Search Results (495)

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

Background/Objectives: Until now, there have been no suitable medicines to treat infections caused by the Ebola virus. Cistus incanus, a traditional medicinal plant, contains several phytocompounds exhibiting antioxidant and anti-inflammatory properties. Methods: In this research, the molecular level interactions of the phytocompounds of Cistus incanus were investigated for their antiviral potential against the active site of VP40 protein of Ebola virus using in silico molecular docking. Further, the potential compounds were assessed for their stability in the protein using molecular dynamics (MD) simulations. Results: Methyl gallate, catechin, and quercetin showed excellent docking scores of −9.8, −8.8, and −7.7 kcal/mol, respectively, and favorable interactions with the target protein. These complexes showed good stability over the 100 ns MD simulation time. In addition, the phytocompounds displayed favorable pharmacokinetics and drug-like properties. Conclusions: Our study offers the antiviral potential of phytocompounds (methyl gallate, catechin, and quercetin) of Cistus incanus, suggesting their suitability as lead candidates for the treatment of Ebola viral infection. 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

Ebola virus disease remains one of the most serious viral infections with no approved small-molecule treatments. The Ebola virus glycoprotein (EBOV-GP), which enables the virus’s entry to host cells, is a promising target for drug discovery. In this study, a multistage computer-aided drug discovery approach was used to identify new specific EBOV-GP inhibitors. A reliable QSAR model was built using 55 terpenoid derivatives. This model was able to predict the activity of newly designed compounds with good accuracy and validated statistical metrics ($R_{tr}^2$= 0.70; $R_{ext}^2$ = 0.73). It was subsequently applied to screen over 15,500 newly generated compounds from three lead molecules by fragment-based design tools. Predicted activity, binding affinity toward EBOV-GP, and good ADMET drug-like properties prioritized the eleven most promising hits. Through 150 ns molecular dynamics simulations, these compounds remained stable in the EBOV-GP binding site. Further binding free energy analysis (MM/PBSA) showed strong binding affinities, especially for the compounds L-60, L-832, M-1618, and L-1366. This study showed how combining QSAR, fragment-based design, docking, ADMET, and molecular dynamics could help in identifying potent and safe small molecules against the EBOV-GP. The top compounds are ready for further experimental and in vitro biological testing. Full article

This study examines the community integration and One Health strategies employed to combat Ebola virus disease in the Democratic Republic of Congo from 2007 to 2022. We synthesized 12 outbreak reports, conducted qualitative interviews with 36 managers, organized three focus groups, and adapted an analytical framework (MATCH) to evaluate three essential dimensions: the integration of the One Health approach, community involvement, and bottom-up approaches. This study evidences progressive improvement in all domains. The first outbreaks (2007–2009) were marked by moderate community engagement and a One Health approach that was largely limited to the human health sector, deemed suboptimal. The 10th outbreak represented an era of transformation, when the Incident Management System (IMS) was adopted to better manage the response to the virus. The latest outbreaks (13th to 15th) demonstrate an “optimal” implementation of the “One Health” approach through effective collaboration between those in charge of ensuring human, animal, and environmental health and that of the community. This study demonstrates that success is largely dependent on bottom-up initiatives in which local populations, their leaders (both traditional and religious), community liaisons, and specific groups (women and youth) are involved in the design and implementation of such measures. The inclusion of anthropologists and psychologists in addressing the psychosocial dimensions—fear, stigma, and distress—has been critical in ensuring the success of these initiatives and the degree to which the public trusts and accepts them. However, many issues still need to be addressed, including poor coordination among sectoral ministries and the partial implementation of IMS at the grassroots level. In summary, the authors of this study propose that these integrated and participatory models are sustainable and imperative to building the resilience of the Congolese health system to future outbreaks. Full article

Effective disinfectants are a requirement for safe operation within Containment Level 4 (CL4) laboratories. High-containment processes often demand that disinfectants remain effective over prolonged periods of time. Four candidate quaternary ammonium-based disinfectants were tested at room temperature for activity against Ebola virus and Nipah virus with a 5 min contact time when disinfectant was freshly prepared and again after disinfectants were aged for 26 weeks. The concentrations tested, based on manufacturer recommendations, were either 5% or 10%. Candidates that demonstrated long-term efficacy were also evaluated for viral breakthrough using reduced disinfectant concentration (1.25% or 2.5%) or reduced contact time (1 min). Breakthrough of Ebola virus was observed with one of the disinfectants using a reduced concentration compared to the manufacturer’s recommendation. Full article

