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DENGUE FEVER

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species. These mosquitoes can also spread the Zika and Chikungunya viruses (see ZIKA VIRUS - MEDICAL MANAGEMENT and ALPHAVIRUS INFECTIONS managements for further information).

Specific Substances

    1) Breakbone Fever
    2) Dandy Fever
    3) Dengue Hemorrhagic Fever
    4) Dengue Infection
    5) Dengue Shock Syndrome
    6) Dengue Virus
    7) Duengero
    8) Seven Day Fever, Dengue Type

Available Forms Sources

    A) SOURCES
    1) BACKGROUND
    a) Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species (World Health Organization (WHO), 2015; Kularatne, 2015). Dengue viruses (arthropod-borne virus; arboviruses) are single-stranded RNA viruses of the flavivirus genus that belongs to the flaviviridae family. Other viruses associated with this family include: Yellow Fever virus, Japanese Encephalitis virus, West Nile virus and Saint-Louis encephalitis. There are 4 dengue virus (DENV) serotypes (DENV-1, -2, -3, -4). All serotypes can cause severe disease. Infection with any of the 4 serotypes can produce the full spectrum of illness, from fever with nonspecific symptoms to classic dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Severe forms usually develop after 2 to 7 days of high fever(Centers for Disease Control and Prevention (CDC), 2014; World Health Organization (WHO), 2015; Kularatne, 2015; Tomashek et al, 2015). Infection with 1 serotype does not protect against the other serotypes. Sequential infections are associated with greater risk for more severe disease (Centers for Disease Control and Prevention (CDC), 2014; World Health Organization (WHO), 2015).
    2) PATHOGENESIS
    a) Pathogenesis involves antigen-presenting dendritic cells, the humoral immune response, and the cell-mediated immune response. Plasma leakage is caused by proliferation of memory T cells and production of pro-inflammatory cytokines (Kularatne, 2015).
    3) SIMILAR VIRAL ILLNESSES
    a) Dengue, Zika and Chikungunya can present with similar symptoms. In most instances, dengue fever will begin with a sudden onset of a high fever and severe headache. Other symptoms can include skin rash and muscle and joint pain, nausea, vomiting and loss of appetite. The dengue illness can last up to 10 days. Individuals with the Zika or chikungunya virus usually have similar symptoms but the illnesses tend to be milder (Auckland Regional Public Health Service, 2016).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) BACKGROUND: Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species Dengue viruses (arthropod-borne virus; arboviruses) are single-stranded RNA viruses of the flavivirus genus that belongs to the flaviviridae family. Other viruses associated with this family include: Yellow Fever virus, Japanese Encephalitis virus, West Nile virus and Saint-Louis encephalitis. There are 4 dengue virus (DENV) serotypes (DENV-1, -2, -3, -4). All serotypes can cause severe disease. Infection with any of the 4 serotypes can produce the full spectrum of illness, from fever with nonspecific symptoms to classic dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Severe forms usually develop after 2 to 7 days of high fever. Infection with 1 serotype does not protect against the other serotypes. Sequential infections are associated with greater risk for more severe disease.
    B) PATHOGENESIS: Pathogenesis involves antigen-presenting dendritic cells, the humoral immune response, and the cell-mediated immune response. Plasma leakage is caused by proliferation of memory T cells and production of pro-inflammatory cytokines.
    C) TRANSMISSION: Transmission to humans is mainly through the bite of an infected Aedes mosquito or Aedes albopictus. These mosquitoes are daytime feeders, with peak biting periods occurring early in the morning and in the evening before dusk. They tolerate temperatures below freezing and survive in cooler temperate regions. For transmission to occur, the mosquito must feed on an infected person during the 5-day period of maximal viremia, which usually begins a short time before the patient becomes symptomatic. The mosquito is infected until it dies, typically days to a few weeks. Less commonly, transmission of dengue virus may occur in the absence of a bite from an infected mosquito. It may occur through infected blood or transplanted organs or tissues, occupational exposure in healthcare settings (eg, needle stick injuries), and from an infected mother to a fetus in utero or to an infant during delivery.
    D) VECTOR: Transmission occurs by the mosquitoes Aedes aegypti and Aedes albopictus.
    E) INCUBATION PERIOD: An infected mosquito can transmit the virus after an incubation period of 3 to 14 days. Once initial symptoms appear in an infected patient, dengue virus can be transmitted for 4 to 5 days (maximum, 12 days).
    F) EPIDEMIOLOGY: About 40% of the world's population live in an area at risk for dengue transmission. About 50 to 100 million dengue infections occur globally every year The average annual number of cases of dengue infection reported to WHO increases exponentially every 10 years. Epidemics are becoming more common.
    G) OUTBREAKS: Dengue fever outbreak occurs in areas where Aedes aegypti and Aedes albopictus mosquitoes are found, including tropical and subtropical urban areas worldwide. Travelers to these areas may also introduce dengue fever to their own countries. Dengue infections are endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Southeast Asia and the Western Pacific are the most seriously affected. Dengue is common in urban areas but is spreading to rural areas. Imported cases are common.
    H) WITH POISONING/EXPOSURE
    1) CLINICAL EVENTS: Up to 50% of persons infected with dengue are asymptomatic. Symptomatic patients may present with undifferentiated fever, dengue fever (DF) with or without hemorrhage, or dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Severe, life-threatening disease occurs in as many as 5% of all dengue patients.
    2) UNDIFFERENTIATED FEVER: Patients with undifferentiated fever have mild nonspecific symptoms and may not receive a definitive diagnosis. Patients are usually young children or patients with a first infection who fully recover as outpatients.
    3) DENGUE FEVER WITH OR WITHOUT HEMORRHAGE: Patients are usually older children or adults. A patient with DF with or without hemorrhage usually presents with 2 to 7 days of high fever and 2 or more of these symptoms: severe headache, retro-orbital eye pain, myalgias, arthralgias, diffuse erythematous maculopapular rash, and mild hemorrhagic manifestation. Patient may also develop petechiae (on lower extremities, buccal mucosa, hard and soft palates, and or subconjunctivae), epistaxis, gingival bleeding, gastrointestinal bleeding, urogenital bleeding (rare), leukopenia, and thrombocytopenia. Nausea and vomiting may be present in children.
    4) DENGUE HEMORRHAGIC FEVER (DHF) OR DENGUE SHOCK SYNDROME (DSS): The more severe forms of dengue fever are dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The presentation of the early phase of DHF is similar to the presentation of DF, and differentiation may be difficult. There are 3 phases of DHF (see below).
    5) Febrile phase (viremia-driven high fevers):
    a) High fever that lasts 2 to 7 days.
    b) Symptoms consistent with dengue fever.
    c) Complications may include dehydration, seizures secondary to high fever, and rarely, severe hemorrhage.
    6) Critical/plasma leak phase (sudden onset of varying degrees of plasma leak into the pleural and abdominal cavities):
    a) Duration of 24 to 48 hours.
    b) Normal or below-normal temperature.
    c) Varying degrees of plasma leak into pleural and peritoneal spaces.
    d) Varying degrees of hemorrhage.
    e) Complications may include hemorrhage or severe plasma leakage resulting in shock, intracranial bleed, metabolic abnormalities, coagulopathy, fulminant hepatic failure, prolonged shock resulting in death.
    7) Convalescent or reabsorption phase (sudden arrest of plasma leak with concomitant reabsorption of extravasated plasma and fluids):
    a) Duration of 2 to 4 days. Plasma leakage and hemorrhage resolves.
    b) Vital signs stabilize.
    c) Fluids, including leaked plasma and administered IV fluids, reabsorb.
    d) Improvement in overall medical condition.
    e) Complications may include intravascular fluid overload related to aggressive volume resuscitation during convalescence phase.
    8) NOTE: In a patient with DF, the development of abdominal pain or tenderness, persistent vomiting, pleural effusion, ascites, mucosal bleeding, lethargy, restlessness, or liver enlargement of 2 or more centimeters, increase in hematocrit concurrent with a rapid decrease in platelet count that occurs at or after defervescence indicates the critical (plasma leak) phase of DHF and the need for immediate medical attention. A sense of well being reported by the patient, return of appetite, stabilizing vital signs, hematocrit levels returning to normal, increased urine output, and appearance of the characteristic convalescence rash of dengue suggests the patient is entering the convalescent (reabsorption) phase of DHF.

