Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock

BACKGROUND:Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. METHODS:In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. RESULTS:In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. CONCLUSIONS:The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle

Rift Valley Fever Outbreak in Livestock in Kenya, 2006–2007

We analyzed the extent of livestock involvement in the latest Rift Valley fever (RVF) outbreak in Kenya that started in December 2006 and continued until June 2007. When compared with previous RVF outbreaks in the country, the 2006–07 outbreak was the most extensive in cattle, sheep, goats, and camels affecting thousands of animals in 29 of 69 administrative districts across six of the eight provinces. This contrasted with the distribution of approximately 700 human RVF cases in the country, where over 85% of these cases were located in four districts; Garissa and Ijara districts in Northeastern Province, Baringo district in Rift Valley Province, and Kilifi district in Coast Province. Analysis of livestock and human data suggests that livestock infections occur before virus detection in humans, as supported by clustering of human RVF cases around livestock cases in Baringo district. The highest livestock morbidity and mortality rates were recorded in Garissa and Baringo districts, the same districts that recorded a high number of human cases. The districts that reported RVF in livestock for the first time in 2006/07 included Kitui, Tharaka, Meru South, Meru central, Mwingi, Embu, and Mbeere in Eastern Province, Malindi and Taita taveta in Coast Province, Kirinyaga and Murang'a in Central Province, and Baringo and Samburu in Rift Valley Province, indicating that the disease was occurring in new regions in the country

Predictive Factors and Risk Mapping for Rift Valley Fever Epidemics in Kenya

BACKGROUND:To-date, Rift Valley fever (RVF) outbreaks have occurred in 38 of the 69 administrative districts in Kenya. Using surveillance records collected between 1951 and 2007, we determined the risk of exposure and outcome of an RVF outbreak, examined the ecological and climatic factors associated with the outbreaks, and used these data to develop an RVF risk map for Kenya. METHODS:Exposure to RVF was evaluated as the proportion of the total outbreak years that each district was involved in prior epizootics, whereas risk of outcome was assessed as severity of observed disease in humans and animals for each district. A probability-impact weighted score (1 to 9) of the combined exposure and outcome risks was used to classify a district as high (score ≥ 5) or medium (score ≥2 - <5) risk, a classification that was subsequently subjected to expert group analysis for final risk level determination at the division levels (total = 391 divisions). Divisions that never reported RVF disease (score < 2) were classified as low risk. Using data from the 2006/07 RVF outbreak, the predictive risk factors for an RVF outbreak were identified. The predictive probabilities from the model were further used to develop an RVF risk map for Kenya. RESULTS:The final output was a RVF risk map that classified 101 of 391 divisions (26%) located in 21 districts as high risk, and 100 of 391 divisions (26%) located in 35 districts as medium risk and 190 divisions (48%) as low risk, including all 97 divisions in Nyanza and Western provinces. The risk of RVF was positively associated with Normalized Difference Vegetation Index (NDVI), low altitude below 1000m and high precipitation in areas with solonertz, luvisols and vertisols soil types (p <0.05). CONCLUSION:RVF risk map serves as an important tool for developing and deploying prevention and control measures against the disease

RVF risk map for Kenya generated from predicted probabilities by administrative divisions based on Centre Merged Analysis of Precipitation (CMAP).

<p>RVF risk map for Kenya generated from predicted probabilities by administrative divisions based on Centre Merged Analysis of Precipitation (CMAP).</p

Rift Valley Fever risk map for Kenya, 2012 based on the semi-quantitative risk assessment for likelihood of RVF epizootic and expert opinion.

<p>Rift Valley Fever risk map for Kenya, 2012 based on the semi-quantitative risk assessment for likelihood of RVF epizootic and expert opinion.</p

Graphical interpretation of the effects of rainfall and soil type on the risk of RVF outbreak.

<p>Graphical interpretation of the effects of rainfall and soil type on the risk of RVF outbreak.</p

Administrative Law -- Power of Board of Education to Abolish Fraternities

<p>Left panel (bottom) shows proportion of cattle with IgG antibodies following vaccination 14 to 366 days post-vaccination. The right panel (bottom) shows proportion of cattle that produced anti-RVF IgM antibodies over the 1 year period. The top panel on the left and right are the placebo-treated animals.</p

Schematic summary of the study design showing the species, the numbers and the physiological status of the study animals.

<p>The study was carried out in three sites (Kabete, Kiboko and Ngong)—all government farms with similar farm management conditions. We used 404 animals in the study, including 85 cattle, 168 sheep, and 151 goats. Of these, 194 were vaccinated with RVF Clone 13 vaccine whereas 210 were injected with placebo. The study animals were divided into 3 groups; Group A included non-pregnant animals, Group B included animal in 1^st half of the pregnancy, and Group C animals in 2^nd half of pregnancy.</p

Proportion of goats positive for anti-RVF antibodies following vaccination with RVF Clone 13 vaccine.

<p>Left panel (bottom) proportion of the goats with IgG antibodies following vaccination within 14 to 366 days post-vaccination. The right panel (bottom) shows proportion of goats that produced anti-RVF IgM antibodies over the 1 year period. The top panel on the left and right are the placebo-treated animals.</p

Odds ratios for sero-conversion by day 14 for vaccinated and placebo groups of cattle, sheep, and goats.

<p>The ratio represents the odds of sero-conversion in the vaccinated group compared to the placebo (reference) group.</p><p>Odds ratios for sero-conversion by day 14 for vaccinated and placebo groups of cattle, sheep, and goats.</p