Overview
Dengue Fever
The "Arbovirus Triad" Differential
The three mosquito-borne viruses that look alike.
| Feature | Dengue | Chikungunya | Zika |
|---|---|---|---|
| Fever | High / Sudden | High / Sudden | Mild / Low Grade |
| Joint Pain | Muscle/Bone pain ("Breakbone") | Severe Arthralgia (Crippling, Chronic) | Mild Joint Pain |
| Rash | Maculopapular (Day 4) | Maculopapular (Early) | Maculopapular (Prominent) |
| Conjunctivitis | Mild | Mild | Prominent (Non-purulent) |
| Complications | Shock / Bleeding | Chronic Arthritis | Microcephaly (Fetus) |
The "Malaria vs Dengue" Dilemma
Common things are common.
| Feature | Dengue | Malaria |
|---|---|---|
| Fever Pattern | Continuous / Saddleback | Periodic (Tertian/Quartan) |
| Rigors | Present | Classic (Shaking chills) |
| Splenomegaly | Mild | Prominent |
| Thrombocytopenia | Severe (<50) | Mild/Moderate |
| Diagnosis | NS1 Ag / PCR | Blood Film (Thick/Thin) |
Topic Overview
Summary
Dengue fever is a mosquito-borne viral infection caused by dengue virus (DENV serotypes 1-4), transmitted by Aedes aegypti mosquitoes. It is endemic in tropical/subtropical regions. It presents with high fever, severe headache, myalgia, arthralgia ("breakbone fever"), and rash. Most cases are self-limiting, but a subset progress to severe dengue (dengue haemorrhagic fever/dengue shock syndrome), characterised by plasma leakage, bleeding, and organ impairment. There is no specific antiviral; management is supportive with careful fluid management.
Key Facts
- Vector: Aedes aegypti mosquito (day-biting)
- Incubation: 4-10 days
- Classic triad: Fever + rash + leucopenia/thrombocytopenia
- Severe dengue: Plasma leakage, haemorrhage, organ impairment
- Treatment: Supportive; careful IV fluid management
- Secondary infection: Higher risk of severe disease
Clinical Pearls
Second dengue infection with a DIFFERENT serotype = higher risk of severe dengue (antibody-dependent enhancement)
Warning signs (days 3-7) predict progression to severe dengue — close monitoring essential
Avoid NSAIDs (bleeding risk) — use paracetamol only for fever
Why This Matters Clinically
Dengue is the most common arboviral infection globally. With increasing travel and climate change, cases are rising in non-endemic areas. Recognising warning signs early prevents deaths from severe dengue.
Visual Summary
Visual assets to be added:
- Dengue clinical phases diagram
- Warning signs checklist
- Dengue rash photos
- Fluid management algorithm
Image 1: "Dengue Phases Graph" - showing the relationship between Fever, Haematocrit (rising), and Platelets (falling) across the Febrile, Critical, and Recovery phases. Image 2: "The Rash" - Photograph of 'Islands of White in a Sea of Red' on a patient's limb. Image 3: "Tourniquet Test" - Illustration of the cuff application and petechiae counting square.
Epidemiology
Incidence
- 100-400 million infections/year globally
- 50% of world population at risk
- Increasing incidence and geographic spread
The Climate Change Factor
Dengue is moving North.
- Vector Expansion: Aedes mosquitoes survive in warmer winters.
- Europe: Autochthonous (local) transmission now seen in France, Italy, Spain.
- USA: Florida and Texas outbreaks.
- Prediction: 2 billion more people at risk by 2080.
Endemic Areas
- Southeast Asia
- Central/South America
- Caribbean
- Africa
- Pacific Islands
Demographics
- All ages
- Travellers returning from endemic areas
- Secondary infection = higher risk of severe disease
Transmission
- Aedes aegypti mosquito (main)
- Aedes albopictus
- Day-biting mosquitoes
- Urban areas
The Urban Predator (Aedes aegypti)
- Breeding: Clean, stagnant water (flower vases, tyres, coconut shells).
- Feeding: Disrupted feeder (bites multiple people for one blood meal -> high transmission).
- Range: Flies only 400m (focal outbreaks).
- Timing: Peak biting at dawn and dusk. This is why bed nets (night) are less effective unless for day naps.
Discussion: The "Wolbachia" Strategy
Biological Warfare against Mosquitoes.
- Concept: Wolbachia is a bacterium that naturally infects insects.
- Mechanism: When introduced into Aedes aegypti, it blocks the dengue virus from replicating within the mosquito.
- Deployment: Release Wolbachia-infected mosquitoes -> They breed -> Population replaced.
- Result: 77% reduction in dengue incidence in Yogyakarta trial (NEJM 2021).
