This document provides an overview of dengue fever management. It discusses the virus and vector, pathogenesis, clinical manifestations, investigations, severity grading, treatment approaches including fluid management, and discharge criteria. Key points include: dengue is caused by a flavivirus with 4 serotypes transmitted by Aedes aegypti mosquitoes; symptoms range from mild fever to potentially fatal shock; grading disease severity is important to determine management; intravenous fluids and monitoring for warning signs are the main treatment approaches.

1. Management of Dengue Fever
Dr. Dinesh

2. Learning objectives
 Overview of Dengue fever
 Management of Dengue fever
• Practical aspects
• Current guidelines and evidence

3. Introduction
• Acute systemic viral disease
• Established itself globally in both endemic & epidemic
transmission cycles

4. Burden of dengue
 40% of the world’s population is at risk
 390 million dengue infections per year
 An estimated 500 000 people with severe dengue
require hospitalization each year and about 2.5% of
those affected die
WHO South-East Asia Journal of Public Health | January-
March 2014
Nature | vol 496 | 25 april 2013

5. Indian scenario
 36 states/UTs, 35 (all except Lakshadweep) have
reported dengue cases during the last two decades
 Case fatality ratio (CFR – deaths per 100 cases) has
declined from 3.3% in 1996 to 0.3% in 2013

6. The Virus and the vector
 Single stranded RNA virus
• Flaviridae family
 4 serotypes
• DENV-1, DENV-2, DENV-3, and DENV-4
Genetically & antigenically different
• Infection with one serotype confers life long immunity to that
serotype only.
• Vector: female Aedes aegypti, daytime feeder, eggs and
larvae in artificial water containers.

7. Pathogenesis

8. Pathogenesis
Endothelium is the main site

9. Pathophysiology of bleeding
 Thrombocytopenia
 Coagulation pathway defect
• Decrease fibrinogen level
• Increase level of fibrinogen degradation product (FDP)
• Increase level of D-Dimer
• Consumptive coagulopathy (activation of mononuclear
phagocytes)
• Sequestration of platelets

10. Symptoms of Dengue fever
 Clinical features
• Fever : mild to moderate (difficult to differentiate from any
other viral fevers in the initial days)
• Headache
• Retro-orbital pain
• Myalgia
• Arthralgia
• Rash
• Hemorrhagic manifestations
Skin bleed, Malena, Hematemesis, Hematuria

11. Clinical features
 Severe manifestation
• Evidence of plasma leakage
• Shock
• Bleeding
• Organ manifestation
 Life threatening bleeding with out any evidence of
capillary leakage/hemo-concentration
 Multiple organ involvement without bleeding or shock

12. System Atypical Manifestations
CNS Involvement Encephalopathy, Encephalitis, IC Bleed, Febrile seizures
GI Involvement Acute hepatitis, Cholecystitis, Cholangitis, Acute Pancreatitis,
Renal Involvement Acute Renal Failure, ATN, HUS
Cardiac
Involvement
Arrhythmia, Pericardial effusion, Myocarditis
Respiratory Pleural effusion, Pulmonary hemorrhage, Pulmonary edema
Expanded Dengue Syndrome

13. Manifestation In Infants
 High fever
• Lasting for 2-7days
 Commonly present as
• URTI, GI symptoms (diarrhea) & febrile convulsions
 Difficult to differentiate from other common febrile
illness in febrile stage
 Hematocrit may not rise in plasma leaks
• Basal values itself may be low
• Concomitant iron deficiency
 Liver involvement commoner

15. Clinical severity
Grade Features
DF Fever of 2-7 days with two or more of following
Headache, Retro orbital pain, Myalgia,
Arthralgia with or without leukopenia, thrombocytopenia and no evidence of
plasma leakage
DHF 1 D F + positive tourniquet test and evidence of plasma leakage
platelet count < 100000/ cu.mm
Hct rise >20% over baseline.
DHF 2 DF1 +
some evidence of spontaneous bleeding in skin /organs and abdominal pain
platelet count less <100000/ cu.mm
Hct rise >20% over baseline
DHF 3
(DSS)
DF2+
circulatory failure
platelet count less <100000/ cu.mm
Hct rise >20% over baseline
DHF 4
(DSS)
Profound shock with undetectable blood pressure or pulse
platelet count l<100000/ cu.mm
Hct rise >20% over baseline

