Dengue Hemorrhagic fever

1. 08/12/12
Dengue Haemorrhagic Fever

Dr San Thitsa Aung

2. 08/12/12
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

3. 08/12/12
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

4. 08/12/12
Vector Borne Diseases
Incidence Rate and Mortality Rate
(per 100,000population)(Health Facts-2009)
Dengue
DHF
Malaria
Typhus
Plague
Yellow Fever
Dengue
DHF
Malaria
Typhus
Plague
Yellow Fever

5. 08/12/12
Number of Dengue Cases by States, Malaysia
Epid Week 1 - 35; Year 2008
No. STATE
No. of
Cases
IR
(per 100,000
pop)
No. STATE
No. of
Cases
IR
1.SELANGOR 13,139 259.1 9.MELAKA 597 79.2
2.WPKL 3,514 215.7 10.PAHANG 814 53.8
3.TERENGGANU 1206 110.2 11.LABUAN 56 63.9
4.PERAK 2,510 106.7 12.KEDAH 914 46.7
5.N. SEMBILAN 931 93.5 13.PERLIS 108 45.7
6.PENANG 1,251 80.9 14.SARAWAK 872 35.6
7.KELANTAN 1,689 105.9 15.SABAH 751 24.0
8.JOHOR 2,501 75.5 Until Wk 36
30,853 cases
(62 deaths)

6. 08/12/12
Total No of admission = 4243 (Health
Facts 2010)

7. 08/12/12
PATHOGENESIS
Incompletely understood

8. 08/12/12
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.

9. 08/12/12
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

10. 08/12/12
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

11. 08/12/12
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

12. 08/12/12
Bleeding Tendency
1.Vasculopathy
2.Thrombocytopenia
3.Platelet dysfunction*
4.Coagulopathy
5.Liver damage

13. 08/12/12
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

14. 08/12/12
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

15. 08/12/12
Thrombocytopenia
Mechanism of thrombocytopaenia
Ø Decreased production and increased peripheral
destruction
§Immune complexes on platelets
§Shortened survival of transfused platelets
§Cross reactive platelet antibodies

16. 08/12/12
Platelet dysfunction
Impaired
ADP-induced platelet aggregation
ADP-releasing ability

17. 08/12/12
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.

18. 08/12/12
Classification

Dengue virus infection
Asymptomatic Symptomatic
Simple fever Dengue fever
(DF)
Dengue
haemorrhagic
fever (DHF)
Without
haemorrhage
With unusual
haemorrhage
No shock Dengue shock
syndrome
(DSS)

19. 08/12/12
Classical Dengue Fever
uInfants &Young children
Disease may be undifferentiated
Characterised by fever 1-5 days,pharyngeal inflammation,
 rhinitis & mild cough
Frequently passed undiagnosed
uOlder children and adult
 high grade fever with chills
 occasionally severe back pain precedes the fever
 severe headache, retro-orbital pain
 myralgia,arthralgia

20. 08/12/12
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

21. 08/12/12
 desqumation may occur
 body temperature slightly elevated
 biphasic temperature pattern

22. 08/12/12
Dengue Haemorrhage Fever

1st phase
• fever
 malaise
 vomiting
 headache
 anorexia
 cough,pharyngeal injection
Conjuntival injection
1st phase
• fever
 malaise
 vomiting
 headache
 anorexia
 cough,pharyngeal
injection
Conjuntival injection

23. 08/12/12
2nd phase
Rapid clinical deteroration & collapse (1-5 days)
Cold &clammy extremities*
Weak rapid thready pulse
Warm trunk,flushed face
Restlessness* ,irritability
Midepigastric pain**
Rapid laboured respiration
Faint heart sounds

24. 08/12/12
Patichiae on forehead and extremities
Spontaneous ecchymosis may appear
Easy bruising and bleeding at venepuncture sites

25. 08/12/12
Recovery
• plasma leakage stop,reabsorption of ECF
•general well being,haemodynamically stable
•GIT symptoms subside
•Classical rash-macular/maculopapular rash may appear*
•HR↓
•PLT recover
•WBCs return to N

26. 08/12/12
Dengue recovery rash

27. 08/12/12
Viraemia
HI Ab IgG
Fever ̊C
Symptoms
Haemorrhage
Shock
Platelet 109/L
Hct %
Days after onset of fever

28. 08/12/12
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

29. 08/12/12
Severe plasma leakage
Plueral
Effusion
Ascites
DSS

30. 08/12/12
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/mm )
³
• Haemoconcentration (Hct 20% relative to baseline) or evidence of
≥
plasma leakage

31. 08/12/12
Other clinical manifestations-
 hepatomegaly
 circulatory disturbances (cool extremities, capillary refil
>2 sec, tachycardia)
 a fall in haematocrit following volume replacement

32. 08/12/12
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)

33. 08/12/12
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

34. 08/12/12
Inclinical practice
Dengue FeverDengue FeverDengue FeverDengue Fever

35. 08/12/12
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

36. 08/12/12
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

37. 08/12/12
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

38. 08/12/12
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

39. 08/12/12
• 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.

40. 08/12/12
Atypical presentationS
Acute abdominal pain, diarrhoea
severe gastrointestinal haemorrhage
Severe headache,convulsion, altered conscious level
(encephalitis)
Hepatic failure,Obstructive jaundice,inceresed liver
enzymes,Reye’s syndrome*
Acute renal failure
Haemolytic Uremic Syndrome
Disseminated intravascular coagulation

41. 08/12/12
Laboratory investigations
FBC- WBC-normal/leucopenia
Platelet count
PCV
BUSE,Creatinine
PT/PTT
GxM
Blood culture
Dengue Blot Test

42. 08/12/12
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

43. 08/12/12
Dengue IgMDengue IgMDengue IgMDengue IgM

44. 08/12/12
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

45. 08/12/12
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.

46. 08/12/12
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

47. 08/12/12

48. 08/12/12

49. 08/12/12
§ 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.

50. 08/12/12
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

51. 08/12/12
§ 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/mm with bleeding
³
- platelet count < 10,000 - 20,000/mm
³
Dose -- 10-20 ml/kg or 4 units/m BSA over 1 hour.
²

52. 08/12/12
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/m BSA over 1 hour)
²
- fresh frozen plasma (10-20 ml/kg)
• monitor coagulation profile regularly. i.e. PT, PTT, fibrinogen, D-
dimer, or FPD and platelet counts.

53. 08/12/12
• 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
• H antagonists and Vitamin K
₂

54. 08/12/12
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

55. 08/12/12
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

56. 08/12/12
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

57. 08/12/12
References
Nelson Text Book of Paed (19th edition)
Illustrated Text Book
Paed: Protocol
CPG ,Ministry of Health Malaysia