3. Dengue Fever: Epidemiology
• Dengue Fever: A mosquito borne viral disease, is a severe,
flu-like illness, transmitted by the infective bite of Aedes
aegypti mosquito with Seasonality of July to November
• WHO estimates : Globally
50-100 million cases in more than 100 endemic
countries of Africa, America, Eastern Mediterranean,
South-East Asia and Western Pacific
DHF: 250,000 – 500,000 cases & 24,000 deaths
30-fold increase in global incidence over the last five
decades.
4. • Factors responsible for Rapid Spread:
-unprecedented population growth
-unplanned urbanization
-inadequate water and waste management
-increased distribution and density of vectors
-lack of effective control of vectors
• Dengue viruses cause symptomatic infections or
asymptomatic seroconversion.
• Patients with asymptomatic infection are viremic and thus
may be a source of infection
Dengue Fever: Epidemiology
5. Pooled estimate of Sero-prevalence in
general population
56.9%
Case fatality 2.6%
Proportion of Primary & secondary
Dengue infection among lab confirmed
cases
42.9 : 57.1
Distribution of predominant and co-
circulating DENV serotypes
In India, all serotypes
are circulating
(DENV-2 & DENV-3
most common)
In India
• In West Bengal, all serotypes are circulating
• In 2019 Most common Circulating Serotypes:
-DENV-2 & DENV-3 in South Bengal
- DEnV-1 in North Bengal
• Circulating Serotypes keep on changing over time
6. Etiology
• The dengue virus is a single stranded, small
enveloped RNA virus
• They possess 4 distinct serotypes DEN1, DEN2,
DEN3 & DEN4
• They possess antigens that cross react with YF, JE &
WN viruses
7. Genomic Structure of Flaviviruses
• Dengue virus is a positive-stranded encapsulated RNA virus
• Belongs to the flavivirus genus of the Flaviviridae family.
• The genomic RNA is approximately 11 kb in length
• Composed of three structural proteins:
• The NS proteins are assumed to be involved in the
replication of viral RNA: NS1 Ag used for diagnosis
8. Pathogenesis and Immunity of Dengue
• After inoculation the virus spreads rapidly to the regional
lymph nodes
• Replicates primarily in phagocytic macrophages and
monocytes- also possibly in various lymphocytes populations as
well
• Viraemia begins 3-7 days after infection/inoculation
• Onset of effective Ab responses –normally resolution of
viraemia and recovery
• Immunity is Ab mediated
• After an acute phase of infection by a particular serotype there
is lifelong immunity to the infecting serotype but only
temporary and partial protection against the other three
serotypes and secondary or sequential infections are possible
after variable time period.
• The waning cross reactive heterotypic Ab is responsible for
DHF
9. Antigen-Antibody Response in Dengue
Infection
• High concentrations of this antigen can be detected in
patients with primary and secondary dengue infections up to
9 days after the onset of illness with the newer kits
• Antigen detection in the acute stage of secondary
infections can be compromised by pre-existing virus–IgG
immune-complexes.
10. DENV
SPECIFIC
HOST CELLS
R
viremia
LUNG
THYMUS
SPLEEN
LYMPH NODES
Mononuclear Phagocyte System
(Macrophage and Macrophage like cells)
BLOOD
MONONUCLEAR
CD4+ NK
CD8+
DENDRITIC
CELLS
ENDOTHELIAL
CELLS
LIVER
TNF-α
IFN-
γ
Other cytokines*
First line
of
defense
Replication
and infection
Nitric
Oxide
(NO)
Endothelium
lining dysfunction
Increased vascular
permeability
DHF/DSS
C
yto
lysis
C
yto
lysis
Pathogenesis
12. Immunopathogenesis of DHF / DSS –
Cytokine overproduction
Serotype cross-reactive antibodies from the previous infection bind to
virions without neutralization and enhance the entry of virus into
monocytes
The number of virus-infected monocytes increases
As a result, the level of T-cell activation is markedly increased, reflecting
the increased antigen presentation
Increased frequency of dengue-virus-specific T cells in secondary infection-
These T cells produce cytokines such as IFN-ƴ, IL-2, and TNF·, and lyse
dengue-virus-infected monocytes
13. Immunopathogenesis – Complement
activation
• The risk of DHF/DSS is higher in secondary infections with dengue
virus of serotype 2 compared to the other serotypes.
• Apparently, viral load is also a contributing factor in the
development of DHF/DSS
• The complement cascade is activated by a virus-antibody complex
as well as by several cytokines to release C3a and C5a that also
have direct effects on vascular permeability.
• The synergistic effects of IFN-ƴ, TNF·, and activated complement
proteins trigger plasma leakage from capillaries in secondary
dengue
• DHF develops rapidly, usually over a period of hours, and resolves
within 1–2 days in patients who receive appropriate fluid
resuscitation.
15. • Symptomatic dengue infection is a systemic and dynamic disease
having wide clinical spectrum that includes both severe and non-
severe clinical manifestations.
• The incubation period lasts for 5 to 7 days and the onset of the
illness is abrupt.
• Common presenting symptoms include high-grade fever,
headache, retro-orbital pain, myalgia, arthralgia, nausea,
vomiting and rash. The symptoms usually last for 2-7 days.
• Three phases: febrile, critical and recovery.
