553

ORIGINAL ARTICLE
Dengue fever in patients admitted in tertiary care hospitals in Pakistan
Muhammad Arif Munir,1 Syed Ejaz Alam,2 Zareef Uddin Khan,3 Quaid Saeed,4 Ambreen Arif,5 Rizwan Iqbal,6
Muhammad Arif Nadeem Saqib,7 Huma Qureshi8

Abstract
Objectives: To assess the gaps in the diagnosis and management of dengue fever cases.
Methods: The retrospective descriptive analytical study was done with a case record analysis of patients with
dengue fever admitted from January to December 2010 at five tertiary care hospitals in different Pakistani cities.
Using a questionnaire, information was gathered on demography, haematological profile, management, use of
blood and platelet transfusions and the outcome. For comparison, data of serologically-confirmed dengue patients
from a private laboratory in Islamabad was collected to see the age, gender and month-wise distribution of cases
tested over the same period. SPSS 16 was used for statistical analysis.
Results: Out of the 841 confirmed dengue cases, 514 (79%) were males and 139 (21%) females. The overall mean
age was 31.3±14.0 years. Dengue fever was seen in 653 (78%) and dengue haemorrhagic fever (DHF) in 188 (22%)
patients. Most cases were between 20 and 49 years of age. A gradual increase in dengue fever and dengue
haemorrhagic fever was seen from August, with a peak in October/November.
Tourniquet test was done only in 20 (2.3%) cases, out of which 11 (55%) were positive and 9 (45%) were negative.
Serial haematocrit was not done in any case. Total deaths were 5 (0.6%).
Conclusions: Most cases were seen in October/November with the majority being in the 20-39 age group.
Tourniquet test and serial haematocrit were infrequently used. No standard national guidelines were employed.
Keywords: Dengue fever, Dengue haemorrhagic fever, Dengue shock syndrome, Retrospective study, Platelets.
(JPMA 64: 553; 2014)

Introduction young adults.7 In Pakistan, the first outbreak of DHF was

Dengue is a mosquito-borne viral disease affecting reported in 1994.8 In 1998 DEN1 and DEN2 was confirmed
humans. Dengue fever (DF) and its more severe form i.e. on enzyme-linked immunosorbent assay (ELISA).9 A DEN3
dengue haemorrhagic fever (DHF), are caused by any one epidemic was reported in 2005.10 The 2006 outbreak was
of the four serotypes of dengue virus (DEN-1, DEN-2, DEN- dominated by DEN2 and DEN311 which was related to
3, DEN-4) belonging to the genus Flavivirus transmitted DEN3 (subtype III) that caused an outbreak in New Delhi
by Aedes aegyptei. Infection by one serotype generates in 200412 and since then increasing frequency and
life-long immunity against the same serotype, but gives severity of dengue infection has been reported from all
transient/partial protection against the other serotypes.1,2 over Pakistan. High levels of anti-dengue
Sequential infection with another serotype can result in immunoglobulin M (IgM) antibodies have been reported
the more severe DHF.3 in children living in Pakistani slums.13
Dengue infection represents a considerable disease The incubation period of DF ranges from 3 to 15 (usually
burden in many tropical and sub-tropical countries, 5-8) days. Clinical manifestations vary from asymptomatic
particularly in children and young adults, living in urban infection to DF, DHF and dengue shock syndrome (DSS).
and semi-urban areas.4 Globally about 50 million Most dengue infections are asymptomatic or cause mild
infections occur which is projected to increase.5 In symptoms of high-grade fever with or without rash and
endemic areas, dengue infection is a leading cause of resolve without specific treatment. Typical dengue fever is
hospitalisation and deaths among children.6 The average characterised by high fever, severe headache, myalgia,
case fatality rate is up to 5% mainly affecting children and arthralagia, retro-orbital pain and maculopapular rash.
About 5-10% patients progress to DHF which is
1,7,8Pakistan Medical Research Council, Islamabad, 2,5Pakistan Medical characterised by high-grade fever, haemorrhagic
Research Council, Research Centre JPMC, Karachi, 3,4World Health phenomenon (presence of at least one i.e. positive
Organization, Country Office, Islamabad, 6Pakistan Medical Research Council, tourniquet test; patechiae, ecchymoses, or purpura;
Research Centre KEMU, Lahore. epistaxis or bleeding from mucosa, gastrointestinal tract,
Correspondence: Ambreen Arif. Email: [email protected] injection sites or others), thrombocytopenia (moderate to