Laboratory Monitoring

    A) Monitor vital signs and liver enzymes (for up to 4 weeks after discharge) in all symptomatic patients.
    B) Monitor CBC with differential. Leukopenia, thrombocytopenia and hemorrhage have been reported in patients with dengue, as compared to patients with Zika infection. Periodically monitor hematocrit (HCT) (every 6 to 12 hours) for hospitalized dengue patients with warning signs and for diagnosed patients with compensated or hypotensive shock. For patients with a presumptive diagnosis, an sudden rise in HCT with a concurrent rapid decrease in platelet count is a warning sign for severe dengue. HCT is used to evaluate hospitalized patients for the need and the adjustment of IV isotonic crystalloid or colloid solution administration and for the possible need for packed red blood cells or whole blood.
    C) Consider tourniquet test (not recommended if platelet count is less than 80,000 cells/mm(3) [less than 80 x 10(9)/L] or spontaneous petechiae).
    D) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    E) DIAGNOSTIC EVALUATION: Diagnosis of dengue virus is by molecular and serologic testing. Reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA in serum within 7 days after onset of symptoms is the preferred test to diagnose dengue virus infection. In addition, the non-structural protein 1 (NS1) of the dengue viral genome is useful as a tool for the diagnosis of acute dengue infection and may be able to differentiate between flaviviruses, but the assay is not widely available in the United States. Serum collected 4 or more days after symptom onset in patients with compatible clinical syndrome can be tested with dengue virus-specific IgM ELISA and a positive result must be confirmed by testing for neutralizing antibodies, using Plaque-reduction neutralization tests (PRNT). IgG testing can be used to distinguish a primary from a secondary dengue infection.
    F) WHO SHOULD BE TESTED: Any patient who presents with an acute febrile illness and have travelled recently (within the past 2 weeks), where there is ongoing dengue infection, or a patient that lives in an at-risk region, should be tested. Testing should include Zika, chikungunya and dengue virus infections.

Treatment Overview

    0.4.7) BITES/STINGS
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. There is no specific antiviral therapy for dengue virus infection. Manage mild hypotension with IV fluids. Monitor serum electrolytes if the patient develops significant vomiting and/or diarrhea. There is also no vaccine or chemoprophylaxis available to prevent dengue. Monitor vital signs, hemodynamic status, fluid balance, and hematologic parameters. Treat symptoms with fluids, rest, analgesics (eg, acetaminophen) and antipyretics. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided due to the potential risk for hemorrhage. If temperature is high, use tepid water to sponge the patient's skin.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine, norepinephrine or pressor of choice if unresponsive to fluids. IV fluids are not always necessary if patients can tolerate oral fluids. If using IV fluids, use the minimum amount to keep the patient well-perfused and decrease the infusion rate as hemodynamic status improves or urine output increases. Monitor HCT in all hospitalized patients with dengue with warning signs and those with compensated or hypotensive shock. HCT levels and clinical status of patients hospitalized with dengue dictate the need for isotonic crystalloids, colloids, and blood products (ie, packed red blood cells or whole blood for significant bleeding). Corticosteroids and platelet transfusions are not recommended. Corticosteroids can increase the risk of gastrointestinal bleeding, hyperglycemia, and immunosuppression. Platelet transfusions do not lower the risk of severe bleeding and can lead to fluid overload.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital GI decontamination including activated charcoal is not indicated. The focus of prehospital care should include supportive care.
    2) HOSPITAL: GI decontamination is not indicated.
    D) ANTIDOTE
    1) No antidote or vaccine is available for human exposure to dengue virus.
    E) AIRWAY MANAGEMENT
    1) Dengue virus typically results in cases of mild, self-limiting illness; airway support is unlikely to be necessary. If airway compromise occurs, supportive measures including endotracheal intubation and mechanical ventilation may be necessary in patients that develop hemodynamic instability (ie, hypotension, shock) and/or severe bleeding.
    F) PREVENTION
    1) SUMMARY: The most important thing to prevent the dengue infection and other related illnesses (ie, Zika and chikungunya) is to avoid mosquito bites. In areas where outbreaks have occurred, individuals should avoid mosquito bites by wearing long sleeve shirts and pants, staying indoors when possible, use of bed nets in areas where air conditioning is not available, use of insect repellents containing DEET, picardin, and IR3535 (follow label directions), and protect infants and children similar to adults, except insect repellent should NOT be used on infants younger than 2 months of age.
    2) PROTECTING OTHERS FROM INFECTION: Patients who have a fever should be under a bed net or use insect repellant to prevent mosquito bites. If a patient with dengue is bitten by a mosquito, that mosquito can pass on dengue to other residents of the house within 2 weeks.
    G) ENHANCED ELIMINATION
    1) Enhanced elimination is not necessary in patients that develop dengue fever.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with dengue and no warning signs may be managed as outpatients with careful monitoring.
    2) OBSERVATION CRITERIA: Patients with worsening symptoms that do not improve with over-the-counter medications (eg, analgesics, antipyretics) and basic home treatments should go to a healthcare facility for evaluation and treatment. In addition, advise a patient to immediately go to a clinic or emergency department if any of the following warning signs occur: severe abdominal pain or persistent vomiting, red spots or patches on the skin, bleeding from the nose or gums, vomiting blood, black, tarry stools, drowsiness or irritability, pale, cold, or clammy skin, and difficulty breathing.
    3) ADMISSION CRITERIA: Patients with dengue and warning signs should be hospitalized for monitoring and possible administration of IV fluids. In addition, the following patients with dengue should be hospitalized: pregnant women, infants, older patients, and patients with diabetes mellitus, poor social situation, or renal failure. Patients with dengue and compensated shock should be admitted to the hospital or an ICU for emergency treatment. Other patients that should be admitted and receive close monitoring and management include those with severe plasma leakage with shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment. Patients with dengue and hypotensive shock should be admitted to the ICU for emergency treatment. Hospitalized patients may be discharged after wellbeing is achieved, temperature is normal for 48 hours, HCT is stable, and platelet count is increasing.
    4) CONSULT CRITERIA: Infectious disease physicians and/or intensivists may be consulted for medical advice. Poison centers can aid treatment by serving as a public health resource by providing advice to the general public, and working with local and regional health departments.
    I) DIFFERENTIAL DIAGNOSIS
    1) In endemic areas, the dengue virus may appear similar to Zika or chikungunya illness. Because of its similar clinical features with other infections, the following should be considered: leptospirosis, malaria, rickettsia, group A streptococcus, rubella, measles, and parvovirus, enterovirus, adenovirus, and other alphavirus infections (eg, Mayaro, Ross River, Barmah Forest, O'nyong-nyong and Sindbis viruses).

