2. Dengue fever , also known as breakbone fever, is an
infectious tropical diseases caused by the dengue
virus.
Dengue virus belongs to flaviviridae family. The
flaviviridae are positive sense , single stranded RNA
viruses.
3. AEDES MOSQUITODengue is transmitted by several species
of mosquito within the genus aedes
principally Ae. Aegypti
Distinct feature is black and white stripes
on its body and legs
Bites during the day.
4. Ae. aegypti females will often feed on several persons during a
single blood meal and, if infective, may transmit dengue
virus to multiple persons in a short period of time even if
they only probe without taking blood.
Ae. aegypti prefers to lay its eggs in artificial water
containers, to live in close proximity to humans, and to feed
on people rather than other vertebrates.
Desert coolers, Drums, Jars, Pots, Buckets, Flower vases,
Plant saucers, Tanks, Cisterns, Bottles, Tins, Tyres, Roof
gutters, Refrigerator drip pans,�Cement blocks
5. With increasing spread of the vector mosquito
throughout the tropics and sub tropics, large areas of
the world have become vulnerable to the introduction
of dengue viruses.
7. An infection can be acquired via a single bite. A female
mosquito that takes a blood meal from a person
during the initial 2-10 days of dengue infection ,
becomes itself infected with the virus in the cells
lining its gut.
8. About 8–10 days later, the virus spreads to other tissues
including the mosquito's salivary glands and is
subsequently released into its saliva. The virus seems
to have no detrimental effect on the mosquito, which
remains infected for life.
9. The virus has four different types; infection with one
type usually gives lifelong immunity to that type, but
only short-term immunity to the others. Subsequent
infection with a different type increases the risk of
severe complications
10. FACTORS RESPONSIBLE FOR THE
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
11. RISK FACTORS
Virus strain (DENV 2 and 3)
Pre-existing anti-dengue antibody Immune
enhancement
Previous infection
Maternal antibodies in infants
Hyperendemic transmission: Two or more serotypes
circulating simultaneously at high levels .
Endemic: only one serotype prevalent in the area
Age: more severe in children
Ethnicity: Africans have less severe illness
Chronic diseases (bronchial asthma, sickle cell anaemia and
diabetes mellitus)
13. PERSONS EXPOSED TO DENGUE VIRUS
SERUM ANTI BODIES NEUTRALIZE THE VIRUS OF
SAME TYPE.
SUBSEQUENT INFECTION --ANTIBODIES FORM
COMPLEXES BUT DO NOT NEUTRALIZE THE NEW VIRUS.
THESE COMPLEXES FACILLITATES THE ENTRY OF THE VIRUS INTO THE
MONONUCLEAR CELLS BY BINDING WITH THE Fc RECEPTORS.
15. Thrombocytopenia
Infection of human haematopoietic cellsinhibits
megakaryocytopoieses
Increased peripheral destruction of antibody coated
platelets
Platelet destruction in the liver and spleen.
Platelet dysfunction(Qualitative defect)
17. WHO 1997/2011 CASE DEFINITION OF DENGUE AND LEVELS OF
SEVERITY
DENGUE FEVER
Probable
An acute febrile illness with 2 or more of the following:
1. Headache
2. retro-orbital pain
3. Arthralgia
4. Rash
5. Hemorhagic manifestations
6. Leukopenia AND
Supportive serology( a reciprocal antibody titre≥1280, a comparable
IgG assay elisa titer or (+) Igm antibody on a late course or acute
convalescent phase serum specium.
Confirmed: by lab criteria
18. DENGUE HEMORRHAGIC FEVER
Fever ,or history of fever lasting for 2-7 days
Hemorrhagic tendencies evidenced by at least one of the
following
1. positive tourniquet test
2. petechiae, ecchymosis, purpura
3. bleeding from the mucosa, GIT, injection sites or other
location.
4. hematemesis or malena
Thrombocytopenia (≤1,00,000 cells/cumm)
19. Evidence of plasma leakage due to increase vascular
permeability manifested by atleast one of the following:
1. a rise in hematocrit ≥20% above average for age sex and
population.