• The severity of the disease becomes apparent during
defervescence (transition from the febrile to the afebrile phase).
• Increased capillary permeability, that lasts approximately for 24
to 48 hours, is more common in secondary dengue infections.
Dengue Fever
17. Febrile or Viremic Phase Critical Phase Recovery Phase
• Lasts for 2 to 7 days.
• Symptoms:
Headache, Myalgia,
Arthralgia, Retro-orbital
pain
• Children: anorexia, N/V
• Progressive decrease in
WBC (TC<5000/ cumm) &
mild Thrombo-cytopenia
+/- mild hemorrhage
• Positive Tourniquet Test
• Warning signs
between days 3 and 7
of illness.
• Increased capillary
permeability causing
plasma leakage.
•A Rising Hematocrit
is the earliest sign of
plasma leakage.
• Gradual re-absorption
of extra-vascular
compartment fluid takes
place in following 48 to
72 hours.
• general well-being
improves
• Isles of white in the sea
of red
• Fluid Overload may
happen
Dehydration, High
fever neurological
disturbances & febrile
seizure
Shock from plasma
leakage: severe
hemorrhage and organ
impairment
Hypervolemia and acute
pulmonary oedema
Course of Dengue illness
19. Clinical Evaluation
• History taking
• Clinical examination
• Investigations
• Diagnosis and assessment of disease phase
and severity
20. Patient’s history to be asked
1. Date of onset of fever (date is
preferable to the number of days
of fever)
6. Shortness of breath
2. A history of dengue fever
among households and neighbor,
living in or recent travel to a
dengue endemic region
7. Bleeding from any orifice, any
bleeding spot on skin/mucosa
3. History of chills, rash and facial
flush
8. Reduced urine output, cold
peripheries
4. Retro-orbital headache,
arthralgia, malaise
9. Profuse sweating, postural
dizziness, blurring of vision5.
5. Persistent vomiting/diarrhea,
pain abdomen
10. Yellowish discoloration of skin
and mucosa, altered sensorium
Step 1: A patient’s history to be asked
21. Assess hydration
status from
history
Ask 3 golden questions
1. Oral fluid intake-quantity and types of fluids
2. Urine output-quantify in terms of frequency and
estimated volume and time of most recent voiding
3. Types of activities performed during this illness
(e.g., can the patient go to school, work, market,
etc.)
These questions, though not
specific to dengue, give a good
indication of patient’s hydration
status and how well the patient
copes with his illness.
• Other fluid losses-such as vomiting
or diarrhea
• Presence of warning signs,
particularly after the first 72 hours of
fever
Other Relevant History
• Medications (including non-
prescription or traditional medicine)
in use and the time they were last
taken
• Risk factors
22. Step 2: Clinical examination: Assess
Temperature
Peripheral Perfusion: Hold the
patient’s hand and assess
peripheral perfusion by the Color,
Capillary refill time, Temperature of
the extremities, Pulse Volume and
Pulse Rate (CCTVR)
Blood pressure
Tachypnea/Acidotic
breathing/Pleural effusion
Mental state
Abdominal
tenderness/Hepatomegaly/ Ascites
Maculopapular or macular
confluent Rash; Conjunctiva
Tourniquet test (repeat if previously
negative)
Hydration status Examine Top Sheet
23. Warning signs in dengue fever
•Bleeding: epistaxis, scanty haemoptysis, hematemesis, gum
bleeding, black coloured stools, excessive menstrual bleeding,
dark-coloured urine or haematuria.
•Lethargy and/or restlessness
•Sudden behavioural changes
•Convulsions.
•Difficulty in breathing or palpitation or breathlessness.
•Persistent vomiting >3 times a day.
•Severe abdominal pain
•Postural hypotension - dizziness.
•Pale, cold clammy extremities.
•Not able to drink and no urine output for 4-6 h or urine output
less than 0.5 ml/kg/h.
Warning and danger signs and symptoms of
dengue fever
24. Warning and danger signs and symptoms of
dengue fever
Additional danger signs for clinicians
•Enlarged and/or tender liver
•Rising haematocrit together with rapid fall in platelet count.
•Metabolic acidosis.
•Derangement of liver/ kidney function tests.
•Pleural effusion/ ascites/ gall bladder oedema clinically or by
imaging.
KEY POINTS:
•Warning signs between days 3 and 7 of illness.
•Increased capillary permeability causing plasma leakage is
the main pathophysiology.
•A rising haematocrits the earliest sign of plasma leakage
25. Criteria Score Interpretation
GCS <15 1 • Score: 0-1
Not high risk
Continue management as
appropriate
• Score: 2-3
High risk of poor outcome
Assess for evidence of Organ
Dysfunction
Respiratory Rate (RR)
≥22 breath /min
1
Systolic Blood Pressure
(SBP) ≤100mm Hg 1
qSofa Score
Quick Sequential Organ Failure Assessment Score
• Implication:
To determine organ function or rate of failure
To screen risk of poor outcome
26. NS1 Antigen Detection
Serology: The study of the diagnosis of disease by measuring
antibody levels in serum is referred to as serology.
