2. Introduction
Agent ▪ Flavi virus , DHF virus serotype
1,2,3 and 4
Vector - Aedes aegypti*
▪ bite during daytime
▪ grow in clear water.
- Aedes albopictus
Host ▪ Common among age less than 15 year
Environment ▪ Epidemic in rainy season
Incubation period ▪ 1-7 days
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3. Endemic in Malaysia
4 serotypes circulating
Trends - cyclical pattern
1st reported in Penang
DHF 1962 (1st DHF outbreak)
Affects all age group
Most common among urban-semiurban population
Highest incidence in working and school-going age
group
Correlate with high Aedes Index in construction
sites, factories and schools
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8. Immune Enhancement Theory
Halstead
Antibody-dependent enhancement
Individuals who have had prior infection with one or
more dengue virus serotype
may develop low level of neutralizing Ab
Infection-enhancing Ab
Virus actually enhance the entry of different serotypes
into mononuclear phagocytes↑replicate*resulting in
the increased activation of complement and cytokines
the release of mediators of vascular permeability.
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9. 1st infection: benign illness which sensitizes the
patient
2nd infection (within 6/12): devastating immune
reaction and circulation of infection-enhancing
antibodies at the time of infection is risk factor for
development of severe disease
Viraemia - directly predict severity
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10. Pathophysiology
In early stage of secondary dengue infections:
ØRapid activation of complement system which
interacts at the endothelial cell to produce increased
vascular permeability
Increased vascular permeability causes- plasma
leakage,haemoconcentration,hypovolaemia,tissue hypoxia ,acidosis.
ØActivation of coagulating cascade & fibrinolytic
system
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11. Increased systemic vascular permeability-cont:
• Intravascular volume depletion
Hemoconcentration
Starts at the end of the febrile stage and continues up to
24-48 hours after defervescence
-- hypoproteinemia/hypoalbuminemia
pleural effusion, ascites
threatened shock and profound shock
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13. Tornique test-Hess test
BP cuff pressure maintained between systolic and
diastolic BP for 5 mins—
Positive-if >20 petechiae/ 2.5 cm 2 area
Increase capillary fragility
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14. Thrombocytopenia
< 100x109/L
Begins to fall in the febrile stage
Lowest in the shock stage
Can reach a nadir of less than 10 x 10 9 /L
Starts to rise by the second afebrile day and normalizes by 7
days
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15. Thrombocytopenia
Mechanism of thrombocytopaenia
Ø Decreased production and increased peripheral
destruction
§ Immune complexes on platelets
§ Shortened survival of transfused platelets
§ Cross reactive platelet antibodies
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17. Coagulopathy
Procoagulant markers increased in severe shock
variable degree of reduction in coagulation factors
II, V, VII, VIII, IX and X and low fibrinogen.
Prolongation of APTT and PT
There may be mild consumption coagulopathy to
overt DIC.
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18. Classification
Dengue virus infection
Asymptomatic Symptomatic
Dengue
Simple fever Dengue fever haemorrhagic
(DF) fever (DHF)
Without With unusual No shock Dengue shock
haemorrhage haemorrhage syndrome
(DSS)
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19. Classical Dengue Fever
u Infants &Young children
Disease may be undifferentiated
Characterised by fever 1-5 days,pharyngeal inflammation,
rhinitis & mild cough
Frequently passed undiagnosed
u Older children and adult
high grade fever with chills
occasionally severe back pain precedes the fever
severe headache, retro-orbital pain
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20. Transient macular gererlised rash that blanches under
pressure(24-48 hr after fever)appear on the limbs and
spread to involve trunk
Generalised lymphadenopathy
Anorexia,Nausea,Vomiting
Cutaneous hyperasthesia or hyperalgesia
1-2 days after defervescence-generalised morbiliform,
maculopapular rash appears that spares the palms&
soles,disappears in 1-5 days
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21. desqumation may occur
body temperature slightly elevated
biphasic temperature pattern
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27. Days after onset of fever
Viraemia
HI Ab IgG
Fever ̊C
Symptoms
Haemorrhage
Shock
Platelet 109/L
Hct %
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28. Clinical Pointers to diagnosis
High fever of 3 or more then duration
§ Petechial haemorrhage, positive tourniquet test or other
bleeding tendencies
§ Hepatomegaly
§ Pleural effusion or ascites
Shock
Fall in platelet count that precedes or occurs with a rise in
haematocrit
§ Normal or low WBC with relative lymphocytosis
Maculopapular rash or generalised flushing
Note: all criteria need not be present at the same time
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30. WHO case definition of DHF
ALL of the following criteria must be present:
• Fever of high grade and continuous for 2-7 days duration.
