Dengue Fever - PowerPoint

							‫بسم اهلل الرحمن الرحيم‬
VIRAL HEMORRHAGIC FEVER.
   A group of illnesses that are caused by
    several distinct families of viruses.
   A severe multisystem syndrome (multiple
    organ systems in the body are affected).
   Vascular system damaged
   Body’s ability to regulate itself is impaired.
   Many cause severe and life-threatening
    disease.
Viral Hemorrhagic Fever
   Viruses of four distinct families
       Arenaviruses
       Filoviruses
       Bunyaviruses
       Flaviviruses
   RNA viruses
     Enveloped in lipid coating
   Survival dependent on an animal or
    insect host, for the natural reservoir
FAMILY/GEOGRAPHY                    AGENT               CASE-FATALITY




Filoviridae               Ebola                              50-75%
Sub-saharan Africa        Marburg                             25%

Arenaviridae              Old World: Lassa            Lassa:1-2% (up to 25%
West Africa (Lassa)       New World: Junin,             in hospitalized pts)
South America,            Machupo, Guanarito
California (Whitewater)   Sabia, Whitewater arroyo     30% for New World
Bunyaviridae              Phlebovirus: Rift Valley    Rift Valley: <1% overall
Sub-saharan Africa        Nairovirus: Crimean Congo    50% in hemorrhagic
Egypt, Yemen              Hantavirus: Sin Nombre
SW US (Hantavirus)
Flaviviridae              Yellow fever                 Yellow Fever: 5-7%
Sub-saharan Africa        Dengue                             overall
Central Asia              Omsk                         50% in hemorrhagic
                          Kyasanur
    Transmission to Humans
   Arthropod vectors:
     Mosquitoes
     ○ Bunyavirus: RVF
     ○ Flaviviruses: Dengue, Yellow fever
     Ticks
      ○ Bunyavirus: CCHF
      ○ Flaviviruses: Kyanasur Forest Disease, Omsk
        HF
     Hematophagous flies:
      ○ Bunyaviruses: RVF
PERSON-TO-PERSON
TRANSMISSION
            Blood and body fluids
    Arenaviruses             Filoviruses
    Bunyaviruses             Flaviviurses
    ○ CCHF, RVF               ○ Yellow Fever



      Respiratory droplet or airborne (?)
    Arenaviruses           Filoviruses ??
    ○ (Lassa, Bolivian HF)    ○ (Ebola Reston:
                                monkey-human)
    Bunyaviruses
    ○ (CCHF)
Flaviviridae Humans
   Yellow Fever
     Incubation period – 3–6 days
     Short remission
   Dengue Hemorrhagic Fever
     Incubation period – 2–5 days
     Infection with different serotype
CRIMEAN CONGO HEMORRHAGIC FEVER
(CCHF)
            Extensive geographic distribution
             (Africa, Balkans, and western Asia)
            Transmission:
              Tick-borne (Hyalomma spp.)
              Contact with animal blood or products
              Person-to-person transmission
                 by contact with infectious body fluids
              Laboratory worker transmission
               documented
            Mortality 15-40%
  CCHF: Clinical features

 4-12   day incubation after tick exposure
 2-7day   incubation after direct contact with infected
  fluids
 Abrupt onset fever, chills, myalgia, severe headache
 Malaise, GI symptoms, anorexia
 Leukopenia, thrombocytopenia, hemoconcentration,
  proteinuria, elevated AST
 Hemorrhages     may be profuse (hematomas,
  ecchymoses)
VHF--Other important diseases
   Yellow fever
     Seen in Africa, South America
     Mosquito-borne
     Monkeys are the main reservoir
     Vaccine available

   Dengue
     Found in tropical areas
     Mosquito-borne
     Called "breakbone fever"
     2008: over 40,000 cases in Brazil

   Rift valley fever
     A disease of livestock
     Mosquito-borne
     Increasing outbreaks in Africa
     Can cause liver failure, blindness
VHF--Other important diseases
   Crimean-Congo hemorrhagic fever
     Found in animals in Europe, Asia and Africa
     Tick-borne
     Nosocomial spread is common

   Chikungunya
     Causing outbreaks in India, Indian Ocean islands, Italy
     Mosquito-borne
     Named for contorted posture due to severe joint pain

   Others
     Hantavirus infection
     Ross river virus
     Sabia virus
     Whitewater Arroyo virus
     Argentinian HF
     Bolivian HF
Clinical Symptoms
 Differ slightly depending on virus
 Initial symptoms
     Marked fever
     Fatigue
     Dizziness
     Muscle aches
     Exhaustion
Clinical Symptoms
   More severe
     Bleeding under skin
      ○ Petechiae, echymoses, conjunctivitis
     Bleeding in internal organs
     Bleeding from orifices
     Blood loss rarely cause of death
TREATMENT
 Supportive treatment
 Ribavirin
     Not approved by FDA
     Effective in some individuals
     Arenaviridae and Bunyaviridae only
   Convalescent-phase plasma
     Argentine HF, Bolivian HF and Ebola
 Strict isolation of affected patients is required
 Report to health authorities
VHF: Differential Diagnosis

