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Dengue Fever • Dengue


									                                          Dengue Fever
•   Dengue virus
•   Most prevalent vector-borne viral illness in the world
•   Main mosquito vector is Aedes aegypti
•   Year round transmission
•   Break bone fever/dandy
                                              Aedes aegypti
•   It is a medium-sized black-colored mosquito having a silvery-white “lyre-shaped” pattern on
    its scutum or shield
•   Highly domesticated
•   Black-and-white tropical insect that prefers to feed on humans
•   The insect typically lays its eggs in artificial containers that contain clean stagnant water
•   The insect is attracted by the body odors, carbon dioxide and heat emitted from animals and
•   Aedes are day biters , most active during dawn and dusk.
•   Incubation 3-14 days
•   Acute illness and viremia 3-7 days
•   Recovery or progression to leakage phase

• Flavivirus family
• Small enveloped viruses containing single stranded positive RNA
• Four distinct viral serotypes (Den-1, Den-2, Den-3, Den-4)
• Dengue virus enters and replicates within monocytes, mast cells, fibroblasts
• Innate and adaptive immune response
• Cytokine release: TNF-a, IL-2, IL-6, IL-8
• Compliment activation
• Antibody dependent enhancement (ADE) thought to contribute to severe infections
• T-cell activation: CD4 and CD8 cells cytokine production
Capillary Leak Syndrome:
• Transient increased capillary permeability due to endothelial cell dysfunction
•  Widening of tight junctions
• Cytokine release and complement activation

Leukopenia, Thrombocytopenia and Hemorrhagic diathesis:
• Direct viral bone marrow suppression
• Platelet destruction in DHF
• Molecular mimicry between viral protein and coagulation factors
                                       Disease Factors
• Dengue-2 serotype most virulent
• Increased severity with secondary infections
• Increased risk in children <15 years and elderly.
• Greatest risk of DHF in infants.
• More severe in females
• Increased mortality with comorbid conditions
                                     Clinical Presentation
Spectrum of illness:
• non-specific febrile illness
• classic dengue
• dengue hemorrhagic fever
• dengue shock syndrome
                                        Classic Dengue
“Break-bone fever”
• High fever, up to 105 F (40.6 C) for 5-7 days
• Followed by marked fatigue
• A rash over most of the body, which may subside after a couple of days and then reappear
• Severe headache, backache or both
• Pain behind your eyes
• Severe joint and muscle pain
• Nausea and vomiting
                                  Dengue Hemorrhagic Fever
WHO classification of DHF
• Thrombocytopenia (platelet count <100,000)
• Fever 2-7 days
• Hemorrhagic manifestations with a positive tourniquet test, petechiae, ecchymoses or mucosal
• Hemoconcentration or evidence of plasma leakage (ascites, effusion, decreased albumin)
                                  Dengue Hemorrhagic Fever
• Usually occurs in secondary infections
• Only 2-4% of secondary infections result in severe disease
• Mortality is 10-20% if untreated, but decreases to <1% if adequately treated
• Plasma leakage may progress to dengue shock syndrome
                     Dengue shock syndrome Four Grades of DHF/ DSS
• Grade 1
  Fever, Constant 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
                                    Criteria for severe dengue
Severe plasma leakage leading to:
   • Shock (DSS)
   • Fluid accumulation with respiratory distress
   • Severe bleeding as evaluated by clinician
   • Severe organ involvement
   • There is severe organ impairment (acute liver failure, acute renal failure, encephalopathy
        or encephalitis, or other unusual manifestations, cardiomyopathy) etc
   • CNS: Impaired consciousness

                                    Course of dengue illness
    •   Febrile phase
    •   Critical phase
    •   Recovery phase

                                            Febrile phase
    •   High-grade fever suddenly
    •   Lasts 2–7 days
    •   Often accompanied by facial flushing, skin erythema, generalized body ache, myalgia,
        arthralgia and headache
    •   Difficult to distinguish clinically from non-dengue febrile diseases
    •   Lab test show: progressive decrease in total white cell count

                                           Critical phase
    •   The temperature drops to 37.5–38C or less usually on days 3–7 of illness
    •   An increase in capillary permeability in parallel with increasing haematocrit levels may
    •   The period of clinically significant plasma leakage usually lasts 24–48 hours.
    •   Progressive leukopenia followed by a rapid decrease in platelet count usually precedes
        plasma leakage.

