19 ]. The MARV, which causes severe MVD and can be fatal, belongs to the family of filoviruses in the order Mononegavirales. It is related to the Ebola virus (EBOV) [ 7 ]. There is just one species of Marburg virus ( Marburg marburgvirus ) in the genus Marburgvirus, and this genus is represented by two viruses—MARV and Ravn virus (RAVV) [ 43 , 51 ]. Although this virus has numerous variants (Marburg Muskoke, Marburg Angola, Ci67, Ozolin, etc.), the severe Marburg hemorrhagic fever (MHF) or MVD is thought to be caused by the Lake Victoria Marburg virus strain [ 49 ]. Natural hosts of MARV The filoviruses, which cause MVD, are thought to have fruit bats of the Pteropodidae family as natural hosts in Africa [ 1 ]. Potential hosts of the MARV are fruit bats in the genus Rousettus ( Rousettus aegyptiacus ) [ 59 ]. Additionally, reports of it have come from various chiropterans, like the Round Leaf Bat ( Hipposideros caffer ) [ 54 ]. The geographic distribution of MARV and fruit bats in the Pteropodidae family is positively correlated. The infected African Green Monkeys ( Cercopithecus aethiops ) transported from Uganda were the most intriguing aspect of the early traced MVD agents [ 42 ]. MARV is unquestionably a zoonotic origin virus that can transmit from a natural reservoir (bats) to primary infected animals like C. aethiops or humans (as aerosols through oral route from fecal infested bat caves or mining grounds or nosocomial route via parenteral exposure) as shown in Fig. 1 [ 4 , 46 , 53 ]. Fig. 1. Open in a new tab Possible routes of transmission of Marburg virus (MARV), where the following possible transmittances have been shown. (A) Transmission Route A : Fruit bats to fruits [ 4 ]. Chiropterans, when fed on fruits, might stay back on partially consumed or bitten fruits. So, direct transmission of MARV from its natural reservoir to fruits can occur as a natural food habit of chiropterans. (B) Transmission Route B : Bats to monkeys [ 1 ]. (a) Chiropterans may attack monkeys, or (b) monkeys may get exposed to the fecal deposits of bats, or (c) previously physically injured monkeys may get exposure to bat-infested regions, or (d) involvement of bat-associated nycteribiid flies ( Eucamsipoda africana ) as transmission vector from infected bats to fruits to monkeys [ 47 ]. All these hypothetical routes can transmit MARV from its natural reservoir (bat) to monkeys. (C) Transmission Route C : Monkeys may feed on fruits either bitten/eaten by bats. In this case, if the viral load can persist till the time of consumption in fruits, it may get transmitted to monkeys. (D) Transmission Route D : Humans, while cleaning/working in the bat-infested mines or visiting bat-infested caves, may get MARV transmitted directly to them. It can occur through aerial rote, either as aerosols or direct contact, while trying to catch chiropterans. (E) Transmission Route E : Humans may also get in contact with bat-infected monkeys having MARV while handling the monkeys. Another way of transmission of MARV from infected monkeys to humans can be attributed to laboratory research works or veterinary care [ 53 ]. And lastly, by the consumption of bush meat. (f) Transmission Route f (Secondary transmission) : Human to human transmission via parenteral introduction of exposed/infected individual to unexposed individuals. (g) Transmission Route g (Secondary transmission) : Human to human transmission via nosocomial infection Africa and its clinical history of MVD The export of diseased African Green monkeys brought MVD dynamics outside of Africa, and into the European countries'limelight as it caused 32 fatalities [ 42 ]. Hemorrhagic fever outbreaks happened concurrently in Belgrade, Yugoslavia, Marburg, and Frankfurt laboratories [ 53 ]. Instances of MVD were first noted on the African continent in Uganda beginning in 1967 [ 62 ]. The Democratic Republic of the Congo (1994, 1998–2000), Angola (2005), Uganda, Kenya (1980, 1987), and Zimbabwe (1975) are the other five nations that have reported occasional cases and MVD epidemics (2007) [ 38 ]. Both the Marburg and Ebola epidemics in South Africa in 1975 and 1996, respectively, were reported as a result of the immigration of infected individuals from Zimbabwe and Gabon [ 17 ]. In 2008, the Netherlands and the USA both reported one case of imported MVD. The two patients were tourists who had visited Python Cave in southeast Uganda's Queen Elizabeth National Park's Maramagambo woodland [ 70 ]. This virus caused severe effects in the Soviet Union, Koltsovo, and Kenya in 1987–1988 that resulted in 100% fatality [ 21 ]. People with MARV infection had a death rate of about 90% in Angola in 2004 [ 62 ]. In 2008, it led to outbreaks in the USA, the Netherlands, and Uganda. MARV outbreaks were notable in Uganda in 2012, 2014, and 2017 [ 70 ]. For the MVD’s geographical spread, recent outbreaks from Ghana and Guinea have contributed additional transmission maps. Transmission Unprotected contact with infected bat feces or aerosols is the most likely