IgM-captured enzyme-linked immunosorbent assay
(MAC ELISA)
Haemagglutination-inhibition
Neutralization
Indirect IgG ELISA
Rapid test
RT-PCR and Real time RT PCR
Virus Isolation and Culture
Laboratory Diagnosis of Dengue Virus
Laboratory Diagnosis of Dengue Virus
27. Step 3 : Investigation for Diagnosis
From onset of Illness to 5 days of
fever
Virus detected in serum, Plasma,
circulating blood cells and tissues
Virus isolation
Nucleic Acid Detection
NS1 Antigen Detection
From 6th Day onwards
Antibody Detection
First antibody to appear –IgM
Secondary Antibody – IgG
Any one of the NS1Ag and IgM assays is confirmatory
for diagnosis of Dengue if done through ELISA
method
28. Collection, storage and transportation of
samples
• 3-5 ml clotted blood to be collected in screw caps vials
• All Samples to be transported in cold chain
• Appropriate labeling is most important
• Serum must be separated before transportation
• No Frozen whole blood
• Other Required Investigations: As per Clinical Judgement
-Complete Blood Count -CXR (PA & Lateral Decubitus)
-Blood Sugar -USG abdomen including IVC
-LFT& RFT diameter
-Serum Amylase/Lipase - ABG
-Serum Electrolytes -Bicarbonate or lactate
-Cardiac enzymes -Electrocardiogram (ECG)
29. Sensitivity and Specificity
• IgM ELISA:
Nearly all patients (93%) develop detectable IgM 6 to 10
days after the onset of fever
However, because IgM circulates for up to three months or
longer, its presence might not be diagnostic of a current
illness. Hence laboratory results should be interpreted in
correlation with clinical findings
In general, 10% false negative and 1.7% false positive
reactions have been observed.
• NS1Ag ELISA: ??
30. • Rapid NS1 Ag/ IgM-based dengue diagnostic tests have
been developed as a quick and easy method for use at
point of care or bedside.
• Usually have variable sensitivity in comparison to
ELISA based Tests.
• False-positive results frequent in patients with malaria,
leptospiral infections, COVID, immune disorders such
as rheumatoid and lupus or previous dengue infections.
Hence, Rapid diagnostic tests are avoided.
Rapid diagnostic tests are preferably avoided
31. RT-PCR for Dengue Virus Detection
Conventional RT-PCR
•This is more specific for Dengue virus detection
•To cover the window period before IgM can be detected in
primary infection
•Usually, RNA can not be detected after the formation of the
antibodies
RT-PCR in real time fashion
•More advantages in respect to rapidity, quantitative, lower rate of
contamination, and high sensitivity/specificity
Used to detect the Serotype of Dengue virus from NS1Ag
+ve Samples : Done in Apex Referral Laboratories
32. Complete Blood Count (CBC):
-Should be done at the first visit to establish the baseline hematocrit
-A normal CBC during the first 72 hours of illness does not exclude dengue
-The hematocrit in the early febrile phase can be used as the patient’s own
baseline
-Should be repeated after the 3rd day of illness or with warning signs and
with risk factors for severe disease
-In the absence of baseline haematocrit, age-specific population
haematocrit levels can be used as a surrogate during the critical phase
-HCT value of >40% in female adults and children aged <12 years and
>45% in male adults should raise the suspicion of plasma leakage.
-Rapid decrease in platelet count with concomitant rising haematocrit as
compared to the baseline, is suggestive of progressive plasma
leakage/critical phase
-Leucopenia usually precedes the onset of the critical phase
Other Investigations:
-AST levels are higher as compared to ALT
-Degree of rise of AST and ALT are significantly more in DHF and DSS, as
compared to DF
Some Diagnostics Clarifications
33. Other Haematological criteria
• Leukopenia with Relative Lymphocytosis
• Thrombocytopenia (100,000 cells or less per mm3)
(A decreasing WBC and platelet count makes the diagnosis
of dengue very likely)
• Haemoconcentration (>20% rise in average haematrocrit for
age and sex)
• > 20% drop in haematocrit following volume replacement
treatment as compared to baseline.
34. 1. Positive Tourniquet Test
2. Relative bradycardia
3. Leucopenia with Relative lymphocytosis
4. Specific Aspartate Aminotransferase [AST] elevation and
Serum Lipase elevation
Distinct clinical and initial parameters to
differentiate from other viral aetiologies
35. Disease
Classical signs and
symptoms
Differentiating feature of Dengue
Influenza
Fever, headache,
myalgia, malaise, RTI
Upper respiratory symptoms like rhinitis and
cough may be present in both. Patients with
dengue usually have gastrointestinal symptoms
(i.e. abdominal discomfort, vomiting and
sometimes diarrhea) during the febrile phase.
Malaria
High fever with chill and
rigor,
Hepatosplenomegaly,
features of complication
sometimes
Splenomegaly and prolonged fever should
prompt the consideration of malaria.
Thrombocytopenia may be present in both,
further diagnostic studies are needed.
Typhoid
fever
Fever, headache, malaise,
anorexia, abdominal
pain, rose spots,
hepatosplenomegaly,
altered mental status
Splenomegaly and prolonged fever should
prompt the consideration of typhoid. Severe
break bone feature usually absent .Very difficult
to differentiate complicated typhoid fever from
DSS; diagnostic studies are needed.