Lassa virus (LASV), a member of the Arenaviridae family, is the causative agent of Lassa fever (LF), an acute zoonotic hemorrhagic disease transmitted by rodents, characterized by high infectivity and mortality rates. Due to the nonspecific nature of early clinical symptoms, the development of rapid, sensitive, and specific diagnostic methods is critical for effective epidemic control. In this study, the Lassa virus glycoprotein complex (LASV-G) was selected as the target antigen. High-affinity rabbit monoclonal antibodies were generated using a single B-cell cloning approach, and an AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay)-based homogeneous, no-wash detection system was established. Sixteen LASV-G-specific monoclonal antibodies were isolated through flow cytometric sorting, and the optimal antibody pair (56–24) was identified by AlphaLISA pairing and performance screening. The established AlphaLISA system exhibited a limit of detection (LOD) of 0.025 ng/mL, representing approximately a 30-fold increase in sensitivity compared with conventional Enzyme Linked Immunosorbent Assay (ELISA), while reducing the total assay time to less than 30 min. The coefficient of variation (CV) was below 8%, and no cross-reactivity was observed with Ebola, dengue, yellow fever, Zika, or influenza virus antigens. These findings demonstrate that the developed AlphaLISA assay possesses high sensitivity, rapid detection, and good tolerance to matrix effects, significantly improving the efficiency of early LASV antigen detection. This work provides a potential platform for the rapid on-site screening and epidemiological surveillance of highly pathogenic viruses. Full article

Viral hemorrhagic fevers (VHFs) are highly lethal diseases that often present non-specific, influenza-like symptoms in their early stages, making clinical recognition and differentiation from other febrile illnesses difficult. This overlap underscores the critical need for diagnostic tests that are both sensitive and specific. Point-of-care (POC) diagnostic tests are an invaluable tool for detecting and controlling the spread of pathogens that threaten public health, such as VHFs, as these require fast, accurate diagnostics to ensure biosafety and appropriate mobilization of resources during outbreaks. Current molecular and serological diagnostic tests, while efficient and effective, lack the characteristics required of a POC test (POCT) to quickly and easily respond to a VHF outbreak while maintaining a low cost. Clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic tests have gained popularity as POCTs due to their inherent attractive qualities, including high sensitivity and specificity, adaptability, low cost, quick turnaround time, and ease of use. However, studies on the development of CRISPR-based POC diagnostic tests for VHFs are limited. This review summarizes the current CRISPR-based POCTs for VHFs, including Ebola virus (EBOV), Lassa virus (LASV), Dengue virus (DENV), and Crimean–Congo hemorrhagic fever virus (CCHF). The isothermal pre-amplification methods commonly paired with CRISPR-based tests, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), are also discussed. Full article

Filoviruses, including Ebola (EBOV) and Marburg (MARV) viruses, are zoonotic pathogens that cause severe hemorrhagic fever in humans, with mortality rates reaching up to 90%. Filovirus egress and spread are driven by the viral matrix protein VP40 and regulated both positively and negatively by a growing number of specific host interactors. Here, we identify tetraspanin protein CD9, a plasma membrane organizing and scaffolding protein, as playing a role in facilitating efficient egress of EBOV and MARV. Indeed, we observed a significant decrease in viral egress of VLPs and live filoviruses from CD9-KD cells as compared to that from WT cells. Moreover, exogenous expression of CD9 rescued egress of VP40 VLPs close to WT levels in the CD9-KD cells. These findings identify tetraspanin CD9 as a positive regulator of filovirus egress, and thus CD9 may represent a potential new target for antiviral therapies targeting the late stage of the filovirus lifecycle. Full article

Millions of healthcare workers experience percutaneous exposure to bloodborne communicable infectious disease pathogens annually, with the risk of contracting occupationally acquired infections. In this study, we aimed to assess the status of occupational safety and outbreak preparedness in Congolese nurses and laboratory technicians in Kongo central and the Katanga area, amidst multiple ongoing public health emergencies in the Democratic Republic of the Congo (DRC). This was a multicenter analytical cross-sectional study conducted in five referral hospitals located in Kongo central province and the Katanga area between 2019 and 2020 amidst Ebola, Yellow fever, Cholera and Chikungunya outbreaks. Participants were adult A0 grade nurses, A1 nurses, A2 nurses and medical laboratory technicians (N = 493). They answered a structured, self-administered questionnaire related to hospital hygiene and standard precautions for occupational infection prevention. The majority of the respondents were females (53.6%), and 30.1% of them have never participated in a training session on hospital infection prevention during their career. The proportions of those who have been immunized against hepatitis B virus (HBV) was markedly low, at 16.5%. Of the respondents, 75.3% have been using safety-engineered medical devices (SEDs), whereas 93.5% consistently disinfected medical devices after use. Moreover, 78% of the respondents used gloves during medical procedures and 92.2% wore masks consistently. A large majority of the respondents, 82.9%, have been recapping the needles after use. Regarding participation in outbreak response, 24.5% and 12.2% of the respondents were Chikungunya and Cholera epidemic responders, respectively; 1.8% have served in Ebola outbreak sites. The proportion of the respondents who sustained at least one percutaneous injury by needlestick or sharp device, blood/body fluid splash or both in the previous 12-month period was high, 89.3% (41.8% for injury, 59.2% for BBF event), and most of them (73%) reported over 11 events. Compared to laboratory technicians, nurses had higher odds for sustaining percutaneous injury and BBF events [OR = 1.38 (0.16); p < 0.01], whereas respondents with longer working experience were less likely to sustain those events [OR = 0.47 (0.11); p < 0.001]. Findings from this study suggest that Congolese nurses and laboratory technicians experience a high frequency of injury and BBF events at work, and remain at high risk for occupationally acquired infection. There is a need for periodic capacity-building training for the healthcare workforce to improve infection prevention in health settings, the provision of sufficient and appropriate PPE and SEDs, post-exposure follow-up and keeping records of occupational injuries in hospitals in Congolese healthcare settings. 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