16. Natural course of dengue
Critical phase:
• 1-4days after
defervesence
• Plasma leakage and
hemoconcentration
• Pleural effusion and
ascites
• Organ dysfunction
• Metabolic
abnormalities

17. Dengue classification

18. Investigations
 Complete Blood Count
• End of febrile phase, leukopenia (WBC ≤ 5000 cells/mm3),
lymphocytosis, thrombocytopenia ≤ 100,000 cells/mm3
 Liver Function Tests
• Elevated AST/ALT
 Serum Glucose
• Hypoglycemia
 Serum Electrolytes and Calcium
• Hyponatremia in DHF/DSS in critical phase

19.  BUN, Creatinine
• Severity of illness
 Coagulation Profile
• Prolonged partial thromboplastin time (PTT) in 50% of
DHF/DSS
• Prolonged thrombin time (TT) in 10%-20%
 Chest X-ray
• Pleural effusion
Investigations

20. Viral Antigen and Antibody Response

21. Test Significance Recommendation
ELISA-based NS1
antigen tests
NS1 is abundant in early phase Diagnosis of acute
infection
IgM capture (MAC-
ELISA)
Appears after 2-3 days
Lasts for 2-3 months
Epidemiological
surveillance in non
endemic area
Diagnosis >5 days of
illness
IgG ELISA To differentiate between
primary and secondary infection
Not as a diagnostic tool
RT-PCR Current standard to detect the
virus
Not useful as a diagnostic
tool
Confirmatory tests

22. Rapid Diagnostic Tests
• NS1 And IgM/IgG Antibodies
• Quick
• 100-200 Rupees Per Kit
• Not Recommended In National
Vector Borne Disease Control
Program

23. NVBDCP Recommendations
 First 5 days (ELISA based) NS1 based assays
 >5 days (ELISA based ) IgM based assays

24. Step wise approach
 Step 1: Overall assessment
• History
• Physical examination
• Investigation
 Step 2: Diagnosis
• Assessment of disease phase and severity
 Step 3: Management
• Disease notification
• Management decisions

25. History
• Onset of fever
• Associated symptoms and
warning signs
• Oral intake
• Urine output
• Change in mental
status/seizures
Examination
• Vitals
• Respiratory
distress/effusion
• Abdominal tenderness,
hepatomegaly, ascites
• Rash
• Bleeding manifestations
Assessment

26. Step 2

27. Group A: Home based care
 Patients who do not have warning signs
 Able to
• Tolerate adequate volumes of oral fluids
• Pass urine at least once every 6 hours
• Don’t belong to high risk category

28. Group A
 Advice for
• Adequate rest & fluid intake
• Paracetamol, 10-15mg/kg (3 gram max. Per day)
• Patients with >3 days fever should be called daily for review
until they are out of critical phase
• To monitor at home
Temperature pattern
Volume of fluid intake
Urine output volume and frequency

29. Group A: Monitoring
 Daily review for disease progression
• Decreasing WBC, Rise of hematocrit and fall in platelets
count.
• Defervescence
• Warning signs (until out of critical period)
• Advice for immediate return to hospital if development of
any warning signs
• Written advice of management

30. Group B: In Hospital Care
 With warning signs/Risk factors
• Obtain a reference HB/TLC/Hematocrit (Hct)
• Isotonic solutions (0.9% saline, RL)
5-7ml/kg for 1-2 hrs
Then 3-5ml/kg for 2-4hrs and then 2-3ml/kg or less as
per response
IV fluids usually needed only for 24-48hrs
• Reassess clinical signs and Hct
 Target Urine output- 0.5ml/kg/hr

