You are on page 1of 106



 PRESENTER : Dr.Mohan.T.Shenoy

 NELSON Textbook of Pediatrics 18th edition
 MEHERBAN SINGH Pediatric Emergencies 4th edition
 IAP Textbook of Pediatrics 4th edition
 Textbook of Pediatric & Neonatal emergencies by SACHDEV
 Textbook of pediatric infectious diseases By Ralph D. Feigin
 Davidson's principles & practice of medicine
 PARK’s Textbook of Preventive and Social medicine 20th edition
 Jornal de Pediatria - Vol. 83, No.2(Suppl), 2007 -Dengue and
dengue hemorrhagic fever – Singhi S et al.
 Emerged among children in Southeast Asia during the 1950s.

 Has since become a major public health problem worldwide

 Significant cause of pediatric morbidity and mortality.

 The affected children need very careful monitoring.

 The fluid therapy is challenging and needs modification frequently.

 Its severe forms (hemorrhagic fever and shock syndrome) may lead
to multisystem involvement and death.

 Early diagnosis, close monitoring for deterioration & response to

treatment are necessary in all cases.
Risk factors for developing DHF / DSS

• Children are more prone to develop DHF / DSS than adults.

• DHF / DSS is associated more with well nourished than

with under nourished children.

• Primary infection in infants born to dengue immune


• Presence of underlying chronic illnesses (eg: heart disease,

anaemia, chronic liver disease)
Warning Signs for Dengue
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
Four Criteria for DHF • Abrupt change from fever
• Fever to hypothermia
• Hemorrhagic manifestations • Change in level of
• Excessive capillary consciousness (irritability
permeability or somnolence)
•  100,000/mm3 platelets

Initial Warning
Signals When Patients Develop
• Disappearance of fever DSS:
• Drop in platelets • 3 to 6 days after onset of
• Increase in hematocrit symptoms
Special attention :High-risk dengue patients
 Infants under 1 year of age

 Overweight/obese patients

 Massive bleeding

 Change of consciousness, esp. restlessness,irritability or


 Presence of underlying diseases e.g. thalassemia, G-6-PD

deficiency, heart disease
Admission in Dengue Fever
 Abdominal pain – may be intense and sustained
 Bleeding tendencies with Positive tourniquet test
 Cold extremities
 Decreased urine output
 Platelet count < 1 Lakh and PCV rise by >20%
 Persistent vomiting
 Altered mental status -Restlessness or somnolence
 No specific therapy – only symptomatic

 Rest and Plenty of oral fluids

 Use Paracetamol
 Avoid Aspirin and NSAIDs

 Follow up preferably everyday - from the 3rd day

until afebrile for 24-48 hours
General measures
 Frequent monitoring of vitals.

 Essential nursing care.

 Stop bleeding with proper techniques

 e.g. anterior nasal packing for massive epistaxis.

 Avoid blind invasive procedures

 e.g. no nasogastric tube insertion, no gastric lavage.
Nutritional support
 Soft, balanced, nutritious diet, juice and electrolyte
solution – plain water is not adequate.

 Avoid black- or red-colored food or drinks (may be

mistaken for bleeding
General measures (continued)
 Sedation is needed in some cases to restrain agitated child.

 Chloral hydrate(12.5-50 mg/kg), orally or rectally recommended.

 Avoid Long-acting sedatives.

 should be preferred if there is Acute respiratory failure
associated with DSS.

 Oxygen via face mask/nasal cannula

 in case of shock/impending shock.

