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Dengue
in children
- Dr. C.S.N.Vittal
Virus
Is an arbovirus composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)
Vector
• Is an arbovirus composed of single-stranded RNA
• Has 4 serotypes (DEN-1, 2, 3, 4)
• Transmitted by mosquitoes of the Stegomyia family,
• Aedes aegypti , a daytime biting mosquito,
Aedes aegypti
• Dengue transmitted by
infected female mosquito
• Primarily a daytime feeder
• Lives around human
habitation
• Lays eggs and produces
larvae preferentially in
artificial containers
Replication and Transmission
of Dengue Virus
1. Virus transmitted
to human in mosquito
saliva
2. Virus replicates
in target organs
3. Virus infects white
blood cells and
lymphatic tissues
4. Virus released and
circulates in blood
3
4
1
2
Infectivity Period
(about 7 days)
Extrinsic Incubation
Period (8–12 days)
Intrinsic Incubation
Period (3–14 days)
Replication and Transmission
of Dengue Virus (Part 2)
5. Second mosquito
ingests virus with blood
6. Virus replicates
in mosquito midgut
and other organs,
infects salivary
glands
7. Virus replicates
in salivary glands
6
7
5
Dengue Epidemiology - WHO
• Dengue is now endemic in over 100 countries.
• As many as 3.6 billion people
• 40% of the world's population, reside in dengue-endemic areas.
• Each year, 400 million people are infected with dengue virus,
• 100 million become ill with dengue
• 21,000 deaths attributed to dengue are detected.
• Early identification of cases and timely initiation of correct clinical
management can reduce the case fatality rate from 10% to 1%.
Pathogenesis
Antibody-dependent enhancement (ADE)
Circulation of infection‐enhancing antibodies at the time of
infection 🢫 strongest risk factor for development of severe disease.
• Rapid activation of the complement system.
• Capillary damage ‐ internal redistribution of fluid, resulting in
• hemoconcentration,
• hypovolemia,
• increased cardiac work,
• tissue hypoxia,
• metabolic acidosis, and
• hyponatremia.
Pathogenesis
Role of NS 1 antigen
In pathogenesis of Dengue
Fever
Clinical Manifestations of Dengue and
Dengue Hemorrhagic Fever
Dengue Viral Infection
Asymptomatic Symptomatic
Dengue Fever
Syndrome
Without
Hemorrhage
DHF
No Shock
With
Hemorrhage DSS
Dengue Hemorrhagic
Fever
Undifferentiated
Viral Syndrome
DF DHF
Dengue Clinical Syndromes
1
2
3
4
Suggested dengue case classification and
levels of severity
Probable dengue
• Live in /travel to dengue
endemic area.
• Fever and
• 2 of the following criteria:
• Nausea, vomiting
• Rash
• Aches and pains
• Tourniquet test positive
• Leukopenia
Any warning sign
Warning signs*
• Abdominal pain or tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleed
• Lethargy, restlessness
• Liver enlargement > 2 cm
• Laboratory: Increase in HCT
concurrent with rapid decrease in
platelet count
*(requiring strict observation and
medical intervention)
CRITERIA FOR DENGUE ± WARNING SIGNS
CRITERIA FOR SEVERE DENGUE
Severe plasma leakage -
leading to:
• Shock
Severe bleeding
• as evaluated by clinician
Severe organ involvement
• Liver:AST orALT > 1000
• CNS: Impaired consciousness
• Heart and other organs
Risk Factors for Severe Dengue
Viral characteristics
- Viral titer
- Inherent
Host factors
- Age (infant)
- Women, esp pregnant
women
- Chronic medical
conditions: diabetes,
asthma, obesity, and
heart disease
- Secondary DENV
infection
Level of neutralizing
antibody
• - Timing of infection
relative to the previous
DENV infection
• - There are no tests or
biomarkers to identify
which patients will
experience severe
disease.
