C07 P02 DENGUE CLI FEATURES.presentation

Ppt

2. Clinical Manifestations of Dengue
and
Dengue Hemorrhagic Fever

3. Dengue virus infection
Asymptomatic infection Symptomatic infection
Undifferentiated
fever
Dengue
fever
Dengue
haemorrhagic
fever
Dengue shock
syndrome

4. Undifferentiated Fever
May be the most common manifestation of
dengue.
Prospective study found that 87% of
students infected were either asymptomatic
or only mildly symptomatic.
Other prospective studies including all age-
groups also demonstrate silent transmission.

5. Clinical Characteristics
of Dengue Fever
Fever
Headache
Muscle and joint pain
Nausea/vomiting
Rash
Anorexia
Retro orbital pain
Facial flushing
Fever Day
0 1 2 3 4 5 6
39.5
39.0
38.5
38.0
37.5
37.0
Temperature (degrees Celsius)

6. Fever
Sudden onset
High fever (39-40C)
Also called
-saddle back fever
-7 days fever
-break bone fever
Rash
Pin point ,fleeting type
Maculo-papular rash

7. Risk Factors Reported for DHF
Virus strain
Pre-existing anti-dengue antibody
•previous infection
•maternal antibodies in infants
Age
Higher risk in secondary infections
Higher risk in locations with two or more
serotypes circulating simultaneously at high levels
(hyper endemic transmission).

8. Increased Probability of DHF
Hyperendemicity
Increased circulation
of viruses
Increased probability
of secondary infection
Increased probability of
occurrence of virulent strains
Increased probability of
immune enhancement
Increased probability of DHF
Gubler & Trent, 1994

9. Hypothesis on Pathogenesis
of DHF (Part 1)
Persons who have experienced a dengue
infection develop serum antibodies that can
neutralize the dengue virus of that same
(homologous) serotype.

10. Neutralizing antibody to Dengue 1 virus
Dengue 1 virus
Homologous Antibodies Form
Non-infectious Complexes
Non-neutralizing antibody
Complex formed by neutralizing antibody and virus

11. Hypothesis on Pathogenesis
of DHF (Part 2)
In a subsequent infection, the pre-existing
heterologousantibodies form complexes
with the new infecting virus serotype, but
do not neutralize the new virus.

12. Non-neutralizing antibody to Dengue 1 virus
Dengue 2 virus
Heterologous Antibodies Form
Infectious Complexes
Complex formed by non-neutralizing antibody
and virus

13. Hypothesis on Pathogenesis
of DHF (Part 3)
Antibody-dependent enhancement
is the process in which certain
strains of dengue virus, complexed
with non-neutralizing antibodies,
can enter a greater proportion of
cells of the mononuclear lineage,
thus increasing virus production.

14. Heterologous Complexes Enter More
Monocytes, Where Virus Replicates
Non-neutralizing antibody
Dengue 2 virus
Complex formed by non-neutralizing
antibody and Dengue 2 virus

15. Hypothesis on Pathogenesis
of DHF (Part 4)
Infected monocytes release vasoactive
mediators, resulting in increased vascular
permeability and hemorrhagic
manifestations that characterize DHF and
DSS.

16. Pathophysiology of Dengue
Haemorrhagic Fever
Sec. infection by same serotype
Ab neutralizes
Sec. infection by other serotypes
Ab complexes but can’t neutralize
Ag-Ab complex enters monocytes
Virus replicates
Virus load increases
Monocyte ruptures

17. Activation of complement
Endothelial injury
Platelet aggregation
DIC
Decreased platelets
Decreased clotting
Protein loss
Altered hemodynamic forces
Release of cytokines & viruses
Widespread formation of Ag-Ab complexes
Fluid deposition in various
cavities
Bleeding tendencies

18. Decreased intravascular volume
Peripheral vasoconstriction
cyanosisrestlessness
Decreased blood supply to brain

19. Clinical features of DHF
IP: 4-6 days
High fever
Head ache
Anorexia
Tenderness at the Rt costal margin
Facial flushing
Maculopapular rash
Haemorrhagic manifestations

20. Hemorrhagic Manifestations
of Dengue
Skin hemorrhages:
petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow

21. Petechiae

22. Haematoma

23. Clinical Case Definition for
Dengue Hemorrhagic Fever
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm
3
or less)
Objective evidence of “leaky capillaries:”
•elevated hematocrit (20% or more over baseline)
•low albumin
•pleural or other effusions
4 Necessary Criteria:

24. Clinical manifestations of Dengue
Shock Syndrome
Restlessness
Lethargy
Cyanosis
Hepatomegaly
Pleural effusion
Ascitis
GI bleeding

25. Pleural effusion

26. Clinical Case Definition for
Dengue Shock Syndrome
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.

27. Four 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)

28. Tourniquet Test
Inflate blood pressure cuff to a point
midway between systolic and diastolic
pressure for 5 minutes.
Positive test: 20 or more petechiae per 1
inch
2
(6.25 cm
2
).
Pan American Health Organization: Dengue and Dengue
Hemorrhagic Fever: Guidelines for Prevention and Control.
PAHO: Washington, D.C., 1994: 12.

29. Positive Tourniquet Test

30. Danger Signs in
Dengue Hemorrhagic Fever
Abdominal pain -intense and
sustained.
Persistent vomiting.
Abrupt change from fever to
hypothermia, with sweating and
prostration.
Restlessness or somnolence.

31. Clinical Laboratory Analyses in
57 Hospitalized Cases of DHF,
Puerto Rico, 1990 -1991
* Average result in the tested cases
Test with Abnormal ResultFrequency* Mean Result (Range)
Thrombocytopenia
Platelet count 57/57 (100%) 45,980 (9 -99,000)
Increased Capillary Permeability
Hemo concentration 0.2034/57 (59.6%) 0.26 (0 -1.0)
Low serum protein 18/51 (35.3%) 6.3 (3.8 -8.3)
Low serum albumin 35/52 (67.3%) 3.5 (2.3 -4.9)

32. Unusual Presentations
of Severe Dengue Fever
Encephalopathy
Hepatic damage
Cardiomyopathy
Severe gastrointestinal hemorrhage

33. Diagnosis

34. Differential Diagnosis of Dengue
Influenza
Measles
Rubella
Malaria
Typhoid fever
Leptospirosis
Meningococcemia
Rickettsial infections
Bacterial sepsis
Other viral hemorrhagic fevers

35. Laboratory Tests
in Dengue Fever
Clinical laboratory tests
•CBC--WBC, platelets, hematocrit
•Albumin
•Liver function tests
•Urine--check for microscopic hematuria
Dengue-specific tests
•Virus isolation –serotype detection
•Serology

36. Collection and Processing of
Samples for Laboratory Diagnosis
Type of
Specimen
Time of
Collection
Type of
Analysis
Acute-phase
blood
(0-5 days after onset)
When patient presents;
collect second sample
during convalescence
Virus isolation
and/or serology
Convalescent-phase
blood
(6 days after onset)
Between days 6 and 21
after onset
Serology

37. Virus Isolation:
Cell Culture

38. Virus Isolation:
Mosquito Inoculation

39. Virus Isolation:
Fluorescent Antibody Test

40. ELISA Plate

43. Thank you