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by WorldWide Antimalarial Resistance Network (WWARN) Methodology Study Group – including Kiechel JR. Malaria Journal, 2019, doi:10.1186/s12936-019-2837-4

Summary: The primary endpoint for therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria is recrudescence of the original infection. In the case of new infections where the parasite load outnumbers existing low levels of parasitaemia, recrudescence may not be detected, thus new infections constitute a ‘competing risk event’. Two methods– 1 minus Kaplan-Meier (K-M), which considers new infections acquired during the follow-up period as censored and the Cumulative Incidence Function (CIF), which accounts for them as a competing risk event – were used to determine the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository in 31,379 patients. The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infections was high. The CIF approach provides an alternative way of deriving failure estimates in antimalarial trials, particularly in high transmission settings.

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by Guidi M, Mercier T, Aouri M, Decosterd LA, Csajka C, Ogutu B, Carn G, Kiechel JR. Malaria Journal 2019, 18:139, doi:10.1186/s12936-019-2754-6.

Summary: WHO has recommended reconsideration of the use of ASMQ in Africa, where it is not frequently used due to perceived poor tolerance of mefloquine. In a large clinical study, the pharmacokinetics of a fixed dose combination of ASMQ was investigated in an African paediatric population. A subset of 50 Kenyan children from this trial underwent intensive sampling to develop population pharmacokinetic models for AS, its metabolite dihydroartemisinin (DHA) and MQ. Body weight was shown to be the largest contributor to variability in drug exposure. This is accommodated for by the ASMQ fixed dose combination dosing recommendation; beyond this there is no indication that the dosage should be modified in children with malaria compared to adults.

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“Malaria, the fever of fevers”

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“Diseases of inequality: the pains that Brazil doesn’t see”

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“Children, the last beneficiaries of medical innovation”

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“Neglected people, global policies”

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“Medicines as a public good”

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