Search Results (258)

Yellow fever virus (YFV) is divided into seven genotypes, including West Africa II (WAII) and South America I (SAI). The first wild-type YFVs isolated, Asibi (Ghana/1927) and French Viscerotropic virus ([FVV] Senegal/1927), are members of WAII. The first YFV strain isolated in South America, JSS (Brazil/1935), was associated with the last outbreak of urban YF in Brazil and has been insufficiently studied. We utilized Next Generation Sequencing to compare JSS with Asibi, FVV, and other South American YFV strains. SAI strains, including JSS, had higher genetic diversity than WAII strains. Phylogenetic and phylogeographic studies of YFV in South America have revealed the circulation of five lineages within Brazil, termed 1A-1E. JSS was found to be distinct from the five genetic lineages currently recognized in Brazil, and so we termed JSS as the currently sole member of Brazilian linage 1F. a comparison of JSS with all other Brazilian genomes of YFV suggests that lineage 1F appears to have become extinct. Full article

Background/Objectives: The envelope (E) protein of orthoflaviviruses contains antigenic sites that are composed of one or more epitopes, which can vary in antigenic specificity, including between viral species, strains, and even substrains. Monoclonal antibodies (mAbs) that bind these epitopes vary in functionality based on their specificity. This makes mAbs useful to study the differences in phenotypes between strains of viruses, such as the wild type (WT) and live attenuated vaccine strains of yellow fever virus (YFV). mAb 2D12 was raised against the 17D-204 YFV vaccine substrain virus (YF VAX^®) by Schlesinger et al. in 1983. However, it only neutralizes Asibi WT virus, not the 17D-204 vaccine substrain virus. Results: We confirmed these results and demonstrated that mAb 2D12 fails to neutralize all 17D vaccine substrains (17D-204, 17DD, and 17D-213), indicating that the minor differences between these virus substrains do not affect the epitope or functionality of mAb 2D12. In addition, mAb 2D12 was found to neutralize WT strain of French viscerotropic virus (FVV), with statistically indistinguishable neutralization from the WT strain Asibi. All but one of the live attenuated French neurotropic vaccine (FNV) derivative viruses had significantly lower neutralization than WT strains Asibi and FVV. FVV, Asibi, 17D, and FNV have many amino acid differences in the membrane (M) and E proteins. It is unclear which of them contributes to this differential neutralization. However, FNV and 17D have common amino acid substitutions from WT FVV and Asibi at positions M-36 and E-331, suggesting that one or both of these residues may contribute to the 2D12 epitope. Conclusions: Overall, mAb 2D12 is a valuable tool to distinguish WT virulent strains of YFV from live attenuated vaccine strains. Full article

Background: Acute lymphoblastic leukemia is the most prevalent childhood cancer and the leading cause of cancer mortality before the age of 20. Although therapeutic advances have significantly improved survival, children and adolescents treated for acute lymphoblastic leukemia remain vulnerable to infections, largely preventable by vaccination, due to humoral and cellular immune dysfunction induced by disease and treatment. Materials and Methods: This systematic review, based on electronic databases, aims to evaluate antibody levels associated with potential protective immunity against vaccine antigens for diphtheria, pertussis, tetanus, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, influenza, varicella-zoster virus, yellow fever, pneumococcal, and meningococcal diseases in children and adolescents treated for acute lymphoblastic leukemia after completion of chemotherapy. Results: A total of twenty-four studies published between 1981 and 2023 were included, comprising 1110 children and adolescents. Protective antibody levels ranged from 11% to 97% for diphtheria, 0% to 90% for pertussis, 20% to 100% for tetanus, and 11% to 95% for poliomyelitis. Haemophilus influenzae type b, protection ranged from 16.7% to 100%. Viral vaccines also showed heterogeneous responses, with protection rates of 25–79% for mumps, 16–86% for measles, 35–98% for rubella, and 23–75% for varicella-zoster virus. Antibody responses to pneumococcal and meningococcal vaccines were consistently low, with protection rates of 5–38% for pneumococcal studies and 12% in a single meningococcal study. Conclusions: This review found a consistent and clinically relevant loss of vaccine-induced immunity in children and adolescents treated for acute lymphoblastic leukemia. The recommendation of vaccine booster doses for this vulnerable population, irrespective of serological status, may represent a more practical approach to ensuring adequate post-chemotherapy treatment protection. Full article

