Search Results (148)

Ebola virus disease (EVD) remains one of the most severe viral hemorrhagic fevers, with recurrent outbreaks challenging global healthcare systems. This narrative review traces the evolving epidemiology of EVD from the first recognized outbreaks in 1976 to the ongoing 2026 Bundibugyo virus public health emergency in the Democratic Republic of the Congo (DRC) and Uganda. Over nearly five decades, the recognized range of Ebola outbreak contexts and amplification mechanisms has broadened considerably: rural zoonotic spillovers remain the predominant mode of emergence, but the scale and reach of subsequent transmission increasingly depend on where introductions occur, on delays in detection, on population mobility, on ecological disruption, on armed conflict, on healthcare-associated transmission, and on viral persistence in survivors. Major advances in molecular epidemiology and genomic surveillance have improved outbreak investigation, enabling real-time transmission reconstruction and detection of survivor-linked resurgence. Vaccination, particularly ring vaccination with rVSV-ZEBOV, has shown high effectiveness against Zaire ebolavirus, yet vaccine equity gaps and the absence of licensed vaccines for Sudan virus and Bundibugyo virus remain critical vulnerabilities, though new candidate vaccines and therapeutics for Bundibugyo virus entered clinical evaluation in mid-2026. Artificial intelligence and digital technologies, including AI-assisted early warning systems, portable sequencing, drones, blockchain, and mobile health platforms, offer promising tools for outbreak preparedness, but robust evidence of their real-world operational impact during filovirus outbreaks remains limited, and their deployment in low-resource settings faces substantial barriers related to infrastructure, literacy, data costs, and governance. Integrated preparedness frameworks that combine ecological surveillance, resilient healthcare systems, community engagement, and international coordination under a One Health umbrella are increasingly viewed as a strategic necessity. The 2026 Bundibugyo outbreak reaffirms that despite decades of lessons, structural weaknesses in surveillance, response timeliness, and community trust continue to recur. Sustainable, multi-year financing, diversified vaccine platforms, regional manufacturing, and local co-design of digital tools are essential to translate lessons into lasting change. Preparedness is best understood as a continuous process rather than a reactive state. Full article

Ebola alerts reveal the truth about preparedness. They show whether a health system can recognize danger early, protect health workers, isolate and care for patients, trace contacts, communicate clearly, and sustain public trust before fear replaces cooperation. In the Pandemic Agreement Era, this truth has become harder to ignore. The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda is a sharp reminder that the principles of pandemic prevention, preparedness, response, equity, and cooperation become meaningful only when they work where the first cases occur. In the absence of licensed vaccines and specific treatments for Bundibugyo virus disease, preparedness depends on the basic functions of public health: surveillance, diagnosis, infection prevention and control, referral, risk communication, community engagement, and operational coordination. These functions are often described as routine. They are not. During high-consequence infectious disease alerts, they serve as the primary protective infrastructure. Ebola also exposes a deeper ethical failure. Frontline countries and communities are expected to contain threats of global relevance, but international support often intensifies only after the risk becomes visible beyond the affected area. This reactive model is neither fair nor efficient. The WHO Pandemic Agreement defines a political direction for a more equitable and coordinated global response. Here, Ebola is not presented as a typical pandemic event but as an operational test of preparedness, solidarity, early support to affected settings, and international cooperation. Ebola alerts test whether that direction can become an operational reality before escalation. Digital tools, telemedicine, and artificial intelligence may strengthen this agenda but only when they make local systems faster, safer, more trusted, and more usable. Ebola preparedness is therefore not only a technical task. It is a test of responsibility. Full article

The ongoing Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda has become the largest documented outbreak caused by this orthoebolavirus and already ranks as the second-largest Ebola disease outbreak recorded in history. This review highlights its major public health relevance, given its cross-border spread, substantial mortality burden, high clinical severity, infections among healthcare workers, and the lack of any approved vaccine or specific treatment for Bundibugyo virus disease. We discuss the epidemiological and virological significance of this exceptional event, the limitations of current diagnostic and therapeutic preparedness beyond Ebola virus, and the urgent need for broader filovirus-focused strategies, including improved diagnostics, genomic surveillance, candidate vaccines, antiviral platforms, and resilient local health systems. The outbreak illustrates how preparedness efforts centered mainly on the Ebola virus have left substantial gaps for other human-pathogenic orthoebolaviruses. Full article