Range Of Toxicity

    A) TOXICITY: Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species One mosquito is enough to cause an infection. Severe, life-threatening disease can develop in up to 5% of patients with dengue. About 500,000 people with dengue hemorrhagic fever are hospitalized every year; about 2.5% of those affected die. Early recognition of signs of shock and initiation of intensive supportive therapy can reduce the risk of death with severe dengue from 10% to less than 1%. The risk of death is 4-fold higher in children 1 to 5 years old compared with children 11 to 15 years old.

Clinical Effects

Summary Of Exposure

    A) BACKGROUND: Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species Dengue viruses (arthropod-borne virus; arboviruses) are single-stranded RNA viruses of the flavivirus genus that belongs to the flaviviridae family. Other viruses associated with this family include: Yellow Fever virus, Japanese Encephalitis virus, West Nile virus and Saint-Louis encephalitis. There are 4 dengue virus (DENV) serotypes (DENV-1, -2, -3, -4). All serotypes can cause severe disease. Infection with any of the 4 serotypes can produce the full spectrum of illness, from fever with nonspecific symptoms to classic dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Severe forms usually develop after 2 to 7 days of high fever. Infection with 1 serotype does not protect against the other serotypes. Sequential infections are associated with greater risk for more severe disease.
    B) PATHOGENESIS: Pathogenesis involves antigen-presenting dendritic cells, the humoral immune response, and the cell-mediated immune response. Plasma leakage is caused by proliferation of memory T cells and production of pro-inflammatory cytokines.
    C) TRANSMISSION: Transmission to humans is mainly through the bite of an infected Aedes mosquito or Aedes albopictus. These mosquitoes are daytime feeders, with peak biting periods occurring early in the morning and in the evening before dusk. They tolerate temperatures below freezing and survive in cooler temperate regions. For transmission to occur, the mosquito must feed on an infected person during the 5-day period of maximal viremia, which usually begins a short time before the patient becomes symptomatic. The mosquito is infected until it dies, typically days to a few weeks. Less commonly, transmission of dengue virus may occur in the absence of a bite from an infected mosquito. It may occur through infected blood or transplanted organs or tissues, occupational exposure in healthcare settings (eg, needle stick injuries), and from an infected mother to a fetus in utero or to an infant during delivery.
    D) VECTOR: Transmission occurs by the mosquitoes Aedes aegypti and Aedes albopictus.
    E) INCUBATION PERIOD: An infected mosquito can transmit the virus after an incubation period of 3 to 14 days. Once initial symptoms appear in an infected patient, dengue virus can be transmitted for 4 to 5 days (maximum, 12 days).
    F) EPIDEMIOLOGY: About 40% of the world's population live in an area at risk for dengue transmission. About 50 to 100 million dengue infections occur globally every year The average annual number of cases of dengue infection reported to WHO increases exponentially every 10 years. Epidemics are becoming more common.
    G) OUTBREAKS: Dengue fever outbreak occurs in areas where Aedes aegypti and Aedes albopictus mosquitoes are found, including tropical and subtropical urban areas worldwide. Travelers to these areas may also introduce dengue fever to their own countries. Dengue infections are endemic in more than 100 countries in Africa, the Americas, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Southeast Asia and the Western Pacific are the most seriously affected. Dengue is common in urban areas but is spreading to rural areas. Imported cases are common.
    H) WITH POISONING/EXPOSURE
    1) CLINICAL EVENTS: Up to 50% of persons infected with dengue are asymptomatic. Symptomatic patients may present with undifferentiated fever, dengue fever (DF) with or without hemorrhage, or dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Severe, life-threatening disease occurs in as many as 5% of all dengue patients.
    2) UNDIFFERENTIATED FEVER: Patients with undifferentiated fever have mild nonspecific symptoms and may not receive a definitive diagnosis. Patients are usually young children or patients with a first infection who fully recover as outpatients.
    3) DENGUE FEVER WITH OR WITHOUT HEMORRHAGE: Patients are usually older children or adults. A patient with DF with or without hemorrhage usually presents with 2 to 7 days of high fever and 2 or more of these symptoms: severe headache, retro-orbital eye pain, myalgias, arthralgias, diffuse erythematous maculopapular rash, and mild hemorrhagic manifestation. Patient may also develop petechiae (on lower extremities, buccal mucosa, hard and soft palates, and or subconjunctivae), epistaxis, gingival bleeding, gastrointestinal bleeding, urogenital bleeding (rare), leukopenia, and thrombocytopenia. Nausea and vomiting may be present in children.
    4) DENGUE HEMORRHAGIC FEVER (DHF) OR DENGUE SHOCK SYNDROME (DSS): The more severe forms of dengue fever are dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The presentation of the early phase of DHF is similar to the presentation of DF, and differentiation may be difficult. There are 3 phases of DHF (see below).
    5) Febrile phase (viremia-driven high fevers):
    a) High fever that lasts 2 to 7 days.
    b) Symptoms consistent with dengue fever.
    c) Complications may include dehydration, seizures secondary to high fever, and rarely, severe hemorrhage.
    6) Critical/plasma leak phase (sudden onset of varying degrees of plasma leak into the pleural and abdominal cavities):
    a) Duration of 24 to 48 hours.
    b) Normal or below-normal temperature.
    c) Varying degrees of plasma leak into pleural and peritoneal spaces.
    d) Varying degrees of hemorrhage.
    e) Complications may include hemorrhage or severe plasma leakage resulting in shock, intracranial bleed, metabolic abnormalities, coagulopathy, fulminant hepatic failure, prolonged shock resulting in death.
    7) Convalescent or reabsorption phase (sudden arrest of plasma leak with concomitant reabsorption of extravasated plasma and fluids):
    a) Duration of 2 to 4 days. Plasma leakage and hemorrhage resolves.
    b) Vital signs stabilize.
    c) Fluids, including leaked plasma and administered IV fluids, reabsorb.
    d) Improvement in overall medical condition.
    e) Complications may include intravascular fluid overload related to aggressive volume resuscitation during convalescence phase.
    8) NOTE: In a patient with DF, the development of abdominal pain or tenderness, persistent vomiting, pleural effusion, ascites, mucosal bleeding, lethargy, restlessness, or liver enlargement of 2 or more centimeters, increase in hematocrit concurrent with a rapid decrease in platelet count that occurs at or after defervescence indicates the critical (plasma leak) phase of DHF and the need for immediate medical attention. A sense of well being reported by the patient, return of appetite, stabilizing vital signs, hematocrit levels returning to normal, increased urine output, and appearance of the characteristic convalescence rash of dengue suggests the patient is entering the convalescent (reabsorption) phase of DHF.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) Patients may have fever with mild nonspecific symptoms and not receive a definitive diagnosis (Centers for Disease Control and Prevention (CDC), 2014).
    2) A patient with dengue fever with or without hemorrhage usually presents with 2 to 7 days of high fever (Centers for Disease Control and Prevention (CDC), 2014).
    3) A sudden change from a high temperature (higher than 38 degrees C) to normal or below normal temperatures suggests that a patient has entered the critical phase (Centers for Disease Control and Prevention (CDC), 2014).
    4) In a study of 100 adult patients with dengue infection, all patients presented with fever (Babaliche & Doshi, 2015).

