demam berdarah

DengueDengueClinical Manifestations Clinical Manifestations

and Epidemiologyand Epidemiology

CENTERS FOR DISEASE CONTROLAND PREVENTION

I. Virus, Vector and TransmissionI. Virus, Vector and Transmission

Dengue VirusDengue Virus

Causes dengue and dengue hemorrhagic Causes dengue and dengue hemorrhagic feverfever

Is an arbovirusIs an arbovirus Transmitted by mosquitoesTransmitted by mosquitoes Composed of single-stranded RNAComposed of single-stranded RNA Has 4 serotypes (DEN-1, 2, 3, 4)Has 4 serotypes (DEN-1, 2, 3, 4)

Dengue VirusesDengue Viruses

Each serotype provides specific lifetime Each serotype provides specific lifetime immunity, and short-term cross-immunityimmunity, and short-term cross-immunity

All serotypes can cause severe and fatal All serotypes can cause severe and fatal diseasedisease

Genetic variation within serotypesGenetic variation within serotypes Some genetic variants within each serotype Some genetic variants within each serotype

appear to be more virulent or have greater appear to be more virulent or have greater epidemic potentialepidemic potential

Transmission of Dengue VirusTransmission of Dengue Virusby by Aedes aegyptiAedes aegypti

Viremia Viremia

Extrinsic incubation

period

DAYS0 5 8 12 16 20 24 28

Human #1 Human #2

Illness

Mosquito feeds /acquires virus

Mosquito refeeds /transmits virus

Intrinsicincubation

period

Illness

Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 1)of Dengue Virus (Part 1)

1. Virus transmitted to human in mosquito saliva

2. Virus replicates in target organs

3. Virus infects white blood cells and lymphatic tissues

4. Virus released and circulates in blood

3

4

1

2

Replication and TransmissionReplication and Transmissionof Dengue Virus (Part 2)of Dengue Virus (Part 2)

5. Second mosquito ingests virus with blood

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

7. Virus replicates in salivary glands

6

7

5

Aedes aegyptiAedes aegypti Mosquito Mosquito

Aedes aegyptiAedes aegypti

Dengue transmitted by infected female Dengue transmitted by infected female mosquitomosquito

Primarily a daytime feederPrimarily a daytime feeder Lives around human habitationLives around human habitation Lays eggs and produces larvae Lays eggs and produces larvae

preferentially in artificial containerspreferentially in artificial containers

II. Disease Surveillance and ControlII. Disease Surveillance and Control

Proactive Surveillance:Proactive Surveillance:Goals and ObjectivesGoals and Objectives

Provide early and precise informationProvide early and precise information• timetime

• locationlocation

• virus serotypevirus serotype

• disease severitydisease severity Predict dengue transmission and guide Predict dengue transmission and guide

implementation of control measuresimplementation of control measures Link clinical and entomologic surveillanceLink clinical and entomologic surveillance

Proactive Surveillance in Puerto RicoProactive Surveillance in Puerto Rico

Blood samples obtained by private physicians, Blood samples obtained by private physicians, health centers, public and private hospitalshealth centers, public and private hospitals

Samples transported by staff from Health Samples transported by staff from Health Department and private laboratoriesDepartment and private laboratories

Samples tested at the CDC Dengue BranchSamples tested at the CDC Dengue Branch Results provided to submitting source and Health Results provided to submitting source and Health

Department vector control staffDepartment vector control staff Analyses disseminated via Dengue Surveillance Analyses disseminated via Dengue Surveillance

SummarySummary

Organization and Functions:Organization and Functions:

Vector Control Methods:Vector Control Methods:Chemical ControlChemical Control

Larvicides may be used to kill immature Larvicides may be used to kill immature aquatic stagesaquatic stages

Ultra-low volume fumigation ineffective Ultra-low volume fumigation ineffective against adult mosquitoesagainst adult mosquitoes

Mosquitoes may have resistance to Mosquitoes may have resistance to commercial aerosol sprayscommercial aerosol sprays

Vector Control Methods:Vector Control Methods:Biological and Environmental ControlBiological and Environmental Control

Biological controlBiological control• Largely experimentalLargely experimental

• Option: place fish in containers to eat larvaeOption: place fish in containers to eat larvae Environmental controlEnvironmental control

• Elimination of larval habitatsElimination of larval habitats

• Most likely method to be effective in the long Most likely method to be effective in the long termterm

Purpose of ControlPurpose of Control

Reduce female vector density to a level Reduce female vector density to a level below which epidemic vector transmission below which epidemic vector transmission will not occurwill not occur

Based on the assumption that eliminating or Based on the assumption that eliminating or reducing the number of larval habitats in the reducing the number of larval habitats in the domestic environment will control the vectordomestic environment will control the vector

The minimum vector density to prevent The minimum vector density to prevent epidemic transmission is unknownepidemic transmission is unknown

