Dengue Hemorrhagic Fever

Dr. Tjatur winarsanto SpPD

Alternative NamesOnyong- Nyang FeverWest Nile FeverBreak Bone FeverDengue like Disease

BackgroundPropagation of viral illnessesTransmission of viral illnessesVarious families of Arbor virusesManifestations of Arborviral illnessesDengue A Flavivirus- EM- Cell cultureTransmitted by mosquitoAedes aegypti

Viral Illnesses - PropagationHumanHumanHumanZoonoticAccidentalVirusArthropodRodent

Transmission of Viral IllnessesDroplet infection as in case ofMeasles, Influenza, Coryza etc.Blood to blood transmission- HIV, HBVFeco-oral Rota, PolioDirect contact Herpes simplex etcArthropod borne Dengue, JE, YFTick borne CEE, Colorado TF

Arthropod borne Viral DiseasesFlavivirus Mosquito borne YF, DF,JEFlavivirus Tick Borne CEE, RSSE, KFDBuniyavirus Mosquito- CEPlebovirus Sandfly FeverArinavirus LCM virusColivirus Colorado Tick feverVesiculovirus Vesicular stomatitisAlphavirus E/W/V equine encephalitides

Manifestations of Arborviral Illnesses Most Arboviral diseases are ruralArboviral illnesses cause typical manifestations Often overlap The following clinical syndromes occurFM Fever Myalgia complexAR Arthritis Rash complexHF Haemorrhagic FeverE Encephalitis

Epidemiology of DengueThe Dengue VirusThe VectorGlobal distribution of DengueTransmission cycle host vectorPropagation of virus I.PNatural History of DengueDengue Hemorrhagic fever Endemicity pattern

Epidemiological TriangleThe HostThe VirusThe VectorInteraction

The AgentDengue Virus

The Dengue VirusFlavivirusPositive senseSingle stranded RNA virus40 to 50 nanometersFour sero-sub typesType 1 to 4Arthropod borne

Dengue VirusElectron Micrograms

Dengue VirusCell CultureOf DengueVirus

The Vector Aedes aegypti(Infected Female Mosquito)(rarely Aedes albapticus)

Peculiarities of A.aegyptiIt is a day biting mosquito when normallycoils, repellents, nets etc are not usedIt breads in fresh water around homesLays eggs preferentially in water jars, discar- ded containers, coconut shells, old tires etc.Can transmit trans-ovarially the infectionYear round breeding 250 N to 250 STropics and sub-tropics are its favorite zones. It is an urban vector

Aedes aegyptiDengue, YF, CGF

Aedes aegyptiDengue

Yellow Fever

ChichungunyaFever

Dengue on the GlobeHighly endemicRecently acquired

Dengue FeverCaused by an arthropod borne virusIt is a zoonotic virusMan is accidentally infectedOther vertebrates are the reservoirsDengue virus has 4 subtypes 1 to 4 Positive sense, single str RNA- 40nmVector mosquito is Aedes aegypti

Mechanism of TransmissionVector is infected after ingestion of blood meal from a viremic vertebrateVirus multiplies in the system of vectorfor 2-3 weeks extrinsic incubation pd.Natural vertebrate partner has onlytransient viremia and doesnt sufferVirus is injected by the A.aegypti into manAfter 2-7 days of IP, man develops FM,HF

Dengue Transmission Cycle

Dengue Transmission

Dengue Illnesses - Propagation

Natural History of DengueHuman InfIn apparentDFMPrimaryDHF/DSS30%69%01%Re infectionSecondaryDHF/DSS10%Recovery100%Death5%95%

DHF Endemicity

Pathogenesis of DHFImmuno-pathogenicCascade

Hypotheses on DHF - DSSNeutralizing Ab are type specific nutralize the homologous sub typeSubsequent infection with heterologous sub type causes immune complexesThese Immune Complexes target the mononuclear lineage foe enhanced viral replicationInfected monocytes release vasoactive mediators causing vascular damage

Initial Immunogenecity

Immune Complexes

Attack on Host Immune Cells

Immunopathogenic Cascade of DHF/DSSMacrophage monocyte infection Previous infection with heterologousDengue serotype results in productionof non protective antiviral antibodiesThese Ab bind to the virions surfaceFc receptor and focus the Dengue viruson to the target cells macro/monocytesT cell - cytokines, interferon, TNF alpha

The DiseaseClinical Features

Dengue PresentationsUndifferentiated feverDengue Fever (DF) with the Fever- Myalgia (FM) presentation (classical)Dengue Hemorrhagic Fever (DHF)Dengue Shock Syndrome (DSS)

Hemorrhagic ManifestationsSkin hemorrhages: petechiae, purpura, ecchymosesGingival bleedingNasal bleedingGastro-intestinal bleeding: hematemesis, melena, hematocheziaHaematuriaIncreased menstrual flow

Clinical Manifestations- DFIP of 2 7 days - typical patient developsSudden onset of fever, chills, headacheBack pain with severe myalgia, arthralgiaRetro-orbital pain break bone feverMacular rash in axillary areaAdenopathy, palatal vesicles, scleral inj.Maculo-papular rash on trunk extremitiesEpistaxis and scattered petechiae

Other manifestations- DFAnorexia. Nausea, vomitingIn apparent illness-to acute incapacitationIllness is about 25 days, biphasic coursePain on eye movementsPain on palpating abdominal musclesPrimarily not a respiratory illnessRare - aseptic meningitis Complete recovery is the rule - asthenia

