In vitro antimalarial therapeutic interventions using various combinations of antibiotics and standard antimalarials against multi drug resistant Indian field isolates of Plasmodium falciparum

Abstract

Resistance to antimalarials is considered to be major cause of increased malaria morbidity and mortality. Present study was undertaken to explore an effective drug combination against selected mutant parasite various combinations using standard antimalarials {Chloroquine diphosphate (CQ), Quinine (QUIN), Mefloquine (MQ), Piperaquine (PPQ), Artemether (ARTM), Arteether (ARTE), Dihydro-artemisinin (DHA), Lumefantrine (LUME)and Atovaquone (ATQ)} belonging to three different classes and two antibiotics, Azithromycin (AZI) and Doxycycline (DOXY) have been tried against K1 (chloroquine-resistant) and 3D7 (chloroquine-sensitive) strains as well as selected arteether torelant parasite (MZRI-R) and field isolates (MZRI & MZRII) of P. falciparum. SYBR Green I fluorescence (MSF) assay was used to determine IC50 values. Results of present studies highlighted that all the combinations used exhibited additive effect with varying intensity depending upon the drug ratios used. We also observed that combination of ARTM plus LUME was more advantageous than DOXY plus DHA/CQ and AZI plus CQ/ATQ for treatment of multidrug resistant parasites whereas combinations of LUME plus PPQ, ATQ plus DOXY/AZI can be used for treatment of CQ resistant parasite