Blood folate concentrations and in vivo sulfadoxine-pyrimethamine failure in Malawian children with uncomplicated Plasmodium falciparum malaria.

Folate antagonizes the antimalarial action of sulfadoxine-pyrimethamine (SP) in vitro, but its role in vivo is not well understood. We measured blood folate concentrations and SP therapeutic outcomes in Malawian children. Children with late treatment failure and those with adequate clinical and parasitologic responses had similar demographic characteristics, prevalence of parasite mutations conferring resistance to SP, and blood concentrations of anti-malarial drugs following treatment. However, a higher folate concentration was associated with late treatment failure. Patients from a low malaria transmission site had higher blood folate concentrations than those in a higher transmission site (mean +/- SEM = 39 +/- 9.3 ng/mL versus 29 +/- 10 ng/mL; P < 0.0001), and there was a higher rate of late treatment failure in the low transmission area (54.4% versus 40.2%; P = 0.010). This study also provides the first evidence of the independent role of physiologic folate concentrations in in vivo SP therapeutic efficacy, and the critical role of pyrimethamine concentrations in the therapeutic efficacy of SP when one controls physiologic folate levels and the frequency of critical dihydrofolate reductase/dihydropteroate synthase mutations.

Feasibility of LDF measurements of optic nerve head blood flow in children with cerebral malaria.

The pathogenesis of cerebral malaria (CM), a significant cause of death in the tropics, is still not understood. Cerebral blood flow measurements would be important but are difficult under the conditions prevailing in CM clinics in the tropics. With the goal of using optic nerve head (ONH) blood flow (F(onh)) instead of cerebral blood flow to help outcome prediction, we have tested the feasibility of performing F(onh) measurements in comatose CM children, using a portable ocular laser Doppler flowmeter (LDF). Measurements were performed in one eye of each of 13 children (2.7 +/- 1.1 years) during a period of about 8 min. The Vel(onh) (the relative blood velocity), Vol(onh) (the relative blood volume), and F(onh) values were determined for each child from three to five measurements of 2 to 20 s. Average Vel(onh), Vol(onh), and F(onh) values were 0.49 +/- 0.08 kHz, 2.4 +/- 1.06 arbitrary units (a.u.), and 89 +/- 16.8 a.u., respectively. The average coefficients of variation of the flow parameters based on all segments in each child were 13 +/- 9% (range 1-29%) for Vel(onh), 27 +/- 13% (range 3-65%) for Vol(onh), and 23 +/- 12% (range 5-42%) for F(onh). This study demonstrates the feasibility of LDF measurements in CM children. The large range of these coefficients of variations could be due to the presence of fluctuations of ONH blood flow on a short time scale in these neurologically unstable children.