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associated with mortality in dengue DOI: 10.1177/0049475517693993
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Atul Saroch1, Vivek Arya2, Nitin Sinha3, RS Taneja2,

Pooja Sahai4 and RK Mahajan5

Abstract
Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the
South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at
our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the
172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered
sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum trans-
aminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise
multivariate logistic regression, altered sensorium (P ¼ 0.006) and hypoalbuminemia (P ¼ 0.013) were identified as inde-
pendent predictors of mortality in dengue. Identification of these parameters early in the course of disease should
prompt intensification of treatment in dengue cases.

Keywords
Dengue, mortality, fever, New Delhi, predictive factors

Introduction myalgia, arthralgia, rash, a positive tourniquet test

Dengue virus (DENV) is transmitted by vectors Aedes
aegypti and Aedes albopictus, and has four serotypes.
Infection by any one of these may be either asymptom-
atic or produce severe symptoms even death. According
to the WHO classification of 2009, dengue can be clas-
sified as with or without warning signs, or severe
(including dengue haemorrhagic fever and dengue
shock syndrome).1 Though there are numerous studies
on factors predicting severity in dengue, there are rela-
tively few studies on factors associated with mortality.
Methods
Our retrospective study was conducted at the Post
Graduate Institute of Medical Education and Research
(PGIMER), Ram Manohar Lohia Hospital (RML),
New Delhi, India, which caters chiefly as a tertiary refer-
ral centre for Delhi and surrounding areas. All patients
with confirmed dengue were admitted to the designated
Dengue Ward, and those cases admitted according to
the register between the months of September and
October 2015 were included in our study. Inclusion cri-
teria were: (1) fever with at least two of the following
symptoms: headache, retro-orbital or ocular pain,
(defined as the presence of  20 petechiae per square
inch) or leucopenia (defined as a white blood cell
count < 5.0  109/L); and (2) dengue confirmed by viral
detection (a) PCR or NS1 antigen, or virus culture
1
Assistant Professor, Department of Medicine, Post Graduate Institute of
Medical Education and Research, Dr Ram Manohar Lohia Hospital,
New Delhi, India
2
Professor, Department of Medicine, Post Graduate Institute of Medical
Education and Research, Dr Ram Manohar Lohia Hospital, New Delhi,
India
3
Associate Professor, Department of Medicine, Post Graduate Institute of
Medical Education and Research, Dr Ram Manohar Lohia Hospital,
New Delhi, India
4
Senior Resident, Department of Microbiology, Post Graduate Institute of
Medical Education and Research, Dr Ram Manohar Lohia Hospital,
New Delhi, India
5
Professor, Department of Microbiology, Post Graduate Institute of
Medical Education and Research, Dr Ram Manohar Lohia Hospital,
New Delhi, India
Corresponding author:
Atul Saroch, Assistant Professor, Department of Medicine, Post Graduate
Institute of Medical Education and Research, Dr Ram Manohar Lohia
Hospital, New Delhi, India.
Email: atulsaroch@gmail.com
2 Tropical Doctor 0(0)
positive; or antibody response (b) IgM seroconversion or
IgG titre increase  4 in paired serum samples.2
Patients with mixed infection, multiple medical
co-morbidity or those aged < 14 years (admitted to the
paediatric wards) were excluded. Patients with underly-
ing medical co-morbidity were excluded to reduce treat-
ment bias, as they were managed with help of different
medical specialties with different protocols.
Cases were divided into two groups: those who sur-
vived and those who died. Parameters compared were:
age, sex, place of residence (Delhi or outside Delhi), dur-
ation of fever (i.e. time between onset of fever and admis-
sion), headache, abdominal pain, vomiting, diarrhoea,
myalgia, arthralgia, lethargy, rash, bleeding from any
site, level of consciousness, respiratory rate and mean
blood pressure (MBP). Laboratory parameters compared
included: haemoglobin (Hb), haematocrit (Hct), platelet
counts, total white cell count, serum creatinine, serum
albumin, aspartate transaminase and alanine transamin-
ase. All patients received care according to WHO guide-
lines.2 Data containing all the above information for each
case at time of admission were recorded on a Proforma.
Data were analysed using STATA SE 12 (Stata
Corp, TX, USA). Variables with normal distribution
were summarised as mean and standard deviations
and compared using the Student’s t-test. Variables
with non-normal distributions were summarised as
median and interquartile ranges (IQR) and compared
using the Mann–Whitney U test. Categorical variables
were expressed as frequencies and percentages and ana-
lysed with 2 tests or Fisher’s exact test, as appropriate.
Univariate analysis to determine all the factors signifi-
cantly affecting mortality was performed, following
which a stepwise multivariate logistic regression was
conducted using the forward selection method to deter-
mine factors independently associated with mortality.
In all tests, P < 0.05 was considered significant.
Results
A total of 268 patients were admitted, of whom 96
patients were excluded because of mixed infection
(n ¼ 32), underlying medical co-morbidity (n ¼ 28),
incomplete medical records (n ¼ 26) or negative con-
firmatory results for dengue (n ¼ 10). Out of 28 patients
with medical co-morbidity, we found chronic liver dis-
ease (n ¼ 9), coronary artery disease (n ¼ 7), chronic
kidney disease (n ¼ 5), active tuberculosis on treatment
(n ¼ 4) and diabetes with nephropathy and retinopathy
(n ¼ 3). Of these, causes of death were: coronary artery
disease with congestive cardiac failure (n ¼ 3), chronic
alcoholic liver disease (n ¼ 1) and active pulmonary
tuberculosis (n ¼ 1). Thus, of the 172 hospitalised
patients with confirmed dengue included in our study,
156 (90.7%) recovered while 16 (9.3%) died.
Altered sensorium was present in a significantly
higher percentage in those who died (37.5%) compared
with survivors (4.5%) (P < 0.001). Of those six patients
who had altered sensorium and died, two had an ence-
phalitis-like presentation, two had an intracranial
haemorrhage and the remaining two were not evaluated
in detail as they died within 24 h of admission. Among
the survivors, seven had altered sensorium related to
hyponatraemia (n ¼ 2), hypernatraemia (n ¼ 2) and an
encephalitis-like presentation (n ¼ 3).
Other patient characteristics such as gender, area of
residence, age, duration of fever, symptoms of lethargy,
myalgia, headache, vomiting, diarrhoea, abdominal
pain, rash and bleeding tendency were not significantly
different (Table 1). Those who died had significantly
lower Hb, lower HCT, higher serum creatinine, higher
liver transaminases and lower serum albumin compared
to survivors (Table 2).
All clinical factors significantly associated with mor-
tality as detected from the univariate analysis were
included in the multivariate logistic regression analysis.
Independently associated factors were altered sensor-
ium (P ¼ 0.006) and hypoalbuminemia (P ¼ 0.013)
only.
Discussion
Dengue is a significant public health problem, particu-
larly in India, and the number of related deaths has
increased dramatically in recent decades. The mortality
rate reported varies from 11%3 to 27.5%,4 somewhat
higher than in our study.
Neurologic manifestations, other than headache,
occur in approximately 4–6% of dengue cases.
Neurological complications have been classified into
dengue virus encephalopathy, dengue virus encephal-
itis, immune-mediated syndromes, neuromuscular com-
plications and dengue-associated stroke. They have
been attributed to different pathophysiological mechan-
isms, such as direct central nervous system (CNS) viral
involvement, metabolic disturbances affecting CNS
function, haemorrhage and virus-generated auto-
immune reactions, leading to CNS inflammation and
demyelination.5,6 Evidence of DENV neurotropism
was also found in autopsy studies. DENV antigens
have been isolated from brain tissues in fatal dengue
cases.7 Altered sensorium as a factor related to
increased mortality was documented in retrospective
study conducted in Pakistan.8
Hypoalbuminemia may result from increased vascular
permeability, a capillary leak syndrome, negative acute
phase reactant or hepatic injury. Hypoproteinaemia or
hypoalbuminemia were seen in 12.9% in a large study
from Kolkata, India,4 while reports are in the range
of 16.5–76% in other studies.9–11 It was likewise
Saroch et al. 3

