Dengue Fever

Dengue Fever
 Dengue virus
 Most prevalent vector-
borne viral illness in the
world
 Main mosquito vector is
Aedes aegypti,
 Year round
transmission
 Dengue Fever
 WHO says some 2.5 billion people, two
fifths of the world's population, are now at
risk from dengue and estimates that there
may be 50 million cases of dengue
infection worldwide every year.
 epidemic in more than 100 countries
 Dengue fever
 genus Flavivirus,
 family Flaviviridae
 also known as breakbone fever.
(bonecrusher disease) -Dandy Fever
 Aedes aegypti - rarely the Aedes
albopictus mosquito,
 African ki denga pepo- evil spirit.
 Distribution
 Endemic in more than
100 tropical and
subtropical countries
 Pandemic began in
Southeast Asia after WW
II with subsequent global
spread
 Several epidemics since
1980s
 Distribution is comparable
to malaria
 Manifestations of dengue virus
infection:

ASYMPTOMATIC

Undifferentiated
Fever

Without haemorrhagic
SYMPTOMATIC Dengue Fever With unusual
haemorrhagic

No shock
Dengue
Haemorrhagic
Fever DSS

Epidemiological Unit, Sri Lanka

 Virology
 Flavivirus family
 Small enveloped
viruses containing
single stranded
positive RNA
 Four distinct viral
serotypes (Den-1,
Den-2, Den-3, Den-4)
 Dengue
Viruses
 Four closely related single-stranded RNA

Dengue viruses (DEN-1, DEN-2, DEN-3 and

DEN-4)

 Each serotype provides specific lifetime

immunity, and short-term cross-immunity (A

person can be infected as many as four times,

 Dengue fever
 S.B. Halstead in the 1970s,
 dengue hemorrhagic fever -secondary
infections by another one of dengue
fever's four serotypes.
 antibody-dependent enhancement (ADE)
 original antigenic sin,
 superinfection
Pathophysiology
 Transmitted by the
bite of Aedes
mosquito (Aedes
aegypti)
 Incubation 3-14 days
 Acute illness and
viremia 3-7 days
 Recovery or
progression to
leakage phase
 Dengue Mosquito

 Aedes aegypti is the most important dengue mosquito

 It breeds in collections of water close to dwellings
 Common breeding sites are;
- Domestic water storage containers - tanks, jars,
drums, flower vases with water
- Roof gutters /sun shades
- Used tyres, discarded tins, cans, pots, yogurt
cups, polythene bags, tree axils &
- Many more places where rain watercollects
                                                                   
The most common epidemic vector of dengue in the world is
the Aedes aegypti mosquito. It can be identified by the white
bands or scale patterns on its legs and thorax.
 Disease Factors
 Dengue-2 serotype most virulent
 Increased severity with secondary infections
 Increased risk in children <15 years and elderly.
 Greatest risk of DHF in infants.
 More severe in females
 Increased mortality with comorbid conditions
 Less common in malnourished children
 Replication and Transmission
of Dengue Virus (Part 1)

1. Virus transmitted 1
to human in mosquito
saliva

2
2. Virus replicates
in target organs 4

3. Virus infects white 3

blood cells and
lymphatic tissues

4. Virus released and

circulates in blood
 Replication and Transmission
of Dengue Virus (Part 2)

5. Second mosquito 6
ingests virus with blood

6. Virus replicates
in mosquito midgut
and other organs, 7
infects salivary
glands

5
7. Virus replicates
in salivary glands
Dengue Clinical Syndromes

 Undifferentiatedfever
 Classic dengue fever
 Dengue hemorrhagic
fever
 Dengue shock syndrome
 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.
 Clinical Characteristics
of Dengue Fever
 Fever
 Headache
 Muscleand joint pain
 Nausea/vomiting
 Rash
 Hemorrhagic manifestations
 Hemorrhagic Manifestations
of Dengue
 Skin hemorrhages:
petechiae, purpura, ecchymoses
 Gingival bleeding
 Nasal bleeding
 Gastro-intestinal bleeding:
hematemesis, melena,
 Hematuria
 Increased menstrual flow
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

 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
 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.

 Unusual Presentations
of Severe Dengue Fever

 Encephalopathy
 Hepatic damage
 Cardiomyopathy
 Severe gastrointestinal
hemorrhage
 Signs and Symptoms of
Encephalitis/Encephalopathy
Associated with Acute Dengue
Infection
 Decreased level of
consciousness: lethargy,
confusion, coma
 Seizures
 Nuchal rigidity
 Paresis
Physical Exam
 Nonspecific findings
 Conjunctival injection,
pharyngeal erythema,
lymphadenopathy,
hepatomegaly (20-
50%)
 Macular or
maculopapular rash
(50%)
 Laboratory Findings
 Leukopenia
 Thrombocytopenia (<100,000)
 Modest liver enzyme elevation (2-5x nml)
 Serology:
 Acute phase serum IgM (+6-90 days) ELISA
 Acute and convalescent IgG (99% sens, 96%
spec)
 Hemagglutination inhibition assay (HI) is gold
standard. Paired acute and convalescent HI
assay, positive if >4 fold titer rise
 tourniquet test
 The tourniquet test is performed by inflating a
blood pressure cuff to a point mid-way between
the systolic and
 diastolic pressures for five minutes. A test is
considered positive when 10 or more petechiae
per 2.5 cm2 (1 inch)
 are observed. In DHF, the test usually gives a
definite positive result (i.e. >20 petechiae). The
test may be
 negative or mildly positive during the phase of
profound shock.
 Incubation period
3-14 days (commonly 4-7 days)
 History
 China : 265-420 A.D. : water
poison
 French West indies 1635
 Panama 1699
 Jakarta 1779
 Cairo 1779
 Philadelphia 1780
1780 Infrequent large epidemics
 History

