Drug treatment of scrub typhus: a systematic review and meta-analysis of controlled clinical trials

Scrub typhus, a potentially fatal infection caused by the pathogen Orientia tsutsugamushi, has a wide geographical distribution. This systematic review analyses the evidence from prospective controlled clinical studies for the efficacy of antibiotics in the treatment of scrub typhus. PubMed, Embase, Scopus, Cochrane Library, CINAHL and clinical trial registries in China, India and Sri Lanka were searched for controlled prospective clinical trials (randomized, quasi-randomized or non-randomized) enrolling patients with confirmed scrub typhus for treatment with antibiotics. The PROSPERO registration number for this review is CRD42017071374. Eleven studies (from Southeast Asia and China) that enrolled 957 patients into 28 study groups met the inclusion criteria. Doxycycline was the most frequent comparator with other antibiotics. Chloramphenicol, tetracycline and azithromycin (limited evidence for roxithromycin, telithromycin, levofloxacin and rifampicin) had equal efficacy to doxycycline in achieving clinical cure. The cure rates in all studies varied from 64 to 100%. Of the antibiotics frequently used in current practice, azithromycin had the best evidence compared with doxycycline for equal efficacy in clinical cure (three trials, 280 participants, moderate quality evidence) with fewer gastrointestinal adverse events. The preferred choice of antibiotics for each patient depends on the adverse effect profile, personal circumstances (e.g., age, pregnancy), cost and local prescription guidelines.