Search Results (240)

Valley fever (coccidioidomycosis) is an infection posing a significant human health risk, resulting from the soil-dwelling fungi Coccidioides. Although incidence and mortality from coccidioidomycosis are underreported in the United States, and this underreporting may impact public health policy in numerous jurisdictions, its incidence is rising. Underreporting may stem from diagnostic and testing difficulties, insufficient environmental sampling for pathogen detection to determine endemicity, and a shortage of data on Coccidioides dispersion. As climate change creates increasingly arid locations in the US favorable for Coccidioides proliferation, determining its total endemicity becomes more difficult. This literature review examining published research from 2000 to 2025 revealed a paucity of publications examining the endemicity of Coccidioides and research gaps in detection methods, including limited studies on the reliability of sampling for geographical and temporal variations, challenges in assessing various sample materials, poorly defined storage conditions, and the lack of precise, less restrictive, cost-effective laboratory procedures. Addressing these challenges requires interdisciplinary collaboration among Coccidioides researchers, wildlife experts, atmospheric and climate scientists, and policymakers. If these obstacles are solved, standardized approaches for identifying Coccidioides, classified by climate zones and ecoregions, could be developed, saving financial resources, labor, and time for future researchers studying the environmental drivers of coccidioidomycosis. Full article

In Kenya, Rift Valley fever (RVF) outbreaks pose significant challenges, being one of the most severe climate-sensitive zoonoses. While machine learning (ML) techniques have shown superior performance in time series forecasting, their application in predicting disease outbreaks in Africa remains underexplored. Leveraging data from the International Livestock Research Institute (ILRI) in Kenya, this study pioneers the use of ML techniques to forecast RVF outbreaks by analyzing climate data spanning from 1981 to 2010, including ML models. Through a comprehensive analysis of ML model performance and the influence of environmental factors on RVF outbreaks, this study provides valuable insights into the intricate dynamics of disease transmission. The XGB Classifier emerged as the top-performing model, exhibiting remarkable accuracy in identifying RVF outbreak cases, with an accuracy score of 0.997310. Additionally, positive correlations were observed between various environmental variables, including rainfall, humidity, clay patterns, and RVF cases, underscoring the critical role of climatic conditions in disease spread. These findings have significant implications for public health strategies, particularly in RVF-endemic regions, where targeted surveillance and control measures are imperative. However, this study also acknowledges the limitations in model accuracy, especially in scenarios involving concurrent infections with multiple diseases, highlighting the need for ongoing research and development to address these challenges. Overall, this study contributes valuable insights to the field of disease prediction and management, paving the way for innovative solutions and improved public health outcomes in RVF-endemic areas and beyond. Full article

Rift Valley fever (RVF) is a zoonotic disease caused by the Rift Valley fever virus (RVFV), affecting humans, livestock, and wild ruminants. This study aimed to characterize and assess the genetic diversity of RVFV strains circulating among livestock in Uganda. Blood samples were collected between January 2021 and May 2024 from apparently healthy cattle, goats, and sheep in four districts. The samples were first screened for RVFV antibodies using ELISA; antibody-positive samples were subsequently tested for viral RNA using reverse transcriptase quantitative PCR (RT-qPCR). The PCR-positive samples underwent targeted amplicon sequencing, and phylogenetic analyses of the small (S) and large (L) genome segments were conducted to determine viral lineages. Of the 833 ELISA-positive samples, 10 (all from cattle) tested positive for RVFV RNA using RT-qPCR. Consensus sequences were successfully generated for six S segments and one L genome segment. A phylogenetic analysis revealed that all sequences belonged to lineage C, showing close genetic similarity to RVFV strains previously identified in Uganda, Kenya, Sudan, Madagascar, and Saudi Arabia. Limited genetic diversity was observed at both the nucleotide and amino acid levels. The detection of RVFV in apparently healthy cattle suggests ongoing, low-level viral circulation in Uganda. These findings offer important insights for guiding RVF surveillance, control, and policymaking in the country. Full article

