Application of Epidemiology and Biostatistics to Malaria Diagnosis in Returning Travellers
Bibliographic record
Abstract
Today, malaria elimination is back on the agenda but for this to be feasible, there must be a coordinated global effort utilizing all available tools. Portable, sensitive diagnostics with a low limit of detection are required to detect the malaria reservoir, and novel antimalarials are required to combat the threat of artemisinin resistance. Returning travellers are a good population in which to investigate malaria physiology and diagnostics because there is a good supply of study participants and an abundance of easily available data. In Canada, a combination of microscopy and rapid diagnostic tests are used to diagnose malaria, but these lack sensitivity and require repeated testing to rule out the condition. A prospective diagnostic trial of the illumigene Malaria, loop-mediated isothermal amplification (LAMP) assay, manufactured by Meridian Bioscience was conducted in symptomatic returning travellers between June 2017 and January 2018. After discrepant resolution with RT-PCR, LAMP had a sensitivity of 100% (95% CI; 95.8-100) and a specificity of 100% (95% CI; 98.7-100). In symptomatic returning travellers, LAMP has the potential to replace traditional malaria diagnostics, allowing for malaria to be ruled out in a timely manner. It is unclear if uncomplicated malaria causes deranged liver enzymes, which has implications for antimalarial drug development. A retrospective cohort study was evaluated in returning travellers (n=4548) who underwent a malaria test and had liver enzymes measured within 31 days from 2010-2017. After adjusting for gender, age, and use of hepatotoxic medications, returning travellers testing positive for malaria had higher odds of having an abnormal TB [(OR: 12.64, 95% CI: 6.32 – 25.29), p<0.001] but not ALP [(OR: 0.32, 95% CI: 0.09 – 1.10), p=0.072], ALT [(OR: 1.01, 95% CI: 0.54 – 1.89), p=0.978] or AST [(OR: 1.26, 95% CI: 0.22 – 7.37), p=0.794], compared to those who tested negative. This is most likely to be due to haemolysis, which normalizes following treatment. LAMP can be used in the diagnosis of malaria in returning travellers, and it may have a role in malaria elimination. Uncomplicated malaria does not appear to cause raised aminotransferases in returning travellers, and consideration must be given to this in antimalarial drug development.
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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 | 0.033 | 0.098 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.006 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".