Abstract:
Background: The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for
continued global surveillance of the efficacy of artemisinin-based combination therapies.
Methods: On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P.
falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from
2005 to 2008. (ISRCTN88705995)
Results: The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005–2006 to 87% in 2007–2008
(odds ratio, 5.4, 95%CI, 2.7–11.1; P,0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7–9.9; P = 0.002) in the DHA-PPQ and AMLM
groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased
from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing
transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005–2006
and 2007–2008 (OR body temperature .37.5uC, 2.8, 1.9–4.1; P,0.001). Neither in vitro sensitivity of parasites to DHA nor
levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof.
Conclusions: The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs
may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level
clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better
understanding of the mechanisms underlying reduced parasite clearance rates.
