Comparative in vitro susceptibility of clinical Leishmania isolates to miltefosine and oleylphosphocholine
Bibliographic record
Abstract
Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania . It poses a significant global health burden, particularly because treatment options are limited. More effective and safer treatments are urgently needed. In previous studies, oleylphosphocholine (OlPC), a novel investigational compound structurally related to miltefosine, exhibited comparable activity to miltefosine in intramacrophage assays across various CL-causing laboratory strains and demonstrated superior efficacy in an experimental CL model. This study investigated the in vitro activity of OlPC against clinical isolates of Leishmania spp., comparing its activity with standard anti-leishmanial drugs, including miltefosine, amphotericin B, and pentavalent antimonial agents. Seventy ex vivo isolates ( L. major and L. tropica ) obtained directly from CL patients before any treatment were used to capture the diversity of drug susceptibilities in circulating parasite populations. Dose-response curves were fitted using a four-parameter log-logistic model to estimate EC 50 and EC 90 values. Additionally, a linear mixed-effects model was applied to examine the influence of drug type and species on EC 50 values while accounting for within-isolate variability. Our findings indicate that OlPC exhibits potent in vitro anti-leishmanial activity, exceeding that of miltefosine in our in vitro intramacrophage model. To facilitate similar analyses, we provide a dedicated wrapper function in R designed to simplify curve fitting and parameter estimation, making the process more accessible to researchers.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".