Dengue diagnosis, treatment, prevention and control

1. Dengue: Diagnosis,
Treatment, Prevention
and Control
Fadel Muhammad Garishah, MD
Department of General Internal Medicine

2. Overview
 Dengue is the most rapidly spreading mosquito-borne viral disease in the
world.
 Dengue has a wide spectrum of clinical presentations, often with
unpredictable clinical evolution and outcome
 In Indonesia, where more than 35% of the country’s population lives in
urban areas, 150 000 cases were reported in 2007 (the highest on record)
with over 25 000 cases reported from both Jakarta and West Java.
 The case-fatality rate was approximately 1%.

3. Countries/Areas at Risk of
Dengue Transmission

4. Clinical Course
 dengue is one disease entity with different clinical
presentations and often with unpredictable clinical
evolution and outcome
 Symptomatic dengue virus infections were grouped into
three categories: undifferentiated fever, dengue fever (DF)
and dengue hemorrhagic fever (DHF).

8. Suggested dengue case classification and levels of severity

9. Dengue Virus (DENV)
 Dengue virus (DEN) is a small single-stranded RNA virus
comprising four distinct serotypes (DEN-1 to-4).
 It belongs to the genus Flavivirus, family Flaviviridae.
 Among them, “Asian” genotypes of DEN-2 and DEN-3 are
frequently associated with severe disease accompanying
secondary dengue infections

10. Tiger Mosquito
 Aedes mosquitoes, principally Ae. aegypti, is a tropical and
subtropical species widely distributed around the world,
mostly between latitudes 35 N and 35 S.
 The immature stages are found in water filled habitats,
mostly in artificial containers closely associated with
human dwellings and often indoors.

11. The Host
 an incubation period of 4--10 days
 Individual risk factors determine the severity of disease and
include secondary infection, age, ethnicity and possibly
chronic diseases (bronchial asthma, sickle cell anaemia and
diabetes mellitus).
 Young children in particular may be less able than adults to
compensate for capillary leakage and are consequently at
greater risk of dengue shock.
 Studies in the American region show the rates of severe
dengue to be lower in individuals of African ancestry than
those in other ethnic groups.

12. Immunology
 Primary infection is thought to induce lifelong protective immunity to the
infecting serotype but with no long-term cross-protective immunity to other
serotypes
 non-neutralizing, cross-reactive antibodies raised during a primary infection
bind to epitopes on the surface of a heterologous infecting virus and facilitate
virus entry into Fc-receptor-bearing cells.
 The increased number of infected cells is predicted to result in a higher viral
burden and induction of a robust host immune response that includes in
inflammatory cytokines and mediators, some of which may contribute to
capillary leakage
 Activation of infected monocytes and T cells, the complement system and the
production of mediators, monokines, cytokines and soluble receptors may also
be involved in endothelial cell dysfunction.
 During a secondary infection, cross-reactive memory T cells are also rapidly
activated, proliferate, express cytokines and die by apoptosis in a manner that
generally correlates with overall disease severity.

13. Hematology
 Thrombocytopenia may be associated with alterations in
megakaryocytopoieses by
 the infection of human hematopoietic cells and impaired
progenitor cell growth,
 resulting in platelet dysfunction (platelet activation and
aggregation),
 increased destruction or
 consumption (peripheral sequestration and consumption).
 Hemorrhage may be a consequence of the
thrombocytopenia and associated platelet dysfunction or
disseminated intravascular coagulation.

14. Keyword
 a transient and reversible imbalance of in inflammatory
mediators, cytokines and chemokines occurs during severe
dengue, probably driven by a high early viral burden, and
leading to dysfunction of vascular endothelial cells,
derangement of the hemocoagulation system then to
plasma leakage, shock and bleeding.

15. Clinical Course of DVI

16. Phases of Dengue
 Febrile Phase
 Critical Phase
 Recovery Phase

17. Febrile Phase
 High grade fever (>3 first day)
 Headache
 Generalized body aches
 Myalgia
 Arthralgia
 Anorexia
 Epigastric Pain
 Nausea/vomitus
 Facial flushing
 Skin erythema
 Sore throat
 injected pharynx
 conjunctival injection
 Petechiae
 Epistaxis
 Gum bleeding
 GI/vaginal bleeding

18. Critical Phase
 Defervescence, restless, lethargy
 Raising hematocrit (sign of plasma leakage)
 Progressing leukopenia
 Progressing thrombocytopenia and thrombocytopathy
 Mild ascites/pleural effusion proved by RLD Xray
 Cold clammy extremities
 Prolonged shock leads to: metabolic acidosis, disseminated
intravascular coagulation, organ impairment (hepatitis,
encephalitis, myocarditis), severe bleeding

19. Improvement after defervescence
 Non severe dengue
 Some cases deteriorate to severe dengue

20. Recovery Phase
 24-48 h post critical phase, following gradual reabsorption
of extravascular fluid by 48-72 hours after
 Hemodynamic issues stabilized
 Gastrointestinal symptoms abate
 WBC and platelets rise up

