Rift Valley Fever Outbreak Research Articles

Tracking Rift Valley fever: From Mali to Europe and other countries, 2016.

On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.

The One Health Approach is Necessary for the Control of Rift Valley Fever Infections in Egypt: A Comprehensive Review

Rift Valley fever (RVF) is an emerging transboundary, mosquito-borne, zoonotic viral disease caused high morbidity and mortality in both human and ruminant populations. It is considered an important threat to both agriculture and public health in African and the Middle Eastern countries including Egypt. Five major RVF epidemics have been reported in Egypt (1977, 1993, 1994, 1997, and 2003). The virus is transmitted in Egypt by different mosquito’s genera such as Aedes, Culex, Anopheles, and Mansonia, leading to abortions in susceptible animal hosts especially sheep, goat, cattle, and buffaloes. Recurrent RVF outbreaks in Egypt have been attributed in part to the lack of routine surveillance for the virus. These periodic epizootics have resulted in severe economic losses. We posit that there is a critical need for new approaches to RVF control that will prevent or at least reduce future morbidity and economic stress. One Health is an integrated approach for the understanding and management of animal, human, and environmental determinants of complex problems such as RVF. Employing the One Health approach, one might engage local communities in surveillance and control of RVF efforts, rather than continuing their current status as passive victims of the periodic RVF incursions. This review focuses upon endemic and epidemic status of RVF in Egypt, the virus vectors and their ecology, transmission dynamics, risk factors, and the ecology of the RVF at the animal/human interface, prevention, and control measures, and the use of environmental and climate data in surveillance systems to predict disease outbreaks.

Distribution and relative densities of Aedes aegypti in Niger.

Its climate and environmental conditions put Niger at particularly high risk of the spread of Aedes mosquitoes, which can transmit arboviruses. In September 2016, the Republic of Niger reported its first outbreak of Rift Valley Fever (RVF) in the northern region of Tahoua, near the Mali border, particularly in the departments of Tchintabaraden, Tassara, and Abalak. The history of RVF has showed that epidemics and epizootics have a considerable socioeconomic impact in affected countries, such as Niger, whose populations are particularly concerned by livestock farming. Cross-sectional studies were conducted to investigate the abundance of Aedes aegypti and the risk of arbovirus transmission in 54 villages between 2002 and 2017. Sampling took place in 27 villages, with three methods used in each village: (a) capture of aggressive female mosquitoes landing on human adult volunteers from three households, both indoors and outdoors, during two consecutive nights; (b) insecticide spray collections of resting mosquitoes early in the morning in five selected dwellings, different from those chosen for landing catches, and (c) capture by four Centers for Disease Control (CDC) light traps, both indoors and outdoors, for two nights. The remaining 27 villages were sampled only by insecticide spray collection of resting mosquitoes. The inventory, distribution, and abundance of mosquito species found at the sampled localities were evaluated. The mosquitoes (Culicidae) caught belonged to four genera, namely: Anopheles spp., Aedes spp., Culex spp. and Mansonia spp. Besides these Culicidae, other biting Diptera (Phlebotomes) were found during the capture. À total of 130,424 adult mosquitoes was caught during the study, 2.6% (3,444/130,423) of them Aedes spp. Aedes aegypti accounted for 96.6% of the Aedes spp. captured. Ae. Aegypti was collected in 41.0% (22/54) of the villages and was abundant (accounting for more than 15% of all mosquitoes captured) in 5 localities. The presence, geographical distribution, and abundance of Ae. aegypti near and in human habitations suggest a high risk of arbovirus transmission in Niger. The high abundance of arbovirus vectors encountered in this study should be a source of concern. Our observations highlight the importance of quantifying and monitoring the risk of arbovirus transmission in Niger. These results are of great importance for public health.