The course of dengue illness
1. Febrile Phase
2. Critical Phase
3. Recovery Phase
The course of dengue illness
The course of dengue illness
Febrile Phase
• Dehydration;
• High fever
• May cause neurological
disturbances and febrile
seizures in young
children
Critical Phase
- Shock from plasma
leakage;
- Severe haemorrhage;
- Organ impairment
Recovery Phase
Hypervolaemia
Worsening effusions
Acute pulmonary edema
Probable adverse events
Diagnosis
Tourniquet Test
1. Take the patient's blood pressure and
record it, for example, 100/70.
2. Inflate the cuff to a point midway between
SBP and DBP and maintain for 5 minutes.
3. Reduce and wait 2 minutes.
4. Count petechiae below antecubital fossa.
A positive test is 10 or more petechiae per 1 square inch.
• More likely to be positive near time of effervescence
• Less likely to be positive in patients with shock
 Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention
and Control. PAHO: Washington, D.C., 1994: 12.
Lab tests
 Antigen NS 1 test
 ELISA- IgG, IgM antibodies
 Blood cultures- isolate the virus
 Full blood count
 Hct
 Liver function test
 PCR- Nucleic acid detection
Interpretation of dengue diagnostic tests
[adapted from Dengue and Control (DENCO) study]
Highly suggestive Confirmed
One of the following:
1. IgM +ve in a single serum
sample
2. IgG +ve in a single serum
sample with a HI titre of
1280 or greater
One of the following:
1. PCR +
2. Virus culture +
3. IgM seroconversion in
paired sera
4. Four fold IgG titer increase
in paired sera
Differential Diagnosis of Dengue
• Influenza
• Measles
• Rubella
• Malaria
• Typhoid fever
• Leptospirosis
• Meningococcemia
• Rickettsial infections
• Bacterial sepsis
• Other viral hemorrhagic fevers
A stepwise approach to the
management of dengue
Step I 1 History, symptoms, past medical & family history
2 Physical examination and mental assessment
3 Investigation, including routine labs and dengue-specific laboratory
Step II Diagnosis, assessment of disease phase and severity
Step III 1 Disease notification
2 Management decisions.
Depending on the clinical manifestations and other circumstances,
patients may be:
– sent home (Group A);
– referred for in-hospital management (Group B);
– require emergency treatment and urgent referral (Group C).
A stepwise approach to the management of dengue
Patient Assessment Steps
Step 1
• History Taking
Step 2
• Clinical Examination
Step 3
• Investigation
Step 4
• Diagnosis, phase of disease and severity
Patient Assessment Steps
Step 1 : History Taking
• Date of onset of fever
• Symptoms and severity
• Three Golden questions
» 1) How much fluid intake : Quantity and quality
» 2) How much urine output: Frequency, volume and time of
most recent voiding?
» 3) What activities could the patient do during the illness
• Other fluid losses: diarrhoea, vomiting
• Present of Warning Signs
• Family or neighbour with dengue OR travel to dengue-endemic area
• Risk Factors
• Infancy, pregnancy, obesity, diabetes mellitus, hypertension, etc.
Patient Assessment Steps
Step 2: ClinicalAssessment
GeneralAssessment:
• Mental state
• Hydration state
• Hemodynamic state
Clinical e/o. warning signs
• Bleeding manifestations: mucosal
bleeding
• Abdominal tenderness
• Liver enlargement
• Fluid accumulation,: pl effusion,
ascites
Other imp signs:
• Rash
• Tachypnoea/acidotic
breathing: indicates shock
• Torniquet test: repeat if –ve
1. Normal peripheral
perfusion
3. Normal brain
perfusion
2. Normal cardiac
output
4. No respiratory
comepnsation
3. Normal kidney
perfusion
Definition of hypotension
Adults:
• Systolic blood pressure of < 90 mm Hg or
• Meal arterial pressure < 70 mm Hg or
• Systolic blood pressure decrease of > 40 mm Hg or
• < 2 SD below normal for age (Hypertensive patients)
Children upto 10 year of age:
• The 5th centile for systolic pressure
• 70 + (age in years X 2) mm HG
Pearls in clnical examination of dentue patients
The “5-in-1 maneuver” magic touch – CCTV-R
Hold patient’s hand to evaluate peripheral perfusion
Save life in 30 seconds by recognizing shock
1
Color
2
Capillary
refill
3
Tempera
ture
4
Pulse
Volume
5
Pulse
Rate
Algorithm for management of Dengue
Warning Signs
Group A
Outpatient Management
 During the febrile phase (may last 2–7 days) and
subsequent critical phase (1–2 days), your clinic
should
• Follow CBCs
• Watch for dehydration
• Watch for warning signs, including decreasing
platelet count and increasing hematocrit
• Watch for defervescence (..beginning of critical phase)
Group A
Advise patient or their family to do the following
 Control the fever
 Prevent dehydration
 Prevent spread of dengue within your house
 Watch for warning signs as temperature declines 3 to 8 days after
symptoms began.
