Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial
Bibliographic record
Abstract
Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.
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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 | 0.006 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.006 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.004 |
| Insufficient payload (model declined to judge) | 0.014 | 0.001 |
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".