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

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

Methods zz Dengue infection with warning signs and symptoms,


DHF-I and II
A revision of the existing Indian National Guideline
zz Dengue infection with high-risk and comorbid
was needed as several advancements have taken place in
understanding the pathogenesis and classification of dengue conditions.
infection.10,11 National and international experts were Moderate dengue with warning signs and symptoms
involved in preparing the guideline. Several issues evolved
during the process mostly related to understanding the The presence of warning signs and symptoms are considered
pathogenesis and case classifications. The clinicians and to be the indicators of severity.9 With the following warning
experts raised the questions regarding the variability of signs and symptoms, dengue infected patients may progress
WHO case classifications. The expert members reviewed into severe stage, which may require close monitoring.
the available published literature and WHO guidelines for DF with warning signs and symptoms
preparing the guideline.12-23 In clinical practice, it is realized
Recurrent vomiting
that DHF cases are misclassified as DF due to complex
mechanisms for confirming the DHF where plasma leakage Abdominal pain/tenderness
is the main underlying cause, but it is difficult to apply this General weakness/lethargy/restlessness
criteria as most of the healthcare settings lack diagnostic
Minor bleeding
facilities necessary for distinguishing DHF/DSS from
DF.18,19,21 Other issues like severe and nonsevere cases, Pleural effusion/ascites
warning sign and organ involvement were critically analyzed Hepatomegaly
for preparing the guideline and to make it user-friendly for
the physicians for proper diagnosis, identifying severity and Increased hematocrit (Hct).
effective timely interventions for better clinical management. DHF Grade I and Grade II with or without minor
Several brain-storming sessions and meetings of experts were bleeding: These patients are DHF without hypotension or
held for bringing the final shape of this guideline. shock. Sometimes, these patients with minor bleeding may
progress to severe plasma leakage and could lead to organ
New Dengue Clinical Management Guideline
involvement, massive bleeding and shock.
The new revised classification aims to distinguish
Moderate dengue with high-risk and comorbid conditions
confidently between mild, moderate and severe dengue
infection for better use in clinical practice.24 All symptoms, Dengue infected patients are likely to progress to severe
signs and presentations are manifested by capillary manifestations in presence of high-risk and comorbid
leakage (vasculopathy), impairment of coagulation profile conditions. The following high-risk and comorbid conditions
(coagulopathy), bleeding or organ involvement. are found to be associated with high chances of progressing
In this guideline, clinically the severity of dengue infection to severe dengue infection:
is divided into three categories, i.e., mild, moderate and Infants
severe as shown in Figure 1. Because often, it becomes
Old age
difficult for the clinician to know whether patient should
be advised home management, close monitoring, possible Diabetes
hospitalization or refer to tertiary level care hospital for Hypertension
better management.
Pregnancy
Mild Dengue Infection Coronary artery disease (CAD)
Mild dengue infections are characterized by undifferentiated
Hemoglobinopathies
DF, fever without complications like bleeding, hypotension,
organ involvement or any evidence of capillary leakage.8 Immunocompromised patient
These patients usually do not have warning signs and
symptoms; hence, can be managed at home with proper Patient on steroids, anticoagulants or immunosuppressants.
counseling. The moderate dengue patients should be closely monitored
or possibly hospitalized for further management as these
Moderate Dengue Infection groups of patients can develop severe dengue manifestation
Moderate dengue infections were characterized into two due to abnormalities in metabolic conditions, severe plasma
groups: leakage and increases the mortality.

Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015 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 symptoms significant hemorrhage
complication like yy Diabetes yy Recurrent vomiting B. DHF with shock (DHF III &
yy Hypertension
bleeding, hypotension yy Abdominal pain/tenderness IV- DSS)
yy Pregnancy
and organ yy CAD yy General weakness/ C. Severe organ involvement
involvement yy Hemoglobinopathies letharginess/restless (Expanded dengue
C. Without evidence of yy Immunocompromised yy Mild pleural effusion/ascites syndrome)
capillary leakage patient yy Hepatomegaly D. Severe metabolic disorder
yy Patient on steroids, yy Increased Hct >20%
anticoagulants or B. DHF I & II with minor bleeds
immunosuppressants

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
Vector-borne diseases special

dengue lies predominantly in infants 4-9 months of age. Clinical management


Upper respiratory tract symptoms (cough, nasal congestion,
running nose, dyspnea), gastrointestinal symptoms Approach to clinical management of DF may vary from mild,
(vomiting, diarrhea) and febrile convulsions are more moderate and aggressive depending on severity of illness.
common in infants with dengue compared to older children. Patients who have simple fever without any danger signs
or complications may be managed with simple approach.
Differentiation between dengue and other common Those who have danger signs should be managed with
infections in infants such as pneumonia, bacterial sepsis, close monitoring for progression of DHF/DSS or severe
meningoencephalitis, measles, rotavirus infection, etc. is bleeding. The patients presenting with Grade III and IV of
often not possible in febrile stage. Hepatomegaly is usually DHF, significant bleeding or involvement of various organs
noted. Splenomegaly is seen in almost 10% of dengue will require aggressive management to reduce morbidity
infants.11 The normal value of hematocrit in infants and mortality. Patient may develop more complications
2-12 months of age is relatively low and may be even lower during later stage of fever (defervescence) or afebrile phase,
in iron deficiency anemia. Severe dengue is uncommon in where clinician should be careful to look for danger signs or
infants but when it occurs, the risk of mortality increases.12 severity of disease.

Neonatal Dengue Management of dengue fever


When a pregnant woman gets dengue infection, the Management of DF is symptomatic and supportive.
diagnosis of dengue should be considered in her neonate Antipyretics may be used to lower the body temperature.
even if it appears well in first days of life. Initial presentation Aspirin/NSAIDs (nonsteroidal anti-inflammatory drugs)
may be confused with bacterial sepsis, birth trauma and like ibuprofen, etc. should be avoided since it may cause
other neonatal illnesses. gastritis, vomiting, acidosis, platelet dysfunction and severe
bleeding complication. Oral fluid and electrolyte therapy
Laboratory Diagnosis is recommended for patients with excessive sweating,
vomiting or hypotension. Patients should be monitored
In endemic areas, early symptoms of DF mimic many
for 24-48 hours in DHF endemic areas until they become
other prevalent diseases such as chikungunya, malaria, viral
afebrile without the use of antipyretics and after hematocrit
infection, urinary tract infection, typhoid, leptospirosis,
determinations are stable, platelet count is >50,000/mm3
etc. Hence, exclusion of other conditions based on clinical
or improving.
manifestation and laboratory investigations is very crucial
for proper management. Management of DHF (Febrile Phase)
National Vector Borne Disease Control Program Management of febrile phase is similar to that of DF.
(NVBDCP), Govt. of India recommends use of enzyme- Paracetamol is recommended to keep the temperature below
linked immunosorbent assay (ELISA)-based antigen 39oC. Copious amounts of fluids should be given orally, to
detection test (NS1) for diagnosing the cases from 1st day the extent the patient tolerates, oral rehydration solution
onwards and antibody detection test immunoglobulin M (ORS), such as those used for the treatment of diarrheal
(IgM) capture ELISA (MAC-ELISA) for diagnosing the diseases and/or fruit juices are preferable to plain water.
cases after 5th day of onset of disease to confirm dengue IV fluids should be administered if the patient is vomiting
infection.14 persistently or refusing to feed.
A number of rapid diagnostic test (RDT) kits for Patients should be closely monitored for the initial signs
NS1 antigen and anti-dengue IgM/IgG antibodies are of shock. The critical period is during the transition from
commercially available at present, which produces the the febrile to the afebrile stage and usually occurs after the
results within 15-25 minutes. However, the accuracy third day of illness. Serial hematocrit determinations are
of most of these tests is not known since they have not essential guide for treatment, since they reflect the degree
yet been properly validated. Some of the RDTs have of plasma leakage and need for IV administration of fluids.
been independently evaluated. The results showed a high Hematocrit should be determined daily from the third day
rate of false positive results compared to standard tests, until the temperature has remained normal for 1-2 days.
while others have agreed closely with standard tests. The
sensitivity and specificity of some RDTs are also found to Management of DHF Grade I and II
vary from lot to lot. Hence, currently, use of RDT is not Any person who has DF with thrombocytopenia and
recommended under the program. hemoconcentration and presents with abdominal pain, black

Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015 199
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 However, in case of persistent shock when, after initial
be hospitalized. All these patients should be observed for fluid replacement and resuscitation with plasma or plasma
signs of shock. The critical period for development of shock expanders, the hematocrit continues to decline, internal
is during transition from febrile to afebrile phase of illness, bleeding should be suspected. It may be difficult to
which usually occurs after third day of illness. recognize and estimate the degree of internal blood loss in
the presence of hemoconcentration. Hence, whole blood in
A rise of hemoconcentration indicates need for IV fluid small volumes of 10 mL/kg/hour for all patients in shock
therapy. If patient develops fall in blood pressure (BP), as a routine precaution is recommended. Oxygen should
decrease in urine output or other features of shock despite be given to all patients in shock. Treatment algorithms
treatment, management for Grade III/IV DHF/DSS should for patients with DHF Grades III and IV are given in
be instituted. Oral rehydration should be given along with Figures 3 and 4.
antipyretics like paracetamol, sponging, etc. as described
Calculation of Fluid
above. The algorithm for fluid replacement therapy in case
of DHF Grade I and II is given in Figure 2. The required amount of fluid should be calculated on the
basis of body weight and charted on 1-3 hourly basis or
Management of Shock (DHF Grade III/IV) even more frequently in the case of shock. For obese and
overweight patients, fluid should be calculated on the basis
Immediately after hospitalization, the platelet count and vital
of ideal body weight. The regimen of the flow of fluid and
signs should be examined to assess the patients condition
the time of infusion are dependent on the severity of DF.
and IV fluid therapy should be started. The patient requires
It is calculated for dehydration of about 5% deficit (plus
regular and continuous monitoring. If the patient has already
received about 1,000 mL of IV fluids, it should be changed maintenance). The maintenance fluid should be calculated
to colloidal solution preferably Dextran 40/haemaccel; using the Holiday-Segar formula.
if the hematocrit is falling, fresh whole blood transfusion For a child weighing 40 kg, the maintenance is: 1,500 + (20
10-20 mL/kg/dose should be given. 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, Dengue Myocarditis