Programs to MinimizePrograms to Minimizethe Impact of Epidemicsthe Impact of Epidemics

Education of the medical communityEducation of the medical community Implementation of emergency contingency Implementation of emergency contingency

planplan Education of the general populationEducation of the general population

III. Clinical Manifestations of Dengue III. Clinical Manifestations of Dengue and Dengue Hemorrhagic Feverand Dengue Hemorrhagic Fever


Dengue Clinical SyndromesDengue Clinical Syndromes

Undifferentiated feverUndifferentiated fever Classic dengue feverClassic dengue fever Dengue hemorrhagic feverDengue hemorrhagic fever Dengue shock syndromeDengue shock syndrome

Undifferentiated FeverUndifferentiated Fever

May be the most common manifestation of May be the most common manifestation of denguedengue

Prospective study found that 87% of Prospective study found that 87% of students infected were either asymptomatic students infected were either asymptomatic or only mildly symptomaticor only mildly symptomatic

Other prospective studies including all age- Other prospective studies including all age- groups also demonstrate silent transmissiongroups also demonstrate silent transmission

DS Burke, et al. A prospective study of dengue infectionsin Bangkok. Am J Trop Med Hyg 1988; 38:172-80.

Clinical CharacteristicsClinical Characteristicsof Dengue Feverof Dengue Fever

FeverFever HeadacheHeadache Muscle and joint painMuscle and joint pain Nausea/vomitingNausea/vomiting RashRash Hemorrhagic manifestationsHemorrhagic manifestations

Signs and Symptoms ofSigns and Symptoms ofEncephalitis/EncephalopathyEncephalitis/Encephalopathy

Associated with Acute Dengue InfectionAssociated with Acute Dengue Infection

Decreased level of consciousness: Decreased level of consciousness: lethargy, confusion, comalethargy, confusion, coma

SeizuresSeizures Nuchal rigidityNuchal rigidity ParesisParesis

Hemorrhagic ManifestationsHemorrhagic Manifestationsof Dengueof Dengue

Skin hemorrhages: petechiae, Skin hemorrhages: petechiae, purpura, ecchymosespurpura, ecchymoses

Gingival bleedingGingival bleeding Nasal bleedingNasal bleeding Gastro-intestinal bleeding: Gastro-intestinal bleeding:

hematemesis, melena, hematocheziahematemesis, melena, hematochezia HematuriaHematuria Increased menstrual flowIncreased menstrual flow

Clinical Case Definition forClinical Case Definition forDengue Hemorrhagic FeverDengue Hemorrhagic Fever

Fever, or recent history of acute feverFever, or recent history of acute fever Hemorrhagic manifestationsHemorrhagic manifestations Low platelet count (100,000/mmLow platelet count (100,000/mm33 or less) or less) Objective evidence of “leaky capillaries:”Objective evidence of “leaky capillaries:”

• elevated hematocrit (20% or more over baseline)elevated hematocrit (20% or more over baseline)

• low albuminlow albumin

• pleural or other effusionspleural or other effusions

4 Necessary Criteria:4 Necessary Criteria:

Clinical Case Definition for Clinical Case Definition for Dengue Shock SyndromeDengue Shock Syndrome

4 criteria for DHF4 criteria for DHF Evidence of circulatory failure manifested Evidence of circulatory failure manifested

indirectly by all of the following:indirectly by all of the following:• Rapid and weak pulseRapid and weak pulse

• Narrow pulse pressure (Narrow pulse pressure ( 20 mm Hg) 20 mm Hg) OR OR hypotension for agehypotension for age

• Cold, clammy skin and altered mental statusCold, clammy skin and altered mental status Frank shock is direct evidence of circulatory Frank shock is direct evidence of circulatory

failurefailure

Four Grades of DHFFour Grades of DHF Grade 1Grade 1

• Fever and nonspecific constitutional symptomsFever and nonspecific constitutional symptoms

• Positive tourniquet test is only hemorrhagic manifestationPositive tourniquet test is only hemorrhagic manifestation Grade 2Grade 2

• Grade 1 manifestations + spontaneous bleedingGrade 1 manifestations + spontaneous bleeding Grade 3Grade 3

• Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin)hypotension, cold/clammy skin)

Grade 4Grade 4• Profound shock (undetectable pulse and BP)Profound shock (undetectable pulse and BP)

Danger Signs inDanger Signs inDengue Hemorrhagic FeverDengue Hemorrhagic Fever

Abdominal pain - intense and sustainedAbdominal pain - intense and sustained Persistent vomitingPersistent vomiting Abrupt change from fever to hypothermia, Abrupt change from fever to hypothermia,

with sweating and prostrationwith sweating and prostration Restlessness or somnolenceRestlessness or somnolence

