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Purpose: To provide an overview of pre-selected emerging arboviruses (arthropod-borne viruses) that cause ocular inflammation in humans. Methods: A comprehensive review of the literature published between 1997 and 2023 was conducted in PubMed database. We describe current insights into epidemiology, systemic and ocular manifestations, diagnosis, treatment, and prognosis of arboviral diseases including West Nile fever, Dengue fever, Chikungunya, Rift Valley fever, Zika, and Yellow fever. Results: Arboviruses refer to a group of ribonucleic acid viruses transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. They mostly circulate in tropical and subtropical zones and pose important public health challenges worldwide because of rising incidence, expanding geographic range, and occurrence of prominent outbreaks as a result of climate change, travel, and globalization. The clinical signs associated with infection from these arboviruses are often inapparent, mild, or non-specific, but they may include serious, potentially disabling or life-threatening complications. A wide spectrum of ophthalmic manifestations has been described including conjunctival involvement, anterior uveitis, intermediate uveitis, various forms of posterior uveitis, maculopathy, optic neuropathy, and other neuro-ophthalmic manifestations. Diagnosis of arboviral diseases is confirmed with either real time polymerase chain reaction or serology. Management involves supportive care as there are currently no specific antiviral drug options. Corticosteroids are often used for the treatment of associated ocular inflammation. Most patients have a good visual prognosis, but there may be permanent visual impairment due to ocular structural complications in some. Community-based integrated mosquito management programs and personal protection measures against mosquito bites are the best ways to prevent human infection and disease. Conclusion: Emerging arboviral diseases should be considered in the differential diagnosis of ocular inflammatory conditions in patients living in or returning from endemic regions. Early clinical consideration followed by confirmatory testing can limit or prevent unnecessary treatments for non-arboviral causes of ocular inflammation. Prevention of these infections is crucial. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus, a pathogen to ruminants, camelids, and humans, is an emerging mosquito-borne bunyavirus currently endemic to Africa and the Arabian Peninsula. Although animals are primarily infected via mosquito bites, humans mainly become infected following contact with infected tissues or fluids of infected animals. There is an urgent need for adequate countermeasures, especially for humans, because effective therapeutics or vaccines are not yet available. Here we assessed the safety, tolerability, and immunogenicity of a next-generation, four-segmented, live-attenuated vaccine candidate, referred to as hRVFV-4s, in humans. A first-in-human, single-centre, randomised, double-blind, placebo-controlled trial was done in Belgium in which a single dose of hRVFV-4s was administered to healthy volunteers aged 18–45 years. Participants were randomly assigned using an interactive web response system. The study population encompassed 75 participants naive to Rift Valley fever virus infection, divided over three dosage groups (cohorts) of 25 participants each. All participants were followed up until 6 months. Using a staggered dose escalating approach, 20 individuals of each cohort were injected in the deltoid muscle of the non-dominant arm with either 104 (low dose), 105 (medium dose), or 106 (high dose) of 50% tissue culture infectious dose of hRVFV-4s as based on animal data, and five individuals per cohort received formulation buffer as a placebo. Primary outcome measures in the intention-to-treat population were adverse events and tolerability. Secondary outcome measures were vaccine-induced viraemia, vaccine virus shedding, Rift Valley fever virus nucleocapsid antibody responses (with ELISA), and neutralising antibody titres. Furthermore, exploratory objectives included the assessment of cellular immune responses by ELISpot. The trial was registered with the EU Clinical Trials Register, 2022-501460-17-00. Between August and December, 2022, all 75 participants were vaccinated. No serious adverse events or vaccine-related severe adverse events were reported. Pain at the injection site (51 [85%] of 60 participants) was most frequently reported as solicited local adverse event, and headache (28 [47%] of 60) and fatigue (28 [47%] of 60) as solicited systemic adverse events in the active group. No vaccine virus RNA was detected in any of the blood, saliva, urine, or semen samples. Rift Valley fever virus nucleocapsid antibody responses were detected in most participants who were vaccinated with hRVFV-4s (43 [72%] of 60 on day 14) irrespective of the administered dose. In contrast, a clear dose–response relationship was observed for neutralising antibodies on day 28 with four (20%) of 20 participants responding in the low-dose group, 13 (65%) of 20 responding in the medium-dose group, and all participants (20 [100%] of 20) responding in the high-dose group. Consistent with the antibody responses, cellular immune responses against the nucleocapsid protein were detected in all dose groups, whereas a more dose-dependent response was observed for the Gn and Gc surface glycoproteins. Neutralising antibody titres declined over time, whereas nucleocapsid antibody responses remained relatively stable for at least 6 months. The hRVFV-4s vaccine showed a high safety profile and excellent tolerability across all tested dose regimens, eliciting robust immune responses, particularly with the high-dose administration. The findings strongly support further clinical development of this candidate vaccine for human use. The Coalition for Epidemic Preparedness Innovations with support from the EU Horizon 2020 programme. [ABSTRACT FROM AUTHOR]

Q fever (QF) and Rift Valley fever (RVF) are endemic zoonotic diseases in African countries, causing significant health and economic burdens. Accurate prevalence estimates, crucial for disease control, rely on robust diagnostic tests. While enzyme-linked immunosorbent assays (ELISA) are not the gold standard, they offer rapid, cost-effective, and practical alternatives. However, varying results from different tests and laboratories can complicate comparing epidemiological studies. This study aimed to assess the agreement of test results for QF and RVF in humans and livestock across different laboratory conditions and, for humans, different types of diagnostic tests. We measured inter-laboratory agreement using concordance, Cohen's kappa, and prevalence and bias-adjusted kappa (PABAK) on 91 human and 102 livestock samples collected from rural regions in Chad. The serum aliquots were tested using ELISA in Chad, and indirect immunofluorescence assay (IFA) (for human QF and RVF) and ELISA (for livestock QF and RVF) in Switzerland and Germany. Additionally, we examined demographic factors influencing test agreement, including district, setting (village vs. camp), sex, age, and livestock species of the sampled individuals. The inter-laboratory agreement ranged from fair to moderate. For humans, QF concordance was 62.5%, Cohen's kappa was 0.31, RVF concordance was 81.1%, and Cohen's kappa was 0.52. For livestock, QF concordance was 92.3%, Cohen's kappa was 0.59, RVF concordance was 94.0%, and Cohen's kappa was 0.59. Multivariable analysis revealed that QF test agreement is significantly higher in younger humans and people living in villages compared to camps and tends to be higher in livestock from Danamadji compared to Yao, and in small ruminants compared to cattle. Additionally, RVF agreement was found to be higher in younger humans. Our findings emphasize the need to consider sample conditions, test performance, and influencing factors when conducting and interpreting epidemiological seroprevalence studies. Author summary: Q fever (QF) and Rift Valley fever (RVF) are zoonotic diseases that can be transmitted from animals to humans, causing health problems and economic losses in African countries. While various diagnostic tests for these diseases are available, they can be impractical, especially in resource-limited settings. For this study, human and livestock samples from Chad were first tested in a local laboratory using a routine test (enzyme-linked immunosorbent assay). Serum aliquots were then sent to laboratories in Germany or Switzerland for retesting, using the same test type for livestock and a different test type for human samples. We analysed the agreement between the test results and investigated the influence of the demographic characteristics of the sampled individual on this agreement. Our findings are crucial as they reveal discrepancies in test results, even though the samples originated from the same individuals. Additionally, we found that factors such as the age of the sampled individual influenced test agreement. This study underscores the importance of considering sample conditions, test performance, and influencing factors when conducting and interpreting disease prevalence studies. Enhancing diagnostic procedures will aid in more effective disease control management, benefiting local communities and global health efforts. [ABSTRACT FROM AUTHOR]

