Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon

Jürgen May, Samuel Adjei, Wibke Busch, Julian J Gabor, Saadou Issifou, Robin Kobbe, Benno Kreuels, Bertrand Lell, Norbert G Schwarz, Ohene Adjei, Peter G Kremsner, Martin P Grobusch, Jürgen May, Samuel Adjei, Wibke Busch, Julian J Gabor, Saadou Issifou, Robin Kobbe, Benno Kreuels, Bertrand Lell, Norbert G Schwarz, Ohene Adjei, Peter G Kremsner, Martin P Grobusch

Abstract

Background: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials.

Methods: Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests.

Results: Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort.

Conclusion: The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low.

Trial registration: Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial) and NCT ID # 00167843 (Lambaréné Trial), http://www.clinicaltrials.gov.

Trial registration: ClinicalTrials.gov NCT00167843 NCT00206739.

Figures

Figure 1
Figure 1
Protective efficacies were calculated for overlapping series of 61-days periods for six months after each IPTi administration (IPTi-1, first IPTi dose at month 3; IPTi-2, second IPTi dose at month 9; IPTi-3, third IPTi dose at month 15). The first 61-day period started at the time of an IPTi application, the last period ended at the time of the next IPTi application or 6 months after the last IPTi application (IPTi-3).
Figure 2
Figure 2
Protective efficacies for intervals of 61 days for six months after each SP administration (A, IPTi-1; B, IPTi-2; C, IPTi-3). Solid lines, protective efficacy; vertical bars, 95% confidence intervals. The first 61-day interval started at the time of an IPTi application and the last interval ended at the time of the next IPTi application or 6 months after the last IPTi application (IPTi-3). Protective efficacy against multiple malaria episodes determined by Poisson regression and defined as one minus rate ratio. Children were not rated at risk for malaria for 21 days after preceding malaria episodes or after antimalarial treatment.

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