DENGUE FEVER

Aedes aegypti Mosquito

World Distribution of Dengue 1999

Areas infested with Aedes aegypti

Areas with Aedes aegypti and recent epidemic dengue
 GLOBAL STATUS

• New infections annually: 50 million

• Deaths: 24,000 annually
• People at risk: 2.5-3 billion
• Hospitalized cases: 500 000/year
(90% of those affected are children)
• Disease burden: 465,000 Disability
Adjusted Life Years (DALY)
DENGUE OUT BREAK IN SOUTH
EAST ASIA IN 2005

2005 Dengue Outbreak

Cases Deaths

100,000

80,000

60,000
Cases
40,000

20,000

0
India, (West
Sri Lanka Thailand Pakistan
Bengal)

Cases 90,000 3,000 31,000 4,800

Deaths 15,000 0 58 50
 DENGUE OUT BREAK IN PAKISTAN
(2006)

Dengue Fever In 2006

Cases Deaths

3500
3000
2500
2000
Cases
1500
1000
500
0
India Pakistan Karachi Lahore
Cases 3331 3230 1836 400
Deaths 49 50 30 4
 Manifestation Of Dengue Virus
Infections

ASYMPTOMATIC
Undifferentiated
Fever
Without haemorrhage

SYMPTOMATIC Dengue Fever

With unusual haemorrhage

Dengue No shock
Haemorrhagic
Fever DSS
 A) Undifferentiated Fever

• May be the most common

manifestation of dengue
• Prospective study found
that 87% of students
infected were either
asymptomatic or only mildly
symptomatic
• Other prospective studies
including all age- groups
also demonstrate silent
transmission
DS Burke, et al. A prospective study of dengue infections
in Bangkok. Am J Trop Med Hyg 1988; 38:172-80.
 2A) Clinical Characteristics
of Dengue Fever

• Fever
• Headache
• Muscle and joint pain
• Nausea/vomiting
• Rash
• Hemorrhagic manifestations
 2B)Hemorrhagic Manifestations
of Dengue

• Skin hemorrhages:
petechiae, purpura, ecchymoses
• Gingival bleeding
• Nasal bleeding
• Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
• Hematuria
• Increased menstrual flow
 C1) Clinical Case Definition for
Dengue Hemorrhagic Fever

4 Necessary Criteria:
• Fever, or recent history of acute fever
• Hemorrhagic manifestations
• Low platelet count (100,000/mm3 or less)
• Objective evidence of “leaky capillaries:”
– elevated hematocrit (20% or more over
baseline)
– low albumin
– pleural or other effusions
 Four Grades of DHF

• Grade 1
– Fever and nonspecific constitutional symptoms
– Positive tourniquet test is only hemorrhagic manifestation
• Grade 2
– Grade 1 manifestations + spontaneous bleeding
• Grade 3
– Signs of circulatory failure (rapid/weak pulse, narrow pulse
pressure, hypotension, cold/clammy skin)
• Grade 4
– Profound shock (undetectable pulse and BP)
 Danger Signs in
Dengue Hemorrhagic Fever

• Abdominal pain - intense and

sustained
• Persistent vomiting
• Abrupt change from fever to
hypothermia, with sweating and
prostration
• Restlessness or somnolence

Martínez Torres E. Salud Pública Mex 37 (supl):29-44, 1995.

 Warning Signs for Dengue Shock
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary permeability
• ≤ 100,000/mm3 platelets
Initial Warning
Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrit
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to hypothermia
• Change in level of
consciousness (irritability
When Patients Develop
DSS:
• 3 to 6 days after onset of
or
somnolence)
 C2) Clinical Case Definition for
Dengue Shock Syndrome

• 4 criteria for DHF

• Evidence of circulatory failure manifested
indirectly by all of the following:
– Rapid and weak pulse
– Narrow pulse pressure (≤ 20 mm Hg) OR
hypotension for age
– Cold, clammy skin and altered mental status
• Frank shock is direct evidence of circulatory
failure
 Unusual Presentations
of Severe Dengue Fever

• Encephalopathy
• Hepatic damage
• Cardiomyopathy
• Severe gastrointestinal
hemorrhage
Risk Factors Reported for DHF

• Virus strain
• Pre-existing anti-dengue antibody
– previous infection
– maternal antibodies in infants
• Host genetics
• Age
 Risk Factors for DHF (continued)

• Higher risk in secondary infections

• Higher risk in locations with two or more
serotypes circulating simultaneously at
high levels (hyperendemic transmission)
 Increased Probability of DHF

Hyperendemicity

Increased circulation Increased probability

of viruses of secondary infection

Increased probability of Increased probability of

occurrence of virulent strains immune enhancement

Increased probability of DHF

Gubler & Trent, 1994
 Viral Risk Factors
for DHF Pathogenesis

• Virus strain (genotype)

– Epidemic potential: viremia level,
infectivity
• Virus serotype
– DHF risk is greatest for DEN-2,
followed by DEN-3, DEN-4 and DEN-1
 Clinical Evaluation in Dengue
Fever

• Blood pressure
• Evidence of bleeding in skin or other
sites
• Hydration status
• Evidence of increased vascular
permeability-- pleural effusions, ascites
• Tourniquet test
Petechiae
Pleural Effusion Index

PEI = A/B x 100

B
A
Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile
phase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.
 Tourniquet Test

• Inflate blood pressure cuff to a point

midway between systolic and
diastolic pressure for 5 minutes
• Positive test: 20 or more petechiae
per 1 inch2 (6.25 cm2)