Differential Diagnosis
36. Lepto-
spirosis
Initial phase-fever
Headache
Chill
Myalgia
transient rash &
non-purulent
conjunctival discharge
Second phase-
meningitis,
renal disease,
liver failure
Jaundice more often associated with
leptospirosis, but ocular pain, arthralgia and
diarrhea could be present as well, whereas
dengue may be associated with elevated liver
enzymes and mild jaundice. Pulmonary
hemorrhage is a particular form of
leptospirosis without jaundice that may be
confused with severe dengue though
uncommon in dengue. Evidence of plasma
leakage would suggest the diagnosis of
dengue. Fever, thrombocytopenia, raised
liver enzyme, renal involvement are common
features in both.
Meningo-
coccemia
Fever, Chills, Malaise,
Prostration, Rash
(macular, maculopapular,
petechial)
can progress to fulminant
with DIC, purpura, shock
& death
DHF and shock due to dengue is sometimes
undistinguishable from meningococcemia.
Diagnostic studies are needed.
37. Chikun-
gunya
Fever
Rash
Arthralgia
Arthritis
Headache
While fever, arthralgia, rash, malaise and
leucopenia are common in both
Chikungunya and dengue, symmetric
arthritis of small joints is pathognomonic of
the former and bleeding tendency and
pronounced thrombocytopenia are more
frequent in dengue.
Scrub
typhus
Fever, chill
Myalgia
Headache
Lymphadenopathy
Rash, usually maculo-
popular. Vital organ
involvement in
complicated stage
Eschar, if present, is a characteristic feature.
History of living in a high endemic place can
provide a clue.
Some degree of thrombocytopaenia may
occur in scrub typhus. However, leucocytosis
is common (unlike leucopaenia in dengue).
Spleen & liver may increase. Dry cough &
pneumonitis may develop. Encephalitis is
more common, as compared to dengue. IgM
ELISA is confirmatory after 5 days of illness.
38. Rubella
Fever, Rash, Posterior
auricular or sub-occipital
lymphadenopathy,Headache
Conjunctivitis, Polyarthritis
The rash associated with rubella has a
particular distribution from the head to the
trunk and extremities, but in dengue the
rash usually first appears on the trunk and
later extends to the face and extremities
Measles
Fever
Maculopapular rash
Sore throat
RTI
The rash associated with measles has a
particular distribution from the head to the
trunk and extremities, but in dengue the
rash usually first appears on the trunk and
later extends to the face and extremities.
Severe thrombocytopenia is uncommon.
39. Mild URTI or mild fever
without any significant
symptom; no h/o close
contact with known
case/ from red zone/
travel to high incidence
State; not HCW CBC
(Complet
e Blood
Count)
Fever> mild , or Fever with other
significant symptoms. Or, a mild case but
with h/o of close contact/from red zone/ or
travel to high incidence State or HCW
Not required if
fever obviously
attributable to
diseases like
UTI etc.
Test for malaria
i.e. RDT or
Malaria
Microscopy
Consideration for testsfor
dengue, Covid-19, scrub
typhus etc.
Givenecessary
treatment.
Advisedomiciliary
management. If positive, treat
for malaria as per
protocol
If case fits
into clinical
case
definition of
dengue
If features point towards the
possibility of covid- 19 test for
covid- 19*/**
If fever exceeds 5
days and features
meet the clinical
criteria
**If hospitalization not required, advise test
and isolation in home or Safe Home
*Please note:
•Until covid-19 test report is available, keep the patient in isolation
bed or in a Pre-Covid Hospital with specific tie-up forthis
purpose.
•Please utilize the covid-19 diagnostic facility available in your
hospital for prompt report i.e. CBNAAT or TrueNat or Rapid
Antigen Test; otherwise try fast-tracking with the tie-up RT-PCR
Lab.
If report is negative, transfer to general ward thereafter
and do not refer out unless essential. Repeat test if strong
suspicion.
If report is positive, send to a suitable COVID Hospital
IgM scrub
typhus
ELISA/IgM
typhoid
/IgM
leptospi
raAb
Test by
Dengue
NS-1
ELISA/
IgM ELISA
Approach to a patient presenting with fever
40. Expanded Dengue Syndrome (EDS)
•“Unusual manifestations of patients with severe organ
involvement such as liver, kidneys, brain or heart associated
with dengue infection”(WHO 2011)
•EDS is also commoner in dengue with co-morbidities.
System Manifestations System Manifestations
Neurological
Encephalopathy
Encephalitis ⁄ aseptic meningitis
Intracranial haemorrhages⁄ thrombosis,
Mononeuropathies⁄ polyneuropathies,
Guillain-Barré syndrome
Myelitis
Cardiac
Myocarditis
Conduction abnormalities
Pericarditis
Gastro-
intestinal ⁄
Hepatic
Hepatitis ⁄fulminant hepatic failure
Acalculouscholecystitis
Acute pancreatitis
Febrile diarrhea
Acute parotitis
Respiratory
ARDS
Pulmonary hemorrhage
Musculo-skeletal
Myositis
Rhabdomyolysis
Lympho-
reticular
Spontaneous splenic rupture,
Lymph node infarction Renal
Hemolytic uremic
syndrome
Renal failure
41. Clinical Management
General management of Dengue Fever (DF):
• Management of dengue fever is symptomatic and supportive
• Bed rest is advisable during the acute phase.
• Use cold/ tepid sponging to keep temperature below 38.5° C.
