Dengue Fever(2),09
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Dengue Fever(2),09

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  • Clinically occurs mainly in two forms.DF AND DHF
  • 20
  • The dss occurs on the basis of dhf.
  • Sepsis, measles, malaria
  • Avoid cerebral edemia

Dengue Fever(2),09 Dengue Fever(2),09 Presentation Transcript

  • Dengue fever Zhao zhixin The 3rd affiliated hospital of Sun Yat-Sen University [email_address]
  • WHAT IS DENGUE FEVER?
    • An acute ,self-limited, febrile disease .
    • Dengue virus are maintained in a cycle that involves humans and Aedes aegypti
    • primarily a disease of the tropics
    • OCCURS IN two forms:
    • Dengue fever(DF)
    • Dengue haemorrhagic fever(DHF)
  • Clinical manifestations
    • DF: fever, headache, myalgias, bone pain.Lymphadenopathy, skin rash.
    • Leukopenia
    • DHF: high fever, haemorrhage,
    • hepatomegaly
    • evidences of “leaky capillaries”
    • signs of circulatory failure(dengue shock syndrome,DSS.)
  • Why should we learn it ?
    • 2500 million at risk from dengue per year.
    • Epidemic in more than 100 countries in Africa, America, Eastern Mediterranean,
    • South –east Asia and the Western pacific.
    • The global prevalence of DHF grown dramatically in recent decades: 1970/1995:4 fold increase.
    • The most important mosquito-transmitted viral disease in term of mortality and morbidity.
  •  
  • Etiology
    • Dengue virus: enveloped RNA virus
    • Classified : family of Flaviviridae.
    • Serum type: 1-4
      • causes closely related illness, severe and fatal disease
      • but antigenically distinct
    • homotypic immunity: lifelong
    • heterotypic immunity :short period
    • but cross-response may worsen the second infection by a another serum type.
  • How DF transmitted?
    • Sources of infection: patients and
    • anyone who with Covert infection
    • Transmitted vectors:
    • Aedes aegypti is the most common vectors
    • other Aedes mosquitos are less effiecitent :
    • Ae.albopictus,Ae.polynesiesis
    • Primarily a daytime feeder
    • Lives around human habitation
    • (Women and children summer time or rainny season)
    • The host: all susceptible if never came across dengue fever.
    • How dengue virus cause the disease ?
    • (pathogenesis and clinical presentations)
  • Dengue virus Blood stream Mononuclear-phagocyte system second viremia Antigen antibody complexes complement system incubation Lymphadenopathy,hepatomegly Bone marrow depress Vascular permeability ↑ Rash, haemarrhagic fever Bone pains,etc Imfllamatory materials
  • risk factors for DHF
    • Important risk factors for DHF include
    • Virus factors:
      • the serotype :2 is the predominating
      • the strain: virulent strain
    • Host factors:
      • genetic predisposition
      • the age
        • Children : experienced a precious dengue infection
        • Infants with waning levels of maternal dengue antibody.
      • immune status: if there are enhancing Ab.
  • Enchancing antibody
    • heterotypic antibodies
      • enhancement of virus replication in macrophages
      • worsen the condition
    • A mechanism of DHF/DSS
  • Neutralizing antibody to Dengue 1 virus Dengue 1 virus Homologous Antibodies( 同型抗体 ) Form Non-infectious Complexes Non-neutralizing antibody Complex formed by neutralizing antibody and virus 1 1 1 1 1
  • Heterologous ( 异型的 )Complexes Enter More Monocytes, Where Virus Replicates Non-neutralizing antibody Dengue 2 virus Complex formed by non-neutralizing antibody and Dengue 2 virus 2 2 2 2 2 2 2 2 2 2 2 2
  • First infection heterotypic antibodies fail to neutralize virus of the other serum type infection the number of infected monocytes activation of cytotoxic lymphocytes rapid release of cytokines plasma leakage viral uptake and the replication in the mononuclear phagocytes. haemorrhage Haemoconcentrationor shock
  • pathophysiological changes occur in DHF/DSS:
    • Increased vascular permeability
    • haemoconcentration(Hct>20%)
    • low pulse pressure
    • other signs of shock.
    • Disorder in haemostaisis :
    • vascular changes
    • thrombocytopenia
    • coagulopathy.
  • CLINICAL PRESENTATIONS
    • Incubation: 5-8 days
    • Clinical features depend on the age of the patient:
    • Infants and young children
    • undifferentiated febrile disease,
    • with maculapapular rash.
    • Older children and adults either
    • a mild febrile syndrome
    • or the classic disease .