In this research, we describe the first aptasensor for the detection of the Rift Valley Fever virus (RVFV). The process involved the selection of aptamers through the systematic evolution of ligands by the exponential enrichment (SELEX) technique. After 12 rounds of selection, 6 aptamers were selected and the corresponding binding affinities were assessed using fluorescence binding assays, revealing dissociation constants ranging from 15.45 to 40.98 nM. Notably, among the aptamers, RV2 and RV3 exhibited the highest binding affinities toward RVFV, with dissociation constants of 15.45 and 18.62 nM, respectively. Thiol-modified aptamers were subsequently immobilized onto screen-printed gold electrodes, facilitating the label-free detection of RVFV through square wave voltammetry. The voltammetric aptasensor demonstrated an excellent sensitivity, with a detection limit of 0.015 ng/mL. In addition, cross-reactivity assessments were conducted, where negligible response was obtained when the aptasensor was exposed to non-specific proteins. [ABSTRACT FROM AUTHOR]

The article explores the use of the rabies virus as a tool for developing vaccines. It discusses the different types of rabies virus-vectored vaccines and their strengths and weaknesses. Live-attenuated vaccines offer long-lasting protection but carry a risk of reversion to virulence, while inactivated vaccines have a good safety profile but may require booster injections. Further research is needed to fully understand and utilize the potential of these vaccines. The document also compiles various scientific studies that demonstrate the efficacy and safety of rabies virus-based vaccines for diseases such as HIV-1, Lassa fever, and SARS-CoV-2. The research suggests that rabies virus vectors have the potential to be effective vaccines for a wide range of infectious diseases. [Extracted from the article]

Rift Valley fever (RVF) is a zoonotic arboviral disease that causes recurrent epidemics in Africa that may trigger fatal neurological disorders. However, the mechanisms of neuroinvasion by which the RVF virus (RVFV) reaches the human central nervous system (CNS) remain poorly characterized. In particular, it is not clear how RVFV is able to cross the human blood-brain barrier (hBBB), which is a neurovascular endothelium that protects the brain by regulating brain and blood exchanges. To explore these mechanisms, we used an in vitro hBBB model to mimic in vivo hBBB selectiveness and apicobasal polarity. Our results highlight the ability of RVFV to cross the hBBB by direct infection in a non-structural protein S (NSs)-independent but strain-dependent manner, leading to astrocyte and pericyte infections. Interestingly, RVFV infection did not induce hBBB disruption and was associated with progressive elimination of infected cells with no impairment of the tight junction protein scaffold and barrier function. Our work also shows that NSs, a well described RVFV virulence factor, limited the establishment of the hBBB-induced innate immune response and subsequent lymphocyte recruitment. These results provide in vitro confirmation of the ability of RVFV to reach human CNS by direct infection of the hBBB without altering its barrier function, and provide new directions to explore human RVFV neurovirulence and neuroinvasion mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Crimean‐Congo haemorrhagic fever (CCHF) is a severe zoonotic arboviral disease that occurs widely in Eastern and Western Europe, Asia and Africa. The disease is becoming of growing public health importance in Senegal. However, analysis of tick infestation, CCHF virus (CCHFV) circulation extent and risk factors during ongoing outbreak are scarce. A thorough outbreak investigation was carried out during a CCHF outbreak in Podor (Northern Senegal) in August 2022. Methods: Ticks and blood samples were collected from animals (cattle, goats and sheep) randomly selected from confirmed CCHF human cases houses, neighbourhoods and surrounding villages. Blood samples were tested for CCHFV antibodies using a commercial enzyme‐linked immunosorbent assay (ELISA) test. Tick samples were screened for CCHFV RNA by RT‐PCR. Results: Overall, tick infestation rate (TIR) and CCHFV seroprevalence of livestock were 52.12% (95% confidence interval (CI): 45.54%–58.64%) and 43.28% (95% CI: 36.33%–50.44%), respectively. The TIRs were 87.7% in cattle, 57.6% in sheep and 20.0% in goats. These rates were significantly associated with location, host species and tick control (p < 0.001) but not with animal age and sex (p > 0.7). CCHFV seroprevalence was 80.4% (95% CI: 67.57%–89.77%) in cattle, 35.4% (95% CI: 25.00%–47.01%) in sheep and 21.2% (95% CI: 12.11%–33.02%) in goats. Age, sex, location, animal host and presence of ticks were significantly associated to the presence of antibodies. The 950 ticks collected included among other species, Hyalomma impeltatum (48.84%) and H. rufipes (10.21%). Five pools of Hyalomma ssp. were found CCHFV RT‐PCR positive. These infected ticks included 0.86% (4/464) of H. impeltatum collected on cattle and sheep and 1.03% (1/97) of H. rufipes collected on a sheep. Conclusions: To our knowledge, this is the first report on the extend of tick infestation and CCHFV infection in livestock during an outbreak in Senegal. The results highlight the risk of human infections and the importance of strengthening vector, animal and human surveillance as well as tick control measures in this area to prevent CCHF infections in humans. [ABSTRACT FROM AUTHOR]

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical and epidemiological characteristics of the first epidemic of Rift Valley Fever retinitis in Rwanda and to report novel imaging findings and a possible role for corticosteroids. Methods: Retrospective analysis of all patients who presented with presumed Rift Valley Fever retinitis at the Rwanda Charity Eye Hospital over a period of 4 months in 2022. Multimodal images are reviewed including optical coherence tomography, fluorescein angiography, color, infrared, red-free, and autofluorescence photography. Results: The newly identified arciform hyporeflective pattern on infrared imaging was present in 100% of patients. Out of 9 patients treated with oral corticosteroids, 7 (78%) experienced a visual acuity increase of at least 0.2 during follow-up, in comparison to only 4 (28%) out of 14 of untreated patients. Out of four patients treated with a subtenon corticosteroid injection, only one (25%) reached this threshold. Post-hoc pairwise comparison with Bonferroni correction revealed a significant difference in average visual acuity improvement (p = 0.034) between patients receiving oral corticosteroids (0.35 ± 0.07) versus no treatment (0.11 ± 0.04). Conclusion: The identified arciform hyporeflective pattern on infrared imaging appears to be characteristic of Rift Valley Fever retinitis and should be known to clinicians working in endemic regions. Compared to a historical cohort and to untreated patients in this non-randomized study, there appears to be a benefit of treatment with oral corticosteroids. ARTICLE SUMMARY STATEMENT: This is the first reported outbreak of Rift Valley Fever retinitis in Rwanda, demonstrating a characteristic arciform peri-macular pattern on infrared imaging not previously published and a possible treatment effect of oral corticosteroids. [ABSTRACT FROM AUTHOR]