J Pak Med Assoc

Dengue fever in patients admitted in tertiary care hospitals in Pakistan 554
marked drop in platelets), and haemoconcentration of kits dengue IgM (Nova Tec Immudiagnostica GMBH)
(raised Packed Cell Volume). Plasma leakage may result in and non-structural protein 1 antigen (NS1Ag) (Inverness
pleural effusion and ascites. Some may progress to DSS medical) used were 97.6%:90% and 71.1%:96%
which is characterised by the presence of all four clinical respectively.17,18
manifestations of DHF along with circulatory failure i.e.
SPSS 16 was used for statistical analysis. Demographic,
rapid and weak pulse, narrow pulse pressure,
clinical, laboratory features and results were presented as
hypotension, cold/clammy skin and altered
mean ± standard deviation for quantitative variables (age,
consciousness. Severe dengue can also produce hepatic
stay in hospital, platelet count and unit of platelet
damage, cardiomyopathy, encephalopathy and
transfused) and number and percentage for qualitative
encephalitis — although these manifestations are rare,
variables (gender, age grouping, clinical presentation,
but the risk of death in such cases is high.14,15 Both
haemorrhage etc.). Statistical comparison was performed
DHF/DSS can cause high mortality if not managed
by using Chi-square/Fisher exact test (less than 5) for
urgently and appropriately.
qualitative variables and student t-test was used for
There are no specific antiviral treatments for dengue compariosn of platelet between DF and DHF, one-way
infection and patients usually recover with timely fluid analysis of variance (ANOVA) was used for the number of
and electrolyte replacement.16 Timely and appropriate trasnfsuions. All p values were two-sided, and considered
case management can reduce the mortality to below 1%. significant if <0.05.

In the absence of national dengue case management Results

guidelines and treatment protocols the clinicians are Out of the 841 dengue cases, 665 (79%) were males and 176
treating patients on the basis of their clinical acumen (21%) females, with an overall mean age of 31.3±14.0 years.
which at times results in over or under management. This Of the total, 653 (78%) cases were suffering from DF and 188
study was conducted to retrospectively analyse clinical (22%) had associated DHF of whom 5 (2.65%) had DSS.
records of all patients admitted with DF and its
complications in 5 tertiary care hospitals of Pakistan, and The overall age distribution of DF and DHF was worked
to assess the gaps in the diagnosis and management of out (Figure-1). Maximum cases of DF 439 (67%) and DHF
these cases. 141 (75%) were seen between 20 to 49 years with highest

Patients and Methods Table-1: Characteristics of patients with dengue fever (DF) and dengue haemorrhagic
The retrospective descriptive analytical study was done fever (DHF).
with a retrieval of case records of all clinically suspected and
laboratory-confirmed cases of DF who were admitted to Characteristics DF (n=653) DHF (n=188) P-value
No. (%) No. (%)
five hospitals from January to December 2010, using a
questionnaire. The hospitals were Jinnah Postgraduate Demographics
Medical Centre, Karachi (335 cases), Civil Hospital, Age in years (Mean ± S.D) 31.5 ± 14.4 30.6 ± 12.1 0.453
Hyderabad (160 cases), Jinnah Hospital, Lahore (222 cases), Gender
Ayub Medical Complex Abbottabad (99 cases), and Male 514 (79) 151 (80) 0.633
Pakistan Institute of Medical Sciences, Islamabad (25 cases). Female 139 (21) 37 (20)
Clinical Presentation
Only dengue IgM/IgG positive cases who had complete Fever 69 (82.1) out of 84 64 (73.6) out of 87 0.177
demographic and laboratory details were included. The Headache 36 (19.5) out of 185 21 (14.6) out of 144 0.246
information included patient's demography, Nausea and /or vomiting 86 (13.4) 39 (20.7) 0.014*
signs/symptoms and blood complete picture (CP) Rash 20 (11.0) out of 182 23 (15.5) out of 148 0.221
Haemorrhage
including haematocrit, treatment given including platelets
Patechiae - 12 (6.4)
transfused and the ultimate outcome i.e. death or Epistaxis - 73 (38.8)
discharge. Patients were classified into DF if they had fever, Malena - 13 (6.9)
while bleeding from any mucosal site along with fever was Other sites of bleeding** - 101 (53.7)
taken as DHF, and those in shock were classified as DSS. Shock - 5 (2.6)

Data of serologically-confirmed dengue patients from a Mean number of days 3.7 days (Range: 3-15 days)
private laboratory (Citi Lab, Islamabad) were also analysed patient's stay at the hospital Median = 3.0 days
to compare the age, gender and the monthly cases tested *Statistically significant p<0.05.
over the same time period. The sensitivity and specificity **Bleeding gum and mouth, haemoptysis, haematuria, etc.