Ten outbreaks of rift valley fever in Uganda 2016-2018: epidemiological and laboratory findings

Ten outbreaks of rift valley fever in Uganda 2016-2018: epidemiological and laboratory findings

Zoonotic Rift Valley fever virus prevalence and risk factors in the Lake Zone of Tanzania

Zoonotic Rift Valley fever virus prevalence and risk factors in the Lake Zone of Tanzania

Arboviruses isolated from the Barkedji mosquito-based surveillance system, 2012-2013

BackgroundA mosquito-based arbovirus surveillance system was set up at Barkedji, Senegal after the first outbreak of Rift valley fever in West Africa in 1988. This system was recently updated using more sampling methods and collecting in greater number of ponds and villages sites.MethodsFor the current study, mosquitoes were sampled biweekly between July and December 2012 and 2013 using CDC+CO2 light traps set at ground and canopy level, mosquito nets baited with goat, sheep, human or chicken, light traps baited with goat, sheep and chicken; bird-baited traps using pigeons or chickens placed either at the ground or canopy level. Collected mosquitoes were identified, pooled and screened for arboviruses.ResultsA total of 42,969 mosquitoes in 4,429 pools were processed for virus isolation. Ten virus species were identified among 103 virus isolates. West Nile virus (WNV; 31 isolates), Barkedji virus (BARV; 18), Sindbis virus (SINV; 13), Usutu virus (USUV; 12), Acado virus (ACAV; 8), Ndumu virus (NDUV; 9), Sanar virus (SANV; 7), Bagaza virus (BAGV; 3), Rift valley fever virus (RVFV; 1), and Yaounde virus (YAOV; 1) were isolated from 9 ponds (91 strains) and 7 villages (12 strains). Only 3 virus species (WNV, NDU and SINV) were isolated from villages. The largest numbers of isolates were collected in October (29.1% of total isolates) and November (50.5%). Viruses were isolated from 14 mosquito species including Cx. neavei (69.9% of the strains), Cx. antennatus (9.7%), and Ma. uniformis (4.8%). NDUV, ACAV, and SINV are herein reported for the first time in the Barkedji area. Isolation of ACAV and SANV from a pool of male Ma. uniformis and USUV and BARV from a pool of male Cx. neavei, are reported for the first time to our knowledge.ConclusionOur data indicate that the Barkedji area is characterized by a high diversity of viruses of medical, veterinary and unknown importance. Arboviruses were first detected in July at the beginning of the rainy season and peaked in abundance in October and November. The Barkedji area, an enzootic focus of several potentially emerging arboviruses, should be surveilled annually to be prepared to deal with future disease emergence events.

Serological evidence of inter-epizootic/inter-epidemic circulation of Rift Valley fever virus in domestic cattle in Kyela and Morogoro, Tanzania.

BackgroundTanzania is among the Rift Valley fever (RVF) epizootic/endemic countries in sub Saharan Africa, where RVF disease outbreaks occur within a range of 3 to 17-year intervals. Detection of Rift Valley fever virus (RVFV) antibodies in animals in regions with no previous history of outbreaks raises the question of whether the disease is overlooked due to lack-of effective surveillance systems, or if there are strains of RVFV with low pathogenicity. Furthermore, which vertebrate hosts are involved in the inter-epidemic and inter-epizootic maintenance of RVFV? In our study region, the Kyela and Morogoro districts in Tanzania, no previous RVF outbreaks have been reported.MethodologyThe study was conducted from June 2014 to October 2015 in the Kyela and Morogoro districts, Tanzania. Samples (n = 356) were retrieved from both the local breed of zebu cattle (Bos indicus) and Bos indicus/Bos Taurus cross breed. RVFV antibodies were analyzed by two enzyme-linked immunosorbent assay (ELISA) approaches. Initially, samples were analyzed by a RVFV multi-species competition ELISA (cELISA), which detected both RVFV IgG and IgM antibodies. All serum samples that were positive with the cELISA method were specifically analysed for the presence of RVFV IgM antibodies to trace recent infection. A plaque reduction neutralization assay (PRNT80) was performed to determine presence of RVFV neutralizing antibodies in all cELISA positive samples.FindingsOverall RVFV seroprevalence rate in cattle by cELISA in both districts was 29.2% (104 of 356) with seroprevalence rates of 33% (47/147) in the Kyela district and 27% (57/209) in the Morogoro district. In total, 8.4% (30/356) of all cattle sampled had RVFV IgM antibodies, indicating current disease transmission. When segregated by districts, the IgM antibody seroprevalence was 2.0% (3/147) and 12.9% (27/209) in Kyela and Morogoro districts respectively. When the 104 cELISA positive samples were analyzed by PRNT80 to confirm that RVFV-specific antibodies were present, the majority (89%, 93/104) had RVFV neutralising antibodies.ConclusionThe results provided evidence of widespread prevalence of RVFV antibody among cattle during an inter-epizootic/inter-epidemic period in Tanzania in regions with no previous history of outbreaks. There is a need for further investigations of RVFV maintenance and transmission in vertebrates and vectors during the long inter-epizootic/inter-epidemic periods.

