What is dengue fever, its transmission, symptoms, diagnosis, treatment, and prevention?

Dengue Fever: Comprehensive Overview

What is Dengue Fever?

Dengue fever is a mosquito-borne viral infection caused by the dengue virus (serotypes 1-4), transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes, presenting as a spectrum from mild febrile illness to life-threatening dengue hemorrhagic fever and dengue shock syndrome. 1, 2

• The disease affects over 100 million people annually in tropical and subtropical regions, with more than 2.5 billion people at risk globally 2, 3
• The incubation period is typically 4-8 days after mosquito exposure 1
• Most infections are asymptomatic, but symptomatic disease ranges from mild dengue fever to severe, potentially fatal complications 3, 4

Transmission

Day-biting mosquitoes of the genus Aedes, particularly Aedes aegypti, are the primary vectors, transmitting the virus from viremic to susceptible humans. 1, 3

• Aedes aegypti mosquitoes are both diurnal (day-active) and container breeders, requiring specific prevention strategies 5
• Climate change and global mobility have led to worldwide increases in dengue cases 2

Clinical Presentation and Symptoms

Dengue Without Warning Signs

The typical presentation includes acute febrile illness with frontal headache, retro-orbital pain, muscle and joint pain (myalgia/arthralgia), and rash. 6, 1

• Fever with at least one of the following: nausea, vomiting, rash, headache, retro-orbital pain, myalgia, arthralgia, positive tourniquet test, or leukopenia 1
• This mild form occurs in more than 90% of cases 2

Warning Signs (Critical Phase - Days 3-7)

Warning signs indicate potential progression to severe dengue and require immediate medical attention and hospitalization. 6, 1

The critical warning signs include:

• Persistent vomiting 6, 1
• Abdominal pain or tenderness (particularly right upper quadrant) 6
• Clinical fluid accumulation (pleural effusion, ascites) 6
• Mucosal bleeding 6
• Lethargy or restlessness 6
• Hepatomegaly 6
• Hematocrit rise (>20% increase from baseline) with concurrent thrombocytopenia 6, 1

Dengue Hemorrhagic Fever (DHF)

DHF is characterized by acute febrile illness with minor or major bleeding phenomena, thrombocytopenia, and evidence of plasma leakage. 6, 1

Dengue Shock Syndrome (DSS)

DSS includes all DHF criteria plus hypotension or narrow pulse pressure, representing the most severe form with 1-5% mortality. 6, 2

Specific criteria for DSS:

• Systolic blood pressure <90 mmHg for >30 minutes 6
• Pulse pressure <20 mmHg persisting despite initial fluid resuscitation 6
• Signs of end-organ hypoperfusion: cold/clammy extremities, livedo reticularis, elevated lactate >2 mmol/L, capillary refill time ≥3 seconds 6

Narrow pulse pressure (<20 mmHg) is an earlier and more sensitive indicator of dengue shock than absolute hypotension and should be monitored closely. 6

Diagnosis

Timing-Based Diagnostic Approach

For symptoms ≤7 days: Nucleic Acid Amplification Test (NAAT/PCR) on serum is the preferred initial test. 1

• PCR testing is most effective in the first few days during viremia 6
• NS1 antigen detection is useful in the acute phase, detectable from day 1 to day 10 after symptom onset 6

For symptoms >7 days: IgM capture ELISA (MAC-ELISA) becomes the primary diagnostic test. 6, 1

• IgM antibody testing becomes appropriate after the first week of illness 6
• Important caveat: IgG antibodies can persist for months to years after dengue infection, so IgG alone does not confirm acute infection 1

Rapid Diagnostic Tests

• Rapid diagnostic tests combining NS1 antigen and IgG have very high positive likelihood ratios and can optimize management 1

Special Considerations

• Document vaccination history to avoid cross-reactivity with other flaviviruses (yellow fever, Japanese encephalitis, tick-borne encephalitis) 1
• Serological diagnosis is challenging due to cross-reactions with other flaviviruses 5
• For pregnant women: Test by NAAT for both dengue and Zika virus regardless of outbreak patterns due to risk of adverse outcomes 1

Differential Diagnosis

Consider other infectious etiologies including:

• Chikungunya 1
• Zika virus 1
• Parvovirus 1
• Adenovirus 1
• Enterovirus 1

Risk Stratification and Hospitalization Criteria

Indications for Hospitalization

Hospitalize patients with any warning signs, severe dengue (severe plasma leakage, severe bleeding, organ failure), dengue shock syndrome, or high-risk populations. 1

Specific criteria:

• Narrow pulse pressure ≤20 mmHg or hypotension 1
• Rising hematocrit (>20% increase from baseline) 1
• Thrombocytopenia ≤100,000/mm³, particularly when declining rapidly 1
• Pregnant women with confirmed or suspected dengue 1
• Presence of any warning signs 6, 1

Outpatient Management Criteria

• Platelet count >100,000/mm³ without rapid decline 1
• Stable hematocrit without evidence of hemoconcentration 1
• No warning signs present 1

The absence of thrombocytopenia significantly reduces the probability of dengue, making it a useful rule-out finding. 1

Treatment

General Principles

Treatment is entirely supportive, as no specific antiviral therapy is available; the key measures are adequate volume replacement and monitoring for complications. 1, 2

