Search Results (68)

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

Artificial intelligence (AI) plays a crucial role in modern healthcare by enhancing disease modeling and outbreak prediction. In this study, we develop an epidemiological model for the Marburg virus, integrating vaccination and treatment strategies while considering vaccine efficacy and treatment failure. The model exhibits mathematical symmetry in its equilibrium analysis, ensuring a balanced assessment of disease dynamics across human and bat reservoir populations. We compute the Marburg-free and endemic equilibrium points, derive the secondary infection threshold, and conduct sensitivity analysis using the PRCC method to identify key disease transmission parameters that are important for disease control. To validate the theory, we optimized a deep neural network (DNN) via grid search and employed it for dynamic analysis, which also validates the cutting-edge application of AI in healthcare. We also compare AI-based predictions with traditional numerical solutions for reproduction number for humans $R_{0h}>1$ and $R_{0h}<1$ for validation and efficacy of the AI approach. The results demonstrate the model’s stability, efficacy, and predictive power, emphasizing the synergy between AI and mathematical epidemiology. This study provides valuable insights for public health interventions and effective disease control strategies by leveraging AI-driven simulations, highlighting AI’s potential to revolutionize and enhance early detection and tailor treatment strategies. Full article

Due to the sudden emergence and burnout nature of Marburg virus (MARV) outbreaks, little is known about MARV’s pathogenicity and immunogenicity. These gaps in knowledge are limiting our understanding of the disease and the implementation of cost-effective prevention and control measures including case management through safe and effective therapeutic modalities. Therefore, this review aims to synthesize and summarize evidence about pathogenicity, immunogenicity, and virulence in humans towards MARV. Upon infection, MARV rapidly disseminates throughout various tissues, provoking severe cellular injury, particularly in lymphatic organs, the liver, kidneys, and the gastrointestinal tract. The virus takes advantage of host cells by avoiding immune responses, mainly by disrupting the function of dendritic cells and blocking the signaling pathways for interferon. As a result, patients experience profound immune dysregulation characterized by early lymphocyte depletion and a shift towards pro-inflammatory cytokine release, resulting in a cytokine storm that can lead to hemorrhagic septic shock. Additionally, adaptive immune responses, including antibody production, are impaired, further complicating recovery and increasing susceptibility to severe disease outcomes. Understanding these intricate host–pathogen interactions is critical for developing effective therapeutic strategies and vaccines against MARV. Continuing research is essential to explain the mechanisms of immune evasion and to identify potential intervention points for improving patient outcomes. Full article

During the current outbreak of Marburg virus disease (MVD) in Rwanda, we synthesized evidence from the literature to improve case management. Accordingly, experimental treatment was offered to patients under close follow-up. Remdesivir alone or in combination with monoclonal antibody treatment (MBP091) complemented with supportive care has improved the clinical outcomes of patients. Additionally, we have identified several experimental therapies currently under investigation, including antiviral drugs such as favipiravir, galidesivir, obeldesivir, and remdesivir, along with monoclonal and polyclonal antibodies (e.g., polyclonal IgG, monoclonal antibody MR-78-N; MR82-N; MR191-N; monoclonal antibodies MR186-YTE and MBP091). Furthermore, substantial progress is being made in vaccine development, with promising candidates including adenovirus-vectored vaccines, DNA vaccines, and the recombinant vesicular stomatitis virus (rVSV) vaccine. Moreover, innovative preventive and treatment strategies—such as synthetic hormones like estradiol benzoate, small interfering RNA (siRNA), interferon-β therapy, and phosphorodiamidate morpholino oligomers—are emerging as potential options for MVD management. Further investment is needed to accelerate research and optimize these therapeutics and preventive modalities. Additional epidemiological, preclinical, and clinical studies are warranted to generate the evidence required to inform policymaking, resource mobilization, and the implementation of cost-effective interventions for the prevention, control, and treatment of MVD. Full article

Marburg virus (MARV) is one of the deadliest human zoonotic pathogens, historically traced back to Uganda, in East African-cave-dwelling Egyptian fruit bats (Rousettus aegyptiacus), the probable cradle of MARV. Since its first identification in Germany and Serbia in 1967 due to laboratory contamination, MARV has caused 18 outbreaks in humans in Sub-Saharan Africa, with the latest in Tanzania in 2025 and 2023, Rwanda in 2024, and Equatorial Guinea in 2023. Efforts to control MARV through bat extermination in Sub-Saharan Africa have been ineffective, likely due to incomplete extermination and the recolonization of infected juvenile fruit bats. Over the past two decades, extensive molecular epidemiological research has generated over 70 complete MARV genomes, enabling detailed phylogenetic analysis, though bat-derived sequences are still rare. Phylogenetic analysis of Sub-Saharan African Marburgviruses from 1975 shows clustering with sequences from humans and bats, indicating that the virus reservoir species in these regions are not considerably distinct. This review aims to consolidate MARV comprehensive genomic data to provide a clearer picture of the current Marburg virus disease situation in Sub-Saharan Africa and, in turn, highlights the need for active genomic surveillance to identify hotspots and prevent future global outbreaks. Full article