Yellow fever (YF) is an infectious disease caused by the yellow fever virus (YFV), an arbovirus of the Flaviviridae family. It is transmitted through the bite of infected mosquitoes of the Culicidae family and affects both humans and non-human primates (NHPs). This study aimed to investigate the sylvatic Culicidae fauna and the occurrence of natural YFV infection in a microregion of southern Santa Catarina, Brazil, an area recently affected by a sylvatic YF outbreak. Entomological collections were conducted between January and February 2023 in five municipalities with confirmed viral circulation. Natural YFV infection was assessed using RT-LAMP. A total of 4352 female culicids were collected, representing at least 32 species, including several key sylvatic YFV vectors. Haemagogus leucocelaenus was identified in all sampled municipalities, whereas Haemagogus (Haemagogus) janthinomys Dyar, 1921, historically considered the primary vector of sylvatic YFV in Brazil, was not detected. Mosquitoes from the genera Aedes Meigen, 1818; Haemagogus Williston, 1896; Psorophora Robineau-Desvoidy, 1827; and Sabethes Robineau-Desvoidy, 1827 were tested for YFV. Only one pool, composed of Sabethes albiprivus, tested positive, yielding a minimum infection rate (MIR) of 11.6. This is the first record of natural YFV infection in Sa. albiprivus in southern Brazil, and only the third record globally, highlighting its potential role as a secondary vector in maintaining viral circulation in sylvatic environments. Based on species presence and abundance, Hg. leucocelaenus is likely to have acted as the primary YFV vector in the study area. The composition of the culicid fauna, coupled with the detection of YFV in sylvatic vectors, indicates an ongoing epidemiological risk. These findings underscore the need to strengthen entomological surveillance and expand YF vaccination coverage in affected and neighbouring regions. Full article

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) represent fundamental cellular adaptive mechanisms that maintain protein homeostasis and metabolic balance. Many RNA viruses, particularly flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), extensively remodel the ER to establish replication compartments and assemble progeny virions. This massive reorganization disrupts ER homeostasis, leading to UPR activation. Emerging evidence reveals that flaviviruses not only trigger but also manipulate the three UPR branches—PERK, IRE1, and ATF6—to optimize viral translation, replication, and egress. In parallel, flavivirus infection profoundly alters host lipid metabolism and promotes dynamic changes in lipid droplets (LDs), key organelles that mediate lipid storage and serve as scaffolds for viral replication and assembly. The UPR intimately connects to LD biogenesis through transcriptional and translational programs mediated by XBP1, ATF4, and ATF6, thereby coupling ER stress responses to lipid remodeling and energy homeostasis. This intricate crosstalk between UPR and LDs creates a metabolic and structural niche favorable for viral replication but detrimental to host cell integrity. This review provides a comprehensive analysis of the molecular mechanisms by which flaviviruses exploit ER stress and the UPR to reprogram lipid metabolism and LD dynamics. We highlight the dual role of UPR signaling in promoting adaptive lipid synthesis and initiating cell death under prolonged stress, discuss recent insights into ER–LD interactions during flavivirus infection, and explore therapeutic opportunities targeting UPR–lipid metabolic pathways as broad-spectrum antiviral strategies. Understanding this interconnected network will advance our knowledge of viral pathogenesis and identify new avenues for host-directed antiviral intervention. 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

Yellow fever (YF) remains a re-emerging vector-borne zoonotic disease in tropical regions of the Americas despite the availability of an effective vaccine. In South America, the virus is maintained through a jungle transmission cycle involving Haemagogus and Sabethes mosquitoes and non-human primates (NHPs), which act as amplifying hosts and key epidemiological sentinels. This narrative review examines the current status of YF epizootics in South America, with a focus on the role of NHPs in viral circulation, early detection, and spillover risk to human populations. We synthesize recent evidence on epizootic patterns across endemic countries, the differential susceptibility of neotropical primates, and the ecological and environmental drivers influencing transmission, including deforestation, habitat fragmentation, and human encroachment into forested areas. In addition, we analyze current surveillance strategies, including wildlife monitoring, entomological and genomic surveillance, and their integration within a One Health framework. This review highlights that YF epizootics are expanding geographically and are closely linked to environmental change and human–ecosystem interactions. Strengthening integrated, multidisciplinary surveillance systems is essential to improve early detection, guide vaccination strategies, and prevent human outbreaks. These findings underscore the critical importance of operationalizing the One Health approach to enhance preparedness and response to YF in South America. 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

Background/Objectives: Chimpanzee adenoviral-vectored vaccines have proven to be both safe and effective, with a manufacturing and distribution pipeline capable of rapid global supply, as demonstrated during the COVID-19 pandemic. Yellow fever is a mosquito-borne viral hemorrhagic disease endemic in parts of Africa and Latin America, and although an effective live attenuated vaccine exists, its use is limited by safety and eligibility restrictions. Moreover, large outbreaks continue to expose critical challenges, such as an insufficient vaccine supply, reliance on fractional dosing, and slow and difficult-to-scale manufacturing processes. Here, we report the design, development and in vivo immunogenicity of multiple yellow fever virus (YFV) antigen constructs based on the pre-membrane (prM) and envelope (E) proteins—with or without the transmembrane domain (TM or ΔTM)—delivered using the ChAdOx1 adenoviral vector. Methods: Four ChAdOx1 YF vaccines were developed, and immunogenicity was evaluated. The efficacy of the full-length YF envelope vaccine was also tested in Balb/c mice. Results/Conclusions: In contrast to previously described orthoflavivirus vaccines on the same platform, the full-length antigen elicited superior immunogenicity and conferred protection against intracranial challenge with the YF17D virus in mice. Notably, this protection was comparable to that induced by the licensed YF17D vaccine, highlighting the promise of this platform as a next-generation yellow fever vaccine candidate. 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

