Dengue is a mosquito-borne viral illness caused by the dengue virus, transmitted by the Aedes mosquito.

  • One of the most common causes of “undifferentiated tropical fevers”.
  • It is associated with higher morbidity and mortality especially in children. The risk of death is fourfold higher in children younger than 15 years of age.

Case Definition

  • Dengue fever: Acute febrile illness  (2-7 days) with one or more of the following: Headache, retrorbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations. OR, non-ELISA based  nonstructural glycoprotein-1 (NS-1) antigen/IgM tested positive.
  • Severe Dengue:  Consider if the patient is from an area of dengue risk presenting with fever of 2–7 days plus any of the following features:
    • Evidence of plasma leakage
      • High or progressively rising haematocrit
      • Pleural effusions or ascites
      • Circulatory compromise or shock (tachycardia, cold and clammy extremities, capillary refill time >3 sec, weak or undetectable pulse, narrow pulse pressure or, in late shock, unrecordable blood pressure).
    • Significant bleeding
    • Altered level of consciousness (lethargy or restlessness, coma, convulsions)
    • Severe gastrointestinal involvement (persistent vomiting, increasing or intense abdominal pain, jaundice)
    • Severe organ impairment (acute liver failure (AST or ALT >1000), acute renal failure, encephalopathy or encephalitis, ARDS or other unusual manifestations.)
Warning Signs in Dengue Fever-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

Clinical Course of Dengue

Febrile phase (2-5 days)Patient remain febrile throughout this period, fever is biphasic
Critical phase (after 3-4 days of onset of fever)-Plasma leakage  and hemoconcentration starts
-May develop hypotensive shock and progressive organ dysfunction
Convalescent phase (Start after 6–7 days of fever and lasts for 2–3 days)-ECF lost due to capillary leakage returns to circularity system
– Clinical status improves

History and Examination

Children living or traveling in endemic areas, recent mosquito bites

Symptoms

  • High fever  (40°C/104°F)
  • Headache
  • Retro-orbital pain
  • Myalgia
  • Arthralgia
  • Nausea and vomiting
  • Rash

Signs

  • Petechiae, ecchymoses, or purpura
  • Hepatomegaly
  • Positive tourniquet test

Differential Diagnosis (D/D) & Complications

D/D

  • Malaria (cyclical fever, anemia, splenomegaly)
  • Leptospirosis (jaundice, renal dysfunction, conjunctival suffusion)
  • Scrub typhus (eschar, lymphadenopathy)
  • Typhoid
  • Bacterial sepsis

Complications

  • Dengue hemorrhagic fever (DHF)
  • Dengue shock syndrome (DSS)
  • Multi-organ failure
  • Hypo/Hyperglycemia
  • Electrolyte abnormalities
  • Nosocomial/Co-infection
  • Metabolic Acidosis

Investigation

  • Investigation of choice
    • NS1 antigen detection (Day 1-5 of illness)
    • IgM
      • Appears after day 5
      • Can be detected up to a year so lower sensitivity and specificity
    • IgG
      • Detected after 1-2 weeks and persist for life
  • Complete blood count (CBC) with platelet count and peripheral smear
    • Leukopenia with lyphocytoses
    • Leukocytosis in recovery phase precedes rise in platelets count
    • Platelets declines in critical phase, rise in platelets in clinical recovery
  • Hematocrit
    • Normal in uncomplicated case, high when capillary refill starts
    • Clinical significant only when 20% rise over the baseline
    • Monitoring it helps in titrating fluid therapy
  • Liver and renal function tests
    • Mild elevated; AST>ALT
    • Low albumin in sever disease
  • Coagulation test
    • Raised PT/INR, and aPTT
  • RFT
    • Increased creatinine, proteinuria, and hyponatremia
  • Blood grouping and Cross Matching
  • ABG:
    • Metabolic acidosis and elevated lactate levels seen in shock
  • Chest x-ray

Admission Criteria

  • Severe dengue (DHF or DSS)
    • Platelet count < 100,000 /cu.mm or rapidly decreasing trend
    • Hematocrit is rising trend.
  • Children with warning signs (persistent vomiting, abdominal pain, rapid decrease in platelet count)
  • Poor oral intake, dehydration
  • Living far from a health facility without reliable means of transport

Indications for Pediatric Intensive Care Unit Admission

  • Severe plasma leakage with hypoperfusion and hypotension
  • Fluid accumulation with respiratory distress
  • Severe bleeding
  • Severe organ impairment:
    • Myocardial dysfunction
    • Acute kidney injury
    • CNS dysfunction (altered consciousness and seizures)
    • Hepatic dysfunction (ALT/AST >1,000 IU)
    • HLH

