2019
DOI: 10.1128/aac.00590-19
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Improving Methods for Analyzing Antimalarial Drug Efficacy Trials: Molecular Correction Based on Length-Polymorphic Markers msp-1 , msp-2 , and glurp

Abstract: Drug efficacy trials monitor the continued efficacy of front-line drugs against falciparum malaria. Overestimating efficacy results in a country retaining a failing drug as first-line treatment with associated increases in morbidity and mortality, while underestimating 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 reinfected … Show more

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Cited by 27 publications
(49 citation statements)
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“…We also did a sensitivity analysis to explore the possibility that some of the recrudescences identified by this PCR correction method could have been misclassified as reinfections. Recent work suggests that the percentage of patients experiencing recrudescence may be around 1-3% higher than estimated by standard PCR correction [64][65][66], with this error being relatively constant across transmission settings. We therefore also repeated our analysis after reclassifying some reinfections in each trial as recrudescences, sampling a number that would achieve a 3% higher recrudescence rate overall.…”
Section: Datamentioning
confidence: 97%
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“…We also did a sensitivity analysis to explore the possibility that some of the recrudescences identified by this PCR correction method could have been misclassified as reinfections. Recent work suggests that the percentage of patients experiencing recrudescence may be around 1-3% higher than estimated by standard PCR correction [64][65][66], with this error being relatively constant across transmission settings. We therefore also repeated our analysis after reclassifying some reinfections in each trial as recrudescences, sampling a number that would achieve a 3% higher recrudescence rate overall.…”
Section: Datamentioning
confidence: 97%
“…We weighted the sampling by timing of recurrent parasitemia in each patient as in Fig. 5 of [66], i.e., to allow for the fact that recrudescences are more likely to occur early during follow-up (see also Additional file 4:…”
Section: Datamentioning
confidence: 99%
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“…It is likely to affect recrudescent and re-infecting clones equally such that we would not expect it to alter how recurrent infections are classified. We did not model parasite sequestration (see (31) for justification). The output of this PK/PD model was, for each patient, the exact number of parasites of each malaria clone (be that clone an initial infection or a reinfection) at each time-step of the model (days); see figure S1 [SI] for an example.…”
Section: And 24 Of [Si]) Transmission Intensity (Quantified By Foi;mentioning
confidence: 99%
“…The genetic diversity and complexity of P. falciparum infections is to a very large extent an important indicator of malaria transmission intensity in a region and is a very useful marker for assessing naturallyacquired anti-malarial immunity as well as the impacts of intervention programmes [11,[33][34][35][36][37].…”
Section: Discussionmentioning
confidence: 99%