Other supportive,symptomatic treatment
 H2-blockers (ranitidine)
 Recommended in case of gastrointestinal bleeding

 Domperidone
 1 mg/kg/day in three divided doses in case of severe
vomiting for 1-2 days.
 One single dose may be adequate

 Antibiotic
 Not necessary; it may lead to complications
 In young infants without shock-
 N/2 saline in 5% dextrose

 In patients who already have volume overload, i.e.,

massive pleural effusion
 colloid solutions

 Hydroxyethyl starch at 6% may be preferred in children

with severe shock; the use of dextran is associated with
various adverse reactions
 WHO guidelines are useful in that they offer an
algorithmic approach to fluid resuscitation in DHF and

 However, the usefulness of these guidelines is limited

beyond the immediate resuscitation

 do not address treatment of complicated forms of the disease,

incl. fluid overload and multiple organ failure, which could cause
disability or death.
In case of no response to IV fluids:
 May have myocardial dysfunction and decreased LV
performance, which may be easily detected by

 Consider and correct

 Massive plasma leakage

 Concealed internal bleeding – decrease in Hct
 Hypoglycemia – Blood sugar < 60 mg%
 Hyponatremia, hypocalcemia – electrolytes
 Acidosis – indicates metabolic acidosis in blood gas analysis
Blood and platelet transfusion
Platelet transfusion
 Thrombocytopenia with significant bleeding.
 Platelet count < 10,000/mm3

10-20 mL/kg
 Platelets or blood should NOT be transfused based upon
platelet count alone.

 Low platelet count may not be predictive of bleeding.

 Only 0.4% of DHF pts need platelet transfusion.

 Mild reductions in platelet counts are usually not associated

with significant bleeding.

 In children with severe thrombocytopenia in absence of

significant bleeding, platelet infusion does not alter the

Platelets return to normal within 7-9 days.

Fresh Whole blood / Packed red cell transfusion

 Significant blood loss > 10% (6-8 mL/kg)

 Concealed internal bleeding
 Hemolysis


 Fresh whole blood 10 mL/kg/dose

 Packed red cells 5 mL/kg/dose
Role of Steroids

Ineffective in preventing shock in DHF

 It may cause harm

 Treatment with methyl-prednisolone did NOT show any benefit in a

double blind placebo-controlled trial in DSS
Complications of DF/DSS

 Myocardial dysfunction incl. Cardiomyopathy
 Hepatitis
 Reye-like syndrome
 Encephalitis
 Glomerulonephritis
Treatment of complications
Fluid overload

 Early IV fluid therapy- in the febrile phase

 Excessive use of hypotonic solutions
 Non-reduction in the rate of IV fluid after initial resuscitation
 Blood loss replaced with fluids in cases with occult bleeding

 Treatment

 Judicious fluid removal

 colloids with controlled diuresis (furosemide 1 mg/kg infusion over 4
hours) or dialysis
Electrolyte imbalance

 Hyponatremia
 Hypocalcemia – 10% Ca gluconate 1 mL/kg/dose, slow IV push
every 6 hour

Large pleural effusions, ascites

 Careful titration of intravenous fluids.

 Avoid insertion of intercostal drains and tracheal intubation.

 Large pleural effusions during recovery phase after 48 hours

furosemide (0.25-0.5 mg/kg at 6 hours’ interval for 1 to 2 doses).
Disseminated intravascular coagulation

 Frequent Clinical assessment

 Regular Coagulation profile

 PT, aPTT, fibrinogen, platelet and FDP mandatory, as indicated.

Seriously sick patients with bleeding & DIC have benefited from :

 Heparin therapy + Cryoprecipitate (1 unit per 5 kg body weight)

 Followed by Platelets (4 units/m2 or 10-20 mL/kg) within 1 hr and

Fresh frozen plasma (FFP 10-20 mL/kg).
 ARDS & Hypotension with Respiratory failure

 Nasal CPAP

 Refractory shock

 Vasopressin
 Desmopressin 0.3 mcg/kg over 30 min 3-4 days
 DF is a very incapacitating disease; however, its prognosis is favorable.

 Significant morbidity and mortality can result if early recognition and

monitoring of severe forms are not done.

 If left untreated, the mortality of DHF or DSS patients may be as high as


 Early recognition of illness, careful monitoring and adequate and

appropriate fluid therapy have decreased mortality to 1%.

 If shock is identified when pulse pressure starts to drop and intravenous

fluids are administered, the outcome will be excellent.
 Recovery is fast and most patients recover in 24-48 hours without
any sequelae.