Heent

    3.4.3) EYES
    A) WITH POISONING/EXPOSURE
    1) EYE PAIN: Retro-orbital eye pain may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    2) In a study of 100 adult patients with dengue infection, 62 patients presented with retro-orbital eye pain (Babaliche & Doshi, 2015).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH POISONING/EXPOSURE
    a) Hypotension, dysrhythmias, myocarditis (some asymptomatic), myocardial depression with symptoms of heart failure and shock, and pericarditis have been reported in patients with severe dengue infection. However, it is difficult to define cardiac involvement in dengue because of the involvement of multiple organs and presence of metabolic derangement in these patients. Although the exact pathophysiology has not been identified, myocardial dysfunction may result from any of the following: direct viral invasion, immune mechanisms, electrolyte imbalance, derangement of intracellular calcium ion storage, lactic acidosis, and ischemia due to hypotension (Shivanthan et al, 2015).
    b) In a study of 100 adult patients with dengue infection, 31% of patients presented with sinus bradycardia (Babaliche & Doshi, 2015).
    c) Early changes in hemodynamic parameters consistent with compensated shock include tachycardia, especially in absence of fever, weak, thready pulse, cool extremities, narrowing pulse pressure (systolic minus diastolic blood pressure of less than 20 mmHg), delayed capillary refill (more than 2 seconds), and oliguria (Centers for Disease Control and Prevention (CDC), 2014).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PLEURAL EFFUSION
    1) WITH POISONING/EXPOSURE
    a) Pleural effusion may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In patients with dengue, evidence of plasma leak include sudden rise in hematocrit of 20% or more from baseline, ascites, new pleural effusion on lateral decubitus chest x-ray, and lower serum albumin or protein for age and gender (Centers for Disease Control and Prevention (CDC), 2014).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In a study of 100 adult patients with dengue infection, 82 patients presented with headache (Babaliche & Doshi, 2015).
    B) RESTLESSNESS
    1) WITH POISONING/EXPOSURE
    a) Restlessness may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    C) LETHARGY
    1) WITH POISONING/EXPOSURE
    a) Lethargy may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    D) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) Dizziness may occur with dengue fever (Kularatne, 2015).
    E) ASTHENIA
    1) WITH POISONING/EXPOSURE
    a) Weakness may occur with dengue fever (Kularatne, 2015).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTROINTESTINAL TRACT FINDING
    1) WITH POISONING/EXPOSURE
    a) Anorexia, nausea, vomiting, and abdominal pain or tenderness may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014; Kularatne, 2015). In a patient with dengue fever, the development of one of these signs at or after defervescence indicates the need for immediate medical attention: abdominal pain or tenderness, persistent vomiting, pleural effusion, ascites, mucosal bleeding, lethargy, restlessness, liver enlargement of 2 or more centimeters, or increase in hematocrit concurrent with rapid decrease in platelet count (Centers for Disease Control and Prevention (CDC), 2014).
    b) Children with dengue fever may also present with nausea and vomiting (Centers for Disease Control and Prevention (CDC), 2014).
    c) In a study of 100 adult patients with dengue infection, 49 patients presented with abdominal pain. Vomiting and diarrhea occurred in 20 and 2 patients, respectively (Babaliche & Doshi, 2015).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) INCREASED LIVER ENZYMES
    1) WITH POISONING/EXPOSURE
    a) Elevated liver enzymes have been reported with dengue infection (Tantawichien, 2015). It usually takes up to 4 weeks for liver enzymes to normalize (Kularatne, 2015).
    b) In a study of 100 adult patients with dengue infection, 76% and 51% of patients presented with elevated SGOT and SGPT, respectively. Mean values were 122.04 +/- 172.27 and 91.81 +/- 123.6 International Units/L, respectively (Babaliche & Doshi, 2015).
    B) FULMINANT HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) Fulminant hepatitis has rarely been reported with dengue infection (Tantawichien, 2015).
    C) LARGE LIVER
    1) WITH POISONING/EXPOSURE
    a) Liver enlargement of 2 or more centimeters may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    D) ASCITES
    1) WITH POISONING/EXPOSURE
    a) Ascites may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In patients with dengue, evidence of plasma leak include a sudden rise in hematocrit of 20% or more from baseline, ascites, new pleural effusion on lateral decubitus chest x-ray, and lower serum albumin or protein for age and gender (Centers for Disease Control and Prevention (CDC), 2014).
    E) SERUM BILIRUBIN RAISED
    1) WITH POISONING/EXPOSURE
    a) In a study of 100 adult patients with dengue infection, 25% of patients presented with elevated total bilirubin (Babaliche & Doshi, 2015).
    F) THROMBOCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) Temporary thrombocytosis may occur during recovery from dengue fever (Kularatne, 2015).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) BLEEDING
    1) WITH POISONING/EXPOSURE
    a) In dengue fever, epistaxis, gingival bleeding, gastrointestinal bleeding, or urogenital bleeding occur rarely (Centers for Disease Control and Prevention (CDC), 2014; Kularatne, 2015). Petechiae, purpura, and menorrhagia have also been reported (Tantawichien, 2015; Kularatne, 2015).
    b) In a patient with dengue fever, the development of one of these signs at or after defervescence indicates the need for immediate medical attention: abdominal pain or tenderness, persistent vomiting, pleural effusion, ascites, mucosal bleeding, lethargy, restlessness, liver enlargement of 2 or more centimeters, increase in hematocrit concurrent with rapid decrease in platelet count (Centers for Disease Control and Prevention (CDC), 2014).
    c) In a study of 100 adult patients with dengue infection, 22 patients presented with bleeding, including 8% with melena (Babaliche & Doshi, 2015).
    B) HEMATOCRIT - FINDING
    1) WITH POISONING/EXPOSURE
    a) For patients with a presumptive dengue diagnosis, an increase in Hematocrit with a concurrent rapid decrease in platelet count is a warning sign for severe dengue (Centers for Disease Control and Prevention (CDC), 2016).
    1) A sudden rise in hematocrit of 20% or more from baseline is evidence of plasma leak and in combination with thrombocytopenia of 100,000 cells/mm(3) or less, sudden change from high to normal or subnormal temperatures, new hypoalbuminemia or hypocholesterolemia, new pleural effusion or ascites, and signs and symptoms of impending or frank shock suggests that a patient has already entered the critical phase (Centers for Disease Control and Prevention (CDC), 2014).
    C) LEUKOPENIA
    1) WITH POISONING/EXPOSURE
    a) Leukopenia is frequently observed in patients with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In a study of 100 adult patients with dengue infection, 16% of patients presented with leukopenia (Babaliche & Doshi, 2015).
    c) New-onset of leukopenia (WBC less than 5000 cells/mm(3)) with a lymphocytosis and increase in atypical lymphocytes signal dissipation of the fever within the next 24 hours and that a patient will be entering the critical phase (Centers for Disease Control and Prevention (CDC), 2014).
    D) PLATELET COUNT BELOW REFERENCE RANGE
    1) WITH POISONING/EXPOSURE
    a) Thrombocytopenia may occur in patients with dengue fever (Centers for Disease Control and Prevention (CDC), 2014; Kularatne, 2015).
    b) In a study of 100 adult patients with dengue infection, 87% of patients presented with thrombocytopenia (Babaliche & Doshi, 2015).
    c) For patients with a presumptive dengue diagnosis, an increase in hematocrit with a concurrent rapid decrease in platelet count is a warning sign for severe dengue (Centers for Disease Control and Prevention (CDC), 2016).
    1) A sudden rise in hematocrit of 20% or more from baseline is evidence of plasma leak and in combination with a thrombocytopenia of 100,000 cells/mm(3) or less, sudden change from high to normal or subnormal temperatures, new hypoalbuminemia or hypocholesterolemia, new pleural effusion or ascites, and signs and symptoms of impending or frank shock suggests that a patient has already entered the critical phase (Centers for Disease Control and Prevention (CDC), 2014).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH POISONING/EXPOSURE
