Rift Valley Fever Research Articles

Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in Aedes albopictus.

Background: The emergence or re-emergence of several orthobunyaviruses (order: Bunyavirales; family: Peribunyaviridae), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Materials and Methods: Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families. In addition, the deletion of Rift Valley fever virus NSs and NSm genes has been shown to reduce transmission by mosquitoes. Results: In this study, the ability of a CVV mutant lacking the NSs and NSm genes (2delCVV) to replicate in intrathoracically injected Aedes albopictus was compared with the parental wild-type CVV (wtCVV) 6V633 strain. In contrast to the robust replication of wtCVV in injected mosquitoes, the multiplication kinetics of the 2delCVV mutant was reduced by more than a 100-fold. Conclusion: These results suggest that the deletion of NSm and NSs genes is a feasible approach to rationally design candidate orthobunyavirus LAVs that are highly attenuated in mosquitoes and, therefore, pose little risk of reversion to virulence and transmission.

Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta.

Rift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and late-gestation miscarriages in women. Here, we use a rat model of congenital RVF to identify tropisms, pathologies, and immune responses in the placenta during vertical transmission. Infection of late-gestation pregnant rats resulted in vertical transmission to the placenta and widespread infection throughout the decidua, basal zone, and labyrinth zone. Some pups from infected dams appeared normal while others had gross signs of teratogenicity including death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had widespread hemorrhage throughout multiple placenta layers. Teratogenic events were associated with significant increases in placental pro-inflammatory cytokines, type I interferons, and chemokines. RVFV displays a high degree of tropism for all placental tissue layers and the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. Given the potential for RVFV to emerge in new locations and the recent evidence of emerging viruses, like Zika and SARS-CoV-2, to undergo vertical transmission, this study provides essential understanding regarding the mechanisms by which RVFV crosses the placenta barrier.

Scoping review on impact of mosquito - borne diseases of man and animals and use of potential bacterial larvicidal agents to control mosquito vectors

Mosquito vector-borne disease which accounts for the transmission of many deadly diseases like dengue, zika, chikungunya, Rift Valley fever, malaria, West Nile fever, heartworm, lumpy skin disease is one of the major causes of mortality, morbidity, and economic loss to human and animal communities. Though there have been several interventions like insecticide-treated nets, spatial repellents, indoor pesticide sprays to control adult mosquitoes, it only remains effective for short time, possibly leading to faster replacement of the adults by immature only achieving lesser mosquito population reduction. Extensive use of synthetic insecticides leads to resistance, affects non-target organisms and cause ecological imbalance. While recognizing the limitations of the synthetic and adulticide-based mosquito control methods, alternatively, microbial larvicidal agents are more feasible, target-specific, environment-friendly, low application rates, and moderate costs when compared with other vector control measures. This review highlights the microbial larvicidal agents as a most promising tool in vector control management to prevent disease transmission and discusses the major mosquito-borne diseases affecting humans and other animals.

Inter-epidemic Rift Valley fever virus infection incidence and risks for zoonotic spillover in northern Tanzania.

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that has caused epidemics involving people and animals across Africa and the Arabian Peninsula. A number of studies have found evidence for the circulation of RVFV among livestock between these epidemics but the population-level incidence of infection during this inter-epidemic period (IEP) is rarely reported. General force of infection (FOI) models were applied to age-adjusted cross-sectional serological data to reconstruct the annual FOI and population-level incidence of RVFV infection among cattle, goats, and sheep in northern Tanzania from 2009 through 2015, a period without reported Rift Valley fever (RVF) cases in people or animals. To evaluate the potential for zoonotic RVFV spillover during this period, the relationship between village-level livestock RVFV FOI and human RVFV seropositivity was quantified using multi-level logistic regression. The predicted average annual incidence was 72 (95% Credible Interval [CrI] 63, 81) RVFV infections per 10,000 animals and 96 (95% CrI 81, 113), 79 (95% CrI 62, 98), and 39 (95% CrI 28, 52) per 10,000 cattle, sheep, and goats, respectively. There was variation in transmission intensity between study villages, with the highest estimated village-level FOI 2.49% (95% CrI 1.89, 3.23) and the lowest 0.12% (95% CrI 0.02, 0.43). The human RVFV seroprevalence was 8.2% (95% Confidence Interval 6.2, 10.9). Human seropositivity was strongly associated with the village-level FOI in livestock, with the odds of seropositivity in an individual person increasing by around 1.2 times (95% CrI 1.1, 1.3) for each additional annual RVFV seroconversion per 1,000 animals. A history of raw milk consumption was also positively associated with human seropositivity. RVFV has circulated at apparently low levels among livestock in northern Tanzania in the period since the last reported epidemic. Although our data do not allow us to confirm human RVFV infections during the IEP, a strong association between human seropositivity and the FOI in cattle, goats, and sheep supports the hypothesis that RVFV circulation among livestock during the IEP poses a risk for undetected zoonotic spillover in northern Tanzania. We provide further evidence for the likely role of raw milk consumption in RVFV transmission from animals to people.