 The outcome may not be so good if the patient develops cold


 Most deaths from DHF/DSS are caused by

 prolonged shock
 massive bleeding
 fluid overload and
 acute liver failure with encephalopathy.

 Severe refractory shock, DIC, ARDS, liver failure and neurological

manifestations singly or in combination were the commonest causes
of death in a recent series.
Criteria for Discharge of patients
 Visible clinical improvement with return of appetite
 Stable pulse, blood pressure and respiratory rate
 Afebrile for 24 hours (without anti-fever therapy)
 Minimum of 3 days after recovery from shock
 Good urinary output and stable haematocrit levels
 Platelet count > 100,000/mm3
 No respiratory distress /pleural effusion /ascites
 No evidence of external or internal bleeding
 Convalescent confluent petechial rash

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for
Prevention and Control. PAHO: Washington, D.C., 1994: 69.
Convalescent confluent petechial rash

BETWEEN 8 –10th day of SICKNESS

Signs of recovery
 Stable pulse/BP/Respiratory rate
 Temperature
 Good urine output
 Stable hematocrit
 No evidence of bleed
 Return of appetite
 Absence of vomiting
Common Misconceptions about
Dengue Hemorrhagic Fever
 Positive tourniquet test = DHF
 Tourniquet test is a nonspecific indicator of capillary
 Dengue + bleeding = DHF
 Need 4 WHO criteria, capillary permeability
 DHF kills only by hemorrhage
 Patient dies as a result of shock

 Poor management turns dengue into DHF

 Poorly managed dengue can be more severe, but DHF is a distinct
condition, which even well-treated patients may develop
Aedes aegypti Breeding Sites

 The control is primarily dependent on eradicating mosquito.

 Public spraying for mosquitoes is the most important aspect of this


 Avoiding endemic areas

 Cover exposed skin
 Mosquito nets, repellents
 Use of DEET-impregnated bed nets
Cascade of DHF/DSS
 Macrophage – monocyte infection
 Previous infection with heterologous
Dengue serotype results in production
of non protective antiviral antibodies
 These Ab bind to the virion’s surface
Fc receptor and focus the Dengue virus
on to the target cells – macro/monocytes
 T cell - cytokines, interferon, TNF alpha
 At present, no specific drug or vaccine is available against the
dengue virus.

 The tetravalent live attenuated DEN vaccine trial has been done in

 Produces 80-90% seroconversion rates to all 4 serotypes after

administration of 2 doses in young children


 Vaccine has moderate, but improvable reactogenicity

 High seroconversion rates against four serotypes of DEN virus

• Endemic in 112 countries
• 40% of the world’s population
•About 2.5 billion people in tropical and subtropical areas at risk.
•Every year about 50-100 million cases of dengue infection
• Hospitalized cases: 5,00,000/year (90% are children)
• At least 12,000 deaths occur worldwide
• Disease burden: 465,000 DALY




The Dengue Virus
 Single stranded RNA virus
 Positive sense
 40 to 50 nanometers
 Flavivirus
 Four sero-sub types
 Type 1 to 4

 Arthropod borne (zoonotic)

 Man is accidentally infected
 Other vertebrates are reservoirs
Aedes aegypti Mosquito

Day-biting urban thriving mosquito

White bands or scale patterns on its legs and thorax.
Highly domesticated tropical mosquito, lives around human habitation
 Single infective mosquito may cause an outbreak
Transmission Cycle
Vector Incubation
Humidity: Period:
Rainfall & Temp. 8-10 days

Intrinsic Incubation Period:

3-14 days

Susceptible hosts,
Viraemia & Fever: 5-7 days Source patients
 During dengue epidemics, attack rates among susceptible
individuals are often 40-50%, but may reach 80-90%.

 An estimated 500,000 cases of DHF require hospitalization

each year, of which a very large proportion are children.

 At least 2.5% of cases die, although case fatality could be

twice as high.

 Without proper treatment, DHF case fatality rates can

exceed 20%.

 With modern intensive supportive therapy, such rates can be

reduced to less than 1%.