• Haemorrhagic diathesis or positive tourniquet test* except in shock.
• Thrombocytopenia (less than 100,000/mm³)
• Haemoconcentration (Hct ≥ 20% relative to baseline) or evidence of
plasma leakage
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31. Other clinical manifestations-
hepatomegaly
circulatory disturbances (cool extremities, capillary refil
>2 sec, tachycardia)
a fall in haematocrit following volume replacement
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32. WHO grading of DHF /DSS
Grade 1
Fever with constitutional symptoms.
A positive Hess test.
Grade 2
Spontaneous bleeding (skin ± other bleeds)
in addition to manifestations of grade 1
Grade 3
Circulatory failure (rapid weak pulse, pulse pressure < 20mmHg)
but systolic BP still normal
Grade 4
Profound shock (hypotension,undetectable blood pressure
and heart rate)
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33. NOTE;
• Grade 3 and 4 = Dengue Shock Syndrome
• Thrombocytopenia and haemoconcentration (rise in PCV by 5 g%)
differentiates Grade 1 and 2 DHF from DF
• Clinical differentiation of grade 1 and 2 DHF from DF is not always
clear cut due to variation in baseline haematocrit
• All patients ill enough to need IV drip* should be notified as DHF if
baseline haematocrit unknown
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35. In clinical practice
Dengue+/- warning /s Severe
Probable -abdo;pain S plasma leakage
-tender enlarged L S bleeding
-persistent V+ S organ impair;
-Mucosal bleed
-fluid accumu:
- ↑PCV
- ↓Plt
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36. DHF can be further graded as follows:
• DHF with no shock
• DHF with shock (DSS) which can be further graded into:
- DHF with compensated shock
• signs of shock – tachycardia out of proportion to temperature,
decreased tissue perfusion as
(cool extremities, late capillary refill time, narrow pulse pressure, weak
pulses, oliguria, encephalopathy)
• systolic pressure within the normal range
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37. DHF with decompensated shock
• signs of shock – tachycardia, cool extremities, late capillary refill
time, weak or absent pulses, oliguria and altered conscious level
• systolic hypotension
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38. Assessment of circulation
• fluid intake for previous 1-2 days, vomiting
• urine output for past 24 hours and time of last micturation
• bleeding* and amount
• degree of dehydration
• peripheral circulation
- temperature and colour of extremities, capillary refill
- distal pulses, pulse volume
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39. • Mental status: headache, irritability, combativeness, drowsiness, coma,
seizures
(may indicate reduce cerebral perfusion, cerebral oedema or
intracranial bleed)
• Pleural effusion and ascites (third space loss*)
• Abdominal pain
(may indicate GI bleed, acute liver enlargement, hypovolaemia with
intestinal ischaemia (shock)
• Hypotension is a late sign.
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42. Laboratory Diagnosis
Serology
• Dengue IgM Dot Enzyme Immunoassay
- interpret results in a clinical context. Serology may be negative in
early. A repeat study in 10 days will help confirm the diagnosis.
Virus isolation
-the most definitive diagnostic test. Availability limited.
• if patient dies soon after admission, a liver biopsy specimen sent in viral
transport media may be useful in confirming the diagnosis.
