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
humans.
• 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

Virology
• Flavivirus family
• Small enveloped viruses containing single stranded positive RNA
• Four distinct viral serotypes (Den-1, Den-2, Den-3, Den-4)
Pathophysiology
• 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
bleeding.
• 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
occur
• 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
• 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
shock
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
• HIV
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
Infectious
• 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)
• SLE
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,

Thrombocytopenia,
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

Further
Improvement
Improvement No Improvement
Unstable Vital Signs

Discontinue IV
after 24 hrs

Reduce IV to
6ml/kg/h
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.

Improvement

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
3ml/kg/hr

Further
Improvement Haematocrit
Haematocrit
Rises
Falls
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
Treatment:
• Intensive Care
• Oxygen
• Rehydration
• Barrier Nursing
• Mosquito Screen

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
Discharge criteria
Clinical
• No fever for 48 hours.
• Improvement in clinical status, general well-being, appetite, haemodynamic status, urine
output
• No respiratory distress
Laboratory
 • 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-
steroidal
• 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

Prevention
• 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