Dengue Fever

Clinical Overview

Dengue fever is the most prevalent mosquito-borne viral infection worldwide, caused by the dengue virus (DENV), a single-stranded RNA virus belonging to the family Flaviviridae. [1] Four antigenically distinct serotypes (DENV-1 through DENV-4) co-circulate globally, each capable of causing the full spectrum of clinical disease. [2] The primary vector, Aedes aegypti, is a highly anthropophilic day-biting mosquito that has expanded its geographic range due to urbanisation, globalisation, and climate change. [3]

The global burden of dengue has increased dramatically over recent decades, with an estimated 390 million infections annually, of which approximately 96 million manifest clinically. [4] Approximately 3.9 billion people living in 129 countries are at risk of infection, with the highest burden in the WHO South-East Asia and Western Pacific regions. [5] The disease presents along a clinical spectrum ranging from undifferentiated febrile illness through classic dengue fever to the severe and potentially fatal manifestations of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). [6]

Understanding the triphasic clinical course—febrile, critical, and recovery phases—is essential for appropriate management, as the timing of clinical deterioration around defervescence represents the critical window for intervention. [7] The phenomenon of antibody-dependent enhancement (ADE) explains why secondary heterotypic infection carries significantly higher risk of severe disease, a concept with profound implications for both clinical management and vaccine development. [8]

Key Clinical Facts

Clinical Pearls

Clinical Pearl: The Defervescence Danger: The most critical period occurs when fever subsides (typically days 3-7). This is when plasma leakage peaks and shock can develop rapidly. Paradoxically, patients may feel temporarily better as fever breaks, leading to false reassurance.

Clinical Pearl: The ADE Paradox: Patients experiencing their second dengue infection with a different serotype face 15-80× increased risk of severe dengue. Pre-existing non-neutralising antibodies enhance viral entry into Fc receptor-bearing cells, leading to higher viral loads and more intense cytokine release. [8]

Clinical Pearl: NSAID Prohibition: Aspirin, ibuprofen, and other NSAIDs are strictly contraindicated due to antiplatelet effects and gastric erosion risk in thrombocytopenic patients. Paracetamol is the only acceptable antipyretic. This is a common exam question and clinical safety point.

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The "Arbovirus Triad" Differential

The three mosquito-borne viruses that mimic each other clinically.

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The "Malaria vs Dengue" Diagnostic Dilemma

In endemic areas, both must be considered—and may coexist.

Clinical Pearl: Co-infection Alert: In hyperendemic regions, dengue-malaria co-infection occurs in 5-7% of febrile patients. Always test for both in appropriate epidemiological settings. [9]

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Epidemiology

Global Burden

Dengue has emerged as the most rapidly spreading vector-borne viral disease, with a 30-fold increase in global incidence over the past 50 years. [1]

Geographic Distribution

Hyperendemic Regions (all 4 serotypes circulating):

• Southeast Asia: Thailand, Vietnam, Philippines, Indonesia, Malaysia, Singapore
• South Asia: India, Bangladesh, Sri Lanka, Pakistan
• Central/South America: Brazil, Mexico, Colombia, Venezuela, Honduras
• Caribbean: Puerto Rico, Dominican Republic, Jamaica

Expanding Frontiers:

• Europe: Autochthonous transmission now documented in France (Côte d'Azur), Italy, Spain, Croatia [10]
• United States: Florida, Texas, Hawaii with increasing local transmission
• Australia: Northern Queensland with periodic outbreaks
• Africa: Underreported but increasing recognition in East Africa

The Climate Change Factor

Evidence Debate: Climate-Driven Expansion: The WHO projects that climate change will put an additional 2 billion people at risk by 2080. [5] Key mechanisms include:

1. Vector range expansion: Aedes aegypti survives in warming temperate climates
2. Extended transmission seasons: Longer warm periods increase vectorial capacity
3. Urbanisation synergy: Urban heat islands extend mosquito breeding periods
4. Altitude expansion: Dengue now reaches previously protected highland areas

The 2023-2024 global surge, with record cases reported across the Americas, South Asia, and Europe, demonstrates this epidemiological transition. [10]

Vector Biology: Aedes aegypti — The Urban Predator

Clinical Pearl: Why Bed Nets Are Less Effective: Unlike malaria mosquitoes (Anopheles) that bite at night, Aedes species bite predominantly during daylight hours. Bed nets only protect during daytime naps. Insecticide-treated clothing and DEET-based repellents are more effective prevention strategies.

