Dengue

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    Last update: October 2022

     

     

    Dengue fever is an arbovirus transmitted to humans by the bite of a mosquito (Aedes). Transmission by transfusion of contaminated blood and transplacental transmission to the foetus have also been reported.

    Four different serotypes of dengue have been described. Infection with one serotype provides a lifelong immunity to that specific serotype, but only partial, short-term immunity to other serotypes. There is no specific antiviral treatment.

     

    Dengue is a mainly urban disease, present in tropical and subtropical regions a Citation a. For more information:
    http://gamapserver.who.int/mapLibrary/Files/Maps/Global_DengueTransmission_ITHRiskMap.png?ua=1
    , in particular in Asia, Central and South America and the Caribbean. Outbreaks have been described in Eastern Africa.

     

    Primary infection may be asymptomatic or present as mild or occasionally severe dengue fever. Subsequent infections increase the risk of severe dengue.

    Clinical features

    After the incubation period (4 to 10 days), the illness occurs in 3 phases:

    • Febrile phase: high fever (39 to 40 °C) lasting 2 to 7 days, often accompanied by generalized aches, a maculopapular rash and mild haemorrhagic manifestations. 
    • Critical phase (between the third and seventh day): at the end of the febrile phase, temperature decreases. The majority of patients will have dengue without warning signs and proceed to the recovery phase. Certain patients will develop dengue with warning sign(s) at this stage. These patients are at higher risk for developing severe dengue.
    • Recovery phase: patient improves, vital signs normalise, gastrointestinal symptoms subside and appetite returns. At times, bradycardia and generalized pruritus.

     

    Symptoms according to severity (adapted from PAHO [1] Citation 1. Pan American Health Organization. Dengue: guidelines for patient care in the Region of the Americas, 2nd edition. Washington, D.C.: PAHO, 2016.
    https://iris.paho.org/bitstream/handle/10665.2/31207/9789275118900-eng.pdf?sequence=1&isAllowed=y [Accessed 23 Aug 2022]
    )

    Dengue
    without warning signs

    Fever + 2 of the following symptoms:

    • Nausea, vomiting
    • Rash resembling measles
    • Generalized aches (headache, retro-orbital pain, myalgias, arthralgias)
    • Benign mucocutaneous bleeding (petechiae, positive tourniquet test (a) Citation a. Tourniquet test: inflate a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressure for 5 min. The test is positive when 20 or more petechiae per 2.5 cm square are observed. , epistaxis, gingival bleeding)
    • Leucopenia

    Dengue
    with warning signs

    Presence of at least one of these symptoms:

    • Intense abdominal pain
    • Persistent vomiting
    • Fluid accumulation (ascites, pleural effusion)
    • Mucosal bleeding
    • Hepatomegaly (> 2 cm)
    • Postural hypotension
    • Agitation or lethargy
    • Increasing haematocrit

    Severe dengue

    • Severe fluid accumulation (ascites, pleural effusion) with respiratory distress and/or shock
    • Severe mucocutaneous bleeding
    • Severe organ involvement (e.g.: transaminases > 1000 IU/litre, myocarditis, altered mental status)

    Major differential diagnoses

    Other conditions to consider include a wide range of acute febrile illnesses, e.g.:  

    Laboratory

    Diagnosis

    • NS-1 antigen detection during febrile phase with rapid diagnostic test or ELISA (serum, plasma or blood). 

    • Antibody detection (complex interpretation): 

    • IgM detection 5 to 6 days after onset of illness may support (but does not confirm) a diagnosis of recent infection;

    • IgG detection may indicate prior infection by, or vaccination against, dengue virus or a closely related virus (e.g. chikungunya, Zika, Japanese encephalitis, yellow fever).

    • PCR may also be available in reference laboratories. 

    • In all cases, rapid test for malaria in endemic regions (and antimalarial treatment if needed, see Malaria, Chapter 6).

    Monitoring disease course

    • Haematocrit (Hct) or if available full blood count (FBC) at baseline, then daily if possible.
      • A progressive increase in Hct is a warning sign. It indicates haemoconcentration due to increased vascular permeability (plasma leakage). Hct should be monitored frequently (before and after fluid administration) in patients with warning signs up to the end of the fluid treatment. 
      • Leukopenia and thrombocytopenia are common and improve as the recovery phase begins. Leukocytosis may occur with severe bleeding.
    • Liver function tests if possible at baseline, then according to results.

    Treatment

    Patients in Group A (outpatients)

    Patients with no warning signs, able to drink sufficiently and with a normal urine output.

