Managing Scrub Typhus in ICU

Dr. Shivakumar IyerProfessor & Head

Dept of Critical Care MedicineBharati Vidyapeeth University Medical College, Pune

PresidentIndian Society of Critical Care Medicine

WFSICCM SEOUL 2015

JOURNAL OF THE ASSOCIATION OF PHYSICIANS OF INDIA JANUARY 2014 VOL. 62

Managing Scrub Typhus in ICU

• History

• Epidemiology

• Pathophysiology

• Pathology

• Clinical features

• ICU presentation

• Diagnosis

• Management

Orientia Tsutsugamushi infection: overview and immune responsesSeung-Yong Seong et al Microbes and Infection 2001

Introduction

• Zoonotic rickettsial illness

• Orientia tsutsugamushi

– Tsutsuga – illness mushi – insect

• Scrub = scrubby vegetation typhus = fever

South-East Asia including India, Bangladesh, China, Taiwan, South Korea, Japan and Northern Australia

Tsutsugamushi triangleNorthern Japan

Far eastern Russia

Pakistan (west)

Northern Australia (south) infection: overview and immune responseset al Microbes and Infection 2001

History

• First described from Japan in 1899

• Severe epidemics of the disease occurred among troops in Burma and Ceylon in WWII

• Several members of the U.S. Army's 5307th Composite Unit Merrill’s Marauders died

• New Guinea 1942-43 WWII

• US troops stationed in Japan after WWII

• No antibiotics or vaccine was available

• Etiology: O tsutsugamushi

• Three major serotypes -Karp, Gilliam & Kato

• Vector: chiggers (larva of trombiculid mite)

• Reservoir: chiggers & rats – Transovarian

transmission– Normal cycle: rat to

mite to rat• Humans are accidentally

infected

Bite by chigger

Incoculation of Orientia tsutsugamushi

Local eschar with regional lymphadenopathy

Rickettsemia

Disseminated vasculitis

DICVascular

leakPulm edema Hepatic inv

Neurologic inv

Myocarditis

Pathogenesis, Pathophysiology, Pathology

Clinical Features

• Incubation period: 1 to 3 weeks

• Sudden onset of fever, headache & myalgia

• Delirium, nausea, vomiting, cough, jaundice

• Maculopapular rash

– Begins on trunk and spreads to extremities (centrifugal spread)

• Eschar

Eschar

Sites of Eschar

Kundavaram A P, Jonathan A J, Nathaniel S D, Varghese G M. Eschar in scrub typhus: A valuable clue to the diagnosis. J Postgrad Med 2013;59:177-8

Clinical Course

Complications• ARDS / Pneumonitis• Myocarditis• Shock• Neurologic complications• Hepatitis• DIC• Thrombocytopenia• Hemophagocytic syndrome• AKI• Acute pancreatitis• Transient adrenal insufficiency• Thyroiditis• Occasionally acute abdomen

JV Peter et alWorld J Crit Care Med 2015 August 4; 4(3): 244-250

When should scrub typhus be suspected?

• Undifferentiated febrile illness with:

– Pathognomonic eschar

– Evidence of multisystem involvement, especially with:

- Transaminase elevation

- Thrombocytopenia

- Leukocytosis

Lab Diagnosis

• Serology– Weil-Felix– Indirect immunofluorescence antibody (IFA) – Indirect immunoperoxidase (IIP)– ELISA for IgG & IgM antibodies (recombinant 56 kd antigen):

sensitivity & specificity >90%– Rapid diagnostic tests

• lateral flow immunochromatographic test (ICT)• Immuno- blot test • Latex agglutination test

• PCR• Culture• Immunohistochemistry

Lab Diagnosis

ICU presentation & Organ dysfunction

Outcome

UnivariateAnalysis

Multivariate analysis

ICU presentation & Organ dysfunction

• 116 patients

• (APACHE) II score was 19.6 ± 8.2

• 91 patients had >= 3 organ dysfunction

• 16 patients (15%) had all 6 organs dysfunction

• Respiratory dysfunction (96.6%)– Ventilatory support required in 87.9%.

• Cardiovascular dysfunction 61.7%

• Renal & Hepatic dysfunction i63.8%

• Thirteen patients (11.2%) were dialyzed

Treatment

Severe scrub typhus infection: Clinical features, diagnostic challenges and management John Victor Peter, Thomas I Sudarsan, John Anthony J Prakash, George M VargheseWorld J Crit Care Med 2015 August 4; 4(3): 244-250

Penicillins, cephalosporins, carbapenems aminoglycosides don’t work!!!

Resistance to quinolones has been reported!!!

Treatment

• Organ support

– Mechanical ventilation NIV may be tried in milder cases

– Fluids and vasopressor support

– Renal replacement therapy

– Platelet transfusions, other blood products

Mortality

• 116 patient ICU cohort (Griffith GM et al 2014) – Mortality was 24.1%

– APACHE- II score and duration of fever were independently associated with mortality.

• 261 patients from Taiwan (Su TH et al 2013)– no mortality was observed

• 623 patients from South India ( Varghese GM et al) – scrub typhus mild to critically ill

– mortality was 9%

– Decreasing trend over 4 years

• Scrub typhus is a not an uncommon cause of Acute Febrile Illness & MODS in ICU

• Diagnosis may be missed if eschar is not sought & typical epidemiology is missed

• Lab confirmation is with IgM ELISA or IFA or IIP

• Severe scrub typhus in ICU has significant mortality

• Early recognition & treatment with Doxy can significantly reduce mortality

Summary

Thank You

• ... the secret of the care of the patient is in caring for the patient.

– Francis Weld Peabody