In Africa, Rift Valley Fever poses a substantial risk to animal health, and human cases occur after contact with infected animals or their tissues. RVF has re-emerged in Uganda after nearly five decades, with multiple outbreaks recorded since 2016. We investigated a unique RVF outbreak associated with an animal abortion storm of 30 events and human cases on a dairy farm in Mbarara District, Western Uganda, in February 2023. Genomic analysis was performed, comparing animal and human RVF viruses (RVFV) circulating in the region. A cluster of thirteen human RVF cases and nine PCR-positive animals could directly be linked with the abortion storm. Overall, during the year 2023, we confirmed 61 human RVFV cases across Uganda, 88.5% of which were reported to have had direct contact with livestock, and a high case fatality rate of 31%. We recommend implementing extensive health education programs in affected communities and using sustainable mosquito control strategies to limit transmission in livestock, coupled with initiating animal vaccination trials in Uganda. Full article

Coccidioidomycosis (Valley fever), caused by Coccidioides spp., is a fungal infection endemic to semi-arid regions of the Americas. Despite 80 years of disease recognition in New Mexico, there is limited disease awareness. We incorporated clinical, epidemiological, and ecological datasets to summarize the knowledge of Valley fever in New Mexico. We analyzed 1541 human cases from 2006 to 2023. On average, 86 cases were reported each year (4.1 cases per 100,000 population per year). The highest levels of incidence were in southwestern New Mexico. American Indian or Alaska Natives in New Mexico had a 1.9 times higher incidence rate of coccidioidomycosis than White people, and among age groups, older populations in New Mexico had the highest incidence rates. We analyzed 300 soil samples near Las Cruces, New Mexico, for the presence of Coccidioides and reported the first known positive soil samples collected from the state, the majority of which were from grassland-dominated sites and from animal burrows. Sequence analyses in clinical specimens, wild animals, and soil samples confirmed that Coccidioides posadasii is the main causative species of coccidioidomycosis in New Mexico. Environmental surveillance validated that locally acquired infections could occur in, but are not limited to, Catron, Doña Ana, Sierra, and Socorro Counties. Full article

Black flies (Diptera: Simuliidae) are important vectors of pathogens, including filarial nematodes, protozoans, and arboviruses, which significantly impact human and animal health. Although their role in arbovirus transmission has not been as thoroughly studied as that of mosquitoes and ticks, advances in molecular tools, particularly metagenomics, have enabled the identification of non-cultivable viruses, significantly enhancing our understanding of black-fly-borne viral diversity and their public and veterinary health implications. However, these methods can also detect insect-specific viruses (i.e., viruses that are unable to replicate in vertebrate hosts), which may lead to the incorrect classification of black flies as potential vectors. This underscores the need for further research into their ecological and epidemiological roles. This systematic review, conducted following the PRISMA protocol, compiled and analyzed evidence on arbovirus detection in Simuliidae from scientific databases. Several arboviruses were identified in these insects, including vesicular stomatitis virus New Jersey serotype (VSVNJ), Venezuelan equine encephalitis virus (VEEV), and Rift Valley fever virus. Additionally, in vitro studies evaluating the vector competence of Simuliidae for arboviruses such as dengue virus, Murray Valley encephalitis virus, and Sindbis virus were reviewed. These findings provide critical insights into the potential role of black flies in arbovirus transmission cycles, emphasizing their importance as vectors in both public and veterinary health contexts. Full article

Handling cultured isolates and clinical, environmental, or wildlife surveillance samples containing Risk Group 3 and 4 pathogens presents considerable biosafety challenges in minimizing human exposure during processing and transport. Safe handling typically requires high- or maximum-containment facilities, demanding substantial logistical planning and resources. We evaluated PrimeStore Molecular Transport Medium (PS-MTM), a guanidine-based solution created to kill pathogens and preserve nucleic acids at ambient temperatures, for inactivating Crimean-Congo hemorrhagic fever, eastern equine encephalitis, Ebola, Hendra, Japanese encephalitis, Lassa, Marburg, Nipah, Rift Valley fever, and West Nile viruses. To mimic diagnostic conditions, human whole blood spiked with any of these viruses was incubated with PS-MTM for 20-, 30-, or 60-min. Samples with titers up to 10⁷ PFU/mL exposed to PS-MTM at all time points resulted in complete loss of infectivity judged by plaque assays. A 30-min incubation provided a 50% safety margin over the minimum inactivation time and was used for quantification with the tissue culture infectious dose (TCID₅₀) assay, enabling evaluation of PS-MTM’s activity for viruses that do or do not produce well-defined plaques. Results confirmed that PS-MTM inactivated all tested viruses at titers up to 10⁷ TCID₅₀/mL, underscoring its reliability for enhancing biosafety in diagnostics, outbreak management, and surveillance. Full article