Demographics and Risk Factors

Host Risk Factors for Severe Disease:

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Virology and Pathophysiology

The Dengue Virus

DENV belongs to the genus Flavivirus, family Flaviviridae, alongside yellow fever, Zika, Japanese encephalitis, and West Nile viruses. [2]

Viral Structure:

• Genome: Single-stranded positive-sense RNA (~11kb)
• Structural proteins: Capsid (C), Pre-membrane/Membrane (prM/M), Envelope (E)
• Non-structural proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5
• Serotypes: DENV-1, DENV-2, DENV-3, DENV-4 (40-60% amino acid sequence homology)

Exam Detail: The NS1 Protein — A Key Pathogenic Driver: NS1 is a 46-50 kDa glycoprotein essential for viral replication and immune evasion. [11]

Functions:

1. Intracellular: Required for viral RNA replication complex formation
2. Cell surface: Target for antibody-dependent cell-mediated cytotoxicity
3. Secreted (sNS1): Directly damages endothelial glycocalyx, triggering plasma leakage

Clinical Utility:

• NS1 antigen ELISA: Sensitivity 80-97% (days 1-7), specificity > 99%
• Detectable before antibody response develops
• Correlates with viraemia levels and disease severity

Transmission Cycle

Infected Human → Aedes Mosquito (blood meal) → 8-12 day extrinsic incubation
→ Infected Mosquito → Uninfected Human (bite) → 4-10 day intrinsic incubation
→ Viraemia (5-7 days) → Symptomatic Illness

Transmission Modes:

• Vector-borne (primary): Aedes aegypti (urban), Aedes albopictus (periurban/rural)
• Vertical: Mother-to-infant (rare but documented)
• Blood transfusion/needle-stick: Case reports in endemic areas
• Sexual transmission: Not documented (unlike Zika)

Antibody-Dependent Enhancement (ADE)

Exam Detail: The Immunological Paradox of Dengue

ADE represents a paradigm-shifting concept explaining why secondary heterotypic dengue infection carries dramatically increased risk of severe disease. [8]

Mechanism:

1. Primary infection: Generates serotype-specific neutralising antibodies (lifelong homotypic immunity) plus cross-reactive non-neutralising antibodies against other serotypes
2. Secondary heterotypic infection: Pre-existing cross-reactive antibodies bind to the new serotype but fail to neutralise
3. Enhanced uptake: Antibody-opsonised virus is actively phagocytosed via Fcγ receptors on monocytes and macrophages
4. "Trojan Horse" effect: Enhanced viral replication within target cells creates "viral factories"
5. Cytokine storm: Massive viral load triggers exaggerated inflammatory response

Clinical Correlates:

• Secondary infections: 2-7× higher viraemia levels
• Secondary infections: 15-80× increased severe dengue risk
• Peak severe disease risk: 6 months to 5 years after primary infection
• Third/fourth infections: Generally mild (broad cross-protection)

Vaccine Implications: The Dengvaxia controversy demonstrated ADE's clinical significance: seronegative children who received vaccine then encountered natural infection experienced higher rates of severe dengue than unvaccinated controls. [12]

The Cytokine Storm and Plasma Leakage

Key Inflammatory Mediators:

Endothelial Glycocalyx Disruption:

The endothelial glycocalyx is a 0.5-3μm layer of proteoglycans and glycosaminoglycans lining blood vessel lumens. [11]

1. sNS1 protein directly damages glycocalyx via TLR4 activation
2. Glycocalyx shedding releases syndecan-1, heparan sulphate (measurable biomarkers)
3. Increased permeability allows plasma proteins and fluid to extravasate
4. Clinical manifestations: Pleural effusion (right > left), ascites, gallbladder wall oedema, haemoconcentration

Coagulopathy Mechanisms

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Clinical Phases of Dengue Infection

The Triphasic Model

Understanding the three phases is fundamental to dengue management. [6,7]

Phase 1: Febrile Phase (Days 1-3)

Clinical Features:

• Fever: Sudden onset, high (39-40°C), continuous or biphasic
• Severe headache: Characteristically retro-orbital (pain behind eyes)
• Myalgia: Intense muscle pain ("breakbone fever" etymology)
• Arthralgia: Joint pain, less prominent than in chikungunya
• Nausea and vomiting: Common, contributes to dehydration
• Facial flushing: Early cutaneous manifestation
• Skin erythema: Diffuse in first 24-48 hours

Laboratory Findings:

• Progressive leucopenia (WBC nadir days 2-4)
• Early thrombocytopenia
• Mildly elevated transaminases
• Positive NS1 antigen (sensitivity highest days 1-3)

Phase 2: Critical Phase (Days 3-7)

⚠️ Red Flag: The Critical Phase Begins at Defervescence

The dangerous paradox: patients often feel subjectively better as fever breaks, but this is precisely when plasma leakage peaks and shock may develop within hours.

