1. DENGUE
Also known as breakbone fever.
is an infectious tropical disease.
 caused by the dengue virus.
There are four strains of the virus, which are
called serotypes, and these are referred to as
DENV-1, DENV-2, DENV-3 and DENV-4.

2.  All four serotypes can cause the full spectrum of
disease.Infection with one serotype is believed to
produce lifelong immunity to that serotype but
only short term protection against the others.
 The severe complications on secondary infection
occurs particularly if someone previously
exposed to one serotype then contracts other
serotype.

3.  Dengue virus is primarily transmitted
by Aedes mosquitoes, particularly A. aegypti.
 Other Aedes species that transmit the disease
include A. albopictus, A. polynesiensis and A.
scutellaris.
 Humans are the primary host of the virus, but it
also circulates in nonhuman primates.

4. The Vector Aedes aegypti
mosquito
Distinct feature is black
and white stripes on
its body and legs
Bites during the day.
Lays its eggs in clean,
stagnant water.

5. Potential breeding grounds

6. Replication and Transmission of
Dengue Virus
1. Transmitted in saliva
2. Replicates in white blood
cells and lymphatic tissues
3. Circulates in blood
4. Second mosquito ingests
virus with blood
5. Replicates in mosquito
midgut, infects and
replicates in salivary
glands

7. Factors responsible for
resurgence of Dengue
 Population growth
 Unplanned and uncontrolled urbanization
 Inadequate & Interrupted water supply-
leading to storage of water
 Deficient waste water management
 Failure of effective mosquito control measures

8. Pathophysiology of DHF and
DSS
 2 main pathophysiological changes:
 Increased vascular permeability
 Haemostatic Disorder:
 Vascular Changes
 Thrombocytopenia
 Coagulopathy

9. Increased Vascular Permeability
Infected monocytes
Vasoactive mediators
Increased vascular permeability
Hemorrhagic manifestations DHF,

10. Thrombocytopenia
 Infection of human haematopoietic
cells megakaryocytopoieses
 Increased peripheral destruction of
antibody coated platelets
 Platelet destruction in the liver and
spleen.
 Platelet dysfunction(Qualitative
defect)

11. Hemorrhage in Dengue
 Vasculopathy
 Thrombocytopenia
 Platelet dysfunction
 DIC
 Coagulopathy

12. Clinical Manifestations of Dengue
Virus Infection

14.  Classic Dengue Fever is Dengue fever
without warning signs
 Dengue Fever with unusual hemorrhage 
Dengue fever with warning signs
 DHF is Dengue fever with warning signs
 DSS is Severe Dengue
 But rather than separate entities, Now it is

15. Dengue Fever is an acute febrile illness of 2-7 days
duration(sometimes with two peaks) with two or more
of the following manifestations:
 headache
 retro-orbital pain
 myalgia/arthralgia
 rash
 haemorrhagic manifestation (petechiae and positive
tourniquet test) and,
 leukopenia

16.  Dengue Haemorrhagic Fever is a probable
case of dengue and haemorrhagic tendency
evidenced by one or more of the following:
 Positive tourniquet test
 Petechiae, ecchymosis or purpura
 Bleeding from mucosa (mostly epistaxis or
bleeding from gums), injection sites or other
sites
 Haematemesis or melena

17.  Thrombocytopaenia (platelets 100,000/cu.mm or less)
and
 Evidence of plasma leakage due to increased capillary
permeability manifested by one or more of the
following:
– A >20% rise in haemotocrit for age and sex
– A >20% drop in haemotocrit following treatment
with
fluids as compared to baseline
– Signs of plasma leakage (pleural effusion, ascites or
hypoproteinaemia).

18.  Dengue Shock Syndrome (DSS) All the above
criteria of DHF plus signs of circulatory failure
manifested by;
 rapid and weak pulse,
 narrow pulse pressure (< or equal to 20 mm
Hg);
 hypotension for age,
 cold and clammy skin and
 restlessness

19. Grading Of DHF/DSS
 Grade I: Fever accompanied by non-specific
constitutional symptoms; the only haemorrhagic
manifestation is a positive tourniquet test and/or easy
bruising.
 Grade II: Spontaneous bleeding in addition to the
manifestations of Grade I patients, usually in the forms
of skin or other haemorrhages.
 Grade III: Circulatory failure manifested by a rapid,
weak pulse and narrowing of pulse pressure or
hypotension, with the presence of cold, clammy skin
and restlessness.
 Grade IV: Profound shock with undetectable blood

20. Clinical course

21. Disease Course
 Febrile phase lasts 2-7 days
 Look for warning signs
 Mild hemorrhagic manifestations may occur
 Critical phase
 Begins after the fever improves
 usually on days 3–7 of illness
 lasts 24–48 hours
 Progressive leucopenia , thrombocytopenia and
plasma leakage
 Recovery phase:
 Gradual reabsorption of fluid in 48-72hrs

23.  The course of infection is divided into three
phases: febrile, critical, and recovery
 The febrile phase involves high fever, often
over 40 °C (104 °F), and is associated with
generalized pain and a headache; this usually
lasts two to seven days

24.  The disease proceeds to a critical phase, which
follows the resolution of the high fever and
typically lasts one to two days.
 During this phase there may be significant
fluidaccumulation in the chest and abdominal
cavity due to increased capillary permeability and
leakage. This leads to depletion of fluid from the
circulation and decreased blood supply to vital
organs.During this phase, organ dysfunction and
severe bleeding, typically from
the gastrointestinal tract, may occur.

