Molecular Epidemiology of Malaria in Cameroon. XXVI. Twelve-Year In Vitro and Molecular Surveillance of Pyrimethamine Resistance and Experimental Studies to Modulate Pyrimethamine Resistance

Abstract

In vitro pyrimethamine response of Plasmodium falciparum isolates and dihydrofolate reductase (dhfr) gene sequences were analyzed in 2004-2005 and compared with our previous data. Most isolates (n = 103, all dhfr mutants) had 50% inhibitory concentrations (IC(50)s) > or = 119 nM, and six isolates had low IC(50)s (five wild-type or mixed dhfr, 0.04-1.37 nM; one triple mutant, 6.4 nM). Of 194 isolates, only 7 had the wild-type dhfr and 187 were mutants. The results of the two methods were highly concordant and indicated a significant increase (P < 0.05) in the prevalence of mutant, pyrimethamine-resistant P. falciparum between 1994 and 2005. The addition of probenecid or sulfinpyrazone to pyrimethamine resulted in a slight-to-moderate decrease in the level of in vitro pyrimethamine resistance without rendering the parasites susceptible to pyrimethamine. Analysis of molecular markers may be useful for the long-term surveillance of antifolate-resistant malaria.

Hitchhiking and Selective Sweeps of Plasmodium falciparum Sulfadoxine and Pyrimethamine Resistance Alleles in a Population from Central Africa

“…DNA was isolated as previously described (8). One hundred fifty samples were analyzed for mutations in codons 16, 51, 59, 108, and 164 of dhfr by direct DNA sequencing, as described previously (36). One hundred eighty-two samples were analyzed for mutations in codons 50, 51, 59, 108, and 164 of dhfr by pyrosequencing, as described previously (40).…”

“…We analyzed 332 random samples collected in Yaoundé, Cameroon, in 2001Cameroon, in , 2002Cameroon, in , 2004Cameroon, in , and 2005. Study details have been described previously (5,36). Whole-blood samples were collected from symptomatic patients Ն12 years old with uncomplicated P. falciparum malaria.…”

A maximum-likelihood method to estimate haplotype frequencies and prevalence alongside multiplicity of infection from SNP data

“…As an application, we estimated the frequency of malaria haplotypes associated with resistance against SP. The data was taken from ( 42 , 48 , 49 ) and is described there in detail. In short, it was collected in Yaoundé, Cameroon in 2001/2002 and 2004/2005.…”

Emergence of Drug Resistance in Plasmodiun falciparum: Reasons of its Dispersal and Transmission in Different Climatic Regions of the World: a Review

“…It also reduces gametocyte carriage and infection rates in patients [147] and is potentially used for treatment of multidrug-resistant malaria in Africa [148] and Cameroon [149]. Similarly, in Vietnam, use of artemisinin derivatives provided initial high success in malaria control [150] but later on malaria parasite become highly resistant to them [151]. Similar cases of artimisin resistance concerned to sulfadoxine/pyrimethamine usage resulted in dhfr quadruple mutants i.e.…”