SPf66 vaccine trial in Brazil: conceptual framework study design and analytical approach

Abstract

This paper describes the study population and the study design of the phase III field trail of the SPf66 vaccine in Brazil. Assessment of validity and precision principles necessary for the appropriate evaluation of the protective effect of the vaccine are discussed, as well as the results of the preliminary analyses of the gathered data. The analytical approach for the estimation of the protective effect of the vaccine is presented. This paper provides the conceptual framework for future publications.

Evaluation of SPf66 malaria vaccine efficacy in Brazil.

“…A preliminary survey that preceded the vaccine trial reported an overall prevalence of 10%, with the ratio of P. falciparum to P. vivax infections being 1:1. 18 Plasmodium falciparum infections are treated with a combination of quinine plus tetracycline in a 10-day schedule because resistance to chloroquine (81.8%), sulfadoxine-pyrimethamine (46.6%), and quinine alone (18.2%) has been reported. 19 Mefloquine is available and prescribed in cases of drug resistance that is confirmed parasitologically.…”

“…Although malaria is considered to be the main health problem in the municipality, mortality is low, probably due to the easy access to diagnosis and specific treatment. 18 Cases accompanied by clinical signs of possible complications such as dehydration, jaundice, and conscience alterations are referred to the main health center in the village.…”

“…The term field direct effectiveness applies to situations in which attempts are made to control for the unknown amount of exposure to infection in the analysis, and when indirect effects of the vaccine interact with estimates of the direct protective effect (vaccine efficacy). 18 A further objective was to detect possible differences in asexual blood-stage parasite densities.…”

“…Both groups were comparable in relation to baseline characteristics at enrollment. 18 Of the initial cohort, 714 received the second dose and 572 received the third dose (28.5% lost to follow-up). The proportion and the average time of survival of the participants lost to follow-up up to the third dose were comparable for both treatment groups (113 vaccinees versus 115 in the placebo group; P ϭ 0.9, by chi-square test and 12.5 versus 11.5 weeks of survival, respectively; P ϭ 0.5, by Student's t-test).…”

Estimation of vaccine efficacy in a repeated measures study under heterogeneity of exposure or susceptibility to infection

“…Although no mosquito surveys were performed in the trial area during the trial period, studies in nearby regions indicated that the intensity of exposure in the region ranged from 0.4 to 2.1 infected mosquito bites/person/night, depending on the season (Klein & Lima 1990; Urdaneta et al . 1996).…”