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Recommendations of DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India

1. Scrub typhus can occur in areas where scrub vegetation consisting of low lying trees and bushes is encountered, and also in habitats as diverse as banks of rivers, rice fields, poorly maintained kitchen gardens8 , grassy lawns which can all be inhabited by chiggers
2. Presenting manifestations Acute fever is the most common presenting symptom often associated with breathlessness, cough, nausea, vomiting, myalgia and headache
3. the presence of eschar is highly variable ranging from 7-97 per cent. Eschars are painless, punched out ulcers upto 1 cm in width, with a black necrotic centre (resembling the mark of a cigarette burn), which is surrounded by an erythematous margin. Eschar is a pathognomonic sign of scrub typhus.
4. untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated
5. Presence of rash is common in spotted fever and is extremely rare in scrub typhus. Rash usually becomes apparent after 3-5 days of onset of symptoms. Initially rash is in the form of pink, blanching, discrete maculae which subsequently becomes maculopapular, petechial or haemorrhagic
6. The complications of scrub typhus usually develop after the first week of illness. Jaundice, renal failure, pneumonitis, acute respiratory distress syndrome (ARDS), septic shock, myocarditis and meningoencephalitis are various complications known with this disease

Guidelines for management
1. Definition of suspected/clinical case: Acute undifferentiated febrile illness of five days or more with or without eschar should be suspected as a case of rickettsial infection (if eschar is present, fever of less than five days duration should be considered as scrub typhus)
2. Definition of probable case: A suspected clinical case showing titres of 1:80 or above in OX2, OX19 and OXK antigens by Weil-Felix test and an optical density (OD) > 0.5 for IgM by ELISA is considered positive for members of typhus and spotted fever groups of Rickettsiae.
3. Definition of confirmed case: A confirmed case is the one in which (a) Rickettsial DNA is detected in eschar samples or whole blood by PCR, or (b) Rising antibody titres on acute and convalescent serum samples detected by indirect immune fluorescecnce assay (IFA).
Laboratory criteria
1. Weil-Felix: This test should be carried out only after 5-7 days of onset of fever. Titre of 1:80 is to be considered possible infection.
2. IgM and IgG ELISA: a significant IgM antibody titre is observed at the end of 1st week, whereas IgG antibodies appear at the end of 2nd week. The cut-off value is optical density of 0.5
3. Polymerase chain reaction (PCR)
4. Immunufluoroscence assay (IFA):
5. Indirect immunoperoxidase assay (IPA)

1. Haematology (i) Total leucocytes count (TLC) during early course of the disease may be normal but later in the course of the disease, leucocytosis is seen, i.e. WBC count > 11,000/µl. (ii) Thrombocytopenia (i.e. < 1,00,000/µl) is seen in majority of patients.
2. Biochemistry: Raised transaminase levels are also observed.
3. Imaging: Chest X-ray shows infilterates, mostly bilateral.

Treatment
Without waiting for laboratory confirmation of the rickettsial infection, antibiotic therapy should be instituted when rickettsial disease is suspected.

In adults: (a) Doxycycline 200 mg/day in two divided doses for individuals above 45 kg for a duration of seven days. Or (b) Azithromycin 500 mg in a single dose for five days.
In children: (a) Doxycycline in the dose of 4.5 mg/ kg body weight/day in two divided doses for children below 45 kg. Or (b) Azithromycin in the dose of 10 mg/kg body weight for five days.
In pregnant women: Azithromycin 500 mg in a single dose for five days. Azithromycin is the drug of choice in pregnant women, as doxycycline is contraindicated.
At secondary and tertiary care level
Intravenous doxycycline (wherever available) 100 mg twice daily in 100 ml normal saline to be administered as infusion over half an hour initially followed by oral therapy to complete 7-15 days of therapy.
Or (b) Intravenous azithromycin in the dose of 500 mg intravenous (iv) in 250 ml normal saline over one hour once daily for 1-2 days followed by oral therapy to complete five days of therapy25.

Or (c) Intravenous chloramphenicol 50-100 mg/kg/day 6-hourly doses to be administered as infusion over one hour initially followed by oral therapy to complete 7-15 days of therapy



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