A group of self-limiting and frequently neglected diseases exist in the literature like Rickettsial disease, Malaria, Dengue fever, Chikungunya, West Nile virus infection, Rift Valley fever, Bartonellosis, or Lyme disease which are poorly understood due to lack of proper diagnostic testing. Currently, multimodal imaging has become a critical modality in the diagnosis and management of ocular diseases. Optical coherence tomography (OCT) is one such remarkable imaging modality in the field of ophthalmology providing high-resolution, cross-sectional images of the retina and choroid with the recent advances such as enhanced depth imaging and swept source OCT. Additionally, OCT angiography (OCTA) has further revolutionised dynamic imaging of retinal and choroidal vasculature non-invasively. This review article highlights the OCT and OCTA biomarkers in the diagnosis and prognosis of the aforementioned neglected diseases. [ABSTRACT FROM AUTHOR]

This article provides an overview of the 2024 outbreaks of Oropouche virus disease, an emerging and re-emerging neurotropic arboviral disease. The Oropouche virus belongs to the Simbu serogroup and is transmitted to humans through bites from midges or mosquitoes. The disease has been endemic to the Amazon basin and has spread to Central and South American countries, as well as the Caribbean. Symptoms of Oropouche virus disease include fever, headache, rash, and neurological complications. There is currently no specific treatment or vaccine for the disease, so prevention strategies focused on vector control and personal protection are important. The article emphasizes the need for further research on diagnostic assays and the development of therapies and vaccines. [Extracted from the article]

A Rift Valley fever epizootic affected livestock in Rwanda during March–October 2022. We confirmed 3,112 infections with the virus, including 1,342 cases, 1,254 abortions, and 516 deaths among cattle, goats, and sheep. We recommend a One Health strategy for investigations and response to protect animal and human health.

Infection of Rift Valley fever virus (RVFV), a highly pathogenic mosquito-borne zoonotic virus, triggers severe inflammatory pathogenesis but the underlying mechanism of inflammation activation is currently unclear. Here, we report that the non-structural protein NSs of RVFV triggers mitochondrial damage to activate the NLRP3 inflammasome leading to viral pathogenesis in vivo. It is found that the host transcription inhibition effect of NSs causes rapid down-regulation of myeloid cell leukemia-1(MCL-1), a pro-survival member of the Bcl-2 (B-cell lymphoma protein 2) protein family. MCL-1 down-regulation led to BAK activation in the mitochondria, which triggered mtROS production and release of oxidized mitochondrial DNA (ox-mtDNA) into the cytosol. Cytosolic ox-mtDNA binds and activates the NLRP3 inflammasome triggering NLRP3-GSDMD pyroptosis in RVFV infected cells. A NSs mutant virus (RVFV-NSsRM) that is compromised in inducing transcription inhibition did not trigger MCL-1 down-regulation nor NLRP3-GSDMD pyroptosis. RVFV infection of the Nlrp3-/- mouse model demonstrated that the RVFV-triggered NLRP3 pyroptosis contributed to RVFV inflammatory pathogenesis and fatal infection in vivo. Infection with the RVFV-NSsRM mutant virus similarly showed alleviated inflammatory pathogenesis and reduced fatality rate. Taken together, these results revealed a mechanism by which a virulence factor activates the mitochondrial MCL-1-BAK axis through inducing host transcription inhibition to trigger NLRP3-dependent inflammatory pathogenesis. Author summary: RVFV is a highly pathogenic mosquito-borne zoonotic virus that infects both ruminants and humans. Humans infected by RVFV can develop acute hepatitis, encephalitis and hemorrhagic fever, which can result in fatal infection in severe cases. RVFV-triggered inflammation is an important driver for severe disease development but the underlying activation mechanism is currently unknown. Here, we found that the major virulence protein NSs of RVFV induces mitochondria damage in infected cells. This is achieved through the transcription inhibition effect of NSs which triggered transcriptional down-regulation of MCL-1 leading to mitochondrial BAK activation. Activated BAK then led to mitochondrial permeabilization and release of ox-mtDNA into the cytosol. The cytoplasmic ox-mtDNA binds and activates NLRP3 inflammasome leading to inflammatory pyroptosis. Using a RVFV infected mouse model and a mutant virus that did not trigger transcription inhibition, we showed that RVFV-triggered NLRP3 activation contributed to viral pathogenesis and fatal infection in vivo. In summary, we showed an important mechanism of RVFV triggered pathogenic inflammation, which may be employed by other viruses that induce transcription inhibition during infection. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a neglected vector-borne disease which is endemic in many countries across Africa and has seen recent geographical expansions into the Arabian Peninsula. RVF can cause severe infections in both animals and humans. RVF infections in livestock can lead to mass fatalities. In humans, the symptoms are nonspecific and can often lead to misdiagnosis. However, a small proportion progresses to haemorrhagic infection with a significantly higher mortality rate. The culmination of this can cause severe socioeconomic impacts. This review aims to identify the main socioeconomic impacts caused by RVF outbreaks as well as existing knowledge gaps. Ninety-three academic and grey papers were selected, covering 19 countries and 10 methodological approaches. A variety of socioeconomic impacts were found across all levels of society: Livestock trade disruptions consequently impacted local food security, local and national economies. Most livestock farmers in endemic countries are subsistence farmers and so rely on their livestock for sustenance and income. RVF outbreaks resulted in a variety of socioeconomic impacts, e.g., the inability to pay for school fees. Main barriers to vaccine uptake in communities were lack of access, funds, interest along with other social aspects. The occupational risks for women (and pregnant women) are largely unknown. To our knowledge, this is the first review on RVF to highlight the clear knowledge gap surrounding the potential gender differences on risks of RVF exposure, as well as differences on occupational health risk in pastoral communities. Further work is required to fill the gaps identified in this review and inform control policies. Author summary: Rift Valley fever (RVF) outbreaks have affected many regions globally with varying severity. The number of reported cases in animals and humans is patchy at best, with some countries not recording animal events. This review focuses on 3 main themes: Health Burden; Economic Impacts; and Prevention and Surveillance. The review explores socioeconomic impacts across local, regional, and national levels. We found women have varying degrees of risk to exposure of RVF; however, more research is required to better understand gender differences. RVF outbreaks tend to begin in livestock and spillover into humans. The complex disease dynamics are poorly understood because of the interactions between animals, humans, and the environment. This cross-boundary dynamics fall outside of the public health remit and into veterinary health. This allows for outbreaks to spread uncontrollably for some time. More research using a One Health Lens is required which explores these complex dynamics with the combination of different social aspects. This review highlights the wider impacts experienced at different levels of society and where there are major gaps in our knowledge. Further analysis into these gaps is required to and will aid policy makers in developing new control measures around RVF. [ABSTRACT FROM AUTHOR]