    •   Shock occurs when a critical volume of plasma is lost through leakage.
    •   With prolonged shock, the consequent organ hypoperfusion results in:
       progressive organ impairment
       metabolic acidosis
       disseminated intravascular coagulation.
    •   This in turn leads to severe hemorrhage causing the hematocrit to decrease in severe
                                          Recovery phase
    •   If the patient survives the 24–48 hour critical phase, a gradual reabsorption of
        extravascular compartment fluid takes place in the following 48–72 hours
    •   General well-being improves, appetite returns, gastrointestinal symptoms abate,
        hemodynamic status stabilizes and diuresis ensues.
    •   Bradycardia is common during this stage.
    •   The haematocrit stabilizes
    •   White blood cell count starts to rise
    •   Recovery of platelet count is typically later than that of white blood cell count
                                     Laboratory Diagnosis
•   Leucopenia.
•   Thrombocytopenia (<100,000)
•   Increased SGOT, SGPT
•   Rising Ab titre in paired sera
•   Antigen detection ELISA
•   IgM-capture ELISA within few hours
•   Reverse transcription PCR confirmatory
•   IgG ELISA significant of past infection

                  Conditions that mimic the febrile phase of dengue infection
Flu-like syndromes
• Influenza
• Measles
• Chikungunya
• Infectious mononucleosis
Diarrhoeal diseases
• Rotavirus
• enteric infections
Diseases with a rash
• Rubella
• Measles
• Scarlet fever
• Meningococcal infection
• Chikungunya
• Drug reactions

Diseases with neurological manifestations
• Meningo/ encephalitis
• Febrile seizures
Conditions that mimic the critical phase of dengue infection
• Acute gastroenteritis
• malaria
• leptospirosis
• typhoid
• typhus
• viral hepatitis
• acute HIV
• bacterial sepsis
• septic shock
• Malignancies
Other clinical pictures
• Acute abdomen
– acute appendicitis
– acute cholecystitis
– perforated viscus
• Diabetic ketoacidosis
• Lactic acidosis
• Leukopenia, thrombocytopenia ± bleeding
• Platelet disorders
• Renal failure
• Respiratory distress (Kussmaul’s breathing)
                              Criteria for dengue ± warning signs
Probable dengue
• Live in / travel to dengue endemic area.
• Fever and 2 of the following criteria:
 Nausea, vomiting

 Rash

 Aches and pains

 Tourniquet test positive

 Leukopenia

• Any warning sign
• Laboratory-confirmed dengue
Warning signs
• Abdominal pain or tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleed
• Lethargy, restlessness
• Liver enlargement >2 cm

• Laboratory: increase in HCT

• concurrent with rapid decrease in platelet count
                                      Admission criteria
   • Warning signs
   • Signs and symptoms related to hypotension
   • Bleeding
   • Organ impairment
   • Findings through further investigations
   • Co-existing conditions
   • Social circumstances
                                       Treatment of DF
• Supportive measures - Vector barrier
• Avoid Aspirin and if possible NSAIDs
• Steroids should not be used
• Fluid replacement to avoid hemoconcentration.
• Children below 12 require careful watch
  for DHF / DSS
• No antiviral agents are of proven value
Volume Replacement Flow Chart for Patients with DHF Grades I and II

                   Haemorrhagic (bleeding) tendencies,
                   Haematocrit rise. Pulse pressure is low

                       Initiate IV Therapy 6m l/kg/hr
                       Crystalloid solution for 1-2 hrs

 Improvement                                                 No Improvement

   Reduce IV 3ml/kg/h

   Crystalloid duration                                   increase IV10 ml/kg/h

   6-12 hrs                                               crystalloid duration 2 hr

                                  Improvement                            No Improvement
                                                                         Unstable Vital Signs

   Discontinue IV
   after 24 hrs

                                  Reduce IV to
                                  crystalloid with
                                  further reduction
                                  to 3 ml/kg/h.
                                  discontinue after
                                  24-48 hrs

        No Improvement , Unstable Vital Signs

Haematocrit                                  Haematocrit
Rises                                        Falls

  IV Colloid                                      Blood
  (Dextran                                        transfusion
  (40)                                            10 ml/kg/hr
  10ml/kg/hr                                      duration 1 h
  duration 1 hr.