Filoviruses cause highly lethal infectious diseases with hemorrhagic symptoms and extremely high fatality rate (up to 90%). Although two vaccines against Ebola virus (EBOV) are licensed for application in endemic areas, vaccines against other filoviruses (SUDV, BDBV, MARV) are still at pre-clinical or clinical stages. The development of vaccines requires protective efficacy studies using animal models of infection. However, animal studies using wild-type filoviruses require maximum biosafety level (BSL-4), which hinders filoviral vaccine advancement. In this study, we developed a surrogate animal model of EBOV-, SUDV-, BDBV- and MARV- GP-mediated entry using Ifnar1-knockout (-/-) mice and recombinant vesicular stomatitis viruses (rVSVs), carrying a genetic sequence of filoviral glycoprotein (GP) and pseudotyped with correspondent GP. We showed that rVSV-EBOV-GP was 100% lethal for Ifnar1(-/-) mice after inoculation by multiple routes, and its active propagation was within 24 h post-infection. We performed dose-dependent lethality assessment in small groups to estimate median lethal doses for rVSV-EBOV-GP, rVSV-SUDV-GP, rVSV-BDBV-GP, rVSV-MARV-GP in Ifnar1-knockout mice and showed high viral load in liver and immune cell reservoirs. The developed models contribute to safe and effective research of filoviral vaccines and therapeutic antibodies under BSL-2 conditions. Full article

Bundibugyo virus disease, caused by Bundibugyo virus (Orthoebolavirus bundibugyoense), is a severe human Ebola disease with substantial mortality, unresolved reservoir ecology, limited diagnostic implementation, and no licensed vaccines or therapeutics specifically approved for this Orthoebolavirus species. The May 2026 public health emergency in the Democratic Republic of the Congo and Uganda renewed the need for a focused synthesis of Bundibugyo virus-specific diagnostics and medical countermeasures. This review synthesizes the peer-reviewed literature, preprints, and official public-health documents on diagnostics, antivirals, therapeutics, vaccines, and post-exposure prophylaxis. Comparative evidence from the Ebola virus, Sudan virus, Marburg virus, and pan-filovirus platforms is included only where it clarifies Bundibugyo virus-specific evidence, exposes unsupported extrapolation, or defines preparedness gaps. The 2007–2008 outbreak showed that assays optimized for known filoviruses can miss divergent ebolaviruses; the 2026 outbreak underscored the importance of diagnostic breadth, sequencing-based confirmation, decentralized laboratory capacity, and regional coordination. Clinical and immunological data indicate that Bundibugyo virus cannot be reduced to an Ebola virus-like model. Countermeasure evidence remains largely preclinical: recombinant vesicular stomatitis virus vaccines expressing Bundibugyo virus glycoprotein provide the strongest direct animal protection data, whereas antiviral and antibody-based evidence varies widely and requires careful separation of direct Bundibugyo virus data from platform-based extrapolation. Full article

Background/Objectives: Ebola Virus Disease (EVD) remains a public health threat in sub-Saharan Africa. The 10th Ebola outbreak in the Democratic Republic of the Congo (DRC) in 2018–2020 led the Rwanda Ministry of Health to launch a large-scale Ebola vaccination campaign using the two-dose Ad26.ZEBOV and MVA-BN-Filo regimen. The campaign was implemented by local organizations, the Center for Family Health Research and Rinda Ubuzima, in partnership with the Rwanda Biomedical Center. Methods: The campaign targeted those who live near or routinely cross the Rwanda/DRC border and unvaccinated first responders. Children <2 years and pregnant women were excluded. Results: Between December 2019 and September 2021, 219,775 individuals attended vaccination sites and 216,108 received the first dose. Of those, 110,699 (51.2%) were adults (≥18 years) and 105,409 (48.8%) were children aged 2–17 years. A total of 118,048 (54.6%) were women and 98,060 (45.4%) were men. Of all first-dose clients, 203,303 (94.1%) received the second dose. Participants who were older, male, in Rubavu district, and urban were more likely (p < 0.05) to be lost between the first and second dose. Most individuals who were ineligible for the second dose were women who fell pregnant after the first dose. Conclusions: Findings highlight that a large-scale vaccination campaign, including remote areas, is feasible with high adherence despite the concurrent COVID-19 pandemic. Early stakeholder engagement and local leadership were critical to success. Future studies of reasons for non-adherence, as well as strategies to integrate family planning into campaign activities to reduce ineligibility due to pregnancy, are warranted. Full article