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

Warning Signs for Dengue ShockWarning Signs for Dengue Shock

When Patients Develop DSS:• 3 to 6 days after onset of symptoms

When Patients Develop DSS:• 3 to 6 days after onset of symptoms

Initial Warning Signals:• Disappearance of fever• Drop in platelets• Increase in hematocrit

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 or somnolence)

Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from fever to hypothermia• Change in level of consciousness (irritability or somnolence)

Four Criteria for DHF:• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets

Four Criteria for DHF:• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets

Signs and Symptoms in 57 Signs and Symptoms in 57 Hospitalized Cases of DHF, Hospitalized Cases of DHF,

Puerto Rico, 1990 - 1991Puerto Rico, 1990 - 1991

* Minimum estimate, search was not uniform for all patients** Only 2 (3.5%) cases had severe hemorrhagic manifestations

SIGNS AND SYMPTOMS FREQUENCY* PERCENT

Fever 57 100 %Rash 27 47.4%Hepatomegaly 6 10.5%Effusions 3 5.3%Frank shock 3 5.3%Coma 2 3.5%Any hemorrhage** 57 100 %

Hemorrhagic Signs and Symptoms Hemorrhagic Signs and Symptoms in 57 Hospitalized Cases of DHF, in 57 Hospitalized Cases of DHF,


SIGNS & SYMPTOMS FREQUENCY* PERCENT**

Microscopic hematuria 28 51.9%Petechiae 26 45.6%Epistaxis 13 22.8%Gingival hemorrhage 8 14.0%Blood in stools 8 14.0%Positive tourniquet test 5 31.3%

* Minimum estimate; the search was not uniform for all patients** Percents were calculated using the number of patients among whom each symptom was sought as the denominator

Hemorrhagic Signs and Symptoms Hemorrhagic Signs and Symptoms in 57 Hospitalized Cases of DHF, in 57 Hospitalized Cases of DHF,


SIGNS & SYMPTOMS FREQUENCY* PERCENT

Blood in vomitus 4 7.0%Bleeding at venipuncture 4 7.0%Hemoptysis 3 5.3%Vaginal hemorrhage 2 3.5%Gross hematuria 2 3.5%Other hemorrhage** 2 3.5%

* Minimum estimate; the search was not uniform for all patients** Only 2 (3.5%) cases had severe hemorrhagic manifestations

Clinical Laboratory Analyses in Clinical Laboratory Analyses in 57 Hospitalized Cases of DHF, 57 Hospitalized Cases of DHF,


* Average result in the tested cases

Test with Abnormal Result Frequency* Mean Result (Range)

Thrombocytopenia Platelet count 57/57 (100%) 45,980 (9 - 99,000)

Increased Capillary Permeability

Hemoconcentration 0.20 34/57 (59.6%) 0.26 (0 - 1.0) Low serum protein 18/51 (35.3%) 6.3 (3.8 - 8.3) Low serum albumin 35/52 (67.3%) 3.5 (2.3 - 4.9)

Profile of the Progression of IllnessProfile of the Progression of IllnessMean Days from Onset of Symptoms, andMean Days from Onset of Symptoms, and

Mean Value (± 2 SD) of Selected Clinical TestsMean Value (± 2 SD) of Selected Clinical Tests

5 6 7 8DAYS AFTER ONSETAverage admission - day 4.5

Average discharge - day 11

Puerto Rico, 1990-1991 (N=57 patients)

MaximumHematocrit

(%)

45.2

57

34

Lowest Diastolic(mm Hg)

88

42

65.6

Plateletsper mm3

99,000

45,980

9,000

MinimumHematocrit (%)

44

36.3

23

Unusual PresentationsUnusual Presentationsof Severe Dengue Feverof Severe Dengue Fever

EncephalopathyEncephalopathy Hepatic damageHepatic damage CardiomyopathyCardiomyopathy Severe gastrointestinal hemorrhageSevere gastrointestinal hemorrhage

IV. EpidemiologyIV. Epidemiology

World Distribution of Dengue 1999World Distribution of Dengue 1999

Areas infested with Aedes aegyptiAreas with Aedes aegypti and recent epidemic dengue

Reported Cases of DengueReported Cases of Denguein the Americas, 1980 - 1999in the Americas, 1980 - 1999

* Provisional data for 1999

0

100

200

300

400

500

600

700

800

Rep

ort

ed C

ases

(T

ho

usa

nd

s)

80 82 84 86 88 90 92 94 96 98

Mean Annual Number of DHF CasesMean Annual Number of DHF CasesThailand, Indonesia and Vietnam, by DecadeThailand, Indonesia and Vietnam, by Decade

* Provisional data through 1998

020406080

100120140160180200

Rep

orte

d C

ases

(T

hou

san

ds)

1950s 1960s 1970s 1980s 1990s*

Reported Cases of DHF Reported Cases of DHF in the Americas, 1970 - 1999in the Americas, 1970 - 1999

* Provisional data through 1999

0

10

20

30

40

50

60

Rep

ort

ed C

ases

(Th

ou

san

ds)