Asymptomatic Clinical Cases 3%


(non-DHF) 99.2%

survive Death
Rates in dengue model by Shepard et al. Vaccine. 2004, 22:1275-1280.
Clinical Features
 Fever – biphasic/saddle-back type
 Headache with retro-orbital pain
 Muscle and joint pain
 Nausea/vomiting
 Rash
 Hemorrhagic manifestations
 Abdominal pain
 Polyserositis
Undifferentiated Fever

• Many silent dengue infections precede and

accompany DHF epidemics.

• During outbreaks,150-200 silent dengue

infections for each dengue shock syndrome

• Uncommon in pediatric age group

DS Burke, et al. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988;

Suffused + Swollen face with purplish lips, injected eyes

Reddened malar regions and ear lobules
Dengue fever with unusual hemorrhage

 Do not satisfy criteria for DHF/DSS

 Seen in significant numbers in epidemics

 Varying degree of mucosal and cutaneous bleeds with

some degree of thrombocytopenia

 Lesser fluid requirement c.t Dengue Hemorrhagic fever

Hemorrhagic Manifestations

 Skin hemorrhages: Petechiae, purpura, ecchymoses

 Gingival bleeding
 Epistaxis
 Gastro-intestinal bleeding: hematemesis, melena
 Hematuria
 Increased bleeding per vaginum
 Intracranial bleed
Four Grades of DHF
 Grade 1
 Fever and nonspecific constitutional symptoms
 Positive tourniquet test is only hemorrhagic
 Grade 2
 Grade 1 manifestations + spontaneous bleeding
 Grade 3
 Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin)
 Grade 4
 Profound shock (undetectable pulse and BP)
Tourniquet Test
 Inflate blood pressure cuff to a point midway between
systolic and diastolic pressure for 5 min

 Positive test: 20 or more petechiae / inch2 (6.25 cm2)

 In an epidemic situation, the test is positive in

 50% on the 1st day, and in
 80% by the end of the febrile phase.

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for
Prevention and Control. PAHO: Washington, D.C., 1994: 12.
Positive Tourniquet Test
Endemic areas -WHO criteria

2 clinical observations
1 laboratory finding


At least a rising hematocrit level

Thrombocytopenia (< 100,000 cells/mm3)
 A rise in hematocrit levels > 20% of the baseline values can be
documented if hematocrit level is monitored regularly from early
stages of illness.

 A drop in hemoglobin or hematocrit > 20% following volume

replacement therapy can be taken as an indication of previous
Clinical Case Definition for DSS
 4 criteria for DHF

 Evidence of circulatory failure

manifested indirectly by :

 Rapid and weak pulse

 Narrow pulse pressure ( 20 mm Hg) OR hypotension for age
 Cold, clammy skin and altered mental status

 Frank shock is direct evidence of circulatory failure

Hypothesis on DHF - DSS
 Neutralizing Ab
 type specific
 neutralize the homologous sub type

 Enhancing Ab
 Serotype independent
 Concentration dependent

 Subsequent infection with heterologous subtype

 causes immune complexes - target the mononuclear lineage for enhanced
viral replication
 Infected monocytes release vasoactive mediators causing vascular damage
Initial Immunogenecity
Immune Complexes
Risk Factors Reported for DHF

 Age – Bimodal ; Children > Adults

 Race – Whites > Black
 Host genetics
 Pre-existing anti-dengue antibody

 maternal antibodies in infants

 previous infection
Risk Factors for DHF (continued)
 Chronic infections

 Hyperendemic transmission

 Locations with 2 or more serotypes circulating

simultaneously at high levels
 Secondary infections

 Cross-reacting Flaviviral (IgM) Antibody


Increased circulation Increased probability

of viruses of secondary infection

Increased probability of Increased probability of

occurrence of virulent strains immune enhancement

Increased probability of DHF

Gubler & Trent, 1994

Viral Risk Factors

 Virus strain (genotype)