  • Manifestation Of Dengue Virus Infections ASYMPTOMATIC DSS SYMPTOMATIC Without haemorrhage With unusual haemorrhage No shock Undifferentiated Fever Dengue Fever Dengue Haemorrhagic Fever
  • Undifferentiated Fever
    • the most common manifestation of dengue
    • 87% of students infected were either asymptomatic or mildly symptomatic
    • studies including all age- groups also demonstrate silent transmission
    • Dengue fever (DF)
  • 1. fever
    • Abrupt onset, rising to 39.5-41.4 C
    • Accompanied by
    • frontal or retro-orbital headache
    • Pain behind the eyes
    • chillness
    • Last 1-7 days
    • Biphasic:
    • defervesce for 1-2 days
    • recurring with second rash
    • but :T not as high
  • 2. Bone pains
    • break bone fever is the another name of DF
    • After onset of fever
    • May last several weeks
    • Increase in severity
    • Most common in legs, joints, and lumbar spine;
    • With muscular and joint pains.
  • 3. Rash
    • first rash: first 1-2 days of fever, transient, generalized, macular and blanching;
    • Second rash
      • 3-6 days.
      • morbilliforms , maculopapular , rubella type
      • Involving the trunk first, spreading to the face and extremities,
    • sparing palms and soles.
    • other rash: petechiae
  •  
  • 4. Hemorrhage
    • Skin he morrhages: petechiae, purpura
    • Gin gi val bleeding
    • Na sal bleeding
    • GI bleeding: hema te mesis, me le na, hemato che zia
    • Hemat u ria
    • Increased menstrual flow
  • Physical exams(1)
    • Fever
    • Conjunct i val injection, pharyngeal eryth e ma
    • Rash: Measles-like rash over chest and upper limbs
    • Generalized lymphade no pathy
  • Physical exams(2) : Tourniquet Test
    • Method:
      • Inflate blood pressure cuff
      • to a point: midway between systolic and diastolic pressure
      • for 5 minutes
    • Positive test:
    • 20 or more petechiae per 1 inch 2
    • (6.25 cm 2 )
  • Clinical forms of DF(china)
    • Mild type
    • Typical type
    • Severe type:
    • Unusual bleedings
    • meningoencephalitis
  • Presentations of DHF/DSS(1)
    • high fever : remains >39 for 2-7days
    • hepatomegaly : varies in size
    • common haemorrhage
      • bleeding at venepuncture sites ( coagulopathy)
      • GI bleeding
    • Evidence of plasma leakage:
      • a rise in he matocrit (Hct):=>20%
      • pleural effusion ,ascites , hypoproteinemia
    • a distinctive laboratory finding :
    • Moderate to marked thrombocytopenia with
    • concurrent haemoconcentration
  • DSS(2)=DHF+SHOCK
    • at the end of the febrile phase
    • signs of circulatory disturbance
      • sweat, cool extremities restless
      • rapid ,weak pulse hypotension
    • varying severity
      • less severe: transient recover spontaneously
      • more severe: uncorrected Shock ensues:
      • metabolic acidosis, severe bleeding
    • Patient may dies or recovers within 12-24hours
  • finding DF DHF
    • (+1-25%,++26-50%,+++51-75%,++++76-100%)
    • Fever ++++ ++++
    • Petechiae ++ ++
    • Lymphadenopathy ++ ++
    • GI bleeding + +
  • finding DF DHF
    • Maculopapular rash ++ +
    • Myalgia/arthralgia +++ +
    • Leukopenia ++++ ++
    • Thrombocytopenia ++ ++++
    • Positive tourniquet test ++ ++++
    • Hepatomegaly 0 ++++
    • Shock 0 ++
  • Lab tests(1)
    • Clinical laboratory tests
      • CBC-- Leukopenia is typical;
      • thrombocytopenia , hematocrit
      • Liver function tests : Albumin
      • Urine--check for microscopic hematuria
  • Lab tests(2) : Dengue-specific tests
    • serologic tests: Antibody assay
    • useful for documenting:
    • IgM and complement fixing (CF)Ab : short –lived
    • Fourfold increase in titer between acute and convalescent sera
    • Viral antigen or viral RNA by PCR :
    • prove the diagnosis
    • Virus isolation:
    • grown in vertebrate and mosquito cell lines
    • Virus is best isolated from serum: febrile patients .
    • but are difficult
  • ELISA Test for Serologic Diagnosis
  • Virus Isolation: Cell Culture
  • Virus Isolation: Mosquito Inoculation
  • Virus Isolation: Fluorescent Antibody Test
  • Diagnosis of DF
    • Epidemiological evidences
    • Clinical presentations
    • Lab tests:
      • Routine test: for monitoring the severity
      • serologic tests: for clinical diagnosis
      • Virus isolate: to distinguish the serum types.