This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article

The recurrent emergence of viral outbreaks, including SARS-CoV-2, influenza, Ebola, and respiratory syncytial virus (RSV), continues to expose critical limitations in conventional antiviral therapies, particularly in terms of targeting specificity, bioavailability, and resistance development. Nanotechnology has emerged as a transformative approach to overcome these challenges. This review provides a comprehensive and critical analysis of nanoparticle-based antiviral systems, including lipid-based, polymeric, inorganic, and hybrid nanocarriers, with a focus on their roles in enhancing drug delivery, targeting precision, and therapeutic efficacy. These platforms exert antiviral effects through multiple coordinated mechanisms, including inhibition of viral entry, suppression of replication, gene silencing, and modulation of host immune responses. The clinical success of lipid nanoparticle-based mRNA vaccines highlights the translational potential of nanotechnology, while emerging nanotherapeutic strategies demonstrate increasing versatility across diverse viral pathogens. However, key challenges—including safety, scalability, formulation stability, and regulatory constraints—continue to limit widespread clinical implementation. Overall, nanoparticle-mediated antiviral systems represent a multifunctional and adaptable platform capable of addressing the limitations of conventional therapies and enabling more effective, resilient, and precision-driven strategies for future pandemic preparedness. Full article

Background/Objectives: Emerging viral zoonoses represent a growing threat to global public health, with most newly emerging infectious diseases originating from animal reservoirs. Recent outbreaks of monkeypox, Ebola virus disease, Marburg virus disease, Rift Valley fever, and avian influenza highlight the capacity of zoonotic viruses to cross species barriers, spread internationally, and generate substantial health, social, and economic consequences. This review examines the ecological, epidemiological, and biological determinants of viral zoonotic emergence and transmission, with particular emphasis on vaccination and outbreak prevention strategies. Methods: A structured narrative review was conducted using a predefined literature search strategy across major scientific databases. Peer-reviewed epidemiological, clinical, and public health publications published between January 2000 and February 2026 were screened and selected according to predefined relevance criteria. Results: The emergence of viral zoonoses is driven by complex interactions among animal reservoirs, environmental and climatic changes, human behavior, and viral adaptation. Although transmission pathways and clinical outcomes differ among pathogens, common determinants of spillover and outbreak amplification were identified. Current evidence supports the importance of integrated surveillance, genomic monitoring, vaccination strategies, and community engagement as key components of preparedness and response. Emerging preventive approaches targeting pathogen transmission, including transmission-blocking strategies and vector-associated microbiota interventions, may provide additional opportunities for disease control. Conclusions: Strengthening preparedness for emerging viral zoonoses requires coordinated One Health approaches integrating human, animal, and environmental health. Future priorities include the development of next-generation vaccines, expansion of digital and genomic surveillance systems, improved equitable access to vaccines, and innovative interventions aimed at reducing zoonotic spillover and interrupting pathogen transmission. Full article

In 2025, tropical medicine was shaped by advances in diagnostic technology, expanding arboviral epidemics, rapid progress in filovirus vaccine development, evolving regulatory responses to newly licensed vaccines, and translational breakthroughs addressing neglected tropical diseases. This review discusses five select developments that significantly influenced clinical practice and global health policy over the past year, highlighting the implications of each for clinicians, researchers, and public health systems. Full article

Background/Objectives: Febrile illness in returning travelers presents a diagnostic and operational challenge for emergency medicine clinicians as early symptoms of high-consequence tropical infections often overlap with common viral syndromes. This review synthesizes current evidence to guide frontline clinicians in the systematic evaluation, diagnosis, and management of internally acquired febrile illnesses with a focus on pathogen of greatest relevance to United States (US) emergency departments (ED). Methods: We conducted a narrative review of the literature addressing epidemiology, clinical presentation, diagnostic testing, and management strategies for key travel-associated infections. Special consideration was given to rapid diagnostic modalities, pediatric risk factors, and infections most frequently implicated in returning travelers, including chikungunya (CHIK), dengue virus (DENV) disease, Ebola virus (EBV) disease, malaria, Mpox, typhoid fever (TF), yellow fever (YF), and Zika virus (ZIKV) disease. Results: Effective evaluation begins with a detailed travel and exposure history, recognition of epidemiologic and clinical red flags, and targeted use of rapid diagnostic tests. Malaria remains the most common life-threatening cause of post-travel fever and the only pathogen with reliable Food and Drug Administration (FDA)-cleared rapid testing available in the ED. Arboviral infections such as DENV, CHIK, ZIKV, and YFrequire region-specific consideration and phase-appropriate molecular or serologic evaluation. Emerging and high-consequence pathogens, including Mpox and EBV, necessitate strict infection control measures and coordination with public health authorities. Pediatric travelers, particularly those visiting friends and relatives, face disproportionate risk for severe systemic infections and often require broader diagnostic testing. Conclusions: A structured approach integrating travel history, focused examination, rapid diagnostics, and early recognition of high-risk features is essential to improving outcomes for febrile returning travelers. Strengthened vector control, enhanced vaccination uptake, and global surveillance are critical to reducing future disease burden. Full article