    a) In patients who developed dengue hemorrhagic fever, a characteristic convalescence rash is an indicator that the patient is entering the convalescent phase. The rash is a confluent, sometimes pruritic, petechial rash with multiple small round islands of unaffected skin (Centers for Disease Control and Prevention (CDC), 2014).
    b) In a study of 100 adult patients with dengue infection, 36 patients presented with rash (Babaliche & Doshi, 2015).
    c) Diffuse erythematous maculopapular rash may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    B) PETECHIAE
    1) WITH POISONING/EXPOSURE
    a) Petechiae and purpura have been reported (Tantawichien, 2015; Kularatne, 2015).
    b) In dengue fever, petechiae is often found on lower extremities but may also be found on buccal mucosa, hard and soft palates, and subconjunctivae. The patient may have a positive tourniquet test (Centers for Disease Control and Prevention (CDC), 2014).
    C) EASY BRUISING
    1) WITH POISONING/EXPOSURE
    a) Easy bruising on the skin may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) WITH POISONING/EXPOSURE
    a) Arthralgias may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In a study of 100 adult patients with dengue infection, 31 patients presented with arthralgia (Babaliche & Doshi, 2015).
    B) MUSCLE PAIN
    1) WITH POISONING/EXPOSURE
    a) Myalgias may occur with dengue fever (Centers for Disease Control and Prevention (CDC), 2014).
    b) In a study of 100 adult patients with dengue infection, 72 patients presented with myalgia (Babaliche & Doshi, 2015).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and liver enzymes (for up to 4 weeks after discharge) in all symptomatic patients.
    B) Monitor CBC with differential. Leukopenia, thrombocytopenia and hemorrhage have been reported in patients with dengue, as compared to patients with Zika infection. Periodically monitor hematocrit (HCT) (every 6 to 12 hours) for hospitalized dengue patients with warning signs and for diagnosed patients with compensated or hypotensive shock. For patients with a presumptive diagnosis, an sudden rise in HCT with a concurrent rapid decrease in platelet count is a warning sign for severe dengue. HCT is used to evaluate hospitalized patients for the need and the adjustment of IV isotonic crystalloid or colloid solution administration and for the possible need for packed red blood cells or whole blood.
    C) Consider tourniquet test (not recommended if platelet count is less than 80,000 cells/mm(3) [less than 80 x 10(9)/L] or spontaneous petechiae).
    D) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    E) DIAGNOSTIC EVALUATION: Diagnosis of dengue virus is by molecular and serologic testing. Reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA in serum within 7 days after onset of symptoms is the preferred test to diagnose dengue virus infection. In addition, the non-structural protein 1 (NS1) of the dengue viral genome is useful as a tool for the diagnosis of acute dengue infection and may be able to differentiate between flaviviruses, but the assay is not widely available in the United States. Serum collected 4 or more days after symptom onset in patients with compatible clinical syndrome can be tested with dengue virus-specific IgM ELISA and a positive result must be confirmed by testing for neutralizing antibodies, using Plaque-reduction neutralization tests (PRNT). IgG testing can be used to distinguish a primary from a secondary dengue infection.
    F) WHO SHOULD BE TESTED: Any patient who presents with an acute febrile illness and have travelled recently (within the past 2 weeks), where there is ongoing dengue infection, or a patient that lives in an at-risk region, should be tested. Testing should include Zika, chikungunya and dengue virus infections.
    4.1.2) SERUM/BLOOD
    A) Monitor CBC and liver enzymes for up to 4 weeks after discharge (Kularatne, 2015).
    B) Consider tourniquet test (not recommended if platelet count less than 80,000 cells/mm(3) [less than 80 x 10(9)/L] or spontaneous petechiae). This test is simple and inexpensive to perform; however, when the test is positive it is suggestive of dengue but a negative test does not exclude disease. Sensitivity and specificity were found to be especially inadequate when performed in children (Tantawichien, 2015).
    C) Periodically monitor HCT (every 6 to 12 hours) for hospitalized dengue patients with warning signs and dengue patients with compensated or hypotensive shock (Centers for Disease Control and Prevention (CDC), 2016; Centers for Disease Control and Prevention (CDC), 2014).
    D) Complications that arise during the critical phase are usually related to prolonged shock and include hemorrhage, metabolic abnormalities (eg, hypocalcemia, hypoglycemia, hyperglycemia, lactic acidosis, and hyponatremia) (Centers for Disease Control and Prevention (CDC), 2014).
    E) COMPLETE BLOOD COUNT
    1) For patients with a presumptive dengue diagnosis, a sudden increase in HCT with a concurrent rapid decrease in platelet count is a warning sign for severe dengue (Centers for Disease Control and Prevention (CDC), 2016). Refer to TREATMENT OF EXPOSURE section for more specific information about measurement of HCT and fluid administration.
    a) A sudden rise in HCT of 20% or more from baseline is evidence of plasma leak in combination with a thrombocytopenia of 100,000 cells/mm(3) or less, a sudden change from high to normal or subnormal temperatures, new hypoalbuminemia or hypocholesterolemia, new pleural effusion or ascites, and signs and symptoms of impending or frank shock suggests that a patient has already entered the critical phase. Complications that arise during the critical phase are usually related to prolonged shock and include hemorrhage, and metabolic abnormalities (eg, hypocalcemia, hypoglycemia, hyperglycemia, lactic acidosis, hyponatremia) (Centers for Disease Control and Prevention (CDC), 2014).
    2) A new-onset of leukopenia (WBC less than 5000 cells/mm(3)) with lymphocytosis and an increase in atypical lymphocytes can signal dissipation of the fever within the next 24 hours and that a patient will be entering the critical phase (Centers for Disease Control and Prevention (CDC), 2014).
    3) OUTPATIENT MANAGEMENT AND NO WARNING SIGNS: A CBC is used to monitor outpatients with a presumptive dengue diagnosis for warning signs of severe dengue (Centers for Disease Control and Prevention (CDC), 2016):
    a) Monitor CBCs during the 2- to 7-day febrile phase and the 1- to 2-day critical phase.
    b) Watch for warning signs, including decreasing platelet count and increasing HCT.
    c) Watch for defervescence (indicating beginning of critical phase).
    4) INPATIENT MANAGEMENT OF DENGUE PATIENTS WITH WARNING SIGNS: A baseline CBC, fluid intake and output, and vital signs (every 4 hours or more frequently) are used to evaluate hospitalized dengue patients with warning signs (Centers for Disease Control and Prevention (CDC), 2016):
    a) Obtain a baseline CBC when the patient is admitted to the hospital.
    b) If the patient has inadequate oral fluid intake, repeat HCT and give IV isotonic crystalloid solution.
    c) Base subsequent IV isotonic crystalloid solution administration on repeated HCT determinations.
    5) EMERGENCY MANAGEMENT FOR DENGUE PATIENTS WITH COMPENSATED SHOCK: A baseline HCT, assess baseline organ function. fluid intake and output, and hemodynamic status are used for the emergency management for dengue patients with compensated shock (Centers for Disease Control and Prevention (CDC), 2016):
    a) Obtain baseline HCT when the patient is admitted to the hospital or ICU for emergency treatment.
    b) Use repeated HCT to determine the need for and adjustment of IV isotonic crystalloid solutions.
    c) Use repeated HCT to determine the need for transfusion of packed red blood cells or whole blood.
    6) EMERGENCY MANAGEMENT FOR DENGUE PATIENTS WITH HYPOTENSIVE SHOCK: A baseline HCT, assess baseline organ function, fluid intake and output, and hemodynamic status are used for the emergency management for dengue patients with hypotensive shock (Centers for Disease Control and Prevention (CDC), 2016):
    a) Obtain baseline HCT when the patient is admitted to the hospital or ICU for emergency treatment.
    b) Use repeated HCT to determine the need for and adjustment of IV colloid or isotonic crystalloid solutions.
    c) Use repeated HCT to determine the need for transfusion of packed red blood cells or whole blood.
    F) Refer to TREATMENT OF EXPOSURE section for more specific information about monitoring of CBC, measurement of HCT and fluid administration.

