What is the recommended first‑line treatment and alternatives for an adult presenting with fever, headache, myalgia, rash and an eschar after exposure in an endemic Asia‑Pacific rural setting (suspected scrub typhus)?

Scrub Typhus: First-Line Treatment and Alternatives

Doxycycline 100 mg twice daily (oral or IV) is the definitive first-line treatment for adults with suspected scrub typhus and should be initiated immediately without waiting for laboratory confirmation. 1, 2

Immediate Empiric Treatment

Start doxycycline immediately when scrub typhus is suspected based on the clinical presentation of fever, headache, myalgia, rash, and eschar in an endemic Asia-Pacific rural setting. 1, 2 Treatment delay can lead to severe complications including acute respiratory distress syndrome (ARDS), cerebrovascular injury, and death. 3, 4, 5

Dosing Regimens

Adults:

• Doxycycline 100 mg twice daily (oral or IV) 1, 2
• Continue for at least 3 days after fever subsides 2
• Minimum treatment course: 5-7 days 2

Children under 45 kg:

• Doxycycline 2.2 mg/kg body weight twice daily 1, 2
• The historical concern about dental staining should not prevent short-course doxycycline use in children under 8 years 2

Expected Clinical Response

Fever typically subsides within 24-48 hours after starting doxycycline in early disease. 6, 1, 2 This rapid response is characteristic and helps confirm the diagnosis. If no improvement occurs within 48 hours in early disease, strongly consider alternative diagnoses. 6, 2 However, severely ill patients with multi-organ dysfunction may require more than 48 hours before clinical improvement is noted. 1, 2

Alternative Antibiotics

Chloramphenicol is the primary alternative when doxycycline cannot be used:

• Dose: 12.5-25 mg/kg every 6 hours IV 1, 2
• Consider when broader differential diagnosis is being entertained 6

Azithromycin may be considered as an alternative, particularly in combination therapy for severe cases. 6, 7 One recent case series from the Maldives demonstrated clinical improvement with combined doxycycline and azithromycin therapy in severe cases with multiorgan dysfunction. 7

Fluoroquinolones are mentioned as alternatives when a wider differential is considered. 6

Critical Clinical Context

Epidemiology and Risk

Scrub typhus is endemic in rural South Asia (especially Laos), Southeast Asia, and the Western Pacific, transmitted by mite bites. 6, 1 The mortality rate can reach 4-32% without adequate treatment, with complications occurring more frequently than previously recognized. 6, 3, 5

Diagnostic Considerations

• Eschar is present in only 60% of cases, so its absence should not exclude the diagnosis. 1, 3
• Serological testing is the primary diagnostic method, but treatment must never be delayed while awaiting laboratory confirmation. 1, 2
• The disease presents with nonspecific flu-like symptoms that can delay diagnosis, particularly when co-infections occur. 8

Severe Complications Requiring Hospitalization

Pulmonary complications occur in up to 36% of cases, with ARDS developing in 15%. 6, 1, 5 Other serious complications include:

• Central nervous system involvement (meningitis/meningoencephalitis) in 20% 1
• Acute renal failure in 9% 1, 5
• Myocarditis, septic shock, and cerebrovascular injury 3, 4, 5

Metabolic acidosis, ARDS, altered sensorium, and shock are independent predictors of mortality. 3

Management of Severe Disease

For patients with multi-organ dysfunction:

• Use IV doxycycline for all hospitalized patients, particularly those vomiting or obtunded 2
• Require hospitalization with intensive supportive care 1
• Careful fluid management is essential—avoid overhydration as pulmonary complications are common 1
• May require mechanical ventilation and renal replacement therapy 7, 5
• Longer treatment courses are needed for severe or complicated disease 2

Common Pitfalls to Avoid

Do not delay treatment while waiting for serological confirmation or the appearance of an eschar—the clinical presentation in an endemic area is sufficient to initiate therapy. 1, 2 Delayed treatment is associated with cerebrovascular injury and increased mortality. 4, 5

Do not underdose children—always calculate doxycycline dose based on actual body weight (2.2 mg/kg), not age alone. 2

Do not withhold doxycycline from children under 8 years due to dental staining concerns—the benefits far outweigh this theoretical risk for short-course treatment. 2

Consider co-infections if fever persists after initial treatment, as scrub typhus can occur concurrently with influenza and other infections. 8