Improving methods for analysing anti-malarial drug efficacy trials: molecular correction based on length-polymorphic markers msp-1, msp-2 and glurp.

Improving methods for analysing anti-malarial drug efficacy trials: molecular correction based on length-polymorphic markers msp-1, msp-2 and glurp. Antimicrob Agents Chemother. 2019 Jul 15;: Authors: Jones S, Kay K, Hodel EM, Chy S, Mbituyumuremyi A, Uwimana A, Menard D, Felger I, Hastings I Abstract BACKGROUND: Drug efficacy trials monitor the continued efficacy of front-line drugs against falciparum malaria. Over-estimates of efficacy result in a country retaining a failing drug as first-line treatment with associated increases in morbidity and mortality, while under-estimating drug effectiveness leads to removal of an effective treatment with substantial practical and economic implications. Trials are challenging: they require long durations of follow-up to detect drug failures, and patients are frequently re-infected during that period. Molecular correction based on parasite genotypes distinguishes reinfections from drug failures to ensure the accuracy of failure rate estimates. Several molecular correction "algorithms" are proposed, but which is most accurate and/or robust remains unknown. METHODS: We used pharmacological modelling to simulate parasite dynamics and genetic signals that occur in patients enrolled in malaria drug clinical trials. We compared estimates of treatment failure obtained from a selection of proposed molecular correction algorithms against the known "true" failure rate in the model. FINDI...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research