Methods

    A) GENERAL GUIDELINES
    1) SUMMARY: Reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA in serum within 7 days after onset of symptoms is the preferred test to diagnose dengue virus infection. In addition, the non-structural protein 1 (NS1) of the dengue viral genome is useful as a tool for the diagnosis of acute dengue infections and may be able to differentiate between flaviviruses , but the assay is not widely available in the United States. Serum collected 4 or more days after symptom onset in patients with compatible clinical syndrome can be tested with dengue virus-specific IgM ELISA and a positive result must be confirmed by testing for neutralizing antibodies, using Plaque-reduction neutralization tests (PRNT) (Centers for Disease Control and Prevention (CDC), 2016). IgG testing can be used to distinguish a primary from a secondary dengue infection (Centers for Disease Control and Prevention (CDC), 2016).
    2) WHO SHOULD BE TESTED: Consider dengue, Zika, and chikungunya virus infections in all patients with acute fever, rash, myalgia, or arthralgia who traveled within the previous 2 weeks to an area of ongoing transmission, or a patient that resides in an area of ongoing transmission. Testing for dengue, Zika, and chikungunya viruses is available at the CDC and several state and territory health departments (Centers for Disease Control and Prevention (CDC), 2016). Testing may retrospectively confirm the diagnosis but are usually not available until the patient has recovered (Centers for Disease Control and Prevention (CDC), 2014).
    3) REPORTABLE DISEASE: Dengue fever and dengue hemorrhagic fever are nationally reportable diseases (Centers for Disease Control and Prevention (CDC), 2016).
    4) LABORATORY SAFETY: Dengue and Zika viruses are classified as biological safety level (BSL) 2 pathogens and chikungunya virus is classified as a BSL 3 agent and all should be handled appropriately with Biosafety in Microbiological and Biomedical Laboratories (BMBL) guidelines (Centers for Disease Control and Prevention (CDC), 2016).
    B) INDICATIONS
    1) SUSPECTED DENGUE VIRUS INFECTION WITHIN THE FIRST 7 DAYS OF ILLNESS: Reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA in serum within 7 days after onset of symptoms is the preferred test to diagnose dengue virus infection. Serum specimens are required for testing, but additional specimens may include urine, amniotic fluid, and tissues (Centers for Disease Control and Prevention (CDC), 2016). RT-PCR tests have a sensitivity of 80% to 90% and a specificity of more than 95% (Centers for Disease Control and Prevention (CDC), 2016). A positive RT-PCR for dengue confirms a dengue virus infection. However, a negative RT-PCR result (indeterminate) on serum obtained 5 to 7 days after symptom onset does not exclude dengue virus disease, and serologic testing should be performed (usually after the 5th day) (Centers for Disease Control and Prevention (CDC), 2016; Centers for Disease Control and Prevention (CDC), 2016).
    a) In addition, the non-structural protein 1 (NS1) of the dengue viral genome has been shown to be useful as a tool for the diagnosis of acute dengue infections and may be useful to differentiate between flaviviruses. Diagnosis of acute or recent dengue infection can be established by testing serum samples during the first 5 days of symptoms. It can detect in the serum of patients with dengue virus infection as early as 1 day post onset of symptoms and up to 18 days post onset. This assay is not widely available in the United States (Centers for Disease Control and Prevention (CDC), 2016; Centers for Disease Control and Prevention (CDC), 2016).
    2) SUSPECTED DENGUE VIRUS INFECTION 4 DAYS OR MORE AFTER SYMPTOM ONSET: Virus-specific IgM antibodies may be detectable 4 or more days after onset of illness and usually persist for about 2 to 12 weeks. Serum detected within 7 days of onset of illness may not have detectable virus-specific IgM antibodies. A positive dengue IgM ELISA result indicates a recent flavivirus infection. A diagnosis of dengue virus infection must be confirmed by testing for neutralizing antibodies (Centers for Disease Control and Prevention (CDC), 2016). False-positive dengue IgM results may be caused by crossreactivity with other flaviviruses, including West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, and yellow fever virus. Anti-dengue false-negative IgM results may be observed during secondary infection, because IgM levels are substantially lower in secondary versus primary dengue infections. The rate of reaction of the IgM response is more variable than IgG (Centers for Disease Control and Prevention (CDC), 2016). However, IgM antibody assays cannot distinguish between dengue and Zika virus infections due to serological cross-reactivity (Centers for Disease Control and Prevention (CDC), 2016). When used 5 or more days (ie, in convalescent phase) after the onset of fever, IgM antibody capture ELISA (MAC-ELISA) has reported a sensitivity and specificity of approximately 90% and 98%, respectively. Serums, blood on filter paper and saliva are useful for IgM detection if samples are taken in the convalescent phase (Centers for Disease Control and Prevention (CDC), 2016).
    3) SUSPECTED DENGUE VIRUS AND POSITIVE DENGUE VIRUS IGM RESULTS: Plaque-reduction neutralization tests (PRNT) can measure virus-specific neutralizing antibodies and may be able to discriminate between cross-reacting antibodies in primary flavivirus infections. In patients with a positive IgM assay with both dengue and Zika antigens, perform PRNT against dengue and Zika viruses and any other flaviviruses in the geographic area, including travel area. Due to cross-reactive antibodies, it may be difficult to determine which flavivirus is causing the current illness in patients who received flavivirus immunization (ie, yellow fever or Japanese encephalitis) or were previously infected with another flavivirus (Centers for Disease Control and Prevention (CDC), 2016).