21. Primary Care Provider
 Distinguishing dengue from other causes of fever
 Recognizing plasma leakage and initiating appropriate fluid
therapy

22. Overall Assessment
 History:
 fever analysis,
 symptoms,
 PMH,
 FH
 Physical Examination
 Laboratory Studies
 CBC
 Serology

23. Management
 Be sent home
 Be referred to hospital
 Emergency treatment

24. Referral centers
 Early shock (2-3 days of illness)
 Severe plasma leakage
 Undetectable and blood pressure
 Severe bleeding
 Fluid overload
 Unusual complications: hepatic damage, cardiomyopathy,
encephalopathy, encephalitis

25. History
 Date of onset of ever/illness
 Oral intake
 Assessment for warning signs
 Diarrhea
 Change in mental state/seizure
 Urine output
 Others: family/neighborhood/school mate with dengue,
pregnancy, obesity, diabetes, hypertension, camping

26. Physical
 General Appearance
 Consciousness level
 Vital signs
 Hemodynamic assessment
 Bleeding signs incl. torniquet test

28. Laboratory Studies
 Full blood count
 Hematocrit base
 WBC count
 Platelet count
 Clinical chemistry: LFT, Glucose, Electrolytes, RFT, BGA,
lactate, cardiac enzymes

29. Diagnostic
 Living in endemic area
 Fever over 3 days
 Epigastric pain
 Platelet lower than 100.000/uL
 WBC < 4000/uL
 NS1
 Serology: Rapidtest, ELISA
 Hemaglutination Inhibition Test
 PCR

30. Laboratory Studies

31. Laboratory Studies

32. Patient A:
Dengue Fever/DHF Grade I
 No warning signs
 Adequate oral intake
 Adequate urine output
 Have bed rest
 Plenty fluids
 Acetaminophen 10-15mg/kg/4-6 hours

33. Patient B: DHF Grade II-III
 Warning signs (+)
 Admission
 Maintenance Fluid (Normal Saline/Lactate’s Ringer)
 Monitoring urine output, warning signs

34. Patient C: DHF Grade IV/Dengue
Shock Syndrome/Expanded
Dengue Syndrome
 Warning signs (+)
 Severe plasma leakage
 Severe bleeding
 Severe organ impairment (expanded dengue syndrome)

35. Reduced Perfusion
Maintained Systolic Pressure
Crystalloid 5-10cc/kg 1 hour
Improvement
5-7cc/kg/hr 1-2 hr
3-5cc/kg/hr 2-4 hr
2-3cc/kg/hr 2-4 hr
Maintained max 48 hr
Hct Monitoring/6-8 hr
No Improvement
HCt Check
HCt Increase
Bolus 10-20cc/kg 1 hr
Improvement
5-7cc/kg/hr 1-2 hr
3-5cc/kg/hr 2-4 hr
2-3cc/kg/hr 2-4 hr
Maintained max 48 hr
Hct Monitoring/6-8 hr
HCt decrease
Suspect Bleeding
Fresh
Whole
Blood
No Improvement
HCt Check

36. Better Perfusion
 Decreasing HR
 Improving BP
 Pulse volume
 Warm extremities
 Capilary refill < 2’’
 Alertness
 Urine output > 0,5cc/kg/hr

37. Hypotensive Shock
Crystalloid/Colloid 20cc/kg 15 minutes
Hct High, no Improvement
Colloid 20cc/kg 30min-1hr
Hct High, no Improvement
Colloid 20cc/kg 30min-1hr
Hct Low, no Improvement
FWB Transfusion
Stable
7-2 cc/kg/hr
Hct monitor/6hr
Hct High, no Improvement
Same Cycle
Consider Vasopressors/Inotropes
Stable
7-2 cc/kg/hr
Hct monitor/6hr
Hct Low, no Improvement
FWB Transfusion
Stable
7-2 cc/kg/hr
Hct monitor/6hr
Hct Low, no Improvement
FWB Transfusion

38. Bleeding Risks
 Prolonged/refractory shock
 Hypotensive shock despite adequate fluid therapy (40-
60cc/kg)
 Given NSAIDs
 Preexisting Peptic Ulcer Disease

39. Blood Products
 5-10cc/kg PRC
 10-20cc/kg FWB

40. Fluid Overload
 Signs: respiratory distress, wheezing, pleural effusion,
ascites
 Oxygen
 Stopping IVFD
 Furosemide 0.1-0.5mg/kg/12-24 hr

41. Differentials
 Influenza,
 measles,
 chikungunya,
 infectious mononucleosis,
 leptospirosis,
 typhoid,
 typhus,
 gastroenteritis,
 Other virus infections

42. Admitting

43. Discharging

44. Mosquito Breeding Site

45. Vector Control
 Environmental modification: piped water
 Environmental manipulation: breeding sites, ovitrap
 Human behavior: repellent, windows closed, bed nets
 Chemical larvicides, insecticides
 Biological: fish, copepods, Wolbachia