DENGUE

Dr. Aniket Mule

MBBS, MD Medicine
• Dengue is the most rapidly spreading mosquito-borne viral disease in
the world.

• In the last 50 years, incidence has increased 30-fold with increasing

geographic expansion to new countries and, in the present decade,
from urban to rural settings.

• An estimated 50 million dengue infections occur annually and

approximately 2.5 billion people live in dengue endemic countries

• Reported case fatality rates for the endemic region are approximately
1%, but in India, Indonesia and Myanmar, focal outbreaks away from
the urban areas have reported case-fatality rates of 3-5%.
Dengue Virus Profile

• Genus Flavivirus

• Family Flaviviridae

• Single-stranded RNA

• 4 serotypes (DEN-1 to 4)

• 50 nm diameter with
multiple copies of 3
structural proteins and 7
non structural proteins
Vector Profile
• Aedes mosquitoes
• A. aegypti
• A. albopictus
• A. polynesiensis

• Usually breed in stagnant water

• Active in dark or shaded places
outdoors
• Most active: 2 hours before
sunset (5-6pm) and morning (8-
9am)
• Identified by the white bands
or scale patterns on its legs and
thorax.
Aedes aegypti Breeding Sites
The Host

• Incubation period: 4-10 days

• Primary infection induce lifelong immunity to the

infecting serotype

• Protection from different serotype within 2-3 months

of primary infection

• No long-term cross-protective immunity

The Host
• Individual risk factors: Age, chronic diseases

• Secondary heterotypic infection:

DENV-1/DENV-2 sequence of infection was associated
with a 500-fold risk of DHF compared with primary
infection.
For the DENV-3/DENV-2 sequence the risk was 150-fold,
and a DENV-4/DENV-2 sequence had a 50-fold risk of
DHF
Asian genotypes of DEN-2 and DEN-3 are frequently
associated with severe disease accompanying
secondary dengue infections
Dengue Fever

• Wide spectrum of clinical presentation, with

unpredictable clinical evolution and outcome

• 80% patients are asymptomatic

• Three phases
• Febrile phase
• Critical phase
• Recovery phase
CLASSIFICATION
• Non severe dengue
Without warning sign
With warning sign

• Severe dengue
Dengue Fever
Febrile Phase

 Facial flushing
 Skin erythema
 Generalized body ache
• Sudden onset of  Myalgia and arthralgia
high-grade fever  Headache
• Lasts for 2-7  Sore throat, injected

days pharynx, and

conjunctival injection
 Anorexia, nausea and
vomiting
Critical Phase
• Temperature drops to 37.5-38 (days 3-7)

• (+) increase in capillary permeability with

increasing hematocrit levels

• Significant plasma leakage lasts for 24-48

hours

• Progressive leukopenia followed by rapid

decrease in platelet precedes plasma
leakage
Critical Phase

• Shock: critical volume of plasma is lost

• Temperature may be subnormal

• Prolonged shock  organ hypoperfusion 

organ impairment, metabolic acidosis, and
DIC  severe hemorrhage

• Severe hepatitis, encephalitis or

myocarditis
Recovery Phase

• Gradual reabsorption of extravascular

compartment fluid (48-72 hours)
• General well-being improves, appetite returns,
GI symptoms abate, hemodynamic status
stabilizes and diuresis ensues
• Hematocrit stabilizes or may be lower due to
dilutional effect of reabsorbed fluid
• WBC starts to rise
• Recovery of platelet count occurs later
Rash of Dengue fever:
Diffuse flushing or fleeting eruptions - first two to
three days

Maculopapular or rubelliform appears on

approximately the third or fourth day.
Convalescent rash is characterized by
confluent petechiae with islands of white patches
LAB DIAGNOSIS

• DIRECT METHODS:(Acute phase )

Virus isolation
Genome detection(PCR)
NS1 detection

• INDIRECT METHODS:(later stage)

Serology detection

DIRECT METHODS
VIRAL ISOLATION
•Diagnosis: Confirmed
•Validity: 1–5days
•Sample : Whole blood
•Time for result: 1–2wks

NUCLEIC ACID DETECTION

•Diagnosis: Confirmed
•Validity: 1–5days
•Sample: Whole blood
•Time for result: 1–2 day
 NS1 DETECTION
• The NS1 gene product is a glycoprotein produced by all flaviviruses
and is essential for replication and viability of the virus.

• Positive from Day 1 after the onset of the fever and declines to
undetectable levels by 5–6 days. Hence, tests based on this antigen
can be used for early diagnosis.

• Commercial kits for the detection of NS1 antigens are now

available; however, these kits do not differentiate between the
serotypes.

• Provides an early diagnostic marker for clinical management, also

facilitate the improvement of epidemiological surveys of dengue
infection.
 IgM-capture enzyme-linked immunosorbent
assay (MAC-ELISA):
• The anti-dengue IgM antibody develops a little earlier
than IgG, and is usually detectable by Day-5 of the
illness

• IgM antibody titers in primary infections are

significantly higher than in secondary infections

• May persist for more than 90 days, but in most

patients, it wanes to an undetectable level by 60 days
IgG-ELISA
• The IgG-ELISA is very non-specific
• Exhibits broad cross-reactivity among flaviviruses

IgM/IgG ratio
• The IgM/IgG ratio is used to distinguish primary
infection from secondary dengue infection .
• A dengue virus infection is defined as primary if the
capture IgM/IgG ratio is greater than 1.2, or as
secondary if the ratio is less than 1.2
DIFFERNTIAL DIAGNOSES
Approach to the Management
Management Decisions
Groups A Groups B Groups C

