O R I G I N A L A RTICL E ASIAN JOURNAL OF MEDICAL SCIENCES

Clinical presentation of scrub typhus during a

major outbreak in central Nepal
Arun Sedhain1, Gandhi R Bhattarai2
1
Associate Professor, Department of Medicine, Nephrology unit, Chitwan Medical College, Bharatpur, Chitwan, Nepal,
2
Director, Health Services Research, United Health Group, OptumInsight, CT, USA.

Submitted: 15-04-2017 Revised: 23-05-2017 Published: 01-07-2017

ABSTRACT
Background: Scrub typhus, an emerging rickettsial disease caused by the organism Access this article online
Orientiatsutsugamushi, is associated with multi-organ involvement. We prospectively Website:
studied the clinical manifestations of the disease during a major outbreak in central
http://nepjol.info/index.php/AJMS
part of Nepal. Aims and Objective: This study was carried out with an aim to analyze
DOI: 10.3126/ajms.v8i4.17163
the clinical presentations, laboratory parameters, complications and outcomes of scrub
E-ISSN: 2091-0576
typhus. Materials and Methods: A prospective observational study was conducted in the P-ISSN: 2467-9100
Department of Medicine in a tertiary teaching hospital. A total of 1398 patients admitted
with acute febrile illness were subjected for Scrub Typhus Detect™ IgM ELISA test, among
which 502 (35.90%) patients tested positive and were included in the study. Acute
kidney injury was defined according to KDIGO guideline. Statistical analysis was done
with SAS University Studio package using t-test for continuous variables and chi-square
test for categorical variables. Results: Mean age of the patients was 30.37±18.81 years
with 26.29% in the pediatric age group (<14 years). Females comprised of 55.98% of
the patients. Majority (97.98%) of the patients were seen between July to November.
Clinical presentations in the descending order of frequency were anorexia (55.18%),
headache (53.39%), lymphadenopathy (15.73%), jaundice (13.35) and eschar (6.57%).
Mean scrub typhus IgM ELISA value was 2.17. Leukocytosis was seen in 5.78% and
thrombocytopenia in 66.73% of patients. Transaminitis was found in 80.68% of patients.
Urinary abnormalities were recorded in 42.3% of patients. Acute kidney injury (AKI) was
seen in 35.8% of patients followed by acute respiratory distress syndrome (24.1%),
pneumonia (22.1%), shock (14.74%), neurologic manifestation (6.37%) and cardiac
manifestations (4.38%). ICU admission was required for 18.73% of patients and 8.57%
required ventilator support. Mortality rate was 1.79%. Conclusion: Scrub typhus, being an
emerging vector borne infectious disease in Nepalese context, is associated with multiple
organ involvement.
Key words: Acute febrile illness, Acute kidney injury (AKI), Hematuria, Albuminuria

INTRODUCTION Scrub typhus as a cause of acute febrile illness in

Nepal was first reported in 1981.3 Hospital based study
Scrub typhus is a rickettsial disease caused by the organism conducted in 2004 in central Nepal found scrub typhus
Orientia tsutsugamushi and transmitted through the bite of as a cause of acute febrile illness in 3% of patients.4 Since
larval forms (chiggers) of trombiculid mites.1 It presents then the disease has been considered to be endemic in
as either a non-specific febrile illness with constitutional different parts of the country, though it did not cause
symptoms such as fever, rash, myalgias and headache significant problems. After a 7.5 magnitude earthquake
or with multi-organ dysfunctions involving organs such in April 2015, major outbreak of scrub typhus was
as kidney, liver, lungs, central nervous system or with noted in different districts of central Nepal. So, this
circulatory collapse.2 study was carried out with an aim to analyze the clinical

Address for correspondence:

Dr. Arun Sedhain, Nephrology Unit, Chitwan Medical College, Bharatpur, Chitwan Nepal. Phone: 00977-9843492908,
E-mail: [email protected]  © Copyright AJMS

