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Indian national guidelines for clinical

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Vector-borne diseases special

Indian National Guidelines for Clinical Management of

Dengue Fever
Ashutosh Biswas1, GHANSHYAM Pangtey2, Veena Devgan3, Paras Singla1, Pavana Murthy4, AC Dhariwal5, PK Sen5,
Kalpana Baruah5

1Dept. of Medicine, All India Institute of Medical Sciences, New Delhi

2Dept. of Medicine, Lady Hardinge Medical College, New Delhi
3Dept. of Pediatrics, Hindu Rao Hospital, Delhi
4WHO Country Office, New Delhi
5Directorate of National Vector Borne Disease Control Program, (Directorate General of Health Services, Ministry of Health and FW, Govt. of India), Delhi

Abstract
The increasing burden of dengue is a matter of serious concern in the world, especially in absence of specific antiviral drug and a great challenge
for the clinicians to recognize the severity of the disease at the early phase for timely effective management to reduce complication and death.
The complexity and variability among the different World Health Organization (WHO) dengue case classifications led to confusions among
the clinicians as to which one should be followed. A need was felt to revise the existing Indian National guideline (2007), which was based on
WHO 1997 case classifications. National and international experts were involved in preparing the guideline. Available literature and WHO
guidelines (2009 and 2011) were reviewed, both the case classifications were debated and recent developments in understanding the pathogenesis
were critically analyzed during several brain-storming sessions and meetings. Finally, harmonizing the available case classifications a user-friendly
Indian National Guideline has been developed to make uniform criteria to grade the severity for better planning and management of dengue
infection in the country. The aim of the revised classification is to distinguish confidently between mild, moderate and severe dengue infection
for the better use in clinical practice. This guideline has been circulated to states for wider circulation and capacity building of the clinicians. In
this communication, an endeavor has been made to present the guideline that attempted to harmonize the complexity and variability that exist
among the available WHO guidelines especially to address the case classification and clinical management.
Keywords: Dengue infection, harmonization of case-classification by severity grading, India

D
engue infection is the most rapidly emerging
vector-borne viral disease with a 30-fold increase
in global incidence over the last five decades. It
is a major public health concern throughout tropical and
subtropical regions of the world.1 In India, every year cases
are spreading to newer geographical areas. All four dengue
virus serotypes have been isolated from different parts
of the country.2 India contributed 6-9% of total cases in
South-East Asian Region (SEAR) countries between 2009
and 2011, which has increased to 19% in 2013.3 After
incubation, the disease begins abruptly and passes through
three phases: Febrile, critical and recovery. Dengue infection
needs to be addressed as a single disease with different
clinical presentations ranging from asymptomatic conditions
to severe clinical courses that may lead to high morbidity
and mortality.4 In the absence of a specific antiviral drug
for dengue infection, it is a great challenge for the clinicians
to recognize the severity of the disease at the early phase
for early intervention and timely effective management to
reduce complication and death.1
Due to complexity and variability among the different World
Health Organization (WHO) dengue case classifications,
most clinicians were confused with multiple guidelines that
which one should be followed.5,6 They were also facing
difficulty in applying the criteria for diagnosis of dengue
hemorrhagic fever/dengue shock syndrome (DHF/DSS) as it
is based on rise in hemoconcentration 20% above baseline,
a positive tourniquet test (low sensitivity) for the diagnosis
of severity of dengue infection.7 The introduction of warning
signs in the 2009 WHO guideline helped clinicians to triage
and monitor carefully for prediction of severity, which could
prevent the fatal outcome.8 However, the warning signs
alerted the clinicians to admit large number of cases that
overburdened the hospital in a resource-limited setting and
during epidemics. Therefore, in this national guideline the
experts recommended to harmonize all previous classifications
and tried to formulate uniform criteria to grade the severity
for better planning and management of dengue patients.9
Objective
To harmonize the dengue case-classification and to prepare
an Indian National Guideline for clinical management of
dengue fever (DF)