Management

Case classification

Mild (Outpatient management)Moderate (Inpatient management)Severe (ICU management)
-Fever for 2-7 days
-Associated features nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, and leukopenia
Dengue with high-risk comorbid condition
-Infants
-Using immunosuppressive drugs or immunocompromised status
-Any coagulation disorder
-Dengue with warning signs

Medical Management

# Out Patient Management

  • Give Paracetamol for fever (Do not prescribe Flexon as it has Ibuprofen like acetylsalicylic acid (aspirin), and like other non-steroidal anti-inflammatory agents are contraindicated in dengue fever because they can aggravate gastritis or bleeding)
  • Adequate rest and fluid intake (Milk, fruit juice, electrolyte solution (ORS) and barley/rice water)
  • Tepid sponging
  • Antibiotics are not necessary

Tell patient party to observe for the following Danger signs and report immediately for hospital admission:

  • Bleeding (Red spots or patches on the skin; bleeding from nose or gums; vomiting blood; black-coloured 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

# In patient management

  • Obtain baseline CBC, monitor intake and output, monitor vital signs 4 hourly or  frequently
  • Good oral fluid intake
    • Encourage oral fluid intake
    • Observe for warning sign
    • Do symptomatic treatment
  • Poor oral fluid intake
    • Check hematocrit (HCT). Obtain baseline hematocrit before starting fluid.
    • Give IV Isotonic crystalloid solution (NS,RL) in step wise manner
      • Start with 5 ml/kg/hour for 1–2 hours, then reduce by 2ml/kg/hour every 2 hours till 2ml/kg/hr provided there is clinical improvement and haematocrit is appropriately improving. IV fluids are usually required for 1-2 days.
      • 5-7 ml/kg/hr for 1-2 hours
      • 3-5 ml/kg/hr for 2-4 hours
    • Recheck HCT and reassess clinical status
      • Reassess the clinical status and repeat the haematocrit after 2 hours: If the haematocrit remains the same, continue with the same rate for another 2–4 hours and reassess. If the vital signs/haematocrit is worsening increase the fluid rate.
      • Clinically stable with no or minimal change in HCT
        • Continue fluid 2-3 ml/kg/hr for 2-4 hours
        • Decrease the fluid as patient become clinically stable, with adequate fluid intake and output, HCT decrease to baseline
      • Worsening vital signs or increasing HCT
        • Increase IV fluid to 5-10 ml/kg/hour for 1-2 hours
        • Recheck the status and HCT
        • If improving, gradually decrease the fluid
        • If not, follow ICU management

# Severe (ICU management)

Inpatient management of dengue patients with dengue shock

  • Dengue shock syndrome (poor peripheral perfusion, hypotension, BP not recordable)
  • Give oxygen via facemask
  • Immediate rapid volume replacement
    • 10-20 ml/kg NS or RL over 30 minutes
      • 10ml/kg for compensated shock
      • 20ml/kg for hypotension
    • Improvement (Decrease HCT, Stable BP and HR, Urine output: 0.5 to 1 ml/kg/hr)
      • Start IV therapy with NS or RL
        • Titrate the flow from
          • 10-7 ml/kg/hr for 2-4 hours
          • 5-3 ml/kg/hr for 2-4 hours
          • 3-1.5 ml/kg/hr for 2-4 hours
      • If patient improve, discontinue fluid after 24 to 48 hours
        • Total fluid therapy usually 24-48 hrs, titrated to adequate urine output. Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Stop fluid when urine output is adequate, patient is stable, adequate oral intake and or hematocrit decreasing below the baseline value.
        • Cautious fluid resuscitation is very important to avoid overloading.
        • When “capillary leak” progress, children have a tendency to develop “fluid creep” and worsening respiratory status.
        • Fluid resuscitation at the cost of respiratory worsening may not culminate in good outcome.
    • No improvement (Rise in HCT or HR, Pulse pressure falls below 20 mm Hg, urine output falls)
      • Repeat second bolus: 10-20 ml/kg of crystalloid (preferably colloid: Dextran 40) over 30 minutes
        • Improvement or rise in HCT (>45%)
          • Repeat third bolus: 10-20 ml/kg of crystalloid (preferably colloid) over one hours
          • No improvement, HCT falls, or suspected bleeding
            • Blood transfusion
              • 10ml/kg whole blood / 5ml/kg PRBC
            • No improvement
              • Look for myocardial dysfunction (ECG), correct acidosis, hypoglycemia, and electrolyte abnormalities
              • Echocardiograpy
              • IV Inotropes with fluid replacement therapy

Indications for platelet transfusion

  • Shock, acidosis with rapidly declining platelets (greatest risk of DIC)
    • Significant mucosal bleeds (harbinger of intracranial hemorrhage)
    • Platelet count < 20,000 cu mm in the acute phase
    • Need for invasive procedures such as central lines maintain platelet count > 50,000 cu mm
    • A low platelet count is less significant after recovery from shock and may not need to be transfused.