Vol. 64, No. 5, May 2014

555 M. A. Munir, S. E. Alam, Z. U. Khan, et al

Table-2: Haemoglobin, white blood cell count, haematocrit and platelet count in
Dengue fever and Dengue haemorrhagic fever patients.

Characteristic DF (n=653) DHF (n=188) P-value

Low Haemoglobin <10 mg/dL 9 (10.2%) 14 (15.2%)

Out of 88 Out of 92 0.316
Leucopaenia (TLC < 4000) 178 (58.4%) 60 (54.5%)
Out of 305 Out of 110 0.487
Leukocytosis (TLC > 10,000) 2 (0.7%) 1 (0.9%)
Out of 305 Out of 110 0.487
Haematocrit (10-20% above normal) 28 (46.7%) 19 (31.7%) 0.092
Out of 60 Out of 60
Platelet Count (Mean ± S.D) 355, 50,000±37000 138, 40,000±37000 0.003
Figure-2: Number of Dengue Fever and Dengue Haemorrhagic Fever cases by month
(Hospital Data).

significantly more in DHF 39 (20.7%) compared to DF 86

(13.2%) (p<0.010), while other symptoms did not show any
significant difference. Tourniquet test was done in 20
(2.3%) cases and was positive in 11(55%). Range of hospital
stay was 3-15 days (mean 3.7±2.44; median 3 days).
Except for platelets count, which was significantly lower in
DHF, no significant difference was found in other
laboratory parametres when compared between DF and
Figure-1: Age (years) distribution of confirmed dengue cases (Hospital Data). DHF patients (Table-2).
Platelets were transfused in 35 (83.3%) of the 42 cases
peak between 20 to 29 years. Slightly more 68 (36%) DHF with severe thrombocytopenia i.e. (platelet count
cases were seen between 20 and 49 years. However, no <10,000), while in among the 449 patient having platelets
case of DHF was found in the age group of 0-9 years. range from 11,000 - >150,000 transfusion was given to 98
(21.8%) (Table-3).
Month-wise distribution showed a gradual increase in the
cases from September DF 39 (6%), DHF 12 (6%) with Overall, 720 (86%) recovered and were discharged, 24
maximum seen in October 278 (43%) DF, 75 (40%) DHF (3%) left against medical advise (LAMA), whereas 5 (0.6%)
and November 317 (48%) DF, 85 (45%) DFH and a decline patients died. No information was available for 92 (11.2%)
thereafter (Figure-2). cases regarding their outcome. Death details were
available in 1 (16.6%) of the 6 patients only. He was a 42-
The common presenting symptoms in patients with DF year male from Karachi who was admitted to a tertiary
and DHF are shown in Table-1. Nausea/vomiting was care hospital with fever (102°F), and massive bleeding. His

Table-3: Platelet transfusions to the admitted dengue patients (n=506).

Platelet count No. (%) of Subject Gender Platelets transfused

M F Yes No DK No. Units transfused Mean ± S.D.

< 10,000 42 (8.3) 37 5 35 (83.3%) - 4 1.17 ± 0.62

11,000-20,000 69 (13.6) 54 15 20 (29.0%) 29 20 1.55 ± 1.31
21,000-50,000 214 (42.3) 175 39 54 (25.2%) 115 45 1.46 ± 0.92
51,000-100,000 142 (28.1) 110 32 19 (13.5%) 81 42 1.32 ± 0.95
101,000-150,000 24 (4.7%) 18 6 3 (12.5%) 16 5 1.33 ± 0.58
>150,000 15 (3.0%) 11 4 2 (13.3%) 7 6 1.00 ± 0.00
P-value 0.001 0.886
DK = don't know.

