ROLL BACK OF PLASMODIUM FALCIPARUM ANTIFOLATE RESISTANCE BY INSECTICIDE-TREATED NETS

Preserving efficacy of the limited arsenal of antimalarial drugs is of critical importance to public health in malariaendemic regions. Of particular concern is the vulnerability of those agents that are most affordable, chloroquine and the antifolate duo, sulfadoxine/pyrimethamine (S/P), or secondgeneration chlorproguanil/dapsone (LAPDAP). On page 238 of the current issue, Alifrangis and others report that an increased frequency of Plasmodium falciparum strains carrying the wild-type dihydrofolate reductase (dhfr) the allele was observed following the use of insecticide-treated nets (ITNs), and suggest that their approach might help to restore sensitivity to S/P. The study of interest was conducted in two neighboring Tanzanian villages, Magoda and Mpapayu, from 1998 to 2000, at a time when complex dhfr and dhps mutation frequencies exceeded 60% and fully wild-type haplotype frequencies ranged from 0% to 5%. Of particular interest, the majority dhfr polymorphism was the triple mutant (108N/51I/59R); data on the quadruple mutant haplotype containing 164L was not reported. ITNs were provided to all households in Magoda, but were not distributed in Mpapayu. In addition to dhfr/dhps polymorphisms, children between the ages of 0.5 and 5 years from both villages were studied for P. falciparum infection and anemia. During the ITN trial, S/P was used as the first-line antimalarial in both villages. At the conclusion of their study fully wild-type dhfr allele frequencies were approaching 20% in Magoda, but remained unchanged in Mpapayu. The investigators conclude that their results are consistent with the Mackinnon/Hastings model, 1 in which the spread of antimalarial drug resistance is constrained by reducing transmission through the use of ITNs.