Treatment of Fluid overload

  • Fluid overload with large pleural effusions and ascites is a common cause of acute respiratory distress and failure in severe dengue.
  •  Other causes of respiratory  distress include acute pulmonary oedema, severe metabolic acidosis from severe shock, and Acute Respiratory Distress Syndrome (ARDS).
  • Do the chest x-ray if find sign of fluid overload
  • Rx:
    • Oxygen therapy/ventilation if indicated should be given immediately.
    • Stopping intravenous fluid therapy during the recovery phase will allow fluid in the pleural and peritoneal cavities to return to the intravascular compartment resulting ion dieresis.
    • Give diuretics if necessary: Oral or intravenous furosemide 0.1–0.5 mg/kg/dose once or twice daily, or a continuous infusion of furosemide 0.1 mg/kg/hour.

Criteria for discharge

  • Absence of fever for at least 24 hrs without any use of antipyretic
  • Return of appetite
  • Clinical improvement
  • Good urine output
  • Stable haematocrit
  • Normal organ function workup results
  • No respiratory distress from pleural effusion and ascites
  • No other complication

Advices

  • Educate the family on mosquito prevention measures (insect repellent, protective clothing, mosquito nets)
  • Encourage oral rehydration

Referral

  • All patients with Warning signs and signs of Severe dengue.
  • Patients not clinically responding to therapy in situation.
  • Patients with serious co-morbid conditions
  • Platelet counts < 50,000/cu.mm with a decreasing trend.

Follow up

  • Schedule a follow-up visit within 7-10 days after recovery
  • Monitor for any complications or signs of post-dengue fatigue

Additional Points

Fluid choice in Dengue

  • Normal saline\Ringer’s lactate
    • In severe/refractory shock, colloids such as Plasma , plasma substitutes (6% hetastarch/dextran/ / 5% albumin /) may be preferred
    • Fresh whole blood or packed red blood cells may be needed for persistent shock despite restoration of fluid volume and a fall in haematocrit, suggesting the possibility of occult blood loss.
    • Rapidly administered dextrose containing solution when used for resuscitation may result in hyperglycemia and osmotic diuresis, delaying correction of hypovolaemia. Secondly, dextrose is rapidly metabolized resulting in a hypotonic solution that is inappropriate for shock correction.

 Recognition of Shock

  • Tachycardia , Low pulse volume
  • Capillary Refill time > 2 sec
  • Narrow pulse pressure
  • Blood pressure less than the 3rd centile for age
  • Cold clammy peripheries
  • Altered sensorium
  • Poor urine output [ <0.5ml/kg/hr consistently ]
  • Tachypnoea
  • Metabolic acidosis

Choice of Vasoactive agents/ post resuscitation fluid removal

  • Shock with low BP for age: Dopamine 10mcg/kg/min OR Noradrenaline/adrenaline 0.1-0.2mcg/kg/min
  • Shock with normal BP for age: Dobutamine 5-10mcg/kg/min
  • Shock with diastolic dysfunction on echo: Milrinone 0.25-0.75mcg/kg/min (no
  • loading dose)
  • Predominant pulmonary edema, haemodynamics stable : Nitroglycerine 1-3mcg/kg/min, furosemide infusion 3- 5mg/kg/day, titrate to urine output of 3-5 ml/kg/hr. Cease infusion and infuse fluid if hypoperfusion occurs.
  • Pulmonary edema, fluid overload, haemodynamics unstable: Ventilation vital (high risk of mortality), can consider peritoneal dialysis if 24 hour experienced nursing and medical staff available in PICU

# Important points

  • Serial haematocrit measurement (if not bleeding), and urine output provide the most objective guides to fluid replacement and prevention of fluid overload.
  • Aim for ≈ 20% fall in haematocrit and adjust fluid rate downwards to avoid overload
  • Aim for minimal acceptable urine output (0.5-1ml/kg/hr)
  • A urine output > 3 ml /kg /hour indicates Hypervolaemia
  • Fluid replacements are dynamic hence require continuous reassessments.
  • No dextrose containing fluid should be used for fluid resuscitation, Separate maintenance fluids are usually not required. Glucose/potassium may need to be given separately. Start enteral feeds early.
  • All invasive procedures must be performed by most experienced person. If possible, aim for platelets > 50,000/cu mm prior to central line insertion.
  • Profuse bleeds may necessitate transfusion of platelets and FFP regardless of lab values: conversely, low platelet counts in the recovering, stable patient may not be an indication for transfusions

References

1. World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention, and Control. Geneva: World Health Organization; 2009.

2. Guzman MG, Harris E. Dengue. Lancet. 2015;385(9966):453-465.

3. Simmons CP, Farrar JJ, Nguyen V, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-1432.