PRESENTED BY: SITI NUR HAMIZAH HAMIDON

DENGUE FEVER
INTRODUCTION

 Ac. Febrile illness
 Viruses belonging to Flaviviridae family

 Characterized by:
      Biphasic   fever
      Myalgia

      Arthralgia

      Rash
EPIDEMIOLOGY

 Endemic in Africa, America, Eastern
  Mediterranean, SEAR, & Western Pacific.
 During epidemics- attack rates may reach
  80-90%.
 Est 500000 cases of DHF requires
  hospitalization each year.
 With modern intensive support therapy DHF
  case fatality rate are reduced to <1%.
SCENARIO IN MALAYSIA
   Increasing trend of DF&DHF.
   Incidence rate in 1999 = 44.3 cases/100000 population
   Incidence rate in 2007 = 181 cases/100000 population.
   National target = <50cases/100000 population
   Incidence rate is higher in age group >15 yrs. Highest
    among working & school going age group.
   Case fatality rate both DF&DHF remain well below 0.3%
    since 2002.
   70-80% cases were reported from urban areas prob due
    to high density of population and rapid development
    activities which favour transmission.
VIRUS
   4 serotypes of dengue viruses
     DENV-1
     DENV-2
     DENV-3
     DENV-4

 Arbovirus-from family Flaviviridae.
 Single stranded RNA virus. Spherical, 50nm
  diameter, envelop protein bears epitopes that
  are unique to serotype.
All four serotypes can be isolated at any one time but the predominant circulating
dengue virus will show sinusoidal pattern.
TRANSMISSION
   Transmitted to humans through bites of
    infective female Aedes mosquitoes.
     Aedes aegypti
     Aedes albopictus

 Humans are the main amplifying host.
 Incubation period 5-8 days.
 The virus circulates in the blood of infected
  humans for 2-7 days, at approximately the
  same time they have fever.
Aedes aegypti




Aedes albopictus
PATHOPHYSIOLOGY OF INFECTION & ITS
CONSEQUENCES.
 Dengue viral infection asso with
  thrombocytopenia, the cause is molecular
  mimicry b/w dengue virus proteins &
  endogenous self-proteins.
 Generation of antibodies against dengue virus
  proteins which cross-react with platelet surface
  proteins and thus cause thrombocytopenia.
 There is activation of blood clotting and
  fibrinolytic pathways.
 Mild DIC, liver injury & thrombocytopenia
  together contribute to hemorrhagic tendency.
   DHF
     Sequential   infection with any 2 of the 4 serotpes
      og dengue virus result in DHF/DSS in endemic
      area.
     How 2nd dengue infection causes severe disease
      and why only some patients get severe disease
      remains unclear.
     Suggested that residual Ab produced during 1st
      infection are able to neutralize a second viral
      infection with the same serotype.
     When no neutralizing Ab are present (i.e:
      infection due to other serotype), the second
      infection is under the influence of enhancing Ab
      & the resulting infection and disease are severe.
 Serotype cross reactive antibodies generated from
  previous primary infection with particular dengue
  viral serotype are not highly specific for the other
  serotypes involve in secondary infections.
 Hence, the bind to virion but do not neutralize them,
  and instead increase their uptake by cells like tissue
  dendritic cells, monocytes and macrophages leading
  to more rapid activation and proliferation of memory
  T-cells
 Cytokines produces by activated T-cells lead to
  pathogenesis of DHF/DSS.
 Cytokines causes vascular compromise and
  hemorrhage. The endothelial cell dysfunction is
  manifested by diffuse increase in capillary
  permeability microvascular
  leakage,hemoconcentration, and circulatory
  insufficientcy.
CLINICAL COURSE OF DENGUE INFECTION
   After the incubation period, the illness begins
    abruptly and will be followed by 3 phases.
     Febrile  phase
     Critical phase

