07 Dengue Treatment Guidelines

8/11/2019 07 Dengue Treatment Guidelines

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Dengue Treatment GuidelinesDengue Treatment Guidelines


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DengueDengue

Dengue is an emerging serious publicDengue is an emerging serious public

health problem in Asia & Pacifichealth problem in Asia & Pacific

It is expanding geographicallyIt is expanding geographically

Epidemics are increasing in frequencyEpidemics are increasing in frequency Disease spreading to rural areasDisease spreading to rural areas


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Dengue Problem is WorseningDengue Problem is Worsening

Unplanned & uncontrolled urbanizationUnplanned & uncontrolled urbanization

Problems relating to disposal of wasteProblems relating to disposal of waste

plastic, tires, etc.plastic, tires, etc.

Increased travel / Movement of populationIncreased travel / Movement of population Inadequate or delayed response toInadequate or delayed response to

epidemicsepidemics


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Global Situation of DF/DHFGlobal Situation of DF/DHF

2.5B at risk worldwide2.5B at risk worldwide

100 M annual dengue cases100 M annual dengue cases

DF/DHF/DSS admissions/year: 500,000DF/DHF/DSS admissions/year: 500,000

casescases Mortality rate: 5%Mortality rate: 5%


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Transmission of Dengue

CDC


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Dengue VirusDengue Virus

Causes dengue fever & dengueCauses dengue fever & dengue

hemorrhagic feverhemorrhagic fever

Is anIs an arbovirusarbovirus

Transmitted by infected femaleTransmitted by infected femalemosquitoesmosquitoes

Composed of singleComposed of single--stranded RNAstranded RNA

Has 4 serotypes (DEN 1, 2, 3 & 4)Has 4 serotypes (DEN 1, 2, 3 & 4)


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Dengue VirusDengue Virus

Each serotype provides specific lifetimeEach serotype provides specific lifetime

immunity & short term cross immunityimmunity & short term cross immunity

All serotypes can cause severe & fatalAll serotypes can cause severe & fatal

diseasedisease

Genetic variation within serotypesGenetic variation within serotypes

Some genetic variants within each serotypeSome genetic variants within each serotype

appear to be more virulent or have greaterappear to be more virulent or have greaterepidemic potentialepidemic potential


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Risk Factors Reported for DHFRisk Factors Reported for DHF Virus strainVirus strain

PrePre--existing antiexisting anti--dengue antibodydengue antibody Previous infectionPrevious infection

Maternal antibodies in infantsMaternal antibodies in infants

AgeAge Higher risks in secondary infectionsHigher risks in secondary infections

Higher risks in locations with two or moreHigher risks in locations with two or more

serotypes circulating simultaneously at highserotypes circulating simultaneously at highlevelslevels


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Manifestations of Dengue Virus InfectionManifestations of Dengue Virus Infection

Dengue Virus

Infection

Asymptomatic Symptomatic

Undifferentiated

Fever

Dengue Fever

Syndrome

Dengue Hemorrhagic

Fever

(Plasma Leakage)

Without

Hemorrhage

Unusual

HemorrhageNo Shock

Dengue Shock

Syndrome

Gubler, 1997


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Diagnosis of Dengue VirusDiagnosis of Dengue Virus

Complicated by Several Factors:Complicated by Several Factors:

Possible coPossible co--circulation with othercirculation with other

flavivirusesflaviviruses

Some reagents needed for dengueSome reagents needed for dengue

diagnosis not commercially availablediagnosis not commercially available Time required to obtain meaningfulTime required to obtain meaningful

laboratory resultslaboratory results


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Collection and Processing ofCollection and Processing ofSamples for Laboratory DiagnosisSamples for Laboratory Diagnosis

Type ofType ofSpecimenSpecimen

Time ofTime ofCollectionCollection

Type ofType ofAnalysisAnalysis

Acute phase period

(0-5 days after onset)

When patient presents;

collect second sampleduring convalescence

Virus isolation

and/or serology

Convalescent phase

blood(>6 days after onset)

Between days 6 and

21 after onset

Serology


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Temperature, VirusTemperature, Virus PositivityPositivity &&

