The Effects of Antimalarial Drugs and Plasmodium Falciparum Drug Resistance Genes on Malaria Treatment Outcome

Abstract

Background: Malaria continues to be a major public health concern with majority of deaths occurring in the tropical regions. Control strategies within the human host have been through drug administration either as treatment of infected persons or prophylaxis. The challenge to effective malaria control is partly due to the emergence and the spread of resistant Plasmodia, especially in endemic countries. Confirmed antimalarial drug resistance is the combination of microscopic analysis of parasitaemia before and after three days of treatment and molecular analysis of resistance associated mutations in a patient. In Ghana, only few studies have reported on the combination of microscopic and molecular analysis in pregnancy associated malaria after the introduction of ACTs, especially in Accra. Aim: To determine the effects of antimalarial drugs and plasmodium falciparum drug resistance genes on malaria treatment outcome. Methodology: This was a longitudinal observational study. Convenient sampling was used to recruit 407 clinically diagnosed participants. The first sample was taken before drug administration and a follow up sample taken after drug administration. Thick and thin films together with rapid dagnostic test (RDTs) were used to confirm malaria. In-vivo and in-vitro hemolysis was also used to access haemolytic effect of antimalarial drugs on red cell indices. DNA was extracted from after treatment malaria positive samples, amplified and sequenced for resistance associated mutations. Results: Out of the participants recruited with malaria, no parasites were seen by microscopy after three days Artermeter lumenfantrine (AL) treatment, suggesting its effectiveness. Effects of the antimalarial on haemoglobin were not significantly different in AL and Sulfadoxine-Pyrimethamine (SP) treatment. With the exception of extraordinarily higher concentrations of the SP drugs which induced in vitro hemolysis in both Glucose-6-Phosphate Dehydrogenase (G6PD) normal and deficient blood samples, there was no hemolytic effect observed in either group with the lower drug concentrations. There was confirmed resistance to Pyramithamine in ten (10) out of eighteen (18) placental suspected samples with resistance-associated mutations (N51I and C59R) in the PfDHFR gene.