way for MARV to spread from its animal host to people, as reported in two instances of tourists visiting Uganda in 2008 [ 70 ]. Following this first transition of the virus from the host animal to people, transmission happens via interpersonal contact [ 21 ]. Mucosal interfaces, cutaneous abrasions, as well as parenteral interactions all play a role in the transmission of MARV [ 62 ]. People who handled diseased non-human primates or had direct contact with their fluids or cell cultures have contracted the disease in prior outbreaks [ 6 ]. Humans have contracted the virus through direct contact and close situations [ 27 ]. A typical example is transmission through carers/nurses in hospitals or at home (nosocomial transmission) [ 49 ]. Epidemiology Fundamentally akin to Ebola, MVD is a very virulent illness that can induce hemorrhagic fever [ 54 ]. The Filoviridae family (filovirus) includes the Marburg and Ebola viruses [ 4 ]. Rousettus bats, a specific kind of fruit bat that may transmit the Marburg virus and are frequently found in mines or caves, are the first source of infection for humans [ 2 , 47 ]. Humans can contract the Marburg virus by coming into intimate contact (via broken skin or mucous membranes) with an infected person's blood, secretions, organs, or other body fluids, as well as by coming into touch with things that have been contaminated by these fluids, like bedding or clothing [ 43 ]. In the past, medical personnel have contracted the infection while caring for patients who had suspected or proven MVD [ 51 ]. The Marburg virus has also been reported to spread during funeral rites as participants come into close contact with the deceased’s corpse. [ 1 ]. The duration of incubation ranges from two to twenty-one days [ 33 ]. Marburg virus illness onset is abrupt, accompanied by a high fever, excruciating headache, and extreme malaise. On the third day, severe watery diarrhea, cramping and pain in the abdomen, nausea, and vomiting may start. Even though not every case has hemorrhagic symptoms, fatal cases typically have some kind of bleeding, frequently from several locations, and severe hemorrhagic manifestations may show up five to seven days after symptoms start. In cases of death, shock, and significant blood loss typically occur 8–9 days following the onset of symptoms. Implications for travelers In modern times, infected people can travel to practically anywhere in the world while incubating the deadly pathogen inside them. Additionally, travelling is a fragmented activity that frequently involves numerous pauses and stopovers [ 9 ]. This implies that travelers, along with trade, which transfers plants, animals, and other materials, are a part of the dynamic global process of shifting biota [ 10 ]. Travelers can act as disease sentinels and so contribute to the system for worldwide disease surveillance [ 58 ]. The risk of newly emerging infectious diseases is significantly raised by traveling [ 10 ]. Person-to-person transmitted illnesses can be easily transmitted by travelers to any location in the world [ 68 ]. A good illustration is the human immunodeficiency virus (HIV), which was pretty much completely brought to every region of the globe by travelers [ 48 ]. The current worldwide spread of the swine flu, avian flu, SARS-CoV-2, and monkeypox viruses was aided by international aviation travel. Travelers who lack immunity are more susceptible to certain illnesses. Prevention/safeguards Several approaches for designing a vaccine against MARV are being followed. This includes vaccines based on viral vectors such as the vesicular stomatitis virus, adenovirus-vectored vaccines, DNA plasmid vaccines, and virus-like particles composed of several MARV proteins [ 33 , 49 , 70 ]. Despite these attempts, there is no approved vaccine against MARV on the market. Therapeutic approaches i. Ray of hope A solitary glimmer of optimism regarding the coming years has come from the findings of a first-in-human clinical investigation assessing a replication-deficient engineered chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in adult healthy individuals [ 22 ]. A single intramuscular administration of the cAd3-Marburg vaccine at either 1 × 10 10 or 1 × 10 11 particle units (pu) was given to competent persons between the ages of 18 and 50 [ 22 ]. Thus far, only typical reactogenicity has been noted; no negative consequences have been documented. Four weeks following vaccination, there was an increase in T-cell responses to the glycoprotein insert and neutralizing responses against the cAd3 vector. The cAd3-Marburg vaccination should be further evaluated in light of the trial's outcomes. Phase 2 research studies in Kenya and Uganda, a phase 1b clinical investigation in the USA ( NCT04723602 ), and an outbreak response clinical protocol (scheduled for Ghana) are among the next efforts [ 22 ]. The trial demonstrated a safety and immunogenicity profile that indicates the potential benefit of utilizing the cAd3-Marburg vaccine in response to the