Pan American Health Organization: Dengue and Dengue

Hemorrhagic Fever: Guidelines for Prevention and Control.
PAHO: Washington, D.C., 1994: 12.
Positive Tourniquet Test
 Laboratory Tests
in Dengue Fever

• Clinical laboratory tests

– CBC--WBC, platelets, hematocrit
– Albumin
– Liver function tests
– Urine--check for microscopic hematuria
• Dengue-specific tests
– Virus isolation
– Serology
Laboratory Methods for Dengue
Diagnosis

• Virus isolation to determine

serotype of the infecting virus
• IgM ELISA test for serologic
diagnosis
 Temperature, Virus Positivity and
Anti-Dengue IgM , by Fever Day
100

Dengue IgM (EIA units)

300
Temperature (degrees Celsius)

39.5
Percent Virus Positive

80
39.0 225
38.5 60
150
38.0 40
37.5 20 75

37.0
0 0
-4 -3 -2 -1 0 1 2 3 4 5 6
Fever Day
Mean Max. Temperature Virus Dengue IgM
Adapted from Figure 1 in Vaughn et al.,
J Infect Dis, 1997; 176:322-30.
 Outpatient Triage

• No hemorrhagic manifestations and

patient is well-hydrated: home treatment
• Hemorrhagic manifestations or hydration
borderline: outpatient observation center
or hospitalization
• Warning signs (even without profound
shock) or DSS: hospitalize
 Patient Follow-Up

• Patients treated at home

– Instruction regarding danger signs
– Consider repeat clinical evaluation
• Patients with bleeding manifestations
– Serial hematocrits and platelets at least daily
until temperature normal for 1 to 2 days
• All patients
– If blood sample taken in first 5 days after
onset, need convalescent sample between
days 6 - 30
– All hospitalized patients need samples on
admission and at discharge or death
 Treatment of Dengue Fever
& DHF I & II

• Fluids
• Rest
• Antipyretics (avoid aspirin and non-
steroidal anti-inflammatory drugs)
• Monitor blood pressure, hematocrit,
platelet count, level of
consciousness
 Treatment of DHF III & IV

All above treatment +

– In case of severe bleeding, give fresh whole
blood 20 ml/kg as a bolus
– Give platelet rich plasma transfusion
exceptionally when platelet counts are below
5,000–10,000/ mm3 .
– After blood transfusion, continue fluid therapy
at 10 ml/kg/h and reduce it stepwise to bring it
down to 3 ml/kg/h and maintain it for 24-48 hrs
 Treatment of DHF III & IV
•1 unit of RD(Random Donor) Plt. (50ml) per 10 Kg body
weight.---- expected to increas the Plt. Count 5000-
10000/uL. (If No splenomegaly, Fever or DIC)
•Alloimmunized (who have received multiple transfusions and
thus sensitized) may have little or no increase in the count.
•They can be best served by SDAP(Single Donor Apheresis
Platelets) as 1 SDAP unit(150ml)=6 RD units
Evaluation of Refractoriness of RD units
Post transfusion count – Pre transfusion count X BSA
CCI= Number of Platelets transfused X 10 11
Appropriate if
-CCI is 10X10 9 /ml in 1 hr post transfusion sample and/or
-CCI is 7.5X10 9/ml in 18-24 hr post transfusion sample.
 Treatment of Dengue Fever

Papaya Juice vs. Dengue ?

Raw papaya leaves, 2 pcs just cleaned and
pound and squeeze with filter cloth. You will only
get one tablespoon per leaf. So two tablespoon per
serving once a day.
Do not boil or cook or rinse with hot water, it will
loose its strength. Only the leafy part and no stem
or sap.
It is very bitter and you have to swallow it like
Won Low Kat. But it works.
Source: from Indonesia March 2005
 Indications for Hospital Discharge

• Absence of fever for 24 hours (without

anti-fever therapy) and return of appetite
• Visible improvement in clinical picture
• Stable hematocrit
• 3 days after recovery from shock
• Platelets ≥ 50,000/mm3
• No respiratory distress from pleural
effusions/ascites

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control.
PAHO: Washington, D.C., 1994: 69.
 Common Misconceptions about
Dengue Hemorrhagic Fever
 Dengue + bleeding = DHF
 Need 4 WHO criteria, capillary permeability

 DHF kills only by hemorrhage

 Patient dies as a result of shock
 Poor management turns dengue into DHF
 Poorly managed dengue can be more severe, but
DHF is a distinct condition, which even well-treated
patients may develop
 Positive tourniquet test = DHF
 Tourniquet test is a nonspecific indicator of capillary
fragility
 More Common Misconceptions
about Dengue Hemorrhagic Fever

 DHF is a pediatric disease

 All age groups are involved in the Americas

 DHF is a problem of low income families

 All socioeconomic groups are affected
 Tourists will certainly get DHF with a
second infection
 Tourists are at low risk to acquire DHF
 Dengue Vaccine?

• No licensed vaccine at present

• Effective vaccine must be tetravalent
• Field testing of an attenuated tetravalent
vaccine currently underway
• Effective, safe and affordable vaccine will not
be available in the immediate future
 Prevention

•The main tactic used in fighting Dengue is

eradicating the mosquito.
•Public spraying for mosquitoes is the most
important aspect of this approach.
•Personal prevention involces the use of mosquito
nets, repellents, cover exposed skin, use of DEET-
impregnated bednets, and avoiding endemic areas.
 CONTACT

alauddinsarwar@gmail.com
doctoralauddin@yahoo.co.in