1970s 1980s 1990s*

Presence of DEN-3 in the Americas, Presence of DEN-3 in the Americas, 1994 -19991994 -1999

19941995

19981997

1999

SOURCE: Pan American Health Organization, 1994 -1999

Recent Dengue in the U.S.A. (Texas)Recent Dengue in the U.S.A. (Texas) Dengue epidemics occurred in the USA in the 1800s and the first half of the Dengue epidemics occurred in the USA in the 1800s and the first half of the

1900s1900s Recent indigenous transmissionRecent indigenous transmission

• 1980: 23 cases, first locally acquired since 19451980: 23 cases, first locally acquired since 1945• 1986: 9 cases1986: 9 cases• 1995: 7 cases1995: 7 cases• 1997: 3 cases1997: 3 cases• 1998: 1 case1998: 1 case• 1999: 18 cases1999: 18 cases

Lack of recent transmission likely due to changes in life-styleLack of recent transmission likely due to changes in life-style

Reasons for Dengue Expansion Reasons for Dengue Expansion in the Americasin the Americas

Extensive vector infestation, with declining Extensive vector infestation, with declining vector controlvector control

Unreliable water supply systemsUnreliable water supply systems Increasing non-biodegradable containers Increasing non-biodegradable containers

and poor solid waste disposaland poor solid waste disposal Increased air travelIncreased air travel Increasing population density in urban areasIncreasing population density in urban areas

Trouble AheadTrouble Ahead

2.5 billion people at risk world-wide2.5 billion people at risk world-wide In the Americas, 50-fold increase in In the Americas, 50-fold increase in

reported cases of DHF (1989-1993 reported cases of DHF (1989-1993 compared to 1984-1988)*compared to 1984-1988)*

Widespread abundance of Widespread abundance of Aedes aegyptiAedes aegypti in in at-risk areasat-risk areas

* Organization of American States, Human Health in the Americas, 1996

V. Disease PathogenesisV. Disease Pathogenesis

Risk Factors Reported for DHFRisk Factors Reported for DHF

Virus strainVirus strain Pre-existing anti-dengue antibodyPre-existing anti-dengue antibody

• previous infectionprevious infection

• maternal antibodies in infantsmaternal antibodies in infants Host geneticsHost genetics AgeAge

Risk Factors for DHF (continued)Risk Factors for DHF (continued)

Higher risk in secondary infectionsHigher risk in secondary infections Higher risk in locations with two or more Higher risk in locations with two or more

serotypes circulating simultaneously at high serotypes circulating simultaneously at high levels (hyperendemic transmission)levels (hyperendemic transmission)

Increased Probability of DHFIncreased Probability of DHFHyperendemicity

Increased circulationof viruses

Increased probabilityof secondary infection

Increased probability ofoccurrence of virulent strains

Increased probability ofimmune enhancement

Increased probability of DHFGubler & Trent, 1994

Hypothesis on PathogenesisHypothesis on Pathogenesisof DHF (Part 1)of DHF (Part 1)

Persons who have experienced a dengue Persons who have experienced a dengue infection develop serum antibodies that can infection develop serum antibodies that can neutralize the dengue virus of that same neutralize the dengue virus of that same ((homologoushomologous) serotype) serotype

Neutralizing antibody to Dengue 1 virus

1

1

Dengue 1 virus 1

Homologous Antibodies Form Homologous Antibodies Form Non-infectious ComplexesNon-infectious Complexes

Non-neutralizing antibody

1

1 Complex formed by neutralizing antibody and virus


In a subsequent infection, the pre-existing In a subsequent infection, the pre-existing heterologousheterologous antibodies form complexes antibodies form complexes with the new infecting virus serotype, but with the new infecting virus serotype, but do not neutralize the new virusdo not neutralize the new virus

Non-neutralizing antibody to Dengue 1 virus

Dengue 2 virus

2 2

2

2

2

Heterologous Antibodies Form Heterologous Antibodies Form Infectious ComplexesInfectious Complexes

Complex formed by non-neutralizing antibody and virus

2


Antibody-dependent enhancement Antibody-dependent enhancement is the process in which certain is the process in which certain strains of dengue virus, complexed strains of dengue virus, complexed with non-neutralizing antibodies, with non-neutralizing antibodies, can enter a greater proportion of can enter a greater proportion of cells of the mononuclear lineage, cells of the mononuclear lineage, thus increasing virus productionthus increasing virus production

2

2

2

2

22

2

22

2

Heterologous Complexes Enter More Heterologous Complexes Enter More Monocytes, Where Virus ReplicatesMonocytes, Where Virus Replicates

Non-neutralizing antibody

Dengue 2 virus 2

Complex formed by non-neutralizing antibody and Dengue 2 virus

2


Infected monocytes release vasoactive Infected monocytes release vasoactive mediators, resulting in increased vascular mediators, resulting in increased vascular permeability and hemorrhagic permeability and hemorrhagic manifestations that characterize DHF and manifestations that characterize DHF and DSSDSS