    • Bed rest and good hydration.
    • Fever and pain: paracetamol PO at the usual doses (see Fever, Chapter 1), maintaining a 6 to 8 hour interval between doses. Do not prescribe acetylsalicylic acid, ibuprofen or other NSAIDs.
    • Seek medical attention if: no clinical improvement, persistent vomiting, cold extremities, agitation or lethargy, breathing difficulties or absence of urine output.
    • If follow-up is impossible or symptoms cannot be monitored at home (patients living far from the health care facility/living alone), hospitalise for observation.

    Patients in Group B (inpatients)

    Patients with any of the following:

    • Warning sign(s) 

    • Acute (e.g. severe dehydation or malaria) or chronic (e.g. diabetes, cardiovascular, renal or haemolytic disease, obesity) co-morbidities

    • Risk factors for bleeding (e.g. anticoagulation, coagulopathy, peptic ulcer or gastritis, treatment with NSAIDs) 

    • Pregnant women, patients under 1 year or 65 years and over or patients with difficulty drinking

     

    In all cases:

    • Place the patient under a mosquito net; encourage oral fluid intake (including oral rehydration solution (ORS) if needed).
    • Avoid invasive procedures (nasogastric tube, IM injections) to minimize the risk of bleeding.
    • Fever and pain: paracetamol PO [2] Citation 2. Pan American Health Organization. Guidelines for the Clinical Diagnosis and Treatment of Dengue, Chikungunya, and Zika. Washington, D.C. : PAHO; 2022.  
      https://iris.paho.org/handle/10665.2/55867 [Accessed 16 Aug 2022]
       with caution and without exceeding:
      • children: 10 mg/kg every 6 to 8 hours
      • adults: 500 mg every 6 to 8 hours
    • In case of elevated transaminases ≥ 10 times the upper limit of normal, do not administer paracetamol. Use tepid sponging for reducing fever.
    • Monitor vital signs, fluid intake (infusion and oral) and urine output every 4 hours b Citation b. Adequate urine output: at least 1 ml/kg/hour in children and 0.5 ml/kg/hour in adults. If unavailable, ensure that the patient is urinating at least every 4 hours. .

     

    If poor oral intake:

    • Place an intravenous line and administer:
      • children: 5% glucose + Ringer lactate solution c Citation c. Remove 50 ml of Ringer lactate (RL) from a 500 ml RL bottle or bag, then add 50 ml of 50% glucose to the remaining 450 ml of RL to obtain 500 ml of 5% glucose-RL solution.
         
        as maintenance fluids, according to the Holliday-Segar formula, i.e. 4 ml/kg/hour for first 10 kg of body weight + 2 ml/kg/hour for next 10 kg + 1 ml/kg/hour for each additional kg above 20 kg.
      • adults: Ringer lactate, 2 to 3 ml/kg/hour
    • Encourage oral intake as soon as possible.

     

    If warning signs:

    • Monitor clinical status (warning signs, general symptoms, vital signs, capillary refill time), IV and oral fluid intake, urine output, hourly for at least 4 hours, then every 4 hours while the patient is on IV fluid treatment.
    • Place an intravenous line and administer a bolus of Ringer lactate:
    • children and adults: 10 ml/kg over one hour
    • patients 65 years and over or with co-morbidities : 5 ml/kg over one hour
    •  Re-assess the patient:
      • If no improvement after first bolus: administer a second bolus as above. If necessary, a total of 3 boluses can be administered. If still no improvement after 3 bolus, consider as severe dengue (patients in Group C) and transfer to intensive care unit.
      • If improvement after the first, second, or third bolus, reduce Ringer lactate:
        • children and adults: 5 to 7 ml/kg/hour over 2 to 4 hours
        • patients 65 years and over or with co-morbidities: 5 ml/kg/hour over 2 to 4 hours
      • If continuing improvement, reduce Ringer lactate (then stop as soon as possible to reduce the risk of fluid overload):
        • children and adults: 3 to 5 ml/kg/hour over 2 to 4 hours, then 2 to 4 ml/kg/hour over 24 to 48 hours
        • patients 65 years and over or with co-morbidities: 3 ml/kg/hour over 2 to 4 hours, then 2 ml/kg/hour over 24 to 48 hours
      • If the patient deteriorates after initial improvement, resume the bolus therapy with Ringer lactate (up to 3 bolus) as above.

    Patients in Group C (intensive care unit)

    Patients with severe dengue requiring emergency treatment for managing shock and other complications (e.g. severe bleeding, acidosis, coagulopathy).

    Prevention

    • Individual protection: long sleeves and trousers, repellents, mosquito net (Aedes bites during the day).
    • Elimination of mosquito breeding sites (small collections of water in discarded tires, flower pots, and other containers).

     

    Footnotes
    • (a)Tourniquet test: inflate a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressure for 5 min. The test is positive when 20 or more petechiae per 2.5 cm square are observed.
    References