The distribution, epidemiology, and socioeconomic impact of Rift Valley fever (RVF) and West Nile (WN) viruses are poorly known in areas of sub‐Saharan countries like Ethiopian pastoral region. The human and livestock density in the area has increased greatly in recent years, but little work has been done on arboviral diseases and their potential impact on human and livestock health. The aim of this study was to detect the circulation of zoonotic arboviruses such as Rift Valley fever virus and West Nile viruses in the livestock population and to estimate seroprevalence in Afar pastoral area northeast Ethiopia. Cross‐sectional serological survey was carried out in 736 serum samples from which cattle (224), camel (155), goats (121), sheep (144), and donkeys (92) were tested for the presence of anti‐RVFV and anti‐WNV IgG using a competitive enzyme‐linked immunosorbent assay (c‐ELISA) in two purposively selected districts of the Afar region. The present study revealed a 9.1% (95% CI = 8.86–9.29) seroprevalence of co‐circulation of RVF and WNV. High 32/155 (20.7%) seroprevalence of co‐circulation was seen in camels, followed by goat 14/121 (11.6%), cattle 16/224 (7.14%), and sheep 5/144 (3.5%), respectively, and higher 41/421 (9.7%) seroprevalence of co‐circulation was observed in Amibara district than Haruka district. Camels were seven times (OR: 7.016, 95% CI = 2.639–18.653) more likely to be seropositive for the co‐circulation than sheep (p ≤ 0.001). Livestock herds found in Amibara district were 1.2 times (OR: 1.165, 95% CI = 0.680–1.996) more likely to be seropositive for RVFV infection than those in Haruka areas. Given the co‐occurrence of RVFV and WNV circulations, along with often suboptimal human and animal health surveillance in many similar areas' attention should be given. Investigation of the potential socioeconomic and health impacts of zoonotic arbovirus infections in such areas is crucial. Since both RVFV and WNFV are transmitted through a mosquito vector, avoiding mosquito bites is the primary method of prevention. [ABSTRACT FROM AUTHOR]

Background: Coxiella burnetii, the causative agent of Q fever, and Rift Valley fever virus are two under-researched zoonotic pathogens in Ethiopia. Potential outbreaks of these diseases, in light of the high dependency of nomadic pastoralists on their livestock, poses a risk to both human and animal health in addition to risking the pastoralists livelihoods. Our study aimed to determine the seroprevalence and associated risk factors for Q fever and Rift Valley fever in pastoral communities in the Afar region of north-eastern Ethiopia. Methodology/Principal findings: This cross-sectional study screened pastoralists (n = 323) and their livestock (n = 1377) for IgG antibodies to Coxiella burnetii and Rift Valley fever virus. A seroprevalence for Q fever of 25.0% (95%CI 18.6–32.6) was found in pastoralists and 34.3% (95%CI 27.9–41.3) in livestock overall; with 51.9% in goats (95%CI 44.9–58.8), 39.9% in sheep (95%CI 24.6–51.2), 16.3% in camels (95%CI 10.4–24.6) and 8.8% in cattle (95%CI 5.0–15.0). For Rift Valley fever the seroprevalence in pastoralists was 6.1% (95%CI 3.3–11.0) and 3.9% (95%CI 2.6–5.7) in livestock overall; cattle had the highest seroprevalence (8.3%, 95%CI 3.3–19.2), followed by goats (2.7%; 95%CI 1.4–5.1), sheep (2.5%; 95%CI 1.0–5.9) and camels (1.8%; 95%CI 0.4–6.9). Human Q fever seropositivity was found to be associated with goat abortions (OR = 2.11, 95%CI 1.18–3.78, p = 0.011), while Rift Valley fever seropositivity in livestock was found to be associated with cattle abortions (OR = 2.52, 95%CI 1.05–6.08, p = 0.039). Conclusions/Significance: This study provides evidence for a notable exposure to both Q fever and Rift Valley fever in pastoralists and livestock in Afar. The outbreak potential of these pathogens warrants ongoing integrated human and animal surveillance requiring close collaboration of the human and animal health sectors with community representatives following a One Health approach. Author summary: Q fever and Rift Valley fever are two diseases that can affect both humans and animals, causing illness and death. These two diseases can cause large-scale outbreaks, not only affecting the health of individuals and communities but also resulting in a substantial economic loss at the individual, community, regional and national levels through losses in livestock products. We conducted a sero-epidemiological study in the Afar region of north-eastern Ethiopia to determine the presence of these two diseases in nomadic pastoralists and their livestock. Our results indicate that 25.0% of the pastoralists and 34.3% of their animals have had previous exposure to Q fever and 6.1% of the pastoralists and 3.9% of their animals have been exposed to Rift Valley fever. Goats appear to be the most common livestock species associated with Q fever in this region, while cattle are the most common species associated with Rift Valley fever. Our findings highlight the importance of continuous surveillance; additionally, we would recommend the development of rapid response plans for potential outbreaks that integrate the human and animal health sectors. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus of the Phlebovirus genus in the phenuviridae family. Its genome is trisegmented with small (S), medium (M) and large (L) fragments. In nature, the virus exists as a single serotype that is responsible for outbreaks of Rift Valley fever (RVF), a zoonotic disease that often occurs in Africa and the Middle East. RVFV genomes are thought to undergo both recombination and reassortment and investigations of these events is important for monitoring the emergence of virulent strains and understanding the evolutionary characteristics of this virus. The aim of this study was to characterize the genomes of RVFV isolates from cattle, sheep, and goats collected during an interepidemic period in Kenya between June 2016 and November 2021. A total of 691 serum samples from cattle (n = 144), goats (n = 185) and sheep (n = 362) were analysed at the Central Veterinary Laboratories. The competitive IgM-capture ELISA, was used to screen the samples; 205 samples (29.67%) tested positive for RVFV. Of the 205 positive samples, 42 (20.5%) were from cattle, 57 (27.8%) from goats, and 106 (51.7%) from sheep. All the IgM-positive samples were further analyzed by qPCR, and 24 (11.71%) tested positive with Ct values ranging from 14.788 to 38.286. Two samples, 201808HABDVS from sheep and 201810CML3DVS from cattle, had Ct values of less than 20.0 and yielded whole genome sequences with 96.8 and 96.4 coverage, respectively. There was no statistically significant evidence of recombination in any of the three segments and also phylogenetic analysis showed no evidence of reassortment in the two isolated RVFV segments when compared with other isolates of different lineages from previous outbreaks whose genomes are deposited in the GenBank. No evidence of reassortment leaves room for other factors to be the most probable contributors of change in virulence, pathogenicity and emergence of highly virulent strains of the RVFV. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that could help to prevent the disease is vaccination of flocks in areas at risk of RVF. Available live attenuated vaccines are an effective means of controlling the disease, but their use is often questioned due to residual virulence, particularly in susceptible hosts such as pregnant sheep. On the other hand, no vaccine is currently licensed for use in humans. The development of safe and effective vaccines is therefore a major area of research. In previous studies, we selected under selective mutagenic pressure a highly attenuated RVFV 56/74 virus variant called 40Fp8. This virus showed an extremely attenuated phenotype in both wild-type and immunodeficient A129 (IFNARKO) mice, yet was still able to induce protective immunity after a single inoculation, thus supporting its use as a safe, live attenuated vaccine. To further investigate its safety, in this work we have analysed the attenuation level of 40Fp8 in immunosuppressed mice (A129) when administered by the intranasal route, and compared it with other attenuated RVF viruses that are the basis of vaccines in use or in development. Our results show that 40Fp8 has a much higher attenuated level than these other viruses and confirm its potential as a candidate for safe RVF vaccine development. Author summary: Vaccines that use attenuated viruses are highly effective in terms of providing protection, duration, breadth, and quality of the immune response. However, they may pose a risk to immunosuppressed individuals or in certain situations, such as during pregnancy. It is therefore important to analyze the residual virulence of attenuated vaccines to ensure their safety. In this work, we analysed the safety of the RVF virus vaccine variant 40Fp8 developed in our laboratory. We studied its effect on immunodeficient mice and used a more aggressive route of administration such as the intranasal delivery route. To assess the degree of attenuation of 40Fp8, we compared it with other attenuated prototype RVF vaccines. The results clearly demonstrate that 40Fp8 is highly attenuated, and its residual virulence level is extremely low compared to other vaccine viruses tested. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus with serious implications for livestock health, human health, and the economy in Africa, and is suspected to be endemic in north-eastern KwaZulu-Natal (KZN), South Africa. The vectors of RVFV in this area are poorly known, although several species, such as Aedes (Neomelaniconion) mcintoshi, Aedes (Neomelaniconion) circumluteolus, Aedes (Aedimorphus) durbanensis, and Culex (Lasioconops) poicilipes may be involved. The aim of the study was to determine the vertebrate blood meal sources of potential RVFV mosquito vectors in north-eastern KZN and to characterize the host-biting network. Methods: Blood-fed mosquitoes were collected monthly from November 2019 to February 2023 using a backpack aspirator, CO2-baited Centers for Disease Control and Prevention (CDC) miniature light traps and tent traps, in the vicinity of water bodies and livestock farming households. The mosquitoes were morphologically identified. DNA was extracted from individual mosquitoes and used as templates to amplify the vertebrate cytochrome c oxidase I (COI) and cytochrome b (cytb) genes using conventional polymerase chain reaction (PCR). Amplicons were sequenced and queried in GenBank and the Barcode of Life Data systems to identify the vertebrate blood meal sources and confirm mosquito identifications. All mosquitoes were screened for RVFV using real time reverse transcription (RT)-PCR. Results: We identified the mammalian (88.8%) and avian (11.3%) blood meal sources from 409 blood-fed mosquitoes. Aedes circumluteolus (n = 128) made up the largest proportion of collected mosquitoes. Cattle (n = 195) and nyala (n = 61) were the most frequent domestic and wild hosts, respectively. Bipartite network analysis showed that the rural network consisted of more host-biting interactions than the reserve network. All mosquitoes tested negative for RVFV. Conclusions: Several mosquito species, including Ae. circumluteolus, and vertebrate host species, including cattle and nyala, could play a central role in RVFV transmission. Future research in this region should focus on these species to better understand RVFV amplification. [ABSTRACT FROM AUTHOR]