Asian Journal of Medical Sciences | Jul-Aug 2017 | Vol 8 | Issue 4 27

 Sedhain and Bhattarai: Scrub typhus in Nepal

presentations, laboratory parameters, complications and Majority of the patients were from the plain area (72%) of
outcomes of scrub typhus. the country and most of them were from the rural (32%)
and semi-urban (24%) areas (Figure 1).
MATERIALS AND METHODS The first case of scrub typhus during this outbreak was
seen in April and majority (97.98%) of the patients were
A prospective analytical study was conducted from April
seen between July to November with highest number of
to December 2016 in the Department of Medicine at
patients seen in October (Figure 2).
Chitwan Medical College Teaching Hospital, a tertiary care
institution located in Central Nepal. Approval from the All 100% patients included in the study had fever. Other
ethical committee and informed written consent from the clinical presentations in the descending order of frequency
patients were taken prior to the study. Patients admitted were anorexia, headache, lymphadenopathy, jaundice and
with acute febrile illness (AFI) who were tested positive eschar. Urinary abnormalities in 42.3% of patients (Table 2).
for Scrub Typhus Detect™ IgM ELISA test (titer equal
or more than 0.5), were included in the study. Patients Most common complication seen was acute kidney injury
who concomitantly had other infections like dengue, (AKI), of which 66% had stage 1, 33% had stage 2 and
laptopirosis, typhoid fever, brucella or malaria were 1% had stage 3 AKI. Hemodialysis was required in 1.79%
excluded from the study. of patients. Other complications in descending order were
Demographic, clinical and laboratory variables were
Table 1: Baseline clinical characteristics
recorded in all patients. All patients had a detailed
clinical history and examination, a standard set of Variables Mean±SD

investigations including complete blood counts, liver Age (years) 30.37±18.81

IgM ELISA value 2.17±1.70
function tests, serum urea, creatinine, electrolytes, chest Days in the hospital 5.39±2.32
radiograph and ultrasonography of abdomen and pelvis. Days in ICU 1.07±2.35
Leukocytosis was defined as white blood cells [WBC] Duration of fever (days) 5.57±1.22
>12000 cells/mm3, anemia as hemoglobin <10 gram/dL,
thrombocytopenia as platelets <1.5 lakhs/mm3, elevated Table 2: Clinical presentations of scrub typhus
bilirubin as total bilirubin >3 mg/dL and elevated
Clinical parameters Number (%)
aspartate aminotransferase and alanine aminotransferase
Anorexia 277 (55.18)
as four times the normal. Urinary abnormalities were
Headache 268 (53.39)
defined by dipstick proteinuria, pyuria, hematuria and casts Lymphadenopathy 79 (15.73)
as seen on urine microscopy and Acute Kidney Injury Jaundice 67 (13.35)
(AKI) was defined as per kidney disease improving global Eschar 33 (6.57)
outcome (KDIGO) guideline.5 Patient characteristics were
summarized using mean and frequency distributions.
Data for continuous variables were expressed as mean ±
standard deviation using t-test for continuous variables
and chi-square test for categorical variables. Analysis
of Variation (ANOVA) tests were done to test the
differences of continuous variables across multiple groups.
Descriptive and inferential statistical analysis were done
by using SAS University Studio package.

RESULTS
Figure 1: Geographic distribution of the patients
Out of 1398 patients with AFI subjected for Scrub
Typhus Detect™ IgM ELISA test, 502 (35.90%)
patients were tested positive. Mean age of the patients
was 30.37±18.81 years with an age range between 1 to
79 years (Table 1). Almost 26% of the patients were in
the pediatric age group (<14 years). Females comprised
of 55.98% of the patients with female to male ratio of
1.26:1. Figure 2: Month-wise distribution of patients

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 Sedhain and Bhattarai: Scrub typhus in Nepal