196 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015

Methods
A revision of the existing Indian National Guideline
was needed as several advancements have taken place in
understanding the pathogenesis and classification of dengue
infection.10,11 National and international experts were
involved in preparing the guideline. Several issues evolved
during the process mostly related to understanding the
pathogenesis and case classifications. The clinicians and
experts raised the questions regarding the variability of
WHO case classifications. The expert members reviewed
the available published literature and WHO guidelines for
preparing the guideline.12-23 In clinical practice, it is realized
that DHF cases are misclassified as DF due to complex
mechanisms for confirming the DHF where plasma leakage
is the main underlying cause, but it is difficult to apply this
criteria as most of the healthcare settings lack diagnostic
facilities necessary for distinguishing DHF/DSS from
DF.18,19,21 Other issues like severe and nonsevere cases,
warning sign and organ involvement were critically analyzed
for preparing the guideline and to make it user-friendly for
the physicians for proper diagnosis, identifying severity and
effective timely interventions for better clinical management.
Several brain-storming sessions and meetings of experts were
held for bringing the final shape of this guideline.
New Dengue Clinical Management Guideline
The new revised classification aims to distinguish
confidently between mild, moderate and severe dengue
infection for better use in clinical practice.24 All symptoms,
signs and presentations are manifested by capillary
leakage (vasculopathy), impairment of coagulation profile
(coagulopathy), bleeding or organ involvement.
In this guideline, clinically the severity of dengue infection
is divided into three categories, i.e., mild, moderate and
severe as shown in Figure 1. Because often, it becomes
difficult for the clinician to know whether patient should
be advised home management, close monitoring, possible
hospitalization or refer to tertiary level care hospital for
better management.
Mild Dengue Infection
Mild dengue infections are characterized by undifferentiated
DF, fever without complications like bleeding, hypotension,
organ involvement or any evidence of capillary leakage.8
These patients usually do not have warning signs and
symptoms; hence, can be managed at home with proper
counseling.
Moderate Dengue Infection
Moderate dengue infections were characterized into two
groups:
Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
Vector-borne diseases special
zz Dengue infection with warning signs and symptoms,
DHF-I and II
zz Dengue infection with high-risk and comorbid
conditions.
Moderate dengue with warning signs and symptoms
The presence of warning signs and symptoms are considered
to be the indicators of severity.9 With the following warning
signs and symptoms, dengue infected patients may progress
into severe stage, which may require close monitoring.
DF with warning signs and symptoms
Recurrent vomiting
Abdominal pain/tenderness
General weakness/lethargy/restlessness
Minor bleeding
Pleural effusion/ascites
Hepatomegaly
Increased hematocrit (Hct).
DHF Grade I and Grade II with or without minor
bleeding: These patients are DHF without hypotension or
shock. Sometimes, these patients with minor bleeding may
progress to severe plasma leakage and could lead to organ
involvement, massive bleeding and shock.
Moderate dengue with high-risk and comorbid conditions
Dengue infected patients are likely to progress to severe
manifestations in presence of high-risk and comorbid
conditions. The following high-risk and comorbid conditions
are found to be associated with high chances of progressing
to severe dengue infection:
Infants
Old age
Diabetes
Hypertension
Pregnancy
Coronary artery disease (CAD)
Hemoglobinopathies
Immunocompromised patient
Patient on steroids, anticoagulants or immunosuppressants.
The moderate dengue patients should be closely monitored
or possibly hospitalized for further management as these
groups of patients can develop severe dengue manifestation
due to abnormalities in metabolic conditions, severe plasma
leakage and increases the mortality.
197
Vector-borne diseases special

Dengue Viral Infection

Symptomatic Asymptomatic

Mild dengue Moderate dengue Severe dengue

DF with high-risk and comorbid DF with warning signs and

conditions symptoms

A. Undifferentiated DF yy Infants A. DF with warning signs and A. DF/DHF with

B. Fever without yy Old age
complication like yy Diabetes
yy Hypertension
bleeding, hypotension
yy Pregnancy
and organ yy CAD
involvement yy Hemoglobinopathies
C. Without evidence of yy Immunocompromised
capillary leakage patient
yy Patient on steroids,
anticoagulants or
immunosuppressants
symptoms
yy Recurrent vomiting
yy Abdominal pain/tenderness
yy General weakness/
letharginess/restless
yy Mild pleural effusion/ascites
yy Hepatomegaly
yy Increased Hct >20%
B. DHF I & II with minor bleeds
significant hemorrhage
B. DHF with shock (DHF III &
IV- DSS)
C. Severe organ involvement
(Expanded dengue
syndrome)
D. Severe metabolic disorder

Home management Close monitoring* and possibly hospitalization Tertiary level care

*Close monitoring: Hct, Plt, Hb, fluid intake/output, HR, RR, BP, Consciousness.

Figure 1. Clinical case classification.