25.  The recovery phase occurs next, with resorption
of the leaked fluid into the bloodstream
 This usually lasts two to three days
 During this stage, a fluid overload state may
occur; if it affects the brain, it may cause
a reduced level of consciousness or seizures.A
feeling of fatigue may last for weeks afterwards.

26. Unusual Manifestations of
Dengue
 Acute liver failure and encephalopathy
which may be present even in the
absence of plasma leakage
 Cardiomyopathy and myocarditis
 Encephalitis and rarely AIDP
 Severe gastrointestinal hemorrhage

27. Clinical Evaluation in Dengue
Fever
 Blood Pressure including pulse pressure
 Pulse rate
 Hydration status
 Capillary refill time
 E/O petechiae, purpura and echymosis
 E/O increased vascular permeability 
Pleural effusion, ascites
 Tourniquet test

28. Differential Diagnosis: Conditions that mimic the
febrile phase of dengue infection
Flu-like syndromes Influenza, measles, Chikungunya,
infectious mononucleosis , HIV
seroconversion illness
Illnesses with a rash Rubella, measles, scarlet fever,
meningococcal infection,
Leptospirosis, Chikungunya,
drug reactions
Diarrhoeal diseases Rotavirus, other enteric
infections
Illnesses with neurological Meningo/encephalitis
manifestations Febrile seizures

29. Differential Diagnosis: Conditions that mimic
the critical phase of dengue infection
Infectious Acute gastroenteritis,
malaria, leptospirosis,
typhoid, typhus, viral
hepatitis, acute HIV
seroconversion illness,
bacterial sepsis, septic
shock
Other Conditions Acute abdomen
Diabetic ketoacidosis
Platelet disorders
Renal failure

30. Laboratory Manifestations
 Hematocrit/ Packed cell volume:
 Crude estimated Hb× 3
 May be altered by bleeding/volume replacement
Increase in Hct by 20%  DHF or plasma leakage
When previous value NA > 45% is significant

31. Other Manifestations
 Peripheral Smear and TLC
 Normal, Leukocytosis Leukopenia
 Lymphocytosis and Atypical lymphocytes
 Thrombocytopenia

32. Other Manifestations
 Hypoalbuminemia
 Hyponatremia
 Mild increase in AST, ALT upto 200-250
 > 250 Hepatic involvement and severe Dengue
 ↑ PT, APTT
 ↑ BUN
 Mild albuminuria
 Reduced Serum Complement

33. Laboratory criteria for
confirmation of dengue fever
 Isolation of the dengue virus from serum or
autopsy samples
 Demonstration of a fourfold or greater change
in reciprocal IgG or IgM antibody titres to one
or more dengue virus antigens in paired serum
samples

34. Dengue NS-1 Antigen
 NS-1 is a non structural protein associated
with intracellular organalles and transported
to the surface by secretory pathways.
 Soluble hexameric form found to circulate in
the blood of patients with acute dengue
 ELISA has been developed for specific
detection of Dengue Type NS-1 Antigen.

36. Treatment
 Management is relatively simple, inexpensive and very
effective in saving lives so long as correct and timely
interventions are instituted.
 Main Pathological Abnormality is LOSS OF PLASMA
VOLUME FROM THE VASCULAR COMPARTMENT
because of increased capillary permeability.
 Loss of plasma volume varies = 5-20%
 Early and effective replacement of plasma losses with
plasma expander or fluid and electrolyte solution results
in a favorable outcome in most cases

37. Management Decisions
 Depending on the clinical
manifestations and other
circumstances, patients may be sent
 Group A : Sent Home
 Group B: In-hospital management
 Group C: Require emergency
treatment

38. Group A Outpatient treatment
Who?
Able to take orally
Pass urine adequately once every 6 hrs
No warning signs particularly atdefervescence of
fever
What to do
Review daily for disease progression ( TLC, Hct
and warning signs)
ORS, juice and other fluids
Paracetamol ( max 4/day)
Instruct to come back in case of warning signs or
decreasing urine output

