Informing Rift Valley Fever preparedness by mapping seasonally varying environmental suitability.

BACKGROUND: Rift Valley Fever (RVF) poses a threat to human and animal health throughout much of Africa and the Middle East and has been recognized as a global health security priority and a key preparedness target. METHODS: We combined RVF occurrence data from a systematic literature review with animal notification data from an online database. Using boosted regression trees, we made monthly environmental suitability predictions from January 1995 to December 2016 at a 5 × 5-km resolution throughout regions of Africa, Europe, and the Middle East. We calculated the average number of months per year suitable for transmission, the mean suitability for each calendar month, and the "spillover potential," a measure incorporating suitability with human and livestock populations. RESULTS: Several countries where cases have not yet been reported are suitable for RVF. Areas across the region of interest are suitable for transmission at different times of the year, and some areas are suitable for multiple seasons each year. Spillover potential results show areas within countries where high populations of humans and livestock are at risk for much of the year. CONCLUSIONS: The widespread environmental suitability of RVF highlights the need for increased preparedness, even in countries that have not previously experienced cases. These maps can aid in prioritizing long-term RVF preparedness activities and determining optimal times for recurring preparedness activities. Given an outbreak, our results can highlight areas often at risk for subsequent transmission that month, enabling decision-makers to target responses effectively.

Rift Valley fever virus: Unanswered questions.

This mosquito-borne pathogen of humans and animals respects no international or geographic boundaries. It is currently found in parts of Africa and the Arabian Peninsula where periodic outbreaks of severe and fatal disease occur, and threatens to spread into other geographic regions. In recent years, modern molecular techniques have led to many breakthroughs deepening our understanding of the mechanisms of RVFV virulence, phylogenetics, and the creation of several next-generation vaccine candidates. Despite tremendous progress in these areas, other challenges remain in RVF disease pathogenesis, the virus life-cycle, and outbreak response preparedness that deserve our attention. Here we discuss and highlight ten key knowledge gaps and challenges in RVFV research. Answers to these key questions may lead to the development of new effective therapeutics and enhanced control strategies for this serious human and veterinary health threat.

Rift Valley fever in kidney transplant recipient returning from Mali with viral RNA detected in semen up to four months from symptom onset, France, autumn 2015.

A 29-year-old kidney transplant recipient returning from Mali was diagnosed with Rift Valley fever (RVF) in France in autumn 2015. The patient was immunosuppressed due to his renal transplant. IgM and IgG specific to RVF virus (RVFV) were detected in cerebrospinal fluid and blood up to two months after symptom onset, whereas in urine, RVFV genomic RNA was detected by RT-PCR up to three months, and in semen up to four months post symptom onset.

Lay perceptions of risk factors for Rift Valley fever in a pastoral community in northeastern Kenya.

BACKGROUND: Human behavioral factors have been found to be central in the transmission of Rift Valley fever. Consumption of contaminated meat and milk in particular have been identified as one of the key risk factors for the transmission of Rift Valley fever in humans. In pastoral communities, livestock is the main source of livelihood from which many benefits such as food as well as economic and cultural services are derived. Zoonotic diseases therefore have a great impact on pastoral communities livelihoods. However, lay perceptions regarding the transmission of these diseases including Rift Valley fever hampers their effective control. This study investigated the lay perceptions of risks for Rift Valley fever transmission in a pastoral community in northeastern Kenya. METHODS: A qualitative study was carried out in Ijara district, Kenya which was one of the hotspots of Rift Valley during the 2006/2007 outbreak. Data were collected using focus group discussions and narratives guided by checklists. Eight focus group discussions consisting of 83 participants and six narratives were conducted. Data was transcribed, coded and analysed according to Emergent themes. RESULTS: The participants reported that they had experienced Rift Valley fever in their livestock especially sheep and in humans both in 1997/1998 and 2006/2007. However, they believed that infections in humans occurred as a result of mosquito bites and had little to do with their consumption of meat, milk and blood from infected livestock. The participants in this study indicated that they had heard of the risks of acquiring the disease through consumption of livestock products but their experiences did not tally with the information they had received hence to them, Rift Valley fever was not transmissible through their dietary practices. CONCLUSIONS: Though the communities in this region were aware of Rift Valley fever, they did not have elaborate information regarding the disease transmission dynamics to humans. To avoid misconception about transmission of the disease, intervention strategies, require to be accompanied by comprehensive explanations of the dynamics of its transmission. It is necessary to develop appropriate interventions that take into consideration, lay perceptions of risk factors for the disease and communities' livelihood strategies.