Severe Dengue Infection DHF are commonly associated with comorbidities and with
Severe dengue patients are recognized by the presence of various other coinfections. Clinical manifestations observed
shock, capillary leakage, significant bleeding, severe organ in expanded dengue syndrome (EDS) are as follows:
involvement and severe metabolic abnormalities.10 This
group of patients should be immediately admitted and System Unusual or atypical manifestations
require intensive care management. They should be properly CNS involvement Encephalopathy, encephalitis, febrile
seizures, intracranial bleed
investigated to look for abnormalities in coagulation profile,
GIT involvement Acute hepatitis/fulminant hepatic
complete hemogram and organ function test, which may failure, cholecystitis, cholangitis, acute
require timely intravenous (IV) fluid, blood or platelet pancreatitis
transfusion.11 Severe shock patients should be managed Renal involvement Acute renal failure, hemolytic uremic
with fluids very carefully to prevent organ damage and syndrome, acute tubular necrosis
pulmonary edema, which is associated with high mortality. Cardiac involvement Cardiac arrhythmia, cardiomyopathy,
Management of organ failure like liver, respiratory, cardiac myocarditis, pericardial effusion
and renal should be targeted as early as possible to prevent Respiratory Pulmonary edema, ARDS, pulmonary
progression of the disease severity.12 Usually, organ failure hemorrhage, pleural effusion
management is done in tertiary level hospitals. Therefore,
Eye Conjunctival bleed, macular hemorrhage,
these patients should be transferred to tertiary level hospitals visual impairment, optic neuritis
when indicated, without delay.

Expanded Dengue Syndrome Dengue in infants

Severe organ involvement may be found in DF and also Spectrum can range from asymptomatic infection to mild
with or without DHF. Unusual manifestations of DF/ or clinically significant severe disease. The burden of severe

198 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015

dengue lies predominantly in infants 4-9 months of age.
Upper respiratory tract symptoms (cough, nasal congestion,
running nose, dyspnea), gastrointestinal symptoms
(vomiting, diarrhea) and febrile convulsions are more
common in infants with dengue compared to older children.
Differentiation between dengue and other common
infections in infants such as pneumonia, bacterial sepsis,
meningoencephalitis, measles, rotavirus infection, etc. is
often not possible in febrile stage. Hepatomegaly is usually
noted. Splenomegaly is seen in almost 10% of dengue
infants.11 The normal value of hematocrit in infants
2-12 months of age is relatively low and may be even lower
in iron deficiency anemia. Severe dengue is uncommon in
infants but when it occurs, the risk of mortality increases.12
Neonatal Dengue
When a pregnant woman gets dengue infection, the
diagnosis of dengue should be considered in her neonate
even if it appears well in first days of life. Initial presentation
may be confused with bacterial sepsis, birth trauma and
other neonatal illnesses.
Laboratory Diagnosis
In endemic areas, early symptoms of DF mimic many
other prevalent diseases such as chikungunya, malaria, viral
infection, urinary tract infection, typhoid, leptospirosis,
etc. Hence, exclusion of other conditions based on clinical
manifestation and laboratory investigations is very crucial
for proper management.
National Vector Borne Disease Control Program
(NVBDCP), Govt. of India recommends use of enzyme-
linked immunosorbent assay (ELISA)-based antigen
detection test (NS1) for diagnosing the cases from 1st day
onwards and antibody detection test immunoglobulin M
(IgM) capture ELISA (MAC-ELISA) for diagnosing the
cases after 5th day of onset of disease to confirm dengue
infection.14
A number of rapid diagnostic test (RDT) kits for
NS1 antigen and anti-dengue IgM/IgG antibodies are
commercially available at present, which produces the
results within 15-25 minutes. However, the accuracy
of most of these tests is not known since they have not
yet been properly validated. Some of the RDTs have
been independently evaluated. The results showed a high
rate of false positive results compared to standard tests,
while others have agreed closely with standard tests. The
sensitivity and specificity of some RDTs are also found to
vary from lot to lot. Hence, currently, use of RDT is not
recommended under the program.
Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
Vector-borne diseases special
Clinical management
Approach to clinical management of DF may vary from mild,
moderate and aggressive depending on severity of illness.
Patients who have simple fever without any danger signs
or complications may be managed with simple approach.
Those who have danger signs should be managed with
close monitoring for progression of DHF/DSS or severe
bleeding. The patients presenting with Grade III and IV of
DHF, significant bleeding or involvement of various organs
will require aggressive management to reduce morbidity
and mortality. Patient may develop more complications
during later stage of fever (defervescence) or afebrile phase,
where clinician should be careful to look for danger signs or
severity of disease.
Management of dengue fever
Management of DF is symptomatic and supportive.
Antipyretics may be used to lower the body temperature.
Aspirin/NSAIDs (nonsteroidal anti-inflammatory drugs)
like ibuprofen, etc. should be avoided since it may cause
gastritis, vomiting, acidosis, platelet dysfunction and severe
bleeding complication. Oral fluid and electrolyte therapy
is recommended for patients with excessive sweating,
vomiting or hypotension. Patients should be monitored
for 24-48 hours in DHF endemic areas until they become
afebrile without the use of antipyretics and after hematocrit
determinations are stable, platelet count is >50,000/mm3
or improving.
Management of DHF (Febrile Phase)
Management of febrile phase is similar to that of DF.
Paracetamol is recommended to keep the temperature below
39oC. Copious amounts of fluids should be given orally, to
the extent the patient tolerates, oral rehydration solution
(ORS), such as those used for the treatment of diarrheal
diseases and/or fruit juices are preferable to plain water.
IV fluids should be administered if the patient is vomiting
persistently or refusing to feed.
Patients should be closely monitored for the initial signs
of shock. The critical period is during the transition from
the febrile to the afebrile stage and usually occurs after the
third day of illness. Serial hematocrit determinations are
essential guide for treatment, since they reflect the degree
of plasma leakage and need for IV administration of fluids.
Hematocrit should be determined daily from the third day
until the temperature has remained normal for 1-2 days.
Management of DHF Grade I and II
Any person who has DF with thrombocytopenia and
hemoconcentration and presents with abdominal pain, black
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Vector-borne diseases special

