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