39. Group B In hospital management
 Warning Signs  Co-existing Conditions
 Abdominal pain or  Pregnancy, Diabetes, renal
tenderness failure, infancy, old age,
 Persistent vomiting obesity, chronic haemolytic
 Clinical fluid accumulation: diseases
PE, ascites  Social Circumstances
 Mucosal bleed
 Lethargy, restlessness
 Liver enlargement >2 cm

40. Dengue without warning signs
Encourage oral fluids
If not tolerated
Start NS or RL at
maintenance rate
No warning Give minimum volume required to
signs patient maintain good perfusion Warning signs or î
improving and urine output Hct
IV fluids for few hrs
switch to oral fluids as Continue IV fluid
soon as possible

41. Obtain Hct
isotonic solutions such as NS or RL
5–7 ml/kg/hr for 1-2 hrs
3–5 ml/kg/hr for 2–4 hr
2–3 ml/kg/hr
Vital signs
worsening Obtain Hct and Hct same or
Hct rising reassess clinically rising minimally
2–3 ml/kg/hr for 2-
4 hrs
Reduce IV fluid as Hct minimum IVF required to maintain
decreases and patient good perfusion and urine output
improves =0.5 ml/kg/hr.
IV Fluid for 24-48hrs

42. Monitoring
 Vital signs and peripheral perfusion 1–4
hourly
 Urine output 4–6 hourly
 Hematocrit before and after fluid
replacement, then 6–12 hourly
 Blood glucose, and other organ functions as
indicated

43. Group C: require urgent treatment in a
high dependency unit
 Early presentation with shock (on days 2 or
3 of illness)
 Severe plasma leakage and/or shock
 Undetectable pulse and blood pressure
 Severe bleeding
 Fluid overload
 Organ impairment (such as hepatic damage,
cardiomyopathy, encephalopathy,
encephalitis)

44. Compensated vs hypotensive shock
Parameter Compensated shock Hypotensive shock
Fluid loss 10-15% >15-20%
Mental status Clear and lucid Change of mental state
Capillary refill Prolonged (>2 sec) Very prolonged, mottled skin
time
Extremities Cool peripheries Cold, clammy extremities
Pulse volume Weak and thready Feeble or absent
Heart rate 100-120 >120
Blood pressure SBP=N, DBP î, PP Hypotension, Unrecordable
decreased, Postural blood pressure, Pulse
hypotension Pressure<20mmHg
Respiratory rate 20-30 >30

45. Management plan of compensated
shock
IV Isotonic Crystalloid
@10ml/kg/hr for 1 hr
Reassess vitals, CRT, Hct, urine output
Yes No
improvement
Hct
IV crystalloid 5–7ml/kg/hr
↑ or >
for 1–2hrs
50%
3–5 ml/kg/hr for 2–4hrs No
10–20
2–3 ml/kg/hr for 2–4hrs ml/kg/hr
Yes Hct low (<45
for 1
in males, <40
hr
in females or
improvement
↓ from
Hct î
Patient improves, baseline
fluid Hct decreases
boluses consider BT Hct stable,↓IVF to
maintenance level Consider occult/
stop after 48hrs significant bleed BT

46. Hypotensive Shock
isotonic crystalloid or colloid 20 ml/kg for 15 min
YES Clinical Improvement NO
Review 1st HCT
Crystalloid/colloid 10
ml/kg/hr for 1 hour
IV crystalloid 5–7ml/kg/hr HCT ↑or high HCT ↓
for 1–2hrs
3–5 ml/kg/hr for 2–4hrs 2nd Bolus: Colloid 10- Consider occult/
2–3 ml/kg/hr for 2–4hrs 20ml/kg over 1hr significant
bleed BT
NO
Patient improves, Improvement Repeat 2nd HCT
Hct stable,↓IVF to
maintenance level HCT ↑ or high HCT ↓
stop after 48hrs
Monitor Hct 6 hrly 3rd Bolus: Colloid 10-
20ml/kg over 1hr
NO
Repeat Hct

47. Criteria for Platelet Transfusion
Platelet counts of dengue patients fluctuate
in an unpredictable manner despite
platelet transfusion
 Stable patients with Platelet Count <10000/cc
 Patients with Platelet Count < 20000/cc with
minor bleeding
 Patients with Platelet Count < 50000/cc with
significant bleeding

48. Role of FFP in Dengue associated
thrombocytopenia
 Antibody concentrates in FFP
block immune mediated platelet destruction
reduction in peripheral platelet destruction
an increase in the platelet count
o Thrombopoeitin activator in FFP directly
stimulates thrombopoeitin in BM

49. Criteria for discharging inpatients
 Absence of fever for at least 24 hours without
the use of antifever therapy
 Return of appetite·
 Visible clinical improvement
 Good urine output
 Stable haematocrit
 Passing of at least 2 days after recovery from
shock
 No respiratory distress from pleural effusion or
ascites