AntiAnti--DengueDengue IgMIgM, by Fever Day, by Fever Day

Anti-DengueIgM(

EIA

unit

s)

Day of defervescence-4 -3 -2 -1 0 1 2 3 4 5 6

Anti-Dengue IgMMean Max. Temperature Virus

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

0

20

40

60

80

100 300

150

0

75

225

PercentVirusPositive

Temperature(C)

39.5

39.0

38.5

38.0

37.5

37.0

CDC


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Dengue FeverDengue Fever -- Suspected CaseSuspected Case

Acute febrile illness of 2Acute febrile illness of 2--7 days duration in7 days duration in

saddlesaddle--back pattern with 2 or more of theback pattern with 2 or more of thefollowing:following:

HeadacheHeadache

RetroRetro--orbital painorbital pain MyalgiaMyalgia//arthralgiaarthralgia

Hemorrhagic manifestationsHemorrhagic manifestations

LeukopeniaLeukopenia

*Gubler, 1997; WHO


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Dengue FeverDengue Fever -- Probable CaseProbable CaseA suspected case with one or more of theA suspected case with one or more of the

following:following: (+) serology(+) serology

Occurrence at the same location andOccurrence at the same location and timetime

as other confirmed cases of dengue feveras other confirmed cases of dengue fever

*Gubler, 1997; WHO


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Dengue FeverDengue Fever -- Confirmed CaseConfirmed Case

A case compatibleA case compatiblewith the clinical descriptionwith the clinical description

and laboratoryand laboratory--confirmedconfirmed

(gold standard(gold standard -- HI orHI or(+) viral isolate/antigen thru PCR)(+) viral isolate/antigen thru PCR)

*Gubler, 1997; WHO


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Dengue Shock SyndromeDengue Shock Syndrome

All of the above criteria for DHF must beAll of the above criteria for DHF must be

present + evidence of circulatory failurepresent + evidence of circulatory failure

manifested as:manifested as:

Rapid and weak pulse;Rapid and weak pulse;

Narrow pulse pressure;Narrow pulse pressure;

Hypotension for age;Hypotension for age;

Cold, clammy skin and restlessnessCold, clammy skin and restlessness

*Gubler, 1997; WHO


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Grading Severity of DHFGrading Severity of DHF

Grade IGrade I -- Fever, nonFever, non--specific s/s, (+) TTspecific s/s, (+) TT

Grade IIGrade II -- s/s of Grade I + spontaneous bleeding;s/s of Grade I + spontaneous bleeding;

Dengue Shock Syndrome:Dengue Shock Syndrome:

Grade IIIGrade III -- s/s of Grade II with more severes/s of Grade II with more severebleeding + evidences of circulatorybleeding + evidences of circulatoryfailurefailure

Grade IVGrade IV -- with profound shock, undetectablewith profound shock, undetectableblood pressure or pulseblood pressure or pulse

Laboratory: Thrombocytopenia +Laboratory: Thrombocytopenia + HemoconcentrationHemoconcentration

WHO, 1997


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Dengue CaseDengue Case

Case

Outpatient Admission(Danger Signs)

In Shock Not In Shock


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OutOut--PatientPatient

DOH Dengue Consensus Management Guideline

History or presence of fever ofHistory or presence of fever of

22--7 days duration, skin flushing or rash,7 days duration, skin flushing or rash,

and/or (+) TT, with no danger signsand/or (+) TT, with no danger signs


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Outpatient CaseOutpatient Case OralOral RehydratingRehydrating SolutionsSolutions

Daily assessments of patients:Daily assessments of patients: Clinical & laboratoryClinical & laboratory

May send patient home with advise to watch outMay send patient home with advise to watch out

for danger signsfor danger signs


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Outpatient CaseOutpatient Case