Pathophysiological Events:

• Plasma leakage duration: 24-48 hours
• Maximum haematocrit rise: 6-24 hours after fever subsides
• Third-spacing: Pleural cavity (right > left), peritoneal cavity, pericardium

Warning Signs Predicting Severe Dengue:

Severe Dengue Manifestations:

Dengue Shock Syndrome (DSS)

DSS represents the most severe manifestation of dengue, occurring in 1-5% of hospitalised cases. [6]

Compensated Shock:

• Tachycardia disproportionate to fever
• Cool, mottled extremities
• Delayed capillary refill (> 2 seconds)
• Narrow pulse pressure (e.g., 100/85 mmHg = 15mmHg)
• Restlessness or agitation
• Reduced urine output

Decompensated (Hypotensive) Shock:

• Systolic BP less than 90mmHg (adults) or less than 5th percentile for age (children)
• Undetectable pulse pressure
• Weak or absent peripheral pulses
• Cold, clammy skin
• Profound lethargy or unconsciousness
• Anuria

Clinical Pearl: Pulse Pressure as the Early Warning Sentinel: In dengue shock, pulse pressure narrows BEFORE systolic BP falls. A BP of 100/90 mmHg (pulse pressure 10mmHg) in a febrile patient should trigger immediate concern—this is NOT a "normal" blood pressure.

Phase 3: Recovery Phase (Days 7-10)

Clinical Features:

• Fluid reabsorption: Over 48-72 hours, extravasated plasma returns to intravascular space
• Diuresis: Marked increase in urine output
• Resolution of fluid collections: Ascites, pleural effusions reabsorb
• Return of appetite: Often dramatic improvement
• Recovery rash: Pruritic, confluent erythema with "islands of white in a sea of red"
• Sinus bradycardia: Common, benign, self-limiting
• Platelet recovery: Rebound thrombocytosis may occur

Dangers in the Recovery Phase:

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Clinical Presentation

Symptoms

Cardinal Symptoms:

Signs

General Examination:

• Fever (core temperature 39-40°C)
• Facial flushing (early)
• Conjunctival injection (mild)
• Cervical lymphadenopathy

The Dengue Rash:

Abdominal Examination:

• Hepatomegaly (common in severe dengue)
• Right upper quadrant tenderness (hepatic capsule distension)
• Ascites (shifting dullness in critical phase)

Cardiovascular Examination:

• Tachycardia (early)
• Narrow pulse pressure (ominous sign)
• Hypotension (late, decompensated shock)
• Muffled heart sounds (pericardial effusion, rare)

Haemorrhagic Manifestations:

The Tourniquet Test

A bedside test for capillary fragility

Technique:

1. Inflate BP cuff to midpoint between systolic and diastolic pressure
2. Maintain inflation for 5 minutes
3. Deflate and wait 1 minute for skin colour to return
4. Count petechiae in a 2.5cm × 2.5cm (1 inch²) area at the antecubital fossa

Interpretation:

• Positive: ≥10 petechiae per square inch (≥20 by WHO criteria)
• Sensitivity: 40-50% (poor)
• Specificity: 70-80% (moderate)
• Clinical utility: Useful in resource-limited settings; negative test does not exclude dengue

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Investigations

First-Line Investigations

Dengue-Specific Diagnostic Tests

Diagnostic Algorithm:

Days 1-5: NS1 antigen ± RT-PCR (if available)
   ↓
NS1 positive → Confirmed dengue
NS1 negative, clinical suspicion high → Repeat day 3-5 or add IgM
   ↓
Day 5 onwards: IgM serology
   ↓
IgM positive, IgG low → Primary infection
IgM positive, IgG high (or early IgG rise) → Secondary infection

Exam Detail: Primary vs Secondary Infection Distinction:

The Haematocrit — The "Leakingometer"