In this review, we investigated the genetic diversity and evolutionary dynamics of the Orthomarburgvirus marburgense species that includes both Marburg virus (MARV) and Ravn virus (RAVV). Using sequence data from natural reservoir hosts and human cases reported during outbreaks, we conducted comprehensive analyses to explore the genetic variability, constructing haplotype networks at both the genome and gene levels to elucidate the viral dynamics and evolutionary pathways. Our results revealed distinct evolutionary trajectories for MARV and RAVV, with MARV exhibiting higher adaptability across different ecological regions. MARV showed substantial genetic diversity and evidence of varied evolutionary pressures, suggesting an ability to adapt to diverse environments. In contrast, RAVV demonstrated limited genetic diversity, with no detected recombination events, suggesting evolutionary stability. These differences indicate that, while MARV continues to diversify and adapt across regions, RAVV may be constrained in its evolutionary potential, possibly reflecting differing roles within the viral ecology of the Orthomarburgvirus marburgense species. Our analysis explains the evolutionary mechanisms of these viruses, highlighting that MARV is going through evolutionary adaptation for human-to-human transmission, alarmingly underscoring the global concern about MARV causing the next pandemic. However, further transdisciplinary One Health research is warranted to answer some remaining questions including the host range and genetic susceptibility of domestic and wildlife species as well as the role of the biodiversity network in the disease’s ecological dynamics. Full article

Background/Objectives: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa. Methods: The review protocol was registered on PROSPERO (ID: CRD42023415358) and previously published. Eighty-seven articles describing 85 studies were included, of which seventy-six measured antibodies to orthoebolaviruses and forty-one measured antibodies to orthomarburgviruses. Results: The results highlight three central findings that may have implications for vaccine development and deployment. First, substantial antibody seropositivity to Ebola virus (EBOV) and Sudan virus (SUDV) was observed in populations from outbreak-affected areas (≤33% seroprevalence among general populations; ≤41% seroprevalence among healthcare workers and close contacts of disease cases). Second, antibody seropositivity to EBOV, SUDV, and Marburg virus (MARV) was observed among populations from areas without reported outbreaks, with seroprevalence ranging from <1 to 21%. Third, in Central and East Africa, MARV antibody seroprevalence was substantially lower than EBOV or SUDV antibody seroprevalence, even in outbreak-affected areas and in populations at a moderate or high risk of infection (with MARV seroprevalence mostly ranging from 0 to 3%). Conclusions: Whilst gaps remain in our understanding of the significance of antibody seropositivity in some settings and contexts, these findings may be important in considering target indications for novel filovirus vaccines, in defining study designs and strategies for demonstrating vaccine efficacy or effectiveness, and in planning and evaluating vaccine deployment strategies to prevent and control outbreaks. Full article

Objectives: Marburg virus disease (MVD) is on the WHO list for pandemic-prone pathogens. The current outbreak in Rwanda provides an opportunity to map outbreaks and generate information to inform policymaking, resource mobilization, and guide the implementation of cost-effective response strategies. Methods: We synthesized available information about MVD to build holistic, up-to-date evidence to inform policymakers, public health leaders, and healthcare and public health services providers in their development and implementation of cost-effective preparedness, prevention, and control measures. Results: We have identified 20 outbreaks of MVD that occurred in 14 countries between 1967 and 2024; these outbreaks led to 580 confirmed cases and 423 deaths in total. We summarize the available information about the main clinical signs, diagnostic tools, primary reservoir, transmission dynamics, and case management protocol. We also document the best practices in the prevention and control of MVD outbreaks, including the implementation of a multisectoral One Health strategy for preparedness, prevention, and response to MVD outbreaks that incorporates the strict implementation of WASH and infection prevention measures, contact tracing, and the isolation of infected and suspected humans and animals, and enhances the implementation of the International Health Regulations, particularly efficient cross-country coordination. Conclusions: In the absence of a licensed treatment or vaccine for MVD, the response strategy to MVD should focus on preventive measures, including community engagement to promote the reduction in contact between humans and reservoirs, the supportive care and isolation of patients, and proper waste management. High risk populations such as frontline responders, including healthcare providers and community health workers, should be prioritized so that they can access all currently available protection measures. Full article

