Search Results (68)

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

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

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

Rift Valley fever virus (RVFV) is an emerging mosquito-borne arbovirus of One Health importance that caused two large outbreaks in Rwanda in 2018 and 2022. Information on vector species with a role in RVFV eco-epidemiology in Rwanda is scarce. Here we sought to identify potential mosquito vectors of RVFV in Rwanda, their distribution and abundance, as well as their infection status. Since an outbreak of RVF occurred during the study period, data were obtained both during an interepidemic period and during the 2022 Rwanda RVF outbreak. Five districts of the eastern province of Rwanda were prospected using a combination of unbaited light traps and Biogents (BG Sentinel and Pro) traps baited with an artificial human scent during three periods, namely mid-August to mid-September 2021, December 2021, and April to May 2022. Trapped mosquitoes were morphologically identified and tested for viral evidence using both RT-PCR and virus isolation methods on a Vero cell line. A total of 14,815 adult mosquitoes belonging to five genera and at least 17 species were collected and tested as 765 monospecific pools. Culex quinquefasciatus was the most predominant species representing 72.7% of total counts. Of 527 mosquito pools collected before the 2022 outbreak, a single pool of Cx. quinquefasciatus showed evidence of RVFV RNA. Of 238 pools collected during the outbreak, RVFV was detected molecularly from five pools (two pools of Cx. quinquefasciatus, two pools of Anopheles ziemanni, and one pool of Anopheles gambiae sensu lato), and RVFV was isolated from the two pools of Cx. quinquefasciatus, from Kayonza and Rwamagana districts, respectively. Minimum infection rates (per 1000 mosquitoes) of 0.4 before the outbreak and 0.6–7 during the outbreak were noted. Maximum-likelihood phylogenetic analysis indicates that RVFV detected in these mosquitoes is closely related to viral strains that circulated in livestock in Rwanda and in Burundi during the same RVF outbreak in 2022. The findings reveal initial evidence for the incrimination of several mosquito species in the transmission of RVFV in Rwanda and highlight the need for more studies to understand the role of each species in supporting the spread and persistence of RVFV in the country. Full article

Rift Valley fever (RVF) is a devastating zoonotic mosquito-borne viral hemorrhagic fever disease that threats human and animal health and biodiversity in Africa, including in Rwanda. RVF is increasingly outbreaking in Africa, leading to devastating impacts on health, socioeconomic stability and growth, and food insecurity in the region, particularly among livestock-dependent communi-ties. This systematic review synthesizes existing evidence on RVF’s epidemiology, transmission dynamics, and the prevention and control measures implemented in Rwanda. Our findings high-light the rapidly increasing prevalence of RVF and the expansion of its geographical distribution and host range in Rwanda. Furthermore, the review reveals gaps in local evidence, including the existence of competent vectors of RVFV and the risk factors associated with the emergence and spread of RVF in the country. This underscores the urgent need for prospective research to inform evidence-based health policymaking, strategic planning, and the development and implementation of cost-effective preventive and control measures, including diagnosis and surveillance for early detection and response. It also calls for the institutionalization of a cost-effective, multisectoral, and transdisciplinary One Health strategy for reducing the burden and risk of climate climate-sensitive and zoonotic diseases, including RVF, in the country. We recommend exploring cost-effective human and/or animal vaccination mechanisms for RVF, integrating AI-powered drones into dis-ease vectors surveillance and control, and the routine implementation of genomics-enhanced xenosurveillance to monitor changes in pathogens and vectors dynamics in order to inform poli-cymaking and guide the control interventions. Full article