     Recovery phase.
NEW CLASSIFICATION OF DENGUE
   Non-severe dengue          Non-severe dengue with             Severe dengue
  without warning signs           warning signs
Probable dengue               •Abdominal pain/             •Severe plasma leakage
•Live in/travel to endemic    tenderness                   leading to
area                          •Persistent vomiting              •Circulatory compromise/
•Fever & 2 of the following   •Clinical fluid accumulation      shock /DSS
criteria:                     •Mucosal bleed                    (tachy,cold&clammy
     •Nausea&vomiting         •Lethargy & restlessness          extremities, cap refill
     •Rash                    •Liver enlargement >2cm           time >3sec, undetectable
     •Aches&pains             •Lab: incrase haematocrit         pulse, late phase:
     •Tourniquet test         concurrent with rapid             unrecordable BP)
     positive                 decrease in platelet count.       •Fluid accumulation with/
     •Leucopenia                                                without respiratory
     •No warning sign                                           distress.
Laboratory-confirmed                                       •Severe bleeding
dengue.                                                    •Severe organ involvement.
                                                                •Liver: AST/ALT >/= 1000
                                                                •CNS: impaired
                                                                consciousness
                                                                •Heart & other organs.
TOURNIQUET TEST
LABORATORY INVESTIGATIONS
   Disease monitoring lab test:
       White cell count
            Early febrile phase usually normal but decrease rapidly as disease
             progresses.
       Haematocrit
            Rising HCT is a marker of plasma leakage and helps to differentiate
             b/t DF & DHF.
            May be masked in patients with concurrent significant bleeding &
             those who received fluid therapy.
            Setting pt’s baselineHCT in early febrile phase will be useful in
             recognition of a rising HCT.
       Thrombocytopenia
            Early febrile phase- platelet count usually w/in normal range.
            Decrease repidly as disease progresses to late febrile phase.
            May remain low for first few days of recovery.
       LFT
            Greater elevation of AST as compared to ALT.
            Degree of elevation higher in DHF compared to DF.
   Diagnostic test:
     Antibody    detection (serology)
        Haemagglutination   Inhibition Test
        Dengue    IgM test
        Indirect IgG ELISA test
 Virusisolation
 Detection of virus genetic materials (PCR)

 Detection of dengue virus protein (NS1 Antigen)




 False   positive dengue serology :
   Cross   reaction with:
      other flaviviris – Japanese Encephalitis
      non-flavivirus – malaria, leptospirosis, toxoplasmosis, syphilis

      Connective issue disease – rheumatoid arthritis.
STEPWISE APPROACH
CRITERIA FOR ADMISSION
TREATMENT

   Symptomatic treatment + aggressive,
    supportive fluid therapy
 Fever (antipyretic; Paracetamol)
  : Max dose: 60mg/kg daily in divided doses
    oral or IV (15mg/kg every 6h)
    Rectal: 20mg/kg every 8h
 Avoid salicylates & NSAIDs (bleeds)

 Monitoring.

 DIC: can give FFP, platelet concentrates
CLINICAL & LAB CRITERIA FOR PT WHO CAN BE
TREATED AT HOME.
DIFFERENTIAL DIAGNOSIS OF DENGUE FEVER
PROGNOSIS

 Left untreated: mortality rate can be upto 40-
  50%
 Early recognition & appropriate fluid therapy
  1-5%
 Early detection of shock → excellent
  prognosis
 Prolonged shock + cold extremities,
  unrecordable BP → difficult
PREVENTION
    No approved vaccines approach yet
    Integrated Vector Control programme
a.   Advocacy, social mobilization, legislation to ensure
     public health bodies & communities are strengthened
b.   Collaboration of health & other sectors
c.   Integrated approach to disease control with maximum
     use of resources
d.   Evidence-based decision making
e.   Capacity building to ensure adequate response
    Eliminate its habitats (empty water container/ +
     insecticides)
    Reducing open collection of water
    Environmental modification
    Mosquito netting & insect repellent
REFERENCE
   Ghai Essential Pediatrics, 7th Edition, CBS publication, page 196-
    200.
   Medicine Prep Manual for Undergraduates, 4th Edition, Elsevier
    Publication, page 751-755.
   Dengue haemorrhagic fever: diagnosis, treatment,
    prevention and control. 2nd edition. Geneva : World Health
    Organization. :
    http://www.who.int/csr/resources/publications/dengue/Denguepub
    lication/en/index.html
   Dengue- Guidelines for Diagnosis, Treatment, Prevention &
    Control. New Edition 2009. world Health Organization:
    http://whqlibdoc.who.int/publications/2009/9789241547871_eng.p
    df
   http://www.who.int/csr/disease/dengue/en/
   Clinical Practice Guidelines- Management of Dengue Infection in
    Adults. Revised 2nd Edition. Ministry of Health Malaysia.: http:
    www.moh.gov.my