 Bacterial
   typhoid fever, meningoccemia,
    rickettsioses, leptospirosis
 Protozoal
    falciparum malaria
 Other
    vasculitis, TTP, HUS, heat stroke
DENGUE FEVER
Dengue Fever
 Dengue virus
 Most prevalent vector-
  borne viral illness in the
  world
 Main mosquito vector
  is Aedes aegypti
 Year round
  transmission
Alternative Names

        Onyong- Nyang Fever
        West Nile Fever
        Break Bone Fever
        Dengue like Disease
The Agent



  DENGUE VIRUS
The Dengue Virus

      Flavivirus
      Positive sense
      Single stranded RNA virus
      40 to 50 nanometers
      Four sero-sub types
      Type 1 to 4
      Arthropod borne
Incidence
   50-100 million dengue fever infections
    per year globally
   500,000 cases of severe dengue,
    dengue hemorrhagic fever or dengue
    shock syndrome
   100-200 cases annually in U.S.
   Average case fatality 5%
Distribution
   Endemic in more than
    100 tropical and
    subtropical countries
   Pandemic began in
    Southeast Asia after WW
    II with subsequent global
    spread
   Several epidemics since
    1980s
   Distribution is
    comparable to malaria
Aedes aegypti
Aedes aegypti
 Dengue transmitted by infected female
  mosquito
 Highly domesticated tropical mosquito.
 Prefer to lay eggs in artificial containers
  e.g. flower vases, automobile tires…etc.
 Prefer to rest indoors.
 Prefer to feed on humans during
  daytime hours.
 Replication and Transmission
 of Dengue Virus (Part 1)
1. Virus transmitted      1
   to human in mosquito
   saliva            2
2. Virus replicates               4
   in target organs
3. Virus infects white
                              3
   blood cells and
   lymphatic tissues
4. Virus released and
   circulates in blood
Replication and Transmission
of Dengue Virus (Part 2)
5. Second mosquito            6
   ingests virus with blood

6. Virus replicates
   in mosquito midgut             7
   and other organs,
   infects salivary
   glands                     5
7. Virus replicates
   in salivary glands
Physical Exam
                 Nonspecific findings
                 Conjunctival
                  injection, pharyngeal
                  erythema,
                  lymphadenopathy,
                  hepatomegaly (20-
                  50%)
                 Macular or
                  maculopapular rash
                  (50%)
The Disease



       Clinical Features
Dengue Presentations

    Undifferentiated fever
    Dengue Fever (DF) with the Fever-
     Myalgia (FM) presentation (classical)
    Dengue Hemorrhagic Fever (DHF)
    Dengue Shock Syndrome (DSS)
Undifferentiated Fever
 May be the most common manifestation
  of dengue
 Prospective study found that 87% of
  students infected were either
  asymptomatic or only mildly
  symptomatic
 Other prospective studies including all
  age- groups also demonstrate silent
  transmission
Clinical Manifestations- DF

  IP of 2 – 7 days - typical patient develops
  Sudden onset of fever, chills, headache
  Back pain with severe myalgia, arthralgia
  Retro-orbital pain – break bone fever
  Macular rash – in axillary area
  Adenopathy, palatal vesicles, scleral inj.
  Maculo-papular rash on trunk – extremities
  Epistaxis and scattered petechiae
Other manifestations- DF

  Anorexia. Nausea, vomiting
  In apparent illness-to acute incapacitation
  Illness is about 2–5 days, biphasic course
  Pain on eye movements
  Pain on palpating abdominal muscles
  Primarily not a respiratory illness
  Rare - aseptic meningitis
  Complete recovery is the rule - asthenia
Dengue Haemorrhagic Fever (DHF)

 Vascular instability
 Decreased vascular integrity
 Assault on macro vasculature
 Decreased platelet function
 Increased vascular permeability
 Vascular disruption and local bleeds
 Hypotension, hemoconcentration- shock
Hemorrhagic Manifestations

     Skin hemorrhages:
      petechiae, purpura, ecchymoses
     Gingival bleeding
     Nasal bleeding
     Gastro-intestinal bleeding:
      hematemesis, melena, hematochezia
     Haematuria
     Increased menstrual flow
Ecchymosis – Periorbital Edema
Capillary Damage
Large Subcutaneous Bleed
CRITERIA FOR DHF