Hemorrhagic (bleeding) tendencies, thrombocytopenia, Hct rise 20%

Initiate IV therapy 6 mL/kg/h crystalloid solution for 1-2 hours

Check Hct

Improvement* No improvement**

IV therapy by crystalloid Hct rises Hct falls

successively reducing the flow from
6 mL/kg/h for 2-4 h to 3 mL/kg/h for
2-4 h and 3-1.5 mL/kg/h for 2-4 h Increase IV 10 mL/kg/h crystalloid for 2 h Suspect internal
hemorrhage

Further improvement
Blood transfusion (10 mL/kg whole blood)/
(5 mL/kg packed RBC)
Discontinue IV after 24-48 h

Improvement

Notes: IV therapy by crystalloid successively

*Improvement: Hct falls, pulse rate and blood pressure stable, urine output rises. reducing the flow from 10 to 6 and later to
**No improvement: Hct or pulse rate rises, pulse pressure falls below 20 mmHg, urine output falls. 3 mL/kg/h. Discontinue after 24-48 h

Figure 2. Volume replacement algorithm for patients with DHF Grades I and II.

Compensated shock
Pulse pressure 20 mmHg, hypotension (SBP <90 mmHg),
high Hct (>20% rise from baseline)

Initiate IV therapy 10-20 mL/kg/h crystalloid solution for 1 h

*Improvement in VS & Hct **No improvement in VS

Start IV therapy by crystalloid Check Hct

successively reducing the flow from
10 mL/kg/h for 1-2 h to 6 mL/kg/h for
2-4 h and 3-1.5 mL/kg/h for 2-4 h Hct rises or is >45% Hct falls

IV colloid/crystalloid Suspect bleeding

10-20 mL/kg over 1 h
Further improvement in VS
Blood transfusion (10 mL/kg whole blood)/
No improvement (5 mL/kg packed RBC)

Refractory
ABCS#
hypotension

Discontinue IV after 24-48 h Improvement in VS No improvement in VS

Crystalloid: Normal saline, ringer lactate.

Colloid: Dextran 40/degraded gelatine polymer (polygeline).
#ABCS = Acidosis, Bleeding, Calcium (Na++ & K+), Sugar. IV inotropes with crystalloid
Notes: maintenance fluid according to
*Improvement: Hct falls, pulse rate and blood pressure stable, urine output rises. Holiday-Segar formula
**No improvement: Hct or pulse rate rises, pulse pressure falls below 20 mmHg, urine output falls.
yy Unstable vital signs: Urine output falls, signs of shock.
yy In cases of acidosis, hyperosmolar or Ringer's lactate solution should not be used.
yy Serial platelet and Hct determinations: Drop in platelets and rise in Hct are essential for early diagnosis of DHF.
yy Cases of DHF should be observed every hour for vital signs and urine output.

Figure 3. Volume replacement algorithm for patients with DHF Grade Ill.

200 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
 Vector-borne diseases special

Profound shock
Signs of shock, hypotension (BP undetectable), high Hct (>20% rise from baseline)

Oxygen

Immediate rapid volume replacement: give 10-20 mL/kg

crystalloid solution as rapid bolus over 15-30 min

*Improvement in VS & Hct **No improvement in VS

Repeat 10-20 mL/kg crystalloid/colloid*

second bolus over 15-30 mins

Start IV therapy by crystalloid, Check Hct

successively reducing the flow from 10 to
6 mL/kg/h for 2 h, 6 to 3 mL/kg/h for 2-4 h Improvement in Hct rises or >45%
and 3-1.5 mL/kg/h for 2-4 h Hct falls
Hct & VS

Further improvement in VS Suspected bleeding

IV colloid/crystalloid
10-20 mL/kg over 1 h
Blood transfusion (10 mL/kg whole
Discontinue IV after 24-48 h
blood)/ (5 mL/kg packed RBC)
No improvement