2. a drop in the hematocrit following volume replacement
treatment ≥20% of baseline.
3. signs of plasma leakage such as pleural effusion, ascites
and hypoproteinemia.
20. DENGUE SHOCK SYNDROME
All of the four criteria for DHF must be present plus evidence
of circulatory failure manifested by
Rapid and weak pulse, AND
Narrow pulse pressure (<20mmHG)
OR
Hypotension for age AND
Cold clammy skin and restlessness
22. Tourniquet test
Blood pressure (BP) cuff should be inflated on the upper arm of
the patient to a point mid way between systolic and diastolic
pressure for 5 min, and the number of resulting petechiae in 2.5
cm2 on the volar aspect of the forearm just distal to the
antecubital fossa should be counted
A test is considered positive when 20 or more petechiae are
observed in the 2.5 cm2 / inch2
Test reflects both capillary fragility and thrombocytopenia
May not be positive in severe shock associated with DSS
Earlier DHF, now part of DF without warning signs
23. 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
24. DISEASE COURSE
FEBRILE PHASE
Sudden onset high grade fever.
Non specific constitutional symptoms like headache,
myalgia, arthralgia, facial flushing etc.
It lasts for 2-7 days.
Mild hemorrhagic manifestation may occur.
Monitor for the warning signs.
25. CRITICAL PHASE
The warning signs marks the beginning of the
critical phase(plasma leakage).
Patients condition worsens when the Temperature
drops to 37.5- 38 C.
It usually lasts for 24-48 hours.
Progressive leucopenia, thombocytopenia are present.
26. RECOVERY PHASE
Gradual reabsorption of fluid in 48-72 hours.
Bradycardia are common during this stage.
WBC count usually starts to rise before platelet count
improves.
Signs of fluid overload.(respiratory distress from
massive pleural effusion and ascites, pulmonary
oedema or congestive heart failure.
27. STEP-WISE APPROACH
STEP I
• Overall assessment
• History-physical exam-routine lab-dengue specific lab
STEP II
• Assess disease phase and severity
STEP III
• NOTIFICATION
• Management decision (A/B/C)
28. Laboratory Manifestations
Hematocrit/ Packed cell volume:
Measured by capillary centrifugation or automated
analyzers
Crude estimate= Hb× 3
Capillary values may be 5-10% higher than venipuncture
values
May be altered by bleeding/volume replacement
Increase in Hct by 20% DHF or plasma leakage
When previous value NA > 45% is significant
29. Other Manifestations
Peripheral Smear and TLC
Normal, Leukocytosis Leukopenia
Lymphocytosis and Atypical lymphocytes
Thrombocytopenia
Automated Platelet Counters : Giant platelets;
pseudothrombocytopenia (EDTA induced platelet
aggregates).
between day 3 - 8 following the onset of illness
30. Other Manifestations
Hypoalbuminemia
Hyponatremia
Mild increase in AST, ALT upto 200-250
> 1000 Hepatic involvement and severe Dengue
↑ PT, APTT
↑ Urea / Creatinine
Mild albuminuria
Reduced Serum Complement
31. Role of Ultrasonoraphy in Dengue
Fluid accumulation:
Pleural effusion: Right side or B/L
Ascites
Pericardial effusion
Acalculous Cholecystitis
GB wall thickening and pericholecystic fluid
>3mm ↑ severity
Hepatosplenomegaly
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 IgG or
IgM antibody titres to one or more dengue virus antigens
in paired serum samples
Demonstration of dengue virus antigen in autopsy tissue,
serum or CSF samples by immunohistochemistry,
immunofluorescence or ELISA
Detection of dengue virus genomic sequences in autopsy
tissue serum or cerebrospinal fluid samples by polymerase
chain reaction (PCR).
34. Serological tests for dengue are not much helpful for the
clinical management except in a minority of cases where the
diagnosis is in doubt. It is mostly done to establish the
diagnosis for epidemiological information.
35. Dengue NS-1 Antigen
NS-1 is a non structural protein associated with
intracellular organalles and transported to the surface
by secretory pathways.