 Fever, or recent history of acute fever
 Hemorrhagic manifestations
 Low platelet count (100,000/mm 3 or
  less)
 Objective evidence of “leaky capillaries:”
     Elevated hematocrit -20% or more
     more over baseline or  50%
     Low albumin, pleural effusion
CRITERIA FOR DSS

      The four criteria of DHF
      Evidence of circulatory failure
      1. Rapid and weak pulse
      2. Narrow pulse pressue (less than 20mm)
      3. Hypotension for the age
      4. Cold clammy skin
      5. Altered mental status
Four Grades of DHF/DSS

  Grade 1
   Fever, Const. Symptoms, +ve tourniquet test
  Grade 2
   Grade 1 + Spontaneous bleeding
  Grade 3
   Signs of circulatory failure
  Grade 4
   Profound shock - B.P. Pulse not recordable
Danger Signs in
Dengue Hemorrhagic Fever

   Abdominal pain - intense and
    sustained
   Persistent vomiting
   Abrupt change from fever to
    hypothermia, with sweating and
    prostration
   Restlessness or somnolence
Unusual Presentations
of Severe Dengue Fever

    Encephalopathy
    Hepatic damage
    Cardiomyopathy
    Severe gastrointestinal hemorrhage
Signs and Symptoms of
Encephalitis/Encephalopathy
Associated with Acute Dengue Infection

      Decreased level of consciousness:
       lethargy, confusion, coma
      Seizures
      Nuchal rigidity
      Paresis
DHF- Poor Prognostic Signs
   Girl children under 12 with DHF/DSS
   Severe hypotension and shock
   Multifocal bleeding – abdominal pain
   CNS encepahlopathy, fits, coma
   Watch for preorbital edema, proteinuria
    postural or otherwise hypotension
   Serotype 2 infection after type 4
   Malnutrition is protective
Differential Diagnosis

        FM complex
        1. Anicteric leptospirosis
        2. Rickettsial fevers
        3. Influenza, Measles, Rubella
        DHF / DSS
        1. Other hemorrhagic fevers
        2. DIC due to septicemia
        3. Complicated Malaria
        4.   Meningococcemia
Clinical tests for DHF

  Petechiae after tourniquet test
  Overt bleed from previous GI lesions
  Platelet count less than 100,000/ul
  Low pulse pressure, cyanosis, effusions
  Hypotension, Shock
Petechiae
Diagnosis for Dengue
 Travel history and symptom profile
 Detection of antibodies against the virus
 Complete blood count
 Chemistry panel
 Liver function test
 Occult blood in stool
 DIC panel
Laboratory Findings
   Leukopenia
   Thrombocytopenia (<100,000)
   Modest liver enzyme elevation (2-5x nml)
   Serology:
•   Acute phase serum IgM (+6-90 days) ELISA
•   Acute and convalescent IgG (99% sens, 96%
    spec)
•   Hemagglutination inhibition assay (HI) is gold
    standard. Paired acute and convalescent HI
    assay, positive if >4 fold titer rise
Laboratory Diagnosis

  Increased SGOT, SGPT
  Reverse transcription PCR confirmatory
  IgG ELISA significant of past infection
TREATMENT OF DF

  Supportive measures - Vector barrier
  Avoid Aspirin and if possible NSAIDs
  Steroids should not be used
  Fluid replacement to avoid hemoconc.
  Children below 12 require careful watch
   for DHF / DSS
  No antiviral agents are of proven value
DHF / DSS

            Intensive Care
            Oxygen
            Rehydration
            Barrier Nursing
            Mosquito Screen
Management of DHF/DSS

  Close monitoring of hypotension/shock
  Oxygen administration
  IV. Infusion of crystalloids/colloids
  Platelet transfusion
  Clotting factors replacement
  Case fatality is 5% in good centers
Vaccination
   No current dengue vaccine
   Estimated availability in 5-10 years
   Vaccine development is problematic as the
    vaccine must provide immunity to all 4
    serotypes
   Lack of dengue animal model
   Live attenuated tetravalent vaccines under
    phase 2 trials
   New approaches include infectious clone
    DNA and naked DNA vaccines
Vector Control
       Biological
       1. Largely experimental
       2. Use of fish to feed on larvae
       Environmental
       1. Elimination of larval habitat
       2. Most likely successful strategy
       Purpose of control
          To reduce female vector density
Vector Control of Dengue

   Mosquito control is expensive –impossible
   Destruction of breeding sites – viable
   Spraying insecticides for adult control- ?
   Individual measures to avoid vector contact
    1. Mosquito screens, repellents (DEET)
    2. Permithrin impregnated clothing
   Non degradable tires, long life plastics-avoid
WRSTA2006, 13 August 2006