Haematocrit monitoring is the cornerstone of dengue fluid management. [7]

Interpretation:

Monitoring Frequency:

• Dengue without warning signs: Daily
• Dengue with warning signs: Every 4-6 hours
• Severe dengue / DSS: Every 1-2 hours during resuscitation

Imaging

Chest X-Ray:

• Pleural effusion (right > left, bilateral in severe cases)
• Cardiomegaly (if fluid overload)
• Pulmonary oedema (over-resuscitation or recovery phase overload)

Abdominal Ultrasound:

• Ascites (early detection before clinical signs)
• Gallbladder wall oedema (> 3mm thickness, "striped" appearance)
• Hepatomegaly
• Pleural effusions (bilateral small effusions)
• Pericardial effusion (rare)

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Classification and Staging

WHO 2009 Revised Classification

The 2009 WHO classification replaced the previous DHF/DSS system with a simpler, more clinically applicable framework. [6]

Warning Signs Checklist

Any warning sign present → Admit for observation and IV fluids

Severe Dengue Criteria

1. Severe Plasma Leakage:

• Shock: SBP less than 90mmHg or MAP less than 65mmHg or pulse pressure less than 20mmHg
• Fluid accumulation with respiratory distress

2. Severe Bleeding:

• Clinically significant: Requiring transfusion or causing haemodynamic instability

3. Severe Organ Involvement:

• Liver: AST or ALT ≥1000 U/L
• CNS: Impaired consciousness, encephalopathy
• Heart: Myocarditis, impaired function
• Other: Any organ failure

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Management

General Principles

1. No specific antiviral therapy exists — Management is entirely supportive
2. Recognise warning signs early — The critical window for intervention is narrow
3. Judicious fluid management — The balance between under- and over-resuscitation determines outcomes
4. Avoid harmful interventions — NSAIDs, unnecessary IV fluids, intramuscular injections
5. Close monitoring — Frequent clinical assessment and haematocrit monitoring

Group A: Outpatient Management (No Warning Signs)

Criteria for Outpatient Care:

• No warning signs
• Able to tolerate oral fluids
• Adequate urine output (≥0.5mL/kg/hr or 4-6 wet nappies/day in children)
• No comorbidities
• Reliable daily review possible

Management:

AVOID:

• ❌ NSAIDs (aspirin, ibuprofen, diclofenac) — Bleeding risk
• ❌ Antibiotics (unless bacterial coinfection confirmed)
• ❌ Steroids (no evidence of benefit)
• ❌ Intramuscular injections (haematoma risk)

Group B: Inpatient Management (Warning Signs)

Criteria for Admission:

• Any warning sign present
• Unable to tolerate oral fluids
• Significant comorbidity (diabetes, renal disease, cardiac disease, pregnancy)
• Social circumstances preventing daily review
• HCT rising or platelets falling rapidly

Fluid Therapy Protocol:

Exam Detail: The WHO Step-Down Fluid Protocol [7]

Principles:

1. Goal: Maintain circulation, NOT normalise haematocrit
2. Fluid type: Isotonic crystalloid (0.9% saline or Ringer's lactate)
3. Avoid: Dextrose-containing solutions, hypotonic fluids
4. Duration: Typically 24-48 hours; stop once clinically stable and HCT stabilising

Initiation (Adults):

1. Start at 5-7 mL/kg/hour for 1-2 hours
2. Reassess: Vital signs, capillary refill, urine output, HCT

Stepwise Reduction:

Target Endpoints:

• Stable vital signs (pulse less than 100, BP adequate, pulse pressure > 20mmHg)
• Warm peripheries, capillary refill less than 2 seconds
• Urine output ≥0.5 mL/kg/hour
• Improving clinical status (appetite, energy)

Duration: Most patients require IV fluids for 24-48 hours during critical phase

Monitoring Schedule:

Group C: Severe Dengue / ICU Management

Indications for ICU Admission:

• Dengue shock syndrome (compensated or decompensated)
• Severe haemorrhage requiring transfusion
• Respiratory distress from fluid accumulation
• Severe organ impairment (liver, CNS, cardiac)
• Failure to respond to standard fluid resuscitation

Shock Resuscitation Protocol:

Exam Detail: Dengue Shock Resuscitation Algorithm [7,13]

Compensated Shock (Pulse Pressure less than 20mmHg, Perfusion Impaired):

