Molecular Analysis of Chloroquine and Sulfadoxine-Pyrimethamine Resistance-Associated Alleles in Plasmodium falciparum Isolates from Nicaragua

Abstract

Abstract. Chloroquine (CQ) is used as a first-line therapy for the treatment of Plasmodium falciparum malaria in Nicaragua. We investigated the prevalence of molecular markers associated with CQ and sulfadoxine-pyrimethamine (SP) resistance in P. falciparum isolates obtained from the North Atlantic Autonomous Region of Nicaragua. Blood spots for this study were made available from a CQ and SP drug efficacy trial conducted in 2005 and also from a surveillance study performed in 2011. Polymorphisms in P. falciparum CQ resistance transporter, dihydrofolate reductase, and dihydropteroate synthase gene loci that are associated with resistance to CQ, pyrimethamine, and sulfadoxine, respectively, were detected by DNA sequencing. In the 2005 dataset, only 2 of 53 isolates had a CQ resistance allele (CVIET), 2 of 52 had a pyrimethamine resistance allele, and 1 of 49 had a sulfadoxine resistance allele. In the 2011 dataset, none of 45 isolates analyzed had CQ or SP resistance alleles.

Plasmodium falciparum Drug-Resistant Haplotypes and Population Structure in Postearthquake Haiti, 2010

“…Fortunately, our findings suggest, as in Honduras and Nicaragua, a nonexistent or a very low prevalence of CQ-resistant alleles in Haiti. 3,4 This supports the current recommendations to use CQ as first-line treatment, while emphasizing the need for continued molecular monitoring for the possible emergence and expansion or introduction and expansion of antimalarialresistant parasite populations.…”

“…However, conducting such trials can be expensive and time consuming in countries where malaria incidence is low; therefore, molecular surveillance has become a valuable tool for assessing the prevalence of CQ-and sulfadoxine-pyrimethamine (SP)-resistant parasites in countries with low malaria transmission. 3,4 Recently, WHO has included in its recommendations that in areas with low to very low transmission, studies with molecular markers should be conducted systematically every year provided that markers are known and validated.…”

Single nucleotide polymorphisms in Plasmodium falciparum V type H+ pyrophosphatase gene (pfvp2) and their associations with pfcrt and pfmdr1 polymorphisms

“…The sample copy numbers were calculated using a The ~100% pfcrt K76 frequency in Honduras and Liberia was in line with continued CQ efficacy in both countries [234,256]. Surprisingly and for principally unknown reasons P. falciparum in Honduras therefore remain susceptible to CQ despite six decades of use, the worldwide spread of CQ resistance and the sporadic occurrence of CQ resistant P. falciparum in Nicaragua [257]. The high pfcrt K76 proportion in Guinea-Bissau concurrently with continued CQ use was also surprising but probably due to the routine use of high doses of CQ (~75mg/kg as 2-3 daily doses for 5 days ) as discussed previously [258].…”

“…Yet this has as yet not happened according to the latest survey conducted in 2011 [256]. Furthermore, neighbouring Nicaragua recently reported the presence of P. falciparum with the CQ resistant pfcrt CVIET haplotype and pfdhfr 51I + 59R and/or 108N and pfdhps 437G SP resistant SNPs in 3/49 samples during a clinical trial conducted in 2005[257]. In a follow up survey in Nicaragua in 2011 no SP resistant SNPs were present.…”

Molecular variation of Plasmodium vivax dehydrofolate reductase in Mexico and Nicaragua contrasts with that occurring in South America

“…Accordingly, no mutations in dhfr were observed in P. falciparum in Honduras 44 or Nicaragua. 45 Interestingly, the variant repeat sequence found in NPC Nicaragua and reported in parasites from Honduras, 44 might not be present in the RACCN of Nicaragua. The synonymous mutation at codon Y69 observed in parasites of Nicaragua, and in those of Honduras, 44 Colombia 32 and French Guiana, 35 seem to be widely distributed: it was reported in parasites of South Korea 46 and Thailand.…”