Although the highlands of East Africa lack the geo-ecological landmarks of Rift Valley fever (RVF) disease hotspots to participate in cyclic RVF epidemics, they have recently reported growing numbers of small RVF clusters. Here, we investigated whether RVF cycling occurred among livestock and humans in the central highlands of Kenya during inter-epidemic periods. A 2-year prospective hospital-based study among febrile patients (March 2022–February 2024) in Murang’a County of Kenya was followed by a cross-sectional human–animal survey. A total of 1468 febrile patients were enrolled at two clinics and sera tested for RVF virus RNA and antiviral antibodies. In the cross-sectional study, humans (n = 282) and livestock (n = 706) from randomly selected households were tested and questionnaire data were used to investigate sociodemographic and environmental risk factors by multivariate logistic regression. No human (n = 1750) or livestock (n = 706) sera tested positive for RVFV RNA. However, 4.4% livestock and 2.0% humans tested positive for anti-RVFV IgG, including 0.27% febrile patients who showed four-fold IgG increase and 2.4% young livestock (<12 months old), indicating recent virus exposure. Among humans, the odds of RVF exposure increased significantly (p < 0.05, 95% CI) in males (aOR: 4.77, 2.08–12.4), those consuming raw milk (aOR: 5.24, 1.13–17.9), milkers (aOR: 2.69, 1.23–6.36), and participants residing near quarries (aOR: 2.4, 1.08–5.72). In livestock, sheep and goats were less likely to be seropositive (aOR: 0.27, 0.12–0.60) than cattle. The increase in RVF disease activities in the highlands represents a widening geographic dispersal of the virus, and a greater risk of more widespread RVF epidemics in the future. Full article

Reports of Rift Valley fever (RVF), a highly climate-sensitive zoonotic disease, have been rather frequent in Kenya. Although multiple empirical analyses have shown that machine learning methods outperform time series models in forecasting time series data, there is limited evidence of their application in predicting disease outbreaks in Africa. In recent times, the literature has reported several applications of machine learning in facilitating intelligent decision-making within the healthcare sector and public health. However, there is a scarcity of information regarding the utilization of the XGBoost model for predicting disease outbreaks. Within the provinces of Kenya, the incidence of Rift Valley fever was more prominent in the Rift Valley (26.80%) and Eastern (20.60%) regions. This study investigated the correlation between the occurrence of RVF (rapid vegetation failure) and several climatic variables, including humidity, clay content, elevation, slope, and rainfall. The correlation matrix revealed a modest linear dependence between different climatic variables and RVF cases, with the highest correlation, a mere 0.02903, observed for rainfall. The XGBoost model was trained using these climate variables and achieved outstanding performance measures including an AUC of 0.8908, accuracy of 99.74%, precision of 99.75%, and recall of 99.99%. The analysis of feature importance revealed that rainfall was the most significant predictor. These findings align with previous studies demonstrating the significance of weather conditions in RVF outbreaks. The study’s results indicate that incorporating advanced machine learning models that consider several climatic variables can significantly enhance the prediction and management of RVF incidence. Full article

Rift Valley fever (RVF) is a mosquito-borne viral disease that primarily affects animals, especially ruminants, but has the capacity to infect humans and result in outbreaks. Infection with the causative agent, RVF virus (RVFV), causes severe disease in domestic animals, especially sheep, resulting in fever, anorexia, immobility, abortion, and high morbidity and mortality rates in neonate animals. Humans become infected through exposure to infected animals and, less frequently, directly via a mosquito bite. A greater awareness of RVFV and its epidemic potential has resulted in increased investment in the development of interventions, especially vaccines. There is currently no substitute for the use of animal models in order to evaluate these vaccines. As outbreaks of RVF disease are difficult to predict or model, conducting Phase III clinical trials will likely not be feasible. Therefore, representative animal model systems are essential for establishing efficacy data to support licensure. Nonhuman primate (NHP) species are often chosen due to their closeness to humans, reflecting similar susceptibility and disease kinetics. This review covers the use of NHP models in RVFV research, with much of the work having been conducted in rhesus macaques and common marmosets. The future direction of RVF work conducted in NHP is discussed in anticipation of the importance of it being a key element in the development and approval of a human vaccine. Full article

