[Show abstract][Hide abstract] ABSTRACT: Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP).
The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria.
SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon.
There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored.
[Show abstract][Hide abstract] ABSTRACT: We evaluated methods for assessing body temperature by comparing subjective assessment of fever by parents and doctors with objective axillary, tympanic, and rectal measurements of body temperature in 1000 children < or = 10-years-old who presented at outpatient clinics with recent history of fever. Sensitivity of subjective assessment of fever were higher at thresholds of > or = 38.3 degrees C with specificity as low as 60%. Axillary methods showed better specificity at fever thresholds of > 38.0 degrees C with maximum sensitivity of 63% at thresholds of > or = 37.5 degrees C. Bland-Altman analysis showed wide limits of agreement between objective methods of measurements: -1 degrees C to 3 degrees C for comparison of rectal and axillary, -1 degrees C to 2 degrees C for rectal and tympanic, and -1 degrees C to 2 degrees C for tympanic and axillary measurements. A choice of method to measure body temperature for diagnosis of fever in African children should be informed by a trade-off between its specificity and sensitivity that considers thresholds > 38.0 degrees C.
The American journal of tropical medicine and hygiene 02/2010; 82(2):215-8. DOI:10.4269/ajtmh.2010.09-0419 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the context of a trial studying intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Lambaréné, Gabon, children aged 18-30 months were followed up after having received their last dose at an age of 15 months. In the intention-to-treat population, the protective efficacy against all malaria episodes was -18.0 (95% confidence interval, -97.4 to 29.5; P = .529). The protective efficacy against first or only anemia episode was -45.3 (95% confidence interval, -234.5 to 36.3; P=.375). The protective efficacies were negative and were not statistically significant. These results do not appear to support the concept of a rebound effect after intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants. Clinical trials registration. NCT00167843.
The Journal of Infectious Diseases 12/2009; 200(11):1658-61. DOI:10.1086/647990 · 5.78 Impact Factor