CML-004: Imatinib is Protective Against Falciparum Malaria: A Case Control Study from a Tertiary Care Centre in West Bengal

Abstract

Context Rising evidence of artemisin resistant malaria in Indian subcontinent and South America has prompted researchers to search for alternative antimalarials. In the last few decades, few reports and subsequent in vitro results have emerged showing dependence of malarial parasites, particularly P falciparum, on RBC tyrosine kinases for its maturation and egress. As there were no clinical data to support the hypothesis, we conducted a case control study with patients of CML-CP on fixed dose imatinib (TKI) as cases and a representative healthy population as control. Objective To compare the prevalence of asymptomatic falciparum and vivax infections in study cases with the prevalence of matched control taken from healthy blood donors. Methods A standard questionnaire and rapid diagnostic test (RDT) for plasmodium antigens from the blood of cases attending CML clinic were used as study tools. 191 CML patients who are on imatinib 400mg/d for a minimum period of 1 year were analysed. Controls were healthy voluntary blood donors attending the hospital during the same time-frame. Study time was April-September (peak malaria season). All RDT +ve cases were internally validated with PCR using two species specific forward primers. Results Out of 54 febrile episodes among cases during the study period, one had vivax malaria. RDT testing on non-febrile participants revealed two samples positive for dual vivax-falciparum antigens and the other two for vivax antigen. PCR showed three cases positive for vivax and one positive for both vivax and falciparum. Among 205 controls, three had vivax infections, three had falciparum infections and four were found to have infections with both. The concordance for positive results among the diagnostic modalities (RDT and PCR) was found to be 93.3%. The prevalence of malarial infections in cases and controls were found to be 2.05% and 4.87% respectively while falciparum parasitemia in cases and controls were found to be 0.51% and 3.41% respectively. Conclusion Analysis showed that the difference of asymptomatic falciparum carriage among cases and control was statistically significant suggesting a protective effect of imatinib against falciparum infections. The association of vivax positivity with imatinib exposure was however not statistically significant.