Petechiae

Dengue Haemorrhagic Fever (DHF)Vascular instabilityDecreased vascular integrityAssault on macro vasculatureDecreased platelet functionIncreased vascular permeabilityVascular disruption and local bleedsHypotension, hemoconcentration- shock

DHF Clinical Criteria

Criteria for DHFFever, or recent history of acute feverHemorrhagic manifestationsLow platelet count (100,000/mm 3 or less)Objective evidence of leaky capillaries:Elevated hematocrit -20% or moremore over baseline or 50%Low albumin, pleural effusion

Criteria for DSSThe four criteria of DHFEvidence of circulatory failureRapid and weak pulseNarrow pulse pressue (less than 20mm)Hypotension for the ageCold clammy skinAltered mental status

Four Grades of DHF/DSSGrade 1Fever, Const. Symptoms, +ve tourniquet testGrade 2Grade 1 + Spontaneous bleedingGrade 3Signs of circulatory failureGrade 4Profound shock - B.P. Pulse not recordable

Ecchymosis Periorbital Edema

Large Subcutaneous Bleed

Capillary Damage

Tourniquet TestInflate blood pressure cuff to a pointmidway between systolic and diastolicpressure for 5 minutes

Positive test: 20 or more petechiaeper 1 inch (6.25 cm)

Tourniquet Test

PEI = A / B x 100Pleural Effusion

Clinical tests for DHFPetechiae after tourniquet testOvert bleed from previous GI lesionsPlatelet count less than 100,000/ulLow pulse pressure, cyanosis, effusionsHypotension, Shock

DHF- Poor Prognostic SignsGirl children under 12 with DHF/DSSSevere hypotension and shockMultifocal bleeding abdominal painCNS encepahlopathy, fits, comaWatch for preorbital edema, proteinuriapostural or otherwise hypotensionSerotype 2 infection after type 4Malnutrition is protective

Unusual Presentations of DengueEncephalopathyHepatic damageCardiomyopathySevere GI bleeding

Differential DiagnosisFM complexAnicteric leptospirosisRickettsial feversInfluenza, Measles, RubellaDHF / DSSOther hemorrhagic feversDIC due to septicemiaComplicated Malaria Meningococcemia

Laboratory DiagnosisComplete Blood CountsHematocritPlatelet CountSerum GOT, GPTSerum AlbuminProteinuria, hematuriaImmunological TestsChest Skiagram

Laboratory DiagnosisLeucopenia. ThrombocytopeniaIncreased SGOT, SGPTRising Ab titre in paired seraAntigen detection ELISAIgM-capture ELISA within few hoursReverse transcription PCR confirmatoryIgG ELISA significant of past infection

Immuno Detection TestsELISA PlateIgM-capture ELISA

Treatment of DFSupportive measures - Vector barrierAvoid Aspirin and if possible NSAIDsSteroids should not be usedFluid replacement to avoid hemoconc.Children below 12 require careful watchfor DHF / DSSNo antiviral agents are of proven value

DHF / DSSIntensive CareOxygenRehydrationBarrier NursingMosquito Screen

Common Misconceptions- DHFDengue + bleeding = DHFDHF is fatal only due to hemorrhageNo Majority of deaths are due to shockPoorly managed DF turns into DHFPositive tourniquet = DHFit is not specific for DHF, it indicates capillary fragility of any origin

More Common MisconceptionsDHF is only a pediatric illness No, All ages may be involvedDHF is a problem of poor families No, in fact they may not have immune complexes to required levelTourists will get DHF No, in fact they are at low risk

Management of DHF/DSSClose monitoring of hypotension/shockOxygen administrationIV. Infusion of crystalloids/colloidsPlatelet transfusionClotting factors replacementCase fatality is 5% in good centers

Fluid BalanceContinue monitoring after defervescenceSerial hematocrits, BP, Urine outputFluid replacement is twice the requirement1500 ml + 2 x (weight-20) for 60 kg wt.Eg. {1500 + 2 x (60-20)} x 2 = {1500 + (2x 40)} x 2 = (1500 + 800) x 2= 2300 x 2 = 4600 ml = 10 pints

ImmunizationEach serotype produces life long immunityThere is not efficacious vaccine availableVaccine needs to be tetravalentLive attenuated vaccines possibleSeveral candidate vaccines are on trialsIt may be harmful to vaccinate in viewof the pathogenesis of DHF/DSS

Vector ControlBiologicalLargely experimentalUse of fish to feed on larvaeEnvironmentalElimination of larval habitatMost likely successful strategyPurpose of controlTo reduce female vector density

Vector Control of DengueMosquito control is expensive impossibleDestruction of breeding sites viableSpraying insecticides for adult control- ?Individual measures to avoid vector contactMosquito screens, repellents (DEET)Permithrin impregnated clothingNon degradable tires, long life plastics-avoid

ChallengeAchieve active community involvementSolicit input from the earliest program planning stagesEncourage community ownershipTrue community participation is key

BibliographyWorld Health Organization ReportsPan American Health OrganizationCenter for Diseases Control, Atlanta National Institute of Communicable Diseases, New DelhiBangladesh Center for DengueHarrison's Principles of Internal Medicine, 15 ed.

Each Patient is a BookEach Day is a Learning OpportunityCME has More RelevanceNow Than Ever

Together We Learn Better

Reach Yours Sincerely @Dr.SARMA RVSNVoice : +91-4116-2309226, 260593Mobile : +91- 93805 21221E-mail : sarma.rvsn@gmail.comWeb site : www.drsarma.inSnail mail :3, Jayanagar, Tiruvallur Tamilnadu, INDIAPin : 602 001

Thank You !