This document provides information on Dengue virus, the mosquito vector Aedes aegypti, pathogenesis of Dengue fever and severe Dengue, classification of Dengue cases, investigations for diagnosis, and management approaches. It describes Dengue as a major public health problem spread by Aedes mosquitoes in tropical regions. It also covers Dengue virus properties, the four serotypes, and structural and non-structural proteins. Classification systems for Dengue fever, Dengue hemorrhagic fever, and Dengue shock syndrome are presented based on symptoms and lab findings.

1. DENGUE
• Presenter- Dr. Survesh

2. • Major public health problem throughout tropical and subtropical
regions in world
• One of the 17 neglected tropical diseases (WHO)
• Among 11 countries of SEAR- 10 endemic ( except Korea)
• Global scenerio- 2018 outbreak in paraguay, argentina,Several
countries of Western pacific region. Cases also reported in India,
Bangladesh Combodia, Pakistan, Mayanmar, Thailand (WHO)

3. Dengue Virus
• Genus – Flavivirus
• Positive sense single-stranded RNA
• Four Serotypes – DENV type 1 to 4
• Differ in nucleotide sequence from each other
• Each serotype provides specific lifetime immunity, and short-
term cross-immunity
Subtype/ Genotype
DENV-1 : three
DENV-2 : two
DENV-3 : four
DENV-4 : four

4. Three structural protein genes encoding the nucleocapsid of core
protein(C)
• A membrane associated protein (M),
• An envelope protein(E)
• Seven non-structural (NS) proteins – NS1, NS2A, NS2B, NS3,
NS4A, NS4B and NS5

5. The Vector
• Female Aedes mosquito
• Ae. aegypti (M/C)
• Spread disease in urban area
• Ae. Albopictus ( some states)
• Spread disease in rural area
• Other - Ae. polynesiensis &
Ae. niveus.

6. • Usually day biting mosquito but can bite at any time of day
• Breeds in domestic man-made water receptacles
• Ae. Albopictus prefers natural larval habitats
• Survive best b/w 16 - 30 0C and a relative humidity of 60–
80%.
• Also transmits chikungunya, yellow fever and Zika infection
Ae. aegypti

7. Intrinsic
incubation
Period
( 3-14d )
Dengue
During viremia (fever)
Virus multiply
Virus injectd

8. Patho-physiology of Dengue fever/ Severe
Dengue
MOSQUITO BITE
DENGUE VIRUS
INFECTION
INDIRECT INJURY
MECHANISM BY
VIRUS
Production of
antibodies
T CELL Activation
Direct cellular
injury
Endothelial cells
damage
Macrophage
activation
Platelet destruction
SEVERE DENGUE
Shock
Massive bleed
Multi organ failure
Antibody dependent
enhancement
Increased
chemical
mediators
Cytokine storm
Ag-Ab deposition
Complement activation
Immune complex
deposition
VASCULOPATHY
COAGULOPATHY
CYTOPATHY
ORGANOPATHY

9. DENGUE CASE CLASSIFICATION
DENGUE
INFECTION
SYMPTOMATIC ASYMPTOMATIC
MILD MODERATE SEVERE
DF with high risk
Co-morbid conditions
DF with warning signs
And symptoms
Fever of 2-7
days with any
one the
following
Nausea
•Vomiting
•Rash
•Headache
•Retro-orbital
pain
•Myalgia
•Infants
•Old age
•Pregnancy
•Chronic infections
like T.B., HIV ,etc
•Any coagulation
disorder
Immunosuppress-ive
drug, NSAIDS,
Antiplatelets,
Anticoagulation
DF with warning signs and
symptoms
Recurrent vomiting
Abdominal pain/tender
Mild pleural
effusion/ascites
Cold clammy extremity
Lethargy/restlessness
Minor bleed
Rapid pulse
Hypotension
Hepatomegaly
Increase in HCT
Rapid fall in platelets
•Any case of Dengue
fever with one or
more of the
following
1. Shock
2. Severe/multipl-e
organ
impairment
3. Severe bleeding

