Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial

Background Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. Methods Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37·3°C). Findings About 12 800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0·01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22·5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27·5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0·02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. Interpretation Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.