What are the current guidelines for diagnosing and managing a patient with suspected dengue fever?

Dengue Fever: Diagnosis and Management Guidelines

Clinical Presentation and When to Suspect Dengue

Suspect dengue 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, 2

• The incubation period ranges from 3-14 days, with most cases developing symptoms 4-8 days after mosquito exposure 3, 2
• Classic presentation includes frontal headache, retro-orbital pain, muscle and joint pain, and rash during the acute febrile phase 3, 2
• The disease follows a triphasic course: febrile phase, critical phase, and recovery phase 4

Diagnostic Testing Algorithm

For Symptoms ≤7 Days from Onset (Acute Phase)

Perform NAAT (PCR) on serum as the preferred initial diagnostic test, or use NS1 antigen detection as an excellent alternative. 1, 3, 2

• NAAT/PCR detects viral RNA for 4-6 days after symptom onset and is most sensitive during the first week 3, 2
• NS1 antigen is detectable as early as 1 day after symptom onset and remains positive for up to 10 days, with peak sensitivity (75-90%) during days 1-5 3, 5, 6, 7
• Both serum and plasma are acceptable specimens; transport at room temperature if processed within 2 hours 3
• The FDA has cleared NAAT for use on serum and whole blood, and NS1 antigen enzyme immunoassay for use on serum 1, 2

A negative IgM test during the first few days does not rule out dengue—antibodies may not have developed yet. 5, 2

• IgM antibodies typically appear 3-5 days after symptom onset 5
• If initial testing at <7 days is negative and clinical suspicion remains high, repeat IgM antibody testing after 5-7 days to allow time for antibody development 5

For Symptoms >7 Days from Onset (Convalescent Phase)

IgM capture ELISA (MAC-ELISA) becomes the primary diagnostic test after the first week of illness. 3, 2

• IgM antibodies develop during the first week and remain detectable for 2-3 months 3, 5, 2
• IgG antibodies develop around day 5-7 in primary infections and earlier in secondary infections 5
• For specimens collected 7 days to 12 weeks after onset, a negative IgM result rules out recent infection 5

Confirmatory Testing for Cross-Reactivity

When IgM or IgG results are positive but definitive diagnosis is needed, perform plaque reduction neutralization test (PRNT) to distinguish dengue from other flaviviruses. 1, 3, 5

• IgM and IgG antibodies cross-react with other flaviviruses (Zika, West Nile, yellow fever, Japanese encephalitis, tick-borne encephalitis) 1, 5, 2
• PRNT titer ≥10 defines a positive result and provides superior specificity over commercial serologic assays 3, 5
• Document complete vaccination history, as prior flavivirus vaccination causes false-positive IgM results 1, 3
• In secondary flavivirus infections, neutralizing antibodies against multiple flaviviruses rise rapidly, potentially precluding conclusive determination of the infecting virus 1

Interpretation of Common Test Result Patterns

NS1 positive with negative IgM/IgG indicates acute primary dengue infection in the very early phase (days 1-5), confirming active viral replication. 5

• Continue clinical monitoring based on warning signs rather than repeat serological testing 5
• PRNT is not indicated for this pattern, as NS1 positivity already confirms acute dengue 5

NS1 negative with both IgM and IgG positive indicates either secondary dengue infection, late primary infection (>7 days), or past infection with persistent IgM. 5

• Perform confirmatory PRNT testing against dengue and other endemic flaviviruses to definitively diagnose dengue 5
• If PRNT unavailable, report as "presumptive recent dengue virus infection" 5
• Do not assume acute infection based on positive antibodies alone—IgM can persist for months 5

IgG antibodies alone (without IgM) indicate past dengue infection, as IgG persists for months to years after infection. 5

Risk Stratification and Admission Criteria

Indications for Hospital Admission

Hospitalize patients with any warning signs of severe dengue: persistent vomiting, abdominal pain, lethargy, restlessness, mucosal bleeding, rising hematocrit with falling platelet count, severe plasma leakage, severe bleeding, organ failure, or dengue shock syndrome. 3

• Dengue shock syndrome is defined by hypotension, narrow pulse pressure ≤20 mmHg, or other signs of hemodynamic instability 3
• Rising hematocrit (>20% increase from baseline) or thrombocytopenia ≤100,000/mm³ with rapid decline warrants hospitalization 3
• Pregnant women with confirmed or suspected dengue require hospitalization due to risk of maternal death, hemorrhage, preeclampsia, and vertical transmission 1, 3, 2