Dengue fever

  • 1.
    PRESENTED BY: SITINUR HAMIZAH HAMIDON DENGUE FEVER
  • 2.
    INTRODUCTION  Ac. Febrileillness  Viruses belonging to Flaviviridae family  Characterized by:  Biphasic fever  Myalgia  Arthralgia  Rash
  • 3.
    EPIDEMIOLOGY  Endemic inAfrica, America, Eastern Mediterranean, SEAR, & Western Pacific.  During epidemics- attack rates may reach 80-90%.  Est 500000 cases of DHF requires hospitalization each year.  With modern intensive support therapy DHF case fatality rate are reduced to <1%.
  • 5.
    SCENARIO IN MALAYSIA  Increasing trend of DF&DHF.  Incidence rate in 1999 = 44.3 cases/100000 population  Incidence rate in 2007 = 181 cases/100000 population.  National target = <50cases/100000 population  Incidence rate is higher in age group >15 yrs. Highest among working & school going age group.  Case fatality rate both DF&DHF remain well below 0.3% since 2002.  70-80% cases were reported from urban areas prob due to high density of population and rapid development activities which favour transmission.
  • 7.
    VIRUS  4 serotypes of dengue viruses  DENV-1  DENV-2  DENV-3  DENV-4  Arbovirus-from family Flaviviridae.  Single stranded RNA virus. Spherical, 50nm diameter, envelop protein bears epitopes that are unique to serotype.
  • 8.
    All four serotypescan be isolated at any one time but the predominant circulating dengue virus will show sinusoidal pattern.
  • 9.
    TRANSMISSION  Transmitted to humans through bites of infective female Aedes mosquitoes.  Aedes aegypti  Aedes albopictus  Humans are the main amplifying host.  Incubation period 5-8 days.  The virus circulates in the blood of infected humans for 2-7 days, at approximately the same time they have fever.
  • 10.
  • 11.
    PATHOPHYSIOLOGY OF INFECTION& ITS CONSEQUENCES.  Dengue viral infection asso with thrombocytopenia, the cause is molecular mimicry b/w dengue virus proteins & endogenous self-proteins.  Generation of antibodies against dengue virus proteins which cross-react with platelet surface proteins and thus cause thrombocytopenia.  There is activation of blood clotting and fibrinolytic pathways.  Mild DIC, liver injury & thrombocytopenia together contribute to hemorrhagic tendency.
  • 12.
    DHF  Sequential infection with any 2 of the 4 serotpes og dengue virus result in DHF/DSS in endemic area.  How 2nd dengue infection causes severe disease and why only some patients get severe disease remains unclear.  Suggested that residual Ab produced during 1st infection are able to neutralize a second viral infection with the same serotype.  When no neutralizing Ab are present (i.e: infection due to other serotype), the second infection is under the influence of enhancing Ab & the resulting infection and disease are severe.
  • 13.
     Serotype crossreactive antibodies generated from previous primary infection with particular dengue viral serotype are not highly specific for the other serotypes involve in secondary infections.  Hence, the bind to virion but do not neutralize them, and instead increase their uptake by cells like tissue dendritic cells, monocytes and macrophages leading to more rapid activation and proliferation of memory T-cells  Cytokines produces by activated T-cells lead to pathogenesis of DHF/DSS.  Cytokines causes vascular compromise and hemorrhage. The endothelial cell dysfunction is manifested by diffuse increase in capillary permeability microvascular leakage,hemoconcentration, and circulatory insufficientcy.
  • 14.
    CLINICAL COURSE OFDENGUE INFECTION  After the incubation period, the illness begins abruptly and will be followed by 3 phases.  Febrile phase  Critical phase  Recovery phase.
  • 16.