Marburg virus outbreak; however, despite the positive results, it has not yet received approval for human use. Preclinical evaluations have been conducted on a range of candidate platforms for the Marburg virus vaccine, including vesicular stomatitis virus or adenoviral vectors, DNA, virus-like replicons, inactivated viruses, and combinatorial modalities [ 16 , 30 , 39 , 41 , 51 , 55 ]. The initially developed filovirus shots to demonstrate 100% protective effectiveness in an NHP Ebola virus test system were replication-deficient adenoviral vectors encoding the Ebola virus glycoprotein [ 37 ]. This effective strategy was then applied to the Marburg virus [ 11 , 14 , 22 , 31 , 39 , 45 ]. Chimpanzee adenovirus type 3 (cAd3) has been identified as a promising candidate for clinical development among the adenoviruses evaluated as vectors for filovirus vaccines. This is due to the minimal human immunity that has previously been observed against the vector [ 31 , 45 ], the strong protective immunity that has been elicited against the vaccine inserts in preclinical models, and the excellent safety profile in Ebola vaccine clinical trials [ 12 , 56 , 57 ]. Phase 2 trials demonstrated the safety and immunogenicity of monovalent and bivalent cAd3-vectored Ebola glycoprotein vaccines, which protected NHPs against deadly Ebola infection five weeks after a single immunization [ 37 ]. The Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) developed a cAd3-Marburg vaccine and tested it preclinically in nonhuman primates (NHPs) based on the safety and immunogenicity of the cAd3 Ebola virus vaccines [ 23 ]. According to research, a dose of 10 10 particle units (pu) of the cAd3-Marburg vaccination offered complete protection against viraemia and death following a one-month exposure to the Marburg virus [ 22 , 31 , 45 ]. Crucially, protection was seen from the first week following immunization and continued for up to a year. The potential effectiveness of the cAd3-Marburg vaccine for ring vaccination strategies and safeguarding the health of people and medical personnel in Marburg-endemic regions is suggested by the vaccine's immediate effect and extended period of immunity [ 12 , 35 , 36 , 72 ]. ii. Ring vaccination The ring vaccination approach, inspired by smallpox eradication [ 18 ] and detailed by Dean and Longini [ 13 ], involves vaccinating contacts and contacts-of-contacts of confirmed cases, either individually or in cluster-randomized trials, to focus on high-risk groups and monitor virus transmission. Its design, influenced by statistical considerations such as per-protocol timing and zero inflation [ 34 ], was first applied during the 2014–2016 West African Ebola outbreak [ 15 , 45 ], to test the rVSV-ZEBOV vaccine [ 24 , 25 ]. The outbreak was unprecedented in scale compared to previous ones [ 68 ], and Phase III trials were recommended by WHO in late 2014 [ 29 ]. Implementation faced challenges, including unpredictable incidence trends, geographic dispersal, and poor trial infrastructure [ 67 ]. WHO’s Strategic Advisory Group of Experts (SAGE) recommended vaccinating healthcare workers and contacts of Ebola Zaire virus disease cases [ 34 , 64 ]. Ring vaccination has since been used in subsequent Ebola outbreaks, with vaccine efficacy further supported [ 26 ], leading to FDA approval of the Merck Ervebo vaccine in 2019 [ 69 ]. This adaptable trial design is especially useful for evaluating fast-acting vaccines during outbreaks with localized but intense transmission, even in resource-limited settings. iii. Miracle drug – Can Remdesivir cure MVD? Remdesivir's potential pharmacological model may prove beneficial for administering treatment against MARV, given its potency against the Ebola virus; however, further clinical trials are needed to confirm this [ 52 , 59 ]. The RNA-dependent RNA polymerase (RdRP) hypothesis of Baltimore classification theory states that RdRP is necessary for the production and replication of RNA virus genomes [ 5 ]. This family of viruses comprises a significant number of highly pathogenic pathogens that infect basically all species of animals and plants, including humans [ 2 ]. Due to the lack of effective preventative and curative measures, infections frequently result in outbreaks and pandemics that continue to be essentially uncontrollable [ 65 ]. Due to its essential role in viral growth, RdRP is one of the main antiviral targets being explored in response to this unmet medical need [ 60 ]. Numerous artificial nucleoside analogs have been shown in recent research to be capable of mimicking the corresponding natural nucleosides [ 65 , 71 ]. These mimics impede virus replication or encourage widespread, fatal mutations by slowing or terminating RdRP or by misincorporating [ 32 ]. A number of these analogs are currently being used in therapy on a regular basis after receiving clinical approval [ 53 , 59 ]. Remdesivir is the only FDA-approved drug for addressing COVID-19 patients who are part of the global pandemic of the twenty-first