SCRUB TYPHUS

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SCRUB TYPHUS:

SCRUB TYPHUS Dr Prashant Makhija

INTRODUCTION:

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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

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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” SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

ETIOPATHOGENESIS:

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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005

Life cycle of Trombiculid mite:

Life cycle of Trombiculid mite

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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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005

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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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Rapsang AG, Bhattacharyya P. Scrub typhus. Indian J Anaesth 2013;57:127-34

EPIDEMIOLOGY:

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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

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SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005

CLINICAL FEATURES:

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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

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

CLINICAL FEATURES:

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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

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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 SK Mahajan. JAPI .VOL. 53. NOVEMBER 2005 Harrison’s Principles of Internal Medicine. 18th ed.Ch174

NEUROLOGICAL COMPLICATIONS:

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 Ann Indian Acad Neurol. 2013 Jan-Mar; 16(1): 131

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Trigeminal neuralgia Brachial plexus neuropathy Guillain–Barre syndrome Cerebral infarction Acute disseminated encephalomyelitis Ann Indian Acad Neurol. 2013 Jan-Mar; 16(1): 131

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

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

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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 diagnostic Lacks sensitivity & specificity ELISA Detects Ab against infectious agents by using pooled human sera Higher 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 sensitive Limited availability, expensive Isolation Can be isolated & cultured by inoculating intraperitoneally into white mice not used routinely

TREATMENT:

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

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

CONCLUSION:

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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THANK YOU