Scrub typhus is a mite-borne infectious disease caused by the bacterium Orientia tsutsugamushi.

  • Common in Asia-Pacific regions, including Nepal and India.
  • Common during rainy season.
  • It is arthropod-borne disease but human are accidental host.

Nepal is also part of Tsutsugamushi Triangle. Scrub typhus is most prevalent rickettsial infection in Nepal.

History and Examination

  • Children living or traveling in endemic areas, recent outdoor activities
  • Risk factors: Contact with vegetation, visit to grassy or shrubby fileds, poor sanitation, crowded living conditions, animal sheds in proximity, contact with pet or animals, exposure to rodents.
  • Diagnosis become difficult as presenting features are non-specific. It is based on high index of clinical suspicions.

Symptoms

  • Fever (without localizing signs and symptoms for > 5 days)
  • Headache
  • Myalgia
  • Rash (It is transient so missed easily)
    • Appear on 4-5 daysMacular/ maculopapular
    • Starts on trunk then spread to peripheries
  • Eschar at the site of the mite bite (Pathognomic sign)
    • Search for it in whole body

Signs

  • Lymphadenopathy (Inguinal)
  • Hepatomegaly
  • Spleenomegaly
  • CNS involvement
    • Typhus means clouding of sensorium
  • Sensorineural hearing loss

Differential Diagnosis (D/D) & Complications

D/D

  • Dengue fever (retro-orbital pain, rash, thrombocytopenia)
  • Malaria (cyclical fever, anemia, splenomegaly)
  • Leptospirosis (jaundice, renal dysfunction, conjunctival suffusion)
  • Typhoid fever
  • Kawasaki disease

Complications

  • Respiratory system (ARDS, Pneumonitis, Pulmonary edema)
  • CVS (Myocarditis, toxic shock, Congestive heart failure, Pericarditis)
  • CNS (Meningoencephalitis, Sensorinerual hearing loss)
  • Liver and GI system (Hepatitis, liver failure, oral ulcer, GI bleed)
  • Renal (Renal failure, HUS)
  • Skin (Purpura fulminans, Gangrene)
  • Hematology ( DIC, Hemophagocytic lymphohistiocytosis)

Investigation

  • Investigation of choice: Serological testing (IgM ELISA)
    • Positive after 1 weeks of illness
    • Other serology test: WEIL-FELIX and Immunofluorescence antibody (Gold standard)
  • Blood culture
  • Complete blood count (CBC)
    • Leukopenia or normal WBC
    • Neutropenia
    • Thrombocytopenia
  • Liver and renal function tests
    • Raised liver enzyme (Transminases)
    • Hypoalbuminemia
  • Chest X-ray (if respiratory symptoms present)
    • Shows infiltrates, mostly bilateral

Admission Criteria

  • Severe or complicated cases
  • Children with altered mental status or multi-organ involvement
  • Ideally, each patient should be admitted for timely management of complication.

Management

  • Immediate administration of antibiotics upon suspicion of scrub typhus. Don’t wait for laboratory confirmation and don’t stop treatment if test showed negative.
  • Continue symptomatic treatment  and management of complication
    • Paracetamol for fever
    • Ranitidine
    • Adequate hydration
    • Nutrition
  • Doxycycline 2.2 mg/kg BID x 7 days (preferred for children ≥8 years)
  • Azithromycin 10 mg/kg/day x 5 days (preferred for children <8 years)

Medical Treatment

Antibiotics:

  • Oral or IV Doxycycline
    • Drug of choice (Monotherapy is sufficient to treat with meningoencephalitis)
    • Dose
      • < 40 kg: Give 2.2 mg/kg BD
      • > 40kg: Give 100mg BD
    • Duration: Total 7 days or 10 days in complicated or severe case
    • Fever subside within 48 hours if not then consider doxycycline resistant
    • Give IV formulation for sick patient
    • Side effects: Diarrhea, nausea, vomiting, incresed risk of sunburn
  • Alternatives drugs
    • Oral or IV Azitrhomycin (Macrolides)
      • Dose: 10 mg/kg/day
      • Duration: Total 5 days
    • IV Chloramphenical
      • 50-100mg/kg/day divided 6 hourly (Max: 3g/day)
      • Duration: 5-7 days
      • Alternative for tetracycline (it cause permanent discoloration of teeth)
      • Agranulocytosis is common side effects
    • Rifampicin
      • Used in doxycycline resistance cases
      • 10mg/kg/ (Max: 300mg) for 5-7 days
    • Tetracycline and clarithromycin can also be used.
    • Fluroqunolones not given in pediatric cases

Advices

  • Educate the family about disease prevention (mite repellent, protective clothing, hygiene)
  • Adequate hydration and rest

Referral

  • If no improvement or worsening after 48 hours of antibiotic therapy
  • Presence of complications or multi-organ involvement

Follow up

  • Schedule a follow-up visit within 7 days after treatment completion
  • Assess for clinical improvement, resolution of symptoms, and monitor for complications

Additional Points

Pathogenesis

  • Bite from larval mite (Chigger) >> multiplication of bacteria at inoculation site>> papule, ulcer, necrosis causing eschar and lymphadenopathy
  • Organism reaches blood stream, infect endothelial cells, phagocystosis to localize infection
    • Vasculitis and perivascular inflammation
    • Thrombus formation
    • End organ tissue injury and tissue hypo perfusion

References

1. Bonell A, Lubell Y, Newton PN, Crump JA, Paris DH. Estimating the burden of scrub typhus: A systematic review. PLoS Negl Trop Dis. 2017;11(9):e0005838.

2. Rajapakse S, Rodrigo C, Fernando SD. Scrub typhus: pathophysiology, clinical manifestations, and prognosis. Asian Pac J Trop Med. 2012;5(4):261-264.

3. Kim DM, Kang DW, Kim JO, Chung JH, Kim HL, Park CY, et al. New Orientia tsutsugamushi genotype in scrub typhus, South Korea. Emerg Infect Dis. 2019;25(12):2293-2300.