which is equivalent to 50 mL/kg. This should be given in
Dengue infection may rarely cause acute myocarditis,15
24 hours to maintain just adequate intravascular volume
which may also contribute to the development of DSS.
and circulation. Therefore, for a child weighing 40 kg the
Cardiac complications may be seen in presence of
fluid required will be 1,900 + (40 50) = 3,900 mL in
CAD, hypertension, diabetes and valvular heart disease.
24 hours. For IV fluid therapy of patients with DHF, four
Management of shock with IV fluids in this case sometimes is
regimens of flow of fluid are suggested: 3 mL/kg/hour;
difficult due to myocardial dysfunction. Patient may develop
6 mL/kg/hour; 10 mL/kg/hour and 20 mL/kg/hour.
pulmonary edema due to improper fluid management.
Management of Severe Bleeding Some CAD patient may be already taking aspirin and other
In case of severe bleeding, patient should be admitted in antiplatelet agents, which may also contribute to severe
the hospital and investigated to look for the cause and site bleeding unless these are stopped during dengue infection.
of bleeding and immediate attempt should be made to stop Cardiac ischemia or electrolyte disturbances may be
the bleeding. Internal bleeding like gastrointestinal (GI) reassessed. Patient may develop congestive or biventricular
bleeding may be sometime severe and difficult to locate. failure and should therefore be treated properly for better
Patients may also have severe epistaxis and hemoptysis and morbidity and mortality outcome.
may present with profound shock. Urgent blood transfusion
is life-saving in this condition. However, if blood is not DF in Diabetes
available shock may be managed with proper IV fluid or Sometimes diabetes patients may present with severe
plasma expander (i.e. haemaccel). complications in DF when target organs are involved like
If the patient has thrombocytopenia with active bleeding, diabetic retinopathy, neuropathy, nephropathy, vasculopathy,
it may be corrected with platelet transfusion. In case of cardiomyopathy and hypertension. Due to dengue infection,
massive hemorrhage, blood should be tested to rule out the blood sugar may become uncontrolled, which may
coagulopathy by testing for prothrombin time (PT) and sometimes require insulin therapy for better management.
activated partial thromboplastin time (aPTT). Patients of
severe bleeding may have liver dysfunction and in this case, Renal Involvement in DF
liver function tests (LFTs) should also be performed. Rarely, Acute tubular necrosis (ATN) may develop during DSS
intracranial bleed may also occur in some patients, who have
and may cause acute kidney injury (AKI) if fluid therapy
severe thrombocytopenia and abnormal coagulation profile.
is not initiated in time. Renal function may be reversible,
Management of Dengue Fever with comorbid illness if shock is corrected within short span of time. But, if
the shock persists for long time patient may develop renal
Different comorbid illness like hypertension, diabetes, complications. Urine output monitoring in dengue infection
thyroid, liver, heart and renal diseases may contribute in the is very important to assess renal involvement. Microscopic
development of severe manifestations in DF. and macroscopic hematuria should be examined in DHF
patients. Other investigations like blood urea, creatinine,
Dengue Hepatitis
electrolytes, glomerular filtration rate (GFR), arterial blood
Some patient may have impairment of LFT due to gas (ABG) should be done in patients with severe dengue/
dengue infection. In some DF patients, the aspartate DHF. Fluid intake should be closely monitored in case of
aminotransferase/alanine aminotransferase (AST/ALT) AKI to avoid fluid overload and pulmonary edema. Dengue
level may be very high and PT may be prolonged. patient may develop severe DHF in presence of diabetic
Hepatic involvement is commonly associated with pre- nephropathy, hypertensive nephropathy, connective tissue
existing conditions like viral hepatitis, cirrhosis of liver and
disorders like systemic lupus erythematosus (SLE) and other
hepatomegaly due to some other cause. Patient may also
pre-existing chronic diseases.
develop hepatic encephalopathy due to severe liver failure.
Liver involvement also sometimes associates with DF in CNS Involvement in DF
pregnancy. Low albumin due to chronic liver disease may
be associated with severe DHF and bleeding. GI bleeding is Altered sensorium may develop in dengue patients due to
common in this condition and patient may go into severe various conditions like shock, (DSS), electrolyte imbalance
DSS. These patients should be managed carefully with (due to persistent vomiting), fluid overload (delusional
hepatic failure regimen with appropriate fluid and blood hyponatremia or other electrolyte), hypoglycemia and also
transfusion. If PT is prolonged, IV vitamin K1 may be due to involvement of central nervous system (CNS) by
initiated in such conditions. dengue virus. Acute encephalopathy or encephalitis may be