Background/Objectives: Marburg virus (MARV) is the etiological agent of Marburg Virus Disease (MVD), a rare but severe hemorrhagic fever disease with high case fatality rates in humans. Smaller outbreaks have frequently been reported in countries in Africa over the last few years, and confirmed human cases outside Africa are, so far, exclusively imported by returning travelers. Over the previous years, MARV has also spread to non-endemic African countries, demonstrating its potential to cause epidemics. Although MARV-specific vaccines are evaluated in preclinical and clinical research, none have been approved for human use. Modified Vaccinia virus Ankara (MVA), a well-established viral vector used to generate vaccines against emerging pathogens, can deliver multiple antigens and has a remarkable clinical safety and immunogenicity record, further supporting its evaluation as a vaccine against MARV. The rapid availability of safe and effective MVA-MARV vaccine candidates would expand the possibilities of multi-factored intervention strategies in endemic countries. Methods: We have used an optimized methodology to rapidly generate and characterize recombinant MVA candidate vaccines that meet the quality requirements to proceed to human clinical trials. As a proof-of-concept for the optimized methodology, we generated two recombinant MVAs that deliver either the MARV glycoprotein (MVA-MARV-GP) or the MARV nucleoprotein (MVA-MARV-NP). Results: Infections of human cell cultures with recombinant MVA-MARV-GP and MVA-MARV-NP confirmed the efficient synthesis of MARV-GP and MARV-NP proteins in mammalian cells, which are non-permissive for MVA replication. Prime-boost immunizations in C57BL/6J mice readily induced circulating serum antibodies binding to recombinant MARV-GP and MARV-NP proteins. Moreover, the MVA-MARV-candidate vaccines elicited MARV-specific T-cell responses in C57BL/6J mice. Conclusions: We confirmed the suitability of our two backbone viruses MVA-mCherry and MVA-GFP in a proof-of-concept study to rapidly generate candidate vaccines against MARV. However, further studies are warranted to characterize the protective efficacy of these recombinant MVA-MARV vaccines in other preclinical models and to evaluate them as vaccine candidates in humans. Full article

Marburg virus disease (MVD) is a zoonotic hemorrhagic disease with an estimated case fatality rate of up to 88%. Ghana recorded its first human MVD outbreak in June 2022 and although the outbreak was quickly brought under control, the transmission dynamics of the disease remained unclear. We assessed the presence of Marburg virus (MARV) antibodies in livestock and dogs and identified associated risk factors that increased the risk of these animals being exposed to MARV in five regions of Ghana. Sera collected from 3113 livestock and dogs in 2 climatic seasons (rainy and dry seasons) were tested for MARV antibodies using an indirect ELISA test. The samples were further tested using dot blotting to substantiate the presence of antibodies against MARV glycoprotein (GP). Overall, MARV antibodies were detected in 20.6% of the animals. The species-specific prevalence was 28.7% in cattle, 21.8% in sheep, 19.5% in goats, 15.3% in dogs and 11.2% in pigs. The seropositivity was higher in the rainy season [RR 1.5; 95% CI 1.3–1.8] and in older animals [RR = 2.6; 95% CI 1.9–3.4]. The findings underscore the importance of regular surveillance using the one health approach and future studies into the role of livestock and dogs as potential intermediaries in the circulation of MARV. Full article

Marburg hemorrhagic fever (MHF) is a fatal infectious disease caused by Marburg virus (MARV) infection, and MARV has been identified as a priority pathogen for vaccine development by the WHO. The glycoprotein (GP) of MARV mediates viral adhesion and invasion of host cells and therefore can be used as an effective target for vaccine development. Moreover, DNA vaccines have unique advantages, such as simple construction processes, low production costs, and few adverse reactions, but their immunogenicity may decrease due to the poor absorption rate of plasmids. Lysosome-associated membrane protein 1 (LAMP1) can direct antigens to lysosomes and endosomes and has great potential for improving the immunogenicity of nucleic acid vaccines. Therefore, we constructed a DNA vaccine based on a codon-optimized MARV GP (ID MF939097.1) fused with LAMP1 and explored the effect of a LAMP targeting strategy on improving the immunogenicity of the MARV DNA vaccine. ELISA, ELISpot, and flow cytometry revealed that the introduction of LAMP1 into the MARV DNA candidate vaccine improved the humoral and cellular immune response, enhanced the secretion of cytokines, and established long-term immune protection. Transcriptome analysis revealed that the LAMP targeting strategy significantly enriched antigen processing and presentation-related pathways, especially the MHC class II-related pathway, in the candidate vaccine. Our study broadens the strategic vision for enhanced DNA vaccine design and provides a promising candidate vaccine for MHF prevention. Full article

