Comparison of In Vivo and In Vitro Tests of Resistance in Plasmodium Falciparum Positive Patients Treated With Artemisinin Based Combination Therapy in Northwestern Nigeria

Comparative studies on in vitro and in vivo drug response of Plasmodium falciparum isolates were carried out among malaria positive resident of Kano and Katsina states of Nigeria, to determine the effectiveness of in vitro antimalarial drug sensitivity test as a substitute for in vivo therapeutic response analysis. The in vitro test was carried out using Schizont growth inhibition assay which was evaluated by comparing its results with the in vivo/therapeutic response determined by 28 days follow-up of the Plasmodium falciparum positive patient treated with different Artemisinin combination therapy (Artemether-lumefantrine, Dihydroartemisinin-piperaquine, Artesunate-amodiaquine). Out of 652 patients enrolled, 227 (34.8%) completed the 28 days follow-up, and 120 isolates from subjects with complete follow-up data yielded an interpretable in vitro test. A total of 100 of 120 patients (83.3%) had adequate clinical and parasitological response. The geometric mean 50% inhibitory concentrations (IC50) of the isolates obtained from these patients were 2.03nM, 3.65nM and 4.68nM for Artemether-lumefantrine (AL), Dihydroartemisinin-piperaquine (DHP) and Artesunate-amodiaquine (AA) respectively (in vitro and in vivo sensitive). Treatment failure was observed in 20 (16.7%) of 120 patients whose IC50 values were 2.11nM, 3.77nM and 4.80nM for AL, DHP and AA respectively. Moreover all the isolates of the patients responding with treatment failure yielded a discordant result (i.e. in vivo resistance and in vitro sensitive). Thus, the result of this study indicates poor agreement between the in vitro and in vivo test (Kappa value = 0) with regards to treatment failure. The in vitro assay cannot therefore be used as a substitute for in vivo therapeutic test for drug efficacy.