Preparatory Mindset
Scrub typhus is the most under-recognised cause of acute undifferentiated fever in rural Asia — caused by *Orientia tsutsugamushi* (a rickettsia), transmitted by the bite of larval-stage trombiculid mites ("chiggers") that live in the "scrub" vegetation of rural Asia-Pacific (CM exam tested). The pathognomonic clinical finding is the eschar — a painless, black, necrotic ulcer at the bite site, often hidden in skin folds, axillae, or under the bra line. The exam mindset: fever + regional lymphadenopathy + eschar (look!) + maculopapular rash + rural/farming exposure in Asia/Pacific → think scrub typhus → doxycycline empirically (do not wait for serology). Untreated, mortality can exceed 30%; with doxycycline, <1%.
Core Concepts
1. Definition
Scrub typhus (tsutsugamushi disease, 恙虫病) = an acute febrile illness caused by *Orientia tsutsugamushi* (family Rickettsiaceae), transmitted to humans by the bite of chiggers (larval trombiculid mites), characterised by fever, eschar at the bite site, regional lymphadenopathy, maculopapular rash, and potential multi-organ involvement (lungs, heart, kidney, CNS).
2. Aetiology
| Feature | Detail |
|---|---|
| Pathogen | *Orientia tsutsugamushi* (formerly *Rickettsia tsutsugamushi*) — Gram-negative obligate intracellular bacterium |
| Reservoir | Larval trombiculid mites (chiggers); vertical transmission in mites (transovarial); rodents amplify |
| Vector | Larval-stage mite bite (only larvae feed on vertebrates); adult mites feed on plants/soil |
| Stability | Inactivated by heat, common disinfectants; stable at −20 °C for years |
| Distribution | Tsutsugamushi triangle — bounded by Japan, Australia, Pakistan, far-eastern Russia (and through China — southern provinces, Yunnan, Fujian, Guangdong, Hainan, Jiangsu, Anhui) |
> Important: chiggers are not lice or ticks — they are the 6-legged larval stage of mites that live in vegetation, grassy fields, riverbanks.
3. Epidemiology
- Endemic in Asia-Pacific "tsutsugamushi triangle" — Japan, Korea, China, India, SE Asia, northern Australia.
- China: endemic in southern provinces; occupational and agricultural exposure; peak in summer and autumn (harvest season).
- Source of infection: chiggers in vegetation; humans are accidental hosts.
- Susceptible population: farmers, forest workers, campers, rural residents; non-immune travellers in endemic areas.
4. Pathogenesis
- Chigger bite (often unnoticed) → organisms inoculated into skin → local replication → eschar formation (necrotic ulcer with black scab).
- Lymphatic spread → regional lymphadenopathy.
- Haematogenous dissemination → systemic vasculitis (small-vessel endothelial injury, characteristic of rickettsial disease) → widespread organ involvement.
- Interstitial pneumonitis, myocarditis, meningoencephalitis, hepatitis, AKI.
5. Clinical features
Incubation: 6–21 days (usually 10–12).
Classic triad (variable presence):
| Feature | Frequency | Notes |
|---|---|---|
| Fever | Near universal | Acute onset, often 39–40 °C, remittent or continuous; may last 2 weeks if untreated |
| Eschar | ~50–80% of patients | Painless black necrotic ulcer (~5–20 mm) at bite site; often in skin folds, axillae, groin, behind ear, under bra; look carefully — single, painless; regional lymphadenopathy drains the site |
| Rash | ~30–50% | Maculopapular, starts on trunk → spreads to extremities (centrifugal); appears ~5–8 days into illness |
| Lymphadenopathy | Common | Regional (drains eschar) + generalised |
| Headache, myalgia, malaise | Common | Nonspecific |
| Conjunctival suffusion | Variable | Non-exudative |
Severe / complicated scrub typhus:
| Complication | Notes |
|---|---|
| Interstitial pneumonitis / ARDS | Common cause of mortality |
| Myocarditis | Arrhythmias, heart failure |
| Meningoencephalitis | Confusion, seizures, coma |
| Hepatitis / AKI | Often subclinical; ↑ AST/ALT, ↑ Cr |
| DIC | In severe cases |
| Multi-organ failure | Without treatment, mortality up to 30% |
6. Laboratory examination
| Test | Pattern |
|---|---|
| CBC | Leukocytosis or leukopenia; thrombocytopenia in severe |
| LFT | AST/ALT mildly elevated |
| CRP / ESR | Elevated |
| Specific diagnosis | Indirect immunofluorescence assay (IFA) — gold standard, paired sera (4-fold rise 1–2 weeks apart); IgM detectable ~7 days; Weil-Felix test (OX-K agglutination) — old screening, less sensitive/specific, still used in resource-limited settings |
| PCR | *O. tsutsugamushi* 56-kDa type-specific antigen gene; sensitive, available in research/reference labs |
| Biopsy of eschar | PCR positive (highest yield) |
> Pitfall: IFA takes weeks for paired sera — do not delay treatment waiting for confirmation.