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Dengue fever in patients admitted in tertiary care hospitals in Pakistan 556
earlier too19,20 which might be due to gender bias in
seeking healthcare.21 Proper covering of body and
maximum indoor stay in females could be another reason
for the low female preponderance.20,21 However, there are
studies that have not reported any gender difference.22,23
DF is regulated by seasonal variations in the South Asian
region where ideal condition for vectors' survival and
propagation exist, especially during monsoon period
when there is abundant rainfall and high humidity, with
daily temperature reaching 30°C. These climatic
NS1Ag: Non-structural protein 1 antigen. IgM: Immunoglobulin M. conditions provide excellent ground for mosquito
breeding.24-27 In the present study a gradual increase in
Figure-3: Age (years) distribution of NS1Ag and IgM positive dengue patients (Lab cases was seen from September with a peak in
Data).
October/November and a decline thereafter, indicating a
post-monsoon infection which has also been observed by
others.28-31 A study from Lahore also showed an increase
in dengue cases in September-December with a peak in
November.19 It appears that in Pakistan, this season is
highly favourable for vector breeding i.e. Aedes aegyptei.
DF and its complications maximally affect young adults
and the same was seen in the present study and those
reported by others from Pakistan.21 This finding is
consistent with other countries in South Asia.29,31 One of
the limitations of the study was that as the present study
retrieved records from adult medical wards and not
paediatric wards, therefore it is difficult to say what
NS1Ag: Non-structural protein 1 antigen. IgM: Immunoglobulin M.
proportion of children got infected with the disease. It
may also be kept in mind that dengue is an emerging
Figure-4: Number of NS1Ag and IgM positive dengue cases by month (Lab Data).
disease in Pakistan, and the population at large is not yet
completely immune, therefore, all age groups can be
infected, particularly the young adults, with this virus. One
haematocrit was 50%, haemoglobin 4.8 gm/dl, and potential source of bias might be the catchment areas and
platelet count 15000/cumm.3 He was transfused 2 units of accessibility, in terms of physical distances and costs
whole blood, 08 bags of fresh frozen plasma, and 02 mega involved of the hospitals from where data was collected.
units of platelets. The patient went into shock and hepatic
coma and was transferred to another private hospital Fever is the commonest symptom in dengue patients19,32
where he expired. The total span from admission to death and the same was found to be true in the present study
was 4 days. which was also in accordance with two earlier studies
reported from Pakistan.19,29 However, according to the
For comparison, data of 354 dengue IgM (ELISA) and World Health Organisation (WHO), the clinical features of
NS1Ag (Early Rapid kits) confirmed cases from a private DF vary according to the age. Adults may have either a
laboratory were analysed to see the age distribution, mild febrile syndrome or the classical incapacitating
gender and the number of cases tested over the study disease with abrupt onset of high-grade fever, severe
period. Age, gender and seasonal distribution of headache, pain behind the eyes, muscle and joint pains,
hospitalised patients was similar to the laboratory data and rash. DHF is a deadly disease characterised by high
(Figures 3 and 4). fever, haemorrhagic tendency and circulatory failure.30
Other symptoms in the present study were headache
Discussion
nausea/vomiting and rash, and these are comparable
The present study showed dengue peak in
with those documented by others though their
October/November with most cases having fever and few
frequencies varied.11,19,33,34
having haemorrhagic tendency and shock. Male
predominance was seen in all ages and has been reported In the current study, key haemorrhagic manifestations

