Comparison of in vivo and in vitro tests of resistance in patients treatedwith chloroquine in Yaounde, Cameroon

The usefulness of an isotopic in vitro assay in the field was evaluated by comparing its results with the therapeutic response-determined by the simpl ified WHO in vivo test in symptomatic Cameroonian patients treated with chl oroquine. Of the 117 enrolled patients, 102 (87%) completed the 14-day foll ow-up, and 95 isolates obtained from these patients (46 children, 49 adults ) yielded an interpretable in vitro test. A total of 57 of 95 patients (60% ; 28 children and 29 adults) had an adequate clinical response with negativ e smears (n = 46) or with an asymptomatic parasitaemia (n = 11) on day 7 an d/or day 14. The geometric mean 50% inhibitory concentration of the isolate s obtained from these patients was 63.3 nmol/l. Late and early treatment fa ilure was observed in 29 (30.5%) and 9 (9.5%) patients, respectively. The g eometric mean 50% inhibitory concentrations of the corresponding isolates w ere 173 nmol/l and 302 nmol/l. Among the patients responding with late and early treatment failure, five isolates and one isolate, respectively, yield ed a discordant result (in vivo resistance and in vitro sensitivity). The s ensitivity, specificity, and predictive value of the in vitro test to detec t chloroquine-sensitive cases was 67%, 84% and 86%, respectively. There was moderate concordance between the in vitro and in vivo tests (kappa value = 0.48). The in vitro assay agrees relatively well with the therapeutic resp onse and excludes several host factors that influence the results of the in vivo test. However, in view of some discordant results, the in vitro test cannot substitute for in vivo data on therapeutic efficacy. The only reliab le definition of "resistance" in malaria parasites is based an clinical and parasitological response in symptomatic patients, and the in vivo test pro vides the standard method to determine drug sensitivity or resistance as we ll as to guide national drug policies.