dengue fever management_pediatrics seminar
DESCRIPTION
Dengue Fever Management_Pediatrics SeminarTRANSCRIPT
SUBJECT SEMINAR SUBJECT SEMINAR MANAGEMENT OF MANAGEMENT OF DENGUE FEVERDENGUE FEVER
PRESENTERPRESENTER : Dr.Mohan.T.Shenoy
CHAIRPERSONCHAIRPERSON: Dr.Nisarga
REFERENCESREFERENCES 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 http://www.who.int/ctd/docs/dengue.pdf http://www.cdc.gov/ 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 mothers.
• Presence of underlying chronic illnesses (eg: heart disease, anaemia, chronic liver disease)
Warning Signs for Dengue Warning Signs for Dengue ShockShock
When Patients Develop DSS:• 3 to 6 days after onset of symptoms
When Patients Develop DSS:• 3 to 6 days after onset of symptoms
Initial Warning Signals• Disappearance of fever• Drop in platelets• Increase in hematocrit
Initial Warning Signals• Disappearance of fever• Drop in platelets• Increase in hematocrit
Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from fever to hypothermia• Change in level of consciousness (irritability or somnolence)
Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from fever to hypothermia• Change in level of consciousness (irritability or somnolence)
Four Criteria for DHF• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets
Four Criteria for DHF• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets
Special attention :High-risk dengue patients
Infants under 1 year of age
Overweight/obese patients
Massive bleeding
Change of consciousness, esp. restlessness,irritability or coma
Presence of underlying diseases e.g. thalassemia, G-6-PD deficiency, heart disease
Admission in Dengue FeverAdmission 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
TREATMENT
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
DENGUE FEVERDENGUE FEVER
General measuresGeneral 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 supportNutritional 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)General measures (continued) SedationSedation is needed in some cases to restrain agitated child.
Chloral hydrate(12.5-50 mg/kg), orally or rectally recommended. Avoid Long-acting sedatives.
NCPAPNCPAP 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 treatmentOther 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
FLUID MANAGEMENT
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
FLUID MANAGEMENT
WHO guidelines are useful in that they offer an algorithmic approach to fluid resuscitation in DHF and DSS.
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 echocardiography.
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 transfusionBlood and platelet transfusion
Platelet transfusion Platelet transfusion
Thrombocytopenia with significant bleeding. Platelet count < 10,000/mm3
DOSE
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 outcome.
Platelets return to normal Platelets return to normal within 7-9 dayswithin 7-9 days. .
Significant blood loss > 10% (6-8 mL/kg) Concealed internal bleeding Hemolysis
DOSE
Fresh whole blood 10 mL/kg/dose Packed red cells 5 mL/kg/dose
Fresh Whole blood / Packed red cell transfusionFresh Whole blood / Packed red cell transfusion
Role of SteroidsRole 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/DSSComplications of DF/DSS
DIC Myocardial dysfunction incl. Cardiomyopathy Hepatitis Reye-like syndrome Encephalitis ARDS Glomerulonephritis
Treatment of Treatment of complicationscomplications
Fluid overload Fluid overload
AVOID
Early IV fluid therapyEarly IV fluid therapy- in the febrile phase- in the febrile phase Excessive use of hypotonic solutionsExcessive use of hypotonic solutions Non-reduction in the rate of IV fluid after initial resuscitationNon-reduction in the rate of IV fluid after initial resuscitation Blood loss replaced with fluids in cases with occult bleedingBlood 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
Hyponatremia Hypocalcemia – 10% Ca gluconate 1 mL/kg/dose, slow IV push
every 6 hour
Large pleural effusions, ascitesLarge pleural effusions, ascites
Careful titration of intravenous fluids.
Avoid insertion of intercostal drains and tracheal intubation.
Large pleural effusions during recovery phase after 48 hoursfurosemide (0.25-0.5 mg/kg at 6 hours’ interval for 1 to 2 doses).
Electrolyte imbalance Electrolyte imbalance
Disseminated intravascular coagulationDisseminated 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 failureARDS & Hypotension with Respiratory failure
Nasal CPAP
Refractory shockRefractory shock
Vasopressin Desmopressin 0.3 mcg/kg over 30 min 3-4 days
Prognosis
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 40-50%.
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 extremities.
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.
The case fatality rate is high with shortage of experienced medical teams..
Criteria for Discharge of patientsCriteria 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 rashConvalescent confluent petechial rash
BETWEEN 8 –10th day of SICKNESS
Signs of recoverySigns 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 aboutCommon Misconceptions aboutDengue Hemorrhagic FeverDengue Hemorrhagic Fever
Positive tourniquet test = DHF Tourniquet test is a nonspecific indicator of capillary
fragility
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 DHFPoor 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
VECTOR CONTROL
The control is primarily dependent on eradicating mosquito. Public spraying for mosquitoes is the most important aspect of this
approach.
PERSONAL PROTECTION
Avoiding endemic areas Cover exposed skin Mosquito nets, repellents Use of DEET-impregnated bed nets
Immunopathogenic 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 Thailand.