Viral hemorrhagic fevers (VHFs) comprise a heterogeneous group of severe infectious diseases that continue to represent a major global health concern. Although many VHFs remain endemic to regions of Africa, Asia, and the Americas, their wide geographic distribution, together with increasing international travel and global trade, facilitates the importation of cases into non-endemic areas and raises the risk of secondary transmission under favorable ecological and epidemiological conditions. These infections are frequently associated with high case-fatality rates and impose a substantial social and economic burden, including pressure on healthcare systems, disruption of essential services, and long-term physical and psychological sequelae among survivors. Despite notable advances in recent years, therapeutic options for VHFs remain limited. Supportive care continues to represent the cornerstone of clinical management for most infections, while pathogen-targeted therapies are available only for a restricted number of diseases. Monoclonal antibody-based therapies have achieved the most significant regulatory success to date, particularly for Ebola virus disease. In parallel, several small-molecule antivirals have been investigated in preclinical and clinical settings, including during outbreak responses, although inconsistent efficacy and safety concerns have limited widespread approval. Vaccine development has progressed further, with licensed vaccines available for selected VHFs, including Ebola, yellow fever, and dengue, and multiple candidates based on diverse technological platforms advancing through clinical evaluation. In addition to summarizing current therapeutic and vaccine strategies, this review highlights pharmaceutical development considerations relevant to biologic therapeutics and selected vaccine platforms, including formulation stability, pharmacokinetic behavior, delivery routes, storage requirements, and logistical constraints affecting deployment during outbreak responses. Using a comparative cross-pathogen framework, the review synthesizes recent literature to identify translational gaps, regulatory challenges, and future priorities for the development of safer and more effective medical countermeasures against VHFs. Full article

In this paper, we extend some existing models of the Ebola virus disease through a hybrid impulsive conformable approach. The base of the introduced model is a class of partial differential equations that incorporate diffusion terms to describe the development of the Ebola virus disease in time and space. In the extended model, we have considered impulsive effects at fixed moments of time, which is of high significance in investigating opportunities for impulsive vaccination strategies and impulsive control drug treatment on disease evolution. In addition, conformable setting is proposed, which provides modeling flexibility without the complications inherent in classical fractional derivatives. Instead of studying the global stability of an equilibrium, the more general notion of stability of sets is introduced and analyzed. The main stability of sets results are obtained by using the impulsive conformable Lyapunov technique and comparison principle. The proposed framework, concepts and techniques may serve as effective tools for analyzing numerous phenomena in medicine and biology. Full article

In human and non-human primates, filoviruses, e.g., Ebolaviruses, cause severe hemorrhagic fever for which there are few therapeutic options. While there are licensed vaccines and therapeutics for Ebola virus disease, there is no approved vaccine or treatment for other Ebola diseases. There is a need for broad-spectrum antivirals to treat Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV). We have previously demonstrated that probenecid, an FDA-approved drug with a safety profile spanning over 7 decades, is safe and effective in preventing the replication of influenza A viruses, SARS-CoV-2, and other RNA respiratory viruses, such as HMPV and RSV, both in vitro and in vivo. In this study, probenecid was shown to inhibit the replication of infectious EBOV, SUDV, and MARV in Vero E6 cells, with IC50 Values of 3 μM, 8 μM, and 13 μM, respectively. It also reduced plaque size in infected Vero cell lawns, suggesting reduced virus spread. These studies show that probenecid is an effective, broad-spectrum, host-directed antiviral drug. Full article

Ebola virus disease (EVD) is an acute illness with a high-case fatality rate (CFR) caused by an RNA virus belonging to the Filoviridae family. Over the past 50 years, regular EVD outbreaks have been reported. The West African EVD outbreak of 2013–2016 proved to be significantly more widespread and complex than previous ones, resulting in approximately 11,000 deaths. A coordinated international effort was required to bring the outbreak under control. One of the main challenges faced by clinicians and researchers combating EVD was the absence of vaccines and preventive treatments. Only recently have efforts led to the development of effective therapeutic options. Among these, monoclonal antibody-based drugs have emerged as the most promising agents for the urgent treatment of EVD. This article aims to review the key milestones in the development of antibody-based therapies for EVD, tracing the journey from the use of convalescent serum to the creation of effective monoclonal antibody-based drugs and their combinations. Full article