Scrub Typhus- case presentation

Dr. D.P.Bansal (M.D.,D.M.)Dr. Mohd Viquasuddin Saim

DNB medicine residentMedwin hospital

Case presentation

• An 18 year old female , resident of Mahbubnagar district was admitted with history of fever since 2 weeks, cough since 2 weeks, vomitings since 10 days, pain abdomen and shortness of breath since 3 days

• Fever was continuous, high grade, subsiding on medication and not associated with chills

• Cough was non productive

Case presentation

• Vomitings were 3 to 4 episodes/day, non projectile, non bilious, associated with nausea aggravated by food intake.

• pain abdomen was diffuse, intermittent, colicky in nature, aggravated on food intake and associated with constipation

• Shortness of breath was present at rest , not asssociated with chest pain. There was no orthopnea or PND.

Case presentation

• o/e : • Conjunctival suffusion +• Lungs : BAE +, b/l basal crepts +• p/a : guarding +• Heart sounds : normal• CNS : NAD

Case presentation

• Evaluation of the patient revealed • Anemia (Hb : 8.1)• Thrombocytopenia (63,000)• WBC : 7500• Chest x ray : b/l diffuse haziness s/o

pneumonia• Weil felix test was positive for OX-K antigen• LFT’s were raised

Case presentation

• Dengue IgG and IgM were negative• Dengue NS1 antigen was negative• HBsAg, HAV, HCV, HIV I & II were negative• Leptospira IgM was negative• Blood culture did not reveal any bacterial

growth , WIDAL test was negative• Smear for Malarial parasite and parasite F and

V were negative

Case presentation

• A diagnosis of scrub typhus was made and patient was treated with Doxycyline, IVF, antipyretics, and antiemetics.

• Daily platelet counts and liver parameters were monitored.

• Patient improved symptomatically and was discharged after 10 days.

Scrub typhus : historical background

• Also known as Japanese river fever• ‘tsutsugamushi’ in japanese means tsutsuga =

disease, mushi = bug• Disease was also endemic in south and

southeast asia• Major infectious disease in asia during second

world war• Scrub typhus research laboratory was

established in Imphal, India

epidemiology

• Important and widespread cause of febrile illness in rural areas of asia

• Caused by Orientia tsutsugamushi ( formerly Rickettsia tsutsugamushi )

• Contracted via the bite of the larval stage ( chigger) of trombiculid mite.

• Infected mites are characteristically found in discrete foci called ‘mite islands’

epidemiology

• Mite islands can occur in a wide range of vegetations types like :

• Scrub (tall-growing coarse grass)• Forests• Gardens, beaches• Paddy fields• Bamboo patches• Oil palm or rubber estates

epidemiology

• O.tsutsugamushi is an obligate intracellular bacterium

• Its maintained transovarially in mite population and rodents

• Larval stages normally feed on rodents• Humans are accidental hosts• Recently a new species O.chuto has been

discovered in UAE

chigger

pathogenesis

• O. tsutsugamuhi infects endothelial cells, macrophages and PMNs.

• Bacteria uses host fibronectin interactions with its 56-kDA antigen (TSA56) for attachment.

• Invades host cell via induced phagocytosis• Enters phagosome and then escapes into

cytoplasm

pathogenesis

• Replicates via binary fission and then is released covered by host cell membrane

• Recent evidence suggests pathophysiology of o.tsutsugamushi is different from endothelium targeting Spotted fever group.