Produces 80-90% seroconversion rates to all 4 serotypes after administration of 2 doses in young children
SUGGESTIONS FROM THE TRIALSUGGESTIONS FROM THE TRIAL
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
GLOBAL STATUS
BURDEN OF DISEASE IN S.E.ASIABURDEN OF DISEASE IN S.E.ASIA
CATEGORY-ACATEGORY-A (INDONESIA,MYANMAR,AND THAILAND)
CATEGORY-B CATEGORY-B (INDIA,BANGALADESH,MALDIVES,AND SRILANKA)
CATEGORY-CCATEGORY-C (BHUTAN, NEPAL)
CATEGORY-DCATEGORY-D (DPR KOREA)
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 aegyptiAedes aegypti Mosquito Mosquito
Day-biting urban thriving mosquito Day-biting urban thriving mosquito White bands or scale patterns on its legs and thorax. White bands or scale patterns on its legs and thorax.
Highly domesticated tropical mosquito, lives around human habitationHighly domesticated tropical mosquito, lives around human habitation Single infective mosquito may cause an outbreakSingle infective mosquito may cause an outbreak
Transmission CycleTransmission Cycle
Intrinsic Incubation Period: 3-14 days
Viraemia & Fever: 5-7 days
VectorHumidity: Rainfall & Temp.
Susceptible hosts,(population)
Source patients
ExtrinsicIncubation Period: 8-10 days
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%.
DENGUE ILLNESS: DISTRIBUTIONDENGUE ILLNESS: DISTRIBUTION
Population
Infection
Clinical Cases
DHF/DSS
AsymptomaticInfection
DF(non-DHF)
survive Death
24%
3%
0.8%
76%
97%
99.2%
Rates in dengue model by Shepard et al. Vaccine. 2004, 22:1275-1280.
SPECTRUM OF DENGUE INFECTIONSPECTRUM OF DENGUE INFECTION
Clinical FeaturesClinical 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; 38:172-80.
ERYTHEMATOUS FLUSHERYTHEMATOUS FLUSH
Suffused + Swollen face with purplish lips, injected eyesReddened malar regions and ear lobules
Dengue fever with unusual hemorrhageDengue 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 ManifestationsHemorrhagic Manifestations
Skin hemorrhages: Petechiae, purpura, ecchymoses Gingival bleeding Epistaxis Gastro-intestinal bleeding: hematemesis, melena Hematuria Increased bleeding per vaginum Intracranial bleed
DENGUE HEMORRHAGIC FEVER
Petechiae
PURPURA
Four Grades of DHFFour Grades of DHF Grade 1
Fever and nonspecific constitutional symptoms Positive tourniquet test is only hemorrhagic
manifestation 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 TestTourniquet 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 TestPositive Tourniquet Test
Endemic areas -WHO criteria Endemic areas -WHO criteria
2 clinical observations
+
1 laboratory finding
OR
At least a rising hematocrit levelAt least a rising hematocrit level
Thrombocytopenia (< 100,000 cells/mm3)
Hemoconcentration
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 hemoconcentration.
Clinical Case Definition for DSSClinical 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 - DSSHypothesis 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 ImmunogenecityInitial Immunogenecity
Immune ComplexesImmune Complexes
Risk Factors Reported for DHFRisk 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)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
Hyperendemicity
Increased circulationof viruses
Increased probabilityof secondary infection
Increased probability ofoccurrence of virulent strains
Increased probability ofimmune enhancement
Increased probability of DHF
Gubler & Trent, 1994
Viral Risk FactorsViral Risk Factors
Virus strain (genotype)
Epidemic potential: viremia level, infectivity
Virus serotype
DEN-2 > DEN-3 > DEN-4 > DEN-1
Risk Factors Reported for DSSRisk Factors Reported for DSS
Younger age at onset Altered sensorium Paralytic ileus Deranged Prothrombin time at
presentation
Clinical Evaluation in Dengue FeverClinical Evaluation in Dengue Fever Blood pressure
Hydration status
Tourniquet test
Evidence of bleeding in skin or other sites
Evidence of increased vascular permeability
DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS
Falciparum malaria Gram-Negative septicemia Leptospirosis Rickettsiosis Typhoid fever Chikungunya Fever
Laboratory TestsLaboratory 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 TestsLaboratory 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 thickening
Transformed lymphocytes (Plasmacytoid ) More than 20% Turk cells in buffy coat smearbuffy coat smear is
characteristic of DHF
Turk Reaction cellTurk Reaction cell
Serological methodsSerological methods
MAC-ELISA -> IgM
Hemagglutination inhibition test -> IgG
Complement fixation test
Dot-Blot immunoassay
RT-PCRRT-PCR 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 Virus isolation
Mosquito cell linesMosquito 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 techniqueMosquito inoculation technique
Vertebral cell cultureVertebral cell culture
Confirmed case - WHO definitionConfirmed case - WHO definition
Positive viral identification
AND/OR
Positive serological test for HI antibody ≥ 1,280
OR
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 irritability
Transmission of Dengue VirusTransmission of Dengue Virusby by Aedes aegyptiAedes aegypti
Viremia Viremia
Extrinsic incubation
period
DAYS0 5 8 12 16 20 24 28
Human #1 Human #2
Illness
Mosquito feeds /acquires virus
Mosquito refeeds /transmits virus
Intrinsicincubation
period
Illness
Temperature, Virus Positivity and Anti-Dengue IgM , by Fever Day
Dengue IgMMean Max. Temperature Virus
Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.
Fever Day
0
20
40
60
80
100
Per
cen
t V
iru
s P
osit
ive
-4 -3 -2 -1 0 1 2 3 4 5 6
39.5
39.0
38.5
38.0
37.5
37.0
Tem
per
atu
re (
deg
rees
Cel
siu
s)
Den
gue
IgM
(E
IA u
nit
s)300
150
0
75
225