Viral Risk FactorsViral Risk Factorsfor DHF Pathogenesisfor DHF Pathogenesis

Virus strain (genotype)Virus strain (genotype)• Epidemic potential: viremia level, infectivityEpidemic potential: viremia level, infectivity

Virus serotypeVirus serotype• DHF risk is greatest for DEN-2, followed by DHF risk is greatest for DEN-2, followed by

DEN-3, DEN-4 and DEN-1DEN-3, DEN-4 and DEN-1

VI. DiagnosisVI. Diagnosis

General RecommendationsGeneral Recommendationsfor Medical Carefor Medical Care

Epidemiologic considerationsEpidemiologic considerations• Season of yearSeason of year

• Travel historyTravel history DiagnosisDiagnosis TreatmentTreatment Follow-upFollow-up

Seasonal Trends in Dengue Incidence: Seasonal Trends in Dengue Incidence: Puerto RicoPuerto Rico

3-week moving average: June, 1990 - December, 1998

Week Number

Tot

al S

amp

les

Rec

eive

dp

er W

eek

‘90 1991 1992 1993 1994 1995 1996 1997 19982000

1500

1000

500

030 50 10 30 50 10 30 50 10 30 50 10 30 50 10 30 50 10 30 50 10 30 50 10 30 50

Travel HistoryTravel History

Important for assessment of symptomatic Important for assessment of symptomatic patients in non-endemic areaspatients in non-endemic areas

Determine whether the patient travelled to a Determine whether the patient travelled to a dengue-endemic areadengue-endemic area

Determine when the travel occurredDetermine when the travel occurred• If the patient developed fever more than 2 If the patient developed fever more than 2

weeks after travel, eliminate dengue from the weeks after travel, eliminate dengue from the differential diagnosisdifferential diagnosis

Differential Diagnosis of DengueDifferential Diagnosis of Dengue InfluenzaInfluenza MeaslesMeasles RubellaRubella MalariaMalaria Typhoid feverTyphoid fever LeptospirosisLeptospirosis MeningococcemiaMeningococcemia Rickettsial infectionsRickettsial infections Bacterial sepsisBacterial sepsis Other viral hemorrhagic feversOther viral hemorrhagic fevers

Clinical Evaluation in Dengue FeverClinical Evaluation in Dengue Fever

Blood pressureBlood pressure Evidence of bleeding in skin or other sitesEvidence of bleeding in skin or other sites Hydration statusHydration status Evidence of increased vascular permeability-- Evidence of increased vascular permeability--

pleural effusions, ascitespleural effusions, ascites Tourniquet testTourniquet test

PetechiaePetechiae

Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrilephase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.


A

B

PEI = A/B x 100

Pleural Effusion IndexPleural Effusion Index

Tourniquet TestTourniquet Test

Inflate blood pressure cuff to a point Inflate blood pressure cuff to a point midway between systolic and midway between systolic and diastolic pressure for 5 minutesdiastolic pressure for 5 minutes

Positive test: 20 or more petechiae per Positive test: 20 or more petechiae per 1 inch1 inch2 2 (6.25 cm(6.25 cm22))

Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 12.

Positive Tourniquet TestPositive Tourniquet Test

Laboratory TestsLaboratory Testsin Dengue Feverin Dengue Fever

Clinical laboratory testsClinical laboratory tests• CBC--WBC, platelets, hematocritCBC--WBC, platelets, hematocrit• AlbuminAlbumin• Liver function testsLiver function tests• Urine--check for microscopic hematuriaUrine--check for microscopic hematuria

Dengue-specific testsDengue-specific tests• Virus isolationVirus isolation• SerologySerology

Laboratory Methods for Dengue Laboratory Methods for Dengue Diagnosis, CDC Dengue BranchDiagnosis, CDC Dengue Branch

Virus isolation to determine serotype of the Virus isolation to determine serotype of the infecting virusinfecting virus

IgM ELISA test for serologic diagnosisIgM ELISA test for serologic diagnosis

Virus Isolation:Virus Isolation:Cell CultureCell Culture

Virus Isolation:Virus Isolation:Cell CultureCell Culture

Virus Isolation:Virus Isolation:Mosquito InoculationMosquito Inoculation

Virus Isolation:Virus Isolation:Fluorescent Antibody TestFluorescent Antibody Test

ELISA Test for ELISA Test for Serologic DiagnosisSerologic Diagnosis

ELISA PlateELISA Plate

Collection and Processing of Collection and Processing of Samples for Laboratory DiagnosisSamples for Laboratory Diagnosis

Type ofSpecimen

Time ofCollection

Type ofAnalysis

Acute-phaseblood

(0-5 days after onset)