•Paracetamol as Antipyretic to lower body temperature is
preferable in the recommended doses
[Note: In children the dose of oral and IV paracetamol is
calculated as per 15 mg/Kg body weight and 10 mg/Kg body
weight respectively per dose at an interval of 6 hrs depending
upon fever and body ache]
• Encourage oral intake of at least 5 glasses of other fluids (with
electrolytes) in addition to normal daily intake of plain fluid.
Small frequent sips for those with nausea and anorexia.
• Patients should be monitored for development of complications
till 24 to 48 hours after they become afebrile.
42. Fluids to be Taken Fluids to be Avoided
Fruit Juices
Coconut Water
Rice Water
Barley Water
Oral Rehydration Solution
Soup
Commercial carbonated drinks
(cold drinks)
Drinks that exceed the isotonic
level (5% sugar)
What should be Done What should not be Done
Adequate bed rest
Do not take NSAIDs like aspirin or
steroids.
Adequate fluid intake
Do not take combination of
paracetamol with NSAIDs
Take paracetamol
Tepid Sponging Antibiotics are not necessary
Look for mosquito breeding places in
and around the home and eliminate
them
43. • 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 I: Above criteria plus positive tourniquet test and evidence of
plasma leakage. Thrombocytopenia with platelet count less than
1,00,000/ mm3 and Hct rise more than 20% over baseline or Fall in
Hct by 20% after Fluid replacement.
• DHF II: Above plus some evidence of spontaneous bleeding in skin
or other organs (black tarry stool, epistaxis, gum bleeds) and
abdominal pain.
• DHF III (DSS): Above plus circulatory failure (weak rapid pulse,
narrow pulse pressure < 20 mm Hg, Hypotension, cold clammy skin,
restlessness).
• DHF IV (DSS): Profound shock with undetectable blood pressure or
pulse.
Grading of DF/ DHF
44. IV Fluids to be Given IV Fluids to be Avoided
• Use isotonic iso-osmolar
solutions
(normal saline, Ringer’s
lactate, Balanced Crystalloid)
• Colloids are preferred if the
blood pressure has to be
restored urgently
• Hypotonic solution, e.g.
0.45% saline, even during the
febrile phase.
• Dextrose containing solutions,
but may be used in
hypoglycaemia with close
blood glucose monitoring.
Choice of IV Fluid
Colloids are used in case of-
• Hypotensive shock
• Repeated shock – 2nd or 3rd shock and onwards
• After >20 to 30 ml/kg of crystalloids
• If Hct does not decrease after crystalloid administration in shock
DOSE: Limited to 30 to 50 ml/kg/day
46. The maintenance fluid should be calculated using the
Holliday-Segar formula as follows:
Maintenance Fluid Therapy
Body weight in kg Maintenance volume for 24 hours
<10kg 100ml/kg
10-20
1000+50 ml / kg body weight exceeding 10 kg
1000 + 50 x ( body weight in kg – 10)ml
More than 20 kg
1500+20 ml / kg body weight exceeding 20 kg
1500 + 20 x ( body weight in kg – 20)ml
•The fluid infusion should be just sufficient to maintain effective
circulation during the period of plasma leakage
•One should keep a watch for urine output, liver size and signs of
pulmonary oedema. Hypervolemia is a common complication.
•Normally intravenous fluids are not required beyond 36 to 48 hrs.
•Normally change should not be drastic. During any changes look for signs of
under and over hydration.
•ONE ML is equal to 15 DROPS. In case of micro drip system, one ml is
equal to 60 drops.
47.
48.
49. Interpretation of rising or persistently high Haematocrit
Haematocrit Vitals Interpretation Action
A rising or
persistently high
Haematocrit
+
Unstable vital
signs
=
Active plasma
Leakage
Need for further
fluid replacement
A rising or
persistently high
Haematocrit
+
Stable
Haemodynamic
status
=
Does not require
extra intravenous
Fluid
Continue to monitor
Closely.
HCT should start to
fall within next 24
hours as plasma
leakage stops.
50. Interpretation of a decrease in Haematocrit
Haematocrit Vitals Interpretation Action
A decrease in
Haematocrit
+
Unstable vital
signs
=
Major
haemorrhage
Need for urgent
Transfusion
A decrease in
Haematocrit
+
Stable
haemodynamic
status
=
Haemodilution
and/
or reabsorption of
extravasated fluids
IV fluids should be
reduced in step-wise
manner or discontinued
immediately to avoid
pulmonary oedema
51. Febrile phase
• Limit IV fluids.
• Early IV therapy may lead to fluid overload especially with non-
isotonic IV fluid
Critical phase
• IV fluids are usually required for 24–48 hours
NOTE: For patients who present with shock, IV therapy should be
<48 hours
Recovery phase
• IV fluids should be stopped so that extravasated fluids can be
reabsorbed
When to start and stop intravenous fluid therapy
Adequate fluid
therapy
Capillary refill 2 seconds
Normal heart rate
Normal blood pressure
Normal pulse pressure
Urine ≥ 0.5 ml/kg/hr
HCT to normal
Improving acid-base
52. Indications for platelet transfusion
• Prophylactic platelet transfusion may be given at levels of
<10,000/mm3 in the absence of bleeding manifestations.