 Epidemic potential: viremia level, infectivity

 Virus serotype

 DEN-2 > DEN-3 > DEN-4 > DEN-1

Risk Factors Reported for DSS

 Younger age at onset

 Altered sensorium
 Paralytic ileus
 Deranged Prothrombin time at
Clinical Evaluation in Dengue Fever
 Blood pressure

 Hydration status

 Tourniquet test

 Evidence of bleeding in skin or other sites

 Evidence of increased vascular permeability

 Falciparum malaria
 Gram-Negative septicemia
 Leptospirosis
 Rickettsiosis
 Typhoid fever
 Chikungunya Fever
Laboratory Tests
 In uncomplicated DHF cases

 Hematocrit and platelet counts are the only necessary tests

 In those at high risk of complicated DHF

 Blood grouping/cross matching

 Blood glucose
 Blood electrolyte (Na, Ca, K, CO2)
 Liver function test
 Renal function test (BUN, creatinine, uric acid)
 Blood gas
 Coagulogram (PTT, PT, TT)
 Complete Blood Count

-WBC (leukopenia with lymphocytosis)

-Platelet count <1,00,000

 Peripheral smear

 PCV (Hematocrit) rise 20% above baseline

 Coagulation profile to rule out DIC

 ABG : Metabolic Acidosis in prolonged shock

 Blood urea and S.Creatinine elevated in terminal stage of shock

Laboratory Tests (continued..)
 Serum electrolytes – Hyponatremia

 Urine--check for microscopic hematuria

 Liver function tests –Hypoproteinemia, SGOT>SGPT

 CXR – Pleural effusion (Right > Left )

 USS Abdomen – Hepatomegaly, Ascites and Gall bladder

Turk Reaction cell
 Transformed lymphocytes (Plasmacytoid )
 More than 20% Turk cells in buffy coat smear is
characteristic of DHF
Serological methods

 Hemagglutination inhibition test -> IgG

 Complement fixation test

 Dot-Blot immunoassay
 Early detection of dengue infection when antibodies are
not yet detectable.

 Less sensitive than viral isolation during early days of fever

 Rapid detection within 24 hours.
 But after 5 days of fever it is more sensitive than virus isolation.
 Able to detect the virus up to 7-8 days of fever.

 Epidemiological studies

 dengue serotypes could be identified without cross reactivity

with other flaviviruses
Virus isolation
 Mosquito cell lines

 Sensitivity of 50 %
 Culture done in cell line derived from A. albopictus cell.
 Can determine serotype of the infecting virus)
 For research and epidemiological studies.

 Mosquito inoculation technique

 Vertebral cell culture

Confirmed case - WHO definition

 Positive viral identification


 Positive serological test for HI antibody ≥ 1,280


 Positive IgM/IgG ELISA test in the convalescence

Important points to evaluate are
 History

 Bleeding, abdominal pain, vomiting, appetite, fluid intake, and urine output

 Physical examination

 Vital signs, liver size and tenderness

 Blood counts

 WBC ≤ 5,000 cells/mm3 with lymphocytosis and increase in atypical lymphocytes

 Platelet counts ≤ 100,000 cells/cumm – indicates progression to critical phase.
 Rising Hct of 10-20% - indicates that the patient has progressed to the critical phase

 Liver function tests

 in every patient who shows a change in consciousness, restlessness, confusion and

Transmission of Dengue Virus
by Aedes aegypti
Mosquito feeds / Mosquito refeeds /
acquires virus transmits virus

Extrinsic Intrinsic
incubation incubation
period period
Viremia Viremia
0 5 8 12 16 20 24 28
Illness Illness
Human #1 Human #2
Temperature, Virus Positivity and
Anti-Dengue IgM , by Fever Day

Dengue IgM (EIA units)

Temperature (degrees Celsius)

Percent Virus Positive

39.0 225
38.5 60
38.0 40
37.5 20 75

0 0
-4 -3 -2 -1 0 1 2 3 4 5 6
Fever Day
Mean Max. Temperature Virus Dengue IgM
Adapted from Figure 1 in Vaughn et al.,
J Infect Dis, 1997; 176:322-30.