INSTITUTE OF MEDICAL SCIENCES AND SUM HOSPITAL

SIKSHA 'O' ANUSANDHAN UNIVERSITY

‘SYNOPSIS OF DISSERTATION’
SCRUB TYPHUS A RE-EMERGING THREAT-AN ANALLYTICAL STUDY
OF CLINICAL MANIFESTATIONS, COMPLICATION AND
EPIDEMIOLOGICAL PROFILE OF PATIENTS

SUBMITTED BY

DR NAVIN KUMAR B.K

POST GRADUATE STUDENT

DEPARTMENT OF GENERAL MEDICINE

FOR THE YEAR 2019-2022

INSTITUTE OF MEDICAL SCIENCES &SUM HOSPITAL

 KALINGA NAGAR, BHUBANESHWAR

THESIS PROTOCOL SUBMISSION FORM

1. Name (In Full) : Dr. NAVIN KUMAR B.K

2. Father’s Name : Mr. BUMINATHAN S

3. Correspondence Address : Institute of Medical Science & SUM Hospital,

Kalinga Nagar, Bhubaneswar.
Mobile No: 9976939898
E mail: navinkumarbk1992@gmail.com
4. Registration Details

a) Reg. No. :120915 TNMC

5. Details of MD Medicine Training:

Subject : Medicine

Date of admission : 27/05/2019

Institute : Institute of Medical Science & SUM Hospital,

State : Odisha

Correspondence Address:ROOM NO 603,CAMPUS NO 2,BOYS HOSTEL

NO 3,K-8,KALINGA NAGAR,ODISHA
751003
TITLE OF THE THESIS PROTOCOL:
SCRUB TYPHUS A RE-EMERGING THREAT-AN ANALLYTICAL STUDY
OF CLINICAL MANIFESTATIONS,COMPLICATION AND
EPIDEMIOLOGICAL PROFILE OF PATIENTS

6. Details of Thesis Protocol:

Subject : Medicine
Name of the Guide: Dr RAJESH PADHI
Professor
Deparment of General Medicine
7. Remarks of the Guide :

8. Signature of the Guide :

INTRODUCTION AND BACKGROUND

Brief Summary:
Scrub typhus infection has been considered as seasonal and endemic
infectious disorder restricted to rural and forest areas with benign
feature. However, in the last 5 years there is an increasing trend in
mortality rate of scrub typhus which has been recently reported in
Southeast Asia and cause of death varies for shock and cardiovascular
dysfunction to neurological complications. Therefore, the association
and predictors for scrub typhus induced morbidity and mortality
indicators should be investigated to provide a timely and appropriate
diagnosis and to reduce the mortality rate of complicated scrub typhus
infection. Therefore, we prospectively investigate the association and
predictors for scrub typhus induced morbidity and mortality indicators in
patients with scrub typhus infection.

This study is especially important as there are no studies with

robust statistical analysis done from Eastern India.