The article discusses the health implications of mass gatherings, specifically focusing on the Kumbh Mela in India. The Kumbh Mela is a significant religious event that attracts millions of pilgrims from around the world. The article highlights the potential for the spread of infectious diseases during the event due to factors such as crowded living conditions and waste production. It emphasizes the need for vigilant planning, coordination, and preventive measures to ensure public health and safety during large gatherings. The article also presents a case study of the impact of the COVID-19 pandemic on the Kumbh Mela in 2021, which resulted in a significant increase in cases. It concludes by discussing the complex nature of prevention efforts and the importance of comprehensive disease surveillance systems, infrastructure improvements, and the use of technology to manage and mitigate risks during mass gatherings. [Extracted from the article]

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal–fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal–fetal interface. IMPORTANCE A direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) causes disease outbreaks in livestock and humans; however, its inter-epidemic circulation is poorly understood, similar to other arboviruses affecting cattle such as bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Serum samples were collected in Baringo County, Kenya from 400 cattle, accompanied by a risk factor questionnaire. Serological tests were then conducted to determine the exposure of cattle to RVFV, BTV, and EHDV. RVFV, BTV, and EHDV IgG seroprevalence rates were 15.5%, 91.5%, and 91%, respectively. Seropositivity for RVFV, BTV, and EHDV was significantly higher in adult cattle, as well as in females for RVFV. Cattle with herd owners aged between 30–39 years were less likely to be seropositive for RVFV compared to those with owners over the age of 60 years. High seroprevalence of BTV and EHDV in cattle indicates significant exposure and the subclinical circulation of these viruses, presenting a risk of outbreaks to sheep and naïve cattle. Moreover, the detection of RVFV-seropositive young cattle born after the last reported outbreak suggests inter-epidemic circulation of the virus. Overall, monitoring these arboviruses in cattle is crucial in understanding their distribution and seroprevalence during inter-epidemic periods. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Rift Valley fever virus (RVFV) belonging to the Phenuiviridae family is responsible for a zoonotic disease called Rift Valley fever (RVF). Currently, RVFV has spread from Africa to Asia, and due to its ability to cause high mortality rates, it has significantly impacted human health and economic development in many societies. Highly specific and sensitive systems for sero-diagnosis of RVFV infection are needed for clinical use. Method: BALB/c mice were immunized with recombinant RVFV nucleocapsid (rRVFV-N) protein and the spleen cells fused with SP2/0 myeloma cells to create hybridoma cell lines. The secreted monoclonal antibodies (MAbs) were purified and characterized. Enzyme-linked immunosorbent assay (ELISA) systems for the detection of IgG and IgM using the new MAbs were established and evaluated. Serum samples from 96 volunteers and 93 patients of suspected RVF from Kenya were tested compared with the ELISA systems based on inactivated viruses and the rabbit polyclonal antibody. Result: Three monoclonal antibodies against rRVFV-N protein were established. The performance of the MAb-based sandwich IgG ELISA and the IgM capture ELISA perfectly matched the ELISA systems using the inactivated virus or the polyclonal antibody. Conclusions: Recombinant RVFV-N protein-specific MAbs were developed and they offer useful tools for RVFV studies. The MAb-based ELISA systems for detecting IgG and IgM offer safe and useful options for diagnosing RVFV infections in humans. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is an encephalitic bunyavirus that can infect neurons in the brain. There are no approved therapeutics that can protect from RVFV encephalitis. Innate immunity, the first line of defense against infection, canonically antagonizes viruses through interferon signaling. We found that interferons did not efficiently protect primary cortical neurons from RVFV, unlike other cell types. To identify alternative neuronal antiviral pathways, we screened innate immune ligands and discovered that the TLR2 ligand Pam3CSK4 inhibited RVFV infection, and other bunyaviruses. Mechanistically, we found that Pam3CSK4 blocks viral fusion, independent of TLR2. In a mouse model of RVFV encephalitis, Pam3CSK4 treatment protected animals from infection and mortality. Overall, Pam3CSK4 is a bunyavirus fusion inhibitor active in primary neurons and the brain, representing a new approach toward the development of treatments for encephalitic bunyavirus infections. Author summary: Rift Valley fever virus (RVFV) is an emerging mosquito-borne pathogen, which has shown the potential to spread geographically, and which can cause severe disease in humans. One of the most serious complications of RVFV infection is invasion into the brain. There are no approved treatments for RVFV infection, or any other bunyavirus that infects the brain. We found that the classically antiviral interferon pathway was not protective in neurons. This led us to screen for new antivirals, and we identified Pam3CSK4, which inhibited RVFV and related bunyaviruses, but not vesicular stomatitis virus. We found that the antiviral activity of Pam3CSK4 was separate from its previously characterized activity as a TLR2 agonist. Instead, Pam3CSK4 blocked RVFV entry at the step of viral membrane fusion. Importantly, we found that Pam3CSK4 prevented RVFV infection in the mouse brain. This work reveals that Pam3CSK4 prevents encephalitic bunyavirus infection in neurons, a vulnerable cell type, and future research should evaluate the therapeutic potential of Pam3CSK4. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) in ungulates and humans is caused by a mosquito-borne RVF phlebovirus (RVFV). Live attenuated vaccines are used in livestock (sheep and cattle) to control RVF in endemic regions during outbreaks. The ability of two or more different RVFV strains to reassort when co-infecting a host cell is a significant veterinary and public health concern due to the potential emergence of newly reassorted viruses, since reassortment of RVFVs has been documented in nature and in experimental infection studies. Due to the very limited information regarding the frequency and dynamics of RVFV reassortment, we evaluated the efficiency of RVFV reassortment in sheep, a natural host for this zoonotic pathogen. Co-infection experiments were performed, first in vitro in sheep-derived cells, and subsequently in vivo in sheep. Two RVFV co-infection groups were evaluated: group I consisted of co-infection with two wild-type (WT) RVFV strains, Kenya 128B-15 (Ken06) and Saudi Arabia SA01-1322 (SA01), while group II consisted of co-infection with the live attenuated virus (LAV) vaccine strain MP-12 and a WT strain, Ken06. In the in vitro experiments, the virus supernatants were collected 24 h post-infection. In the in vivo experiments, clinical signs were monitored, and blood and tissues were collected at various time points up to nine days post-challenge for analyses. Cell culture supernatants and samples from sheep were processed, and plaque-isolated viruses were genotyped to determine reassortment frequency. Our results show that RVFV reassortment is more efficient in co-infected sheep-derived cells compared to co-infected sheep. In vitro, the reassortment frequencies reached 37.9% for the group I co-infected cells and 25.4% for the group II co-infected cells. In contrast, we detected just 1.7% reassortant viruses from group I sheep co-infected with the two WT strains, while no reassortants were detected from group II sheep co-infected with the WT and LAV strains. The results indicate that RVFV reassortment occurs at a lower frequency in vivo in sheep when compared to in vitro conditions in sheep-derived cells. Further studies are needed to better understand the implications of RVFV reassortment in relation to virulence and transmission dynamics in the host and the vector. The knowledge learned from these studies on reassortment is important for understanding the dynamics of RVFV evolution. [ABSTRACT FROM AUTHOR]

Background: Heterophilic antibodies (HA) are one of the main substances that interfere with immunology, especially chemiluminescence immunoassay. Non-specific binding, labeling antibodies, bridging to capture antibodies, or labeling antigens can interfere with the detection process, leading to serious discrepancies between the measured results and clinical manifestations, and even delaying clinical diagnosis and treatment. Methods: This paper is a case of epidemic hemorrhagic fever causing pseudo CEA elevation caused by heterophagy induced antibodies in the body. Results: The patient's CEA detected on the ABBOTT detection platform was 51.1 ng/mL, and on the ROCHE detection platforms it was 4.66 ng/mL, and treated by PEG precipitation it was 45.2 ng/mL, after diluting the sample the CEA was 50.2 ng/mL, meanwhile the patient's platelets were 96 x 109/L and serum creatinine was 188.4 µmol/L, epidemic hemorrhagic fever IgM antibody was positive. Conclusions: When the test results do not match clinical symptoms, further confirmation is required through additional testing. Patients who use mouse monoclonal antibody preparations for diagnosis or treatment may have human anti-mouse antibodies in their serum, and the test results may falsely increase or decrease. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is an adaptable arbovirus that can be transmitted by a wide variety of arthropods. Widespread urban transmission of RVFV has not yet occurred, but peri-urban outbreaks of RVFV have recently been documented in East Africa. We previously reported low-level exposure in urban communities and highlighted the risk of introduction via live animal influx. We deployed a slaughtered animal testing framework in response to an early warning system at two urban slaughterhouses and tested animals entering the meat value chain for anti-RVFV IgG and IgM antibodies. We simultaneously trapped mosquitoes for RVFV and bloodmeal testing. Out of 923 animals tested, an 8.5% IgG seroprevalence was identified but no evidence of recent livestock exposure was detected. Mosquito species abundance varied greatly by slaughterhouse site, which explained 52% of the variance in blood meals. We captured many Culex spp., a known RVFV amplifying vector, at one of the sites (p < 0.001), and this species had the most diverse blood meals. No mosquito pools tested positive for RVFV antigen using a rapid VecTOR test. These results expand understanding of potential RVF urban disease ecology, and highlight that slaughterhouses are key locations for future surveillance, modelling, and monitoring efforts. [ABSTRACT FROM AUTHOR]

A Rift Valley fever epizootic affected livestock in Rwanda during March–October 2022. We confirmed 3,112 infections with the virus, including 1,342 cases, 1,254 abortions, and 516 deaths among cattle, goats, and sheep. We recommend a One Health strategy for investigations and response to protect animal and human health. [ABSTRACT FROM AUTHOR]

The infection caused by Rift Valley fever (RVF) virus is a dangerous vector-borne disease found in humans, domestic, and wild animals. It is transferred through insect vectors to ruminant host and then spread through direct contact of infected animals with their body fluid or organs. In this paper, a fractal-fractional model for the transmission of RVF in the Caputo's sense was presented. We analyzed the model and determined the basic reproduction number through the next-generation matrix technique, indicated by $ \mathcal{R}_0 $. The global sensitivity technique is used for the sensitivity test of $ \mathcal{R}_0 $ to find out the most sensitive input-factors to the reproduction parameter $ \mathcal{R}_0 $. The existence and uniqueness results of the proposed fractal-fractional model were established. Then, we presented the fractal-fractional dynamics of the proposed RVF model through a novel numerical scheme under the fractal-fractional Caputo operator. In the end, the recommended model of RVF was highlighted numerically with the variation of different input parameters of the system. The key factors of the system were highlighted to the policymakers for the control and prevention of the infection.

