Search Results (280)

Malaria coinfections with other infectious agents represent a clinically relevant epidemiological challenge, but evidence remains fragmented across individual systematic reviews. This umbrella systematic review synthesized review-level evidence on the prevalence and epidemiological patterns of concurrent malaria coinfections in human populations. PubMed/MEDLINE, Scopus, Web of Science, Embase, and LILACS/BVS were searched for systematic reviews published from 1 January 2000 to March 2026. Risk of bias, certainty of evidence, and primary-study overlap were assessed using ROBIS, an adapted GRADE framework for prevalence evidence, and citation-matrix/corrected-covered-area methods, respectively. Twenty-one systematic reviews were included, of which 16 contributed meta-analytical prevalence estimates. Among acute-pattern coinfections, review-level prevalence estimates ranged from 3.0% (95% CI: 2.0–5.0) for malaria–influenza to 21.7% (95% CI: 18.7–25.1) for malaria–Ebola virus disease. Among chronic or persistent-pattern coinfections, estimates ranged from 6.0% (95% CI: 4.0–7.0) for malaria–hepatitis B to 50.0% (95% CI: 28.0–72.0) for malaria–human African trypanosomiasis; the latter reflects Plasmodium positivity among patients with human African trypanosomiasis and should not be interpreted as a population-level prevalence. Sub-Saharan Africa was the most represented region. Certainty of evidence was generally low or very low, largely because of substantial heterogeneity, diagnostic variability, geographic concentration, and overlap among some source reviews. Malaria coinfections are clinically and epidemiologically relevant in endemic settings, but available prevalence estimates should be interpreted as context-dependent review-level summaries rather than globally comparable burden estimates. Full article

The ongoing 2026 Bundibugyo ebolavirus outbreak in eastern Democratic Republic of the Congo highlights the continued vulnerability of Central Africa to recurrent Ebola emergence. This outbreak emerged less than six months after the previous one ended, appears to represent one of the shortest documented inter-epidemic intervals in the Democratic Republic of the Congo based on currently available outbreak reports. Current surveillance systems remain largely reactive, focusing on the detection of human cases after zoonotic spillover has occurred. While strengthening health systems, diagnostic capacity, and early case detection remains the cornerstone of Ebola preparedness, growing research suggests that environmental and climatic information may eventually contribute to a broader understanding of spillover risk within a One Health framework. However, current evidence remains insufficient to identify validated environmental indicators or operational thresholds capable of predicting Ebola spillover events. Recent modeling studies have demonstrated that environmental drivers of Ebola emergence remain highly context-dependent and cannot yet support operational early warning systems. This commentary argues that continued research integrating environmental monitoring, remote sensing, ecological observations, and epidemiological data may improve understanding of Ebola emergence and eventually contribute to future preparedness strategies. Rather than proposing climate-informed preparedness approaches as an operational prediction tool, we emphasize its potential as a complementary research priority requiring further validation before any operational implementation. 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

Ebola virus disease (EVD) has traditionally been considered an acute infection characterized by high mortality and severe systemic inflammation. However, growing evidence accumulated over the last decade has progressively challenged this view, demonstrating that Ebola virus may persist long after apparent clinical recovery within immune-privileged anatomical compartments, including the male genital tract, ocular tissues, central nervous system, and breast milk. Persistent viral reservoirs have been associated with prolonged RNA shedding, sexual transmission, recrudescence phenomena, and outbreak resurgence, highlighting the clinical and public health relevance of post-acute Ebola persistence. At the same time, increasing evidence suggests that EVD survivors frequently exhibit chronic inflammatory activation and long-lasting immune dysfunction. Persistent alterations involving cytokine signaling, T-cell responses, and antiviral immune regulation may contribute to incomplete viral clearance and reservoir maintenance. In this context, the potential interaction between Ebola virus persistence and HIV-associated immune dysregulation remains poorly explored despite the substantial geographical overlap between both infections in sub-Saharan Africa. This narrative review examines current evidence regarding Ebola virus persistence, immune-privileged reservoirs, survivor immune dysfunction, and persistence-associated transmission. Additionally, we discuss the biological plausibility that chronic immune activation, T-cell exhaustion, and impaired antiviral surveillance observed in people living with HIV (PWH) could theoretically influence persistence dynamics and long-term reservoir biology. Understanding these interactions may have implications for survivor monitoring, outbreak preparedness, and future research on post-acute viral reservoir diseases. Importantly, this review does not argue that HIV has been clinically established as a modifier of Ebola virus persistence. Rather, it examines Ebola virus persistence as an established post-acute phenomenon and considers whether HIV-associated immune dysregulation in people living with HIV (PWH) may represent a biologically plausible, but still untested, determinant of viral clearance and reservoir biology. 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

Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-β while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFNβ and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFNβ and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85. Full article