Immune correlates of protection following Rift Valley fever virus vaccination

Rift Valley fever virus (RVFV) is a hemorrhagic fever virus with the potential for significant economic and public health impact. Vaccination with an attenuated strain, DelNSsRVFV, provides protection from an otherwise lethal RVFV challenge, but mechanistic determinants of protection are undefined. In this study, a murine model was used to assess the contributions of humoral and cellular immunity to DelNSsRVFV-mediated protection. Vaccinated mice depleted of T cells were protected against subsequent challenge, and passive transfer of immune serum from vaccinated animals to naïve animals was also protective, demonstrating that T cells were dispensable in the presence of humoral immunity and that humoral immunity alone was sufficient. Animals depleted of B cells and then vaccinated were protected against challenge. Total splenocytes, but not T cells alone, B cells alone, or B + T cells harvested from vaccinated animals and then transferred to naïve animals were sufficient to confer protection, suggesting that multiple cellular interactions were required for effective cellular immunity. Together, these data indicate that humoral immunity is sufficient to confer vaccine-mediated protection and suggests that cellular immunity plays a role in protection that requires the interaction of various cellular components.

Changing gear: Experiences of how existing qualitative research can adapt to an unfolding health emergency.

Long-term research projects are not always able to adapt to a new crisis and incorporate characteristics and approaches of rapid research to produce useful data quickly. Project AViD was a programme of research that ran between 2018 and 2022 to examine factors that shape vaccine confidence. The project initially focused on five country case studies looking at vaccines for Ebola, Measles, Rift Valley Fever and Zika. The COVID-19 pandemic emerged during this time and provided an opportunity to contribute to the pandemic's 'million-dollar question'-how to deploy COVID-19 vaccines. Drawing on our experience as researchers, and specifically from AViD, we propose seven factors that can influence when and how longer-term qualitative research projects can adapt and contribute to the response to an unfolding health emergency. These include: (1) the phase of research in which the emergency hits; (2) the relative significance of the emergency in the research setting; (3) the specific methods and research team capacities; (4) existing operational links; (5) supportive ecosystems; (6) flexibility in research contracting and funding; and (7) the research team attitude and approach. We close with two considerations for longer-term research projects that find themselves having to "change gear" amid a public health emergency-the need to re-assess risks and benefits and the need to protect equitable partnerships.

An Overview of Rift Valley Fever Vaccine Development Strategies.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality in ruminants and a mild to fatal hemorrhagic fever in humans. There are no licensed RVF vaccines for human use while for livestock, commercially available vaccines are all either live attenuated or inactivated and have undesirable characteristics. The live attenuated RVF vaccines are associated with teratogenicity and residual virulence in ruminants while the inactivated ones require multiple immunisations to induce and maintain protective immunity. Additionally, nearly all licensed RVF vaccines lack the differentiating infected from vaccinated animals (DIVA) property making them inappropriate for use in RVF nonendemic countries. To address these limitations, novel DIVA-compatible RVF vaccines with better safety and efficacy than the licensed ones are being developed, aided fundamentally by a better understanding of the molecular biology of the RVF virus and advancements in recombinant DNA technology. For some of these candidate RVF vaccines, sterilizing immunity has been demonstrated in the discovery/feasibility phase with minimal adverse effects. This review highlights the progress made to date in RVF vaccine research and development and discusses the outstanding research gaps.

