Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 – 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36–17.97, P < 0.001) were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

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Abstract. Rapid diagnosis and accurate quantification of Plasmodium falciparum parasitemia are important for the management of malaria. The assessment of disease severity also depends on evaluation of metabolic indexes such as blood glucose and lactate concentrations. Here we describe an accurate and rapid alternative to conventional thick film examination (Lambaréné method). We also assess near-patient methods for measuring blood glucose (OneTouch) and lactate (Accusport). The accuracy of the Lambaréné method is similar to that of thin films. Results from the OneTouch glucose meter also are in good agreement with a YSI 2300 reference meter. Overall, the Accusport lactate meter agrees poorly with the YSI 2300 reference meter. However, the sensitivity and specificity to detect hyperlactatemia (blood lactate Ն 5 mmol/L) are 0.94 and 0.98, respectively.

This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed-dose formulation; both treatments provided high PCR-adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.

Background: An assessment of the accuracy of two malaria rapid diagnostic tests (RDT) for the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) or Pf lactate dehydrogenase (PfLDH) was undertaken in children aged between six and 59 months included in an anti-malarial efficacy study in Benin.