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HEMORRHAGIC FEVER
Kuliah Blok Kedokteran Tropis
INTRODUCTION
Dengue is a viral infection transmitted by mosquitoes, mainly
the Aedes aegypti species.
The virus is contracted from the bite of a striped Aedes
aegypti mosquito that has previously bitten an infected
person. One mosquito bite can inflict the disease.
There are four strains or serotypes of dengue virus namely
DEN-1, DEN-2, DEN-3 and DEN-4.
The mosquito flourishes during rainy seasons but can breed in
water-filled containers, year-round.
The virus is not contagious and cannot be spread directly from
person to person. There must be a person-to-mosquito-toanother-person pathway.
Dengue haemorrhagic fever severe form of dengue. A
second attack by dengue virus of a different serotype from the
first infection.
Dengue fever
Main hosts- non human
primates
Human-to-human
transmission through
Aedes spp.
2.5 billion individuals at
risk
40-80 million infected
each year with thousands
of deaths
Bauman, R., (2006). Microbiology disease by systems. San Francisco , CA: Pearson
Benjamin Cumming Publishers
Dengue Virus
1. Causes dengue and dengue hemorrhagic fever
2. It is an arbovirus
3. Transmitted by mosquitoes
4. Composed of single-stranded RNA
5. Has 4 serotypes (DEN-1, 2, 3, 4)
Dengue Virus
Each serotype provides specific lifetime immunity,
and short-term cross-immunity
All serotypes can cause severe and fatal disease
Genetic variation within serotypes
Some genetic variants within each serotype appear
to be more virulent or have greater epidemic potential
WORLD-WIDE DENGUE
DISTRIBUTION
Geography distribution of
Dengue
BBB
IR per 100,000
No of City/Districts Infected
Dengue (DHF)
Outbreak in
Indonesia (2004)
Outbreak areas
Potential Outbreak areas
Aedes aegypti
Dengue transmitted by infected female
mosquito
Primarily a daytime feeder
Lives around human habitation
Lays eggs and produces larvae
preferentially in artificial containers
2-7 days
>4 days
2 days
The transmission cycle of dengue virus by the mosquito Aedes aegypti begins
with a dengue-infected person. This person will have virus circulating in the blood
a viremia that lasts for about five days. During the viremic period, an uninfected
female Aedes aegypti mosquito bites the person and ingests blood that contains
dengue virus. Although there is some evidence of transovarial transmission of
dengue virus in Aedes aegypti, usually mosquitoes are only infected by biting a
viremic person.
Then, within the mosquito, the virus replicates during an extrinsic incubation
period of eight to twelve days.
The mosquito then bites a susceptible person and transmits the virus to him or
her, as well as to every other susceptible person the mosquito bites for the rest of
its lifetime.
The virus then replicates in the second person and produces symptoms. The
symptoms begin to appear an average of four to seven days after the mosquito
bitethis is the intrinsic incubation period, within humans. While the intrinsic
incubation period averages from four to seven days, it can range from three to 14
days.
The viremia begins slightly before the onset of symptoms. Symptoms caused by
dengue infection may last three to 10 days, with an average of five days, after the
onset of symptomsso the illness persists several days after the viremia has
ended.
Population
5%
Infection
76%
Asymptomatic
Infection
24%
Clinical Cases 6%
94%
DF
(non-DHF)
99.2%
survive
DHF/DSS
0.8%
Death
DENGUE
FEVER
Incubation period = 5 days
Fever = 5 days
Leukopenia
Moderate thrombocytopenia
Simmons et al
Phil J Sci 44:1-252, 1931
Clinical Manifestations- DF
Other manifestations- DF
Treatment of DF
DISEASE SPECTRUM
MILD
DF
SEVERE
DHF
DENGUE HEMORRHAGIC
FEVER/DENGUE SHOCK
SYNDROME (DHF/DSS)
Dengue vasculopathy
Vascular instability
Decreased vascular integrity
Assault on macro vasculature
Decreased platelet function
Increased vascular permeability
Vascular disruption and local bleeds
Hypotension, hemoconcentration- shock
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 inch (6.25 cm)
Tourniquet Test
Hemorrhagic Manifestations
Skin hemorrhages:
petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding:
hematemesis, melena, hematochezia
Haematuria
Increased menstrual flow
Petechiae
+
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
Capillary Damage
Ecchymosis Periorbital
Edema
Pleural Effusion
PEI = A / B x 100
DSS GRADE IV
DHF
DHF / DSS
Intensive Care
Oxygen
Rehydration
Barrier Nursing
Mosquito Screen
Management of DHF/DSS
Fluid Balance
Unusual Presentations of
Dengue
Encephalopathy
Hepatic damage
Cardiomyopathy
Severe GI bleeding
Differential Diagnosis
FM complex
1. Anicteric leptospirosis
2. Rickettsial fevers
3. Influenza, Measles, Rubella
DHF / DSS
1.
2.
3.
4.