More efficient with acute phase sera of primary
infection as compared to secondary dengue infection
Soluble hexameric form found to circulate in the blood
of patients with acute dengue
ELISA has been developed for specific detection of
Dengue NS-1 type Antigen.
36.
37. Serological tests available for
Dengue
Hemagglutination inhibition (HI) test
Neutralization test
Indirect immunofluorescent-antibody test
Complement fixation
Dot blotting
Western blotting
Rapid immunochromatography test
ELISA
38. MAC-ELISA ( IgM-Antibody
Capture ELISA)
Cross reactivity between other circulating flaviviruses.
Can not be used to determine the type of virus.
antigens used for this assay are derived from the
dengue virus envelope protein
MAC-ELISA has a sensitivity and specificity of
approximately 90% and 98%, respectively but only
when used five or more days after onset of fever.
39. IgG ELISA
Utilizes the same viral antigens as the MAC ELISA
Similar principle
10 Dengue: negative IgG in the acute phase and a positive
IgG in the convalescent phase of the infection
20 Dengue: positive IgG in the acute phase and a 4 fold
rise in IgG titer in the convalescent phase
Requires paired sera with at least 7 day interval between
the 2 samples
41. Hemagglutination inhibition (HI)
test
Requires paired sera with at least 7 day interval between
the 2 samples
Cross reaction with other flaviviruses
HI assay does not differentiate between IgM and IgG
10 dengue: low-undetectable levels in acute sera HI
titer < 1:1280
20 dengue: 4 fold rise between 2 samples with peak titers
> 1:2560
42. Rapid Tests
Various tests are available
Most based on “Immunochromatography”
Give results in 30-60 minutes.
Various commercial kits are available
Variable sensitivity and specificity
Accuracy in testing for IgM antibodies is lower than
ELISA.
However, their accuracy in testing for IgG antibodies
seems to be greater than ELISA
Can not be used for reporting or in surveillance
43. 10 Dengue vs 20 Dengue
10 Dengue 20 Dengue
NS-1 High Low
IgM High Low /undetectable
IgM/IgG ratio >1.2 <1.2
HI titer < 1:2560 > 1:2560
IgG paired sample
ELISA
-ve +ve Both sample +ve
with 4 fold rise
44. Final Interpretation of Diagnostic tests
Highly suggestive
IgM + in a single serum sample
IgG + in a single serum sample with a HI titre of 1280 or greater
Confirmed
PCR +
Virus culture +
IgM seroconversion in paired sera
IgG seroconversion in paired sera; or
Fourfold IgG titer increase in paired sera
45. 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.
Early and effective replacement of plasma losses with
plasma expander or fluid and electrolyte solution results in
a favorable outcome in most cases.
47. Management Decisions
Depending on the clinical manifestations and
other circumstances,
Group A : Sent Home
Group B: In-hospital management
Group C: Require emergency
treatment
48. Group A Outpatient treatment
Who?
Able to take orally
Pass urine adequately once every 6 hrs
No warning signs particularly at defervescence of fever
What to do
Review daily for disease progression ( TLC, Hct and warning
signs)
ORS, juice and other fluids
Paracetamol (max 3gm/day)
Instruct to come back in case of warning signs or decreasing
urine output
49. Group B In hospital management
Warning Signs
Abdominal pain or
tenderness
Persistent vomiting
Clinical fluid accumulation:
PE, ascites
Mucosal bleed
Lethargy, restlessness
Liver enlargement >2 cm
↑ Hct with
thrombocytopenia
Co-existing Conditions:
Pregnancy, Diabetes, renal
failure, infancy, old age,
obesity, chronic haemolytic
diseases.
