Scrub Typhus Antibiotic Resistance Trial

Inclusion Criteria:

• Age ≥ 15 years old
• Hospitalization with acute undifferentiated fever (temperature > 37.5°C, tympanic) ≤14days or patients admitted to hospital with a history of fever ≤ 14 days whosubsequently develop fever within 24 hours of admission
• Clinically suspected scrub typhus: defined as acute undifferentiated fever with noclear focus of infection and negative malaria blood smear and/or negative malaria RDT.Patients may have one, none, or a combination of other clinical findings such aseschar, rash, lymphadenopathy, headache, myalgia, cough, nausea and abdominaldiscomfort.
• A positive scrub typhus RDT (Scrub Typhus IgM RDT, InBios International, Seattle, WA,USA) and/or positive PCR-based detection of O. tsutsugamushi DNA from the admissionblood sample
• Written informed consent and/or, written informed assent as required
• Able to take oral medication

Exclusion Criteria:

• Known hypersensitivity to tetracycline, doxycycline or azithromycin
• Administration of doxycycline, azithromycin, chloramphenicol, rifampicin, ortetracycline during the preceding 7 days
• Pregnancy or breast-feeding
• Patients with myasthenia gravis or systemic lupus erythematosus
• Patients with an established infection (diagnostic test required) e.g. acute malaria,dengue, leptospirosis, typhoid, Japanese encephalitis etc.
• Current TB or TB treatment in ≤ 6 months (contain active antibiotics against Orientiaspp.)
• Current HAART use for HIV, long term use of immunosuppressants (e.g. steroids,chemotherapy, TNF-inhibitors and related agents)
• Patients with severe disease whom the clinical team feel their condition necessitatesthe need for additional scrub typhus treatment beyond the allocated antibiotictreatment assigned at randomization (e.g. IV chloramphenicol and/or PO/NG rifampicin)