(Not the mainstay of treatment in patients with DF and no need for
prophylactic transfusion even if platelet count <40,000/mm3)
• Haemorrhage with or without thrombocytopenia.
• Prolonged shock with coagulopathy and abnormal coagulogram.
• In case of systemic bleeding, platelet transfusion may be needed in
addition to red cell transfusion (Whole fresh blood transfusion
doesn’t have any role in managing thrombocytopenia)
Indications for blood transfusion
• Loss of blood (overt blood)—10% or more of total blood volume
• Refractory shock despite adequate fluid administration, and
declining Hct
• Replacement volume should be 10 ml/kg body weight at a time and
coagulogram should be done.
• If fluid overload is present, packed cell transfusion is to be given.
Management of Severe Bleeding
53. Admission criteria
Warning signs
Persistent high grade fever (≥38.5o C). Any of the
warning signs including sudden drop of temperature
Signs and symptoms
related to
hypotension
(possible plasma
leakage)
-Dehydrated patient, unable to tolerate oral fluids
-Dizziness or postural hypotension
-Profuse perspiration, fainting, prostration during
defervescence
-Hypotension or cold extremities
-Difficulty in breathing or deep sighing breaths
Bleeding
Organ impairment
-Spontaneous bleeding, independent of the platelet
count
-Renal, hepatic, neurological or cardiac dysfunction
– enlarged, tender liver, although not yet in shock
– chest pain or respiratory distress, cyanosis
54. Admission criteria
Findings through
further
Investigations
-Rising haematocrit
-Pleural effusion,
-Ascites or asymptomatic gall-bladder thickening (in
USG)
Co-existing
conditions/ Co-
morbidities
-Pregnancy
-Co-morbid conditions e.g. diabetes mellitus,
hypertension, peptic ulcer, haemolytic anaemias and
others
-Overweight or obese (rapid venous access difficult in
emergency).
-Infancy or old age
Social circumstances
-Living alone
-Living far from health facility;
-No reliable means of transport
55. Discharge
criteria
The admitted patients who have recovered from acute
dengue infection with visible clinical improvement
- having no fever for at least 24 - 48 hours,
- normal blood pressure,
- no respiratory distress from pleural effusion or
ascites,
- improvement in clinical status (general well-being,
return of appetite, adequate urine output, no
respiratory distress),
- persistent platelet count >50,000/cu.mm
May be discharged from hospital
58. • RAPID DIAGNOSTIC TEST for Dengue is not recommended under NVBDCP.
• According to some studies, false reported dengue IgM positive cases (by using
RDT kit) may happen in Covid-19 infected patients.
• DIAGNOSIS OF COVID 19: laboratory confirmed Covid-19 as per existing
Govt guideline.
• Treatment of Dengue-COVID 19 coinfection is very difficult especially in
situations like ARDS, myocarditis and shock state. Individualized approach with
risk-benefit ratio should be taken for severe cases, patients with co-morbidities
and those who are at high risk. There are no such guidelines for combating the co-
infections.
• Treatment of Dengue: As per Medical Officer Guideline, Govt of WB
• COVID 19 Treatment: As per management protocol for covid-19, published by
Department of health and family welfare, Govt of WB.
DIAGNOSIS & MANAGEMENT OF CO-
INFECTION
59. • STEROIDS: There is no evidence of viremia and no significant side effects after
the administration of corticosteroids, irrespective of doses and route. Safety
concern with steroid use is not a big; benefits in Covid-19 overweigh the risk of
using it in dengue.
• TOCILIZUMAB: Tocilizumab should be used cautiously because there may be
overlapping of raised bio markers like CRP, ferritin, IL6 in both the diseases.
Chance of secondary bacterial infection and Tocilizumab induced neutropenia
may deteriorate dengue related pancytopenia.
• CONVALESCENT PLASMA TRANSFUSION: Not contraindicated in
presence of Dengue co-infection.
• ANTICOAGULATION: Padua score and improve Bleeding risk Score
calculation is required before initiating LMWH in dengue-Covid19 co existence.
LMWH use generally not associated with thrombocytopenia. As per Covid-19
treatment protocol the LMWH used as prophylactic dose.
Special considerations in dengue-Covid 19 co-
infection
60. • Hemodynamics and Volume assessment
• Balanced approach should be judiciously used to avoid both over and under
resuscitation.
• Cytokine storm in Covid-19 and Dengue shock syndrome have a similar
presentation and may even coexist . Judicious use of Tocilizumab.
•
• Dengue Shock syndrome on the other hand does not have any specific treatment
and the management is largely supportive with vasopressors and volume support ,
which is similar to in Covid Cytokine storm.
• Severe Covid-19 usually requires respiratory support with invasive mechanical
ventilation and when associated with Dengue infection requires some special
precautions during airway management and ventilation.
Special considerations in dengue-Covid 19 co-
infection
62. • Incidence of dengue during pregnancy still underestimated.
• Infection in pregnancy carries more risk.
• Severe bleeding may complicate delivery and/or surgical procedures
performed on pregnancy.
• Involvement of lungs and liver is also common in pregnancy.
• Complications of DF depend on the different stages of pregnancy like
early, late, peri-partum and post partum periods
•Misdiagnosis or delayed diagnosis due to some overlapping clinical and/or
laboratory features :
HELLP syndrome, pneumonia, pulmonary embolism, various
obstetric causes of per-vaginal bleeding , other infectious diseases.
