What are the diagnostic criteria and management for dengue?

Diagnostic Criteria and Management of Dengue

Clinical Diagnostic Criteria

Dengue should be suspected in any patient presenting with fever plus at least one of the following: nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, positive tourniquet test, or leukopenia, particularly with travel to or residence in endemic areas within the past 14 days. 1

Core Clinical Features

• Fever is the hallmark symptom, typically appearing 4-8 days after mosquito exposure (incubation range 3-14 days) 2, 3
• Characteristic symptoms include frontal headache, retro-orbital pain, severe muscle and joint pain ("breakbone fever"), and rash 2, 3
• The disease follows a triphasic course: febrile phase, critical phase (days 3-7 around defervescence), and recovery phase 4, 5

Warning Signs Requiring Immediate Attention

Any of these warning signs mandate close monitoring and consideration for hospitalization: 4

• Persistent vomiting (unable to tolerate oral fluids)
• Severe abdominal pain or tenderness
• Clinical fluid accumulation (pleural effusion, ascites)
• Mucosal bleeding
• Lethargy or restlessness
• Hepatomegaly >2 cm
• Rising hematocrit with concurrent rapid platelet decline

Laboratory Diagnostic Approach

Timing-Based Testing Strategy

For symptoms ≤7 days: 1, 3

• Nucleic Acid Amplification Test (NAAT/PCR) on serum is the preferred initial test
• NS1 antigen detection is an excellent alternative, detectable from day 1 to day 10 after symptom onset 3, 4
• If NAAT is negative, proceed to IgM antibody testing (negative NAAT does not exclude dengue due to declining viremia or inaccurate symptom onset dates) 1

For symptoms >7 days: 1, 3

• IgM capture ELISA (MAC-ELISA) becomes the primary diagnostic test
• IgM antibodies develop during the first week and remain detectable for 2-3 months 3
• Some laboratories perform NAAT and IgM simultaneously rather than sequentially to avoid delays 3

Diagnostic Confirmation Criteria

Confirmed case requires one of the following: 3

• Isolation of dengue virus from serum/tissue
• Fourfold or greater change in antibody titers in paired samples
• Detection of dengue virus antigen or viral nucleic acid by NAAT

Probable case: 3

• Clinically compatible illness with IgG titer ≥1280 or positive IgM on single specimen

Critical Testing Pitfalls

• IgM collected <7 days after onset may be falsely negative due to collection before antibody development 3
• IgG antibodies persist for months to years and do not confirm acute infection alone 2
• Cross-reactivity with other flaviviruses (Zika, West Nile, yellow fever, Japanese encephalitis) complicates serological diagnosis 3
• Document vaccination history to avoid cross-reactivity 2

Disease Classification and Risk Stratification

Dengue Without Warning Signs

• Acute febrile illness with characteristic symptoms but no warning signs 4
• Outpatient management is appropriate with aggressive oral hydration (>2500 mL daily), acetaminophen for symptom relief, and daily monitoring 2

Dengue With Warning Signs

• Presence of any warning sign listed above 4
• Hospitalization warranted for close monitoring 4
• Daily complete blood count monitoring essential to track platelets and hematocrit 2

Severe Dengue (Dengue Hemorrhagic Fever/Dengue Shock Syndrome)

Dengue Hemorrhagic Fever (DHF): 4

• Minor or major bleeding phenomena
• Thrombocytopenia (platelets ≤100,000/mm³)
• Evidence of plasma leakage

Dengue Shock Syndrome (DSS): 4

• All DHF criteria PLUS:
• Hypotension (systolic BP <90 mmHg for >30 minutes) OR
• Narrow pulse pressure ≤20 mmHg (more sensitive early indicator than absolute hypotension) 4
• Signs of end-organ hypoperfusion: cold/clammy extremities, capillary refill ≥3 seconds, elevated lactate >2 mmol/L 4

Management Approach

Outpatient Management (No Warning Signs)

• Aggressive oral hydration: oral rehydration solutions, aim for >2500 mL daily 2
• Acetaminophen at standard doses for fever and pain (NEVER aspirin or NSAIDs due to bleeding risk) 2
• Daily monitoring for warning signs 2
• Patient education on warning signs and when to return immediately 2

Inpatient Management (Warning Signs Present)

• Daily CBC monitoring to track platelet counts and hematocrit levels 2
• Adequate fluid management: ensure oral hydration or IV fluids if unable to tolerate oral intake 2
• Monitor for progression to severe dengue 2

Management of Dengue Shock Syndrome

Initial resuscitation: 2, 4

• Administer 20 mL/kg isotonic crystalloid bolus over 5-10 minutes
• Reassess immediately after bolus completion
• Consider additional boluses if necessary
• For severe shock with pulse pressure <10 mmHg, consider colloid solutions 2, 4

Critical considerations: 2

• Dengue shock behaves differently from bacterial septic shock
• Avoid over-resuscitation—excessive fluids worsen outcomes due to underlying plasma leakage pathophysiology 4
• Monitor with continuous cardiac telemetry and pulse oximetry 2

Management of Complications

• For significant bleeding: blood transfusion may be necessary 2
• For persistent tissue hypoperfusion despite adequate fluid resuscitation: vasopressors (dopamine or epinephrine) may be required 2
• If fever persists with hemodynamic instability: broaden management to cover potential secondary bacterial infections (though bacterial co-infection occurs in <10% of cases) 2

Special Populations

Pregnant Women

Pregnant women require comprehensive testing with both NAAT and serology for dengue (and Zika if relevant) regardless of outbreak patterns due to risk of: 1, 3

• Maternal death

• Hemorrhage

• Preeclampsia/eclampsia

• Vertical transmission

• Acetaminophen remains the safest analgesic option 2

Children

• Acetaminophen dosing should be carefully calculated based on weight 2

Discharge Criteria

Patients can be safely discharged when ALL of the following are met: 2

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

Post-Discharge Instructions

• Monitor temperature twice daily 2
• Return immediately if: temperature ≥38°C on two consecutive readings, any warning signs develop, or persistent/recurrent vomiting 2
• Follow-up laboratory monitoring: repeat CBC and liver function tests at 3-5 days post-discharge 2

Critical Pitfalls to Avoid

• NEVER use aspirin or NSAIDs when dengue cannot be excluded—high bleeding risk 2
• Do not delay fluid resuscitation in patients showing signs of shock 2
• Do not prescribe antibiotics empirically without evidence of bacterial co-infection—contributes to antimicrobial resistance without benefit 2
• Do not change management based solely on persistent fever without clinical deterioration or new findings 2
• Narrow pulse pressure (<20 mmHg) is an earlier indicator than absolute hypotension—monitor closely 4

Differential Diagnosis

Consider other infectious etiologies: 1

• Chikungunya, Zika virus
• Malaria
• Rubella, measles
• Hepatitis A
• Parvovirus, adenovirus, enterovirus
• Leptospirosis
• Rickettsiosis
• Group A streptococcal infections