Coccidioidomycosis is a fungal disease affecting humans and other mammals caused by environmental pathogens of the genus Coccidioides. Human exposure to the pathogen occurs via inhalation of spores aerosolized from soil. Thus, understanding the ecological factors that shape the distribution of Coccidioides in soils is important for minimizing the risk of human exposure, though this task remains challenging due to the pathogen’s highly variable spatial distribution. Here, we examined the associations between the soil microbial community and Coccidioides immitis’ presence within the Carrizo Plain National Monument, a minimally disturbed grassland ecosystem, and the site of a longitudinal study examining the effects of rodents and their burrows on C. immitis’ presence in soils. Using internal transcribed spacer 2 (ITS2) and 16S amplicon sequencing to characterize the soil fungal and bacterial communities, we found over 30 fungal species, including several other members of the Onygenales order, that co-occurred with C. immitis more frequently than would be expected by chance. Coccidioides-positive samples were significantly higher in fungal and bacterial diversity than negative samples, an association partly driven by higher Coccidioides presence within rodent burrows compared to surface soils. Soil source (i.e., rodent burrow versus surface soil) explained the largest amount of variation in bacterial and fungal community diversity and composition, with soils collected from rodent burrows having higher fungal and bacterial diversity than those collected from adjacent surface soils. While prior evidence is mixed regarding the relationship between the presence of Coccidioides and microbial diversity, we find that favorable microhabitats, such as rodent burrows, lead to a positive association between soil microbial diversity and Coccidioides presence, particularly in otherwise resource-limited natural environments. Full article

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that can cause substantial morbidity and mortality in livestock and humans, for which there are no currently available licensed human therapeutics or vaccines. Therefore, the development of safe and effective antivirals is both necessary and urgent. The Gc protein is the primary target of the neutralizing antibody response related to Rift Valley fever virus. Here, we report one Gc-specific neutralizing antibody (NA137) isolated from an alpaca and one bispecific antibody (E2-NA137), the protective efficacies of which we evaluated in A129 mice. In this prophylactic study, the survival rates of the NA137 and E2-NA137 groups were both 80%, and in the treatment study, the survival rates were 20% and 60%, respectively. Altogether, our results emphasize that NA137 and E2-NA137 provide a potential approach for treating RVFV either prophylactically or therapeutically. Full article

Insect-borne viruses may account for a significant proportion of non-malaria and non-bacterial febrile illnesses in Liberia. Although the presence of many arthropod vectors has been documented, the collective burden of arbovirus infections and baseline pre-existing immunity remains enigmatic. Our goal was to determine the seroprevalence of arbovirus exposure across the country using a resource-sparing, multiplex immunoassay to determine IgG responses to immunodominant antigens. 532 human serum samples, from healthy adults, collected from 10 counties across Liberia, were measured for IgG reactivity against antigens of eight common flavi-, alpha-, and orthobunya/nairoviruses suspected to be present in West Africa. Approximately 32.5% of our samples were reactive to alphavirus (CHIKV) E2, ~7% were reactive separately to West Nile (WNV) and Zika virus (ZIKV) NS1, while 4.3 and 3.2% were reactive to Rift Valley Fever virus (RVFV) N and Dengue virus-2 (DENV-2) NS1, respectively. Altogether, 21.6% of our samples were reactive to ≥1 flavivirus NS1s. Of the CHIKV E2 reactive samples, 8.5% were also reactive to at least one flavivirus NS1, and six samples were concurrently reactive to antigens of all three arbovirus groups, suggesting a high burden of multiple arbovirus infections for some participants. These insights suggest the presence of these four arbovirus families in Liberia with low and moderate rates of flavi- and alphavirus infections, respectively, in healthy adults. Further confirmational investigation, such as mosquito surveillance or other serological tests, is warranted and should be conducted before initiating additional flavivirus vaccination campaigns. The findings of these studies can help guide healthcare resource mobilization, vector control, and animal husbandry practices. Full article