Mosquito Bite and the Deadly Duo

Avoiding a mosquito bite can prevent a number of viral as well as parasitic diseases like Chikungunya, Dengue,Japanese encephalitis, Rift valley fever, Yellow fever, Zika, Malaria and Lymphatic Filariasis. Of all theseinfections, malaria has been our nemesis right from the dawn of history. However, it is Dengue which has established itself as the most successful arthropod-borne viral infection not only in Pakistan but globally.1The first case of Dengue in Pakistan was reported in 1994 from Karachi, after which it went quiet for almosttwelve years to return in the form of an epidemic in 2006, which again remained limited to Karachi. However, itspread to many other parts of the country in the next few years on endemic scales.A person can get infected four times as the Dengue virus has four serotypes (DEN1, DEN2, DEN3 and DEN4) eachof which confers monotypic immunity. It is now a recognized acute febrile illness of the monsoon season (July-September), when a drop temperature and increased humidity provide optimal conditions for this urbandwelling, dawn and dusk, vector mosquito, Aedes aegypti. This vector now seems to be defying these climaticconditions as patients continue to report to hospitals in the winter months as well.The textbook diagnosis of Dengue looks simple; by detecting the virus either (by viral culture), its nucleic acid(by PCR), its components like the non-structural protein (NS-1), or the evidence of infection (IgM), or if none ofthese is available, then the surrogate markers like the typical bicytopenia showing reduced neutrophils andplatelets are indicators of the disease. Similarly, the clinical diagnosis is not very difficult once the epidemic isestablished, due to its peculiar symptoms like retro-orbital pain and body aches , so severe as if the bones willbreak, hence the name 'Break Bone' fever.Dengue is temporarily incapacitating but rarely fatal, and in Pakistan it has a case fatality rate around 0.4 percent.2 This low fatality rate should not lead to complacency as every life is precious. A few fundamentals,however, need emphasis especially for the young doctors and the medical staff attending the patients ofDengue. Like many other infectious diseases, Dengue follows the principle of the “tip of the iceberg”. Majorityof those infected with the virus, remain either asymptomatic or present with minimum symptoms including lowgrade fever. However, a small percentage of patients may proceed to the critical stage called the DengueHaemmorhagic Fever (DHF)/Dengue Shock Syndrome (DSS) and warrant special attention. These are basicallythe manifestations of underlying plasma leakage and it is this cohort of patients that are at an increased risk ofan adverse outcome.The parameter which helps in this situation is the packed cell volume (haematocrit), an increase of about 15% ofwhich is a reliable indicator of internal dehydration. DHF/DSS occur as a result of a second exposure by a different serotype, and a still not completely understood phenomenon, known as the Antibody Dependent Enhancement (ADE).Pakistan has barely recovered from the COVID19 pandemic, hit by the economic crisis and now unprecedentedfloods in Sindh and Baluchistan, where most parts are still inundated and are likely to be so for another severalweeks, we are indeed in a very difficult situation. An estimated 6.4 million people require immediate assistanceas around 1.96 million houses, 22,000 schools and 12,716 km of roads have been either destroyed or damagedin 81 districts.3 Ironically these two provinces have bulk of the country's falciparum malaria cases, which is themost lethal form with severe complications like heavy parasitaemia, cerebral malaria, black water fever andchloroquine resistance.
 Stagnant water all around the stranded people is a perfect mosquito breeding haven. It is difficult tocomprehend the plight of people now living along the roadside under a tent in hot and humid conditions, asthey are exposed twenty-four seven, either to the Dengue mosquito at dawn and dusk or, malaria causinganopheles mosquito at night.The magnitude of this problem is much bigger than the resources of any medical community and thegovernment. Spraying insecticides over this volume is logistically not feasible. The only practical solution isthe use of personal protective measures.Deaths from these two diseases along with gastroenteritis have already started to occur. The exact toll of thesemosquito bites will be written by the medical historians or the statisticians sometime in the future. It is theyouth of Pakistan which has once again risen to the occasion and is working relentlessly on volunteer basis, toreach out to these people not only providing them with mosquito nets and repellants but explaining theirproper use. This altruistic effort will definitely save many lives.Editor-in-ChiefHow to cite this: Alamgir W, Usman J. Mosquito Bite and the Deadly Duo. Life and Science. 2022; 3(4): 149-150. doi: http://doi.org/10.37185/LnS.1.1.288

Establishment of a Culex tarsalis (Diptera: Culicidae) Cell Line and its Permissiveness to Arbovirus Infection.