The 2025 Ebola outbreak that ravaged the Bulape Health District (HD) in Kasai, Democratic Republic of Congo (DRC), was tackled using the incident management system (IMS) model. The Bulape HD is located in the Mweka territory, which has experienced two Ebola epidemics: one in 2007 and another in 2008. The IMS comprises seven strategies recommended for an effective response to an Ebola outbreak: (i) thorough investigation, (ii) strengthening infection prevention and control measures in the community, (iii) ensuring that medical care is provided by experienced professionals, (iv) strengthening risk communication and community engagement (RCCE), (v) ring vaccination, (vi) operational research, and (vii) anchoring interventions in the existing health system. We share our experience implementing these seven strategies and compare them with those utilized during three previous Ebola outbreaks. This paper describes our achievements, the resulting benefits, and the factors that facilitated the implementation of the aforementioned strategies. A literature review and interviews were conducted. The atlas.ti 22 software was used for data analysis. Implementing these seven strategies contributed to an effective response, largely due to the experience and expertise of those involved but also thanks to the support of technical and financial partners (TFPs) and the engagement of the local community. Challenges such as geographical accessibility, the fragile health system, the community’s strong attachment to traditional practices, and negative reactions to healthcare—which was widely discredited, with many of those involved expressing a lack of faith in its effectiveness—were major obstacles. To overcome these challenges, an integrated approach was utilized, combining a rapid comprehensive response with deep and respectful community engagement. The support and alignment of TFPs were invaluable during this process. The RCCE pillar proved key to successful IMS implementation. Our experiences will be useful during the next Ebola outbreak in the DRC; additionally, they may also help to inform the response to similar outbreaks in other countries. Full article

Orthoebolaviruses (OEV) are highly pathogenic viruses responsible for the Ebola virus disease (EVD). To establish a successful infection, OEV hijacks the host cell machinery, which in turn responds to infection by activating cellular antiviral pathways. These processes are regulated via post-translational modifications (PTMs) of both cellular and viral proteins. The most common PTMs include phosphorylation, ubiquitination, acetylation, methylation, and glycosylation. These modifications regulate stability, activity, and interactions between proteins that control the immune response, cell metabolism, and cell death, among others. PTMs are critical during the viral replication cycle as they can be either proviral, facilitating adequate virus replication inside the infected cell, or antiviral, most commonly hindering essential viral processes such as viral genome transcription or replication. Here, we review the different roles of PTMs known to occur during OEV infection in both viral and cellular proteins. Understanding how OEV modulates the fate of host cell proteins through specific PTMs can provide a basis for the development of novel therapeutic strategies. Full article

Ebola virus (EBOV) infection constitutes a significant global public health threat, and no curative treatment is currently available for it. Rapid and accurate detection of EBOV nucleic acid is crucial for controlling the spread of Ebola virus disease (EVD). The gold standard for EBOV diagnosis is real-time reverse transcription polymerase chain reaction (RT-qPCR), which requires costly equipment and skilled personnel, potentially hindering its application for rapid detection, especially in resource-limited settings. Consequently, there is an urgent need to develop a simple, accurate, and rapid diagnostic method for EVD. In this study, a real-time reverse transcription recombinase-aided amplification (RT-RAA) assay was developed for the specific visual detection of the conserved region of the EBOV nucleoprotein (NP) gene. The RT-RAA assay can be completed within 30 min at 42 °C, and results can be visualized using a portable blue light imager. The assay exhibited strong analytical specificity toward EBOV. No cross-reactivity was observed with any of the other public-health-relevant viruses tested. The visual RT-RAA assay demonstrated sensitivity comparable to RT-qPCR, detecting 52 copies per reaction at a 95% probability level, whereas RT-qPCR required 74 copies per reaction. The RAA method demonstrated excellent repeatability and stability, with intra-assay and inter-assay CVs less than 5% and 7%, respectively. These results clearly indicate that the visual RT-RAA method is specific, accurate, simple, rapid, and reliable for EBOV detection. Full article