2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
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2026-07-11 | Epidemiology and containment of the first Marburg virus disease outbreak in Ethiopia in 2025: A retrospective descriptive study.
In November 2025, Ethiopia confirmed its first Marburg Virus Disease (MVD) outbreak in Jinka, marking a significant geographical expansion of the virus with a 64% case fatality rate. This study characterizes the transmission dynamics of the 2025 MVD outbreak in Ethiopia and evaluates the impact of the national public health containment strategy on the epidemic trajectory. We conducted a retrospective descriptive analysis using surveillance and laboratory data from November 14 to December 30, 2025. Transmission intensity was quantified using basic (R0) and effective (Rt) reproduction numbers. We further evaluated the deployment of the investigational cAd3-Marburg vaccine and the feasibility of drone-assisted ultra-cold chain logistics under the national Evidence Generation during an Emergency (EGE) framework. The outbreak involved 14 confirmed cases and 9 fatalities (CFR: 64%). The initial R0 was 2.34, driven by nosocomial and religious clusters. Following the activation of the Incident Management System, diagnostic testing increased by over 1000%, and 2500 vaccine doses were deployed to high-risk groups. The use of drone logistics was observed to support the -80 °C cold chain for deliveries in remote areas. Rt fell below 1.0 within 14 days of formal intervention. The findings are consistent with the hypothesis that the combination of rapid diagnostic scaling decentralized incident management and technological integration were temporally associated with the truncation of MVD transmission chains. The integrated approach of decentralized management and rapid technological deployment offers a framework for viral hemorrhagic fever preparedness in similar resource-limited settings.
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2026-07-10 | Integrative reverse vaccinology and computational modeling for the rational design of a broadly immunogenic multi-epitope vaccine against Marburg virus infection.
Marburg virus (MARV), a member of the Filoviridae family, causes severe hemorrhagic fever in humans with case fatality rates exceeding 90%, and currently, no approved vaccines or therapeutics are available. To address this urgent need, we employed comprehensive immunoinformatics and computational approaches to design a multi-epitope subunit vaccine (MESV) capable of eliciting robust immune responses. Highly antigenic, non-allergenic, and non-toxic cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes derived from MARV glycoprotein (GP) and nucleoprotein (NP) were selected and assembled using appropriate linkers and adjuvant sequences. The designed vaccine construct exhibited favorable physicochemical characteristics, structural stability, and strong immunogenic potential. Solubility analysis predicted a score of 0.835, while structural validation revealed an ERRAT score of 94.11%, with 89.4% of residues located in the most favored regions of the Ramachandran plot. The ProSA analysis yielded a Z-score of - 5.31, confirming the reliability of the modeled structure. Molecular docking studies demonstrated strong interactions between the vaccine construct and Toll-like receptor 7, while molecular dynamics simulations confirmed the stability of the docked complex. Codon optimization and in silico cloning indicated efficient expression potential in Escherichia coli, with a codon adaptation index (CAI) of 0.9805 and GC content of 55.39%. Furthermore, immune simulations predicted a robust and sustained immune response. These computational findings suggest that the designed MESV is a promising vaccine candidate for MARV and warrants further experimental validation through in vitro and in vivo studies.
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