 1789 -first definitive case report -

Benjamin Rush, "breakbone fever"
 The world's largest known epidemic of
DHF/DSS- Cuba in 1981
 with more than 116,000 persons
hospitalized and as many as 11,000 cases
reported in a single day
 History

 Albert Sabin –
 first isolated the Dengue virus: type 1 in
the Mediterranean area, during the
Second World War,
 World War II
Chinese India (South East Asia).
 Manila 1953-54
 India
 Pakistan
(the leading cause of
hospitalization and death among
children in SEA 1970s).
 Americas 1970
 Africa
 Before 1980.
 1980 West Africa.
 1980s Central Africa
 1991 Djibouti
 ---------------------------------
 1994 Saudi Arabia
 1997 Worldwide disease
 Dengue is currently classified as
an emerging or re-emerging
infectious disease

1. Overcrowded population.
2. Unplanned & uncontrolled
urbanization.
3. Lack of effective mosquito
control.
4. Increased air travel.
5. Decay of public health measures.
 Treatment
 No specific therapy
 Supportive measures:
adequate hydration
acetaminophen (if no liver dysfunction)
avoid ASA and NSAIDs
 DHF or DHF w/ shock:
IV fluid resuscitation and hospitalization
blood or platelet transfusion as needed
 Treatment
 Treatment with corticosteroids shown not to
reduce mortality with severe dengue shock
 2 studies of 63 and 92 pediatric DHF shock pts
treated w/ hydrocortisone 50mg/kg x1 or
methylprednisolone 30mg/kg x1 dose vs
placebo.
 Study of 95 pediatric DHF shock pts treated with
carbazochrome sodium sulfate (AC-17) vs B
vitamins for 3 days
 Ribavirin very weak in vitro and in vivo activity
against flaviviruses
 Traditional and emerging treatments

 Emerging evidence suggests that

mycophenolic acid and ribavirin inhibit
dengue replication.
 Brazilian traditional medicine,-cat's claw
herb
 Malaysia,-natural medicine. Mas Amirtha
and Semalu
 Philippines -tawa-tawa herbs and sweet
potato tops juice
 Mortality/Morbidity

 Treated DHF/DSS is associated with a 3%

mortality rate.
 Untreated DHF/DSS is associated with a
50% mortality rate.
 Differential Diagnoses

 Hepatitis
 Tick-Borne Diseases, Rocky Mountain Sp
otted Fever
 Malaria
 Yellow Fever
 Meningitis
 Pediatrics, Bacteremia and Sepsis
 Pediatrics, Meningitis and Encephalitis
 Prevention
Biological:
 Target larval stage of Aedes in large water
storage containers
 Larvivorous fish (Gambusia), endotoxin
producing bacteria (Bacillus), copepod
crustaceans (mesocyclops)
Chemical:
 Insecticide treatment of water containers
 Space spraying (thermal fogs)
 Use as a biological weapon
 Dengue fever was one of more than a
dozen agents that the United States
researched as potential
biological weapons before the nation
suspended its biological weapons
program.[45]
 Public Health
 Major and escalating global public health
problem
 Global demographic changes: urbanization and
population growth with substandard housing,
water, and waster management systems
 Deteriorating public health infrastructure with
limited resources resulting in “crisis
management” not prevention
 Increased travel
 Lack of effective mosquito control
Mosquito control:
Options available

“Mosquitoes take
about 7 days to
complete life
cycle.
The first three
Stages: eggs,larva
and pupa are
aquatic.
Therefore, the
best way to
prevent mosquito
breeding is
to remove
stagnant clear
water”
 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
 DHF is a pediatric disease
 All age groups are involved
 DHF is a problem of low income families
 All socioeconomic groups are affected
Important Instructions for
Treatment of DHF
Ø Cases of DHF should be observed every hour.
Ø Serial platelet and hematocrit determinations, drop
in
platelets and rise in hematocrits are essential for early
diagnosis of DHF.
Ø Timely intravenous therapy – isotonic crystalloid
solution –
can prevent shock and/or lessen its severity.
Ø If the patient’s condition becomes worse despite
giving
20ml/kg/hr for one hour, replace crystalloid solution
with
colloid solution such as Dextran or plasma. As soon as
improvement occurs replace with crystalloid.
 Important Instructions for
Treatment of DHF

Ø In case of shock, give oxygen.

Ø For correction of acidosis (sign: deep

breathing), use sodium bicarbonate.
 What not to do

 Ø Do not give Aspirin or Brufen for treatment of fever.

 Ø Avoid giving intravenous therapy before there is evidence of
 haemorrhage and bleeding.
 Ø Avoid giving blood transfusion unless indicated, reduction in
 haematocrit or severe bleeding.
 Ø Avoid giving steroids. They do not show any benefit.
 Ø Do not use antibiotics
 Ø Do not change the speed of fluid rapidly, i.e. avoid rapidly
 increasing or rapidly slowing the speed of fluids.
 Ø Insertion of nasogastric tube to determine concealed
 bleeding or to stop bleeding (by cold lavage) is not
 recommended since it is hazardous.
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