Safety of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Kenya, including among HIV-infected and HIV-exposed infants.

Two multicenter Phase III trials were conducted in five countries from March 2007 to March 2009 to evaluate the safety and efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Africa and Asia. In this report, we evaluate the safety of this vaccine, including among HIV-infected and HIV-exposed infants, in Kenya. 1308 Infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. HIV counseling and testing were offered to all participants. A positive PCR result indicated HIV infection; the presence of HIV antibody in PCR-negative children indicated HIV exposure without HIV infection. All serious adverse events (SAE) within 14 days of any dose, and vaccine-related SAEs, intussusception, and deaths occurring at any time during the study, were reported ("SAE surveillance"). In addition, 297 participants were followed for 42 days after any dose for any adverse event (AE), regardless of severity ("intensive safety surveillance"). The safety evaluation was stratified by HIV status. SAEs were reported in 20/649 vaccine recipients (3.1%) and 21/643 placebo recipients (3.3%) within 14 days following vaccination (p = 0.9). The most common SAE in the vaccinated group was pneumonia (1.7%). No individual SAE was significantly more common among vaccine vs. placebo recipients. Seventy-two deaths were reported, 38 (5.9%) and 34 (5.3%) among vaccine and placebo recipients, respectively (p = 0.66). No cases of intussusception were reported. During intensive safety surveillance, 137/147 (93.2%) vaccine recipients and 147/150 (98.0%) placebo recipients experienced one or more AEs (risk ratio = 0.95; 95% CI: 0.91-1.0; p = 0.05). 88.5% of the infants were tested for HIV infection; 21/581 (3.6%) children in the vaccine group and 17/577 (2.9%) in the placebo group were HIV-infected. Among the 37 HIV-infected infants with full safety follow-up, 5/21 (23.8%) vaccine recipients and 2/16 (12.5%) placebo recipients reported an SAE (p = 0.67). In total, 12 deaths occurred among identified HIV-infected infants: 8 (38%) receiving vaccine vs. 4 (23.5%) receiving placebo (RR = 1.6, 95% CI: 0.59-4.5). Among the 21 HIV-infected infants in the vaccine group, 2 of 8 deaths were gastroenteritis-related; among the 17 HIV-infected infants in the placebo group, 3 of 4 deaths were gastroenteritis-related. There were no significant differences in serious or non-serious AEs, including vaccine-related SAEs, between the 88 HIV-exposed vaccine recipients vs. the 89 HIV-exposed placebo recipients. PRV appears to be a safe intervention against rotavirus gastroenteritis among infants in Kenya. AEs, including serious AEs, were not associated with receipt of vaccine. Further, SAEs were not significantly more common among HIV-infected or HIV-exposed participants; however, the low number of HIV-infected infants did not provide sufficient power to fully assess safety in HIV-infected vaccine recipients.

Establishing a malaria diagnostics centre of excellence in Kisumu, Kenya.

BACKGROUND: Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists. CASE DESCRIPTION: A twelve-day "long" and a four-day "short" training course consisting of supervised laboratory practicals, lectures, group discussions, demonstrations, and take home assignments were developed. Well characterized slides were developed and training materials iteratively improved. Objective pre- and post-course evaluations consisted of 30 slides (19 negative, 11 positive) with a density range of 50-660 parasites/mul, a written examination (65 questions), a photographic image examination (30 images of artifacts and species specific characteristics), and a parasite counting examination. DISCUSSION AND EVALUATION: To date, 209 microscopists have participated from 11 countries. Seventy-seven experienced microscopists participated in the "long" courses, including 47 research microscopists. Sensitivity improved by a mean of 14% (CI 9-19%) from 77% baseline (CI 73-81 %), while specificity improved by a mean of 17% (CI 11-23%) from 76% (CI 70-82%) baseline. Twenty-three microscopists who had been selected for a four-day refresher course showed continued improvement with a mean final sensitivity of 95% (CI 91-98%) and specificity of 97% (CI 95-100%). Only 9% of those taking the pre-test in the "long" course achieved a 90% sensitivity and 95% specificity, which increased to 61% of those completing the "short" course. All measures of performance improved substantially across each of the five organization types and in each course offered. CONCLUSION: The data clearly illustrated that false positive and negative malaria smears are a serious problem, even with research microscopists. Training dramatically improved performance. Quality microscopy can be provided by the Centre of Excellence concept. This concept can be extended to other diagnostics of public health importance, and comprehensive disease control strategies.