Seroepidemiological Study of Interepidemic Rift Valley Fever Virus Infection Among Persons with Intense Ruminant Exposure in Madagascar and Kenya.

In this cross-sectional seroepidemiological study we sought to examine the evidence for circulation of Rift Valley fever virus (RVFV) among herders in Madagascar and Kenya. From July 2010 to June 2012, we enrolled 459 herders and 98 controls (without ruminant exposures) and studied their sera (immunoglobulin G [IgG] and IgM through enzyme-linked immunosorbent assay [ELISA] and plaque reduction neutralization test [PRNT] assays) for evidence of previous RVFV infection. Overall, 59 (12.9%) of 459 herders and 7 (7.1%) of the 98 controls were positive by the IgG ELISA assay. Of the 59 ELISA-positive herders, 23 (38.9%) were confirmed by the PRNT assay (21 from eastern Kenya). Two of the 21 PRNT-positive study subjects also had elevated IgM antibodies against RVFV suggesting recent infection. Multivariate modeling in this study revealed that being seminomadic (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 2.1-15.4) was most strongly associated with antibodies against RVFV. Although we cannot know when these infections occurred, it seems likely that some interepidemic RVFV infections are occurring among herders. As there are disincentives regarding reporting RVFV outbreaks in livestock or wildlife, it may be prudent to conduct periodic, limited, active seroepidemiological surveillance for RVFV infections in herders, especially in eastern Kenya.

Knowledge, attitudes and practices on Rift Valley fever among agro pastoral communities in Kongwa and Kilombero districts, Tanzania.

BACKGROUND: Rift valley fever (RVF) is a re-emerging viral vector-borne disease with rapid global socio-economic impact. A large RVF outbreak occurred in Tanzania in 2007 and affected more than half of the regions with high (47 %) case fatality rate. Little is known about RVF and its dynamics. A cross sectional study was conducted to assess the knowledge, attitudes and practices regarding RVF in Kongwa and Kilombero districts, Tanzania. METHODS: We conducted a cross sectional survey among a randomly selected sample of individuals in 2011. We administered questionnaires to collect data on demographic characteristics, knowledge on symptoms, mode of transmission, prevention, attitudes and health seeking practices. RESULTS: A total of 463 community members participated in this study. The mean (±SD) age was 39.8 ± 14.4 years and 238 (51.4 %) were female. Majority of respondents had heard of RVF. However, only 8.8 % knew that mosquitoes were transmitting vectors. Male respondents were more likely to have greater knowledge about RVF. A small proportion mentioned clinical signs and symptoms of RVF in animals while 73.7 % mentioned unhealthy practices related to handling and consumption of dead animals. Thorough boiling of milk and cooking of meat were commonly mentioned as preventive measures for RVF. Majority (74.6 %) sought care for febrile illness at health facilities. Few (24.3 %) reported the use of protective gears to handle dead/sick animal while 15.5 % were consuming dead animals. CONCLUSION: Our study highlights the need to address the limited knowledge about RVF and promoting appropriate and timely health seeking practices. Rift valley fever outbreaks can be effectively managed with collaborative efforts of lay and professional communities with a shared perception that it poses a serious threat to public and animal health. The fact that this study was conducted in "high risk transmission areas" warrants further inquiry in other geographic regions with relatively low risk of RVF.

Factors associated with severe human Rift Valley fever in Sangailu, Garissa County, Kenya.

BACKGROUND: Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya. METHODOLOGY/PRINCIPAL FINDINGS: A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ≤15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool for RVF screening during epidemics in high-risk rural settings.

Inter-epidemic acquisition of Rift Valley fever virus in humans in Tanzania.