• Mononuclear cell activation was more prominent than endothelial cell activation

• Primary cytopathic destruction of endothelium of blood vessels causing vasculitis

Clinical features

• Presents as a systemic vasculitic infection• Most of the pathogenesis is unknown• Symptoms occur between 6 to 10 days after

mite bite• Typically presents with fever,

lymphadenopathy, macular-maculopapular rash, severe headache and myalgia

• muscle tenderness is minimal or absent

Clinical features

• Also seen are• Nausea and vomiting• Diarrhea• Constipation• Conjunctival suffusion• Reversible sensorineural deafness

Clinical features

• A painless papule occurs at the site of the bite prior to the onset of disease symptoms

• This painless papule later ulcerates and transforms into a black crust or ‘eschar’ in variable proportion of patients

• eschar is not noticed in all patients because of variability in thoroughness of physical examinations and immunological factors

Eschar

complications

• Jaundice• Meningoencephalitis• Myocarditis• Interstitial pneumonia leading to ARDS• Renal failure• Mortality was 42 % in preantibiotic era• Mortality still high in rural areas

Immunity

• Remarkably short lived• Lasts only a few months• Highly strain specific• Insufficient to protect from infection with

other strains

diagnosis

• Gold standard diagnostic tests are• Immunofluorescent assay (IFA) and indirect

immunoperoxidase test (IIP) based on cell-culture derived O.tsutsugamushi antigens

• These antigens are applied to paired admission and convalescent samples

• These are not standardized and are usually unavailable in poor tropical areas

diagnosis

• WEIL-FELIX test• This test was developed in 1916 for typhus fever• This is based on positive agglutination of Proteus

vulgaris (OX19) by the serum from patients with all forms of typhus except scrub typhus

• In 1924, Dr. AN Kingsbury unknowingly introduced a strain of Proteus mirabilis in malaya where scrub typhus is endemic and strong agglutinations were seen

diagnosis

• WEIL-FELIX test• The antigen was termed as OXK (K=Kingsbury)• The discovery of this antigen led to the

identification of two different types of typhus fevers (scrub typhus and murine typhus)

• Sensitivity and specificity is low• its predictive value can be increased by testing

both acute and convalescent phase samples and observing rise in antibody titre

diagnosis

• WEIL-FELIX test• low sensitivity means it gives high percentage

of false negative results. • common in case of Scrub Typhus.• low specificity meaning false positive results

are obtained in leptospirosis, and relapsing fever , Proteus infections, brucellosis and acute febrile illness

Diagnosis

• Anti-O.tsutsugamushi IgM and IgG based rapid diagnostic tests have been developed but evaluation is pending

• ELISA also can be used• Benefits of ELISA include multiple tests at one

time, inexpensive, sensitive, specific.• PCR methods have also been developed • Target genes are 47 Kda, groEL genes

diagnosis

• Can be cultured from blood• takes several weeks• Special tissue culture techniques• A bioSafety level 3 facility is mandatory• Samples taken from eschars can be used for

both PCR-based or immunohistochemical diagnosis due to high bacterial loads

Differential diagnosis

• Typhus : distinguished only be serological tests• Malaria : by stained blood films• Arbovirus infections : by serological methods• Leptospirosis : by PCR or culture• Relapsing fever : by blood smear, serology• Meningococcal disease : by blood and CSF

cultures• Typhoid : blood and bone marrow cultures• Viral fevers

treatment

• It is very responsive to treatment• Appropriate antibiotics should be given

empirically if the diagnosis is suspected• D.O.C is Doxycycline if there are no

contraindications• Adult oral dose of 100mg twice daily for 7 days• Tetracycline 500mg every 6 hours for 7 days

can also be used

treatment

• Azithromycin (1000-500mg) on the first day followed by 500-250mg daily for 2 days is an effective alternative

• Azithromycin has also been shown to be effective in single dose

• Azithromycin is particularly useful in pregnancy where tetracyclines are contraindicated

treatment

• Chloramphenicol is an alternative to the tetracyclines (500 mg every 6 hours in adults or 50-75 mg/kg per day in children for 7 days)

• Other antibiotics which have been used successfully are Roxithromycin, telithromycin and Rifampicin

• Fluoroquinolones have been assocaited with treatment failures and should not be used.

prevention

• Preventive measures include :• Wearing protective clothing• Treatment of clothing with repellants or

acaricides• Application of DEET to exposed skin• No protective vaccine is available

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