• Severe abdominal pain or persistent vomiting
• Red spots/patches on skin
• Bleeding from nose or gums
• Vomiting blood, Black, tarry stools
• Drowsiness or irritability
• Pale, cold, or clammy skin
• Difficulty breathing
Group B
Pts with Waning Signs
Admit
Obtain baseline
CBC
Monitor fluid I/O
Encourge oral fluids
Monitor vital sings q4h
Adequate? • Check Hct
• IV fluids
• Keep
monitoring
• Check Hct
• Observe for
shock,
warning signs
• Group C
management
Initiate Intravenous
therapy @ 10ml/kg
over 1 hour
Reduce to 3-5
ml/kg/hr for 2-4
hours
Reduce to 2-3
ml/kg/hr or less acc
to clincial response
If worsening 10-20
ml/kg for 1 hour
If improvement after 2nd
bolus, reduce to
7-10 ml/kg for 1-2 hours
If no improvement & if HCT
decreases > blood transfusion
Group C
Pts with Compensated Shock
Check Hematocrite
Improvement
Crystalloid/Colloid
10 ml/kg for 1 hr,
then
reduce to 5-7 ml/kg 1-2 hrs
3-5 ml/kg/hr for 2-4 hrs
2-3 ml/kg/hr for 2-4 hrs
If Hct increases or is
high adm 3rd bolus
fluid (colloid) 10-20
ml/kg over 2 hrs
HCT decreasing
Consider significant
occult /overt bleed
Initiate blood transfusion
HCT dincreasing or high
Adm 2nd bolus fluid
(colloid) 10-20 ml/kg
over ½ to 1 hr
No improvement
Y
es No
Stop
After
48 hrs
Group C
Pts with Hypotensive Shock
Fluid resuscitation with 20 ml/kg over 15 minutes isotonic crystalloid or colloid
WHEN TO STOP INTRAVENOUS FLUIDS
 Features of intra vascular compartment
overload •
• Hypertension with good volume pulse.
• Breathing difficulties, pulmonary edema.
 48 hours after defervescence.
Discharge criteria
(all of the following conditions must be present)
Clinical • No fever for 48 hours.
• Improvement in clinical status
• general well-being,
• appetite,
• haemodynamic status,
• urine output,
• no respiratory distress
Laboratory • Increasing trend of platelet count.
• Stable haematocrite without intravenous fluids.
Dengue Vaccine?
 No licensed vaccine at present
 Effective vaccine must be tetravalent
 Field testing of an attenuated tetravalent
vaccine currently underway
 Effective, safe and affordable vaccine will
not be available in the immediate future
• Avoidmosquitobiteswhentravelingintropical areas:
• Use mosquito repellents on skin and clothing.
• Wear long-sleeved shirts and long pants tucked into socks.
• Avoid heavily populated residential areas.
• When indoors, stay in air-conditioned or screened areas.
• Use bednets if sleeping areas are not screened or air-conditioned.
• If you have symptoms of dengue, report your travel history
• Eliminate mosquitobreedingsites in areaswheredenguemightoccur:
• Eliminate mosquito breeding sites around homes.