Rift Valley fever is a vector-borne zoonosis that can affect various species, including ruminants and camels. The present study reports the first serological detection of the Rift Valley fever virus in sheep and goats, along with an analysis of risk factors in Fars province, located in the south of Iran. The province of Fars was distributed into three climate zones, and three cities were accidentally chosen for each climatic zone. Two epidemiologic units were selected in each city, and samples of all the sheep and goats were collected from each unit. In total, 540 serum samples (391 from sheep and 149 from goats) were gathered and tested by a commercial ELISA kit. Out of 540 samples tested, 12 (2.2%) were found to be seropositive for the Rift Valley fever virus, with 10 from sheep and 2 from goats, indicating the presence of specific antibodies. The correlation between seropositivity and risk factors such as age, sex, climate, animal type, and, history of abortion was not significant. In conclusion, the Rift Valley fever virus is not endemic in Fars province. Further studies are recommended to investigate the distribution of mosquito vectors and their genotype in Fars province, isolate the virus, and develop vaccines.

Rift Valley fever (RVF) is an emerging zoonotic mosquito-borne disease caused by Rift Valley Fever virus (RVFV), affecting both humans and animals. It is endemic to Rwanda and Tanzania and Uganda which are adjacent countries, with possible transboundary transmissions. Despite the various outbreak reports in Rwanda since 2012, information on the intensity and spread of these outbreaks and their management is scarce. We describe the 2022 outbreak that happened in Rwanda and provide insights into the One Health response implemented during the outbreak.There were no human cases officially reported. A total of 1339 confirmed RVF animal cases were identified from 21 March until 31 December 2022. The breakdown of the cases per livestock species showed 1285 (96%) cases in cattle, 34 (3%) in goats and 20 (1%) in sheep. Of the confirmed livestock cases, 516 died and 1254 abortions were registered, in all affected species.The outbreak response was characterized by extensive interventions such as animal spraying with pyrethroid insecticides, vaccinations, and active follow-up of animals and humans in the households with animal cases. In the first phase of the outbreak, animal movements and slaughtering were restricted in the highly affected regions. Gradually, the abattoir slaughter activities were resumed with all animals required to test negative by RT-PCR before slaughter. Remarkably, the public services and hospital laboratories supported both capacity building of veterinary laboratory scientists and testing of animals' samples. The overall response was coordinated by district cross-sectoral teams linking national and community-level actors. Outbreak-related information was synthesized by the district teams and shared at national level while national strategies were communicated to the affected communities through the district structures.Rwanda's response to RVF provides a proof of concept that multisectoral efforts involving community members in a One Health approach can offer efficient response to zoonotic outbreaks while still protecting the country's economy.

Themosquito-borne Rift Valley fever virus (RVFV) fromthe Phenuiviridae family is a single-stranded RNA virus that causes the re-emerging zoonotic disease Rift Valley fever (RVF). Classified as a Category A agent by the NIH, RVFV infection can cause debilitating disease or death in humans and lead to devastating economic impacts by causing abortion storms in pregnant cattle. In a previous study, we showed that the host chaperone protein HSP90 is an RVFV-associated host factor that plays a critical role post viral entry, during the active phase of viral genome replication/transcription. In this study, we have elucidated themolecular mechanisms behind the regulatory effect of HSP90 during infection with RVFV. Our results demonstrate that during the early infection phase, host HSP90 associates with the viral RNA-dependent RNA polymerase (L protein) and prevents its degradation through the proteasome, resulting in increased viral replication. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda. Methods: Between November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software. Results: Overall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days. Conclusion: RVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible. Author summary: The majority of zoonoses originate in wildlife and tend to emerge from biodiverse regions in low to middle income countries, frequently among deprived populations of at-risk people with a lack of access to diagnostic capacity or surveillance. Diseases such as Crimean-Congo hemorrhagic fever, Rift Valley fever, Ebola virus disease, Marburg virus disease and Lassa fever are viral hemorrhagic fevers (VHFs) and rank among the most neglected and serious threats to global public health. This threat is partly due to the severity of disease caused by these pathogens, but also because their geographical distribution is close to human populations with often limited access to medical or diagnostic laboratory services. In our study we describe techniques for PCR based detection of five VHF viruses using a synthetic, multi-target non-infectious positive control. Our work has applications in assay design and optimization, particularly where access to source material is problematic or requires high level biosafety containment, as is the case with VHF viruses. This approach can help learners train in techniques used in nucleic acid extraction, amplification, and sequencing of VHF viruses and can be used for any targets, with potential for multiplexing from a single positive control. [ABSTRACT FROM AUTHOR]

This research examined the positivity ratio of Crimean–Congo haemorrhagic fever (CCHF) antibodies in cattle and sheep within Namibia's Omaheke region after a human disease outbreak in the same geographical area. A total of 200 samples (100 cattle and 100 sheep) were randomly collected from animals brought to two regional auction sites, and then tested using the ID Screen® CCHF Double Antigen Multi-Species Enzyme-Linked Immunosorbent Assay kit. Of the cattle samples, 36% tested positive, while 22% of the sheep samples were seropositive. The cattle had a significantly higher positivity ratio than sheep at the individual animal level (p = 0.0291). At the herd level, 62.5% of cattle herds and 45.5% of sheep flocks had at least one positive animal, but this difference was statistically insignificant (p = 0.2475). The fourteen cattle farms with at least one seropositive animal were dispersed across the Omaheke region. In contrast, the ten sheep farms with seropositive cases were predominantly situated in the southern half of the region. The study concluded that the CCHF is endemic in the Omaheke region and likely in most of Namibia, underscoring the importance of continued surveillance and preventive measures to mitigate the impact of CCHFV on animal health and potential spillover into human populations. [ABSTRACT FROM AUTHOR]

Rift Valley fever is a vector-borne zoonosis that can affect various species, including ruminants and camels. The present study reports the first serological detection of the Rift Valley fever virus in sheep and goats, along with an analysis of risk factors in Fars province, located in the south of Iran. The province of Fars was distributed into three climate zones, and three cities were accidentally chosen for each climatic zone. Two epidemiologic units were selected in each city, and samples of all the sheep and goats were collected from each unit. In total, 540 serum samples (391 from sheep and 149 from goats) were gathered and tested by a commercial ELISA kit. Out of 540 samples tested, 12 (2.2%) were found to be seropositive for the Rift Valley fever virus, with 10 from sheep and 2 from goats, indicating the presence of specific antibodies. The correlation between seropositivity and risk factors such as age, sex, climate, animal type, and, history of abortion was not significant. In conclusion, the Rift Valley fever virus is not endemic in Fars province. Further studies are recommended to investigate the distribution of mosquito vectors and their genotype in Fars province, isolate the virus, and develop vaccines. [ABSTRACT FROM AUTHOR]

