Abstract:We compare the frequency of resistant genes of malaria parasites before treatment and at first malaria incidence after treatment. The data come from a clinical trial at two health facilities in Tanzania and concerns single nucleotide polymorphisms (SNPs) at three positions believed to be related to resistance to malaria treatment. A problem is that mixed infections are common, which both obscures the underlying frequency of alleles at each locus as well as the associations between loci in samples where alleles are mixed. We use combinatorics and quite involved probability methods to handle multiple infections and multiple haplotypes. The infection with the different haplotypes seemed to be independent of each other. We showed that at two of the three studied SNPs, the proportion of resistant genes had increased after treatment with sulfadoxine-pyrimethamine alone but when treated in combination with artesunate, no effect was noticed. First recurrences of malaria associated more with sulfadoxine-pyrimethamine alone as treatment than when in combination with artesunate. We also found that the recruited children had two different ongoing malaria infections where the parasites had different gene types.

Two treatment regimens for malaria are compared in their abilities to cure and combat reinfection. Bayesian analysis techniques are used to compare two typical treatment therapies for uncomplicated malaria in children under five years, not only in their power to resist recrudescence, but also how long they can postpone recrudescence or reinfection in case of failure. We present a new way of analysing this type of data using Markov Chain Monte Carlo techniques. This is done using data from clinical trials at two different centres. The results which give the full posterior distributions show that artemisinin-based combination therapy is more efficacious than sulfadoxine-pyrimethamine. It both reduced the risk of recrudescence and delayed the time until recrudescence.

Many investigations have shown that artemisinin-based combination therapies are effective in the treatment of uncomplicated malaria and that they do not increase parasite resistance to treatment as much as treatment with single substance. We study the relation between some biological covariates and the time to first recurrence of malaria for children treated for malaria in a clinical trial. One group received artesunate plus sulfadoxine-pyrimethamine and the other only sulfadoxine-pyrimethamine. We consider the event malaria-free for the first 42 (and 84) days. We use logistic regression models for the analyses. The main results show that the probability of no recurrence is higher if the parasite density in the blood is high. The results are inconclusive for other explanatory biological variables. The infecting parasites having genes that indicate resistance, gave different results at the two different treatment centres. There was no appreciable difference in the effects of treatment over the two follow-up periods and these treatments do not have any effect on the probability of a recurrence.