Causal prophylactic efficacy of atovaquone-proguanil (MalaroneTM) in a human challenge model
Bibliographic record
Abstract
Plasmodia infect the liver for about 7 days before subsequently infecting the blood. Present prophylaxis against Plasmodium falciparum malaria employs agents that primarily kill blood stages and must be continued for 28 days after the last exposure. Atovaquone-proguanil (Malarone) is a new antimalarial agent that is licensed in 35 countries as treatment against blood-stage infection, but its components (atovaquone and proguanil) have separately been shown to be active also against liver stages. To determine whether atovaquone-proguanil is sufficiently active against liver stages to be discontinued 7 days after exposure, we challenged 16 volunteers with P. falciparum via infected mosquitoes. Twelve volunteers received atovaquone-proguanil (1 tablet daily) on the day prior to challenge, on the day of challenge, and for the next 6 days; 4 volunteers received matching placebo. All placebo volunteers demonstrated parasitaemia and malarial symptoms beginning on days 11-12 after challenge. No atovaquone-proguanil volunteer acquired malaria. Atovaquone-proguanil is the first licensed antimalarial agent that kills P. falciparum in the liver and that may be discontinued 7 days after the last exposure.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".