10. Classification
WHO National guideline
Dengue without warning signs Mild Dengue
( Undifferentiated DF)
Dengue with warning signs Moderate Dengue
+
High risk/Comorbid condition
Or
Warning sign/ DHF 1&2 minor bleed
Severe dengue
1.Severe plasma leak,
2. Severe bleed,
3. Severe organ impairment
Severe dengue
1. DF /DHF + significant bleed
2. DHF with shock (DHF III & IV- DSS)
3. Severe organ involvement (EDS)

11. CASE CLASSIFICATION OF CO-INFECTION (COVID-
19 & DENGUE)
Co-infection
COVID-19 & Dengue
Asymptomatic
both COVID-19 &
Dengue
Symptomatic
Either or Both
Predominant COVID-
19 with mild or mod
Dengue
Dengue & COVID-19
Co-dominant
Both are SEVERE
Predominant Dengue
with mild or mod
COVID-19

12. •Asymptomatic Co-infection
•Symptomatic Co-infection
a) Predominant Corona Viral Diseases (P-CVD)
b) Predominant Dengue Viral Diseases (P-DVD)
c) Co-dominant co-infection (CDCI)
1. P-CVD: a case having LRTI like features cough, fever, SOB,
having CXR or CT changes suggestive of Covid-19 and has
signs and symptoms of mild or moderate dengue fever.
2. P-DVD: a case presenting with fever, headache, retro-orbital
pain later on manifesting respiratory symptoms CT/CXR
changes suggestive of mild or moderate Covid-19
3. CD-CI: concurrent manifestations of respiratory symtoms
cough, sore throat, SOB, and typical dengue symptoms such
as headache, retro-orbital pain, joint pain or pain abdomen.

13. Case Definition
Probable DF/DHF
A case compatible with clinical description of Dengue Fever during
outbreak. i.e.
“Acute febrile illness of 2-7d + > 2 of the following-
i. Headache
ii. Retrorbital pain
iii. Myalgia
iv. Arthralgia
v. Rash
vi. Hemorrhagiac manifestation
AND/OR
• Non-ELISA based NS1 antigen/ IgM positive.
( Due to poor sensitivity and Specificity of RDTs.)

14. Conifrmed dengue Fever
A case compatible with the clinical description of dengue
fever
with at least one of the following
1. Isolation of the dengue virus (Virus culture +VE) from
serum, plasma, leucocytes.
2. Demonstration of IgM antibody titre by ELISA positive in
single serum sample.
3. Demonstration of dengue virus antigen in serum sample by
NS1-ELISA.
4. IgG seroconversion in paired sera after 2 weeks with Four
fold increase of IgG titre.
5. Detection of viral nucleic acid by polymerase chain
reaction (RT-PCR).

15. Dengue Haemorrhagic Fever (DHF)
A probable/confirmed case of dengue
+
Haemorrhagic tendencies evidenced by- one or more of the following
• 1. Positive tourniquet test
• 2. Petechiae, ecchymoses or purpura
• 3. Bleeding from mucosa, gastrointestinal tract, injection sites or other sites
• +
Thrombocytopenia (<1 lac cells/mm3
)
 +
 Plasma leakage- > 1 of the following:
• 1. Arise in average haematocrit for age and sex > 20%
• 2. A more than 20% drop in haematocrit following volume
replacement treatment compared to baseline
• 3. Signs of plasma leakage (pleural effusion, ascites,
hypoproteinemia)

16. Dengue Shock Syndrome
• All the criteria for DHF
+
• evidence of circulatory failure manifested by
• rapid and weak pulse
• narrow pulse pressure (<20mmhg) or hypotension for age ,
• cold and clammy skin
• restlessness