Vol. 64, No. 5, May 2014

557 M. A. Munir, S. E. Alam, Z. U. Khan, et al

were seen in lesser number of patients (6.4-53.7%) as DHF. In the present study, the review of hospital record
compared to 67% reported from Malaysia.35 showed that haematocrit is not being monitored as per
WHO guidelines and most cases had only one or two
Thrombocytopaenia constitutes one of the most laboratory readings available in the followup.
common clinical findings in dengue disease36-38 and low
platelet count is currently used as a criterion for the The current study showed leucopenia in over 55% cases.
diagnosis of DHF.39 The cause of thrombocytopaenia in Leucopenia, or low white blood cell (WBC) count, has
dengue is unknown but decreased production of been reported among dengue patients in many studies,
platelets has been described.40,41 In the present study as well as by the WHO, except a retrospective study which
thrombocytopenia was seen in 92% cases which is much did not show any association between low WBC and
higher than 8.6% reported from Indonesia,42 48% in Sri dengue.30,54,55
Lanka,43 54% in Bangladesh,44 70% in India45 and 78% in
Tourniquet test (TT) is recommended as a screening tool
Cuba.46 Thrombocytopenia has also been reported in
for dengue infection. A positive TT indicates
other studies from Pakistan.19 Thrombocytopenia is a risk
haemorrhage30 and, according to WHO guidelines, a
factor for haemorrhage and the threshold for
positive test with leucopenia (< 5000 cells/mm3) at an
prophylactic platelet transfusion is 10,000/mm3 in non-
early stage is suggestive of dengue illness.47 In the current
dengue patients.45 The WHO recommends platelet
study, TT was done in 2.3% cases only. The validity and
transfusion in adults only with underlying hypertension
sensitivity of this test has been debated in some
and very severe thrombocytopenia (less then 10,000
studies.32,56-58
cell/mm3).47 No association has been found between the
degree of thrombocytopenia and active bleeding in The variation in the diagnosis and management of
other studies.48-51 It has been suggested that since there dengue patients in Pakistan showed lack of standard
is no specific treatment for DHF/DSS, therefore patients operating procedures according to international
with bleeding tendency and those having a platelet guidelines. National guidelines need to be developed
count of less than 20,000/mm3 may be empirically urgently so that healthcare providers can be trained
transfused platelets.52 The crux of treatment of dengue timely. Till then revised WHO guidelines 2011 can be
patients is maintenance of good hydration, monitoring adapted and endorsement by the national and provincial
for any overt bleeding and not to "panic" if the platelet authorities is mandatory. Furthermore, data management
count is less than 50,000/mm3 (normal platelet count is and record keeping in hospitals need to be strengthened
150,000-450,000/mm3).52 Most patients as well as as per WHO requirements which may help in future
healthcare providers often get panicky and tend to chase planning to optimally manage the dengue cases and for
platelet counts; this was evident in the present study and epidemic preparedness and response. Community
also in an outbreak in north India53 where it was labelled awareness campaign for prevention against dengue
as "Dengue Panic Syndrome". The role of platelet needs to be more vigorously pursued.
transfusion in the management of dengue patients in a
tertiary care hospital was studied and it was Conclusion
recommended that patients with <20,000/cumm are at Keeping in view the rising trend in the dengue cases in
high risk of bleeding and require urgent platelet Pakistan, it is recommended that dengue prevention and
transfusion, whereas patients with a count between control should be made part of the provincial malaria
21000-40,000/cumm are at moderate risk and require control programmes for regular surveillance, monitoring
platelet transfusion only if they have haemorrhagic and control.
manifestations.48 The role of platelet transfusion for the
management of dengue needs special attention.
Acknowledgments
The study was carried out under the World Health
In the present study, raised haematocrit (above 10-20%) Organization-sponsored Agreement of Performance of
was observed in 47% DF and 32% DHF patients. However, Work. We are grateful to the chief executives, physicians
according to WHO,30 a rise in the haematocrit level, and staff of the five participating hospitals for their
indicating plasma leakage, is present even in non-shock extreme cooperation. Dr Tasneem Ahsan, Director, Jinnah
cases but is more pronounced in shock cases. Postgraduate Medical Centre, Karachi, deserves a special
Haemoconcentration with increase in haematocrit of 20% mention. Thanks are also due to all Pakistan Medical
or more is considered to be a definitive evidence of Research Council colleagues; Dr. Waqar-ud-Din Ahmed,
increased vascular permeability and plasma leakage. A Dr. Shamoona Fareeha, Dr. Javeria Waqar, Mr. Kashif Munir,
rising haematocrit and falling platelet count is typical of Dr. Kanya Lal Talreja, Mr. Rizwanullah, Mr. Khalid

J Pak Med Assoc

Dengue fever in patients admitted in tertiary care hospitals in Pakistan 558
Mehmood and Mr. Mehmood Ahmed for support in data changing epidemiology. Emerg Themes Epidemiol 2005; 2: 1.
collection, entry and analysis. Further, we are grateful to 22. Jamaih I, Rohela M, Nissapatorn V, Hiew FT, Mohammed HA, Noo
LH, et al. Retrospective study of dengue fever (DF) and dengue
Citilab, Islamabad, for sharing data on serologically- haemorrhagic fever (DHF) patients at University Malaya Medical
confirmed dengue patients. Centre, Kuala Lumpar Malaysia in the year 2005. Southeast Asian J
Trop Med Public Health 2007; 38 (Suppl 1): 224-30.
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