Ex vivo drug sensitivity of malaria parasites under selective pressure in Tororo, UgandaAmerican Society of Tropical Medicine and Hygiene Meeting (2011)
Artemisinin-based combination therapies (ACTs) are standard treatments for uncomplicated malaria in Africa. ACTs provide highly effective treatment, and regular use may offer protection against malaria in high risk populations. However, increased use of ACTs may select for parasites with decreased sensitivity. We studied the ex vivo sensitivity of malaria parasites collected from children enrolled in treatment and prevention trials in Tororo, Uganda from June, 2010 to August, 2011. When P. falciparum malaria was diagnosed, blood was obtained, parasites were cultured with serial dilutions of chloroquine (CQ), monodesethylamodiaquine (AQ), quinine (QN), dihydroartemisinin (DHA), lumefantrine (LM), and piperaquine (PQ) for 72 hours, and the ex vivo activity of antimalarial drugs was assessed by HRP-2-based ELISA. Preliminary findings based on evaluations of 153 isolates are presented here. Sensitivities to CQ (median IC50 283 nM; IQR 99.0-585), AQ (83.8 nM; 45.6-140), and QN (73.4 nM; 41.6-113) varied widely. Parasites were generally highly sensitive to LM (1.3 nM; 0.7-3.1) and DHA (1.7 nM; 0.9-3.0), but sensitivities to PQ varied over a fairly wide range (9.2 nM; 4.0-31.5). Considering results longitudinally, IC50 values for 4 successive intervals, each containing 38-39 isolates, varied little for control parasite strains and all drugs except LM and PQ, which each showed a trend toward increasing IC50 over time. However, considering drug exposure, neither receiving monthly DHA-PQ nor having received artemether-LM (AL) as treatment for a prior episode of malaria within 60 days was associated with decreased sensitivity to the relevant drugs. In summary, recent isolates of P. falciparum in Tororo had varied sensitivity to CQ, AQ and QN and remained highly sensitive to components of AL and DHA-PQ, the current national treatment regimens. However, although parasites were generally highly sensitive to LM and PQ, sensitivities may be decreasing. Longitudinal surveillance of ex vivo sensitivities of isolates under different clinical selective pressures continues.
Publication DateDecember, 2011
Citation InformationP. K. Tumebaze, O. Byaruhanga, J. Okiring, S. L. Nsobya, et al.. "Ex vivo drug sensitivity of malaria parasites under selective pressure in Tororo, Uganda" American Society of Tropical Medicine and Hygiene Meeting (2011)
Available at: http://works.bepress.com/roland_cooper/38/