63. More common during pregnancy
• Neurological – Encephalopathy , encephalitis, thrombosis
• Gastrointestinal – Hepatitis, acute pancreatitis
• Renal –Renal failure, haemolytic uremic syndrome
• Cardiac – Myocarditis & pericarditis
• Musculoskeletal – Myositis & rhabdomyositis
Atypical Manifestations in Pregnancy
Effect of Dengue Fever on Pregnancy
• First trimester -Abortion, Secondary infections
• Second Trimester- Severe bleeding ,abruption , threatened preterm labour,
deranged coagulation profile, frequent transfusions
• Third trimester -Abruption ,increased incidence of Caesarean section,
DIC, PPH, Haematoma formation, Infections , Delayed wound healing
• Maternal death due to DIC , Coagulopathy
• Low birth weight babies, Pre maturity
64. • Conservative medical and obstetrical management is the
treatment of choice.
• Outcome seemed to correlate with the gestational age at
which dengue infection was acquired.
• No vaccination & only supportive medication.
• Pregnancies complicated by dengue infection require
close monitoring for potential maternal and fetal
complications.
• Timely Referral to higher centres
Take Home Message
66. Highlights
• Dengue in Neonates
• Dengue in Infants( may be upto 2 yrs)
• Assessment of Pediatric Patient
• Severe dengue – Bundle of intervention
67. Features of Dengue in neonates
Full spectrum of disease can occur
• Fever, skin rash
• Bleeding manifestation:
- Purpura - Nose bleeding
- Gi bleeding - Pulmonary haemorrhage
- Intracranial bleeding
• Hepatic & Multi-organ failure
• Maternal Dengue near term: May be an important clue
• Anaemia, leucopenia, thrombocytopenia
• Close D/D –Neonatal sepsis, Congenital Infection
Strong clinical Suspicion required for Diagnosis
68. Dengue in infants
• Most susceptible: Babies between 4 to 9 months
• Severe dengue is common
•NS1Ag detection may be missed before 6months of age due to
presence of maternal antibody
• Convulsions and hepatic dysfunction more commonly
affect infants
• Dengue in infants can be severe (DHF/ DSS/ their
complications) in primary infection .
• Complications of fluid overload were found more often in the
infants than in the children
• Mortality in this age group is 4 times higher
69. Clinical features of DF in infants
• “Flu” like features:
High fever
Running nose
Cough
Conjunctival congestion
Vomiting, nausea, anorexia
Irritability / excessive cry
• Diarrhoea like Presentation
• Bleeding gum, nose, easy
bruisability – common.
• Positive tourniquet test -
infants - sensitivity of 33%,
specificity of 76%
Measly look + blanchable erythematous
flush /skin rash
70. Clinical features of DF in toddlers and
older children
• Abrupt onset high fever
• Headache
• Pain in orbits
• Extreme myalgia, arthralgia ( “Break bone fever”)
• Vomiting, pain abdomen
• Sore throat
• Skin rash
• Minor bleeding – nose/gum/easy bruisability
71. • Normal heart rates by age
• Newborn-3months:85-205/min
(140)
• 3months-2 years:100-190/min
(130)
• 2-10years:60-140/min (80)
• >10years: 60-100/min (75)
• Normal urine output
• Infants-young children: 1-2
ml/kg/hr
• Older children-adolescents:
0.5-1ml/kg/hr
• Least acceptable systolic
BP (mm of Hg)
• Birth -1 month - 60
• 1m- 1yr - 70
• 1 - 10 yrs
[Formula for approx.
calculation:
70+ (2 X age in years)]
• >10 yrs - 90
• MAP (50th percentile at
50th height percentile) =
1.5 x age in years + 55
Circulation
72. Advice
What should be done ?
• Adequate bed rest
• Adequate fluid intake : Daily intake plus 5% Deficit (50ml/kg/day)
• Note: Plain water alone may cause electrolyte imbalance . Oral
rehydration solution (ORS) or barley/rice water/coconut water
• Paracetamol - every 6 hours (maximum 4 doses per day)
• Tepid sponging
• What should be avoided?
• Do not take acetylsalicylic acid (aspirin), mefenamic acid, ibuprofen or
other NSAIDs or steroids.
• Do not take combination of paracetamol with above mentioned drugs.
• Antibiotics are not necessary
• Educate parents regarding warning signs
• Close monitoring
• Prevent spread of dengue within house
73. Chart 3 : Management of compensated shock in children
74. Chart 4 : Management of hypotensive shock in children
76. DENGUE IN HYPERTENSION
• Hypertension effects modification on the risk of DHF outcome in
dengue patients.
• BP of these patient perceived to be normal may infact be low for
these patients.
Recommendations :-
• Dose of antihypertensive drugs should be titrated according to blood
pressure. Target MAP (mean arterial pressure) should be more than
or equal to 65 mm of Hg.
• Diuretics should be avoided in critical phase or during
hemoconcentration.
• Beta blockers should be withdrawn in presence of shock or heart
failure.
• History regarding Beta Blocker to be elicited prior to checking Pulse
• Calcium channel blockers, ACE Inhibitors, ARBs are relatively safe
unless renal function deteriorates.
