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Scrub Typhus- case presentation 
Dr. D.P.Bansal (M.D.,D.M.) 
Dr. Mohd Viquasuddin Saim 
DNB medicine resident 
Medwin 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
----------------- 
• Thank you

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Scrub typhus

  • 1. Scrub Typhus- case presentation Dr. D.P.Bansal (M.D.,D.M.) Dr. Mohd Viquasuddin Saim DNB medicine resident Medwin hospital
  • 2. 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
  • 3. 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.
  • 4. Case presentation • o/e : • Conjunctival suffusion + • Lungs : BAE +, b/l basal crepts + • p/a : guarding + • Heart sounds : normal • CNS : NAD
  • 5. 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
  • 6. 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
  • 7. 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.
  • 8. 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
  • 9. 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’
  • 10. 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
  • 11. 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
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. Clinical features • Also seen are • Nausea and vomiting • Diarrhea • Constipation • Conjunctival suffusion • Reversible sensorineural deafness
  • 17. 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
  • 19. complications • Jaundice • Meningoencephalitis • Myocarditis • Interstitial pneumonia leading to ARDS • Renal failure • Mortality was 42 % in preantibiotic era • Mortality still high in rural areas
  • 20. Immunity • Remarkably short lived • Lasts only a few months • Highly strain specific • Insufficient to protect from infection with other strains
  • 21. 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
  • 22. 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
  • 23. 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
  • 24. 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
  • 25. 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
  • 26. 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
  • 27. 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
  • 28. 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
  • 29. 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
  • 30. 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.
  • 31. 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