Therapeutic Efficacy Trial (TET)

EFFICACY OF ARTEMETHER-LUMEFANTRINE AND AMODIAQUINE-ARTESUNATE FOR TREATMENT OF UNCOMPLICATED MALARIA IN CHILDREN IN UGANDA

Principal Investigator: Professor Moses Kamya, Makerere University

Co-Investigators: Adoke Yeka, Makerere Univerity; Okui Albert Peter, Uganda National Malaria Control Program ; Lugemwa Myers, National Malaria Control Program; Katureebe Charles, WHO-Uganda; Grant Dorsey, UCSF; Sarah Staedke, LSHTM; Phil Rosenthal, UCSF

Location: The studies will be conducted at 3 of the Uganda Malaria Surveillance Project (UMSP) sentinel sites. These sites were originally established in 1998 by the Ugandan Ministry of Health (MOH) in collaboration with the East African Network for Monitoring Antimalarial Treatment (EANMAT).


Sponsor: CDC

There is a genuine fear that resistance against ACTs may develop. Although there is no direct evidence of full-blown clinical treatment failure of artemisinin derivatives, there are some worrying findings suggesting a reduced susceptibility of parasite isolates for ACTs. An increased resistance of parasite isolates to different artemisinin derivatives was observed in vitro for P. falciparum field isolates from Cambodia and reduced efficacy to artemisinin derivatives has been observed in the same region. Delayed parasite clearance is the clinical phenotype of artemisinin resistance. Studies on the development of resistance to ACT and the spread of ACT resistant parasite strains in the population are extremely relevant from a public health perspective. The data that are collected in this study will be available to the Ugandan MOH to assist in drug policy decision-making.

This study will be randomized, single blinded trials at three sites in Uganda designed according to 2009 World Health Organization (WHO) guidelines for assessment of therapeutic efficacy of antimalarial agents in areas of low, moderate and intense transmission with slight modifications. The target populations shall include residents of the catchment areas of the three district health centers where the studies will be performed. The available populations includes residents aged 6 – 59 months who present to the study clinics with symptoms suggestive of malaria and who have a positive screening thick blood smear. Subjects who meet the selection criteria will be randomized to treatment with one of the two study regimens and will be followed for 28 days. Repeat evaluations will be performed on days 1, 2, 3, 7, 14, 21, and 28 (and any unscheduled day) and will include assessment for the occurrence of adverse events. Treatment efficacy outcomes will be assessed using WHO outcome classification criteria. Study patients will be classified as therapeutic failures (early or late) or adequate responders based on the results of these assessments. The proportion of patients experiencing a therapeutic failure during the follow-up period will be used to estimate the efficacy of the study drugs. Polymerase Chain Reaction (PCR) analysis will help to distinguish between a true recrudescence due to treatment failure and episodes of re-infection.