Improvement in VS Refractory hypotension

Crystalloid: Normal saline, ringer lactate.
Colloid: Dextran 40/degraded gelatine polymer (polygeline). Look for ABCS
ABCS = Acidosis, Bleeding, Calcium (Na++ & K+), Sugar.
Notes:
*Improvement: Hct falls, pulse rate and blood pressure stable, urine output rises. No improvement in VS
** No improvement: Hct or pulse rate rises, pulse pressure falls bellow 20 mmHg, urine output falls.
Unstable vital signs: Urine output falls, signs of shock.
In case of acidosis, hyperosmolar or Ringer's lactate solution should not be used. IV inotropes with crystalloid
Serial platelet and Hct determinations: Drop in platelets and rise in Hct are essential for early diagnosis of DHF. maintenance fluid according to
Cases of DHF should be observed every hour for vital signs and urine output. Holiday-Segar formula

Figure 4. Volume replacement algorithm for patients with DHF IV (DSS).

tarry stools, epistaxis, bleeding from the gums, etc. needs to
be hospitalized. All these patients should be observed for
signs of shock. The critical period for development of shock
is during transition from febrile to afebrile phase of illness,
which usually occurs after third day of illness.
A rise of hemoconcentration indicates need for IV fluid
therapy. If patient develops fall in blood pressure (BP),
decrease in urine output or other features of shock despite
treatment, management for Grade III/IV DHF/DSS should
be instituted. Oral rehydration should be given along with
antipyretics like paracetamol, sponging, etc. as described
above. The algorithm for fluid replacement therapy in case
of DHF Grade I and II is given in Figure 2.
Management of Shock (DHF Grade III/IV)
Immediately after hospitalization, the platelet count and vital
signs should be examined to assess the patients condition
and IV fluid therapy should be started. The patient requires
regular and continuous monitoring. If the patient has already
received about 1,000 mL of IV fluids, it should be changed
to colloidal solution preferably Dextran 40/haemaccel;
if the hematocrit is falling, fresh whole blood transfusion
10-20 mL/kg/dose should be given.
However, in case of persistent shock when, after initial
fluid replacement and resuscitation with plasma or plasma
expanders, the hematocrit continues to decline, internal
bleeding should be suspected. It may be difficult to
recognize and estimate the degree of internal blood loss in
the presence of hemoconcentration. Hence, whole blood in
small volumes of 10 mL/kg/hour for all patients in shock
as a routine precaution is recommended. Oxygen should
be given to all patients in shock. Treatment algorithms
for patients with DHF Grades III and IV are given in
Figures 3 and 4.
Calculation of Fluid
The required amount of fluid should be calculated on the
basis of body weight and charted on 1-3 hourly basis or
even more frequently in the case of shock. For obese and
overweight patients, fluid should be calculated on the basis
of ideal body weight. The regimen of the flow of fluid and
the time of infusion are dependent on the severity of DF.
It is calculated for dehydration of about 5% deficit (plus
maintenance). The maintenance fluid should be calculated
using the Holiday-Segar formula.
For a child weighing 40 kg, the maintenance is: 1,500 + (20
20) = 1,900 mL. Amount of fluid to be given in 24 hours

Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015 201
Vector-borne diseases special
is calculated by adding maintenance + 5% dehydration,
which is equivalent to 50 mL/kg. This should be given in
24 hours to maintain just adequate intravascular volume
and circulation. Therefore, for a child weighing 40 kg the
fluid required will be 1,900 + (40 50) = 3,900 mL in
24 hours. For IV fluid therapy of patients with DHF, four
regimens of flow of fluid are suggested: 3 mL/kg/hour;
6 mL/kg/hour; 10 mL/kg/hour and 20 mL/kg/hour.
Management of Severe Bleeding
In case of severe bleeding, patient should be admitted in
the hospital and investigated to look for the cause and site
of bleeding and immediate attempt should be made to stop
the bleeding. Internal bleeding like gastrointestinal (GI)
bleeding may be sometime severe and difficult to locate.
Patients may also have severe epistaxis and hemoptysis and
may present with profound shock. Urgent blood transfusion
is life-saving in this condition. However, if blood is not
available shock may be managed with proper IV fluid or
plasma expander (i.e. haemaccel).
If the patient has thrombocytopenia with active bleeding,
it may be corrected with platelet transfusion. In case of
massive hemorrhage, blood should be tested to rule out
coagulopathy by testing for prothrombin time (PT) and
activated partial thromboplastin time (aPTT). Patients of
severe bleeding may have liver dysfunction and in this case,
liver function tests (LFTs) should also be performed. Rarely,
intracranial bleed may also occur in some patients, who have
severe thrombocytopenia and abnormal coagulation profile.
Management of Dengue Fever with comorbid illness
Different comorbid illness like hypertension, diabetes,
thyroid, liver, heart and renal diseases may contribute in the
development of severe manifestations in DF.
Dengue Hepatitis
Some patient may have impairment of LFT due to
dengue infection. In some DF patients, the aspartate
aminotransferase/alanine aminotransferase (AST/ALT)
level may be very high and PT may be prolonged.
Hepatic involvement is commonly associated with pre-
existing conditions like viral hepatitis, cirrhosis of liver and
hepatomegaly due to some other cause. Patient may also
develop hepatic encephalopathy due to severe liver failure.
Liver involvement also sometimes associates with DF in
pregnancy. Low albumin due to chronic liver disease may
be associated with severe DHF and bleeding. GI bleeding is
common in this condition and patient may go into severe
DSS. These patients should be managed carefully with
hepatic failure regimen with appropriate fluid and blood
transfusion. If PT is prolonged, IV vitamin K1 may be
initiated in such conditions.
202 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
Dengue Myocarditis
Dengue infection may rarely cause acute myocarditis,15
which may also contribute to the development of DSS.
Cardiac complications may be seen in presence of
CAD, hypertension, diabetes and valvular heart disease.
Management of shock with IV fluids in this case sometimes is
difficult due to myocardial dysfunction. Patient may develop
pulmonary edema due to improper fluid management.
Some CAD patient may be already taking aspirin and other
antiplatelet agents, which may also contribute to severe
bleeding unless these are stopped during dengue infection.
Cardiac ischemia or electrolyte disturbances may be
reassessed. Patient may develop congestive or biventricular
failure and should therefore be treated properly for better
morbidity and mortality outcome.
DF in Diabetes
Sometimes diabetes patients may present with severe
complications in DF when target organs are involved like
diabetic retinopathy, neuropathy, nephropathy, vasculopathy,
cardiomyopathy and hypertension. Due to dengue infection,
the blood sugar may become uncontrolled, which may
sometimes require insulin therapy for better management.
Renal Involvement in DF
Acute tubular necrosis (ATN) may develop during DSS
and may cause acute kidney injury (AKI) if fluid therapy
is not initiated in time. Renal function may be reversible,
if shock is corrected within short span of time. But, if
the shock persists for long time patient may develop renal
complications. Urine output monitoring in dengue infection
is very important to assess renal involvement. Microscopic
and macroscopic hematuria should be examined in DHF
patients. Other investigations like blood urea, creatinine,
electrolytes, glomerular filtration rate (GFR), arterial blood
gas (ABG) should be done in patients with severe dengue/
DHF. Fluid intake should be closely monitored in case of
AKI to avoid fluid overload and pulmonary edema. Dengue
patient may develop severe DHF in presence of diabetic
nephropathy, hypertensive nephropathy, connective tissue
disorders like systemic lupus erythematosus (SLE) and other
pre-existing chronic diseases.
CNS Involvement in DF
Altered sensorium may develop in dengue patients due to
various conditions like shock, (DSS), electrolyte imbalance
(due to persistent vomiting), fluid overload (delusional
hyponatremia or other electrolyte), hypoglycemia and also
due to involvement of central nervous system (CNS) by
dengue virus. Acute encephalopathy or encephalitis may be