Scrub typhus also known as tsutsugamushi disease is an acute

febrile illness caused by orientia tsutsugamushi, a bacterium
from the family rickettsiaceae. Scrub typhus is widespread in so
called ”tsutsugamushi triangle” which extend from Pakistan,
India and Nepal in the west, to south-eastern Siberia, Japan,
China and Korea in the north to Indonesia, the Philippines,
northern Australia and the pacific islands in the south In India,
epidemics of scrub typhus have been reported from Pondicherry
and Goa in south, Uttrakhand in north India.Cases of scrub
typhus were also reported from eastern India among the
paediatric age group.8 Although the disease is endemic in our
country, it grossly remains under diagnosed owing to the non-
specific clinical presentation, lack of access to the specific
diagnostic facility and low index of suspicion by the clinician.
Majority of cases are seen during the month of July to
November but it is not uncommon to find cases in the rest of the
year. In spite of being an endemic disease in this part of India
many cases have remained undiagnosed mostly due to lack of
high index of suspicion by the clinician and non availability of
specific diagnostic test for the disease. It is a common
observation that when the disease like malaria, typhoid,
leptospirosis and fever due to localized causes were excluded, a
good percentage of cases among the patients with acute febrile
illness were ultimately diagnosed to have scrub typhus.
CLINICALL FEATURES
Scrub typhus presents as an acute undifferentiated fever. The
incubation period for symptoms is between six and twenty-one
days from exposure. The clinical picture is characterized by
sudden onset of fever with chills, headache, backache and
myalgia, profuse sweating, vomiting and enlarged lymph nodes.
In some patients, an eschar may develop at the site of chigger
feeding, usually at sites where the skin surfaces meet, such as
axilla, groin and inguinal areas. Although the eschar is reported
to be less frequently observed in South Asian patients than in East
Asian or Caucasians, 55% of patients had an eschar in a recent
study from South India[please give a reference in reference
section and chronological numbering – number to be put in
bracked]. In females it was primarily present in the chest and
abdomen (42.3%), while in males it was present in the axilla,
groin and genitalia (55.8%). Unusual sites of eschar were reported
to be in the cheek, ear lobe and dorsum of the feet. [again
reference is missing] Five to eight days after the onset of fever, a
macular or maculopapular rash may appear on the trunk and later
extend to the arms and the legs in a small proportion of patients[
reference missing ]
COMPLICATIONS
Complications of scrub typhus infection include pneumonia,
acute respiratory distress syndrome (ARDS) like picture,
myocarditis, encephalitis, hepatitis, DIC, hemophagocytic
syndrome, acute kidney injury, acute pancreatitis, transient
adrenal insufficiency, subacute painful thyroiditis and
presentation as an acute abdomen.[ reference missing ]
Several neurological manifestations have been observed in the
setting of scrub typhus infection. The most common
neurological presentation in scrub typhus is as meningitis,
meningoencephalitis or encephalitis. Others include cerebral
venous thrombosis, Guillain-Barre Syndrome, transient
Parkinsonism and myoclonus, opsoclonus, cerebellitis,
transverse myelitis, polyneuropathy, facial palsy, abducens
nerve palsy and bilateral optic neuritis [ reference missing ]
DIAGNOSIS
The diagnostic methods available for laboratory confirmation
include identification of the organism in cell culture, detection of
the antigen by immune-histochemical methods or the antibodies
by the indirect immunofluorescence assay (IFA) and finding
specific nucleic acid targets using molecular methods. The
success of a test in confirming the diagnosis of scrub typhus is
dependent on the type of sample taken[57] and the timing of the
specimen. Cell culture or molecular assays performed using
eschar (when present) or buffy coat are more likely to be positive
in the first two weeks of illness. Antibody levels reach detectable
levels by day seven; paired sera obtained at least two weeks apart
are necessary for serologically confirming the diagnosis by
demonstration of a ≥ 4 fold rise in titre.[ reference missing ]
Diagnosis and Treatment Serologic assays for IgM antibodies against
Scrub typhus by indirect fluorescent antibody, indirect
immunoperoxidase, and enzyme immunoassays) are the mainstays of
laboratory diagnosis.[ reference missing ]
Although not widely available , PCR amplification of Orientia genes
from eschars and blood also is effective. Reference missing ]
Patients are treated with oral doxycycline (100 mg twice daily for 7–15
days), azithromycin (500 mg for 3 days), in our institution, although
chlroramphenicol is also effective. Resistant cases are emerging which
need addition of Rifampicin to treatment regimen.[ reference missing ]

AIM:
To study the clinical, laboratory features of scrub typhus
To bring out new/ unknown clinical, laboratory features associated with scrub typhus
OBJECTIVE:
To quantify the severity of critical illness objectively by use of APACHE II and
SOFA Scores.
To study the pattern of clinical presentation in scrub typhus
To study the laboratory and radiological changes associated with scrub typhus
To study the known/unknown complications of scrub typhus

MATERIALS AND METHODS:

 1. SOURCE OF DATA:The present study will be carried out in the, inpatient
of IMS and SUM Hospital, Bhubaneswar. Study group comprises of patients
with scrub typhus infection
2. METHODS OF COLLECTION OF DATA:
Data will be collected according to the Performa (annexure – 1) attached below

Data collected will include:

1. Detailed history

2. Clinical examination findings

3. Routine and special investigations including 2D-ECHO ; MRI BRAIN;

TRIPLE PHASE LIVER CT – IN APPROIRIATELY SELECTED CASES WITH
CLINICAL FINDINGS SUGGESTIVE OF CARDIAC, NEUROLOGICALN,
HEPATIC DYSFUNCTION.

4. Routine CSF analysis will be performed in cases with meningeal signs.

SAMPLE SIZE:

Inclusion criteria: Acute Febrile illness Indoor patients, > 14 yrs of age with IGM
scrub typhus positive in IMS and SUM Hospital

Exclusion criteria:

1. Pediatric group

2. Outdoor patients of scrub typhus

3. STUDY TOOLS AND TECHNIQUE

1. Laboratory parameters –scrub typhus will be screened by positive IgM

antibodies against O.tsutsugamushi. Other lab parameters- total leucocyte count,
total platelet count, hematocrit, liver function test, renal function tests and other
relevant tests will be performed..