Rift Valley fever (RVF) is a vector-borne zoonotic viral disease that causes abortion storms, fetal malformations, and neonatal mortality in livestock ruminants. In humans, RVF can lead to hemorrhagic fever, encephalitis, retinitis, or blindness, and about 1% of patients die. Since there are no registered vaccines for human use, developing RVF vaccines for use in animals is crucial to protect animals and prevent the spread of the virus from infecting humans. We recently developed a live bovine herpesvirus type 1 quadruple gene-mutant vector (BoHV-1qmv) that lacks virulence and immunosuppressive properties. Further, we engineered a BoHV-1qmv-vectored subunit Rift Valley fever virus (RVFV) vaccine (BoHV-1qmv Sub-RVFV) for cattle, in which a chimeric polyprotein coding for the RVFV Gc, Gn, and bovine granulocyte–macrophage colony-stimulating factor (GMCSF) proteins is fused but cleaved proteolytically in infected cells into individual membrane-anchored Gc and secreted Gn-GMCSF proteins. Calves vaccinated with the BoHV-1qmv Sub-RVFV vaccine generated moderate levels of RVFV-specific serum-neutralizing (SN) antibodies and cellular immune responses. In the current study, we repurposed the BoHV-1qmv Sub-RVFV for sheep by replacing the RVFV Gc and Gn ORF sequences codon-optimized for bovines with the corresponding ovine-codon-optimized sequences and by fusing the sheep GM-CSF ORF sequences with the Gn ORF sequence. A combined primary intranasal-plus-subcutaneous primary immunization induced a moderate level of BoHV-1 (vector)- and vaccine strain MP12-specific SN antibodies and MP-12-specific cellular immune responses. Notably, an intranasal booster vaccination after 29 days triggered a rapid (within 7 days) rise in MP-12-specific SN antibody titers. Therefore, the BoHV-1qmv-vectored subunit RVFV vaccine is safe and highly immunogenic in sheep and can potentially be an efficient subunit vaccine for sheep against RVFV. Full article

There are scarce data comparing inpatient mortality, length of stay (LOS) and all-cause hospital costs in disseminated coccidioidomycosis (DCM) vs. isolated pulmonary coccidioidomycosis (IPCM). We assessed the burden of hospital illness associated with DCM versus IPCM. This study was performed using National Inpatient Sample data from 2019 to 2021. DCM was defined as having a primary International Classification of Diseases—Tenth Revision (ICD-10) code for coccidioidal meningitis, a non-primary code for coccidioidal meningitis in the presence of a primary code for a meningitis complication or a procedure code depicting the need for a meningitis-related procedure, or a primary code for DCM without a code for unspecified disease. IPCM was defined as a primary code for pulmonary coccidioidomycosis without codes for DCM or unspecified disease. Multivariable regression was used to compare the odds of in-hospital mortality, LOS and all-cause hospital costs (2023 US$) for DCM versus IPCM, after covariate adjustment. A total of 6195 hospitalizations were identified, 2305 for DCM and 3890 for IPCM. Patients experiencing a DCM hospitalization had a 19.7% incidence of concomitant pulmonary coccidioidomycosis. Coccidioidal meningitis constituted 81.3% of all DCM hospitalizations, of which 78.1% received a meningitis-related procedure or were admitted for a meningitis complication. DCM was associated with an increased odds of death (odds ratio = 2.76, 95% confidence interval [CI] = 1.26–6.04) versus IPCM. DCM was associated with a longer mean hospital LOS (4.51 days, 95%CI = 3.39–5.63) and higher mean all-cause costs ($20,008, 95%CI = $15,313–$24,704) versus IPCM. DCM hospitalizations were associated with higher odds of inpatient mortality, longer LOS, and higher costs versus IPCM. Full article

