Abstract

Olusegun Wale, Abeeb V. E, Kolawale O. Femi and Oluwatoyin David

In vitro assays still remain a vital stage of antimalarial drug development process and resistance monitoring. This study assessed the sensitivity patterns of isolates of Plasmodium falciparum to amodiaquine (AQ) alone or in combination with verapamil (VER), chlorpheniramine (CP) and promethazine (PRO) as resistance reversing compounds. The test involves monitoring the ability of antimalarial drugs to prevent parasite transition from trophozoites to schizont stages over a 24-48 h incubation period in vitro by World Health Organization (WHO) schizont inhibition assay. The MIC of AQ alone ranged from 6.2-500.0 ng/ml while those of its reversing agents ranged from 2.1-500.0 ng/ml. Mean MIC for AQ=120.51±15.10. Based on the cut-off value for AQ in vitro susceptibility, 73% (76/104) of the P. falciparum isolates were sensitive to AQ while 27% (28/104) were resistant. The mean MIC values for AQ + VER, AQ + CP and AQ + PRO were 83.08 ± 9.39, 106.93 ± 13.28 and 111.09 ± 14.82 respectively. Based on the reversal phenomenon, 75% (78/104) of the isolates were classified sensitive to amodiaquine, while 25% (26/104) were classified resistant with verapamil as reversing agent (P<0.05). Furthermore, 85% (88/104) were sensitive to amodiaquine while 15% (16/104) were resistant with chlorpheniramine as reversing agent (P<0.05). In the same vein, 78% (81/104) were sensitive to amodiaquine while 22% (23/104) were resistant with promethazine as reversing agent (P<0.05). The present results demonstrated high sensitivity pattern to the drug combinations. However, the very low levels of in vitro P. falciparum resistance against chlorpheniramine may demonstrate its pharmacological advantage as a better reversing agent over others. Subsequent surveillance should, in addition, integrate both in vivo and molecular surveillance to characterize the true nature of P. falciparum isolates in this area.