• Discard items that can collect rain or run-off water, esp. old tires.
• Regularly change the water in outdoor bird baths and pet and
animal water containers.
Prevention
- C.S.N.Vittal

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dengue (1).pptx

  • 2. Virus Is an arbovirus composed of single-stranded RNA Has 4 serotypes (DEN-1, 2, 3, 4)
  • 3. Vector • Is an arbovirus composed of single-stranded RNA • Has 4 serotypes (DEN-1, 2, 3, 4) • Transmitted by mosquitoes of the Stegomyia family, • Aedes aegypti , a daytime biting mosquito,
  • 4. Aedes aegypti • Dengue transmitted by infected female mosquito • Primarily a daytime feeder • Lives around human habitation • Lays eggs and produces larvae preferentially in artificial containers
  • 5. Replication and Transmission of Dengue Virus 1. Virus transmitted to human in mosquito saliva 2. Virus replicates in target organs 3. Virus infects white blood cells and lymphatic tissues 4. Virus released and circulates in blood 3 4 1 2 Infectivity Period (about 7 days) Extrinsic Incubation Period (8–12 days) Intrinsic Incubation Period (3–14 days)
  • 6. Replication and Transmission of Dengue Virus (Part 2) 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito midgut and other organs, infects salivary glands 7. Virus replicates in salivary glands 6 7 5
  • 7. Dengue Epidemiology - WHO • Dengue is now endemic in over 100 countries. • As many as 3.6 billion people • 40% of the world's population, reside in dengue-endemic areas. • Each year, 400 million people are infected with dengue virus, • 100 million become ill with dengue • 21,000 deaths attributed to dengue are detected. • Early identification of cases and timely initiation of correct clinical management can reduce the case fatality rate from 10% to 1%.
  • 8. Pathogenesis Antibody-dependent enhancement (ADE) Circulation of infection‐enhancing antibodies at the time of infection 🢫 strongest risk factor for development of severe disease. • Rapid activation of the complement system. • Capillary damage ‐ internal redistribution of fluid, resulting in • hemoconcentration, • hypovolemia, • increased cardiac work, • tissue hypoxia, • metabolic acidosis, and • hyponatremia.
  • 9. Pathogenesis Role of NS 1 antigen In pathogenesis of Dengue Fever
  • 10. Clinical Manifestations of Dengue and Dengue Hemorrhagic Fever
  • 11. Dengue Viral Infection Asymptomatic Symptomatic Dengue Fever Syndrome Without Hemorrhage DHF No Shock With Hemorrhage DSS Dengue Hemorrhagic Fever Undifferentiated Viral Syndrome DF DHF
  • 13. Suggested dengue case classification and levels of severity
  • 14. Probable dengue • Live in /travel to dengue endemic area. • Fever and • 2 of the following criteria: • Nausea, vomiting • Rash • Aches and pains • Tourniquet test positive • Leukopenia Any warning sign Warning signs* • Abdominal pain or tenderness • Persistent vomiting • Clinical fluid accumulation • Mucosal bleed • Lethargy, restlessness • Liver enlargement > 2 cm • Laboratory: Increase in HCT concurrent with rapid decrease in platelet count *(requiring strict observation and medical intervention) CRITERIA FOR DENGUE ± WARNING SIGNS
  • 15. CRITERIA FOR SEVERE DENGUE Severe plasma leakage - leading to: • Shock Severe bleeding • as evaluated by clinician Severe organ involvement • Liver:AST orALT > 1000 • CNS: Impaired consciousness • Heart and other organs
  • 16. Risk Factors for Severe Dengue Viral characteristics - Viral titer - Inherent Host factors - Age (infant) - Women, esp pregnant women - Chronic medical conditions: diabetes, asthma, obesity, and heart disease - Secondary DENV infection Level of neutralizing antibody • - Timing of infection relative to the previous DENV infection • - There are no tests or biomarkers to identify which patients will experience severe disease.