A cell line was established from Culex tarsalis Coquillett embryonated eggs and designated as CxTr. The cell line is heterogeneous, composed predominantly of small, round cells, and spindle-shaped cells with a doubling time of approximately 52-60 h. The identity of the cell line was verified as Cx. tarsalis by sequencing of cytochrome oxidase I and the cells were found to be free of contaminating cells, bacteria, fungi, and mycoplasma. The permissiveness of CxTr cells to arbovirus infection was investigated with vaccine and wildtype arboviruses from four viral families: Flaviviridae (Japanese encephalitis virus), Phenuiviridae (Rift Valley fever phlebovirus), Rhabdoviridae (vesicular stomatitis virus), and Togaviridae (Mayaro virus). All viruses were able to infect and replicate within CxTr cells.

Intact Type I Interferon Receptor Signaling Prevents Hepatocellular Necrosis but Not Encephalitis in a Dose-Dependent Manner in Rift Valley Fever Virus Infected Mice.

Rift Valley fever (RVF) is a zoonotic and emerging disease, caused by the RVF virus (RVFV). In ruminants, it leads to “abortion storms” and enhanced mortality rates in young animals, whereas in humans it can cause symptoms like severe hemorrhagic fever or encephalitis. The role of the innate and adaptive immune response in disease initiation and progression is still poorly defined. The present study used the attenuated RVFV strain clone 13 to investigate viral spread, tissue tropism, and histopathological lesions after intranasal infection in C57BL/6 wild type (WT) and type I interferon (IFN-I) receptor I knockout (IFNAR−/−) mice. In WT mice, 104 PFU RVFV (high dose) resulted in a fatal encephalitis, but no hepatitis 7–11 days post infection (dpi), whereas 103 PFU RVFV (low dose) did not cause clinical disease or significant histopathological lesions in liver and the central nervous system (CNS). In contrast, IFNAR−/− mice infected with 103 PFU RVFV developed hepatocellular necrosis resulting in death at 2–5 dpi and lacked encephalitis. These results show that IFNAR signaling prevents systemic spread of the attenuated RVFV strain clone 13, but not the dissemination to the CNS and subsequent fatal disease. Consequently, neurotropic viruses may be able to evade antiviral IFN-I signaling pathways by using the transneuronal instead of the hematogenous route.

COP27 Climate Change Conference: urgent action needed for Africa and the world

COP27 Climate Change Conference: urgent action needed for Africa and the world

Investigation of the outbreaks of abortions and orchitis in livestock in Namibia during 2016-2018.

This study investigated outbreaks of seemingly related abortions and orchitis which occurred in the Khomas, Omaheke and Otjozondjupa regions of Namibia from 2016 to 2018, affecting cattle, sheep and goats. Fifty-nine questionnaires were administered, and 48 were completed giving an 81.4% return. The outbreaks were limited to Namibia's east and central regions, mainly on farms rearing cattle, sheep and goats and on farms with a mixture of these species. There was no significant difference between Khomas and other regions on abortion reporting at the farm level [X2(1,N = 48) = 0.0002,p = 0.987851]. However, there was a significant difference in the abortions at the animal level among the three regions [X2(2,N = 6246) = 239.8339,p = .00001]. In addition, the proportions of abortions calculated at the animal level at each farm were significantly different when the Khomas region was compared to the other regions. Seventeen cattle sera, 35 sheep sera, 52 caprine sera, 18 bovine liver samples, one caprine liver, five aborted cattle foetuses, two cattle placentas, 18 testes (one bull, eight bucks and nine rams) and ten bull sheath scrapings were collected and tested. Histopathology, microbiology, serology, immunohistochemistry, real-time PCR and mineral analytical techniques were used to establish the aetiology of the abortion and orchitis outbreaks. The gross and histopathological findings on the 18 testicles were characteristic of chronic orchitis. In aborted foetuses, significant histopathological findings included meconium aspiration, funisitis and cardiomyopathy. Placentitis and endometritis were the primary pathologies observed in cows. The bacteria isolated from microbiological samples included Enterococcus spp. (65.5% [19/29]), Enterobacter spp. (6.9% [2/29]) and Streptococcus spp. (10.3% [3/29]), Trueperella pyogenes (3.4% [1/29]), Stenotrophomonas maltophilia (3.4% [1/29]), Staphylococcus epidermidis (3.4% [1/29]), Providencia rettgeri (3.4% [1/29]) and Acinetobacter lwoffii (3.4% [1/29]), mostly opportunistic bacteria. On mineral analysis, 28%, 33%, 83%, 33% and 17% (n = 18) of cattle livers were low in copper, zinc, manganese, selenium and iron, respectively. Twenty-three percent (12/52) of the caprine sera were positive for Brucella melitensis on the Rose Bengal and complement fixation tests. Thirty-five ovine sera were tested for B. melitensis, B. ovis and Coxiella burnetii, and the prevalence for each was 2.9% (1/35). PCR tests on foetuses were all negative for Brucella spp., Coxiella burnetii, Chlamydia spp., Listeria monocytogenes, Salmonella spp., Campylobacter fetus spp., Leptospira pathogenic strains, bovine viral diarrhoea virus, Rift Valley fever virus, Anaplasma phagocytophilum and bovine herpes virus 4 Campylobacter fetus spp. and Trichomonas foetus spp. The authors concluded that Brucella spp., Enterococcus spp., Escherichia coli, Streptococcus spp., Trueperella pyogenes and Coxiella burnetii could have contributed to this outbreak. Micronutrient imbalances and pathogenic abiotic nanoparticles were also identified as possible contributors to the abortion outbreaks.