4. STUDY DESIGN

Study Type – Prospective , randomised , case control plus observational

study Estimated Enrollment – 100
Obsevational model – Cohort
Experimental Model – Randomised Case
control Actual Start Date – 15th October 2019
Estimated Primary Completion : 31st March 2021
Estimated Detailed Analysis and study conclusion : 31st March 2021

Outcome Measures :
I. Primary – Cure vs Death
II. Secondary
Outcome study Duration of stay
till fever remission Length of
Hospital Stay
Length of ICU stay
Need and duration of RRT [Renal Replacement Therapy}
Need for Supplemental Oxygen
Mechanical Ventilation Via NIV
Invasive Mechanical
Ventilation
Shock state
Need for Inotropes and
Vasopressors Neurological –
Delirium
Altered
Sensorium
Meningeal Signs
Seizures
Focal Neurological
deficits Lateralizing signs
Hepatic Dysfunction
Bleeding and
coagulopathy

Statistical Analysis

The study is originally designed to enroll 100 patients. the sample size
may be increased to if we get additional cases , thereby increasing the
statistical power of the study. All data to be analysed according to the
intention-to-treat principle, with no imputation for missing values. The
primary analysis for death at 90 days will be performed with the use of
an unadjusted chi-square test. A secondary analysis will be based on
logistic regression, with the strata used for randomization (type of
admission and geographic region) as covariates, as well as age, location
before ICU admission, APACHE II score, and use or nonuse of
mechanical ventilation at baseline. Other binary end points as mentioned
above will be analyzed by means of a chi-square test or Fisher's exact
test. Continuous variables will be compared with the use of unpaired t-
tests, Welch's tests, or Wilcoxon rank-sum tests. All odds ratios and their
corresponding 95% confidence intervals were calculated according to
the profile-likelihood method. The time from randomization to death in
the two treatment groups to be compared with the use of the log-rank
test, and the results are presented as Kaplan–Meier curves. Hazard ratios
will be obtained from Cox models.

Subgroup analyses for the primary outcome will be based on an

unadjusted test of interaction in a logistic model.
All analyses were conducted with the use of S-PLUS software (version
8.0) and R software (version 2.7.0), and the results to be verified
independently with SPSS software.

PROFORMA FOR SCRUB TYPHUS PATIENT DATA COLLECTION

(Admitted to IMS & SUM Hospital, Bhubaneswar)

Name of the patient:

Age: Gender:
Address:

Place of disease detection:

Clinical manifestation (At the time of admission):
Escar Present – Yes/No
Symptoms Yes No Duration
1.Fever
Myalgia
Headache
Body ache
Nausea
Vomiting
Dizziness
Retro orbital pain
Arthralgia
Skin rash
Itching
Abdominal pain
Loose motion
Oliguria
Bleeding
manifestation
Convulsions
Neck stiffness
Chest pain
Breathlessness
Blurring of vision
Diminished vision
Clinical examination
Temperature Pulse
BP _

Orthostatic hypertension Yes no

Pulse pressure:
Respiration rate:
Pallor yes No
Edema yes No
Icterus yes no
Ascites yes no
Hepatomegaly yes no
Palpable spleen yes no
Conjunctional suffusion yes no
Lymphadenopathy yes no
Meningeal signs Yes
no

Investigations
Lymphocyts: Eosinophils:
RBC Count: Metamylelocytes:
Hb:
T.W.B.C:
WBC Differential:Neutrophils:
Basophils: Mylocytes:
MCV:
MCH:
MCHC:
PCV:
TPC:
 LFT: Bilirubin (D) Bilirubin (Total)
SGOT: SGPT: ALP:
Serum albumin:
RFT: Serum urea: Serum creatinine:
Urine:
Serum Na: Serum K: Serum Cl:
ECG:
MP ICT:
X-Ray chest (PA):

USG abdominal:

Scrub typhus IgM:

Special investigations*:
PT: PT-INR:
Serum fibrinogen level:
CT Brain:

CSF Study:

2D-Echocardiography:

Fundoscopy:
Serum lipase: Serum amylase: Serum LDH:
Serum CPK:

*Investigations are done with good clinical suspicion

Any other findings:
Hospital course and follow up

Treatment given:

New findings during hospital stay:

Date of defervesce:
Complications (if any):
Outcome:

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