202 Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015
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seen in some patients with severe dengue. Sometimes, it may Management of Dengue in pregnancy
be difficult to exclude clinically cerebral malaria and enteric
encephalopathy, which are also seen during the same period DF infection in pregnancy carries the risk of more bleeding,
(epidemic). Dengue serology (IgM) in cerebrospinal fluid fetal complications, low-birth-weight and premature birth.
may help to confirm dengue encephalopathy or encephalitis. Risk of vertical transmission also increases during pregnancy.
Pleural effusion, ascites, hypotension are commonly
Management of DF with coinfections associated with DF in pregnancy. Involvement of lungs
and liver are also common in pregnancy. Patients may have
It is sometimes difficult to manage DF with coinfections respiratory symptoms due to massive pleural effusion and
like malaria, chikungunya, tuberculosis (TB), human high serum glutamic-oxaloacetic transaminase (SGOT)
immunodeficiency virus (HIV), enteric fever and and serum glutamic-pyruvic transaminase (SGPT) due to
Leptospirosis because clinical presentations are mostly severe liver involvement. Complications of DF depend on the
in the presence of these coinfections. different stages of pregnancy like early, late, peripartum and
Malaria: Malaria is a common coinfection in dengue as postpartum period.
it is prevalent across our country and transmission also Pregnancy is a state of hyperdynamic circulation and fluid
coincides during the same period/season. Malaria should replacement should be carefully done to prevent pulmonary
be excluded in the beginning without loss of much time edema. Frequent platelet count and coagulation profile
as it has its specific management. Antimalarial treatment testing should be done during DF in pregnancy along with
should be started as soon as possible to prevent regular monitoring of BP. Fulminant hepatic failure, ARDS
complication and better outcome during coinfection. and acute renal failure in pregnancy may be associated
Chikungunya: In some geographical areas, both with dengue infection. Management of dengue infection
infections are prevalent at the same time. Acute in pregnancy should be taken seriously to reduce morbidity
complications are sometimes severe in DF in presence of and mortality in mother as well as fetus.
chikungunya. In case of predominant joint involvement
in a DF patient, chikungunya should be investigated and Management of neonatal Dengue
proper management should be carried out accordingly. After delivery, the newborn may go into shock, which may
TB: Patients may develop breathlessness and massive be confused with septic shock or birth trauma. In this case,
hemoptysis in pulmonary TB. These patients may also history of febrile illness during pregnancy is important,
develop moderate-to-massive pleural effusion and acute which may help to diagnose DSS among neonates and
respiratory distress syndrome (ARDS). If patient has DF infants. Close observation, symptomatic and supportive
in presence of TB and is on anti-TB treatment (ATT), treatment are the mainstay of management.
then he/she should be closely monitored for further
development of respiratory/pulmonary complications to Management of Dengue in infants
prevent morbidity and mortality.
HIV: Dengue patients may have severe complications like Dengue Without Warning Signs
DHF, DSS, significant bleeding and organ involvement Oral rehydration with oral rehydration solution (ORS),
among HIV/AIDS patients. Outcome of DF is poor fruit juice and other fluids containing electrolytes and
amongst severely immune compromised patients who sugar should be encouraged together with breastfeeding or
have opportunistic infections and very low CD4 counts. formula feeding. Parents or caregivers should be instructed
Multiorgan involvement may be common in DF and about fever control with antipyretics and tepid sponging.
is responsible for high-mortality. Management of DF They should be advised to bring the infant back to the
with HIV and AIDS should be undertaken with HIV nearest hospital immediately if the infant has any of the
specialist consultation. warning signs.
Enteric fever: Water-borne diseases like typhoid
fever and gastroenteritis are also common during the Dengue with Warning Signs
monsoons when dengue infection is also reported in When the infant has dengue with warning signs, IV
large numbers. In the initial phase, DF patient may be fluid therapy is indicated. In the early stage, judicious
more complicated with typhoid if antibiotic treatment volume replacement by IV fluid therapy may modify
is started late. In high suspected cases, blood culture the course and severity of the illness. Initially, isotonic
for typhoid fever should be sent to confirm diagnosis as crystalloid solutions such as Ringers lactate (RL),
Widal test may not be positive before 2 weeks of fever. Ringers acetate (RA) or 0.9% saline solution should

Journal of the Indian Medical Association, Vol. 113, No. 12, December 2015 203
Vector-borne diseases special

be used. The capillary leak resolves spontaneously after with bleeding should be as per the advice of physician and
24-48 hours in most of the patients. patients condition.