Whole-genome sequencing (WGS) is central to outbreak response for high-consequence ribonucleic acid (RNA) viruses, but useful genomes depend on workflow design, sample quality, biosafety, diagnostic breadth, infrastructure, and bioinformatics as much as sequencing platform. The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda provides a case example. Bundibugyo virus (BDBV) was already known from the 2007–2008 Uganda and 2012 Democratic Republic of the Congo outbreaks, but sparse historical genome sampling, Ebola virus-centered diagnostic assumptions, non-specific febrile and viral hemorrhagic fever presentations, and difficult field conditions created a need for broad differential diagnosis, rapid species assignment, and representative genome generation. This review compares outbreak WGS strategies by the degree of prior viral sequence knowledge required, distinguishing direct RNA sequencing, random-primed complementary DNA (cDNA) sequencing, sequence-independent amplified cDNA sequencing, background-depleted or particle-enriched cDNA sequencing, probe-based hybrid capture, tiled amplicon sequencing, portable field sequencing, culture-derived sequencing, and associated bioinformatics workflows. For BDBV-like outbreaks, the most defensible strategy is staged and adaptive: broad viral hemorrhagic fever and febrile illness differential testing at recognition; Filoviridae-wide testing when filovirus disease remains plausible; divergence-tolerant first-genome recovery; quantification-cycle-informed sequencing prioritization without BDBV-only diagnostic narrowing; validated amplicon scale-up; and representative sequencing across locations and time. 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

Orthoebolavirus causes severe Ebola virus disease (EVD) and deadly outbreaks in humans. This infection occurs through macropinocytosis and trafficking to late endosomes or lysosomes that utilize the receptor Niemann–Pick C1 (NPC1) to enter the cell cytoplasm. We designed peptide inhibitors based on the NPC1 receptor to target the NPC1 binding site to block viral entry. The results indicated that the ligand-based peptide inhibitors showed potent inhibition activities in vitro studies against pseudotyped or replication-competent Orthoebolavirus. Therefore, we further evaluated one of them in a mouse model challenged with mice-adapted Ebola viruses, which showed some protection efficacy compared with the control group. This study suggests that ligand-based peptides are encouraging inhibitors in the development of inhibitors against Ebola virus infection. Full article

In 2025, the Democratic Republic of the Congo (DRC) experienced its 16th Ebola Virus Disease (EVD) outbreak, centered in the Bulape Health Zone of Kasai Province, amid multiple concurrent epidemics and limited health infrastructure. Genomic sequencing revealed a novel zoonotic spillover genetically related to the 1976 Yambuku strain. A Root Cause Analysis (RCA) using the “5 Whys” framework, integrating epidemiological data, genomic analysis, and surveillance reports, identified key contributors to delayed detection and response, with comparative insights drawn from the 2018–2020 North Kivu outbreak. The Mweka outbreak resulted in 28 confirmed, probable, or suspected cases and 15 deaths, including four healthcare workers. Root causes included inadequate ecological surveillance, weak community alert systems, diagnostic delays due to reliance on centralized laboratories, health system overload from concurrent outbreaks, and structural underfunding of preparedness and coordination. Unlike North Kivu, where security issues drove response delays, systemic and ecological vulnerabilities predominated in Mweka. These findings highlight how ecological and structural weaknesses facilitate novel Ebola spillovers and their escalation, emphasizing the need for sustained investment in One Health surveillance, decentralized diagnostics, and resilient public health governance to strengthen outbreak response capacity. Full article

The National Special Pathogens System (NSPS) stratifies U.S. healthcare facilities by their readiness level to care for patients with high-consequence infectious diseases (HCIDs). While NSPS Level 1 and 2 facilities possess advanced biocontainment capabilities to care for patients for the duration of their illness, most U.S. hospitals fall under a NSPS Level 3 or 4 designation, with limited resources to manage patients with a suspected or confirmed HCID. However, emerging zoonotic threats like H5N1 underscore the need to bolster HCID preparedness across all NSPS Levels. Beginning in March 2024, the U.S. H5N1 outbreak has primarily impacted wild bird flocks, poultry, and cattle, along with some human infections. The continuation of this outbreak in wild and domesticated animals increases the likelihood of further human spillover and eventual viral evolution in human hosts. At the frontlines, rural farming communities are likely to be most affected, with potential outbreaks exacerbated by a lack of accessible NSPS Level 1, 2, or 3 facilities in these regions. Thus, strengthening the HCID preparedness of local NSPS Level 4 facilities is critical to preventing transmission, minimizing societal disruption, protecting communities and the healthcare workforce, along with ensuring an equitable, coordinated response to future emerging infectious disease threats. This manuscript explores the financial, societal and health system impacts of HCID outbreaks to delineate the necessity of strengthening the preparedness of NSPS Level 4 facilities. 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