1. IV crystalloid bolus: 10-20 mL/kg over 1 hour
2. Reassess every 15-30 minutes
3. If improving: Reduce to 7-10 mL/kg/hr, then stepwise reduction
4. If not improving: Second bolus 10-20 mL/kg over 1 hour

Decompensated Shock (Hypotension):

1. IV crystalloid bolus: 20 mL/kg over 15-30 minutes
2. If still shocked: Second bolus 20 mL/kg
3. If still shocked after 2 boluses:
   • Check haematocrit urgently
   • HCT high (> 45%): Continue crystalloid OR consider colloid (controversial)
   • HCT low or falling with instability: Suspect internal bleeding → Blood transfusion 10 mL/kg

Colloid Use (Controversial):

• Consider if unresponsive to 40-60 mL/kg crystalloid
• Options: 6% Dextran 70, Gelatin solutions
• Avoid HES (hydroxyethyl starch) — Renal toxicity concerns
• Limited evidence of benefit over crystalloids [14]

Monitoring in ICU:

• Arterial line for continuous BP monitoring
• Central venous access (consider CVP monitoring)
• Urinary catheter for hourly output
• Serial blood gases (lactate as perfusion marker)
• Continuous ECG monitoring

Blood Product Transfusion

Platelet Transfusion:

Clinical Pearl: The Platelet Paradox: Prophylactic platelet transfusions in non-bleeding dengue patients have NOT been shown to reduce bleeding risk or improve outcomes. [15] In fact, they may trigger inflammatory responses and theoretically worsen capillary leak. Reserve platelets for active bleeding or invasive procedures.

Packed Red Blood Cells:

• Indicated for clinically significant bleeding
• Target: Maintain haemoglobin > 7-8 g/dL (higher targets for cardiac comorbidity)
• Transfuse 10 mL/kg; reassess after each unit

Fresh Frozen Plasma:

• Consider if PT/INR significantly prolonged with active bleeding
• Typical dose: 10-15 mL/kg

Avoiding Complications: The Fluid Balance Challenge

Signs of Fluid Overload:

• Respiratory distress (tachypnoea, desaturation)
• Facial puffiness, peripheral oedema
• Rising JVP
• Hepatomegaly progression
• Worsening pleural effusions despite recovery phase

Management of Fluid Overload:

• Stop IV fluids immediately
• Sit patient upright
• Supplemental oxygen
• Diuretics (furosemide 0.5-1 mg/kg IV) — Use cautiously, may precipitate shock if still in leakage phase

Discharge Criteria

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Special Populations

Pregnancy and Dengue

Dengue in pregnancy carries risks for both mother and fetus. [16]

Maternal Risks:

• Increased severe dengue risk (altered immunity)
• Haemorrhage risk during labour if thrombocytopenic
• Difficult fluid balance management

Fetal/Neonatal Risks:

• Vertical transmission (rare, but documented)
• Neonatal dengue if infected near delivery
• Preterm labour
• Low birth weight

Management Considerations:

• Avoid NSAIDs (teratogenic, premature ductus arteriosus closure)
• Careful fluid balance (physiological fluid overload in pregnancy)
• Coordinate with obstetric team
• Timing of delivery: Avoid during critical phase if possible
• Platelet transfusion thresholds may be higher pre-delivery

Paediatric Considerations

Key Differences from Adults:

• More likely to have asymptomatic or undifferentiated febrile illness
• Compensated shock may be maintained longer (higher sympathetic tone)
• Decompensation is rapid and catastrophic
• Cold extremities and prolonged CRT are early shock signs
• Hepatomegaly more prominent
• Febrile convulsions common with rapid fever onset

Fluid Calculations:

• Use ideal body weight for obese children
• Holliday-Segar formula for maintenance:
  • First 10 kg: 100 mL/kg/day
  • 10-20 kg: 1000 mL + 50 mL/kg/day for each kg above 10

  • 20 kg: 1500 mL + 20 mL/kg/day for each kg above 20

Elderly and Comorbid Patients

Challenges:

• Atypical presentations (less fever, more confusion)
• Multiple comorbidities complicating fluid management
• Cardiac disease limits fluid resuscitation
• Polypharmacy (anticoagulants, NSAIDs increase bleeding risk)
• Higher mortality in severe disease

