With the spread of @entity503 (CQ)-resistant @entity311 in India, @entity1484 (SP) alone or in combination with @entity506 is used as an alternative antimalarial drug. Due to continuous drug pressure, the @entity3964 parasite is exhibiting resistance to antifolates because of mutations in candidate genes @entity9796 reductase (dhfr) and @entity9795 synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the @entity4765 resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian @entity3964 isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (H(e)) around mutant dhps alleles (H(e) = 0.55; n = 81) associated with @entity9230 resistance was lower (P  <= 0.05) than the mean H(e) around the wild-type dhps allele (H(e) = 0.80; n = 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of @entity503 - and @entity4765 -resistant parasites in the past.

Multiple origins of @entity3964 XXXX synthetase mutant alleles associated with @entity9230 resistance in India.

@entity9795 :: ('MESH:C000978', 'Chemical') :: ['dihydropteroate'] @entity1484 :: ('MESH:C001205', 'Chemical') :: ['sulfadoxine-pyrimethamine'] @entity9796 :: ('MESH:C010920', 'Chemical') :: ['dihydrofolate'] @entity9230 :: ('MESH:D013413', 'Chemical') :: ['sulfadoxine'] @entity3964 :: ('5833', 'Species') :: ['P. falciparum', 'Plasmodium falciparum'] @entity506 :: ('MESH:C039726', 'Chemical') :: ['artesunate'] @entity311 :: ('MESH:D008288', 'Disease') :: ['malaria'] @entity503 :: ('MESH:D002738', 'Chemical') :: ['chloroquine'] @entity4765 :: ('MESH:D011739', 'Chemical') :: ['pyrimethamine']
@entity9795 :: (MESH:C000978,Chemical) :: ['dihydropteroate']