First occurrence of Rift Valley fever outbreak in Niger, 2016.

Rift Valley fever (RVF) is a mosquito‐borne viral zoonosis causing abortions and high mortality among animals, whereas in humans, the disease is usually mild or asymptomatic. In September 2016, the Republic of Niger declared the first RVF outbreak in the northern region of Tahoua near the Malian border. This study describes the outbreak and reports the results of serological and molecular investigations of the human and animal samples collected. Serum samples from both human and animal suspected cases have been confirmed at the Centre de Recherche Médicale et Sanitaire (CERMES) and the Laboratoire Centrale d'Elevage (LABOCEL) public health and animal reference laboratories, respectively. Techniques for biological confirmation were real time reverse transcription polymerase chain reaction (RT‐PCR) and enzyme linked immunosorbent assay (ELISA). Phylogenetic trees were established after genetic sequencing of the small and medium segments of the RVF virus (RVFV) genome. Out of the 399 human samples collected, 17 (4.3%) were confirmed positive for RVFV. Overall, 33 (8.3%) deaths occurred out of which five (29%) were among the 17 confirmed cases. Regarding animals, 45 samples were tested, three of which were RT‐PCR positive and 24 were IgG positive. The phylogenetic analyses showed that the Niger strains clustered with Senegal 2013 and Mauritania 2015 RVFV strains. This first outbreak of RVF was very challenging for public and animal health laboratories in Niger. Besides resulting in human deaths, important loss of cattle has been reported. Therefore, vigilance has to be strengthened emphasising vector control strategies and active surveillance among animals.

Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep.

Rift Valley fever (RVF) is a mosquito-borne disease that affects both ruminants and humans, with epidemics occurring more frequently in recent years in Africa and the Middle East, probably as a result of climate change and intensified livestock trade. Sheep necropsied during the 2010 RVF outbreak in South Africa were examined by histopathology and immunohistochemistry (IHC). A total of 124 sheep were available for study, of which 99 cases were positive for RVF. Multifocal-random, necrotizing hepatitis was confirmed as the most distinctive lesion of RVF cases in adult sheep. Of cases where liver, spleen, and kidney tissues were available, 45 of 70 had foci of acute renal tubular epithelial injury in addition to necrosis in both the liver and spleen. In some cases, acute renal injury was the most significant RVF lesion. Immunolabeling for RVFV was most consistent and unequivocal in liver, followed by spleen, kidney, lung, and skin. RVFV antigen-positive cells included hepatocytes, adrenocortical epithelial cells, renal tubular epithelial cells, macrophages, neutrophils, epidermal keratinocytes, microvascular endothelial cells, and vascular smooth muscle. The minimum set of specimens to be submitted for histopathology and IHC to confirm or exclude a diagnosis of RVFV are liver, spleen, and kidney. Skin from areas with visible crusts and lung could be useful additional samples. In endemic areas, cases of acute renal tubular injury should be investigated further if other more common causes of renal lesions have already been excluded. RVFV can also cause an acute infection in the testis, which requires further investigation.

Approaches of the JICA-AMED SATREPS Project to Controlling Outbreaks of Yellow Fever and Rift Valley Fever in Kenya

Nagasaki University has conducted a JICA-AMED SATREPS project entitled “Development of Rapid Diagnostics and the Establishment of an Alert System for Outbreaks of Yellow Fever and Rift Valley Fever in Kenya.” This project, which ran for the 5-year period from January 2012 to January 2017, aimed to tackle yellow fever and Rift Valley fever in Kenya, as the name implies. The project was carried out in conjunction with the Kenya Medical Research Institute (KEMRI) and the Ministry of Health (MOH) of Kenya. The specific aims of this project were (1) the development of new diagnostics, (2) the strengthening of reference laboratories, and (3) the development of a disease outbreak alert system, particularly to control outbreaks of yellow fever (YF) and Rift Valley fever (RVF). The RVF virus IgM-capture ICT kit, “ImmunoLineTM,” and YF virus IgM-capture ELISA, “KemLisaTM,” were developed as new point-of-care tests. A neutralization test for the confirmation of these arbovirus infections was introduced to the central and local reference laboratories. This project also developed a new disease outbreak alert system, “mSOS,” which the MOH of Kenya has extended nationwide by integrating it into the national health information system (DHIS2).

