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Dengue
Dengue is a serious viral disease transmitted by thebite of the mosquito, Aedes aegypti.
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Dengue Virus
Causes dengue and dengue hemorrhagic fever
Is an arbovirus Transmitted by mosquitoes
Composed of single-stranded RNA
Has 4 serotypes (DEN-1, 2, 3, 4)
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Dengue Viruses
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 epidemicpotential
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Replication and Transmissionof Dengue Virus
Virus transmitted to human in mosquito saliva
Virus replicates in target organs
Virus infects white blood cells and lymphatic tissues Virus released and circulates in blood
Second mosquito ingests virus with blood
Virus replicates in mosquito midgut and other
organs, infects salivary glands
Virus replicates in salivary glands
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Aedes aegyptiMosquito
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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
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World Distribution of Dengue 1999
Areas infested with Aedes aegypti
Areas with Aedes aegyptiand recent epidemic dengue
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Jogjakarta ProvinceAverage of monthly incidence rate / 100,000
(1997-2006)
02
4
6
8
10
12
14
16
18
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
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Jogjakarta provinceDHF mortality rate (%)
0
0,5
1
1,5
2
2,5
3
3,5
4
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
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Risk Factors Reported for DHF
Virus strain
Pre-existing anti-dengue antibody
previous infection
maternal antibodies in infants Host genetics
Age
Higher risk in secondary infections
Higher risk in locations with two or more serotypes
circulating simultaneously at high levels
(hyperendemic transmission)
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Hypothesis on Pathogenesis of DHF
Persons who have experienced a dengue infection develop serum
antibodies that can neutralize the dengue virus of that same
(homologous) serotype
In a subsequent infection, the pre-existing heterologous antibodies
form complexes with the new infecting virus serotype, but do notneutralize the new virus
Antibody-dependent enhancement is the process in which certain
strains of dengue virus, complexed with non-neutralizing antibodies,
can enter a greater proportion of cells of the mononuclear lineage,
thus increasing virus production
Infected monocytes release vasoactive mediators, resulting in
increased vascular permeability and hemorrhagic manifestations that
characterize DHF and DSS
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Viral Risk Factorsfor 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
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Dengue Clinical Syndromes
Undifferentiated fever
Classic dengue fever
Dengue hemorrhagic fever
Dengue shock syndrome
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Undifferentiated Fever
May be the most common manifestation of dengue
Prospective study found that 87% of studentsinfected were either asymptomatic or only mildly
symptomatic
Other prospective studies including all age- groups
also demonstrate silent transmission
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Clinical Characteristicsof Dengue Fever
Fever
Headache Muscle and joint pain
Nausea/vomiting
Rash
Hemorrhagic manifestations
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Dengue Fever
is an acute febrile illness of 2-7 days duration (sometimes with
two peaks) with two or more of the following manifestations:
headache
retro-orbital pain
myalgia/arthralgia
rash
haemorrhagic manifestation (petechiae and positive tourniquettest) and,
leukopenia.
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Dengue Haemorrhagic Fever
is a probable case of dengue and haemorrhagic tendency evidencedby one or more of the following:
Positive tourniquet test
Petechiae, ecchymosis or purpura
Bleeding from mucosa (mostly epistaxis or bleeding from gums), injectionsites or other sites
Haematemesis or melena
Thrombocytopaenia (platelets 100,000/cu.mm or less) and
Evidence of plasma leakage due to increased capillary permeabilitymanifested by one or more of the following:
A >20% rise in haemotocrit for age and sex
A >20% drop in haemotocrit following treatment with fluids as compared tobaseline
Signs of plasma leakage (pleural effusion, ascites or hypoproteinaemia).
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Dengue Shock Syndrome (DSS)
All the above criteria of DHF plus signs of
circulatory failure manifested by rapid and weakpulse, narrow pulse pressure (< or equal to 20 mm
Hg); hypotension for age, cold and clammy skin
and restlessness.
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Petechiae
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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 consideredpositive 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.
Signs and Symptoms of
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Signs and Symptoms ofEncephalitis/Encephalopathy
Associated with Acute Dengue Infection
Decreased level of consciousness: lethargy,
confusion, coma Seizures
Nuchal rigidity
Paresis
H h i M if t ti
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Hemorrhagic Manifestationsof Dengue
Skin hemorrhages: petechiae, purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastro-intestinal bleeding: hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow
Cli i l C D fi iti f
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Clinical Case Definition forDengue Hemorrhagic Fever
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
4 Necessary Criteria:
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Cli i l C D fi iti f D
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Clinical Case Definition for DengueShock Syndrome
4 criteria for DHF
Evidence of circulatory failure manifestedindirectly by all of the following:
Rapid and weak pulse
Narrow pulse pressure ( 20 mm Hg) ORhypotension for age
Cold, clammy skin and altered mental status
Frank shock is direct evidence of circulatoryfailure
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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)
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WHO guidelines for the diagnosis of dengue haemorrhagic fever(DHF) and dengue shock syndrome (DSS).