ORESOLORESOLIn adults: replace fluids as in moderateIn adults: replace fluids as in moderate

dehydration atdehydration at

75 ml/KBW in 475 ml/KBW in 4--6 hrs or up to 26 hrs or up to 2--3 L/day3 L/day


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ORESOLORESOL

900900--140014001212--1919 kgskgs22--5 yrs5 yrs

700700--9009001010--1212 kgskgs11--2 yrs2 yrs

400400--70070066--1010 kgskgs44--1212 mosmos

200200--400400< 6< 6 kgskgsup to 4up to 4 mosmos

AMOUNT (ml)AMOUNT (ml)WEIGHTWEIGHTAGEAGE


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3 Essential Laboratory Tests:3 Essential Laboratory Tests: Total White Blood Cell CountTotal White Blood Cell Count

Platelet CountPlatelet Count

HematocritHematocrit


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Useful ParametersUseful Parameters

HematocritHematocrit degree of plasma leakagedegree of plasma leakagechanges usually precede BPchanges usually precede BP

and pulse changesand pulse changes

sudden rise/persistentlysudden rise/persistentlyelevatedelevatedimpliesimplies

IMPENDING SHOCKIMPENDING SHOCK

Dynamic disease process demandsDynamic disease process demandsCLOSE MONITORINGCLOSE MONITORING


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Mainstay in TherapyMainstay in Therapy

Intravenous FluidsIntravenous Fluids CrystalloidsCrystalloids

ColloidsColloids

Blood / Blood ComponentBlood / Blood Component


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Fluids RequiredFluids RequiredCrystalloids or Colloids ?Crystalloids or Colloids ?

Blood/blood Components ?Blood/blood Components ?

Reassess periodically: BP, PP, UO,Reassess periodically: BP, PP, UO, HctHct


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Crystalloids:Crystalloids:AdvantagesAdvantages

inexpensiveinexpensive readily availablereadily available

no allergic reactionsno allergic reactions

effectively expands the interstitial water spaceeffectively expands the interstitial water spaceand current NA deficitand current NA deficit

DisadvantageDisadvantage

remain in the intravascular compartment for aremain in the intravascular compartment for afew minutesfew minutes


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ColloidsColloidsAdvantages:Advantages:

Remain in the IV compartment longer thanRemain in the IV compartment longer thancrystalloidscrystalloids

more effective volume expandermore effective volume expander

Disadvantages:Disadvantages:

cause sensitivity reactioncause sensitivity reaction

when GFR is reduced , viscosity impedes thewhen GFR is reduced , viscosity impedes the

flow of fluid through the tubulesflow of fluid through the tubules


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DHF Danger SignsDHF Danger Signs

DOH Dengue Consensus Management Guideline

Spontaneous bleeding

Persistent abdominal.pain

Persistent vomiting

Listlessness Changes in mental

status

Restlessness

Moderate to severe

dehydration

Weak and rapid pulse

Cold, clammy skin

Circumoral cyanosis

Dyspnea

Seizures Hypotension

Thrombocytopenia - less

than 100,000/cu.mm. Hemoconcentration


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Inpatient Category: Not in shock!Inpatient Category: Not in shock!Crystalloid:Crystalloid:

DD55LRS / DLRS / D550.9 NSS / Plain LRS / Plain NSS at 50.9 NSS / Plain LRS / Plain NSS at 5--7 ml/KBW/hr.7 ml/KBW/hr.

With Improvement:With Improvement:

Reduce IVF to 3 ml/KBW/hr (up to 2Reduce IVF to 3 ml/KBW/hr (up to 2--3 L/day in3 L/day in

adults) & maintain at same rate for 24adults) & maintain at same rate for 24--48 hrs48 hrs

using Dusing D

55LRS alternating with DLRS alternating with D

55IMB (2 y/o).


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Inpatient Category: Not in shock!Inpatient Category: Not in shock!

If there is no improvement:If there is no improvement:Increase IVF by 3Increase IVF by 3--5 ml/KBW/hr increments up5 ml/KBW/hr increments up

to 15 ml/KBW/hr then adjust accordingly.to 15 ml/KBW/hr then adjust accordingly.


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Flow Chart for Patients with DSSFlow Chart for Patients with DSSUnstable vital signsUnstable vital signs

Urine output falls, signs of shockUrine output falls, signs of shock

Crystalloids* (1-2 x)

Improvement No Improvement Monitor patient

clinically + lab.