When patient presents;collect second sampleduring convalescence

Virus isolationand/or serology

Convalescent-phaseblood

(6 days after onset)

Between days 6 and 21after onset

Serology

Procedures for DiagnosingProcedures for Diagnosinga Suspected Dengue Fatalitya Suspected Dengue Fatality

Inform the laboratory processing the Inform the laboratory processing the samples that the case was fatalsamples that the case was fatal

Obtain a blood sample to attempt virus Obtain a blood sample to attempt virus isolation and serologyisolation and serology

Obtain tissue samples for separate tests of Obtain tissue samples for separate tests of virus isolation and immunohistochemistryvirus isolation and immunohistochemistry

Temperature, Virus Positivity and Temperature, Virus Positivity and Anti-Dengue IgM , by Fever DayAnti-Dengue IgM , by Fever Day

Dengue IgMMean Max. Temperature Virus

Adapted from Figure 1 in Vaughn et al.,J Infect Dis, 1997; 176:322-30.

Fever Day

0

20

40

60

80

100P

erce

nt

Vir

us

Pos

itiv

e

-4 -3 -2 -1 0 1 2 3 4 5 6

39.5

39.0

38.5

38.0

37.5

37.0

Tem

per

atu

re (

deg

rees

Cel

siu

s)

Den

gue

IgM

(E

IA u

nit

s)300

150

0

75

225

VII. TreatmentVII. Treatment

Outpatient TriageOutpatient Triage

No hemorrhagic manifestations and patient No hemorrhagic manifestations and patient is well-hydrated: is well-hydrated: home treatmenthome treatment

Hemorrhagic manifestations or hydration Hemorrhagic manifestations or hydration borderline: borderline: outpatient observation center or outpatient observation center or hospitalizationhospitalization

Warning signs (even without profound Warning signs (even without profound shock) or DSS: shock) or DSS: hospitalizehospitalize

Patient Follow-UpPatient Follow-Up Patients treated at homePatients treated at home

• Instruction regarding danger signsInstruction regarding danger signs• Consider repeat clinical evaluationConsider repeat clinical evaluation

Patients with bleeding manifestationsPatients with bleeding manifestations• Serial hematocrits and platelets at least daily until Serial hematocrits and platelets at least daily until

temperature normal for 1 to 2 daystemperature normal for 1 to 2 days All patientsAll patients

• If blood sample taken in first 5 days after onset, need If blood sample taken in first 5 days after onset, need convalescent sample between days 6 - 30convalescent sample between days 6 - 30

• All hospitalized patients need samples on admission and at All hospitalized patients need samples on admission and at discharge or deathdischarge or death

Treatment of Dengue FeverTreatment of Dengue Fever(Part 1)(Part 1)

FluidsFluids RestRest Antipyretics (avoid aspirin and non-steroidal Antipyretics (avoid aspirin and non-steroidal

anti-inflammatory drugs)anti-inflammatory drugs) Monitor blood pressure, hematocrit, platelet Monitor blood pressure, hematocrit, platelet

count, level of consciousnesscount, level of consciousness

Mosquito BarriersMosquito Barriers

Only needed until fever subsides, to prevent Only needed until fever subsides, to prevent Aedes aegyptiAedes aegypti mosquitoes from biting mosquitoes from biting patients and acquiring viruspatients and acquiring virus

Keep patient in screened sickroom or under Keep patient in screened sickroom or under a mosquito neta mosquito net


Continue monitoring after defervescenceContinue monitoring after defervescence If any doubt, provide intravenous fluids, If any doubt, provide intravenous fluids,

guided by serial hematocrits, blood guided by serial hematocrits, blood pressure, and urine outputpressure, and urine output

The volume of fluid needed is similar to the The volume of fluid needed is similar to the treatment of diarrhea with mild to moderate treatment of diarrhea with mild to moderate isotonic dehydration (5%-8% deficit)isotonic dehydration (5%-8% deficit)

Fluid for Moderate DehydrationFluid for Moderate Dehydration(Intravenous)(Intravenous)

weight in lbs ml/lb/day weight in kgs ml/kg/day

< 15 100 < 7 220

16 - 25 75 7 - 11 165

26 - 40 60 12 - 18 132

41 - 88 40 19 - 40 88

Adapted from Guidelines for Treatment of Dengue Fever/Dengue Haemorrhagic Fever in Small Hospitals, WHO, 1999.

Rehydrating Patients Over 40 kgRehydrating Patients Over 40 kg Volume required for rehydration is Volume required for rehydration is twicetwice the the

recommended maintenance requirementrecommended maintenance requirement Formula for calculating maintenance volume: Formula for calculating maintenance volume:

1500 + 20 x (weight in kg - 20)1500 + 20 x (weight in kg - 20) For example, maintenance volume for 55 kg For example, maintenance volume for 55 kg

patient is: 1500 + 20 x (55-20) = 2200 mlpatient is: 1500 + 20 x (55-20) = 2200 ml For this patient, the rehydration volume For this patient, the rehydration volume

would be 2 x 2200, or 4400 mlwould be 2 x 2200, or 4400 mlPan American Health Organization: Dengue and DengueHemorrhagic Fever: Guidelines for Prevention and Control.PAHO: Washington, D.C., 1994: 67.