17. Grading the severity of Dengue Infection
DF/DHF GRADE SYMPTOMS/SIGNS LABORTARY
DF Fever with two or more of following
-Headache
-Retro-orbital pain
-Myalgia
-Arthralgia
Leucopenia
Thrombocytopenia
DHF I Above criteria for DF plus positive tourniquet test,
evidence of plasma leakage
Thrombocytopenia:
P lt<20000/cu.mm
Haematocrit rise20% or
more
DHF II Above signs and symptoms plus some evidence of
spontaneous bleeding in skin or other organs (black
tarry stools, epistaxis , bleeding from gums) and
abdominal pain
Thrombocytopenia:
P lt<20000/cu.mm
Haematocrit rise20% or
more
DHF III Above signs and symptoms plus circulatory failure (
weak rapid pulse, narrow pulse pressure,
hypotension with the presence of cold clammy skin
and restlessness)
Thrombocytopenia:
P lt<20000/cu.mm
Haematocrit rise20% or
more
DHF IV Profound shock with undetectable blood pressure or
pulse
Thrombocytopenia:
P lt<20000/cu.mm
Haematocrit rise20% or

18. Tourniquet test
• Inflating a blood pressure cuff
• Midpoint between the systolic and diastolic pressure ( 5
minute )
• > 10 petechiae/inch2
over forearm – Test is considered
positive
• In DHF test usually gives a definite positive test with 20
petechiae or more .
• in DSS(in profound shock)- negative/ mildly positive

20. Course of Dengue illness
1. Febrile phase-
• Fever-biphasic
• 2-7 day
• A/w headache, flushing, rash, pain in retro-orbital area,
joint or bone.
• Rash- after 3rd/4th day of fever

21. 2. Critical phase (Leakage phase)
• After 5 to 6 days of onset of fever
• Plasma leakage usually persists for 36-48 hrs.
• Febrile to afebrile
• Progressive leukopenia f/b thrombocytopenia usually
precede plasma leakage
• Warning sign
• Plasma leakage and high haemoconcentration
• Patients may develop hypotension & shock,
hemorrhage, organ impairment
• TLC may increase as a stress response in severe
bleeding

22. 3.Convalescent phase
(recovery phase)
• After 6-7 days of fever
• last for 2-3 days.
• ECF returns to the circulatory system and signs and symptoms
improve.
• A confluent erythematous rash with round islands of normal
skin might appear
• The rash can be very pruritic and desquamate.
• WBC rise f/b platelet rise
• May develop pulmonary oedema due to fluid overload
(observe pedal edema, neck vein engorgement, resp. distress)

23. Investigations

24. DIAGNOSIS : COMPERATIVE MERITS OF TESTS

25. Investigations :
• CBC ( should be repeated daily untill critical phase is over)
• Dengue specific lab tests
• LFT, RFT, Blood sugar, Serum electrolytes
• CXR :Pleural effusion
• USG Abd,Chest:
• Evidence of free fluid
• Gall bladder wall edema
During convalescence phase- size of platelets markedly increases so
calculated as WBCs (by automated counter) - false thrombocytopenia.
So, Manual platelet count during recovery.
There are various serological test for diagnosis of dengue infection
-Haemagglutination-inhibtion
-Complement fixation
-Neutralisation test
-Indirect IgG ELISA

26. ELISA TEST
 Sensitivity: 90%, Specificity : 97.6%
 Primary dengue infection :
 80% of individuals demonstrate detectable
IgM MAC ELISA antibodies by day 5 and 99%
by day 10-12.
 IgM antibodies peak at two weeks and then
decline over the next 2-3 months.
 IgG antibodies rise later(14 days) and to lower
levels as compared to IgM, then decline
gradually but persist at low levels for life.

