Reply to Colebunders
Bibliographic record
Abstract
To the Editor–We read with interest the letter by Colebunders [1] regarding our recently published article in Clinical Infectious Diseases [2]. In our study, we found an association between Plasmodium parasitemia and survival of Ebola virus–infected individuals. Patients coinfected with Plasmodium parasites were 20% more likely to survive the Ebola virus infection. This effect was dose dependent as survival in the group with the highest level of parasitemia was 83% compared to 46% in patients infected with Ebola virus alone. All patients in our cohort received antimalarial artemether–lumefantrine (AL) treatment, independent of the outcome of the malaria diagnostic test. In his letter, Colebunders questions whether there really is an association between Plasmodium parasitemia and survival or whether this effect is somehow explained by the AL treatment. He states that Ebola virus–infected patients with an untreated Plasmodium coinfection may have an increased mortality risk compared with patients infected with Ebola virus alone and that antimalarial treatment would thus benefit coinfected patients. Although this is an interesting hypothesis, our cohort only consisted of AL-treated patients either infected with Ebola virus alone or patients coinfected with Ebola virus and Plasmodium parasites. The increased survival in the coinfected patients thus cannot be due to the resolution of the Plasmodium coinfection by the antimalarial treatment, as the other group was not infected with Plasmodium to begin with. Colebunders further argues that AL treatment itself may be detrimental to Ebola virus–infected patients by prolonging the QT interval. Although AL treatment can indeed result in QT interval prolongation, it is not clear how this could have a selective effect only in patients infected with Ebola virus alone. The study by Gignoux et al from Foya, Liberia [3], and referenced by Colebunders, included a group of patients infected with Ebola virus alone who were not treated with antimalarial drugs. When survival in this group was compared to that of patients infected with Ebola virus alone who did receive AL treatment, there was no statistically significant difference in survival, suggesting that AL treatment did not have a negative effect on patient outcome [3]. If there is an indication that AL treatment can have a negative effect on patient outcome in Ebola virus–infected patients, we should consider replacing this treatment scheme with a more appropriate choice of antimalarial drugs, as suggested by Gignoux et al [3] and by Colebunders [1]. However, this does not change our observation of increased survival in patients coinfected with Plasmodium parasites in the patient cohort from Monrovia, Liberia. Potential conflicts of interest. The authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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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 | 0.002 | 0.017 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.033 | 0.030 |
| Insufficient payload (model declined to judge) | 0.012 | 0.009 |
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".