Yellow fever (YF) and malaria co-infections are real public health concerns in Africa, especially in countries such as Nigeria, where mosquitoes carrying both pathogens (Aedes for YF, Anopheles for malaria) coexist. A mathematical model that considers the critical factors influencing the transmission dynamics and control interventions of YF and malaria co-infections is formulated and used to analyse the problem. The essential dynamical features of the model, such as the basic reproduction number and disease-free equilibrium, are determined and analysed. The qualitative analysis of the model illustrates the conditions under which the disease can be eradicated or persists. Further analysis, supported by numerical simulations, reveals the intrinsic dynamics of the model and the impact of control interventions such as yellow fever vaccination, use of insecticide-treated mosquito nets, treatment of malaria-infected humans, and use of insecticides. The results of the analysis demonstrate the impact of interventions; specifically, effective implementations of interventions such as yellow fever vaccination, use of insecticide-treated mosquito nets, and use of insecticides appear to have a significant impact in eradicating YF and malaria co-infections in endemic areas. Effective treatment of malaria-infected humans may lead to a decrease in infections but might not necessarily lead to eradicating infections in endemic areas. These findings are expected to aid in improving the management of YF and malaria co-infections in endemic regions for expeditious disease eradication. Full article

The flavivirus NS1 protein is a component of the viral replication complex and plays diverse, yet poorly understood, roles in the viral life cycle. To enable real-time visualization of the developing replication organelle and biochemical analysis of tagged NS1 and its interacting partners, we engineered a replication-competent yellow fever virus (YFV) replicon encoding a C-terminal fusion of NS1 with green fluorescent protein (NS1-GFP). The initial variant was non-viable in the absence of trans-complementation with wild-type NS1; however, viability was partially restored through the introduction of co-adaptive mutations in GFP (Q204R/A206V) and NS4A (M108L). Subsequent cell culture adaptation generated a 17-nucleotide frameshift within the NS1-GFP linker, resulting in a more flexible and less hydrophobic linker sequence. The optimized genome, in the form of a replicon, replicates in packaging cells that produce YFV structural proteins, as well as in naive BHK-21 cells. In the packaging cells, the adapted NS1-GFP replicon produces titers of infectious particles of approximately 10⁶ FFU/mL and is genetically stable over five passages. The expressed NS1-GFP fusion protein localizes to the endoplasmic reticulum and co-fractionates with detergent-resistant heavy membranes, a hallmark of flavivirus replication organelles. This NS1-GFP replicon provides a novel platform for studying NS1 functions and can be further adapted for proximity-labeling strategies aimed at identifying the still-unknown protease responsible for NS1-NS2A cleavage. Full article

Mosquito-borne flaviviruses, including Dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Yellow fever virus (YFV), and Zika virus (ZIKV), continue to present a significant threat to public health worldwide. In 2024, these viruses accounted for 11,717 reported cases in the United States and more than 7.6 million cases globally. As of early 2025, according to CDC data, 1830 cases of dengue had already been reported, with 1584 transmitted locally within the U.S. Despite the considerable burden that these diseases pose, no specific antiviral treatments exist. A very limited number of virus-specific vaccines have been licensed, such as those for YFV, JEV, and, with specific constraints, for DENV. To date, no pan-flavivirus vaccine is available. This review examines the potential of emerging vaccine platforms—particularly messenger RNA and virus-like particles—as promising tools in the pursuit of a broadly protective flavivirus vaccine. We analyze current strategies for inducing cross-neutralizing immune responses and discuss how these technologies could support the presentation of conserved quaternary epitope conformations, which are increasingly recognized as critical targets for establishing potent immune responses. We review key advances in virology, immune response, and immunogen delivery systems to highlight the potential for developing a pan-flavivirus vaccine. Full article

Arboviral diseases are emerging public health challenges in Burkina Faso, largely driven by the proliferation of Aedes aegypti mosquitoes in the environment. Effective surveillance of arbovirus circulation is critical to inform interventions. From August 2022 to June 2023, we implemented a comprehensive entomological surveillance platform in five sectors of Bobo-Dioulasso. Surveillance methods included oviposition traps to collect eggs, larval surveys in some concessions per sector conducted bimonthly, and adult mosquito collections using BG-Sentinel traps and Prokopack aspirators. Mosquito samples colonized by Ae. aegypti were identified morphologically, confirmed by conventional PCR, and screened by RT-PCR for dengue (DENV), chikungunya (CHIKV), yellow fever (YFV), and Zika (ZIKV) viruses. Molecular analysis detected dengue virus and yellow fever virus in mosquito pools from sector 22 and chikungunya virus in sectors 9 and 26; no Zika virus was found. This study demonstrates the successful establishment of an integrated entomological surveillance platform capable of capturing the spatial and temporal dynamics of arboviral vectors and virus circulation in Bobo-Dioulasso. The identification of active dengue and chikungunya transmission underlines the urgent need for sustained vector monitoring and targeted control strategies. Our approach provides a scalable model for arboviral disease surveillance and epidemic preparedness in West African urban settings. 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