Social Circumstances
50. Dengue without warning signs
Encourage oral fluids
Start NS or RL at
maintenance rate
If not tolerated
Give minimum volume required to
maintain good perfusion
and urine output
*IV fluids for few hrs
*switch to oral fluids as
soon as possible
Continue IV fluid as per next slide
No warning
signs
patient
improving
Warning signs or
↑ Hct
51. 3–5 ml/kg/hr for 2–4 hr
isotonic solutions such as NS or RL
5–7 ml/kg/hr for 1-2 hrs
Obtain Hct
2–3 ml/kg/hr
Obtain Hct and reassess
clinically
Hct same or
rising minimally
2–3 ml/kg/hr for 2-4 hrs
Minimum fluid to maintain
good perfusion and urine
output =0.5 ml/kg/hr.
Reduce IV fluid as Hct decreases
and patient improves
*IV Fluid for 24-48hrs
Vital signs
worsening;
Hct rising
52. 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
Till the patient is out of critical period
53. 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)
54. Fluid resuscitation
Fluid resuscitation in severe dengue is different from fluid
administration.
Larger volumes of fluids administered for a limited period
Goal is to improve central and peripheral circulation and
maintain end-organ perfusion.
Degree of intravascular volume deficit in dengue shock varies.
Input/output ratio is of no utility for judging the adequacy of
fluid resuscitation.
Instead of 5-7ml/kg/hr give @ 10-20 mkl/kg/hr, if HCT dec
consider BT, if same, then maintenance dose of IVF, if increas
then give bolus again.
55. Hypotensive Shock
isotonic crystalloid or colloid 20 ml/kg for 15 min
Clinical ImprovementYES
Crystalloid/colloid 10 ml/kg/hr
for 1 hour
IV crystalloid 5–7ml/kg/hr for 1–
2hrs
3–5 ml/kg/hr for 2–4hrs
2–3 ml/kg/hr for 2–4hrs
Patient improves, Hct
stable:
↓IVF to maintenance
level stop after 48hrs
Monitor Hct 6 hrly
NO
Review HCT
HCT ↑or high
2nd Bolus: Colloid 10-
20ml/kg over 30 min to 1hr
Improvement
NO
Repeat 2nd HCT
HCT ↑or high
3rd Bolus: Colloid 10-
20ml/kg over 1hr
Consider occult/
significant bleed
BT
HCT ↓
HCT ↓
Repeat Hct
NO
56. Monitoring of patient in severe
Dengue (DSS)
Alertnesss level and comfort
Vital signs and peripheral perfusion: 15–30 minutes
1–2 hourly
Urine output: hourly 1–2 hourly
Hematocrit: before and after fluid boluses until stable and
then 4-6 hrly
ABG: 30 min to 1 hrly until stable and then as indicated
Blood glucose: before fluid resuscitation and repeat as
indicated
KFT, LFT as indicated
57. Interpretation of Hematocrit
↑ Hct + Unstable vitals Active Plasma Leakage
↑ Hct + stable vital signs no need for extra IV fluids
↓ Hct + stable vitals + adequate output
haemodilution and/or reabsorption
↓ Hct + unstable vitals Continued hemorrhage
58. Fluids to be used in Dengue
Crystalloids: use isotonic solutions
NS ( Osm= 308mOsm/L)
suitable option for initial fluid resuscitation
large volumes hyperchloraemic acidosis
RL ( Osm= 273mOsm/L)
may not be suitable for resuscitation of patients with
severe hyponatremia
Can be used after initial fluid resuscitation with NS
avoid in liver failure and in patients taking metformin
59. Fluids to be used in Dengue
Colloids:
Dextran
Starch
Gelatin Haemaccel
Benefits:
Distributed in vascular compartment
Increase oncotic pressure
Disadvantages:
May effect coagulation (vWF/Factor VIII)
Allergic reactions
May cross into the interstitium Reverse osmosis
60. WHO-2012:
Use Crystalloids first ( NS preferred as initial
resuscitation fluid over RL).
Colloids may be used in hypotensive patients who
do not respond to a bolus of crystalloids or
PP<10mmHg.
Colloids may also be used in patients with
obvious fluid overload but vital signs are not
stable and high Hct.
Avoid hypotonic fluids like 5% D, N/2
*N Engl J Med 2005; 353:877-889
61. When to stop IV fluids
IV Fluid therapy can be stopped when Hct drops to 45%
in adults, 40% in children and adult females and 35% in
infants.