    4) SUSPECTED DENGUE INFECTION TO DIFFERENTIATE A PRIMARY FROM A SECONDARY INFECTION: IgG cannot differentiate between dengue virus serotypes. With a primary dengue infection, anti-dengue IgG is detectable at a low titer at the end of the first week of illness, then slowly increases. During a secondary infection, antibody titers rise extremely rapidly and antibody reacts with many flaviviruses. High levels of IgG are detectable even in the acute phase, and levels increase dramatically over the next 2 weeks. With a primary dengue infection, IgG is negative in the acute phase and positive in the convalescent phase. With secondary dengue infection, IgG is positive in the acute phase and shows a 4-fold increase in the convalescent phase (with at least 7 days between samples) (Centers for Disease Control and Prevention (CDC), 2016).
    C) SPECIMEN TESTING AND COLLECTION
    1) Zika, chikungunya and dengue virus testing can be performed at the Centers for Disease Control (CDC) and some state health departments that already perform testing for the West Nile virus RT-PCR assay (Centers for Disease Control and Prevention (CDC), 2016). Tests performed at the CDC include Zika, chikungunya and dengue virus RT-PCR, IgM ELISA, and plaque reduction neutralization tests (PRNT). If testing is needed, contact your state health department for further information (Centers for Disease Control and Prevention (CDC), 2016).
    2) Results are usually available 4 to 14 days after receipt of the specimen. Once testing is completed, ALL results will be sent to the appropriate state health department. In addition, state health departments should be notified of any direct submissions to the CDC (Centers for Disease Control and Prevention (CDC), 2016)
    3) For additional assistance in collecting or sending laboratory samples to CDC, contact the Arboviral Diseases Branch on-call epidemiologist at 970-221-6400 or contact them at http://www.cdc.gov/ncezid/dvbd/specimensub/arboviral-shipping.html (Centers for Disease Control and Prevention (CDC), 2016).
    4) Within Puerto Rico, please call 787-706-2399 for further questions about testing (Centers for Disease Control and Prevention (CDC), 2016).
    D) IMAGING
    1) Chest radiograph to detect pleural perfusion in the early phase of plasma leakage and ultrasonography of the abdomen to detect ascites and plasma leak or other diseases such as liver, gallbladder, and kidneys may be required (Kularatne, 2015).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.6) DISPOSITION/BITE-STING EXPOSURE
    6.3.6.1) ADMISSION CRITERIA/BITE-STING
    A) Patients with dengue and warning signs should be hospitalized for monitoring and possible administration of IV fluids. In addition, the following patients with dengue should be hospitalized: pregnant women, infants, older patients, and patients with diabetes mellitus, poor social situation, or renal failure (Centers for Disease Control and Prevention (CDC), 2016).
    B) Patients with dengue and compensated shock should be admitted to the hospital or an ICU for emergency treatment. Other patients that should be admitted and receive close monitoring and management include those with severe plasma leakage with shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment. Compensated shock is characterized by tachypnea, decreased urine output, narrowing pulse pressure, postural hypotension, tachycardia, weak and thready peripheral pulse, cool extremities, and delayed capillary refill (Centers for Disease Control and Prevention (CDC), 2016).
    C) Patients with dengue and hypotensive shock should be admitted to the ICU for emergency treatment. Characteristics consistent with hypotensive shock are restless or combative behavior, prolonged capillary refill, mottled skin, cold and clammy extremities, feeble or absent peripheral pulses, severe tachycardia or bradycardia, narrow pulse pressure, hypotension, unrecordable blood pressure, hyperpnea or Kussmaul's breathing, and oliguria or anuria (Centers for Disease Control and Prevention (CDC), 2016).
    D) Hospitalized patients may be discharged after wellbeing is achieved, temperature is normal for 48 hours, HCT is stable, and platelet count is increasing (Kularatne, 2015).
    6.3.6.2) HOME CRITERIA/BITE-STING
    A) Patients with dengue and no warning signs may be managed as outpatients with careful monitoring (Centers for Disease Control and Prevention (CDC), 2016).
    6.3.6.3) CONSULT CRITERIA/BITE-STING
    A) Infectious disease physicians and/or intensivists may be consulted for medical advice. Poison centers can aid treatment by serving as a public health resource by providing advice to the general public, and working with local and regional health departments.
    6.3.6.5) OBSERVATION CRITERIA/BITE-STING
    A) Patients with worsening symptoms that do not improve with over-the-counter medications (eg, analgesics, antipyretics) and basic home treatments should go to a healthcare facility for evaluation and treatment.
    B) In addition, advise patient to immediately go to the clinic or emergency department if any of the following warning signs occur: severe abdominal pain or persistent vomiting, red spots or patches on the skin, bleeding from the nose or gums, vomiting blood, black, tarry stools, drowsiness or irritability, pale, cold, or clammy skin, and difficulty breathing (Centers for Disease Control and Prevention (CDC), 2016).

