1. Dengue infection
ReviseD Who
guiDelines 2009

2. Dengue viral infection
● The most rapidly spreading mosquito-borne viral
disease in the world
● Dengue virus :
4 serotypes : DEN1, DEN2,DEN3, and DEN4
Family Flaviviridae
Genus Flavivirus
Single stranded RNA virus
● “Asian” genotypes of DEN-2 and DEN-3 :
frequently associated with severe disease
accompanying secondary dengue infections

4. Average annual number of DF and DHF cases reported to WHO, and of countries reporting dengue,
1955–2007

5. Dengue Virus Infection
● Immunity : long lasting in same serotype, partial and
transient to other serotypes
● Primary infection, secondary infection
● Greater risk of serious symptoms in secondary
infection
• Plasma leakage distinguishes dengue fever from
dengue hemorrhagic fever
• Plasma leakage,hemoconcentration and abnormalities
in homeostasis characterize severe dengue

6. Dengue Virus Infection:
Clinical Syndromes
● Undifferentiated fever
● Dengue fever: fever, headache, muscle pain,
nausea/vomiting, rash
● DHF
● DSS
Gr I, II
Plasma leakage
Gr III, IV

7. Definition of Dengue Hemorrhagic
Fever
4 necessary criteria:
• Fever, or recent history of acute fever
• Hemorrhagic manifestations
● Low platelet count (100,000/mm3 or less)
● Objective evidence of “leaky capillaries”
 elevated hematocrit (20% or more over baseline)
 pleural or other effusions
 Fall in hematocrit >20% after I.V Fluids

8. Definition of Dengue Shock Syndrone
4 criteria for DHF
● Evidence of circulatory failure manifested indirectly
by all of the following:
 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

9. WHO classification
● Undifferentiated fever
● Dengue fever (DF)
● Dengue haemorrhagic fever (DHF)
4 severity grades
grades III and IV : dengue shock syndrome (DSS)
● Currently the classification into DF/DHF/DSS
continues to be widely used

10. WHO classification

11. ● patients with non-severe dengue
patients with warning signs
patients without warning signs
● “dengue is one disease entity with different clinical
presentations and often with unpredictable clinical
evolution and outcome”

13. Vectors
● Aedes aegypti
Stegomyia aegypti
(formerly Aedes aegypti)

14. Dengue
● incubation period of 4-10 days
● wide spectrum of illness (most, asymptomatic or
subclinical)
● Primary infection : induce lifelong protective
immunity to the infecting serotype
● Individuals suffering an infection are protected
from clinical illness with a different serotype
within 2-3 months of the primary infection
● no long-term cross-protective immunity

15. Risk factors (determine the severity of disease
and secondary infection)
● Age
● Ethnicity
● Possibly chronic diseases (bronchial asthma, sickle
cell anemia and DM)
● Young children (less able to compensate for capillary
leakage and are consequently at greater risk of
dengue shock)
● Secondary heterotypic infection as risk factor for
severe dengue

16. The course of dengue illness

17. Febrile phase
● High-grade fever, 2–7 days
● facial flushing, skin erythema, body ache, myalgia, arthralgia,
headache and N/V
● Indistinguishable between severe and non-severe dengue cases
● Monitoring for warning signs
● Mild hemorrhagic manifestations : petechiae and mucosal
membrane bleeding (e.g. nose and gums)
● Liver often enlarged and tender after a few days of fever
● The earliest abnormality in CBC : progressive decrease in
WBC

18. The course of dengue illness
Dengue: Guidelines for diagnosis, treatment, prevention and control. WHO 2009

19. Critical phase
● Day 3–7 of illness
● Progressive leukopenia  rapid ↓platelet count plasma
leakage
● Patients without ↑capillary permeability will improve
● Patients with ↑capillary permeability : worse, lose plasma
volume
● The degree of increase above the baseline HCT reflects
severity of plasma leakage
• Shock-WBC may increase in patients with severe bleeding

20. The course of dengue illness
Dengue: Guidelines for diagnosis, treatment, prevention and control. WHO 2009

21. Recovery phase
● Gradual reabsorption of extravascular compartment fluid
takes place in the following 48–72 hours
● Well-being improves, appetite returns, GI symptoms abate,
hemodynamic status stabilizes and diuresis ensues
● Rash : “isles of white in the sea of red” Some may
experience generalized pruritus
● Hct stabilizes or lower due to the dilutional effect of
reabsorbed fluid
● WBC usually rise soon after defervescence but the recovery
of platelet count is typically later than that of WBC