    NEW CLASSIFICATION OFDENGUE Non-severe dengue Non-severe dengue with Severe dengue without warning signs warning signs Probable dengue •Abdominal pain/ •Severe plasma leakage •Live in/travel to endemic tenderness leading to area •Persistent vomiting •Circulatory compromise/ •Fever & 2 of the following •Clinical fluid accumulation shock /DSS criteria: •Mucosal bleed (tachy,cold&clammy •Nausea&vomiting •Lethargy & restlessness extremities, cap refill •Rash •Liver enlargement >2cm time >3sec, undetectable •Aches&pains •Lab: incrase haematocrit pulse, late phase: •Tourniquet test concurrent with rapid unrecordable BP) positive decrease in platelet count. •Fluid accumulation with/ •Leucopenia without respiratory •No warning sign distress. Laboratory-confirmed •Severe bleeding dengue. •Severe organ involvement. •Liver: AST/ALT >/= 1000 •CNS: impaired consciousness •Heart & other organs.
  • 18.
  • 19.
    LABORATORY INVESTIGATIONS  Disease monitoring lab test:  White cell count  Early febrile phase usually normal but decrease rapidly as disease progresses.  Haematocrit  Rising HCT is a marker of plasma leakage and helps to differentiate b/t DF & DHF.  May be masked in patients with concurrent significant bleeding & those who received fluid therapy.  Setting pt’s baselineHCT in early febrile phase will be useful in recognition of a rising HCT.  Thrombocytopenia  Early febrile phase- platelet count usually w/in normal range.  Decrease repidly as disease progresses to late febrile phase.  May remain low for first few days of recovery.  LFT  Greater elevation of AST as compared to ALT.  Degree of elevation higher in DHF compared to DF.
  • 20.
    Diagnostic test:  Antibody detection (serology)  Haemagglutination Inhibition Test  Dengue IgM test  Indirect IgG ELISA test
  • 21.
     Virusisolation  Detectionof virus genetic materials (PCR)  Detection of dengue virus protein (NS1 Antigen)  False positive dengue serology :  Cross reaction with:  other flaviviris – Japanese Encephalitis  non-flavivirus – malaria, leptospirosis, toxoplasmosis, syphilis  Connective issue disease – rheumatoid arthritis.
  • 22.
  • 25.
  • 26.
    TREATMENT  Symptomatic treatment + aggressive, supportive fluid therapy
  • 27.
     Fever (antipyretic;Paracetamol) : Max dose: 60mg/kg daily in divided doses oral or IV (15mg/kg every 6h) Rectal: 20mg/kg every 8h  Avoid salicylates & NSAIDs (bleeds)  Monitoring.  DIC: can give FFP, platelet concentrates
  • 30.
    CLINICAL & LABCRITERIA FOR PT WHO CAN BE TREATED AT HOME.
  • 35.
  • 36.
    PROGNOSIS  Left untreated:mortality rate can be upto 40- 50%  Early recognition & appropriate fluid therapy 1-5%  Early detection of shock → excellent prognosis  Prolonged shock + cold extremities, unrecordable BP → difficult
  • 37.
    PREVENTION  No approved vaccines approach yet  Integrated Vector Control programme a. Advocacy, social mobilization, legislation to ensure public health bodies & communities are strengthened b. Collaboration of health & other sectors c. Integrated approach to disease control with maximum use of resources d. Evidence-based decision making e. Capacity building to ensure adequate response  Eliminate its habitats (empty water container/ + insecticides)  Reducing open collection of water  Environmental modification  Mosquito netting & insect repellent
  • 38.
    REFERENCE  Ghai Essential Pediatrics, 7th Edition, CBS publication, page 196- 200.  Medicine Prep Manual for Undergraduates, 4th Edition, Elsevier Publication, page 751-755.  Dengue haemorrhagic fever: diagnosis, treatment, prevention and control. 2nd edition. Geneva : World Health Organization. : http://www.who.int/csr/resources/publications/dengue/Denguepub lication/en/index.html  Dengue- Guidelines for Diagnosis, Treatment, Prevention & Control. New Edition 2009. world Health Organization: http://whqlibdoc.who.int/publications/2009/9789241547871_eng.p df  http://www.who.int/csr/disease/dengue/en/  Clinical Practice Guidelines- Management of Dengue Infection in Adults. Revised 2nd Edition. Ministry of Health Malaysia.: http: www.moh.gov.my