Outpatient Management (Dengue Without Warning Signs)

Manage with aggressive oral hydration (>2500ml daily), acetaminophen for symptom relief, and daily monitoring for warning signs. 1

• Ensure adequate oral hydration using oral rehydration solutions for moderate dehydration 1
• Daily complete blood count monitoring to track platelet counts and hematocrit levels 1

Pain and Fever Management

Acetaminophen at standard doses is the ONLY recommended analgesic for pain and fever relief. 1

Critical pitfall: NEVER use aspirin or NSAIDs under any circumstances due to high bleeding risk. 1

• Acetaminophen remains the safest analgesic option for pregnant women 1
• In children, acetaminophen dosing should be carefully calculated based on weight 1
• Consider alternative cooling measures (tepid water sponging) if fever recurs rather than increasing acetaminophen dose 1

Fluid Management for Dengue Shock Syndrome

Administer an initial fluid bolus of 20 mL/kg isotonic crystalloid over 5-10 minutes with immediate reassessment. 6, 1

• Reassess immediately after bolus completion and consider additional boluses if necessary 1
• Consider colloid solutions for severe dengue shock with pulse pressure <10 mmHg 6, 1

Critical consideration: Dengue shock behaves differently from bacterial septic shock—avoid over-resuscitation as excessive fluids can worsen outcomes given the underlying plasma leakage pathophysiology. 6

• In resource-limited settings without mechanical ventilation and inotropic support, aggressive fluid boluses may increase mortality 1
• For dengue shock specifically, colloids show benefit for time to resolution of shock compared to crystalloids alone 1

Management of Complications

For significant bleeding, blood transfusion may be necessary. 1

For persistent tissue hypoperfusion despite adequate fluid resuscitation, vasopressors such as dopamine or epinephrine may be required. 1

• Monitor with continuous cardiac telemetry and pulse oximetry for patients with dengue shock syndrome 1

Monitoring During Hospitalization

• Daily complete blood count monitoring is essential to track platelet counts and hematocrit levels 1
• Monitor CBC daily during the critical phase to guide fluid management and identify progression to severe disease 1
• Monitor vital signs and laboratory parameters closely 7

Management of Persistent or Recurrent Fever

Fever recurring after 4 afebrile days falls outside the expected dengue illness pattern and mandates investigation for alternative causes, particularly secondary bacterial infections. 7

Immediate Diagnostic Workup

• Perform chest radiography to evaluate for pneumonia or pleural effusions 7
• Obtain blood and urine cultures 1, 7
• Check complete blood count with attention to platelet count and hematocrit 7
• Conduct meticulous physical examination focusing on new infection sites, catheter entry/exit sites, and signs of progressive disease 7
• Evaluate for warning signs of severe dengue 7

Management Approach

Initiate broad-spectrum antibiotic coverage empirically while awaiting culture results if bacterial co-infection is suspected. 7

Critical pitfall: The most critical error is prescribing antibiotics like azithromycin empirically for dengue fever without evidence of bacterial co-infection, which contributes to antimicrobial resistance without providing clinical benefit. 1

• Secondary bacterial infections occur in less than 10% of viral illness cases 1
• Patients who remain hemodynamically unstable should have management broadened to include coverage for potential secondary infections 1
• Do not change antibiotics or management based solely on persistent fever pattern without clinical deterioration or new findings 1

Discharge Criteria

Patients can be safely discharged when they meet ALL of the following criteria: 1

• Afebrile for at least 48 hours without the use of antipyretics 1
• Resolution or significant improvement of symptoms 1
• Improved general condition and return to baseline mental status 1
• Stable hemodynamic parameters for at least 24 hours without support (normal heart rate, stable blood pressure, normal capillary refill time) 1
• Adequate oral intake 1
• Adequate urine output (>0.5 mL/kg/hour in adults) 1
• Laboratory parameters returning to normal ranges 1

Post-Discharge Instructions

Patients must monitor and record their temperature twice daily after discharge. 1

Return to the healthcare facility immediately if:

• Temperature rises to ≥38°C on two consecutive readings 1
• Any warning signs develop 1
• Persistent or recurrent vomiting occurs (unable to tolerate oral fluids) 1

Post-Discharge Laboratory Monitoring

• Repeat complete blood count and liver function tests at 3-5 days post-discharge 1
• If transaminases were elevated 2-5× normal at discharge, monitor weekly until normalized 1
• If transaminases were >5× normal at discharge, monitor every 3 days initially 1

Prevention

Prevention strategies include vaccination after a documented initial infection and meticulous avoidance of mosquito bites. 2

• Vector control is the primary alternative for stopping disease spread, as no vaccine is commercially available for primary prevention 3
• Day-biting mosquitoes require specific prevention measures focused on eliminating container breeding sites 1, 5
• Work is ongoing to develop vaccines and medications targeted directly at the virus 4

Prognosis

Early recognition of warning signs and appropriate management can reduce case-fatality rate to <0.5%. 6

• Typical dengue fever resolves within 5-7 days 7
• The disease characteristically takes a triphasic course: febrile phase, critical phase (days 3-7), and recovery phase 2
• Severe dengue fever carries a mortality of 1-5% when complications occur 2