The infection caused by Rift Valley fever (RVF) virus is a dangerous vector-borne disease found in humans, domestic, and wild animals. It is transferred through insect vectors to ruminant host and then spread through direct contact of infected animals with their body fluid or organs. In this paper, a fractal-fractional model for the transmission of RVF in the Caputo's sense was presented. We analyzed the model and determined the basic reproduction number through the next-generation matrix technique, indicated by R0. The global sensitivity technique is used for the sensitivity test of R0 to find out the most sensitive input-factors to the reproduction parameter R0. The existence and uniqueness results of the proposed fractal-fractional model were established. Then, we presented the fractal-fractional dynamics of the proposed RVF model through a novel numerical scheme under the fractal-fractional Caputo operator. In the end, the recommended model of RVF was highlighted numerically with the variation of different input parameters of the system. The key factors of the system were highlighted to the policymakers for the control and prevention of the infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence of six viruses, from two families of the order Bunyavirales, in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean–Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas (p < 0.001); 92.3% had animals in their living quarters (p = 0.009); and 70.8% lived in the vicinity of stagnant water (p = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases (p = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is a viral zoonosis that causes severe disease in ruminants and humans. The nonstructural small (NSs) protein is the primary virulence factor of RVFV that suppresses the host's antiviral innate immune response. Bioinformatic analysis and AlphaFold structural modeling identified four putative LC3-interacting regions (LIR) motifs (NSs 1–4) in the RVFV NSs protein, which suggest that NSs interacts with the host LC3-family proteins. Using, isothermal titration calorimetry, X-ray crystallography, co-immunoprecipitation, and co-localization experiments, the C-terminal LIR motif (NSs4) was confirmed to interact with all six human LC3 proteins. Phenylalanine at position 261 (F261) within NSs4 was found to be critical for the interaction of NSs with LC3, retention of LC3 in the nucleus, as well as the inhibition of autophagy in RVFV infected cells. These results provide mechanistic insights into the ability of RVFV to overcome antiviral autophagy through the interaction of NSs with LC3 proteins. Author summary: Rift Valley fever virus (RVFV) infection can cause severe illnesses including liver disease, encephalitis, and hemorrhagic fever. Unfortunately, there are no FDA-approved vaccines or therapeutics for human use. The NSs protein is the main virulence factor of RVFV and is a potent inhibitor of the host antiviral immune responses. Autophagy has been previously shown to be antiviral in RVFV infected cells, but RVFV can suppress this antiviral pathway by a previously undetermined mechanism. In this manuscript, we demonstrate that NSs interacts with host LC3-family proteins through an LC3 interacting region (LIR) within its C-terminus. This interaction results in LC3 being retained in the nucleus and autophagy inhibition. Our studies provide mechanistic insights by which NSs subverts antiviral autophagy during RVFV infection. [ABSTRACT FROM AUTHOR]

Background: The dynamic nature of zoonotic emergence, spillover and spread necessitates multisectoral coordination beyond national borders to encompass cross-boundary and regional cooperation. Designated points of entry (POEs), specifically ground crossings, serve as critical locales for establishing and maintaining robust prevention, detection, notification, coordination, and response mechanisms to transboundary emerging and re-emerging disease threats. In order to better assess One Health capacities for transboundary zoonotic diseases (TZD) prevention, detection and response we adapted an existing tool, One Health Systems Assessment for Priority Zoonoses (OHSAPZ), for a cross-border, POE setting in North Africa. Methods: The One Health Transboundary Assessment for Priority Zoonoses (OHTAPZ) tool was used to support prioritization of transboundary zoonoses and analyze operational capacities between national and subnational-level human and animal health stakeholders from Libya and Tunisia. Country partners jointly identified and prioritized five TZDs of concern. Case study scenarios for each priority pathogen were used to elicit current disease operations, as well as multisectoral and bilateral engagement networks. Finally, a gap analysis was performed to determine bilateral strengths and weaknesses to TZDs. Results: The five priority TZDs jointly confirmed to undergo One Health assessment were avian influenza (low and high pathogenic strains); brucellosis; Rift Valley fever; Crimean-Congo hemorrhagic fever; and rabies. Using the qualitative information collected, a transboundary systems map schematic was developed outlining the movement of human patients, animals, diagnostic samples, and routes of communication and coordination both within and between countries for zoonotic diseases. Conclusions: Analysis of current operations (prevention, detection, surveillance, laboratory capacity, quarantine/isolation, and response) and the resulting transboundary systems map schematic helped identify existing capacity strengths for certain priority pathogens, as well as challenges to timely information-sharing and coordination. We developed targeted recommendations to address these limitations for joint action planning between Libya and Tunisia. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV) that can infect domestic and wild animals. Although the RVFV transmission cycle has been well documented across Africa in savanna ecosystems, little is known about its transmission in tropical rainforest settings, particularly in Central Africa. We therefore conducted a survey in northeastern Gabon to assess RVFV circulation among wild and domestic animals. Among 163 wildlife samples tested using RVFV-specific RT-qPCR, four ruminants belonging to subfamily Cephalophinae were detected positive. The phylogenetic analysis revealed that the four RVFV sequences clustered together with a virus isolated in Namibia within the well-structured Egyptian clade. A cross-sectional survey conducted on sheep, goats and dogs living in villages within the same area determined the IgG RVFV-specific antibody prevalence using cELISA. Out of the 306 small ruminants tested (214 goats, 92 sheep), an overall antibody prevalence of 15.4% (95% CI [11.5–19.9]) was observed with a higher rate in goats than in sheep (20.1% versus 3.3%). RVFV-specific antibodies were detected in a single dog out of the 26 tested. Neither age, sex of domestic animals nor season was found to be significant risk factors of RVFV occurrence. Our findings highlight sylvatic circulation of RVFV for the first time in Gabon. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of RVFV. Author summary: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV) that can affect wild and domestic animals. Although the RVFV transmission cycle has been well documented across Africa in savanna ecosystems, little is known about its transmission in tropical rainforests, especially in Central Africa. We thus conducted a survey in northeastern Gabon to assess RVFV circulation among wild and domestic animals. In this study, we demonstrated for the first time in Gabon the presence of the RVFV in two wildlife species (Peter's duiker Cephalophus callipygus and the blue duiker Philantomba monticola). In addition, we detected RVFV-specific antibodies in small domestic ruminants (sheep and goats) at an overall antibody prevalence of 15.4%, with a much higher seroprevalence rate in goats than sheep (20.1% versus 3.3%). Furthermore, RVFV-specific antibodies were also observed in a single (hunting) dog out of the 26 tested. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of RVFV. [ABSTRACT FROM AUTHOR]