BACKGROUND: In East Africa, epidemics of Rift Valley fever (RVF) occur in cycles of 5-15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP) generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection. METHODOLOGY: Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression. FINDINGS: RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71). Four of 16 (25.0%) IgM positives and 11/71 (15.5%) of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2-14.5) and risk was elevated with age (odds ratio (OR) 1.03 per year; 95% CI 1.01-1.04), among milkers (OR 2.19; 95% CI 1.23-3.91), and individuals eating raw meat (OR 4.17; 95% CI 1.18-14.66). Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42-6.48) than those that do not keep livestock. CONCLUSION: There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study's population. However, at least part of RVFV transmission appears to have occurred through bites of infected mosquitoes.

Risk factors associated with human Rift Valley fever infection: systematic review and meta-analysis.

OBJECTIVE: To identify risk factors for human Rift Valley fever virus (RVFV) infection. METHODS: A systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies. RESULTS: Being male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta-analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids. CONCLUSIONS: Based on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation.

[Experimental and clinicolaboratory evaluation of complex therapy efficacy in arboviral infections].

Search for drugs efficient in prophylaxis and treatment of dangerous infections (especially arboviral ones) is rather actual, since no specific therapy is available. Many-year investigations of interferon inductors showed that they had immunomodulating, antiviral and antiinflammatory effects and were low toxic. The present study demonstrated that the protective effect was the following: Venezuelan equine encephalitis (VEE)--cycloferon > amixin = ridostin, Rift Valley fever (RVF)--cycloferon > amixin > ridostin, predator pox (PP)--cycloferon > amixin = ridostin, that was obvious that cycloferon was the most active agent in the treatment of VEE, RVF and PP, thus making it possible to acknowledge its priority in prophylaxis and therapy of dangerous viral infections (DVI). Ribavirin in combination with cycloferon solution or cycloferon tablets provided shorter periods of the fever, minimized the intoxication syndrome, promoted earlier resolution of hemorrhagic eruption and lowered the frequency of complications, which was in favour of the disease prognosis.

Rift Valley fever--a threat for Europe?

Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants, caused by a Phlebovirus (Bunyaviridae). It is widespread in Africa and has recently spread to Yemen and Saudi Arabia. RVF epidemics are more and more frequent in Africa and the Middle East, probably in relation with climatic changes (episodes of heavy rainfall in eastern and southern Africa), as well as intensified livestock trade. The probability of introduction and large-scale spread of RVF in Europe is very low, but localized RVF outbreaks may occur in humid areas with a large population of ruminants. Should this happen, human cases would probably occur in exposed individuals: farmers, veterinarians, slaughterhouse employees etc. Surveillance and diagnostic methods are available, but control tools are limited: vector control is difficult to implement, and vaccines are only available for ruminants, with either a limited efficacy (inactivated vaccines) or a residual pathogenic effect. The best strategy to protect Europe and the rest of the world against RVF is to develop more efficient surveillance and control tools and to implement coordinated regional monitoring and control programmes.

A Rift Valley fever atlas for Africa.

Rift Valley fever (RVF) epidemics have serious consequences for human and animal health and the livestock trade. Recent epidemics have occurred in previously unaffected regions, increasing concerns that the geographical range of RVF will continue to expand. We conducted an extensive, systematic review of the literature to obtain serological data for RVF in Africa, collected between 1970 and 2000 from human, livestock and wild ungulate populations. Aims were to calculate sub-national estimates of RVF infection prevalence and to define areas where no information was available. We presented the data (aggregated at the first administrative level of countries) using a geographical information system. Data from 71 publications were used to build a spatially explicit Bayesian logistic-regression model, with spatial and non-spatial random effects, allowing us to identify clusters of high and low RVF seroprevalence, and fixed effects that described the disparate nature of the survey subjects and methods. Significant high-prevalence clusters encompassed areas that had experienced epidemics during the late 20th century and significant low-prevalence clusters were located in contiguous areas of Western and Central Africa.

Rift valley fever.

Rift Valley fever is a viral disease that affects domestic animals and humans. In humans, Rift Valley fever causes a flu-like disease but occasionally leads to high morbidity and mortality. The disease is generally known in the African continent. However, cases started to appear in Saudi Arabia and Yemen. The objective of this review is to give a general briefing about the epidemiology, ecology and management of the disease.