           IV therapy by crystalloid Successively
            reduce the flow from 10 to 6, 6 to
            3ml/kg/hr Discontinue after 24-48 hrs
         Volume Replacement Flow Chart for Patients with DHF Grades III and IV
                                 UNSTABLE VITAL SIGNS
                                   Urine Output Falls
                                    Signs Of Shock

                Immediate, rapid volume replacement*: Initiate IV therapy
                    10-20ml/kg/h Crystalloid solution for 1 hr

           Improvement                                          No Improvement

     IV Therapy by crystalloid                                     Oxygen
     successively reducing
     from 20
     to10, 10 to 6, and 6 to

     Improvement                          Haematocrit
                                      IV Colloid (Dextran 40)
                                      or plasma 10ml/kg/hr as          blood transfusion
        Discontinue                      intravenous bolus             (10ml/kg/hr) if
        intravenous                    (repeat if necessary              hematocrit >35
        therapy after 24-
        48 hrs                                          improvement
                                                   IV therapy by crystalloid,
                                                   successively reducing the flow
                                                   from 10 to 6, 6 to 3ml/kg/hr
                                                   Discontinue after 24-48 hrs

                                                    DHF / DSS
    • Intensive Care
    • Oxygen
    • Rehydration
    • Barrier Nursing
    • Mosquito Screen

•  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
                                        Discharge criteria
    • No fever for 48 hours.
    • Improvement in clinical status, general well-being, appetite, haemodynamic status, urine
    • No respiratory distress
    • Increasing trend of platelet count.
    • Stable hematocrit without intravenous fluids
                                     Home care card for dengue
What should be done?
     • Adequate bed rest
     • Adequate fluid intake (>5 glasses for average-sized adults or accordingly in children)
     • Milk, fruit juice (caution with diabetes patient)
     • Isotonic electrolyte solution (ORS)
     • Barley/ rice water.
     • Plain water alone may cause electrolyte imbalance.
     • Take paracetamol (not more than 4 grams/ day for adults and accordingly in children)
     • Tepid sponging
     • Look for mosquito breeding places in and around the home and eliminate them
What should be avoided?
• Do not take acetylsalicylic acid (aspirin), mefenemic acid (ponstan), ibuprofen or other non-
• Anti-inflammatory agents (nsaids), or steroids.
• Antibiotics are not necessary
If any of following is observed, take the patient immediately to the nearest hospital. These are
    warning signs for danger:
• Bleeding:
    - red spots or patches on the skin
    - bleeding from nose or gums
    - vomiting blood
    - black-colored stools
    - heavy menstruation/vaginal bleeding
• Frequent vomiting
• Severe abdominal pain
• Drowsiness, mental confusion or seizures
• Pale, cold or clammy hands and feet
• Difficulty in breathing

                                  Common Misconceptions- DHF
• Dengue + bleeding = DHF
• DHF is fatal only due to hemorrhage
   No, Majority of deaths are due to shock

• Poorly managed DF turns into DHF
• Positive tourniquet = DHF
   it is not specific for DHF,
   it indicates capillary fragility of any origin

• DHF is only a pediatric illness
   No, All ages may be involved

• DHF is a problem of poor families
   No, in fact they may not have
   immune complexes to required level

• Tourists will get DHF
   No, in fact they are at low risk
•   Personal:
•   clothing to reduce exposed skin
•   insect repellent especially in early morning, late afternoon. Bed netting is of little utility.
•   Environmental:
•   reduced vector breeding sites
•   solid waste management
•   public education
•   Biological:
•   Target larval stage of Aedes in large water storage containers
•   Chemical:
•   Insecticide treatment of water containers
•   Space spraying (thermal fogs)
                                              THE END

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