Common pathways targeted by viral hemorrhagic fever viruses to infect the placenta and increase the risk of stillbirth

Viral hemorrhagic fevers (VHF) are endemic to Africa, South America and Asia and contribute to significant maternal and fetal morbidity and mortality. Viruses causing VHFs are typically zoonotic, spreading to humans through livestock, wildlife, or mosquito vectors. Some of the most lethal VHF viruses also impart a high-risk of stillbirth including ebolaviruses, Marburg virus (MARV), Lassa virus (LASV), and Rift Valley Fever Virus (RVFV). Large outbreaks and epidemics are common, though the impact on the mother, fetus and placenta is understudied from a public health, clinical and basic science perspective. Notably, these viruses utilize ubiquitous cellular surface entry receptors critical for normal placental function to enable viral invasion into multiple key cell types of the placenta and set the stage for maternal-fetal transmission and stillbirth. We employ insights from molecular virology and viral immunology to discuss how trophoblast expression of viral entry receptors for VHF viruses may increase the risk for viral transmission to the fetus and stillbirth. As the frequency of VHF outbreaks is expected to increase with worsening climate change, understanding the pathogenesis of VHF-related diseases in the placenta is paramount to predicting the impact of emerging viruses on the placenta and perinatal outcomes.

Diversity, composition, altitude, and seasonality of high-altitude windborne migrating mosquitoes in the Sahel: Implications for disease transmission.

Recent studies have reported Anopheles mosquitoes captured at high-altitude (40-290 m above ground) in the Sahel. Here, we describe this migration modality across genera and species of African Culicidae and examine its implications for disease transmission and control. As well as Anopheles, six other genera-Culex, Aedes, Mansonia, Mimomyia, Lutzia, and Eretmapodites comprised 90% of the 2,340 mosquitoes captured at altitude. Of the 50 molecularly confirmed species (N = 2,107), 33 species represented by multiple specimens were conservatively considered high-altitude windborne migrants, suggesting it is a common migration modality in mosquitoes (31-47% of the known species in Mali), and especially in Culex (45-59%). Overall species abundance varied between 2 and 710 specimens/species (in Ae. vittatus and Cx. perexiguus, respectively). At altitude, females outnumbered males 6:1, and 93% of the females have taken at least one blood meal on a vertebrate host prior to their departure. Most taxa were more common at higher sampling altitudes, indicating that total abundance and diversity are underestimated. High-altitude flight activity was concentrated between June and November coinciding with availability of surface waters and peak disease transmission by mosquitoes. These hallmarks of windborne mosquito migration bolster their role as carriers of mosquito-borne pathogens (MBPs). Screening 921 mosquitoes using pan-Plasmodium assays revealed that thoracic infection rate in these high-altitude migrants was 2.4%, providing a proof of concept that vertebrate pathogens are transported by windborne mosquitoes at altitude. Fourteen of the 33 windborne mosquito species had been reported as vectors to 25 MBPs in West Africa, which represent 32% of the MBPs known in that region and include those that inflict the heaviest burden on human and animal health, such as malaria, yellow fever, dengue, and Rift Valley fever. We highlight five arboviruses that are most likely affected by windborne mosquitoes in West Africa: Rift Valley fever, O'nyong'nyong, Ngari, Pangola, and Ndumu. We conclude that the study of windborne spread of diseases by migrating insects and the development of surveillance to map the sources, routes, and destinations of vectors and pathogens is key to understand, predict, and mitigate existing and new threats of public health.

