Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali.

BACKGROUND: Artemisinin-based combination therapy is the recommended first-line treatment for uncomplicated falciparum malaria worldwide. However, recent studies conducted in Mali showed an increased frequency of recurrent parasitaemia following artemether-lumefantrine (AL) treatment. METHODS: Study samples were collected during a large WANECAM study. Ex-vivo Plasmodium falciparum sensitivity to artemether and lumefantrine was assessed using the tritiated hypoxanthine-based assay. The prevalence of molecular markers of anti-malarial drug resistance (pfcrt K76T, pfmdr1 N86Y and K13-propeller) were measured by PCR and/or sequencing. RESULTS: Overall 61 samples were successfully analysed in ex vivo studies. Mean IC50s increased significantly between baseline and recurrent parasites for both artemether (1.6 nM vs 3.2 nM, p < 0.001) and lumefantrine (1.4 nM vs 3.4 nM, p = 0.004). Wild type Pfmdr1 N86 allele was selected after treatment (71 vs 91%, 112 of 158 vs 95 of 105, p < 0.001) but not the wild type pfcrt K76 variant (23.5 vs 24.8%, 40 of 170 vs 26 of 105, p = 0.9). Three non-synonymous K13-propeller SNPs (A522C, A578S, and G638R) were found with allele frequencies <2%. CONCLUSION: Malian post-AL P. falciparum isolates were less susceptible to artemether and lumefantrine than baseline isolates.

Evaluation of the Mercy weight estimation method in Ouelessebougou, Mali.

BACKGROUND: This study evaluated the performance of a new weight estimation strategy (Mercy Method) with four existing weight-estimation methods (APLS, ARC, Broselow, and Nelson) in children from Ouelessebougou, Mali. METHODS: Otherwise healthy children, 2 mos to 16 yrs, were enrolled and weight, height, humeral length (HL) and mid-upper arm circumference (MUAC) obtained by trained raters. Weight estimation was performed as described for each method. Predicted weights were regressed against actual weights. Agreement between estimated and actual weight was determined using Bland-Altman plots with log-transformation. Predictive performance of each method was assessed using residual error (RE), percentage error (PE), root mean square error (RMSE), and percent predicted within 10, 20 and 30% of actual weight. RESULTS: 473 children (8.1±4.8 yr, 25.1±14.5 kg, 120.9±29.5 cm) participated in this study. The Mercy Method (MM) offered the best correlation between actual and estimated weight when compared with the other methods (r2=0.97 vs. 0.80-0.94). The MM also demonstrated the lowest ME (0.06 vs. 0.92-4.1 kg), MPE (1.6 vs. 7.8-19.8%) and RMSE (2.6 vs. 3.0-6.7). Finally, the MM estimated weight within 20% of actual for nearly all children (97%) as opposed to the other methods for which these values ranged from 50-69%. CONCLUSIONS: The MM performed extremely well in Malian children with performance characteristics comparable to those observed for U.S and India and could be used in sub-Saharan African children without modification extending the utility of this weight estimation strategy.