Avoid invasive procedures when possibleAvoid invasive procedures when possible Unknown if the use of steroids, intravenous Unknown if the use of steroids, intravenous

immune globulin, or platelet transfusions to immune globulin, or platelet transfusions to shorten the duration or decrease the severity shorten the duration or decrease the severity of thrombocytopenia is effectiveof thrombocytopenia is effective

Patients in shock may require treatment in Patients in shock may require treatment in an intensive care unitan intensive care unit

Indications for Hospital DischargeIndications for Hospital Discharge Absence of fever for 24 hours (without anti-Absence of fever for 24 hours (without anti-

fever therapy) and return of appetitefever therapy) and return of appetite Visible improvement in clinical pictureVisible improvement in clinical picture Stable hematocritStable hematocrit 3 days after recovery from shock3 days after recovery from shock Platelets Platelets 50,000/mm 50,000/mm33

No respiratory distress from pleural No respiratory distress from pleural effusions/asciteseffusions/ascites

Pan American Health Organization: Dengue and DengueHemorrhagic Fever: Guidelines for Prevention and Control.PAHO: Washington, D.C., 1994: 69.

Common Misconceptions aboutCommon Misconceptions aboutDengue Hemorrhagic FeverDengue Hemorrhagic Fever

Dengue + bleeding = DHFDengue + bleeding = DHF Need 4 WHO criteria, capillary permeabilityNeed 4 WHO criteria, capillary permeability

DHF kills only by hemorrhageDHF kills only by hemorrhage Patient dies as a result of shockPatient dies as a result of shock

Poor management turns dengue into DHFPoor management turns dengue into DHF Poorly managed dengue can be more severe, Poorly managed dengue can be more severe, butbut DHF is a distinct DHF is a distinct

condition, which even well-treated patients may developcondition, which even well-treated patients may develop

Positive tourniquet test = DHFPositive tourniquet test = DHF Tourniquet test is a nonspecific indicator of capillary fragilityTourniquet test is a nonspecific indicator of capillary fragility

More Common Misconceptions More Common Misconceptions about Dengue Hemorrhagic Feverabout Dengue Hemorrhagic Fever

DHF is a pediatric diseaseDHF is a pediatric disease All age groups are involved in the AmericasAll age groups are involved in the Americas

DHF is a problem of low income familiesDHF is a problem of low income families All socioeconomic groups are affectedAll socioeconomic groups are affected

Tourists will certainly get DHF with a Tourists will certainly get DHF with a second infectionsecond infection Tourists are at low risk to acquire DHFTourists are at low risk to acquire DHF

Dengue Vaccine?Dengue Vaccine?

No licensed vaccine at presentNo licensed vaccine at present Effective vaccine must be tetravalentEffective vaccine must be tetravalent Field testing of an attenuated tetravalent Field testing of an attenuated tetravalent

vaccine currently underwayvaccine currently underway Effective, safe and affordable vaccine will Effective, safe and affordable vaccine will

not be available in the immediate futurenot be available in the immediate future

VIII. PreventionVIII. Prevention

Early Eradication CampaignsEarly Eradication CampaignsSucceededSucceeded

Adequate local and external funding for Adequate local and external funding for personnel, equipment and insecticidespersonnel, equipment and insecticides

Emphasis on source reductionEmphasis on source reduction Effective residual insecticideEffective residual insecticide Centralized, vertically-structured programs Centralized, vertically-structured programs

with military-type organization, strict with military-type organization, strict supervision, high level of disciplinesupervision, high level of discipline

Reinfestation by Reinfestation by Aedes aegyptiAedes aegypti

1930s 1970 1998

Hemispheric Eradication ofHemispheric Eradication ofAedes aegyptiAedes aegypti No Longer Realistic No Longer Realistic

Problem greater than during previous Problem greater than during previous campaigncampaign

Insufficient resourcesInsufficient resources Resistance to vertical disease control Resistance to vertical disease control

programs and use of insecticidesprograms and use of insecticides Lack of effective insecticidesLack of effective insecticides Low priority, lack of sustainabilityLow priority, lack of sustainability

Lessons for FutureLessons for FutureDengue Prevention ProgramsDengue Prevention Programs

Efforts should focus on sustainable Efforts should focus on sustainable environmental control rather than eradicationenvironmental control rather than eradication

Control programs should be community-Control programs should be community-based and -integrated. They cannot rely based and -integrated. They cannot rely solely on insecticides nor require large solely on insecticides nor require large budgetsbudgets