Pathogenesis of a phleboviral infection (Punta Toro virus) in golden Syrian hamsters.

The hamster, Mesocricetus auratus, was examined as a possible model for investigating the poorly defined pathogenesis of the family Bunyaviridae, genus Phlebovirus. Punta Toro virus (PTV) isolates from Eastern Panama were highly virulent for two outbred and five inbred hamster strains, while isolates from western Panama were of low virulence. The Adames strain (eastern Panama) of PTV (LD50 approximately 1 PFU, sc) caused an acute fatal disease (average survival time, 3.8 days) in 10-week-old Lak: LVG (SYR) hamsters. Severe necrosis of the liver, spleen, and small intestine was associated with extensive expression of viral antigen in these organs. The Balliet strain (western Panama) of PTV (LD50 greater than 6 log10 PFU, subcutaneously) caused a mild hepatocellular infection with peak viral liver titers of 3-4 log10 PFU/g compared to 8-9 log10 PFU/g for the Adames strain. We observed histological lesions in the red pulp of the spleen or the lamina propria of the small intestine with the Adames strain. Lesions in the hamsters had characteristics of disseminated intravascular coagulation (DIC). The PTV-hamster model shares similarities to Rift Valley fever (phleboviral disease), which causes fatal disease in man and domesticated ruminants.

Pathogenesis of viral hemorrhagic fevers: Rift Valley fever and Lassa fever contrasted.

Although many viral infections have on occasion been associated with hemorrhagic complications, infection with any of several RNA viruses regularly results in vascular involvement and the syndrome called viral hemorrhagic fever (VHF). In spite of clinically useful similarities among various VHFs, there are significant differences in their pathogenesis and clinical evolution; these are often related to characteristics of their viral taxon. Infection with Rift Valley fever (RVF) virus, a phlebovirus, appears to be regulated by interferon and terminated by neutralizing antibody. In contrast, Lassa fever (LF) virus, an arenavirus, is resistant to interferon, and LF is terminated by cellular immune effector mechanisms. The lytic virus-cell interaction typical of RVF virus suggests its major effects occur by direct, virus-induced cellular necrosis, particularly in the liver. In the primate RVF model, disseminated intravascular coagulation (DIC) may be important. LF virus--characteristically noncytopathic--may exert its effects through induction of mediator secretion from infected macrophages. DIC does not appear to be a central pathogenetic mechanism in LF. Pichinde virus, which is not pathogenic for humans, provides an alternate model for study of LF. Infected guinea pigs do not show histologic lesions that could explain their body wasting, cardiovascular deterioration, and pulmonary edema. In the heart, for example, loss of tissue mass, protein, and contractile function proceed without direct viral involvement or myocarditis. Sulfidopeptide leukotrienes have been implicated as one relevant soluble mediator participating in the disease state.

The gerbil, Meriones unguiculatus, a model for Rift Valley fever viral encephalitis.

The gerbil, Meriones unguiculatus, was investigated as a model for the encephalitic form of Rift Valley fever. Resistance to necrotizing encephalitis was age-dependent with 100% mortality at 3 weeks, decreasing to approximately 20% by 10 weeks of age in outbred gerbils inoculated subcutaneously. Fatal encephalitis in the 10-week-old adults was dose-independent [1.0-7.0 log10 plaque forming units (PFU), subcutaneously]. Viral replication and histological lesions were followed serially throughout the course of the infection in young (4 week) and adult (10 week) gerbils. Viral replication was evident in the brain tissue of young gerbils from day 4 (3.0 log10 PFU/g) through day 7 (6.0 log10 PFU/g), the last day the young gerbils survived. Virus was only detected in the brain tissue of a single adult gerbil (day 7, 4.0 log10 PFU/g) of 26 studied in the sequential survey. In contrast, two moribund adult gerbils had approximately 7.0 log10 PFU/g of virus in the brain tissue on days 8 and 11. When young and adult gerbils were inoculated with a low dose (50 PFU) of virus intracranially, there were no detectable differences in the course of infection with all animals succumbing to fatal necrotizing encephalitis approximately 7 days postinoculation. The young gerbil becomes the first animal model in which uniformly fatal RVFV-induced encephalitis is produced without significant extraneural lesions.