Adjust IV therapyColloids + Oxygen therapy

Hct Falls by 20% Hct Rises

Blood transfusion** Plasma, plasmasubstitute, albumin

*In cases of acidosis, hyperosmolar or Ringers lactate solution should not be used.

**Prolonged PTT, PT, 25% blood loss, 20% fall in Hct - refer to Blood/bloodcomponent therapy.


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When to Discontinue Fluid Therapy?When to Discontinue Fluid Therapy?

HematocritHematocrit falls to around 40%falls to around 40%

strong pulse and blood pressurestrong pulse and blood pressure

good urine flowgood urine flow return of appetitereturn of appetite


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Blood/Blood Products in DHF:Blood/Blood Products in DHF:

Fresh whole blood: 20 ml/KBWFresh whole blood: 20 ml/KBW

Gross bleeding or significant blood loss;Gross bleeding or significant blood loss;

Blood loss is 25% or more of bloodBlood loss is 25% or more of blood

volume;volume; Hct falls by 20% (>10% blood loss inHct falls by 20% (>10% blood loss in

adults or >25% blood loss in pediatrics ofadults or >25% blood loss in pediatrics of

total blood volume of 80 ml/kg)total blood volume of 80 ml/kg)


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Packed Red Blood Cells : 10 ml/KBWPacked Red Blood Cells : 10 ml/KBWWhen blood loss isWhen blood loss is


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Fresh Frozen Plasma: 15 ml/KgFresh Frozen Plasma: 15 ml/Kg

Patients with prolonged PT (2x thePatients with prolonged PT (2x the

control);control);

Patients in impending shock despitePatients in impending shock despitecrystalloid infusion in the absence ofcrystalloid infusion in the absence of

colloidscolloids


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Cryoprecipitate: 1 unit/5Cryoprecipitate: 1 unit/5 kgskgs

Patients with prolongedPatients with prolonged aPTTaPTT::

>50 secs if no reference value;>50 secs if no reference value;

10 secs more than upper limit of normal;10 secs more than upper limit of normal; 20 secs. more than control;20 secs. more than control;

With signs of DICWith signs of DIC



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Platelet concentrate: 1 unit/7Platelet concentrate: 1 unit/7 kgskgs Platelet count is


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When to send patients home?When to send patients home? 22--3 days after3 days after

complete recoverycomplete recoveryfrom shockfrom shock

SymptomSymptom--free orfree or

absence of dangerabsence of dangersignssigns

Good appetiteGood appetite

Good urine outputGood urine output

Rising platelet countRising platelet count

(at least on 2(at least on 2occasions)occasions)

No evidence ofNo evidence of

cardiac or CNScardiac or CNSinvolvement or otherinvolvement or other

complicationscomplications

Complete recoveryComplete recoveryfrom shockfrom shock


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Dengue Vaccine?Dengue Vaccine?(WHO, 2003)(WHO, 2003)

No licensed vaccine at presentNo licensed vaccine at present

Effective vaccine must be tetravalentEffective vaccine must be tetravalent

Field testing of attenuated tetravalent vaccinesField testing of attenuated tetravalent vaccines

currently underwaycurrently underway

No effective, safe and affordable vaccine will beNo effective, safe and affordable vaccine will be

available in the next 5 yearsavailable in the next 5 years

Slow progress in vaccine development:Slow progress in vaccine development:

poor growth in cell culturepoor growth in cell culture no acceptable animal model for DHFno acceptable animal model for DHF


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FOURmulaFOURmula (4S)(4S) LabanLaban sasa DengueDengue

Search & DestroySearch & Destroy

SelfSelf--Protection MeasuresProtection Measures

Seek Early ConsultationSeek Early Consultation

Say NO to indiscriminate foggingSay NO to indiscriminate fogging


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Dengue ControlDengue ControlEveryoneEveryones concern. Thes concern. The

success depends on thesuccess depends on the

involvement of all levelsinvolvement of all levels

from household, family,from household, family,

community, NGOs, socialcommunity, NGOs, social

organizations, local &organizations, local &

national authorities.national authorities.


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PreventionPreventionisis

Primary!Primary!


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07 Dengue Treatment Guidelines

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