22. Febrile, critical and recovery phases in
dengue
Febrile phase Dehydration; high fever may cause
neurological disturbances and febrile
seizures in young children
Critical phase Shock from plasma leakage; severe
hemorrhage; organ impairment
Recovery phase Hypervolemia (only if iv fluid therapy
has been excessive and/or
has extended into this period)

23. Severe dengue
● Fever of 2–7 days plus any of the following
 Evidence of plasma leakage :
 high or progressively rising Hct
 pleural effusions or ascites
 circulatory compromise or shock (tachycardia, cold and clammy
extremities, capillary refill time > 3 seconds, weak or undetectable
pulse, narrow PP or, in late shock, unrecordable BP)
 Significant bleeding
 Altered level of consciousness (lethargy or restlessness, coma,
convulsions)
 Severe GI involvement (persistent vomiting, increasing or intense
abdominal pain, jaundice)
 Severe organ impairment (acute liver failure, ARF, encephalopathy or
encephalitis, or other unusual manifestations, cardiomyopathy)

24. Diagnosis of Dengue Infection
● Antibody detection
 Hemagglutination Inhibition (HAI)
 ELISA (IgG/IgM)
 Rapid test (IgG/IgM)
● Antigen detection
 NS1 & E/M antigen
● RNA detection
 PCR
● Viral isolation

25. Diagnosis
• Approximate time-line of primary and
secondary dengue virus infections and
the diagnostic methods that can be used
to detect infection

26. Interpretation of dengue diagnostic tests

27. Primary Infection
● NS1 antigen : Day 1 after onset of fever and up to day 9
● IgM antibody :
Day 5 of infection, sometimes as early as Day 3
IgM levels : peak in 2 weeks, followed by a 2 week rapid
decay
Undetectable 2 to 3 months after infection
● Low levels of IgG are detected in the early convalescent
phase, not during the acute phase

28. Secondary Infection
● NS1 antigen : day 1 after onset of fever and up to day 9
● IgM response is more varied
● Usually preceded by IgG and appears quite late during the
febrile phase
● Minority of patients will show no detectable levels of IgM
● May not be produced until 20 days after onset of infection
● High levels of IgG are detectable during the acute phase
● Persist for 30-40 days then decline to levels found in primary
or past infection

29. Atypical neurological manifestations
of dengue
● Neurologic abnormalities : uncommon during dengue
fever
● DHF, encephalopathy is well recognized, from
several factors
cerebral anoxia
cerebral edema
cerebral hemorrhage
hyponatremia
toxicity secondary to liver failure
● Studies in southeast Asia, encephalopathy associated
with classic DF can occur in up to half of the cases

30. Atypical gastrointestinal
manifestations of dengue
• Hepatitis
 Hepatomegaly, jaundice and raised aminotransferase levels
(AST>ALT)
 caused by the dengue virus and ⁄or Hypoxia and tissue ischemia
in cases of shock
• Fulminant hepatic failure
 Severe hepatic dysfunction (ALT and AST >10x normal) was
seen with DHF associated with spontaneous bleeding tendencies
 tends to occur more often in DHF or DSS compared to classic
dengue infections
• Acalculous cholecystitis
• Acute pancreatitis

31. Atypical cardiovascular manifestations
of dengue fever
● uncommon
● Cardiac rhythm disorders :
atrioventricular blocks
atrial fibrillation
sinus node dysfunction
ectopic ventricular beats
● Most are asymptomatic, benign self limiting course with
resolution of infection
● Attributed to viral myocarditis

32. Atypical respiratory manifestations of
dengue
● ARDS
● Pulmonary hemorrhage : thrombocytopenia,
changes in vascular permeability, platelet
dysfunction

33. Dengue myositis
● Dengue fever : break bone fever, severe muscle, joint
and bone pain
● Acute benign myositis : elevated SGOT, SGPT, and
CPK
● Dengue virus infection may also cause persisting,
severe, myositis for weeks

34. Lymphoreticular complications of
dengue
● Dengue virus antigen is found predominantly in cells
of the spleen, thymus and lymph nodes
● DHF, lymphadenopathy is observed in half of the
cases
● Splenomegaly is rarely observed
● Splenic rupture and lymph node infarction in DHF
are rare

