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

TY - JOUR

T1 - Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon

AU - May, Jürgen

AU - Adjei, Samuel

AU - Busch, Wibke

AU - Gabor, Julian J

AU - Issifou, Saadou

AU - Kobbe, Robin

AU - Kreuels, Benno

AU - Lell, Bertrand

AU - Schwarz, Norbert G

AU - Adjei, Ohene

AU - Kremsner, Peter G

AU - Grobusch, Martin P

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

KW - Antimalarials

KW - Drug Administration Schedule

KW - Drug Combinations

KW - Gabon

KW - Ghana

KW - Humans

KW - Infant

KW - Malaria, Falciparum

KW - Pyrimethamine

KW - Regression Analysis

KW - Sulfadoxine

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1186/1475-2875-7-198

DO - 10.1186/1475-2875-7-198

M3 - SCORING: Journal article

C2 - 18828899

VL - 7

SP - 198

JO - MALARIA J

JF - MALARIA J

SN - 1475-2875

ER -