Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.

Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

Assessment of community awareness and risk perceptions of zoonotic causes of abortion in cattle at three selected livestock-wildlife interface areas of Zimbabwe.

A study was conducted to assess the awareness of cattle abortions due to brucellosis, Rift Valley fever (RVF) and leptospirosis, and to compare frequencies of reported abortions in communities living at the periphery of the Great Limpopo Transfrontier Conservation Area in southeastern Zimbabwe. Three study sites were selected based on the type of livestock-wildlife interface: porous livestock-wildlife interface (unrestricted); non-porous livestock-wildlife interface (restricted by fencing); and livestock-wildlife non-interface (totally absent or control). Respondents randomly selected from a list of potential cattle farmers (N = 379) distributed at porous (40·1%), non-interface (35·5%) and non-porous (26·4%), were interviewed using a combined close- and open-ended questionnaire. Focus group discussions were conducted with 10-12 members of each community. More abortions in the last 5 years were reported from the porous interface (52%) and a significantly higher per cent of respondents from the porous interface (P < 0·05) perceived wildlife as playing a role in livestock abortions compared with the other interface types. The odds of reporting abortions in cattle were higher in large herd sizes (odds ratio (OR) = 2·6; 95% confidence interval (CI) 1·5-4·3), porous (OR = 1·9; 95% CI 1·0-3·5) and non-porous interface (OR = 2·2; 95% CI 1·1-4·3) compared with livestock-wildlife non-interface areas. About 21·6% of the respondents knew brucellosis as a cause of abortion, compared with RVF (9·8%) and leptospirosis (3·7%). These results explain to some extent, the existence of human/wildlife conflict in the studied livestock-wildlife interface areas of Zimbabwe, which militates against biodiversity conservation efforts. The low awareness of zoonoses means the public is at risk of contracting some of these infections. Thus, further studies should focus on livestock-wildlife interface areas to assess if the increased rates of abortions reported in cattle may be due to exposure to wildlife or other factors. The government of Zimbabwe needs to launch educational programmes on public health awareness in these remote areas at the periphery of transfrontier conservation areas where livestock-wildlife interface exists to help mitigate the morbidity and mortality of people from some of the known zoonotic diseases.

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.

Distribution of viral antigen in tissues of new-born lambs infected with Rift Valley fever virus.

The distribution of Rift Valley fever (RVF) viral antigen was studied by immunohistochemistry in the liver, spleen, prescapular lymph node, lungs and kidneys ot eight experimentally infected new-born lambs and in four new-born lambs that died of RVF during the 1974-75 RVF epidemic. The eight experimentally infected lambs were euthanazed at 6, 12, 18, 24, 30, 33, 48 and 51 h post-infection (p.i.), respectively. Immunohistochemical staining utilized polyclonal hyperimmune mouse ascites fluid to RVF virus and peroxidase-diaminobenzidine was substrate. Virus antigen was most prominent in the liver and was detected as early as 18 h p.i. in the cytoplasm of hepatocytes that were sparsely scattered throughout the lobules. At 24-33 h p.i. antigen was also present in or adjacent to small foci of hepatocellular necrosis. At 48-51 h p.i. and in one of the field cases, positive staining was widespread and most consistently present in the cytoplasm of large numbers of degenerated or necrotic hepatocytes and in a new acidophilic bodies. Immunohistochemical staining was rarely observed in hepatocyte nuclei. Almost diffuse histochemical staining was observed in disintegrated cells and in the cytoplasm of necrotic hepatocytes throughout the liver in the other three field cases with pannecrosis; only the primary foci necrosis and a narrow periportal rim of intact hepatocytes did not stain. No staining was observed in bile duct epithelium, endothelial and Kupffer cells in the initial stages of Infection, supporting the contention that hepatocytes constitute the primary site of RVF virus replication in new-born lambs. Few cells stained positively in the spleen, prescapular lymph node, lungs and kidneys.

Comparison of the pathogenicity for pregnant sheep of Rift Valley fever virus and a live attenuated vaccine.

A live attenuated mutant of Rift Valley fever virus, MV P12, was previously shown to be non-pathogenic in young lambs, but capable of producing protective immunity. The studies reported here show that the abortion in sheep caused by an infection with virulent virus is the result of necrosis of the maternal villi and cotyledons arising from an acute inflammation of the maternal caruncles. Pregnant ewes infected with the attenuated mutant virus MV P12 showed none of these lesions in the placenta and gave birth to healthy lambs. Colostrum from ewes infected with MV P12 virus was able to induce protective immunity in the offspring. These data along with previously published results suggest that the mutant virus MV P12 is an excellent candidate for use as a live attenuated veterinary vaccine.

Rift Valley fever on the east coast of Madagascar.