Dengue RNA PCR
• may be indicated to confirm diagnosis
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44. Management of Grade 1 & 2 DHF
Admission,place IV cannulae
Encourage oral fluids,IV ½ NS+D5% if unable to take
orally/evidence of plasma leakage
Paracetamol for fever
Avoid NSAIDS
Monitor –clinical;PR,T o,HR,RR, BP, I/O,Urine specific
gravity
PCV,PLT, Hb -8 to 12 hrly
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45. Cont;
monitor- until T o returns to normal,in 1-2 days,
throughout the critical period
during the transition from febrile to afebrile
phase(after 3rd day)
haemoconcentration usually precedes changes in pulse
pressure and rate.
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46. Management of DSS
• Admit to ICU.
• Obtain IV access.
• Resuscitation: *
• Monitor:
- vital signs, peripheral perfusion - blood pressure hourly till stable
- PCV or haematocrit & platelet count 6 hrly
- urea & ectrolytes, serum creatinine - urine output
- ABG
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49. § Fluid maintenance:
- following fluid resuscitation, continue with 0.45%saline 5%
dextrose at 1-2 times maintenance, guided by haematocrit, urine
output and vital signs.
- in general, the duration of vascular permeability lasts 1-2 days
following onset of shock
- after which further infusion of large volume of fluids may result in
pulmonary oedema and pleural effusion.
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50. Electrolyte and metabolic disturbances:
- hyponatremia and metabolic acidosis occur in DSS.
Isotonic fluids and restoration of tissue perfusion correct both problems.
- correct hypoglycaemia that may occur in liver failure
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51. § Transfusion of blood and blood products.
• Blood transfusion. Indications:
- significant haemorrhage
- persistent shock despite crystalloids and low or
declining haematocrit
Fresh whole blood is preferable.
• Platelet concentrate :Indications;
- platelet count < 50,000/mm³ with bleeding
- platelet count < 10,000 - 20,000/mm³
Dose -- 10-20 ml/kg or 4 units/m² BSA over 1 hour.
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52. In the presence of Disseminated Intravascular coagulaton (DIC)
Tx- cryoprecipitate (1 unit per 5 kg body weight ) followed by
platelet concentrate (10-20 ml/kg or
4units/m² BSA over 1 hour)
- fresh frozen plasma (10-20 ml/kg)
• monitor coagulation profile regularly. i.e. PT, PTT, fibrinogen, D-
dimer, or FPD and platelet counts.
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53. • oxygen supplement via nasal cannula or mask
• consider mechanical ventilation in
- respiratory distress from massive pleural effusion,
ascites or pulmonary oedema
- severe shock with multi-organ failure
- encephalopathy for cerebral resuscitation
• H₂ antagonists and Vitamin K
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54. Complications of DSS
• Shock either persistent or recurrent
• Pleural effusion and ascites
• Bleeding - usually gastrointestinal
• Hepatic dysfunction may result from dengue viral hepatitis or shock
• Encephalopathy, usually occurs early before onset of plasma leakage
• Beware of fluid overload and cardiac failure during the reabsorption
phase
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55. Special Notes
§ Insertion of nasogastric tube carries risk of trauma and bleeding. If
required, use an oral route.
§ Blood product transfusion carry risk of disease transmission. Avoid if vital
signs stable
§ Insertion of chest tubes carries risk of haemorrhage. Careful titration of iv
fluids with doses of frusemide 0.25-0.5 mg/kg for 1-2 doses should make
it possible to avoid chest tube insertion.
§ Central line insertion carries risk of bleeding. Intraosseous route is acceptable.
§ Use of steroids and immunoglobulin in DSS has no beneficial effect
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56. Preventive measures
Vaccine underdevelopment
Avoiding mosquito bites by use of
insecticides,repellents,body covering with clothing ,
Destruction of mosquito breeding sites
Larvicide- Abate added safely to drinking water
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57. References
Nelson Text Book of Paed (19th edition)
Illustrated Text Book
Paed: Protocol
CPG ,Ministry of Health Malaysia
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Editor's Notes
Most common arboviral/arthropod born d/s transmitted worldwide,tropical/subtropical.One of the leading cause of hospital admission; and death of children in SEA. ----- Meeting Notes (3/27/12 14:40) -----
Aedes Index=NO: of house with Aedes larvae x 100 NO: of house inspected
*Virus replication takes place in RE cells-dendritic cells,Hepatocytes,Endothelial cells