7. Diagnosis
Combination of epidemiology (Asia-Pacific, rural, agricultural, seasonal) + eschar (if found) + clinical syndrome + serology (IFA / Weil-Felix). Treatment is empirical on clinical suspicion — never wait for confirmation.
Differential diagnosis:
| Mimic | Distinguishing |
|---|---|
| Dengue | Travel SE Asia, no eschar, saddleback fever, thrombocytopenia, NS1 + |
| Murine typhus (*Rickettsia typhi*) | Rats/ fleas, no eschar, urban; doxycycline same |
| Typhoid fever | Relative bradycardia, rose spots, no eschar |
| Leptospirosis | Water exposure, conjunctival suffusion, myalgia, biphasic |
| Malaria | Paroxysmal fever, blood film + |
| HFRS / dengue / chikungunya | Travel + exposure; check serology |
8. Treatment
| Setting | Drug | Dose | Duration |
|---|---|---|---|
| Uncomplicated | Doxycycline | 100 mg bid (PO or IV) | 5–7 days (continue until 3 days after defervescence) |
| Alternative | Azithromycin 500 mg day 1, then 250 mg daily × 4 days | 5 days | Pregnancy, children <8, doxycycline intolerance |
| Alternative | Chloramphenicol | (less used; risk of aplastic anaemia) | — |
| Severe / complications | IV doxycycline + supportive care (ICU, oxygen, AKI support, myocarditis management) |
Doxycycline is the cornerstone — single dose 200 mg may be curative in mild disease; recommended 5–7 days. Azithromycin is the preferred alternative in pregnancy and children <8 (avoid doxycycline).
9. Prevention
- No vaccine.
- Avoid chigger bites: long sleeves/pants, tuck trousers into socks, DEET-containing repellent on skin and clothing, permethrin-treated clothing.
- Rodent + mite control: vegetation clearance around dwellings, reduce rodent reservoirs.
- No chemoprophylaxis routinely; consider weekly doxycycline for very high-risk exposures.
- Notification: Class B notifiable disease (24 h) in China.
High-Yield Points
| Topic | Must-remember |
|---|---|
| Pathogen | *Orientia tsutsugamushi* (rickettsia); tsutsugamushi triangle |
| Vector | Larval trombiculid mite (chigger) bite |
| Hallmark | Eschar (painless black ulcer), often in skin folds |
| Clinical | Fever + eschar + regional lymphadenopathy + rash |
| Severe | ARDS, myocarditis, meningoencephalitis, AKI |
| Diagnosis | IFA (gold standard, paired sera); Weil-Felix OX-K (old screen); empirical treatment — don't wait |
| Treatment | Doxycycline 100 mg bid × 5–7 days (first-line); azithromycin in pregnancy/children |
| Mortality | <1% with doxycycline; up to 30% untreated |
| Prevention | Long sleeves/pants, DEET, permethrin-treated clothing |
| Season | Summer–autumn in China; farming |
Topic Summary
Scrub typhus is a rickettsial disease transmitted by chigger (mite larva) bites in rural Asia-Pacific, presenting with fever + painless black eschar + regional lymphadenopathy + maculopapular rash. The eschar is the pathognomonic clue — search skin folds carefully. Diagnosis: IFA (paired sera) + clinical; Weil-Felix OX-K (legacy). Treatment: doxycycline 5–7 days (first-line; azithromycin in pregnancy). With treatment, mortality <1%; without, up to 30%. Prevention: protective clothing, DEET, rodent control. Class B notifiable disease.
LMCHK OSCE Practice — Bushwalker with Fever and Rash
Station setup: 35-year-old male returned from a 10-day hiking trip in Chiang Mai, northern Thailand. Day 7 post-return: fever to 39 °C, severe headache, myalgia, dry cough. Examination: T 39.2 °C, HR 96, BP 110/70. Right inguinal region shows a 1-cm painless black-crusted ulcer with surrounding erythema and tender inguinal lymphadenopathy. Sparse maculopapular rash on the trunk.
Candidate tasks (8 min):
- Take a focused travel + exposure history (rural, brush, sleeping conditions, repellent use).
- State the most likely diagnosis (scrub typhus) and explain the basis (eschar + rural Asia + fever + rash).
- List first-line investigations (CBC, LFT, renal, IFA paired sera, eschar PCR if available) — but emphasise do NOT wait for serology.
- Outline immediate treatment — doxycycline 100 mg bid × 5–7 days; admit if systemic signs.
- Discuss prevention for future travel (long clothing, DEET, permethrin-treated clothing, tuck trousers into socks).
Key marking cues:
- Recognises eschar + regional lymphadenopathy + rural Asia + fever = scrub typhus.
- Empirical doxycycline without waiting for IFA result.
- Differentiates from dengue (no eschar, saddleback fever), leptospirosis (water exposure, conjunctival suffusion), typhoid (rose spots, relative bradycardia).
- Identifies the mite larval stage (not adult) as the vector — and the bite is painless, so the patient may not recall it.
- Counsels on protective clothing + repellent for future trips.