  • 17. The course of dengue illness 1. Febrile Phase 2. Critical Phase 3. Recovery Phase
  • 18. The course of dengue illness
  • 19. The course of dengue illness Febrile Phase • Dehydration; • High fever • May cause neurological disturbances and febrile seizures in young children Critical Phase - Shock from plasma leakage; - Severe haemorrhage; - Organ impairment Recovery Phase Hypervolaemia Worsening effusions Acute pulmonary edema Probable adverse events
  • 21. Tourniquet Test 1. Take the patient's blood pressure and record it, for example, 100/70. 2. Inflate the cuff to a point midway between SBP and DBP and maintain for 5 minutes. 3. Reduce and wait 2 minutes. 4. Count petechiae below antecubital fossa. A positive test is 10 or more petechiae per 1 square inch. • More likely to be positive near time of effervescence • Less likely to be positive in patients with shock  Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 12.
  • 22. Lab tests  Antigen NS 1 test  ELISA- IgG, IgM antibodies  Blood cultures- isolate the virus  Full blood count  Hct  Liver function test  PCR- Nucleic acid detection
  • 23.
  • 24. Interpretation of dengue diagnostic tests [adapted from Dengue and Control (DENCO) study] Highly suggestive Confirmed One of the following: 1. IgM +ve in a single serum sample 2. IgG +ve in a single serum sample with a HI titre of 1280 or greater One of the following: 1. PCR + 2. Virus culture + 3. IgM seroconversion in paired sera 4. Four fold IgG titer increase in paired sera
  • 25. Differential Diagnosis of Dengue • Influenza • Measles • Rubella • Malaria • Typhoid fever • Leptospirosis • Meningococcemia • Rickettsial infections • Bacterial sepsis • Other viral hemorrhagic fevers
  • 26. A stepwise approach to the management of dengue
  • 27. Step I 1 History, symptoms, past medical & family history 2 Physical examination and mental assessment 3 Investigation, including routine labs and dengue-specific laboratory Step II Diagnosis, assessment of disease phase and severity Step III 1 Disease notification 2 Management decisions. Depending on the clinical manifestations and other circumstances, patients may be: – sent home (Group A); – referred for in-hospital management (Group B); – require emergency treatment and urgent referral (Group C). A stepwise approach to the management of dengue
  • 28. Patient Assessment Steps Step 1 • History Taking Step 2 • Clinical Examination Step 3 • Investigation Step 4 • Diagnosis, phase of disease and severity
  • 29. Patient Assessment Steps Step 1 : History Taking • Date of onset of fever • Symptoms and severity • Three Golden questions » 1) How much fluid intake : Quantity and quality » 2) How much urine output: Frequency, volume and time of most recent voiding? » 3) What activities could the patient do during the illness • Other fluid losses: diarrhoea, vomiting • Present of Warning Signs • Family or neighbour with dengue OR travel to dengue-endemic area • Risk Factors • Infancy, pregnancy, obesity, diabetes mellitus, hypertension, etc.
  • 30. Patient Assessment Steps Step 2: ClinicalAssessment GeneralAssessment: • Mental state • Hydration state • Hemodynamic state Clinical e/o. warning signs • Bleeding manifestations: mucosal bleeding • Abdominal tenderness • Liver enlargement • Fluid accumulation,: pl effusion, ascites Other imp signs: • Rash • Tachypnoea/acidotic breathing: indicates shock • Torniquet test: repeat if –ve
  • 31.
  • 32. 1. Normal peripheral perfusion 3. Normal brain perfusion 2. Normal cardiac output 4. No respiratory comepnsation 3. Normal kidney perfusion
  • 33.
  • 34.
  • 35.