seen in some patients with severe dengue. Sometimes, it may
be difficult to exclude clinically cerebral malaria and enteric
encephalopathy, which are also seen during the same period
(epidemic). Dengue serology (IgM) in cerebrospinal fluid
may help to confirm dengue encephalopathy or encephalitis.
Management of DF with coinfections
It is sometimes difficult to manage DF with coinfections
like malaria, chikungunya, tuberculosis (TB), human
immunodeficiency virus (HIV), enteric fever and
Leptospirosis because clinical presentations are mostly severe
in the presence of these coinfections.
Malaria: Malaria is a common coinfection in dengue as
it is prevalent across our country and transmission also
coincides during the same period/season. Malaria should
be excluded in the beginning without loss of much time
as it has its specific management. Antimalarial treatment
should be started as soon as possible to prevent
complication and better outcome during coinfection.
Chikungunya: In some geographical areas, both
infections are prevalent at the same time. Acute
complications are sometimes severe in DF in presence of
chikungunya. In case of predominant joint involvement
in a DF patient, chikungunya should be investigated and
proper management should be carried out accordingly.
TB: Patients may develop breathlessness and massive
hemoptysis in pulmonary TB. These patients may also
develop moderate-to-massive pleural effusion and acute
respiratory distress syndrome (ARDS). If patient has DF
in presence of TB and is on anti-TB treatment (ATT),
then he/she should be closely monitored for further
development of respiratory/pulmonary complications to
prevent morbidity and mortality.
HIV: Dengue patients may have severe complications like
DHF, DSS, significant bleeding and organ involvement
among HIV/AIDS patients. Outcome of DF is poor
amongst severely immune compromised patients who
have opportunistic infections and very low CD4 counts.
Multiorgan involvement may be common in DF and
is responsible for high-mortality. Management of DF
with HIV and AIDS should be undertaken with HIV
specialist consultation.
Enteric fever: Water-borne diseases like typhoid
fever and gastroenteritis are also common during the
monsoons when dengue infection is also reported in
large numbers. In the initial phase, DF patient may be
more complicated with typhoid if antibiotic treatment
is started late. In high suspected cases, blood culture
for typhoid fever should be sent to confirm diagnosis as
Widal test may not be positive before 2 weeks of fever.
Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
Vector-borne diseases special
Management of Dengue in pregnancy
DF infection in pregnancy carries the risk of more bleeding,
fetal complications, low-birth-weight and premature birth.
Risk of vertical transmission also increases during pregnancy.
Pleural effusion, ascites, hypotension are commonly
associated with DF in pregnancy. Involvement of lungs
and liver are also common in pregnancy. Patients may have
respiratory symptoms due to massive pleural effusion and
high serum glutamic-oxaloacetic transaminase (SGOT)
and serum glutamic-pyruvic transaminase (SGPT) due to
liver involvement. Complications of DF depend on the
different stages of pregnancy like early, late, peripartum and
postpartum period.
Pregnancy is a state of hyperdynamic circulation and fluid
replacement should be carefully done to prevent pulmonary
edema. Frequent platelet count and coagulation profile
testing should be done during DF in pregnancy along with
regular monitoring of BP. Fulminant hepatic failure, ARDS
and acute renal failure in pregnancy may be associated
with dengue infection. Management of dengue infection
in pregnancy should be taken seriously to reduce morbidity
and mortality in mother as well as fetus.
Management of neonatal Dengue
After delivery, the newborn may go into shock, which may
be confused with septic shock or birth trauma. In this case,
history of febrile illness during pregnancy is important,
which may help to diagnose DSS among neonates and
infants. Close observation, symptomatic and supportive
treatment are the mainstay of management.
Management of Dengue in infants
Dengue Without Warning Signs
Oral rehydration with oral rehydration solution (ORS),
fruit juice and other fluids containing electrolytes and
sugar should be encouraged together with breastfeeding or
formula feeding. Parents or caregivers should be instructed
about fever control with antipyretics and tepid sponging.
They should be advised to bring the infant back to the
nearest hospital immediately if the infant has any of the
warning signs.
Dengue with Warning Signs
When the infant has dengue with warning signs, IV
fluid therapy is indicated. In the early stage, judicious
volume replacement by IV fluid therapy may modify
the course and severity of the illness. Initially, isotonic
crystalloid solutions such as Ringers lactate (RL),
Ringers acetate (RA) or 0.9% saline solution should
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Vector-borne diseases special
be used. The capillary leak resolves spontaneously after
24-48 hours in most of the patients.
Severe Dengue: Treatment of shock
Volume replacement in infants with dengue shock is very
challenging and it should be done promptly during the
period of effervescence. Each and every case should be
critically analyzed separately and following points in general
should be kept in mind during management.
Management of Dengue Infection in outbreak
situation
During outbreak situation, dengue patient turnover may
increase exceptionally. All hospitals in endemic areas should
have a plan dealing with emergency hospitalization to make
the most effective use of hospital and treatment facilities in
case of outbreak occurs.
Criteria for admission of a patient
If a DF patient presents with significant bleeding from any
site, signs of hypotension, persistent high-grade fever, rapid
fall of platelet count, sudden drop in temperature, he/she
should be admitted in hospital. However, those patients who
have evidence of organ involvement should also be admitted
for proper monitoring and management. Dengue patients
with warning signs and symptoms should be admitted and
closely monitored.
Criteria for discharge of patients
Hospitalized patients who have recovered from acute dengue
infection and have no fever for at least 24 hours, normal
BP, adequate urine output, no respiratory distress, persistent
platelet count >50,000/mm3 should be discharged from
hospital.
Indications of platelet transfusion
In general, there is no need to give prophylactic platelets
even at <20,000/mm3. Prophylactic platelet transfusion
may be given at level of <10,000/mm3 in absence of
bleeding manifestations. Platelet transfusion may also be
given in prolonged shock with coagulopathy and abnormal
coagulogram. In case of systemic massive bleeding,
platelet transfusion may be needed in addition to red cell
transfusion.
Standard dose for adults is 5-6 units of random donor
platelets or 1 unit of apheresis platelets or 1 unit of BCPP
equivalent to 3 1011 platelets. For neonates/infants, the
dose of platelets should be 10-15 mL/kg of body weight.
Use of fresh frozen plasma/cryoprecipitate in coagulopathy
204 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
with bleeding should be as per the advice of physician and
patients condition.
Discussion
This new case-classification for dengue diagnosis would
definitely clear the confusion created by availability of
different WHO case classification among the clinicians
and would help in better understanding to classify severity
of dengue correctly for effective clinical management.17,21
Clinical as well as biochemical criteria have been considered
to understand the severity and grading.18 It has been
observed that the available case classifications fail to correctly
identify and classify the severity of dengue.20 It is very
important for the clinician to classify clinically severe and
nonsevere dengue infection before initiating and planning
clinical management.4 The basic management of dengue
infection is targeted symptomatically. In the early stage, if
signs and symptoms are identified to grade the severity, it
could help the clinicians for appropriate intervention and
better outcome for reducing the morbidity and mortality.
The WHO classification used since the 70s classifies dengue
into DF, DHF and DSS.24,25 In 2009, a new classification
of dengue proposed by WHO Tropical Disease Research
(TDR) was published in which dengue was classified as
dengue (D), dengue with warning signs (DW) and severe
dengue (SD).21
DHF gradation alone was not sufficient to classify mild,
moderate and severe dengue.12 As per this gradation, severe
cases like organ involvement, metabolic abnormalities such
as dyselectrolytemia, acidosis or alkalosis were not taken
into account. Some warning signs and symptoms of dengue
infection have been correlated with the progression of the
disease to severe manifestations. Warning signs were taken
as criteria for hospital admission, which overburdened the
hospitals and also the clinicians.17 Many of these patients
require observations and close monitoring to look for
progression of the disease. However, there was no hardcore
evidence that these patients with warning signs would
develop severe dengue.
In this guideline, the severity has been grouped into three
grades such as mild, moderate and severe dengue. Severe
dengue has been classified and defined in WHO guideline,
whereas nonsevere dengue has been classified into dengue
with warning signs and without warning signs.8 However,
in this revised guideline, nonsevere dengue is classified into
mild and moderate grade (Fig. 1). Mild dengue is defined
as fever in absence of bleeding, capillary leakage and organ
involvement while moderate dengue is classified into two
grades, one with warning signs and other with high-risk
conditions and comorbid illness.