century [ 32 ]. The active form of remdesivir functions as a nucleoside analog to block the RNA-dependent RNA polymerase (RdRp) of coronaviruses, including SARS-CoV-2 [ 3 ]. Remdesivir is incorporated into the growing RNA product by the RdRp, allowing for the insertion of three more nucleotides before RNA synthesis stalls. Following remdesivir incorporation into the RNA product, a barrier to additional RNA translocation inhibits the inclusion of the fourth nucleotide [ 20 ]. This translocation barrier stops the RNA 3Ϲ-nucleotide from leaving the substrate-binding site and stops the following nucleoside triphosphate from entering, which causes RdRp to stall [ 32 ]. Travel advisory Tourists, business persons, travelers, including health aid workers, free health service providers such as NGOs and freelancers, traveling to Rwanda or any “Areas of Concern” (AoC) have to follow some strict protocols to safeguard their host native population from being exposed to the Marburg virus. Post-COVID-19, newer, stricter, corrective, and punitive measures have already been issued globally as guidelines to check and control the spread of MVD. Such travelers may be referred to as “Suspected People of Concern (SPC)”. Here are some of the health regimes that may be followed by such travelers have been suggested: i. Every Foreign Ministry and its respective embassies are to monitor the timeline and in-depth work schedule of such travelers (SPC). Contact tracing is of utmost importance. So, unbiased and complete cooperation should be provided to the authorities whenever deemed necessary. ii. Before traveling, they (SPC) must document their travel history and should be mentally prepared for all the quarantine and health procedures to be undergone in the future. Without appropriate disclosure, a visa shall not be obtained or may be terminated. iii. For any travel advisory, the WHO website must be consulted for a timely update. iv. All the local health guidelines as laid by the Rwanda or AoC must be adhered to in all circumstances. v. Travelers (SPC) should avoid any visit to local healthcare institutions or centers. For any emergency-related issues, appropriate measures as per WHO guidelines must be followed. vi. Any contact with a person showing symptoms of MVD, such as fever, diarrhea, vomiting, or hemorrhage, should be avoided at any cost. If contacted under unavoidable circumstances, then it has to be reported to the Embassy and the WHO healthcare workers. vii. Strict adherence to avoid any wild meat or bats, and consumption of meat of wild animals is completely prohibited. viii. Travelling should not interfere with any health service being provided at local centers or cause any hindrance in the disbursal of emergency services. ix. Health facilities should follow IPC (Infection Prevention and Control) and WASH (Water, Sanitation, and Hygiene) assessments as advised by WHO guidelines. x. Proper quarantine should be followed on return to the native country, and contact tracing protocols need to be established with SPC. The way forward Without vaccination, policymakers must work with medical professionals to develop appropriate safety and prevention protocols to stop the spread of the disease and control the current outbreak situation. To encourage health professionals to put in more time and effort during the outbreak, additional benefits should be provided. Additionally, the nation's monitoring programmes need to be improved, especially in and around the borders and hotspot regions. Speculative West African nations should strengthen their procedures for preparing for and responding to epidemics. At the numerous ports and borders, immigration, health, and policy officials must screen people coming into and leaving the country. The World Health Organization (WHO), which has a significant influence on the global community, as a result of the MARV outbreak, should jump in and help with the distribution of the resources required to combat the disease. Social media and other contemporary information-dissemination tools should be used to improve sensitization and other public health efforts. It would be beneficial for health practitioners to engage the community in spreading awareness of the condition, especially among those living in high-risk locations. The international community should intensify efforts to help Ghana and any other affected countries fight the disease with the haste it requires because of the potentially disastrous effects MARV could have on the entire planet, similar to the lines of COVID-19. Acknowledgements The authors are grateful to their Vice Chancellor for the encouragement for this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Funding We have not received any specific funding for this work. Declarations Conflict of Interest Authors declare no conflict of interest. Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Contributor Information Nagendra Thakur, Email: nthakur@cus.ac.in. Shailendra K. 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