Background: Rift Valley fever virus (RVFV) is a zoonotic virus that poses a significant threat to both livestock and human health and has caused outbreaks in endemic regions. In humans, most patients experience a febrile illness; however, in some patients, RVF disease may result in hemorrhagic fever, retinitis, or encephalitis. While several veterinary vaccines are being utilized in endemic countries, currently, there are no licensed RVF vaccines or therapeutics for human use. Neutralizing antibodies specifically targeting vulnerable pathogen epitopes are promising candidates for prophylactic and therapeutic interventions. In the case of RVFV, the surface glycoproteins Gc and Gn, which harbor neutralizing epitopes, represent the primary targets for vaccine and neutralizing antibody development. Methods: We report the implementation of advanced 10x Genomics technology, enabling high-throughput single-cell analysis for the identification of rare and potent antibodies against RVFV. Following the immunization of mice with live attenuated rMP-12-GFP virus and successive Gc/Gn boosts, memory B cell populations (both general and antigen-specific) were sorted from splenocytes by flow cytometry. Deep sequencing of the antibody repertoire at a single-cell resolution, together with bioinformatic analyses, was applied for BCR pair selection based on their abundance and specificity. Results: Twenty-three recombinant monoclonal antibodies (mAbs) were selected and expressed, and their antigen-binding capacities were characterized. About half of them demonstrated specific binding to their cognate antigen with relatively high binding affinities. Conclusions: These antibodies could be used for the future development of efficacious therapeutics, as well as for studying virus-neutralizing mechanisms. The current study, in which the single-cell sequencing approach was implemented for the development of antibodies targeting the RVFV surface proteins Gc and Gn, demonstrates the effective applicability of this technique for antibody discovery purposes. Full article

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic disease within the genus Phlebovirus. Symptoms of the disease in animals range from moderate to severe febrile illness, which significantly impacts the livestock industry and causes severe health complications in humans. Similar to bunyaviruses in the genus Orthobunyavirus transmitted by mosquitoes, RVFV progression is dependent on the susceptibility of the physical, cellular, microbial, and immune response barriers of the vectors. These barriers, shaped by the genetic makeup of the mosquito species and the surrounding environmental temperature, exert strong selective pressure on the virus, affecting its replication, evolution, and spread. The changing climate coupled with the aforementioned bottlenecks are significant drivers of RVF epidemics and expansion into previously nonendemic areas. Despite the link between microclimatic changes and RVF outbreaks, there is still a dearth of knowledge on how these temperature effects impact RVF transmission and vector competence and virus persistence during interepidemic years. This intricate interdependence between the virus, larval habitat temperatures, and vector competence necessitates increased efforts in addressing RVFV disease burden. This review highlights recent advancements made in response to shifting demographics, weather patterns, and conveyance of RVFV. Additionally, ongoing studies related to temperature-sensitive variations in RVFV–vector interactions and knowledge gaps are discussed. Full article

Aedes aegypti is of great public health concern because of its vectorial capacity to transmit various arboviruses such as Zika, yellow fever, dengue, and chikungunya. In California, its expanding geographic distribution has been unrestrained. This urgently calls for innovative tools such as the use of sterile insect technique (SIT) to strengthen invasive Aedes control. This study aimed to determine the efficacy of combining an SIT application into integrated vector management (IVM) strategies in invasive Aedes control in the West Valley region of southern California. A total of 25 Aedes hotspots, grouped into two cohorts—sites that received SIT treatment only (n = 9) and sites that received both SIT and In2Care^® Mosquito Stations (n = 16)—were selected for this study. Biweekly, X-ray irradiated male Ae. aegypti mosquitoes were released between April and November 2024. Data from weekly BG Sentinel-2 traps were utilized to compare the mosquito densities between the pre-intervention (2023) and intervention (2024) periods for both cohorts. In addition, a subset of samples (n = 50) of irradiated male mosquitoes were placed in a separate cage with freshly emerged unirradiated female mosquitoes to evaluate the level of sterility of the eggs from these mosquitoes. Aedes-related service requests made by the District’s residents were also compared between the pre-intervention and intervention periods to indirectly determine the effect of optimizing the control strategies on overall mosquito problems. A total of 106,608 sterile male Ae. aegypti were released between April and November 2024. The cohort with the SIT only application showed a 44% reduction in the number of female Ae. aegypti per trap-night during the intervention period compared with the pre-intervention period. At sites with In2Care Mosquito Stations that also received SIT treatment, the mosquito density dropped by 65% during the intervention period compared with the pre-intervention period. The number of Aedes-related service requests during the intervention year (n = 367) was 45% lower than the pre-intervention year (n = 656). Over 99.6% eggs collected from female mosquitoes mated with irradiated males did not hatch, indicating a high level of sterility of the irradiated males utilized for our SIT application. Here, we demonstrated the potential of SIT when combined with IVM strategies such as In2Care^® Mosquito Stations, offering a holistic approach to reducing the public health risks associated with Aedes-borne diseases. Full article