  • four criteria for DHF
    • Fever , last for 2-7days
    • at least one of Hemorrhage evidences
    • Thrombocytopenia :PLT<100,000/mm 3
    • Evidence of plasma leakage:
      • a rise in Hct:>=20%
      • pleural effusion ,ascites and
    • hypoprotinemia
  • Diagnosis criteria for DSS
    • four criteria for DHF
    • Evidence of shock
      • sweat, restless, cool extremities
      • rapid ,weak pulse
      • narrowing of pulse pressure<2.7kpa
      • hypotension
  • Differencial diagnosis
    • Include a wide spectrum of
    • viral
    • bacterial
    • Parasitic infections
  • prognosis
    • Self-limit disease
    • Convalescence may be prolonged
      • with weakness and mental depression
      • Continued bone pains, bradycardia
    • Survival is related to
      • early hospitalization
      • aggressive supportive care
  • Treatment of DF
    • complicated, no specific trx
    • Fluid replacement: adequate hydration
    • Bed Rest
    • Antipyretics
      • ace ta minophen (if no liver dysfunction)
      • No aspirin( association with Reye syndrome ) ,
      • steroids, avoid NSAIDS( anticoagulant properties).
  • Continuous Monitoring of
    • VS
    • Diuresis,mental status
    • Evidence of bleeding
    • Hydration status
    • Evidence of increased vascular permeability
    • hematocrit, platelet count(manual)
  • Management for DHF
    • Prevent and Treatment of shock:
    • mild to moderate isotonic dehydration (5%-8% deficit)
      • Iv cr y stalloids ; colloids; central line
      • Correct electrolyte abnormalities and acidemia
      • Monitor the vital signs: avoid hypovolemia or fluid overload.
    • therapy for DIC: if indicated
    • Unknown effective = steroid ,immune globulin
      • platelet transfusions
  • prevention
    • Three operations
    • must be conducted
    • isolation of patients.
    • emergency mosquito control simultaneously
    • Personal protection
  • vaccine
    • no vaccine currently available
    • research is underway for the development of a vaccine.
    • vaccine will not available for 5 to 10 years.
    • as
      • it must provide immunity to all 4 serotypes
      • Lack of dengue animal model
  • Personal protection
    • remain in well-screened or completely enclosed, air-conditioned areas;
    • wear light-colored clothing with full-length pant legs and sleeves;
    • use insect repellent on exposed skin.
    • Use netting when sleeping
  • thanks!
  • Discharge criteria
    • afebrile for 24 h appetite
    • clinical improvement 3 days post shock
    • Stable Hct Platelets  50,000/ mm 3
    • Eupnea: No respiratory distress from pleural effusions/ascites
  • Common Misconceptions about DHF
    • Dengue + bleeding = DHF
      • Need 4 WHO criteria, capillary permeability
    • DHF kills only by hemorrhage
      • Patient dies as a result of shock
    • Poor management turns dengue into DHF
      • Poorly managed dengue can be more severe, but DHF is a distinct condition, which even well-treated patients may develop
    • Positive tourniquet test = DHF
      • Tourniquet test is a nonspecific indicator of capillary fragility
  • Rehydrating Patients Over 40 kg
    • Volume required: twice the recommended maintenance volume
    • For mula for calculating maintenance volume: 1500 + 20 x (weight in kg - 20)
    • For example
      • 55 kg patient: maintenance volume :
      • 1500 + 20 x (55-20) = 2200 ml
      • For this patient, the rehydration volume would be 2 x 2200 , or 4400 ml
  • Dengue virus infection Asymptomatic symptomatic Undifferentiated fever (viral syndrome) dengue hemorrhagic fever (plasma leakage) dengue fever syndrome no shock DSS Without hemorrhage with unusual hemorrhage DF DHF
  • Fever tournigeut test(+) Increased vascular permeability heptomegaly thrombocytopenia Dengue infection Other haemorrhagic manifestations Leakage of plasma Rising haematocrit Hypoproteinaemia Serous effusion coapulopathy hypovolaemia shock DIC Severe bleeding death
  • Antiinflamatory agents Monitor vital sings q2h Provide oral hydration Same as above + type and cross match Determine PT AND PTT Same as above+ iv isotonic fluids, monitor q30mins, follow urine output Same as above+ Iv colloids or plasma Provide critical care support 1.Four Criteria for DHF 1+spontaneaous bleeding 1+Sings of shock: hypotention 1+undetectalbe pulse and blood pressure Grade 1 Grade 2 Grade 3 Grade 4