acute respiratory distress syndrome (ARDS), pneumonia, Australia in the south and to Pakistan in the west.8 In
shock, neurologic manifestation and cardiac manifestations. Nepal, first study to detect scrub typhus was done in
Admission to ICU was required for 18.73% of patients 1981 in eastern part of the country where 10% of study
with mean duration of ICU stay of 1.06 days. Mechanical population were found to have antibodies to scrub-typhus
ventilation was needed for 8.57% of patients. Nine patients rickettsiae, indicating that the infection occurred widely in
died with a mortality rate of 1.79% (Table 3). eastern Nepal.3 In another study, up to 3% of in-hospital
patients in central Nepal were found to be infected with
Leukocytosis (WBC count >11,000/mm3) was seen in the scrub typhus.4 However, till date there had not been
5.78% and thrombocytopenia in 66.73% of patients. such a large outbreak and clinical study of scrub typhus
Transaminitis was seen in 80.68% of patients with majority in the country. Current outbreak of scrub typhus in Nepal
having raised AST than ALT (90.63 versus 86.65%; p=0.531). was seen from those areas which were affected by the 7.8
Mean scrub typhus IgM ELISA value was 2.17 (Table 4). magnitude earthquake in April 2015.9 These outbreaks were
thought to be due to people and rodents living in close
DISCUSSION proximity in temporary shelters after the earthquake.10,11
Majorities of the patients included in our study were from
This is the first report to comprehensively document the the earthquake affected areas (Figure 1).
clinical presentation, laboratory investigation, pattern of
renal involvement and outcome in a cohort of patients of The bite of the mite leaves a characteristic black eschar.
scrub typhus in Nepal. We have found that scrub typhus The adult mites have a four-staged lifecycle viz. egg,
was responsible for about 36% of patients presenting with larva, nymph and adult. The larval stage, also known as
unexplained febrile illness. chigger, is the only stage that can transmit the disease to
humans and other vertebrates.6 The incubation period
Scrub typhus is a vector borne disease caused by Orientia of scrub typhus in human is around 10-12 days and the
tsutsugamushi, an obligate intracellular gram negative clinical manifestation varies from mild febrile illness to
bacteria and transmitted by the bite of an infected severely fatal multiorgan dysfunction syndrome. Apart
Trombiculid mite larva.6 The disease was first described from the non-specific generalized clinical features like
from Japan in 1899 and in the initial days the overall fever, malaise, anorexia, headache, lymphadenopathy and
mortality varied from 7% to 9%.7 In the current days scrub cough,12 the significant findings of scrub typhus is eschar
typhus is endemic to a part of the world known as the formation at the site of bite, the prevalence of which is
“tsutsugamushi triangle”, which extends from northern variable ranging from 7% to 80%.13,14 However, eschar is
Japan and far-eastern Russia in the north, to northern rarely seen in south East Asia and Indian subcontinent.15,16
Lymphadenopathy usually painful, is a common finding in
Table 3: Complications in scrub typhus scrub typhus reported in 13 to 18% of patients.17-19 In this
Complications Number Percentage (mean±SD)
study, all patients had fever followed by anorexia, headache,
jaundice and lymphadenopathy. Eschar formation was seen
AKI 180 35.82±23.72
ARDS 120 24.10±42.81 only in 8% of the patients.
Pneumonia 110 22.1±41.54
ICU admission 94 18.73±58.24 Diagnosis of scrub typhus requires a high degree of clinical
Shock 74 14.74±35.49 suspicion, which is confirmed serologically by different
Ventilatory support 43 8.57±28.01
Neurologic manifestation 32 6.37±24.45 laboratory investigations.20 The cheapest test currently
Cardiac manifestation 22 4.38±20.49 available and used extensively in Indian subcontinent is
Death 9 1.79±13.28 Weil- Felix test which is highly specific, but lacks sensitivity.21,22
Immunoglobulin M (IgM) enzyme-linked immunosorbent
Table 4: Baseline laboratory parameters assay (ELISA) using the 56 kDa antigen has been widely
Parameter Value (mean±SD)
used, which is easy to perform, gives quick results and has
sensitivity of 84 to 86% and a specificity of 98%23,24 and
TLC (cumm) 7327.63±2364.82
Hb (gm%) 10.26±0.98 is well validated.25 No current diagnostic test is sufficiently
PLC (cumm) 116689.86±58172.49 practical for use by physicians working in rural areas. A new
AST (U/L) 72.48±53.09 dipstick test using a dot blot immunoassay format appears
ALT (U/L) 64.40±44.93
Urea (mg/dL) 30.09±12.05
to be the best currently available test for diagnosing scrub
Creat (mg/dL) 1.36±0.69 typhus in rural areas where this disease predominates.26
Scrub ELISA 2.17±1.70
TLC: Total leucocyte count, PLC: Patelet count, AST : Aspartate aminotransferase, Reported severe clinical manifestations or complications
ALT: Alanine aminotransferase
of scrub typhus include AKI, meningoencephalitis,

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 Sedhain and Bhattarai: Scrub typhus in Nepal

myocarditis, pneumonia, ARDS, AKI, GI bleeding, septic be part of the differential diagnosis in patients with acute
shock, and multiple organ failures which may be potentially febrile illness.
fatal if there is a delay in diagnosis and treatment.27-33
Acute kidney injury (AKI) and renal involvement in scrub
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Authors Contribution:
AS- Concept and design of the study, collection of data, reviewed the literature, manuscript preparation and critical revision of the manuscript; GRB- Data
analysis, literature review and review of manuscript

Orcid ID:
Dr. Arun Sedhain: http://orcid.org/0000-0003-2590-9096
Dr. Gandhi R Bhattarai: http://orcid.org/0000-0002-5914-5090

Source of Support: Nil, Conflict of Interest: Nil.

Asian Journal of Medical Sciences | Jul-Aug 2017 | Vol 8 | Issue 4 31