Stable blood pressure, pulse and peripheral perfusion
Afebrile for more than 24–48 days (without the use of
antipyretics)
Resolving bowel/abdominal symptoms
Improving urine output
62. Risk factors of major bleeding
Prolonged/refractory shock;
Hypotensive shock and renal or liver failure and/or severe
and persistent metabolic acidosis;
Use of NSAIDs
Pre-existing peptic ulcer disease
Anticoagulant therapy
Any form of trauma, including intramuscular injection.
63. Clinical indicators of severe
bleeding
Persistent and/or severe overt bleeding in the presence of
unstable haemodynamic status
↓ Hct + unstable vitals after fluid resuscitation
Refractory shock that fails to respond to consecutive fluid
resuscitation of 40-60 ml/kg
Hypotensive shock with low/normal hematocrit before
fluid resuscitation
64. Treatment of haemorrhagic
complications
5–10ml/kg of fresh-packed red cells
Or 10–20 ml/kg of fresh whole blood (FWB)
Fresh Whole blood is preferred
Where possible Use fresh blood/Packed Cells
In cases of severe bleeding, use of blood is
preferable instead of platelets and FFP
65. Issues in Platelet transfusion
Platelet rich plasma (PRP) when managing
thrombocytopenia
Platelets present a strong antigenic stimulus
Evoking an exaggerated immune response
Further immune mediated platelet destruction
66. Criteria for Platelet Transfusion
Platelet counts of dengue patients fluctuate in an
unpredictable manner despite platelet transfusion
Prophylactic platelet transfusions are not necessary
Stable patients with Platelet Count <10,000/cc*
Patients with Platelet Count < 20,000/cc with minor
bleeding
Patients with Platelet Count < 50,000/cc with significant
bleeding
*Lyons V, Triulzi D. Transfusion Medicine Update September 1999.
67. Platelet Concentrate vs Apheretic
Platelets
Platelet Concentrate(Random Donor) Apheretic Platelet(SDP)
5 x 1010/unit 3.5 x 1011
1 unit increases by 5k-10k/µL 1 unit increase by 30k-60k
Loss of platelet function little loss of platelet function
Differential centrifugation from freshly
drawn blood units
by platelet-pheresis technique
Cheaper Costly
More exposure to TTI Less exposure to TTI
68. Dose of Platelet Transfusion
If using Platelet Concentrate:
10-20 ml/kg or 4 units/m² BSA over 1 hour
If using apheretic platelet:
1 unit of apheretic platelet over 1 hr
WHO does not recommend use of FFP in bleeding in
Dengue
69. Fluid Overload: Causes
Excessive and/or too rapid intravenous fluids
Incorrect use of hypotonic rather than isotonic crystalloid
solutions
Inappropriate use of large volumes of intravenous fluids in
patients with unrecognized severe bleeding
Inappropriate transfusion of FFP, PRP and Cryoprecipitate
Continuation of intravenous fluids after plasma leakage has
resolved
Co-morbid conditions: CHD, IHD, COPD,CKD
71. Management of fluid overload
O2 Inhalation
Critical Phase
Out of Critical
Phase
Hemodynamic
ally stable
Reduce IV
fluids
Avoid diuretics
Shock with
low Hct
May have occult
bleeding slow
cautious BT
Reduce IV fluids
May give furosemide
0.1–0.5 mg/kg OD or BD
Shock with
high Hct
Consider
colloids
72. Criteria for discharging inpatients
Absence of fever for at least 24 hours without the use of
antipyretic 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
Platelet count >50 000 per mm3.
73. Prevention of mosquito bite
• Install Iron Mesh at doors and
Window
• Sleep under mosquito net
• Use mosquito repellant coil
/mats
• Apply mosquito repellant oil/
cream on skin
• Cover your body with clothes as
much as possible
• Allow indoor insecticide spray
by health staff
• tetravalent, live attenuated,
recombinant vaccine, which is
currently in Phase III clinical
trials.