In March 1990, a Rift Valley fever virus (RVFV) outbreak was suspected in the district of Fenerive on the east coast of Madagascar after an abnormally high incidence of abortions and disease in livestock. Sera from humans and cattle were tested for RVFV antibodies by immunofluorescence assay (IFA) and ELISA-IgM capture. Sera and mosquitoes collected in the same area were tested for virus isolation by tissue culture and suckling mouse intracerebral inoculation, and for antigen detection by an ELISA antigen capture assay. Among cattle from the area, RVFV antibody prevalence was 58.6% by IFA and 29.6% by ELISA-IgM. In contrast, human populations in the same area had a lower RVFV antibody prevalence, with 8.01% IFA and 5.4% IgM-positive sera. No RVFV antigen was detected and virus isolation was unsuccessful from the sera and mosquito pools tested. Different hypotheses concerning the emergence and diffusion of RVFV in this area and the occurrence of the outbreak are discussed.

Antigenic analysis of Rift Valley fever virus isolates: monoclonal antibodies distinguish between wild-type and neurotropic virus strains.

Rift Valley fever virus (RVFV) isolates from southern Africa were analysed for possible strain variation using monoclonal antibodies prepared against the South African prototype RVF 1830 strain. By the indirect immunofluorescence antibody assay and neutralization tests, the wild type southern African isolates were found to be antigenically similar to RVFV strains from other parts of Africa. In contrast, differences in several biologically important neutralizing and haemagglutination epitopes on both the G1 and G2 glycoproteins of the attenuated Onderstepoort veterinary vaccine and the Smithburn neurotropic strain were identified.

Infection of inbred rat strains with Rift Valley fever virus: development of a congenic resistant strain and observations on age-dependence of resistance.

A congenic rat strain (WF.LEW) was derived from the susceptible Wistar-Furth (WF) (background strain) and the resistant LEW (donor strain) inbred strains and was used to evaluate the phenotypic expression of a dominant Mendelian gene that confers resistance to fatal hepatic disease caused by the ZH501 strain of Rift Valley fever virus (RVFV). Resistance to hepatic disease developed gradually with age, with full expression at approximately 10 weeks in the WF.LEW and LEW rat strains. The ZH501 strain caused fatal hepatitis in WF rats regardless of age. However, resistance to the SA75 RVFV strain (relatively non-pathogenic for adult rats), was age- and dose-dependent in both WF and LEW rats. The resistance gene transferred to the newly derived WF.LEW congenic rat strain appears to amplify age-dependent resistance of adult rats, resulting in protection against fatal hepatic disease caused by the virulent ZH501 strain. The congenic rat strain will be a valuable asset in elucidating the mechanism of resistance to Rift Valley fever virus governed by the dominant Mendelian gene.

Isolation of Rift Valley fever virus from human peripheral blood mononuclear cells: Mauritanian epidemic.

During the Mauritanian Rift Valley fever (RVF) epidemic of 1987, peripheral blood mononuclear cells (PBMC) were studied from 78 sick patients. RVF virus (RVFV) was isolated in 5 cases, on Aedes pseudoscutellaris AP61, from both PBMC and serum. Among the 78 cases studied, RVF was proven in 19 cases (24.3%) by specific IgM detection, and in 12 cases (15.3%) by virus isolation from serum, of which 3 also exhibited anti-RVF IgM. Among the 5 PBMC-positive RVFV cases, 2 strains were isolated in the presence of specific IgM from patients presenting with neurologic signs. These observations raised the question as to the role of specific IgM in cellular infection, and suggest that, in certain cases, mononuclear cells may promote RVFV dissemination into brain cells. Further investigations need to be undertaken to determine the RVFV receptor expressed on PBMC membranes.

Comparison of in vitro and in vivo systems for propagation of Rift Valley fever virus from clinical specimens.

Several cell cultures and animals were compared for their relative sensitivity as primary isolation systems for Rift Valley fever virus (RVFV) and to determine if virulence characteristics of the isolates were altered in these systems. Eleven human sera from known cases of Rift Valley fever (RVF) were obtained from the 1987 epidemic in Mauritania and served as the source of virus for these studies. Sera were inoculated directly into cell cultures (Vero, C6/36 and DBS-FRhL-2) and animals (ICR suckling mice, Lak:LVG(SYR) hamsters and WF rats) concurrently. The cell lines provided a quick method to propagate, quantitate and identify these specimens without prior adaption. The isolates were highly virulent for suckling mice and hamsters, but not for WF rats, even after cell culture passage, which indicated that the Mauritanian isolates more closely resembled those strains from sub-Saharan Africa than those from the 1977-78 Egyptian epidemic.

Rift Valley fever infection of rhesus monkeys: implications for rapid diagnosis of human disease.

Rhesus monkeys inoculated with Rift Valley fever (RVF) virus provide a model in which serial observations of serum viral antigen and antibodies can be made. In 9 non-fatal and 3 fatal infections, either antigen or IgM enzyme-linked immunosorbent assay (ELISA) antibodies were detected in every serum sample during the acute phase. Furthermore, viral nucleic acid could be detected by filter hybridization in most samples taken on days 1 to 3. Circulation of significant quantities of viral RNA provides an additional approach to the diagnosis and study of RVF.