Danger Signs in
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Danger Signs inDengue Hemorrhagic Fever
Abdominal pain - intense and sustained Persistent vomiting
Abrupt change from fever to hypothermia, with
sweating and prostration
Restlessness or somnolence
Martnez Torres E. Salud Pblica Mex 37 (supl):29-44, 1995.
Laboratory Tests
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Laboratory Testsin Dengue Fever
Clinical laboratory tests
CBC--WBC, platelets, hematocrit
Albumin
Liver function tests
Urine--check for microscopic hematuria
Dengue-specific tests
Virus isolation
Serology (IgM & IgG anti Den)
General Recommendations
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General Recommendationsfor Medical Care
Epidemiologic considerations
Season of year Travel history
Diagnosis
Treatment
Follow-up
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Differential Diagnosis of Dengue
Influenza
Measles
Rubella
Malaria Typhoid fever
Leptospirosis
Meningococcemia
Rickettsial infections
Bacterial sepsis Other viral hemorrhagic fevers
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Management of DF
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Management of DHF Grade I/II
V l R l t Fl Ch t f P ti t ith
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Volume Replacement Flow Chart for Patients withDHF Grades I and II
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V l R l t Fl Ch t f ti t ith
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Volume Replacement Flow Chart for patient withDHF Grades III and IV
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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
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Important Instructions for Treatment of DHF
Cases of DHF should be observed every hour. Serial platelet and haematocrit determinations, drop in plaelets and rise in
haematocrits are essential for early diagnosis of DHF.
Timely intravenous therapy isotonic crystalloid solution can prevent shockand/or lessen its severity.
If the patients condition becomes worse despite giving 20ml/kg/hr for onehour, replace crystalloid solution with colloid solution such as Dextran or
plasma. As soon as improvement occurs replace with crystalloid. If improvement occurs, reduce the speed from 20 ml to 10 ml, then to 6 ml,
and finally to 3 ml/kg.
If haematocrit falls, give blood transfusion 10 ml/kg and then give crystalloidIV fluids at the rate of 10ml/kg/hr.
In case of severe bleeding, give fresh blood transfusion about 20 ml/kg fortwo hours. Then give crystalloid at 10 ml/kg/hr for a short time (30-60
minutes) and later reduce the speed. In case of shock, give oxygen.
For correction of acidosis (sign: deep breathing), use sodium bicarbonate7.
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Criteria for Discharging Patients
Absence of fever for at least 24 hours without the
use of anti-fever therapy
Return of appetite
Visible clinical improvement Good urine output
Minimum of three days after recovery from shock
No respiratory distress from pleural effusion and no
ascites Platelet count of more than 50,000/mm3
Prevention Elimination of mosquito
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Prevention - Elimination of mosquitobreeding places
Cover water containersTight covers on water storage containers,will prevent the mosquitos laying their eggs there. If the cover isloose, mosquitos can go in and out.
Septic tanks and soak-away pitsCover and seal these, so thatdengue mosquitos cannot breed there.
Removal of rubbishGarbage articles and other rubbish foundaround houses can collect rain water. They should be removed orsmashed and buried in the ground or burned, where this ispermissible.
Biological controlMosquito wigglers can be controlled by smalllarva-eating fish, such as guppies. These fish can be found instreams or ponds or obtained through pet shops. Bacterial pesticides
will also kill mosquito wigglers.
Chemical controlSafe and easily used larvicides such astemephos sand core granules can be placed in water containers tokill developing wigglers.
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Prevention - prevent mosquito bites
Mosquito coils and electric vapour matsSlow burning mosquito coils orelectric vapour mats are effective in the rainy season, just after sunrise and/orin the afternoon hours before sunset, when dengue mosquitos bite.
Mosquito netsNets placed over sleeping places can protect small childrenand others who may rest during the day. The effectiveness of such nets canbe improved by treating them with permethrin (a pyrethroid insecticide).Curtains (cloth or bamboo) can also be treated with insecticide and hung at
windows or doorways, to repel or kill mosquitos.
RepellentsMosquito repellents can be applied to exposed parts of thebody where mosquitos bite. Care should be taken in using repellents on smallchildren and the elderly.
ScreensScreens on windows and doorways are effective protectionagainst the entry of mosquitos in homes.
Protection of people sick with dengueMosquitos become infected whenthey bite people who are sick with dengue. Mosquito nets and mosquito coilswill effectively prevent mosquitos from biting sick people and help stop thespread of dengue.