Special Issue on Infectious Disease Control in SATREPS Projects

The Science and Technology Research Partnership for Sustainable Development (SATREPS) is a Japanese government program that promotes international joint research. The program is structured as a collaboration between the Japan Science and Technology Agency (JST) and the Japan International Cooperation Agency (JICA). The program includes various fields, such as Environment and Energy, Bioresources, Disaster Prevention and Mitigation, and Infectious Disease Control, and a total 52 projects were currently in progress as of May, 2018. It is expected that the promotion of international joint research under this program will enable Japanese research institutions to conduct research more effectively in fields and having targets that make it advantageous to do that research in developing countries, including countries in Latin America and the Caribbean, Asia, and Africa. Recently, SATREPS projects in the field of Infectious Disease have been but under the control of the Japan Agency for Medical Research and Development (AMED). Although adult maladies, such as malignant tumors, heart disease, and cerebral apoplexy, are major causes of death in the developed countries including Japan, infectious diseases are still responsible for the high mortality rates in developing countries. Therefore, Infectious Disease Control is the important field of SATREPS. Infectious Disease Control projects are progressing in several countries, including Kenya, Zambia, Bangladesh, the Philippines, and Brazil, and various infectious diseases and pathogens have been targeted. In this special issue on Infectious Disease Control, the following reports from three projects have been selected: “The JICA-AMED SATREPS Project to Control Outbreaks of Yellow Fever and Rift Valley Fever in Kenya” by Nagasaki University, “Comprehensive Etiological and Epidemiological Study on Acute Respiratory Infections in Children in the Philippines” by Tohoku University, and “International Joint Research on Antifungal Resistant Fungi in Brazil” by Chiba University. These projects include viral, bacterial, and fungal infections. If they become available, further supplementary reports from other projects in this field will be published in a future issue.

Sero-prevalence and spatial distribution of Rift Valley fever infection among agro-pastoral and pastoral communities during Interepidemic period in the Serengeti ecosystem, northern Tanzania

BackgroundIn the past two decades, Rift Valley Fever (RVF) outbreaks have been reported twice in Tanzania, with the most recent outbreak occurring in 2006/07. Given the ecology and climatic factors that support mosquito vectors in the Serengeti ecosystem, we hypothesized a continued transmission of RVF virus (RVFV) during interepidemic periods. This study was carried out to determine sero-prevalence, spatial distribution and factors associated with RVF in at-risk agro-pastoral and pastoral communities in the Serengeti Ecosystem in northern Tanzania.MethodsA cross sectional study was carried out to establish the general exposure to RVFV by detecting anti–RVFV IgG and anti–RVFV IgM using ELISA techniques. The health facilities where human subjects were blood sampled concurrent with interviews included Bunda District Designated Hospital, Wasso DDH, Endulen hospital, Arash, Malambo, Olbabal, and Piyaya dispenaries (Ngorongoro district) and Nyerere DDH (Serengeti district) respectively. In addition, human subjects from Lamadi ward (Busega district) were recruited while receiving medical service at Bunda DDH. We conducted logistic regression to assess independent risk factor and mapped the hotspot areas for exposure to RVFV.ResultsA total of 751 subjects (males = 41.5%; females = 58.5%) with a median age of 35.5 years were enrolled at out-patient clinics. Of them, 34 (4.5, 95%CI 3.3–6.3%) tested positive for anti–RVFV IgG. Of the 34 that tested positive for anti–RVFV IgG, six (17.6%) tested positive for anti–RVFV IgM. Odds of exposure were higher among pastoral communities (aOR 2.9, 95% C.I: 1.21–6.89, p < 0.01), and agro-pastoral communities residing in Ngorongoro District (aOR 1.8, 95% C.I 1.14–3.39, p = 0.03). Hotspot areas for exposure to RVFV were Malambo, Olbalbal and Piyaya wards in Ngorongoro district, and Lamadi ward in Busega district.ConclusionsThe study found both previous and recent exposure of RVFV in humans residing in the Serengeti ecosystem as antibodies against both IgG and IgM were detected. Detection of anti-RVF IgM suggests an ongoing transmission of RVFV in humans during inter-epidemic periods. Residents of Ngorongoro district were most exposed to RVFV compared to Bunda and Serengeti districts. Therefore, the risk of exposure to RVFV was higher among pastoral communities compared to farming communities.