Evaluation of Extreme Soil Moisture Conditions During the 2020 Sahel Floods and Implications for Disease Outbreaks

AbstractThe June‐October 2020 growing season was characterized by sustained and extreme flooding across the African Sahel. One consequence of flooding events such as this is outbreaks of vector borne diseases (VBDs) which are often associated with climate anomalies. In this study, data from the soil moisture active passive (SMAP) mission is used with other soil moisture and precipitation data to show that the 2020 Sahelian growing season was the most extreme over the past four decades, ranking first in seasonally accumulated precipitation, which on average exceeded the climatology by around 300 mm. VBD outbreaks of Rift Valley fever and Chikungunya followed in Mauritania/Senegal and Chad, respectively. In some cases, soil moisture is a better indicator of VBD outbreak risk than precipitation, which has so far been more commonly used in studies of VBD outbreaks. It is expected that this finding will inform future monitoring and prediction efforts for VBD risk.

A Review of Omics Studies on Arboviruses: Alphavirus, Orthobunyavirus and Phlebovirus.

Since the intricate and complex steps in pathogenesis and host-viral interactions of arthropod-borne viruses or arboviruses are not completely understood, the multi-omics approaches, which encompass proteomics, transcriptomics, genomics and metabolomics network analysis, are of great importance. We have reviewed the omics studies on mosquito-borne viruses of the Togaviridae, Peribuyaviridae and Phenuiviridae families, specifically for Chikungunya, Mayaro, Oropouche and Rift Valley Fever viruses. Omics studies can potentially provide a new perspective on the pathophysiology of arboviruses, contributing to a better comprehension of these diseases and their effects and, hence, provide novel insights for the development of new antiviral drugs or therapies.

Rift Valley Fever Virus Infects the Posterior Segment of the Eye and Induces Inflammation in a Rat Model of Ocular Disease.

ABSTRACTPeople infected with the mosquito-borne Rift Valley fever virus (RVFV) can suffer from eye-related problems resulting in ongoing vision issues or even permanent blindness. Despite ocular disease being the most frequently reported severe outcome, it is vastly understudied compared to other disease outcomes caused by RVFV. Ocular manifestations of RVFV include blurred vision, uveitis, and retinitis. When an infected individual develops macular or paramacular lesions, there is a 50% chance of permanent vision loss in one or both eyes. The cause of blinding ocular pathology remains unknown in part due to the lack of a tractable animal model. Using 3 relevant exposure routes, both subcutaneous (SC) and aerosol inoculation of Sprague Dawley rats led to RVFV infection of the eye. Surprisingly, direct inoculation of the conjunctiva did not result in successful ocular infection. The posterior segment of the eye, including the optic nerve, choroid, ciliary body, and retina, were all positive for RVFV antigen in SC-infected rats, and live virus was isolated from the eyes. Proinflammatory cytokines and increased leukocyte counts were also found in the eyes of infected rats. Additionally, human ocular cell lines were permissive for Lrp1-dependent RVFV infection. This study experimentally defines viral tropism of RVFV in the posterior segment of the rat eye and characterizes virally-mediated ocular inflammation, providing a foundation for evaluation of vaccines and therapeutics to protect against adverse ocular outcomes.IMPORTANCE Rift Valley fever virus (RVFV) infection leads to eye damage in humans in up to 10% of reported cases. Permanent blindness occurs in 50% of individuals with significant retinal scarring. Despite the prevalence and severity of this outcome, very little is known about the mechanisms of pathogenesis. We addressed this gap by developing a rodent model of ocular disease. Subcutaneous infection of Sprague Dawley rats resulted in infection of the uvea, retina, and optic nerve along with the induction of inflammation within the posterior eye. Infection of human ocular cells induced inflammatory responses and required host entry factors for RVFV infection similar to rodents. This work provides evidence of how RVFV infects the eye, and this information can be applied to help mitigate the devastating outcomes of RVF ocular disease through vaccines or treatments.