Antigenic and biological properties of Rift Valley fever virus isolated during the 1987 Mauritanian epidemic.

The antigenic and biological properties of three strains of Rift Valley fever virus (RVFV) isolated during the 1987 epidemic in Mauritania were compared with those of strains isolated previously in West Africa and with other selected African strains. Neither the antigenic characteristics of the Mauritanian isolates, as monitored by the binding of 59 monoclonal antibodies, nor the electrophoretic migration of the virus-specific structural and non-structural proteins were significantly different from other strains of RVFV isolated in this region or elsewhere in sub-Saharan Africa. Biological and antigenic traits which distinguished the strains isolated from the 1977 Egyptian epidemic were not associated with the Mauritanian isolates.

Viral determinants of virulence for Rift Valley fever (RVF) in rats.

Rift Valley fever viral strains or variants (RVFV) were compared with respect to (a) virulence for Wistar-Furth rats; (b) in vitro sensitivity to rat and human interferon; (c) ability to form plaques in primary hepatocyte cultures from genetically resistant or susceptible rat strains, and (d) replicative potential in continuous rat cell lines. Egyptian strains were highly virulent for Wistar-Furth rats; relatively resistant to rat interferon-alpha/beta; capable of producing plaques in primary hepatocyte monolayers; and, in general, replicated more rapidly than the low-virulent, sub-Saharan strains. Virtually all strains from sub-Saharan Africa were sensitive to rat interferon and did not form plaques in rat hepatocyte monolayers. An exception was the 2269/74 strain from Zimbabwe, which had characteristics of the Egyptian strains including increased virulence for Wistar-Furth rats. The relative virulence of RVFV strains for rats did not correlate with interferon sensitivity when human recombinant interferon-alpha was tested on A-549 cells. Thus, several in vitro phenotypic characteristics of RVFV strains tend to correlate with virulence for Wistar-Furth rats and with geographical origin of the viral strains.

[Rift Valley Fever and phleboviroses in the Central African Republic]. / La fièvre de la Vallée du Rift et les phléboviroses en République centrafricaine.

During 1984 and 1985, six Rift Valley Fever virus strains (RVF) were isolated in Central African Republic, among them five from human samples. Three strains were isolated in 1985 at the end of the rainy season, from sera of patients dead with severe jaundice with haemorrhagic syndrome, what could evoke a little outbreak. At this occasion, these RVF strains and the other strains of phleboviruses previously isolated in CAR, were antigenically compared by Immuno-fluorescent assay (IFA) and Complement Fixation Test (CF), using mice immuno ascitic fluids prepared against each strain. A lot of cross reactions were noted between the different strains, but all the RVF strains seem to have the same antigenic outline.

Ranking of prophylactic efficacy of poly(ICLC) against Rift Valley fever virus infection in mice by incremental relative risk of death.

The prophylactic efficacy of poly(ICLC) (stabilized, synthetic, double-stranded polyriboinosinic-polyribocytidylic acid) against Rift Valley fever virus infection in Swiss-Webster mice was dependent on the treatment schedule. The treatment schedule was optimized by ranking the results of various treatments by the Cox proportional-hazard model based on the incremental relative risk of death. With this ranking procedure, the schedule of choice was three doses of 20 micrograms each given 5 days apart. This regimen yielded a 90% survival rate. Additional parameters were determined, including the timing of the first and second drug dose, the temporal relationship of these treatments to the day of challenge, and the minimal effective dose (1 microgram per mouse).

[Rift valley fever and Zinga virus: a pathogenic arbovirus in man and animal new for Madagascar]. / Fievre de la vallee du Rift et virus Zinga: un arbovirus pathogene pour l'homme et l'animal nouveau pour Madagascar.

Virus Zinga strains have been isolated from several pools of mosquitoes collected in Perinet area, 130 km far from Tananarive, at the Institut Pasteur of Madagascar in 1980. Although this virus is pathogenic for man, it seemed to give only a mild illness and did not appear to constitute a problem of Public Health. But today it is seen in quite a different way; since the WHO Center for Arbovirus Reference and Research of New Haven has shown the serologic identity between virus Zinga and an another arbovirus, Rift Valley Fever virus. This latter is in fact very pathogenic for man and domestic animal, he is responsible of important epizootics characterized by many abortions in pregnancies and death of newborn animals, many infections have occurred in man during these epizootics and the disease is able to give a mortal haemorragic syndrome. Until now, no particular aggressivity has been shown by virus Zinga in Madagascar, but it remains a real potential danger for man and for domestic animals.

Inhibition of RNA viruses in vitro and in Rift Valley fever-infected mice by didemnins A and B.

Didemnins, a new class of depsipeptides isolated from a Caribbean tunicate, have been shown to have potent antiviral activity against a broad range of RNA viruses in vitro. Didemnins A and B both protected mice against a lethal challenge of Rift Valley fever virus.