32. Group C: Severe Dengue
• With compensated shock
• With hypotensive shock

33. Compensated shock

34. Decompensated shock

35. Checklist for Non Improvement in Shock
• Persistent plasma leakage
• External/Internal bleeding
• Hypoglycemia/Hypocalcemia
• Myocardial involvement
• Persistent metabolic acidosis
• Acute coronary syndromes
• Dengue associated haemophagocytic syndrome

36. Which fluid ?
• Crystalloids (NS/RL) or Colloids

37. • Three RCTs
• Different fluid resuscitation regimes among children with dengue
shock syndrome
• No clear advantage to the use of colloids over crystalloids in terms
of hospital stay and mortality
• Colloids might be the preferred choice if the blood pressure has to
be restored urgently (e.g., in those with pulse pressure < 10 mm Hg)
• Colloids have been shown to restore the cardiac index faster than
crystalloids in severe dengue
Comparison of Three Fluid Solutions for
Resuscitation in Dengue Shock Syndrome

38. Fluids in Dengue
 Repeated large volumes of 0.9% normal saline
• Lead to hyperchloremic acidosis
• Confused with lactic acidosis from prolonged shock
• Monitoring the chloride and lactate levels
 Serum chloride level exceeds the normal range
• Advisable to change to other alternatives such as Ringer’s Lactate
 Colloid solutions including gelatin, dextran & starches
• Impact on coagulation
• Renal functions

39. WHO Guidelines
 Crystalloids are the preferred choice of fluids in the
initial resuscitation of dengue shock
 Colloid may be considered
• In intractable shock (Pulse pressure <10mmhg)

40. Criteria for stopping IV Fluid
• Stable BP, pulse and peripheral perfusion
• Hematocrit decreases in the presence of a good
pulse volume
• Resolving bowel/abdominal symptoms
• Signs of cessation of plasma leakage
• Improving urine output

41. Who are at risk for bleeding ?
 Profound/prolonged/refractory shock
 MODS
 Severe and persistent metabolic acidosis
 H/O NSAIDs intake
 Pre-existing peptic ulcer disease
 Intramuscular injection

42. Platelet Transfusion: Threshold
 Significant clinical bleeding
 Prolonged shock with coagulopathy
 Prophylactic:
• <10,000/mm3 in absence of clinical manifestations

43. What not to in Dengue Fever ?

44. Criteria for Discharge
• Afebrile at last 24 hours without antipyretics
• No respiratory distress
• Platelet > 50,000/mm3
• Return of appetite
• Urine output > 1 ml/kg/hour

45. DENGVAXIA (DENGUE VACCINE)
• The first dengue vaccine, DENGVAXIA (CYD-TDV) by
Sanofi Pasteur, was first registered in Mexico in
December, 2015.
• Live attenuated tetravalent dengue vaccine that has
been evaluated as a 3-dose series on a 0/6/12 month
schedule.
• It has been registered for use in individuals 9-45 years
of age living in endemic areas.

46. THANK YOU

47. DENGUE ENCEPHALITIS
• The spectrum of neurological manifestations seen
in dengue has been classified into 3 categories.
1. Due to neurotropic effect of the virus –
encephalitis, meningitis, myositis and myelitis.
2.Due to the systemic complications of infection- encephalopathy,
stroke and hypokalemic paralysis.
3.Due to post-infectious complications- encephalomyelitis, optic
neuritis and Guillain Barré syndrome.

48. DENGUE ENCEPHALITIS
The main symptoms of dengue encephalitis are
• headache,
• Seizures
• Altered consciousness
• Typical symptoms of dengue fever like
myalgias, rash and
bleeding are seen in less than 50% of
encephalitis cases.

49. Diagnosis
The criteria for dengue encephalitis are:
i) fever;
ii) acute signs of cerebral involvement;
iii) presence of anti-dengue IgM antibodies or
dengue genomic material in the serum and/or
cerebrospinal fluid;
iv) exclusion of other causes of viral encephalitis
and encephalopathy

50. Neuroimaging
MRI is the modality of choice which shows-
• cerebral edema,
• white matter changes,
• necrosis
• brain atrophy.
• Encephalitis features in brain (Hyperintense
areas) can be seen in global pallidus,temporal
lobes ,thalamus hippocampus,pons and spinal
cord.