27. Aedes Mosquito-
Chickengunya,
Dengue
Yellow fever
Zika virus

28. Indications for domiciliary
management
If patient has only Dengue Fever and on physical examination has
No sign of
• Tachycardia
• Hypotension
• Narrowing of pulse pressure
• Bleeding
• Haemoconcentration
• Followup after 24 hr / any warning sign

29. Admission Criteria

30. Management of dengue
fever
• Symptomatic and supportive
• Bed rest
• Use tepid sponging to keep temperature below 38.5 C.
• Antipyretics- Paracetamol prefer
• Avoid Aspirin/NSAIDS like Ibuprofen, etc because may
cause gastritis, vomiting, acidosis, platelet dysfunction
and severe bleeding

31. • Oral fluid and electrolyte therapy is recommended for
patients with excessive sweating or vomiting.
• Patients should be monitored for 24 to 48 hours after they
become afebrile for development of complications.
• ORS, fruit juice, Coconut water, soup prefer than plain
water to prevent electrolyte imbalance
• If persistent vomiting/ refusal to feed- Start IVF
• Monitor the initial sign of shock.
• Critical period- during the transition from febrile to afebrile
stage.

32. Choice of IVF
• Prefer isotonic fluid
• Crystalloids or Colloids
• No clear advantage to the use of colloids over
crystalloids in terms of the overall outcome.
• If haemodynamic unstable with high hct = 2-3 boluses
crystalloid = Not improove= switch to colloid

33. Normal Saline
• Sodium (154 mmol/L) & Chloride (154 mmol/L)
• Osmolarity - 308 mOsm/L
• Lead to hyperchloremic acidosis which may confused
or aggrevate lactic acidosis from profond shock
• So monitor chloride & lactate
• So when chloride exceed than normal range change
fluid (RL)

34. Ringer lactate
• Lower sodium (131 mmol/L) &chloride (115 mmol/L)
• Osmolality of 273 mOsm/L.
• Not suitable for resuscitation of patients with severe hyponatremia.
• Suitable solution after 0.9 Saline has been given and the serum
chloride level has exceeded the normal range.
• Avoided in liver failure and acidosis

35. COLLOID
• 1. Dextran-based,
• 2. Hydroxyethyl starch
• 3. Gelatin-based solutions.
• Advantage:
• 1. BP restore fast,
• 2. Restore the cardiac index
• 3. Reduce the level of haematocrit faster than crystalloids in
patients with intractable shock and PP <10mmHg

36. Stepwise approach to the management of Dengue

37. Step 1- Overall assessment
1. History :-
 date of onset of fever/ illness
Quantity of oral fluid intake
Diarrhoea
Urine output (frequency, volume and last time of voiding)
Assessment of warning signs
Change in mental state/ seizure/ dizziness
Other relevant history- family/ neighbourhood dengue,
travel to dengue endemic area etc.

38. 2. Physical examination :
Assessment of mental state
Assessment of hydration status
Assessment of haemodynamic status
Checking for quiet tachypnoea/acidotic breathing/ pleural
effusion
Checking for abdominal tenderness/hepatomegaly/ascites;
Examination for rash and bleeding manifestations;
Torniquet test ( repeat if previously negative or if there is no
bleeding).
3. Investigations

39. Step 2- Diagnosis,
assessment of disease
phase & severity
• By history, Physical examination, CBC – Dengue?
• Phase- Febrile/critical/recovery
• Warning sign+/-
• Severity
• Admission/ home

40. Step 3 Management
1. Dengue notification
• Cases of probable and confirmed dengue should be notified
early so that appropriate public health measures can be
initiated.(In dengue endemic countries)
• Laboratory confirmation is not necessary before notification,
but it should be obtained. (WHO)
2. Dengue case management
• Group- A corresponds to DF (acc to national guidelines)
• Group- B corresponds to DHF I&II (acc to national
guidelines)
• Group- C corresponds to DHF III & IV(acc to national
guidelines)