DF with warning signs is kept in the moderate dengue
infection as these patients have high chances of developing
severe dengue. Patients with comorbid illness having dengue
infection are likely to behave differently than simple mild
dengue infection and they are more likely to develop severe
dengue. Therefore, comorbid patient with dengue infection
are considered to be moderate dengue even though there is
no evidence of capillary leakage or bleeding.
For management of mild, moderate, severe dengue cases,
different approaches are needed, which were included in this
guideline. Management of high-risk groups with comorbid
conditions, coinfections, pregnancy, infants, etc. were also
included. Fluid replacement therapy is very crucial in
management of dengue cases.
Conclusion
In this guideline, an attempt has been made by the national
and international experts to harmonize the complexity and
variability that exist among the available WHO guidelines,
especially to address the case classification.
Dengue infection is classified into three categories of
severity: mild, moderate and severe infection. All categories
of severity have been clearly defined. The classification
of severity are mostly based on clinical and biochemical
criteria and simplified to make it more user-friendly for the
clinicians. Mild dengue infection is defined as those who have
undifferentiated DF, fever without bleeding, hypotension,
organ involvement or evidence of capillary leakage.
Moderate dengue infection is classified as those who have
warning signs and symptoms, high-risk group and comorbid
condition because these patients have more chances of
progressing to severe dengue infection. Patients with severe
bleeding, profound shock, severe organ involvement or
severe metabolic abnormalities are classified as severe dengue
infection. Currently this guideline is being used under Indian
National Program for clinical management of dengue cases.
Acknowledgment
The Authors are grateful to Prof Jagdish Prasad, Director General of
Health Services, Government of India for the Technical Guidance
and encouragement for preparing the Guideline. Authors are also
grateful to Prof AP Dash, former Regional Advisor, WHO, SEARO
for his thought-provoking initiation for harmonizing the existing
WHO Guidelines to make a user-friendly case classification.
Valuable technical suggestions on the guidelines given by Prof
Siripen Kalayanarooj, Former Director, Queen Sirikit, NICH,
Bangkok, Thailand is gratefully acknowledged. Suggestions given
by Dr Ahmed Jamsheed Mohamed, Medical Officer-VBN WHO,
SEARO are also gratefully acknowledged. Authors are grateful
to all contributors for their valuable inputs while developing the
guidelines.
Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
Vector-borne diseases special
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