Browsing by Author "Zaman, K."
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Item Analyses of health outcomes from the 5 sites participating in the Africa and Asia clinical efficacy trials of the oral pentavalent rotavirus vaccine(Vaccine, 2012-04) Breiman, R.F.; Zaman, K.; Armah, G.; Sow, S.O.; Anh, D.D.; Victor, J.C.; Hille, D.; Ciarlet, M.; Neuzil, K.M.Background: Efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq®, against severe rotavirus gastroenteritis (RVGE) was evaluated in two double-blind, placebo-controlled, multicenter Phase III clinical trials conducted in GAVI-eligible countries in Africa (Ghana, Kenya, and Mali) and in Asia (Bangladesh and Vietnam) from March 2007 through March 2009. The findings from each continent have been analyzed and presented separately, according to a single identical protocol. Ad hoc analyses combining data from the five sites were performed to further assess the impact of PRV. Methods: 6674 infants (4705 infants from Africa and 1969 infants from Asia), randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age according to each country's EPI schedule, were included in the per protocol efficacy analysis. Breastfeeding and concomitant administration of EPI vaccines, including OPV, were allowed. Episodes of gastroenteritis (GE) in infants who presented to study facilities were captured and scored using the 20-point Vesikari scale. Stool samples were analyzed by rotavirus-specific EIA to detect presence of rotavirus antigen and RT-PCR to determine the G/P genotypes. We assessed efficacy to prevent all-cause GE and RVGE at a variety of cut-off points (score ≥ 11, severe; score ≥ 15, very severe). Results: Vaccine efficacy (VE) against RVGE, regardless of serotype, through the entire follow-up period for any severity, severe (score ≥ 11), and very severe (score ≥ 15) was 33.9%, 95% CI (22.7, 43.5), 42.5%, 95% CI (27.4, 54.6), and 51.2%, 95% CI (26.3, 68.2), respectively. Through the first year of life, VE against severe RVGE was 58.9%, 95% CI (40.0, 72.3) and against all-cause severe GE was 23.0%, 95% CI (5.4, 37.3). VE against severe RVGE caused by non-vaccine G serotypes, G8 and G9, through the entire follow-up period was 87.5%, 95% CI (6.8, 99.7) and 48.0%, 95% CI (-5.5, 75.6), respectively. All G8 strains were associated with P2A[6] (a P-type not contained in PRV), while the majority of the G9 strains were associated with P1A[8] (a P-type contained in PRV). Conclusions: Combining data from the 5 sites strengthens the precision of VE estimates and reveals rising VE with increased RVGE severity. Extrapolating data from VE against severe GE and RVGE suggest that 39% of severe GE episodes during the first year of life were due to rotavirus, highlighting substantial, potentially preventable, public health burden of RVGE. PRV provides protection against non-vaccine serotypes (G8P2A[6]). © 2011.Item Comparison of two clinical severity scoring systems in two multi-center, developing country rotavirus vaccine trials in Africa and Asia(Vaccine, 2012-04) Lewis, K.D.C.; Dallas, M.J.; Victor, J.C.; Ciarlet, M.; Mast, T.C.; Ji, M.; Armah, G.; Zaman, K.; Ferraro, A.; Neuzil, K.M.Background: Clinical severity scoring systems are used in rotavirus vaccine efficacy and effectiveness studies to define the primary endpoint, severe rotavirus gastroenteritis (RVGE). Understanding how scoring systems perform in diverse settings is critical for proper design and interpretation. This investigation aims to understand how the Vesikari scoring system (VSS) and Clark scoring system (CSS) categorize severe disease among children under 2 years of age using data from two Phase III efficacy trials conducted in five developing countries in Africa and Asia. Methods: Signs and symptoms were collected on trial participants who presented to a medical facility with study-defined gastroenteritis. Severity scores were calculated using pre-established VSS and CSS criteria and compared to identify differences in the proportions of severe RVGE within regions and sites, and by gender and age. Results: In Africa and Asia, 40.6% and 56.0% of rotavirus-positive episodes were severe according to the VSS, while 9.5% and 6.3% of episodes were severe according to the CSS (Fisher's Exact, p≤ 0.001). Using the mean scores in these trials (VSS: ≥10 Africa, ≥11 Asia; CSS: Africa and Asia ≥10) as the severity thresholds, agreement between scoring system severity classifications improved substantially within each region (Africa: kappa = 0.67; Asia: kappa = 0.78) as compared to the original severity classification (Africa: kappa = 0.27; Asia: kappa = 0.10). Using the mean score, 17.1% and 9.5% of severe VSS cases in Africa and Asia, respectively, were classified as not severe according to the CSS and 14.7% and 9.5% of severe CSS cases in Africa and Asia were classified as not severe according to the VSS. Conclusion: The two scoring systems performed differently among developing country populations in Africa and Asia, with the VSS classifying more cases as severe in both regions. One accurate and reliable scoring system should be developed and implemented for all trials so that results may be more comparable. © 2011 Elsevier Ltd.Item Rotavirus vaccine efficacy in African and Asian countries Reply(The Lancet, 2010-12) Breiman, R.F.; Armah, G.; Zaman, K.; Sow, S.; Anh, D.D.; Ciarlet, M.; Neuzil, K.M.The pentavalent rotavirus vaccine offers an opportunity to affect child health positively, particularly in regions of the world with high diarrhoea morbidity and mortality. Although our study focused on the prevention of severe gastroenteritis, we agree with Stephen Obaro that the vaccine might be effective against less common outcomes, including mortality. In fact, such an effect has been shown in postmarketing studies, most notably in Mexico, where introduction of a rotavirus vaccine into the national immunisation programme correlated with a significant reduction in all-cause diarrhoea mortality.1 Our studies used a passive “catchment” design to identify cases of rotavirus gastroenteritis, and, as Obaro suggests, health-care use did interfere with optimum case ascertainment. Indeed, in the Mali site, gastroenteritis episodes were managed largely by traditional healers during the first year of the study, resulting in very few cases identified and a limited capacity to contribute to vaccine efficacy calculations. When this problem was identified and addressed at the end of the first rotavirus season, the number of cases identified increased substantially.