41. WHO handboook

42. DENGUE FEVER
• May be sent home
• Criteria:-
1. Patients who do not have warning signs
and
2. Tolerate adequate volume of oral feed
3. Passes urine once in every 6 hours

43. Treatment:-
 Adequate bed rest;
 Adequate fluid intake;
 Paracetamol for fever
Monitoring includes
Daily review of disease progression
Decreasing WBC, defervescence
Warning signs
Written advice of management

44. DHF I & II

46. DHF III & IV (DSS)
If patient with any of –
1. Severe plasma leakage leading to dengue shock and/or
fluid accumulation with respiratory distress
2. Severe haemorrhages
3. Severe organ impairment (hepatic damage, renal
impairment, cardiomyopathy, encephalopathy or
encephalitis).
 Compensated shock / Hypotensive shock

50. Indication of vasopressor and
inotropes-
As a temporary measure to prevent life threatening
hypotension in dengue shock, during induction for
intubation and while correction of intravascular
volume is vigorously carried out – Dopamine ( DOC )
Cardiogenic shock- d/t myocarditis or ischaemic
heart disease- Dobutamine ( DOC )
In concomitant septic shock- Dopamine or NE (
DOC )

51. Indication of platelet transfusion
 Prophylactic platelet transfusion may be given at level
of <10000/cumm in absence of bleeding manifestations.
 Prolonged shock with coagulopathy and abnormal
cougalogram.
 In case of systemic massive bleed, platelet transfusion
may be needed in addition to red cell transfusion.
Indication of red cell transfusion
• Loss of blood (overt blood) – 10% or more total blood
volume
• Refractory shock despite adequate fluid administration
and declining haematocrit
• Replacement should be given at 10ml/kg body wt at a
time and coagulogram should be done.

54. When to stop IV fluid
 Stop or reduce IV fluid If any one of following :
1. Cessation of plasma leakage;
2. Stable BP, pulse and peripheral perfusion;
3. Haematocrit decreases in the presence of a good pulse
volume;
4. Apyrexia (without the use of antipyretics) for more than 24–
48 hours;
5. Resolving bowel/abdominal symptoms;
6. Improving urine output.
Continuing IV therapy beyond the 48 hours of the critical
phase will put the patient at risk of pulmonary oedema and
other complications such as thrombophlebitis.

55. Criteria for discharge
1. Absence of fever for at least 24 hours without antipyretic
2. No respiratory distress from pleural effusion or ascites
3. Return of appetite
4. Good urine output
5. Minimum of 2 to 3 days after recovery from shock
6. Visible clinical improvement
7. Platelet count > 50,000/mm and improving trend
8. Stable hematocrit without IV fluid

56. Prevention and control
• Preventing mosquitoes from accessing egg-laying habitats by
environmental management and modification
• Disposing of solid waste properly and removing artificial man-
made habitats;
• Covering, emptying and cleaning of domestic water storage
containers on a weekly basis;
• Applying appropriate insecticides to water storage outdoor
containers;
• Using of personal household protection such as window screens,
long-sleeved clothes, insecticide treated materials, coils and
vaporizers;

57. • Improving community participation and mobilization for
sustained vector control;
• Applying insecticides as space spraying during
outbreaks as one of the emergency vector-control
measures;
• Active monitoring and surveillance of vectors should be
carried out to determine effectiveness of control
interventions.

58. Key home message
• Assessement and f/u of patients with nonsevere dengue .
• HCT should be done before and after fluid bolus.
• Clinical assessment of hemodynmaic status before and after
fluid boluses.
• IVF therapy is life saving in dengue shock, but has narrow
therapeutic index.
• Inotropes – use cautiously because there could be
unrecognized hypovolemia/ severe bleeding/ myocardidits.
• Recognise co-infections like malaria, chikunguniya,
leptospirosis, typhus and enteric fever in those with clinical
presentation of prolonged fever, pulmonary haemorrhage,
unexplained renal/liver failure in the absence of shock.

59. Thank you