Marburg virus (MARV), a filovirus, was first identified in 1967 in Marburg, Germany, and Belgrade, former Yugoslavia. Since then, MARV has caused sporadic outbreaks of human disease with high case fatality rates in parts of Africa, with the largest outbreak occurring in 2004/05 in Angola. From 2021 to 2023, MARV outbreaks occurred in Guinea, Ghana, New Guinea, and Tanzania, emphasizing the expansion of its endemic area into new geographical regions. There are currently no approved vaccines or therapeutics targeting MARV, but several vaccine candidates have shown promise in preclinical studies. We compared three vaccine platforms simultaneously by vaccinating hamsters with either a single dose of an adenovirus-based (ChAdOx-1 MARV) vaccine, an alphavirus replicon-based RNA (LION-MARV) vaccine, or a recombinant vesicular stomatitis virus-based (VSV-MARV) vaccine, all expressing the MARV glycoprotein as the antigen. Lethal challenge with hamster-adapted MARV 4 weeks after vaccination resulted in uniform protection of the VSV-MARV and LION-MARV groups and 83% of the ChAdOx-1 MARV group. Assessment of the antigen-specific humoral response and its functionality revealed vaccine-platform-dependent differences, particularly in the Fc effector functions. Full article

Filoviruses are negative-sense single-stranded RNA viruses often associated with severe and highly lethal hemorrhagic fever in humans and nonhuman primates, with case fatality rates as high as 90%. Of the known filoviruses, Ebola virus (EBOV), the prototype of the genus Orthoebolavirus, has been a major public health concern as it frequently causes outbreaks and was associated with an unprecedented outbreak in several Western African countries in 2013–2016, affecting 28,610 people, 11,308 of whom died. Thereafter, filovirus research mostly focused on EBOV, paying less attention to other equally deadly orthoebolaviruses (Sudan, Bundibugyo, and Taï Forest viruses) and orthomarburgviruses (Marburg and Ravn viruses). Some of these filoviruses have emerged in nonendemic areas, as exemplified by four Marburg disease outbreaks recorded in Guinea, Ghana, Tanzania, and Equatorial Guinea between 2021 and 2023. Similarly, the Sudan virus has reemerged in Uganda 10 years after the last recorded outbreak. Moreover, several novel bat-derived filoviruses have been discovered in the last 15 years (Lloviu virus, Bombali virus, Měnglà virus, and Dehong virus), most of which are poorly characterized but may display a wide host range. These novel viruses have the potential to cause outbreaks in humans. Several gaps are yet to be addressed regarding known and emerging filoviruses. These gaps include the virus ecology and pathogenicity, mechanisms of zoonotic transmission, host range and susceptibility, and the development of specific medical countermeasures. In this review, we summarize the current knowledge on non-Ebola filoviruses (Bombali virus, Bundibugyo virus, Reston virus, Sudan virus, Tai Forest virus, Marburg virus, Ravn virus, Lloviu virus, Měnglà virus, and Dehong virus) and suggest some strategies to accelerate specific countermeasure development. Full article

The Marburg virus (MARV), the virus responsible for Marburg hemorrhagic fever (MHF), is considered a top-priority pathogen for vaccine development. Recent outbreaks in Equatorial Africa have highlighted the urgency of MARV because of its high fatality rate and historical concerns about potential weaponization. Currently, there are no licensed vaccines for MARV. Existing vaccine candidates rely on attenuated recombinant vesicular stomatitis virus carrying MARV glycoprotein (VSVΔG) or the chimpanzee replication-defective adenovirus 3 vector ChAd3-MARV. Although these platforms provide significant protection in animal models, they face challenges because of their limited thermal stability and the need for cold storage during deployment in resource-poor areas. An alternative approach involves using adjuvanted poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with synthetic peptides representing MHC class I—restricted T cell epitopes. This vaccine platform has demonstrated effectiveness in protecting against SARS-CoV-2 and EBoV disease in animal models and has the advantage of not requiring cold storage and remaining stable at room temperature for over six months. This report outlines the design, manufacturing, and in vivo immunogenicity testing of PLGA microparticle human vaccines designed to prevent Marburg hemorrhagic fever. Full article