What is the cause, symptoms, investigation, treatment, and potential complications of scrub typhus?

Scrub Typhus: Comprehensive Clinical Overview

Cause

Scrub typhus is caused by the obligate intracellular bacterium Orientia tsutsugamushi, transmitted through the bite of infected larval mites (chiggers). 1, 2 The pathogen multiplies in endothelial cells, causing a vasculitis that is responsible for the clinical manifestations of the disease. 1

• Endemic to the "Tsutsugamushi Triangle" encompassing South Asia, Southeast Asia, and the Western Pacific regions, though cases are now emerging beyond this traditional range 1, 3
• Particularly significant in rural areas of Laos and Southeast Asia 1
• Mortality rates up to 4% have been reported, with higher rates when diagnosis and treatment are delayed 1, 4

Clinical Symptoms

Classic Presentation

Fever is the most consistent symptom (100% of cases), typically beginning 6-10 days after the chigger bite. 1, 4, 5

Common symptoms include:

• Headache (21-72%) 6, 4, 5
• Myalgia (51-68%) 6, 5
• Malaise (77%) 6
• Gastrointestinal symptoms: nausea (57%), vomiting (47%), diarrhea (18-25%), abdominal pain 6, 4, 5
• Cough and respiratory symptoms (24-28%) 6, 4
• Chills (39%) 4

Pathognomonic Finding

The eschar—a painless, necrotic lesion with a black crust surrounded by erythema at the site of the chigger bite—is characteristic but present in only 60% of cases. 1, 4 The absence of eschar should not exclude the diagnosis, as atypical presentations are common and complicate early recognition. 2

Additional Physical Findings

• Lymphadenopathy (33%) 4
• Rash (21%) - varies from petechial to maculopapular patterns 6, 4
• Altered mental status and meningeal signs (20%) 5

Investigation

Laboratory Findings

Characteristic laboratory abnormalities include thrombocytopenia (44%), elevated transaminases (AST 81%, ALT 75%), and variable white blood cell counts. 4

Specific findings:

• Leukopenia (<4,000/mm³) in 19% of cases 4
• Leukocytosis (>10,000/mm³) in 34% of cases 4
• Thrombocytopenia (<100,000/mm³) in 44% of cases 4
• Elevated hepatic transaminases in 75-81% of cases 4

Diagnostic Testing

Serological testing is the primary diagnostic method, though treatment should never be delayed while awaiting laboratory confirmation. 1 The Weil-Felix test has been used historically, though more specific serological methods are preferred when available. 5

• Blood cultures should be obtained before initiating therapy when possible 7
• High clinical suspicion is essential in endemic regions, particularly with fever, respiratory distress, and history of environmental exposure 4

Treatment

First-Line Therapy

Doxycycline is the drug of choice for scrub typhus in patients of all ages, including children under 8 years, and should be initiated immediately when scrub typhus is suspected. 1

Adult Dosing

• Doxycycline 100 mg twice daily (orally or intravenously) 1
• Continue for at least 3 days after fever subsides and until evidence of clinical improvement 1
• Minimum treatment course of 5-7 days 1

Pediatric Dosing

• For children under 45 kg: doxycycline 2.2 mg/kg body weight twice daily 1
• For children 45 kg or above: adult dosing (100 mg twice daily) 1
• The historical concern about dental staining should not prevent short-course doxycycline use in children under 8 years 1

Alternative Therapy

Chloramphenicol 12.5-25 mg/kg every 6 hours IV can be used as an alternative agent. 1

Combined Therapy for Severe Disease

In severe cases with multiorgan dysfunction, combined antimicrobial therapy with doxycycline and azithromycin has shown clinical benefit. 2

Expected Response

Patients typically respond to appropriate antibiotics within 24-48 hours; lack of response within this timeframe should prompt consideration of alternative diagnoses or resistant organisms. 1

Complications

Pulmonary Complications

Pneumonitis occurs in 36% of cases and acute respiratory distress syndrome (ARDS) in 15% of cases. 4

• Pulmonary infiltrates are common in severe disease 2, 4
• Mechanical ventilation may be required for severe respiratory compromise 2
• ARDS is a life-threatening complication that can result in death if diagnosis and treatment are delayed 4

Renal Complications

Acute renal failure occurs in 9% of cases and may require renal replacement therapy. 2, 4

Cardiovascular Complications

Myocarditis (3%) and septic shock (3%) are less common but serious complications. 4

Neurological Complications

Central nervous system involvement, including meningitis or meningoencephalitis, is present in approximately 20% of patients. 6

• Altered sensorium and meningeal signs occur in 20% of cases 5

Metabolic Complications

Severe hyperglycemia and metabolic acidosis can occur, mimicking diabetic emergencies. 2

Other Severe Manifestations

• Hepatic failure 6
• Coagulopathies 6
• Multiorgan dysfunction syndrome (MODS) 2

Critical Pitfalls to Avoid

• Never delay treatment while awaiting laboratory confirmation, as delay can lead to severe disease, long-term sequelae, or death 1
• Do not exclude scrub typhus based on absence of eschar alone—atypical presentations without classic findings are common 2
• Always calculate pediatric doses based on actual body weight, not age alone, to avoid underdosing 1
• Maintain high clinical suspicion in patients with fever and respiratory distress from endemic areas, even without obvious exposure history 4, 5
• Recognize that emerging virulent strains may cause more severe disease than historically reported 4