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality rates in ruminants and sometimes severe to fatal complications like encephalitis and hemorrhagic fever in humans. There is no licensed RVF vaccine for human use while approved livestock vaccines have suboptimal safety or efficacy. We designed self-amplifying RNA (saRNA) RVF vaccines and assessed their humoral immunogenicity in mice. Plasmid DNA encoding the Rift Valley fever virus (RVFV) medium (M) segment consensus sequence (WT consensus) and its derivatives mutated to enhance cell membrane expression of the viral surface glycoproteins n (Gn) and c (Gc) were assessed for in vitro expression. The WT consensus and best-expressing derivative (furin-T2A) were cloned into a Venezuelan equine encephalitis virus (VEEV) plasmid DNA replicon and in vitro transcribed into saRNA. The saRNA was formulated in lipid nanoparticles and its humoral immunogenicity in BALB/c mice was assessed. High quantities of dose-dependent RVFV Gn IgG antibodies were detected in the serum of all mice immunized with either WT consensus or furin-T2A saRNA RVF vaccines. Significant RVFV pseudovirus-neutralizing activity was induced in mice immunized with 1 µg or 10 µg of the WT consensus saRNA vaccine. The WT consensus saRNA RVF vaccine warrants further development. Full article

Crimean-Congo hemorrhagic fever (CCHF) and Rift Valley fever (RVF) are among the list of emerging zoonotic diseases that require special attention and priority. RVF is one of the six priority diseases selected by the Senegalese government. Repeated epidemic episodes and sporadic cases of CCHF and RVF in Senegal motivated this study, involving a national cross-sectional serological survey to assess the distribution of the two diseases in this country throughout the small ruminant population. A total of 2127 sera from small ruminants (goat and sheep) were collected in all regions of Senegal. The overall seroprevalence of CCHF and RVF was 14.1% (IC 95%: 12.5–15.5) and 4.4% (95% CI: 3.5–5.3), respectively. The regions of Saint-Louis (38.4%; 95% CI: 30.4–46.2), Kolda (28.3%; 95% CI: 20.9–35.7), Tambacounda (22.2%; 95% CI: 15.8–28.6) and Kédougou (20.9%; 95% CI: 14.4–27.4) were the most affected areas. The risk factors identified during this study show that the age, species and sex of the animals are key factors in determining exposure to these two viruses. This study confirms the active circulation of CCHF in Senegal and provides important and consistent data that can be used to improve the surveillance strategy of a two-in-one health approach to zoonoses. Full article

Capripoxviruses are the causative agents of sheeppox, goatpox, and lumpy skin disease (LSD) in cattle, which cause economic losses to the livestock industry in Africa and Asia. Capripoxviruses are currently controlled using several live attenuated vaccines. It was previously demonstrated that a lumpy skin disease virus (LSDV) field isolate from Warmbaths (WB) South Africa, ORF 005 (IL-10) gene-deleted virus (LSDV WB005KO), was able to protect sheep and goats against sheeppox and goatpox. Subsequently, genes encoding the protective antigens for peste des petits ruminants (PPR) and Rift Valley fever (RVF) viruses have been inserted in the LSDV WB005KO construct in three different antigen forms (native, secreted, and fusion). These three multivalent vaccine candidates were evaluated for protection against PPR using a single immunization of 10⁴ TCID₅₀ in sheep. The vaccine candidates with the native and secreted antigens protected sheep against PPR clinical disease and decreased viral shedding, as detected using real-time RT-PCR in oral and nasal swabs. An anamnestic antibody response, measured using PPR virus-neutralizing antibody response production, was observed in sheep following infection. The vaccine candidates with the antigens expressed in their native form were evaluated for protection against RVF using a single immunization with doses of 10⁴ or 10⁵ TCID₅₀ in sheep and goats. Following RVF virus infection, sheep and goats were protected against clinical disease and no viremia was detected in serum compared to control animals, where viremia was detected one day following infection. Sheep and goats developed RVFV-neutralizing antibodies prior to infection, and the antibody responses increased following infection. These results demonstrate that an LSD virus-vectored vaccine candidate can be used in sheep and goats to protect against multiple viral infections. Full article

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies. Full article