Monitoring

    A) Monitor vital signs and liver enzymes (for up to 4 weeks after discharge) in all symptomatic patients.
    B) Monitor CBC with differential. Leukopenia, thrombocytopenia and hemorrhage have been reported in patients with dengue, as compared to patients with Zika infection. Periodically monitor hematocrit (HCT) (every 6 to 12 hours) for hospitalized dengue patients with warning signs and for diagnosed patients with compensated or hypotensive shock. For patients with a presumptive diagnosis, an sudden rise in HCT with a concurrent rapid decrease in platelet count is a warning sign for severe dengue. HCT is used to evaluate hospitalized patients for the need and the adjustment of IV isotonic crystalloid or colloid solution administration and for the possible need for packed red blood cells or whole blood.
    C) Consider tourniquet test (not recommended if platelet count is less than 80,000 cells/mm(3) [less than 80 x 10(9)/L] or spontaneous petechiae).
    D) Monitor fluid status and electrolytes in patients that develop significant vomiting and/or diarrhea.
    E) DIAGNOSTIC EVALUATION: Diagnosis of dengue virus is by molecular and serologic testing. Reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA in serum within 7 days after onset of symptoms is the preferred test to diagnose dengue virus infection. In addition, the non-structural protein 1 (NS1) of the dengue viral genome is useful as a tool for the diagnosis of acute dengue infection and may be able to differentiate between flaviviruses, but the assay is not widely available in the United States. Serum collected 4 or more days after symptom onset in patients with compatible clinical syndrome can be tested with dengue virus-specific IgM ELISA and a positive result must be confirmed by testing for neutralizing antibodies, using Plaque-reduction neutralization tests (PRNT). IgG testing can be used to distinguish a primary from a secondary dengue infection.
    F) WHO SHOULD BE TESTED: Any patient who presents with an acute febrile illness and have travelled recently (within the past 2 weeks), where there is ongoing dengue infection, or a patient that lives in an at-risk region, should be tested. Testing should include Zika, chikungunya and dengue virus infections.

Range Of Toxicity

Summary

    A) TOXICITY: Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species One mosquito is enough to cause an infection. Severe, life-threatening disease can develop in up to 5% of patients with dengue. About 500,000 people with dengue hemorrhagic fever are hospitalized every year; about 2.5% of those affected die. Early recognition of signs of shock and initiation of intensive supportive therapy can reduce the risk of death with severe dengue from 10% to less than 1%. The risk of death is 4-fold higher in children 1 to 5 years old compared with children 11 to 15 years old.

Minimum Lethal Exposure

    A) Severe, life-threatening disease can develop in up to 5% of patients with dengue (Tomashek et al, 2015). About 500,000 people with dengue hemorrhagic fever are hospitalized every year; about 2.5% of those affected die (WHO Regional Office for South-East Asia, 2011). Early recognition of signs of shock and initiation of intensive supportive therapy can reduce the risk of death with severe dengue from 10% to less than 1% (Tomashek et al, 2015). The risk of death is 4-fold higher in children 1 to 5 years old compared with children 11 to 15 years old (Kularatne, 2015).

Maximum Tolerated Exposure

    A) Dengue is a mosquito-borne viral illness that is transmitted to humans primarily through the bite of an infected female mosquito of the Aedes aegypti and Aedes albopictus species (World Health Organization (WHO), 2015). One mosquito is enough to cause an infection.

References

General Bibliography

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