Prevalence of Rift Valley Fever Virus in Febrile Malaria Patients using Serological and Molecular-based Evidence

Abstract Rift Valley fever virus (RVFV) is a zoonotic virus classified as category A priority pathogen. Rift Valley fever (RVF) has been poorly investigated in Nigeria with the infection among Nigerians last reported in 1996. Two hundred (200) febrile subjects with symptoms of malaria attending local hospitals in Ilorin, Nigeria were investigated for malaria, malaria positive subjects were investigated for the presence of RVF. Malaria screening was done using Carestart TM malaria HRP2(pf), while RVF antibodies were tested for using anti-RVF IgM ELISA. Molecular identification of the viral genome was carried out using RNA extraction (QIAGEN) and quantitative Polymerase Chain Reaction (qPCR). Of the 200 subjects tested for malaria infection, 93 (46.5%) were positive, while 20 (21.5%) of the 93 subjects were seropositive for RVF. RVF virus genome was found in 5 (25%) of the 20 positive subjects. The high prevalence of RVF among malaria positive subjects show that there is a risk of a RVF outbreak if its prevalence remains unchecked.

Diagnosis of a Suspected Rift Valley Fever Outbreak Using Capture IgM ELISA in the Sudan

Diagnosis of a Suspected Rift Valley Fever Outbreak Using Capture IgM ELISA in the Sudan

Enhanced surveillance for Rift Valley Fever in livestock during El Niño rains and threat of RVF outbreak, Kenya, 2015-2016

BackgroundIn mid-2015, the United States’ Pandemic Prediction and Forecasting Science and Technical Working Group of the National Science and Technology Council, Food and Agriculture Organization Emergency Prevention Systems, and Kenya Meteorological Department issued an alert predicting a high possibility of El-Niño rainfall and Rift Valley Fever (RVF) epidemic in Eastern Africa.Methodology/Principal findingsIn response to the alert, the Kenya Directorate of Veterinary Services (KDVS) carried out an enhanced syndromic surveillance system between November 2015 and February 2016, targeting 22 RVF high-risk counties in the country as identified previously through risk mapping. The surveillance collected data on RVF-associated syndromes in cattle, sheep, goats, and camels from >1100 farmers through 66 surveillance officers. During the 14-week surveillance period, the KDVS received 10,958 reports from participating farmers and surveillance officers, of which 362 (3.3%) had at least one syndrome. The reported syndromes included 196 (54.1%) deaths in young livestock, 133 (36.7%) abortions, and 33 (9.1%) hemorrhagic diseases, with most occurring in November and December, the period of heaviest rainfall. Of the 69 herds that met the suspect RVF herd definition (abortion in flooded area), 24 (34.8%) were defined as probable (abortions, mortalities in the young ones, and/or hemorrhagic signs) but none were confirmed.Conclusion/SignificanceThis surveillance activity served as an early warning system that could detect RVF disease in animals before spillover to humans. It was also an excellent pilot for designing and implementing syndromic surveillance in animals in the country, which is now being rolled out using a mobile phone-based data reporting technology as part of the global health security system.

A phytosociological analysis and description of wetland vegetation and ecological factors associated with locations of high mortality for the 2010-11 Rift Valley fever outbreak in South Africa.

