Abstract
BACKGROUND: The genetic complexity and the existence of several polymorphisms in parasites are the major hindrances for the malaria control programmes of the country. The genetic profiling in the parasite populations in India will provide useful baseline data for future studies elucidating the parasite structure and distribution of drug resistance genotypes in different regions. METHODS: The blood samples of symptomatic patients were collected and analysed for drug resistance genes (Pfcrt, Pfmdr-1, dhfr, dhps and k13) and gametocyte genes (Pfs25, Pfg377); in vitro drug sensitivity assay by schizont maturation inhibition (SMI) was also performed in adapted field isolates. RESULTS: Of the 122 field isolates analysed; 65.5% showed Pfcrt K76T mutant alleles, 61.4% Pfmdr-1 N86Y mutants, 59.5% dhfr mutants, 59.8% dhps mutants was observed, but no polymorphism was seen for k13. The sequence analysis of Pfg377 gene revealed five types of populations in the field isolates. The inhibitory concentrations (IC(50)) for anti-malarial drugs viz chloroquine (CQ), artesunate (AS), were in the range of 10.11-113.2 nM and 2.26-4.08 nM, respectively, in the field isolates evaluate by in vitro assay. The IC(50) values for CQ have shown a remarkable reduction on comparison with the previous available data, whereas a slight increase in the IC(50) values for AS was observed in the study. CONCLUSIONS: The increase in mutation rate in drug resistance allelic loci with inhibitory concentration of CQ and AS drugs was observed in the field isolates and high diversity in Pfg377 gametocyte gene indicate towards parasite multifactorial behaviour. The knowledge of the prevalent drug resistance genes is important for intervention measures to be successful and efforts should also be made to prevent transmission of P. falciparum.