Mutations in P. falciparum K13 propeller gene from Bangladesh: emerging resistance?
Bibliographic record
Abstract
Bangladesh is a malaria hypo-endemic country sharing borders with India and Myanmar. ACT remains quite successful in Bangladesh. An increase of heritable artemisinin resistant malaria parasites on the Thai-Cambodia border and subsequently the Thai-Myanmar border is worrisome. K13 propeller gene (PF3D7_1343700 (PF13_0238) mutations have been linked to both in vitro artemisinin resistance and in vivo slow parasite clearance rates and therefore proposed as a marker of artemisinin resistance. We evaluated if mutations seen in Cambodia have emerged in Bangladesh where ACT use is now standard for over a decade. Samples were obtained from P. falciparum infected malaria patients from Upazila Health Complexes (UHC) of seven endemic districts of Bangladesh. These districts included Khagrachhari (Matiranga UHC), Rangamati (Rajsthali UHC), Cox’s Bazar (Ramu and Ukhia UHC), Bandarban (Lama UHC), Mymensingh (Haluaghat UHC), Netrokona (Durgapur and Kalmakanda UHC) and Moulvibazar (Srimongol and Kamalganj UHC). Out of 296 microscopically positive P. falciparum samples, 271(91.6%) were confirmed by both real-time PCR and nested PCR to have pure infection. Nested PCR of the K13 gene amplified 253 (93.4%) samples. After ClustalW alignment and Jalview analysis, we initially found three non-synonymous mutations (A578S, W470C, and Y604H) in Bangladeshi clinical isolates. The A578S mutation was confirmed and lies adjacent to the C580Y mutation, the major mutation observed in Cambodia, and based on computational modeling should have a significant effect on tertiary structure. We conclude that novel mutations that may confer artemisinin resistance are present in certain districts of Bangladesh.
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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 | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".