Rift Valley fever (RVF) is endemic in Africa and parts of the Middle East. It is an emerging zoonotic disease threat to veterinary and public health. Outbreaks of the disease have severe socio-economic impacts. RVF virus emergence is closely associated with specific endorheic wetlands that are utilized by the virus’ mosquito vectors. Limited botanical vegetation surveys had been published with regard to RVF virus (RVFV) ecology. We report on a phytosociological classification, analysis and description of wetland vegetation and related abiotic parameters to elucidate factors possibly associated with the 2010–2011 RVFV disease outbreak in South Africa. The study sites were located in the western Free State and adjacent Northern Cape covering an area of ~40,000 km2 with wetlands associated with high RVF mortality rates in livestock. Other study sites included areas where no RVF activity was reported during the 2010–11 RVF outbreak. A total of 129 plots (30 m2) were selected where a visible difference could be seen in the wetland and upland vegetation. The Braun-Blanquet method was used for plant sampling. Classification was done using modified Two-Way Indicator Species Analysis. The vegetation analysis resulted in the identification of eight plant communities, seven sub-communities and two variants. Indirect ordination was carried out using CANOCO to investigate the relationship between species and wetland ecology. The study also identified 5 categories of wetlands including anthropogenic wetlands. Locations of reported RVF cases overlapped sites characterized by high clay-content soils and specific wetland vegetation. These findings indicate ecological and environmental parameters that represent preferred breeding habitat for RVFV competent mosquito vectors.

The first reported human Rift Valley Fever outbreak in Uganda, 2016

Introduction : on 8 March 2016, the Ministry of Health received a report of a suspected case of viral hemorrhagic fever (VHF) in Kabale Regional Referral Hospital. By 15th March, there were two laboratory confirmed cases of Rift Valley Fever (RVF). We conducted the investigation to assess the scope of the outbreak, identify its source and risk factors in order to inform public health interventions for controlling the outbreak. Methods : a suspected case was defined as acute onset of fever (> 37.5°C), negative malaria test, and at least two of the following three symptoms: Headache, Muscle or joint pain and any gastroenteritis symptom (nausea, vomiting, abdominal pain, and diarrhea). A Probable Case was any person meeting the suspect case definition with deranged liver functions tests plus at least one of the following; bleeding symptoms, such as: bleeding from the nose, vomiting blood, coughing out blood (without history of TB), blood in stool, blood in urine; sudden change in vision, jaundice, any unexplained death. A confirmed case was a suspected or probable case that is laboratory confirmed by detection of RVF nucleic acid by reverse-transcriptase polymerase chain reaction (RT-PCR) or demonstration of serum IgM or IgG antibodies by ELISA. We found cases by going to the affected communities and health facilities in the catchment areas where the confirmed cases came from. Results : the investigation revealed 2 confirmed cases. In-depth interviews revealed that the symptom onset for the primary case was February 13th while onset date for the secondary case was February 18th. A review of the records in the health centers in the vicinity of the area where the primary case originated also did not reveal any increase in febrile illnesses. Prior to symptom onset of the primary case, one farmer reported 3 successive goat abortions every month from October 2015 to December 2015. In February 2015, one farmer also reported 3 cow abortions within the same week. Conclusion : There appears to be an outbreak among the livestock however there is no increase in febrile illnesses in the community. Health education should be done in the community to promote use of mosquito nets and protection of abattoir workers. The ministry of Agriculture, Animal Industries and Fisheries (MAAIF) should work with the Ministry of Health to assess the existence of the virus among the animals and mosquitoes. MAAIF should also ensure enforcement of the laws prohibiting the sale and consumption of sick or dead animals. All animals in the area should be vaccinated against RVF and health workers should be sensitized to consider RVF as a differential diagnosis in non-malaria febrile illness.

Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries.

Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

Rift Valley fever virus and European mosquitoes: vector competence of Culex pipiens and Stegomyia albopicta (= Aedes albopictus).

Rift Valley fever (RVF) is a mosquito-borne disease caused by the Rift Valley fever virus (RVFV). Rift Valley fever affects a large number of species, including human, and has severe impact on public health and the economy, especially in African countries. The present study examined the vector competence of three different European mosquito species, Culex pipiens (Linnaeus, 1758) form molestus (Diptera: Culicidae), Culex pipiens hybrid form and Stegomyia albopicta (= Aedes albopictus) (Skuse, 1894) (Diptera: Culicidae). Mosquitoes were artificially fed with blood containing RVFV. Infection, disseminated infection and transmission efficiency were evaluated. This is the first study to assess the transmission efficiency of European mosquito species using a virulent RVFV strain. The virus disseminated in Cx.pipiens hybrid form and in S.albopicta. Moreover, infectious viral particles were isolated from saliva of both species, showing their RVFV transmission capacity. The presence of competent Cx.pipiens and S.albopicta in Spain indicates that an autochthonous outbreak of RVF may occur if the virus is introduced. These findings provide information that will help health authorities to set up efficient entomological surveillance and RVFV vector control programmes.