Need to promote dengue as a priority among Need to promote dengue as a priority among health officials and the general publichealth officials and the general public

Community ApproachesCommunity Approaches

Typically define communities geographicallyTypically define communities geographically More likely to be sustainableMore likely to be sustainable Advantages: built-in manpower, help Advantages: built-in manpower, help

develop resources and empower community develop resources and empower community organizationsorganizations

Disadvantages: more difficult to organize, Disadvantages: more difficult to organize, take longer to get off the groundtake longer to get off the ground

Community ParticipationCommunity Participation

First must educate the public in the basics First must educate the public in the basics of dengue, such as:of dengue, such as:• Where the mosquito lays her eggsWhere the mosquito lays her eggs

• The link between larvae and adult mosquitoesThe link between larvae and adult mosquitoes

• General information about dengue General information about dengue transmission, symptoms and treatmenttransmission, symptoms and treatment

Skills DeficitSkills Deficit

Knowledge is not sufficient to produce Knowledge is not sufficient to produce behavior changebehavior change

People may lack the skills necessary to People may lack the skills necessary to carry out the recommended behaviorscarry out the recommended behaviors

Need to address this skills deficitNeed to address this skills deficit

Barriers and Motivation (Part 1)Barriers and Motivation (Part 1)

Knowledge combined with skills still may Knowledge combined with skills still may not be sufficient to change behaviornot be sufficient to change behavior

Need to understand what barriers may Need to understand what barriers may prevent the behavior, and what factors may prevent the behavior, and what factors may motivate people to take the desired actionmotivate people to take the desired action

Barriers and motivating factors vary in Barriers and motivating factors vary in different regions different regions

Barriers and Motivation (Part 2)Barriers and Motivation (Part 2) Structural factorsStructural factors

• laws regarding laws regarding Aedes aegyptiAedes aegypti habitats habitats Environmental factorsEnvironmental factors

• lack of potable water, need to store waterlack of potable water, need to store water• inadequate solid waste disposalinadequate solid waste disposal

Attitudinal factorsAttitudinal factors• beliefs: causes, treatment, prevention of febrile illnessesbeliefs: causes, treatment, prevention of febrile illnesses

Community factorsCommunity factors• community history and structurecommunity history and structure• other priority problems in the communityother priority problems in the community

Cues for Cues for Dengue Preventive BehaviorsDengue Preventive Behaviors

People need reminders when they are People need reminders when they are learning a new behaviorlearning a new behavior

Behavioral cues are prompts or signals to Behavioral cues are prompts or signals to remind the person to engage in the desired remind the person to engage in the desired behaviorbehavior

Cues: FeedbackCues: Feedback

Use regular feedback of entomologic and Use regular feedback of entomologic and epidemiologic dataepidemiologic data

Every time someone receives the Every time someone receives the information, it can serve as a reminder to information, it can serve as a reminder to actact

If the data indicate control activities are If the data indicate control activities are successful, they serve as positive successful, they serve as positive reinforcementreinforcement

Cues: Presence ofCues: Presence ofAdult MosquitoesAdult Mosquitoes

Idea to promote:Idea to promote:• Person sees adult mosquitoPerson sees adult mosquito

• Asks him/herself, “Where did it come from?”Asks him/herself, “Where did it come from?”

• Immediately searches for larval habitatsImmediately searches for larval habitats

• Eliminates or controls all potential habitats Eliminates or controls all potential habitats foundfound

Cues: Water ShortagesCues: Water Shortagesand Rationingand Rationing

For locations where there are seasonal or For locations where there are seasonal or other temporary water shortagesother temporary water shortages

Provide information on how to properly Provide information on how to properly store waterstore water

Cues: RainfallCues: Rainfall

Link rainfall to the creation of larval Link rainfall to the creation of larval habitatshabitats

This mental link can remind people to look This mental link can remind people to look for and eliminate larval habitats after it for and eliminate larval habitats after it rainsrains

Eliminates larval habitats influenced by Eliminates larval habitats influenced by rainfall, and perhaps others as wellrainfall, and perhaps others as well

Example of Community Programs: Example of Community Programs: Puerto RicoPuerto Rico

Elementary school and Head Start programs Elementary school and Head Start programs to teach children about dengue controlto teach children about dengue control

Public service announcementsPublic service announcements Interactive exhibit at the Children’s Interactive exhibit at the Children’s

MuseumMuseum Boy Scout merit badge programBoy Scout merit badge program

The ChallengeThe Challenge

Achieve active community involvementAchieve active community involvement Solicit input from the earliest program planning Solicit input from the earliest program planning

stagesstages Encourage community ownershipEncourage community ownership Programs that emphasize telling communities Programs that emphasize telling communities

what to do, without involving them or taking their what to do, without involving them or taking their views into account, are not likely to be effectiveviews into account, are not likely to be effective

True community participation is keyTrue community participation is key

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