Climate change and Rift Valley fever disease outbreak: implications for the food environment of pastoralists

BackgroundRift Valley fever disease affects both livestock and humans. Variations in rainfall patterns have contributed to more frequent intense floods which favour the vector mosquito and associated Rift Valley fever outbreaks. Pastoralists living on poor rangelands depend on livestock for food and livelihood. Rift Valley fever outbreak control and management measures such as quarantine and trade bans of livestock and associated products disrupt the food systems in pastoralist settings. This contributes to poor food availability, access, and affordability leading to poor food choice and consumption, and potential negative nutrition, especially in women of reproductive age (WRA) and children younger than 5 years. Evidence on the effects of Rift Valley fever outbreaks on the food environment and nutrition security is scarce. This study analysed the effect of Rift Valley fever outbreak on various domains of the food environment to inform future Rift Valley fever outbreak response, to be comprehensive, and to consider nutrition. MethodsThis was a mixed-methods study done in pastoralist Isiolo County, Kenya, purposively selected owing to a Rift Valley fever outbreak in 2020. A cross-sectional household survey (n=767), focus group discussions, and in-depth interviews were done. Data on 24-h dietary recall and dietary practices was collected and analysed by means of the NutriSurvey tool and NVivo software for qualitative data. FindingsMortality in sheep, goat, and cattle was 40·2%; 52·8%, and 19·6% respectively; about 70–92% households depended on income from livestock sales. Livestock sales reduced; food prices increased; flesh-meat consumption declined from 19·7% to 14·2% before and during Rift Valley fever outbreak. Only 23·6% of the WRA achieved the minimum dietary diversity score; about 55% of the children consumed insufficient energy, protein, and vitamin A. InterpretationFuture Rift Valley fever responses need to consider nutrition because the disease and mortality reduce livestock productivity and associated foods, while Rift Valley fever control measures reduce food access and income, and raise food prices, which contribute to purchase and consumption of inadequate, cheap, and less nutritious foods with potentially negative nutrition outcomes. FundingThe United States Agency for International Development and the Office of Foreign Disaster Assistance.

Advances in Understanding Neuropathogenesis of Rift Valley Fever Virus.

Rift Valley fever virus (RVFV) is an emerging arboviral pathogen that causes disease in both livestock and humans. Severe disease manifestations of Rift Valley fever (RVF) in humans include hemorrhagic fever, ocular disease, and encephalitis. This review describes the current understanding of the pathogenesis of RVF encephalitis. While some data from human studies exist, the development of several animal models has accelerated studies of the neuropathogenesis of RVFV. We review current animal models and discuss what they have taught us about RVFV encephalitis. We briefly describe alternative models that have been used to study other neurotropic arboviruses and how these models may help contribute to our understanding RVFV encephalitis. We conclude with some unanswered questions and future directions.

Evaluations of rationally designed rift valley fever vaccine candidate RVax-1 in mosquito and rodent models

Rift Valley fever (RVF) is a mosquito-borne zoonosis endemic to Africa and the Arabian Peninsula, which causes large outbreaks among humans and ruminants. Single dose vaccinations using live-attenuated RVF virus (RVFV) support effective prevention of viral spread in endemic countries. Due to the segmented nature of RVFV genomic RNA, segments of vaccine strain-derived genomic RNA could be incorporated into wild-type RVFV within co-infected mosquitoes or animals. Rationally designed vaccine candidate RVax-1 displays protective epitopes fully identical to the previously characterized MP-12 vaccine. Additionally, all genome segments of RVax-1 contribute to the attenuation phenotype, which prevents the formation of pathogenic reassortant strains. This study demonstrated that RVax-1 cannot replicate efficiently in orally fed Aedes aegypti mosquitoes, while retaining strong immunogenicity and protective efficacy in an inbred mouse model, which were indistinguishable from the MP-12 vaccine. These findings support further development of RVax-1 as the next generation MP-12-based vaccine for prevention of Rift Valley fever in humans and animals.