High-risk populations requiring lower threshold for admission include patients >60 years, those with comorbidities (diabetes, hypertension, heart disease), and immunocompromised patients. 3

• Patients with diabetes and hypertension have 2.16 times higher risk of dengue hemorrhagic fever 3

Criteria for Outpatient Management

Patients may be managed as outpatients only if they have no warning signs, no comorbidities, platelet count >100,000/mm³ without rapid decline, stable hematocrit, reliable daily follow-up available, and can maintain adequate oral hydration. 3

Management Approach

Fluid Management

For patients without shock, ensure adequate oral hydration with oral rehydration solutions, aiming for >2500 mL daily. 3

For dengue shock syndrome, administer an initial fluid bolus of 20 mL/kg isotonic crystalloid over 5-10 minutes with immediate reassessment. 3

• Consider colloid solutions for severe shock with pulse pressure <10 mmHg 3
• Reassess immediately after bolus completion and consider additional boluses if necessary 3
• In resource-limited settings without mechanical ventilation and inotropic support, aggressive fluid boluses may increase mortality, but for dengue shock specifically, colloids show benefit for time to resolution of shock 3

Pain and Fever Management

Use acetaminophen at standard doses for pain and fever relief—never use aspirin or NSAIDs due to increased bleeding risk. 3

• Acetaminophen remains the safest analgesic option for pregnant women and children (dose by weight in children) 3
• Consider alternative cooling measures (tepid water sponging) if fever recurs rather than increasing acetaminophen dose 3

Monitoring

Perform daily complete blood count monitoring to track platelet counts and hematocrit levels, watching for warning signs of progression to severe dengue. 3

• Monitor continuously with cardiac telemetry and pulse oximetry for patients with dengue shock syndrome 3
• The absence of thrombocytopenia significantly reduces the probability of dengue 3

Management of Complications

For significant bleeding, blood transfusion may be necessary; for persistent tissue hypoperfusion despite adequate fluid resuscitation, use vasopressors (dopamine or epinephrine). 3

• Obtain blood and urine cultures and chest radiograph if fever persists to diagnose secondary bacterial infections 3
• Persistent fever typically resolves within 5 days of treatment initiation 3
• Do not change antibiotics based solely on persistent fever pattern without clinical deterioration or new findings 3

The most critical error is prescribing antibiotics empirically for dengue fever without evidence of bacterial co-infection—bacterial co-infection occurs in <10% of viral illness cases. 3

Discharge Criteria

Patients can be safely discharged when they meet all of the following criteria: 3

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

Post-Discharge Instructions

Instruct patients to monitor temperature twice daily and return immediately if temperature rises to ≥38°C on two consecutive readings or if any warning signs develop. 3

• Repeat complete blood count and liver function tests at 3-5 days post-discharge 3
• If transaminases were elevated 2-5× normal at discharge, monitor weekly until normalized 3
• If transaminases were >5× normal at discharge, monitor every 3 days initially 3
• Return immediately for persistent or recurrent vomiting unable to tolerate oral fluids 3

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 with either infection. 1, 3, 2

• Dengue infection during pregnancy increases risk for maternal death, hemorrhage, preeclampsia/eclampsia, and vertical transmission 1, 3, 2
• During dengue or Zika outbreaks, nonpregnant persons may have testing for the non-outbreak virus deferred, but pregnant women require comprehensive testing for both viruses 1

Differential Diagnosis

Consider other infectious etiologies including chikungunya, Zika virus, malaria, rubella, measles, hepatitis A, parvovirus, adenovirus, enterovirus, leptospirosis, rickettsiosis, and group A streptococcal infections. 1, 2

• Zika virus testing should also be considered in symptomatic patients who had sex with someone who lives in or recently traveled to endemic areas 1

Prevention

Day-biting mosquitoes of the genus Aedes (particularly Aedes aegypti and Aedes albopictus) are the primary vectors of dengue fever. 3, 4

• Preventive steps include vaccination after a documented initial infection and meticulous avoidance of mosquito bites 4

Common Pitfalls to Avoid

• Never use aspirin or NSAIDs when dengue cannot be excluded 3
• Do not delay fluid resuscitation in patients showing signs of shock 3
• Do not assume acute infection based on positive antibodies alone—IgM can persist for months after initial infection 5
• Do not rule out dengue based on a negative IgM test collected during the first few days of illness 5, 2
• Do not interpret NS1 positivity as a predictor of severe dengue—admission decisions should be based on clinical warning signs, not NS1 status alone 8