  • 36. Definition of hypotension Adults: • Systolic blood pressure of < 90 mm Hg or • Meal arterial pressure < 70 mm Hg or • Systolic blood pressure decrease of > 40 mm Hg or • < 2 SD below normal for age (Hypertensive patients) Children upto 10 year of age: • The 5th centile for systolic pressure • 70 + (age in years X 2) mm HG
  • 37. Pearls in clnical examination of dentue patients The “5-in-1 maneuver” magic touch – CCTV-R Hold patient’s hand to evaluate peripheral perfusion Save life in 30 seconds by recognizing shock 1 Color 2 Capillary refill 3 Tempera ture 4 Pulse Volume 5 Pulse Rate
  • 38. Algorithm for management of Dengue Warning Signs
  • 39. Group A Outpatient Management  During the febrile phase (may last 2–7 days) and subsequent critical phase (1–2 days), your clinic should • Follow CBCs • Watch for dehydration • Watch for warning signs, including decreasing platelet count and increasing hematocrit • Watch for defervescence (..beginning of critical phase)
  • 40. Group A Advise patient or their family to do the following  Control the fever  Prevent dehydration  Prevent spread of dengue within your house  Watch for warning signs as temperature declines 3 to 8 days after symptoms began. • Severe abdominal pain or persistent vomiting • Red spots/patches on skin • Bleeding from nose or gums • Vomiting blood, Black, tarry stools • Drowsiness or irritability • Pale, cold, or clammy skin • Difficulty breathing
  • 41. Group B Pts with Waning Signs Admit Obtain baseline CBC Monitor fluid I/O Encourge oral fluids Monitor vital sings q4h Adequate? • Check Hct • IV fluids • Keep monitoring • Check Hct • Observe for shock, warning signs • Group C management
  • 42. Initiate Intravenous therapy @ 10ml/kg over 1 hour Reduce to 3-5 ml/kg/hr for 2-4 hours Reduce to 2-3 ml/kg/hr or less acc to clincial response If worsening 10-20 ml/kg for 1 hour If improvement after 2nd bolus, reduce to 7-10 ml/kg for 1-2 hours If no improvement & if HCT decreases > blood transfusion Group C Pts with Compensated Shock
  • 43. Check Hematocrite Improvement Crystalloid/Colloid 10 ml/kg for 1 hr, then reduce to 5-7 ml/kg 1-2 hrs 3-5 ml/kg/hr for 2-4 hrs 2-3 ml/kg/hr for 2-4 hrs If Hct increases or is high adm 3rd bolus fluid (colloid) 10-20 ml/kg over 2 hrs HCT decreasing Consider significant occult /overt bleed Initiate blood transfusion HCT dincreasing or high Adm 2nd bolus fluid (colloid) 10-20 ml/kg over ½ to 1 hr No improvement Y es No Stop After 48 hrs Group C Pts with Hypotensive Shock Fluid resuscitation with 20 ml/kg over 15 minutes isotonic crystalloid or colloid
  • 44. WHEN TO STOP INTRAVENOUS FLUIDS  Features of intra vascular compartment overload • • Hypertension with good volume pulse. • Breathing difficulties, pulmonary edema.  48 hours after defervescence.
  • 45. Discharge criteria (all of the following conditions must be present) Clinical • No fever for 48 hours. • Improvement in clinical status • general well-being, • appetite, • haemodynamic status, • urine output, • no respiratory distress Laboratory • Increasing trend of platelet count. • Stable haematocrite without intravenous fluids.
  • 46. Dengue Vaccine?  No licensed vaccine at present  Effective vaccine must be tetravalent  Field testing of an attenuated tetravalent vaccine currently underway  Effective, safe and affordable vaccine will not be available in the immediate future
  • 47. • Avoidmosquitobiteswhentravelingintropical areas: • Use mosquito repellents on skin and clothing. • Wear long-sleeved shirts and long pants tucked into socks. • Avoid heavily populated residential areas. • When indoors, stay in air-conditioned or screened areas. • Use bednets if sleeping areas are not screened or air-conditioned. • If you have symptoms of dengue, report your travel history • Eliminate mosquitobreedingsites in areaswheredenguemightoccur: • Eliminate mosquito breeding sites around homes. • Discard items that can collect rain or run-off water, esp. old tires. • Regularly change the water in outdoor bird baths and pet and animal water containers. Prevention