Severe Dengue: Treatment of shock Discussion


Volume replacement in infants with dengue shock is very This new case-classification for dengue diagnosis would
challenging and it should be done promptly during the definitely clear the confusion created by availability of
period of effervescence. Each and every case should be different WHO case classification among the clinicians
critically analyzed separately and following points in general and would help in better understanding to classify severity
should be kept in mind during management. of dengue correctly for effective clinical management.17,21
Clinical as well as biochemical criteria have been considered
Management of Dengue Infection in outbreak to understand the severity and grading.18 It has been
situation observed that the available case classifications fail to correctly
During outbreak situation, dengue patient turnover may identify and classify the severity of dengue.20 It is very
increase exceptionally. All hospitals in endemic areas should important for the clinician to classify clinically severe and
have a plan dealing with emergency hospitalization to make nonsevere dengue infection before initiating and planning
the most effective use of hospital and treatment facilities in clinical management.4 The basic management of dengue
case of outbreak occurs. infection is targeted symptomatically. In the early stage, if
signs and symptoms are identified to grade the severity, it
Criteria for admission of a patient could help the clinicians for appropriate intervention and
better outcome for reducing the morbidity and mortality.
If a DF patient presents with significant bleeding from any
site, signs of hypotension, persistent high-grade fever, rapid The WHO classification used since the 70s classifies dengue
fall of platelet count, sudden drop in temperature, he/she into DF, DHF and DSS.24,25 In 2009, a new classification
should be admitted in hospital. However, those patients who of dengue proposed by WHO Tropical Disease Research
have evidence of organ involvement should also be admitted (TDR) was published in which dengue was classified as
for proper monitoring and management. Dengue patients dengue (D), dengue with warning signs (DW) and severe
with warning signs and symptoms should be admitted and dengue (SD).21
closely monitored. DHF gradation alone was not sufficient to classify mild,
moderate and severe dengue.12 As per this gradation, severe
Criteria for discharge of patients cases like organ involvement, metabolic abnormalities such
Hospitalized patients who have recovered from acute dengue as dyselectrolytemia, acidosis or alkalosis were not taken
into account. Some warning signs and symptoms of dengue
infection and have no fever for at least 24 hours, normal
infection have been correlated with the progression of the
BP, adequate urine output, no respiratory distress, persistent
disease to severe manifestations. Warning signs were taken
platelet count >50,000/mm3 should be discharged from
as criteria for hospital admission, which overburdened the
hospital.
hospitals and also the clinicians.17 Many of these patients
Indications of platelet transfusion require observations and close monitoring to look for
progression of the disease. However, there was no hardcore
In general, there is no need to give prophylactic platelets evidence that these patients with warning signs would
even at <20,000/mm3. Prophylactic platelet transfusion develop severe dengue.
may be given at level of <10,000/mm3 in absence of
In this guideline, the severity has been grouped into three
bleeding manifestations. Platelet transfusion may also be
grades such as mild, moderate and severe dengue. Severe
given in prolonged shock with coagulopathy and abnormal
dengue has been classified and defined in WHO guideline,
coagulogram. In case of systemic massive bleeding,
whereas nonsevere dengue has been classified into dengue
platelet transfusion may be needed in addition to red cell
with warning signs and without warning signs.8 However,
transfusion. in this revised guideline, nonsevere dengue is classified into
Standard dose for adults is 5-6 units of random donor mild and moderate grade (Fig. 1). Mild dengue is defined
platelets or 1 unit of apheresis platelets or 1 unit of BCPP as fever in absence of bleeding, capillary leakage and organ
equivalent to 3 1011 platelets. For neonates/infants, the involvement while moderate dengue is classified into two
dose of platelets should be 10-15 mL/kg of body weight. grades, one with warning signs and other with high-risk
Use of fresh frozen plasma/cryoprecipitate in coagulopathy conditions and comorbid illness.

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

DF with warning signs is kept in the moderate dengue References


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