Laboratory Diagnosis
Laboratory Diagnosis
Leucopenia. Thrombocytopenia
Increased SGOT, SGPT
Rising Ab titre in paired sera
Antigen detection ELISA
IgM-capture ELISA within few hours
Reverse transcription PCR confirmatory
IgG ELISA significant of past infection
LABORATORY CRITERIA
ELISA Plate
IgM-capture ELISA
Immunization
PRIMARY INFECTIONS
Clinical Features
!
In children
DEN 1 & 3 mild illness
DEN 2 & 4 no illness
In adults
DEN 1 & 3 Disease/Infection ~1; g.i. hemorrhages
may accompany peptic ulcer disease.
DEN 2 & 4 - mild - moderate
Two-infections
The epidemiological data
DHF documented in children (> 1 yr)
who circulate infection-acquired
dengue antibody. Four prospective
cohort and 6 prospective
population-based studies.
In most studies, DHF comprises 25% of secondary infections
DHF/2 DHF/1000
o
Den Inf. 2 Den Inf.
Russell et al, AJTMH
3/83
36.1
17:600,1968
Sangawibha et al, AJE 4/112
35.7
120:653, 1984
Burke et al, AJTMH
7/59
118.6
38:172, 1988
Graham et al,
7/120
58.3
AJTMH 61:412, 1999
DHF IN CHILDREN:
PROSPECTIVE POPULATIONBASED STUDIES
References
DHF/ DHF/1000
2o Den Inf 2o Den Inf
Halstead Acad
2528/
20.1
Press 107,1980
125,728
Russell et al AJTMH 33/2700
12.2
18:600,1968
Sangkawibha et al
18/920
19.6
AJE 120:653,1984
AJE
DHF IN CHILDREN:
PROSPECTIVE POPULATIONBASED STUDIES
References
DHF/2 DHF/1000
o
Den Inf 2 Den Inf
Guzman et al
1213/
20.3
AJTMH 42:179,1990 59,875
Thein et al AJTMH 138/4181
33.0
56:566,1997
Guzman et al AJE
202/4810
42.0
152:793, 2000
21
31
12
32
42
13
23
14
24
34
Thailand; Indonesia
Thailand
Cuba, 1981; Cuba 1997; Thailand
Thailand
Thailand
Cuba, 2001; Thailand; Indonesia
Thailand, DF in Cuba
Thailand
Indonesia
Thailand
DIAGNOSIS
Classic symptoms : high fever, a petechial rash
with thrombocytopenia & relative leukopenia
(decrease in the number of circulating WBC in the
blood).
WHO definition of DHF :
Fever
Haemorrhagic tendency [positive tourniquet test
(> than 20 petechiae per square inch),
spontaneous bruising, bleeding from mucosa,
gingiva, injection sites, vomiting blood or bloody
diarrhea].
Thrombocytopaenia [<100,000 platelets per mm].
Evidence of plasma leakage [rise in hematocrit
level > than 20%].
Serology (identification of antibodies in the blood
serum) & polymerase chain reaction (PCR) to
confirm the diagnosis of dengue if clinically
indicated.
SYMPTOMS
Sudden high fever (39-41.5C)
for 2 to 7 days
Headache
Pain behind the eyes
Muscle pain, joint pain, bone
pain (break-bone fever)
After 1 to 2 days of fever, the
patient develops initial rash
with discoloured spots, often
described as Isles of white in
a sea of red
Second rash may develop to
palms and soles, and skin
may peel off (desquamate) &
body temperature drops
TREATMENTS
No specific antiviral treatment, only supportive
treatment is given to such patients.
If the patient is dehydrating, adequate fluids are
to be taken.
Intravenous fluid is administered if the patient is
unable to maintain oral intake.
For severe body ache, painkillers may be needed.
For severe headache and for joint and muscle
pain, acetaminophen/paracetamol and codeine
may be given.
If there is significant bleeding, blood or platelet
transfusion will be carried out.
Note : Aspirin should be avoided as this drug
may worsen the bleeding tendency (because
of its anticoagulant effects & the increased
risk of developing Reye syndrome).
PREVENTIONS
There is currently no vaccine
STRATEGIES
available
for
the
dengue
fever.
Individual roles. People are urged to
empty stagnant water from old tires,
trash cans & flower pots.
Mosquito control. Place larvicide e.g.
Abate or any other suitable insecticides
into any exposed water container. Use
mosquito repellant sprays that contain
NNDB or DEET.
Enforcement. Local authorities from
Ministry of Health conduct on-site check &
destroy larvae at residential premises &
construction sites. Fines may be imposed
on the owner of properties.
PREVENTIONS
Fogging with insecticide. Fogging
would be carried out by local
authorities in housing area where 2 or
more cases of dengue fever are
reported within one week.
Information. In Nov 2007, the
Ministry of Health carried out a major
campaign against Aedes. During the
campaign free packages of Abate
were distributed. Leaflets & brochures
to inform the public on ways to
prevent & curb Aedes breeding are
distributed.
Awareness campaign. Schools &
local communities are encouraged to
carry out communal cleaning
activities. Public awareness
campaigns through strategically
placed posters & television
advertisements are also done.
Unwanted items