What are the diagnostic and treatment approaches for dengue (Dengue Virus) fever?

Dengue Fever: Diagnostic and Treatment Approach

For patients with suspected dengue fever, perform nucleic acid amplification testing (NAAT) on serum collected within 7 days of symptom onset, and manage with supportive care including aggressive oral hydration, acetaminophen for fever/pain, and daily monitoring for warning signs of severe disease progression. 1, 2

Clinical Presentation and Diagnosis

Key Clinical Features

• Dengue presents with fever plus one or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, nausea, vomiting, positive tourniquet test, or leukopenia 1, 2
• The incubation period is 4-8 days after mosquito exposure, with illness following a characteristic triphasic course: febrile phase, critical phase, and recovery phase 2, 3, 4
• The exanthem occurs in up to 50% of patients and can aid in early recognition 5

Diagnostic Testing Algorithm

For specimens collected ≤7 days after symptom onset:

• Perform dengue NAAT (RT-PCR) on serum as the preferred initial test 1, 2, 4
• NAAT can also be performed on plasma, whole blood, or cerebrospinal fluid 1
• If NAAT is positive, no antibody testing is needed unless the diagnosis has significant epidemiologic or clinical implications 1
• If NAAT is negative, proceed to IgM antibody testing on the same specimen 1, 2

For specimens collected >7 days after symptom onset:

• Perform IgM capture ELISA as the primary test 1, 2, 3
• A negative IgM result from 7 days to 12 weeks after symptom onset rules out recent dengue infection 1

For positive IgM results without positive NAAT:

• Perform plaque reduction neutralization tests (PRNTs) when definitive diagnosis is needed for clinical or epidemiologic purposes 1
• Be aware that PRNT may not reliably differentiate dengue from other flaviviruses (especially Zika) in areas with high prevalence of both viruses 1

Differential Diagnosis Considerations

• Consider chikungunya, malaria, rubella, measles, hepatitis A, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsiosis, and group A streptococcal infections in the differential 1
• In areas with both dengue and Zika virus circulation, test for both viruses simultaneously in symptomatic patients 1, 3

Risk Stratification and Monitoring

Warning Signs Requiring Immediate Attention

Monitor daily for the following warning signs that indicate progression to severe dengue:

• Persistent vomiting 1, 6, 2, 3
• Severe abdominal pain 6, 2, 3
• Lethargy or restlessness 6, 2, 3
• Mucosal bleeding 6, 2, 3
• Rising hematocrit (>20% increase from baseline) with falling platelet count 2, 3

Laboratory Monitoring

• Perform daily complete blood count to track platelet counts and hematocrit levels 6, 2, 3
• Thrombocytopenia ≤100,000/mm³, particularly when declining rapidly, requires hospitalization 2
• Lower platelet, white blood cell, and neutrophil counts distinguish dengue from other febrile illnesses 7

Hospitalization Criteria

Admit patients with any of the following:

• Severe plasma leakage, severe bleeding, or organ failure 2
• Dengue shock syndrome (narrow pulse pressure ≤20 mmHg or hypotension) 2
• Rising hematocrit >20% from baseline or thrombocytopenia ≤100,000/mm³ with rapid decline 2
• Pregnant women with confirmed or suspected dengue due to risk of maternal death, hemorrhage, preeclampsia, and vertical transmission 1, 2

Treatment Approach

Supportive Care (Cornerstone of Management)

There is no specific antiviral therapy currently approved for dengue 6, 2

Fluid Management:

• For patients without shock: ensure adequate oral hydration with oral rehydration solutions, aiming for >2500 mL daily 2
• For dengue shock syndrome: administer initial fluid bolus of 20 mL/kg isotonic crystalloid over 5-10 minutes with immediate reassessment 2, 3
• Consider colloid solutions for severe shock with pulse pressure <10 mmHg 2, 3

Pain and Fever Management:

• Acetaminophen (paracetamol) at standard doses is the ONLY recommended analgesic 2, 3
• NEVER use aspirin or NSAIDs due to increased bleeding risk with thrombocytopenia 6, 2, 3
• This is a critical pitfall to avoid—aspirin and NSAIDs are absolutely contraindicated when dengue cannot be excluded 2, 3

Management of Complications

• For significant bleeding, blood transfusion may be necessary 2
• For persistent tissue hypoperfusion despite adequate fluid resuscitation, consider vasopressors such as dopamine or epinephrine 2
• Avoid invasive procedures when possible during the acute phase, especially if coagulopathy is present 6

Critical Pitfalls to Avoid

• Do NOT administer excessive fluid boluses in patients without shock—this can lead to fluid overload and respiratory complications 6, 3
• Do NOT delay fluid resuscitation in patients showing signs of dengue shock 2, 3
• Do NOT change management based solely on persistent fever pattern without clinical deterioration or new findings 2
• Do NOT fail to recognize the critical phase when plasma leakage can rapidly progress to shock 6

Special Populations

Pregnant Women

• Test pregnant women by NAAT for both dengue and Zika virus regardless of outbreak patterns due to risk of adverse outcomes 1, 2, 3
• Dengue infection increases risk for maternal death, hemorrhage, preeclampsia, eclampsia, and vertical transmission during the peripartum period 1
• Acetaminophen remains the safest analgesic option in pregnancy 2, 3

Children

• Acetaminophen dosing should be carefully calculated based on weight 2
• Note that some clinical features that distinguish dengue from other febrile illnesses in adults (myalgia, rash, hemorrhagic signs, lethargy, arthralgia, higher hematocrit) may not be as prominent in children 7

Discharge Criteria

Patients can be safely discharged when ALL of the following criteria are met:

• Afebrile for ≥48 hours without antipyretics 2, 3
• Resolution or significant improvement of symptoms 2
• Stable hemodynamic parameters for ≥24 hours without support (normal heart rate, stable blood pressure, normal capillary refill) 2
• Adequate oral intake 2
• Adequate urine output (>0.5 mL/kg/hour in adults) 2
• Laboratory parameters returning to normal ranges 2

Post-Discharge Instructions

• Monitor and record temperature twice daily 2
• Return immediately if temperature rises to ≥38°C on two consecutive readings or if any warning signs develop 2

Public Health Considerations

• Dengue is a nationally notifiable condition—report all cases to public health authorities 1
• Advise patients about prevention of mosquito bites to prevent further transmission 8
• The primary vector is Aedes aegypti, a day-biting mosquito 2, 4