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Complications

Severe Dengue Complications

Long-Term Sequelae

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Prevention

Personal Protective Measures

Environmental Control

Biological Control: The Wolbachia Strategy

Evidence Debate: Wolbachia-mediated Dengue Control

Wolbachia pipientis is an intracellular bacterium that, when introduced into Aedes aegypti, blocks dengue virus replication within the mosquito. [17]

Mechanism:

• Competes for cellular resources needed for viral replication
• Primes innate immune responses in the mosquito
• Induces cytoplasmic incompatibility (spreads through population)

Evidence: The AWED cluster-randomised trial in Yogyakarta, Indonesia demonstrated:

• 77% reduction in virologically confirmed dengue (OR 0.23, 95% CI 0.15-0.35)
• 86% reduction in dengue hospitalisations
• Sustained population replacement at 2-year follow-up

Current Deployment: Active programs in Indonesia, Brazil, Colombia, Australia, and expanding globally through the World Mosquito Program.

Vaccines

Evidence Debate: The Dengvaxia Controversy (2016-2017)

In 2017, post-licensure surveillance in the Philippines revealed that seronegative children who received Dengvaxia had higher rates of severe dengue upon subsequent natural infection compared to unvaccinated controls—a manifestation of vaccine-induced ADE. [12]

This led to:

• Programme suspension in the Philippines
• Criminal charges against health officials
• WHO recommendation restricting use to confirmed seropositives only
• Development of pre-vaccination screening strategies

The controversy highlighted the unique challenge of dengue vaccinology: a vaccine must provide balanced protection against all four serotypes simultaneously to avoid mimicking natural ADE.

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Prognosis

Outcomes

Prognostic Factors

Poor Prognosis:

• Secondary heterotypic infection
• Delayed presentation (beyond day 3 of critical phase)
• Inadequate fluid resuscitation
• Comorbidities (diabetes, cardiac disease, obesity)
• Extremes of age
• DENV-2 or DENV-3 infection

Good Prognosis:

• Primary infection
• Early recognition of warning signs
• Timely, appropriate fluid management
• Young, healthy adults

Post-Recovery Immunity

• Lifelong homotypic immunity: Complete protection against same serotype
• Transient heterotypic immunity: 2-3 months cross-protection against other serotypes
• Subsequent infections: Generally milder after third/fourth infections (broad cross-protection)

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Notification and Public Health

Dengue is a notifiable disease in most jurisdictions, including:

• United Kingdom (Public Health England/UKHSA)
• Australia (National Notifiable Diseases Surveillance System)
• United States (CDC ArboNET)
• WHO IHR reportable in outbreak situations

Notification triggers:

• Confirmed case (laboratory evidence)
• Probable case (clinical syndrome + epidemiological link in outbreak)

Public Health Response:

• Case investigation and contact tracing
• Vector surveillance and control measures
• Travel-related case monitoring
• Outbreak investigation and response

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Exam-Focused Content

Common Examination Questions

1. "Describe the phases of dengue infection and their clinical significance"
2. "What are the warning signs of severe dengue?"
3. "Explain the mechanism of antibody-dependent enhancement"
4. "How would you manage a patient with dengue shock syndrome?"
5. "What are the criteria for platelet transfusion in dengue?"
6. "Differentiate between dengue, chikungunya, and Zika clinically"

Viva Points

Viva Point: Opening Statement: "Dengue fever is an acute mosquito-borne viral infection caused by the dengue virus, a flavivirus with four serotypes transmitted primarily by Aedes aegypti. It is the most common arboviral infection globally, with 390 million infections annually. The clinical spectrum ranges from asymptomatic infection to severe dengue, characterised by plasma leakage, haemorrhage, and organ dysfunction."

Key Facts to Cite:

1. "The critical phase occurs around defervescence, typically days 3-7"
2. "Secondary heterotypic infection increases severe dengue risk 15-80-fold through antibody-dependent enhancement"
3. "Fluid management is titrated to haematocrit—a rising HCT indicates plasma leakage requiring increased fluids; a falling HCT with instability suggests bleeding"
4. "Platelet transfusion is NOT routinely indicated in the absence of bleeding"

Common Mistakes in Examinations

❌ Mistakes that fail candidates:

• Recommending NSAIDs for fever
• Suggesting aggressive IV fluids throughout illness (→ fluid overload in recovery)
• Missing warning signs as indication for admission
• Transfusing platelets prophylactically without bleeding
• Confusing primary and secondary infection risks

✅ What examiners want to hear:

• Recognition of the triphasic clinical course
• Understanding of ADE and secondary infection risk
• Knowledge of WHO classification (2009)
• Rational approach to fluid management
• Appropriate haematocrit-guided resuscitation

Model Answer

Q: A 32-year-old returns from Thailand with fever, headache, and myalgia for 3 days. Today she is afebrile but has abdominal pain. How would you assess and manage her?

