Mutant <it>pfcrt </it>"SVMNT" haplotype and wild type <it>pfmdr1 </it>"N86" are endemic in <it>Plasmodium vivax </it>dominated areas of India under high chloroquine exposure

<p>Abstract</p> <p>Background</p> <p>Chloroquine resistance (CQR) phenotype in <it>Plasmodium falciparum </it>is associated with mutations in <it>pfcrt </it>and <it>pfmdr-1 </it>genes. Mutations at amino acid position 72-76 of <it>pfcrt </it>gene, here defined as <it>pfcrt </it>haplotype are associated with the geographic origin of chloroquine resistant parasite. Here, mutations at 72-76 and codon 220 of <it>pfcrt </it>gene and N86Y <it>pfmdr-1 </it>mutation were studied in blood samples collected across 11 field sites, inclusive of high and low <it>P. falciparum </it>prevalent areas in India. Any probable correlation between these mutations and clinical outcome of CQ treatment was also investigated.</p> <p>Methods</p> <p>Finger pricked blood spotted on Whatman No.3 papers were collected from falciparum malaria patients of high and low <it>P. falciparum </it>prevalent areas. For <it>pfcrt </it>haplotype investigation, the parasite DNA was extracted from blood samples and used for PCR amplification, followed by partial sequencing of the <it>pfcrt </it>gene. For <it>pfmdr-1 </it>N86Y mutation, the PCR product was subjected to restriction digestion with AflIII endonuclease enzyme.</p> <p>Results</p> <p>In 240 <it>P. falciparum </it>isolates with reported <it>in vivo </it>CQ therapeutic efficacy, the analysis of mutations in <it>pfcrt </it>gene shows that mutant SVMNT-S (67.50%) and CVIET-S (23.75%) occurred irrespective of clinical outcome and wild type CVMNK-A (7.91%) occurred only in adequate clinical and parasitological response samples. Of 287 <it>P. falciparum </it>isolates, SVMNTS 192 (66.89%) prevailed in all study sites and showed almost monomorphic existence (98.42% isolates) in low <it>P. falciparum </it>prevalent areas. However, CVIETS-S (19.51%) and CVMNK-A (11.84%) occurrence was limited to high <it>P. falciparum </it>prevalent areas. Investigation of <it>pfmdr-1 </it>N86Y mutation shows no correlation with clinical outcomes. The wild type N86 was prevalent in all the low <it>P. falciparum </it>prevalent areas (94.48%). However, mutant N86Y was comparably higher in numbers at the high <it>P. falciparum </it>prevalent areas (42.76%).</p> <p>Conclusions</p> <p>The wild type <it>pfcrt </it>gene is linked to chloroquine sensitivity; however, presence of mutation cannot explain the therapeutic efficacy of CQ in the current scenario of chloroquine resistance. The monomorphic existence of mutant SVMNT haplotype, infer inbreeding and faster spread of CQR parasite in areas with higher <it>P. vivax </it>prevalance and chloroquine exposure, whereas, diversity is maintained in <it>pfcrt </it>gene at high <it>P. falciparum </it>prevalent areas.</p

HIV Protease Inhibitors, Indinavir or Nelfinavir, Augment Antimalarial Action of Artemisinin in vitro

Most malaria endemic regions are co-infested with HIV infection. Treatment of one may affect outcome of the other in co-infected individuals. HIV protease inhibitors, indinavir or nelfinavir, are important antiretroviral drugs and artemisinin is central to malaria treatment. We show these protease inhibitors augment the antimalarial activity of artemisinin against P. falciparum in vitro