Table 1. Baseline characteristics and clinical parameters at admission of 172 hospitalised adult
patients with dengue.

Patients who Patients who

survived (n ¼ 156) died (n ¼ 16) P value

Baseline characteristics
Male 98 (62.8%) 9 (56.2%) 0.377
Female 58 (37.2%) 7 (43.8%)
Residential area 0.392
Delhi 135 (86.5%) 13 (81.2%)
Outside Delhi 21 (13.5%) 3 (18.8%)
Clinical parameters
Vital signs
HR median (IQR), beats/minute 90 (82–98) 88 (84–110) 0.330
MAP, median (IQR), mmHg 81.7 (73–86) 71.3 (60–90) 0.160

History and physical examination

Symptoms and signs n (%) n (%)
Myalgia 75 (48.1) 8 (50.0) 0.545
Lethargy 92 (59.0) 9 (56.2) 0.477
Headache 80 (51.3) 9 (56.2) 0.565
Fever > 4 days 84 (53.8) 12 (75.0) 0.366
RR > 18 breaths/min 135 (86.5) 14 (87.5) 1.000
Bleeding 52 (33.3) 4 (25.0) 0.457
Rash 48 (30.8) 3 (18.8) 0.051
Arthralgias 45 (28.8) 4 (25.0) 0.384
Abdominal pain 90 (57.7) 7 (43.8) 0.209
Persistent vomiting 106 (67.9) 8 (50.0) 0.122
Diarrhoea 34 (21.79) 6 (37.5) 0.201
Altered sensorium 7 (4.48) 6 (37.5) <0.01
HR, heart rate; MAP, mean arterial pressure; RR, respiratory rate.

Table 2. Laboratory parameters at admission of 172 hospitalised adult patients with dengue.

Patients who Patients who

survived (n ¼ 156) died (n ¼ 16)

Median (IQR) Median (IQR) P value

Haemoglobin (g/L) 127 (109–143) 113 (102–120) 0.002

Haematocrit (%) 38 (33.7–42.0) 33 (27.7–34.4) <0.001
TLC (cells  109/L) 5.0 (3.4–6.9) 8.2 (4.8–10.9) 0.025
Platelet count (cells per mL) 40,000 30,000 0.738
(median)
Platelet counts
100  109/L 130 (83.33%) 12 (75%) 0.733
>100  109/L 26 (16.66%) 04 (25%) 0.501
Creatinine (mmol/L) 70 (53–88) 176(70–300) 0.003
Albumin (g/L) 33 (29–36) 27 (21–29) 0.003
AST (IU/L) 134.5 (73.7–233) 285 (161–2797) 0.008
ALT (IU/L) 83.5 (47–137) 539 (111–1356) 0.005
IQR, interquartile range; TLC, total leucocyte count.
4 Tropical Doctor 0(0)
significantly associated with mortality in studies from
Brazil and India.12,13
While other factors such as low Hb, low HCT, low
platelet count and deranged liver function have else-
where been associated with mortality,14 these were
not significant in our findings. This may be explained
by closer attention and treatment of these correctable
factors in institutions from where these patients were
referred. Early recognition of altered sensorium and
hypoalbuminemia appear, though, to sound the alarm
for intensification of care in an attempt to reduce
mortality.
Acknowledgements
The authors thank the Medical Record Department at
Dr RML Hospital for the help they extended in retrieving
the patient records.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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