35. Management of dengue infection

36. A stepwise approach to the
management of dengue
Step I. Overall assessment
 History : symptoms, past medical and family history
 Physical examination : full physical and mental assessment
 Investigation : routine laboratory and dengue-specific
laboratory
Step II. Diagnosis, assessment of disease phase and severity
Step III. Management
 Disease notification
 Management decisions. Depending on the clinical
manifestations and other circumstances, patients may:
– be sent home (Group A);
– be referred for in-hospital management (Group B);
– require emergency treatment and urgent referral (Group C).

38. Groups A-Patients who are sent
home
• Encourage plenty of oral fluids
• Inform about the warning signs
• Paracetamol for high fever. Never aspirin,ibuprofen or
other NSAIDS

39. Admission criteria

40. Group B-In Patient Hospital
Management

41. Algorithm for fluid management in compensated shock
Compensated shock (SBP maintained but has signs of reduced perfusion)
Fluid resuscitation with isotonic crystalloid 5–10 ml/kg/hr over 1 hour
Improvement
NO
YES
Check HCT
IV crystalloid 5–7 ml/kg/hr for 1–2 HCT↑ or high HCT↓
hours, then:
reduce to 3–5 ml/kg/hr for 2–4 hours; Administer 2nd bolus of fluid Consider significant
reduce to 2–3 ml/kg/hr for 2–4 hours. 10–20 ml/kg/hr for 1 hour occult/overt bleed
Initiate transfusion
If patient continues to improve, fluid can be Improvement with fresh whole
further reduced. blood
Monitor HCT 6–8 hourly.
YES NO
If the patient is not stable, act according
to HCT levels:
If patient improves,
if HCT ↑, consider bolus fluid administration
reduce to 7–10 ml/kg/hr
or increase fluid administration;
for 1–2 hours
if HCT ↓, consider transfusion with fresh
Then reduce further
whole transfusion.
Stop at 48 hours.

42. Algorithm for fluid management in hypotensive shock
Hypotensive shock Fluid resuscitation with 20 ml/kg isotonic crystalloid or colloid over 15 minutes.
Try to obtain a HCT level before fluid resuscitation
Improvement
YES NO
Review 1st HCT
Crystalloid/colloid 10 ml/kg/hr for 1 hour, HCT↓
then continue with: HCT↑ or high
IV crystalloid 5–7 ml/kg/hr for 1– 2 hours; Administer 2nd bolus fluid (colloid) Consider significant
reduce to 3–5 ml/kg/hr for 2–4 hours; 10–20 ml/kg over ½-1 hour occult/overt bleed
reduce to 2–3 ml/kg/hr for 2–4 hours. Initiate transfusion with
Improvement fresh whole blood
If patient continues to improve, fluid can be
further reduced.
YES NO
Monitor HCT 6-hourly. Repeat 2nd HCT
If the patient is not stable, act according
HCT↑ or high HCT↓
to HCT levels:
if HCT ↑, consider bolus fluid administration
Administer 3rd bolus fluid (colloid)
or increase fluid administration;
10–20 ml/kg over 1 hour
if HCT ↓, consider transfusion with fresh
whole transfusion.
Improvement
Stop at 48 hours.
YES NO
Repeat 3rd HCT

43. Treatment of hemorrhagic
complications
● Mucosal bleeding :
 if patient remains stable with fluid resuscitation/replacement,
considered as minor
● Bleeding improves rapidly during recovery phase
● Patients with profound thrombocytopenia :
 strict bed rest and protect from trauma
 not give i.m injections (avoid hematoma)
 prophylactic platelet transfusions for severe thrombocytopaenia in
hemodynamically stable patients not shown to be effective and not
necessary

44. Management of Dengue Infection
● No hemorrhagic manifestations and patient is well-
hydrated:
 home treatment
● Hemorrhagic manifestations or hydration borderline:
 outpatient observation center or hospitalization
● Warning signs (even without profound shock) or
DSS:
 hospitalize

45. Treatment of Dengue Fever
● Fluids
● Rest
● Antipyretics (avoid aspirin and NSAIDs)
● Monitor blood pressure, hematocrit, platelet
count, level of consciousness