scrub typhus

SCRUB TYPHUS

Dr Prashant Makhija

INTRODUCTION

Rickettsiae- heterogeneous group of small, obligatory intracellular, gram-negative coccobacilli and short bacilli, transmitted by a tick, mite, flea, or louse vector

Typhus- Greek word ‘Typos’, for ‘fever with stupor’, caused by rickettsial organisms that result in an acute febrile illness

Earliest medical accounts of typhus were written by Cardano in 1536 and Fracastroin 1546

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Scrub typhus- illness was described by Hashimoto in 1810

Ogata in 1931 isolated the organism and named it Rickettsia tsutsugamushi, now reclassified as Orientia tsutsugamushi

Tsutsugamushi- “dangerous bug”

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ETIOPATHOGENESIS

Vector- larva of Trombiculid mite (berry bugs, harvest mites, red bugs, scrub-itch mites )

Trans-ovarian transmission maintains the infection in nature

Mites have a four-stage lifecycle: egg, larva, nymph and adult

Chigger phase (Larval stage) is the only stage that is parasitic on animals or humans

Larvae feed on small rodents particularly wild rats of subgenus Rattus, Man gets infected accidentally

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Life cycle of Trombiculid mite

Chiggers have grasped a passing host, insert their mouthparts down hair follicles or pores

inject a liquid that dissolves the tissue around the feeding site

liquefied tissue is then sucked up as sustenance for the chigger

R.tsutsugamushi organisms are found in the salivary glands of the chigger, they are injected into its host when it feeds

Bacterium is an intracellular organism living and breeding within the cells of its host

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Organisms proliferate on the endothelium of small blood vessels releasing cytokines which damage endothelial integrity, causing fluid leakage, platelet aggregation, polymorphs and monocyte proliferation

Focal occlusive end-angiitis causing microinfarcts- especially affects skeletal muscles, skin, lungs, kidneys, brain and cardiac muscles

Can also cause venous thrombosis and peripheral gangrene

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Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

EPIDEMIOLOGY

An estimated one billion people are at risk for scrub typhus and one million cases occur annually

Endemic in Asia and Pacific Islands- Asia, Australia, New Guinea, Pacific Islands

Scrub typhus is known to occur all over India including the hills of North India

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SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005

CLINICAL FEATURES Illness varies from mild, self-limiting to fatal

Incubation period - 6-21 days

Onset & Initial clinical manifestations

fever, headache, myalgia, cough, gastrointestinal symptoms a primary papular lesion(where the chigger has fed) enlarges, undergoes central necrosis, and crusts to form a flat

black eschar Associated regional and later generalized lymphadenopathy and a macular rash may appear on the trunk

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

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Ann Indian Acad Neurol. 2012 Apr-Jun; 15(2): 141–144

CLINICAL FEATURES

Untreated self-limiting ds.- febrile for about 2 weeks and have a long convalescence of 4 to 6 weeks thereafter

Fulminant course- complications usually develop after the first week of illness

Complications

Neurological- meningoencephalitis Pulmonary- interstitial pneumonia

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

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GI- superficial mucosal hemorrhage, multiple erosions, and ulcers

Cardiac- Myocarditis with conduction blocks & CCF

Septicemic shock with ARDS, DIC, with renal & hepatic dysfunction

Mortality- 7-30%

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

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Harrison’s Principles of Internal Medicine. 18th ed.Ch174

NEUROLOGICAL COMPLICATIONS

Most case series report Meningitis/meningoencephalitis as the most common neurological complication of Scrub Typhus

Other reports of Neurological complications

Isolated abducens (VI) nerve palsy

Bilateral simultaneous facial nerve palsy in convalescent period

Scrub typhus associated with opsoclonus, transient Parkinsonism, and myoclonus has been observed

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Trigeminal neuralgia

Brachial plexus neuropathy

Guillain–Barre syndrome

Cerebral infarction

Acute disseminated encephalomyelitis

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Author No of Pts Neurological features

Outcome

Vivekanandan et.al (2004)

50 Meningitis-14%Altered sensorium-

20%

Mortality-2%

Razak et.al(2004) 29 Meningoencephalitis-20%

Cerebellar signs-3%

All improved

Mahajan et.al(2006) 27 Meningoencephalitis-14.8%

Mortality-3.7%

Mahajan et.al(2010) 21 Seiures-19%Altered sensorium-

23.8%

Mortality-14.2%

Chrispal et.al(2010) 189 Altered sensorium-22.2%

Seizures-6.3%Meningitis-20.6%

Mortality-12.2%

INVESTIGATIONS

Routine blood investigations Hemogram- Leukopenia and thrombocytopenia Coagulopathy Elevation of liver enzymes and bilirubin - indicating

hepatocellular damage ↑ Creatinine, Proteinuria

Chest X-rays- Reticulonodular infiltrates

CSF examinations show a mild mononuclear pleocytosis with normal glucose levels

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

Test Comments

Weil Felix Detects cross-reacting antibodies to Proteus mirabilis OXK 4-fold ↑ in titre to OXK single titre ≥ 1:160 also diagnosticLacks sensitivity & specificity

ELISA Detects Ab against infectious agents by using pooled human seraHigher sens. & spec.

Western Blot(KpKtGm) Presence of a 41-kD band Higher sens. & spec.

Indirect Fluorescent Assay Conclusive diagnosis: 4-fold ↑ in IFAs in paired serum obtained 2 wks apart Currently considered gold standard

PCR amplification most sensitiveLimited availability, expensive

Isolation Can be isolated & cultured by inoculating intraperitoneally into white mice not used routinely

TREATMENT

Preventive avoidance of the chiggers that transmit O. Tsutsugamushi

insect repellents and by the use of protective clothing impregnated with benzyl benzoate

natural strains are highly heterogeneous, infection does not complete protection against reinfection

Vaccines tried

short exposure, chemoprophylaxis with Doxycycline (200 mg weekly) can prevent infection

Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

Definitive therapy therapeutic trial of tetracycline in suspected patients

Recommended regimen- Doxycycline (2.2 mg/kg/dose bid PO or IV, maximum 200 mg/day for 7-15 days)

Alternative regimens : Tetracycline- 25-50 mg/kg/day divided every 6 h PO, maximum

2 g/day Chloramphenicol (50-100 mg/kg/day divided every 6 h IV,

maximum 3 g/24 h, or 500 mg qid orally for 7-15 days for adults Azithromycin (500 mg orally for 3 days) Rifampicin (600 to 900 mg/day) Intensive care may be required for haemodynamic management of

severely affected individualsRapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

CONCLUSION

Scrub typhus is a growing and emerging disease grossly under-diagnosed due to its non-specific clinical presentation, limited awareness, and low index of suspicion

Early diagnosis and treatment are imperative to reduce the mortality and the complications associated with the disease

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