Weight-related malaria treatment failure with artemether-lumefantrine
Bibliographic record
Abstract
We describe a case of symptomatic Plasmodium falciparum recrudescence following the completion of artemether and lumefantrine (AL) therapy likely due to weight-based under-dosing of these antimalarial medications. AL is an antimalarial drug combination that may be used for self-treatment.1 This patient weighed 90 kg and was potentially under-dosed with AL. Sondén et al. reported a case series of non-immune travellers with P. falciparum infection in Sweden from 2000 to 2015.2 In total, 95 patients received AL and five treatment failures were reported.2 Amongst these five cases, genotyping confirmed no significant resistance patterns.2 All cases of AL treatment failure were in European men, and in the 61 patients for whom weight was measured, AL was 100% effective in those whose weight was less than or equal to 65 kg whilst only 90.4% effective in those whose weight was above 65 kg.2 Lumefantrine concentrations were subtherapeutic in at least two individuals.2 Bourque et al. described a case of a returned traveller from Liberia with symptomatic malaria recrudescence 10 days after treatment with AL, who then recovered with atovaquone-proguanil.3 There were no P. falciparum kelch13 (pfk13) mutations found, which confers reduced susceptibility to artemisinin. A study of 165 non-immune patients from Europe and areas of Colombia that are non-endemic for malaria noted that in their subgroup analysis patients who weighted 65 kg or less had a cure rate of 100% but those who weighed ˃65 kg had 93.4% cure rate at 28 days.4 Pharmacokinetic data from studies measuring lumefantrine and desbutyl-lumefantrine concentrations did not demonstrate strong correlations with weight,4 however, weight may still be a contributing factor to some treatment failures.3
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".