Background: Malaria microscopy, while the gold standard for malaria diagnosis, has limitations. Efficacy estimates in drug and vaccine malaria trials are very sensitive to small errors in microscopy endpoints. This fact led to the establishment of a Malaria Diagnostics Centre of Excellence in Kisumu, Kenya. The primary objective was to ensure valid clinical trial and diagnostic test evaluations. Key secondary objectives were technology transfer to host countries, establishment of partnerships, and training of clinical microscopists.

Abstract. The use of reversing agents to overcome drug resistance is a potential new treatment strategy for both malaria and cancer. Laboratory studies have raised questions about the safety of this therapeutic approach, but data in humans are lacking. We therefore assessed the toxic potential of reversing agent therapy in Thai patients receiving quinine (17 mg/kg given over 4.5 hr) for falciparum malaria by serial measurements of the QT, interval, an electrocardiographic (ECG) marker of the effect of quinine. Six patients were randomly assigned to receive intravenous quinine alone while another six received one intramuscular injection of 12.5 mg of the reversing agent prochlorperazine (PC; compazine®, stemetil®) 2.5 hr after the quinine infusion had begun. Compared with baseline values at 2.5 hr, there was prolongation of the QTc interval 30, 60, 90, and 120 min after PC was injected (P < 0.05) but no further lengthening with quinine alone (P > 0.2). Prochlorperazine alone did not lengthen the QT, interval in six healthy volunteers. Neither total nor free quinine plasma levels increased after PC was injected, suggesting that ECG changes may have been due to PC-induced intracellular accumulation of quinine. Although only minor quinine ECG effects were amplified by the reversing agent PC in this study, resistance-reversing therapy could potentiate more serious drug effects. The possibility that more serious toxic effects could be produced by this therapeutic approach should be investigated further.Infection with drug-resistant strains of Plas-intracellular concentrations of chloroquine in modium falciparum is a growing public health cultured hepatocytes. 6 It has also been observed problem in most malaria-endemic areas. Mech-that when mice were given the anticancer comanisms of resistance remain poorly understood, pound vincristine with the reversi ig agent verbut some resistant parasites can rapidly release apamil, vincristine tissue levels were increased, antimalarial compounds, thereby reducing drug with more deaths following the combination than accumulation.' Greater drug efflux is one of sev-in mice given vincristine alone.' eral features resistant malaria parasites share withWe therefore investigated the possible toxicity drug-resistant cancer cells, in which the efflux is of reversing agent treatment by measuring delays mediated by a transport protein, P-glycopro-in myocardial repolarization in patients receivtein.-I ing quinine for falciparum malaria. Such delays, A new, as yet unproven approach to malaria manifested as a prolonged QT, interval on the treatment involves reversing resistance by using electrocardiogram (ECG), occur commonly at calcium antagonists and other reversing agents therapeutic plasma quinine levels but are not to inhibit the parasite's drug efflux pump." How-associated with cardiac or other serious adverse ever, the rationale for reversing agent therapy is effects.8-,o A prolongation of the QTc interval is perhaps compromised by the fact that normal therefore an objective, safe mea...

Mefloquine, a new antimalarial which has been effective in curing malaria due to Plasmodium falciparum and P. vivax, was used for the first time in a patient infected with P. malariae. Treatment was successful, and the relatively long parasite clearance time and fever clearance time were probably characteristic of P. malariae rather than true drug resistance.