A: "This patient with recent travel to a dengue-endemic area presenting with classic features of dengue fever—fever, headache, severe myalgia—is now in the critical phase, as indicated by defervescence with new abdominal pain, which is a warning sign.

My assessment would include:

• Clinical: Vital signs including pulse pressure, peripheral perfusion, capillary refill, hydration status, signs of fluid accumulation (ascites, pleural effusion), hepatomegaly, any bleeding
• Laboratory: FBC (expect thrombocytopenia, leucopenia), haematocrit (baseline and trend), LFTs, U&E, coagulation screen
• Diagnostic: NS1 antigen (likely positive if within first week), dengue IgM/IgG

Given she has a warning sign (abdominal pain), she meets criteria for Group B (Dengue with Warning Signs) and requires hospital admission.

Management:

1. IV crystalloid at 5-7 mL/kg/hour initially, titrated to haematocrit response
2. Strict fluid balance with hourly urine output monitoring
3. Vital signs and HCT every 4-6 hours
4. Paracetamol only for fever (avoid NSAIDs)
5. Written warning signs for nursing staff to escalate

I would anticipate the critical phase lasting 24-48 hours, with transition to recovery marked by diuresis and improving appetite. At that point, IV fluids should be reduced or stopped to avoid fluid overload.

If she develops shock (narrow pulse pressure, cold peripheries), I would increase fluids to 10-20 mL/kg/hour and involve critical care early."

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Patient Information

What is Dengue Fever?

Dengue is a viral infection spread by mosquito bites, particularly the Aedes aegypti mosquito, which bites during the day. It is common in tropical and subtropical regions of Asia, Central and South America, Africa, and the Pacific Islands.

Symptoms

• Sudden high fever
• Severe headache, especially behind the eyes
• Intense muscle and joint pain ("breakbone fever")
• Nausea and vomiting
• Rash appearing after 3-4 days
• Mild bleeding (nose, gums)

When to Seek Urgent Medical Care

Warning signs—go to hospital immediately:

• Severe abdominal pain
• Persistent vomiting (3 or more times in 24 hours)
• Bleeding from gums, nose, or unusual bruising
• Blood in vomit or stools (black, tarry stools)
• Feeling extremely tired or restless
• Difficulty breathing
• Cold, clammy skin

Treatment

• Most cases recover at home with rest and fluids
• Take paracetamol for fever and pain
• DO NOT take aspirin, ibuprofen, or other anti-inflammatory medicines (increases bleeding risk)
• Drink plenty of fluids (water, oral rehydration solution, coconut water, fruit juice)
• Rest
• Return for daily check-ups until fever has been gone for 48 hours

Prevention

• Use insect repellent containing DEET (20-50%) on exposed skin
• Wear long sleeves and trousers, especially at dawn and late afternoon
• Stay in air-conditioned or well-screened accommodation
• Remove standing water around your home where mosquitoes breed (flower pots, containers, old tyres)
• Consider vaccination if recommended for your travel destination

Resources

• NHS - Dengue
• CDC - Dengue
• WHO - Dengue and Severe Dengue
• Travel Health Pro (UK)

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References

1. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-507. doi:10.1038/nature12060

2. Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016;2:16055. doi:10.1038/nrdp.2016.55

3. Messina JP, Brady OJ, Golding N, et al. The current and future global distribution and population at risk of dengue. Nat Microbiol. 2019;4(9):1508-1515. doi:10.1038/s41564-019-0476-8

4. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-507. doi:10.1038/nature12060

5. World Health Organization. Dengue and Severe Dengue Fact Sheet. WHO; 2024. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue

6. World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. WHO Press; 2009.

7. Simmons CP, Farrar JJ, Nguyen VV, Wills B. Dengue. N Engl J Med. 2012;366(15):1423-1432. doi:10.1056/NEJMra1110265

8. Katzelnick LC, Gresh L, Halloran ME, et al. Antibody-dependent enhancement of severe dengue disease in humans. Science. 2017;358(6365):929-932. doi:10.1126/science.aan6836

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