• require
• may be sent • referred for in- emergency
home hospital treatment and
• tolerate management urgent referral
adequate • with warning
volumes of oral signs, co-existing
fluids and pass • severe
urine at least
conditions,
• with certain dengue (in
once every 6 critical phase)
hours social
• no warning signs circumstances
DAILY MONITERING

• Hematocrit

• Platelet count

• White blood cell count

Group A Action Plan
• Encourage intake of ORS, fruit juice and other fluids

• Paracetamol and tepid sponge for fever

• Advise to come back if with

no clinical improvement
severe abdominal pain
persistent vomiting
cold and clammy extremities,
lethargy or irritability or restlessness,
bleeding
not passing urine for more than 4–6 hours.
Group B (with warning signs)
Action Plan

• Reference hematocrit before fluid therapy

• Isotonic solutions
5–7 ml/kg/hour for 1–2 hours, then reduce
to 3–5 ml/kg/hr for 2–4 hours, and then reduce
to 2–3 ml/kg/hr or less according to the clinical
response
Reassess:
• hematocrit remains the same or rises only minimally  2–3 ml/kg/hr for
another 2–4 hours
• worsening vital signs and rising hematocrit rising  5–10 ml/kg/hour for 1–2
hours
Give minimum intravenous fluid volume: maintain
good perfusion and urine output of about 0.5
ml/kg/hr
• Intravenous fluids are usually needed for only 24–48 hours.
• Reduce intravenous fluids gradually when the rate of plasma
leakage decreases towards the end of the critical phase.

monitor:
• vital signs and peripheral perfusion (1–4 hourly until the patient is
out of the critical phase)
• urine output (4–6 hourly)
• hematocrit (before and after fluid replacement, then 6–12 hourly)
• blood glucose
• organ functions (renal profile, liver profile, coagulation profile)
Group B (without warning signs)
Action Plan
• Encourage oral fluids

• If not tolerated, start intravenous fluid therapy

of 0.9% saline or Ringer’s lactate with or without
dextrose at maintenance rate
• Give the minimum volume required to maintain
good perfusion and urine output.
• Intravenous fluids are usually needed only for
24–48 hours.

• Close monitoring
Group C Action Plan

• Admit to a hospital with access to intensive care

facilities and blood transfusion
• Plasma losses should be replaced immediately and
rapidly with isotonic crystalloid solution or, in the case
of hypotensive shock, colloid solutions

• Blood transfusion: with suspected/severe bleeding

• Judicious intravenous fluid

resuscitation: sole intervention required
Group C Action Plan

Goals of fluid resuscitation:

• Improving central and peripheral circulation

(decreasing tachycardia, improving BP, warm and
pink extremities, and capillary refill time <2 seconds)
•Improving end-organ perfusion
– i.e. stable conscious level (more alert or less
restless), urine output ≥ 0.5 ml/kg/hour,
decreasing metabolic acidosis.
FLUID REPLACEMENT
• Treatment of hypotensive shock
• Initiate IV fluid resuscitation with crystalloid or colloid solution at 20 ml/kg as a
bolus for 15 minutes. If patient improves give a crystalloid/colloid solution of 10
ml/kg/hr for 1 hour, then reduce gradually.
• If patient is still unstable : review the HCT taken before the first bolus;
• if HCT was low (<40% in children and adult females, <45% in adult males) this
indicates bleeding, the need to cross-match and transfuse
• if HCT was high compared to baseline value, change to IV colloids at 10–20 ml/kg
as a second bolus over 30 minutes to 1 hour;
• reassess after second bolus.
• If patient is improving reduce the rate to 7–10ml/kg/hr for 1–2 hours, then back
to IV crystalloids and reduce rates
• if patient’s condition is still unstable, repeat HCT after second bolus.
• If HCT decreases, this indicates bleeding (see above);
• if HCT increases/remains high (>50%), continue colloid infusion at 10–20 ml/kg
as a third bolus over 1 hour,
then reduce to 7–10 ml/kg/h 1–2 hours, then change back to crystalloid solution
and reduce rate as above.
Treatment of Hemorrhagic Complications

Patients at risk of major bleeding are those who:

• Prolonged/refractory shock;
• Hypotensive shock and renal or liver failure and/or
severe and persistent metabolic acidosis
•Given non-steroidal anti-inflammatory agents
• Pre-existing peptic ulcer disease
• Anticoagulant therapy
• Any form of trauma
Treatment of Hemorrhagic Complications

• Blood transfusion is life-saving and should be

given as soon as severe bleeding is suspected or
recognized

• Do not wait for the hematocrit to drop too low

before deciding on blood transfusion

• Risk of fluid overload.

Treatment of Hemorrhagic Complications

• blood transfusion if with bleeding +

• 5-10 ml/kg of PRBC or 10-20 ml/kg FWB
• repeat if with further blood loss or no rise in
hematocrit after transfusion

Indication of platelet transfusion:

• Platelets less than 50000/dl with bleeding
• Platelets less than 10000/dl with/without bleeding
• SDP preferred over RDP
Criteria for Discharge

Clinical:

1. No fever for 48 hours,

2. Improvement in clinical status(general well being,
appetite, haemodynamic status, urine output, no
respiratory distress

Laboratory:

1. Increasing trend of platelet count

2. Stable haematocrit without iv fluids
 DENGUE VACCINE
• Live attenuated viruses
• Tetravalent
• Based on attenuated yellow fever
vaccine 17D
• Dengavaxia for Subcutaneous use
• Safety and effectiveness have not
been established
THANK YOU