77. Dengue in Tuberculosis patients:
Key points:
1. Check LFT at regular interval and consider for dose adjustment if
hepatitis develops
2. Be alert if patient develops hemoptysis.
Dengue and Malaria co-infection:
Key points:
1. For all dengue positive cases, routinely send blood for MP and
MPDA.
2. Start anti-malarial as soon as possible if malaria co-infection found.
Dengue in Chikungunya:
Key points:
1. Acute complications are sometimes severe in DF in co-infection
2. In case of predominant joint involvement in a DF patient, Chikungunya
should be investigated and proper management to be carried out
78. Dengue in Diabetics
Recommendations:
1. If patient is on insulin, dose adjustment may be considered
according to patient’s CBG.
2. Hold OHA in DSS.
3. Timely referral
Beware of and Timely Referral to Secondary and Tertiary Tier
Hospital required for:
1. Co-infection with Enteric Fever
2. Co-infection with HIV
3. Patient requiring any Surgical Intervention
4. Co-infection with Chickunguniya, Malaria
5. Co-infection with TB
Dengue with other special conditions
79. DENGUE WITH CNS MANIFESTATIONS
• In recent years, neurological manifestations of dengue has been
documented, most commonly associated with DEN2 and DEN3
HOW TO DIAGNOSE?
The following criteria is to be satisfied-
1. Fever
2. Acute signs of cerebral involvement
3. Presence of IgM DENGUE Antibody (ELISA) or dengue genomic
material in the serum and/or CSF
4. Exclusion of other causes of viral encephalitis
MANAGEMENT
•General management includes monitoring and maintenance of airway,
adequate oxygenation, Left lateral position
•Standard fluid therapy guidelines for severe dengue should be followed
•Seizures should be controlled by standard anti-epileptics
•Timely Referral to Higher Centre after stabilisation
80. Nosocomial infection in Dengue fever
• Includes Pneumonia, urinary tract infections, gastroenteritis, co-infection with
malaria, leptospira, scrub typhus, chikungunya.
• Elderly patients and children are more susceptible.
• DIAGNOSIS: BACTERIAL CO-INFECTION
-CRP, Procalcitonin might be helpful
-A DDIS of ≥ 4 had a specificity of 94.4%
• It is important to identify patients who are
unlikely to need empirical antibiotics and select
patients who will benefit most from early therapy
• Empirical antibiotics can be started with strong clinical and laboratorial
suspicion
The Dengue Dual
Infection Score
[DDIS] :
One point to each of
five risk factors for
bacterial coinfection:
• Pulse rate ≥ 90
beats/minute,
• Total white cell
count ≥ 6 × 109/L
Hematocrit < 40%
• serum sodium <
135 mmol/L
• serum urea ≥ 5
mmol/L.
81. Dengue in Renal Failure
• The Difficulty in diagnosis and the Treatment dilemma in patients with CRF
cause high risk of mortality
• Challenges:
- Elevated liver enzymes, proteinuria, hypoalbuminaemia
-Extensive petechie/echymosis, overt bleeding, marked thrombocytopenia
- Low baseline haematocrit
-Low baseline platelet count in dialysis patients due to uremia and use of
-Ignorance of clinical symptoms/signs and misinterpretation of the laboratory
data may play big role
-fluid management, electrolyte balance, bleeding control
• Urine output can not be an indicator for monitoring of fluid status in CRF
• Cautious use of Ringer lactate solution otherwise it may cause hyperkalemia
leading to tissue acidosis
• Timely Referral to Higher Centre with facility of Dialysis
83. ICU management
• Severe Dengue
• Dengue shock syndrome
• Dengue haemorrhagic fever
• Expanded Dengue syndrome
-Oxygen therapy
-Fluid management
-Airway management
-Mechanical ventilation
General Supportive Measures Specific Supportive Therapy
-Hematological and coagulation
abnormalities
-Renal, Hepatic, Cardiac, Neurological
support
-Prevention and Treatment of
superinfection/ co-infection
84. Scenario 1
• You are asked to see a patient admitted in ICU with Dengue who is
short of breath and have an oxygen saturation of 85% . what steps
would you take to increase the oxygenation.
• Positioning:
-Propped up : Ascites, Volume overload
-Lateral: Pleural effusion
• Check Oxygen saturation:
If < 90% in room air
-Supplemental oxygen
-Target SPO2 > 95%
If Pulse oximetry not available or not picking up signal
-Supplemental oxygen if patient is breathless
ABG analysis if available and PaO2 may be measured if SpO2
signal not picking up
86. Nasal cannula
USE:
• Oxygen flow titrated to 1-6 L/min
to keep the saturation around
95%.
• Humidified oxygen to avoid
irritation to the nose
• FIO2: Available 24-40%
Oxygen Face Mask
USE:
• If the flow requirement is more
than 6 L/min
• If a patient is mouth breather
• Flow rate : 5-10 L/min
• FIO2 : Avilable 40-50%
87. Scenario 3
• The patients work of breathing still remains high and is
saturation remains below 90% and he is becoming restless.
What should be done now
High Flow Nasal Cannula (HFNC)/ BIPAP
Scenario 4
The patient failed to improve on HFNC and subsequent BIPAP
with increasing oxygen requirement and tachypnea. He is
unable to speak a full sentence and has increased use of
accessory muscles of breathing. What should be done next ?
Intubation & Mechanical ventilation