The Vaccine Landscape
- Dengvaxia (CYD-TDV): Sanofi Pasteur.
- Controversy: If given to seronegative (naive) children, it acts like a first infection. When they catch natural dengue later, they get severe ADE (Severe Dengue).
- Rule: Only approved for those with prior confirmed infection (Seropositives).
- Qdenga (TAK-003): Takeda.
- New: Approved 2023. Live attenuated.
- Advantage: Safe for seronegatives? (Still under surveillance).
- Indication: Travellers and endemic populations >4 years.
Pathophysiology
Mechanism
- Mosquito bite inoculates virus
- Virus replicates in dendritic cells, macrophages
- Viraemia → systemic symptoms
- Immune response → cytokine release
- Plasma leakage (capillary leak)
- Thrombocytopenia, coagulopathy
Antibody-Dependent Enhancement (ADE)
The Trojan Horse Mechanism.
- Primary Infection: Generates lifelong immunity to THAT serotype (homotypic).
- Secondary Infection: Antibodies from the first infection bind to the NEW serotype but cannot neutralise it.
- Enhancement: These Antibody-Virus complexes are actively taken up by monocytes/macrophages via Fc receptors.
- Result: "Viral factories" -> Massive viral load -> Cytokine Storm.
The "Cytokine Tsunami" (NS1 Protein)
- NS1 Antigen: A viral protein that directly damages the endothelial glycocalyx (the vessel lining).
- Leakage: Causes massive plasma extravasation (Pleural effusions, Ascites).
- Coagulopathy: Consumptive thrombocytopenia + Liver damage.
Phases of Illness
| Phase | Timing | Features |
|---|---|---|
| Febrile | Days 1-3 | High fever, myalgia, headache |
| Critical | Days 3-7 (defervescence) | Plasma leakage, warning signs |
| Recovery | Days 7-10 | Fluid reabsorption, rash |
Clinical Presentation
Symptoms
The Enigmatic Rash("Islands of White")
Signs
Warning Signs (Predict Severe Dengue)
| Warning Sign | Notes |
|---|---|
| Abdominal pain | Tender |
| Persistent vomiting | |
| Clinical fluid accumulation | Ascites, pleural effusion |
| Mucosal bleeding | Gums, nose |
| Lethargy, restlessness | |
| Hepatomegaly over 2cm | |
| Rising HCT with falling platelets | Plasma leakage |
Severe Dengue
| Feature | Description |
|---|---|
| Dengue Shock Syndrome | Plasma leakage → shock |
| Severe bleeding | GI, vaginal |
| Organ impairment | Liver (AST/ALT over 1000), encephalopathy |
Paediatric Spectrum (Kids are Different)
High fever (40°C) — sudden onset
Common presentation.
Severe headache (retro-orbital pain)
Common presentation.
Myalgia, arthralgia ("breakbone fever")
Common presentation.
Nausea, vomiting
Common presentation.
Rash (maculopapular, "islands of white in a sea of red")
Common presentation.
Clinical Examination
General
- High fever
- Rash
- Flushing
Skin
- Maculopapular rash
- Petechiae
- Tourniquet test positive (over 10 petechiae in 1 inch square)
How to: The Tourniquet Test
A bedside test for capillary fragility.
- Inflate: BP cuff to midway between Systolic and Diastolic pressure.
- Wait: Hold for 5 minutes.
- Release: Deflate and wait 1 minute for skin to return to normal colour.
- Count: Look at the antecubital fossa. Count petechiae in a 2.5cm (1 inch) square.
- Result: >10 petechiae = Positive (Suggests capillary fragility/thrombocytopenia).
- Validity: Low sensitivity (~50%), High specificity. Still useful in low-resource settings.
Abdominal
- Hepatomegaly
- Abdominal tenderness
- Ascites
Cardiovascular
- Tachycardia
- Hypotension (shock)
- Narrow pulse pressure (less than 20 mmHg)
Investigations
Blood Tests
| Test | Finding |
|---|---|
| FBC | Leucopenia, thrombocytopenia |
| Haematocrit | Rising HCT = plasma leakage |
| LFTs | Raised AST/ALT |
| Coagulation | Prolonged PT/APTT |
| U&E | Baseline |
The "Haematocrit" Logic
Why do we obsess over HCT?
- Pathophysiology: Plasma leaks OUT of vessels -> Red cells are left behind -> Blood becomes concentrated -> HCT rises.
- Significance: A rise of >20% above baseline is a critical warning sign of leakage.
- Drop in HCT:
- Good News: Reabsorption phase (Recovery).
- Bad News: Bleeding (if unstable).
Dengue-Specific Tests
| Test | Timing |
|---|---|
| NS1 antigen | Days 1-7 (early) |
| Dengue IgM | Day 5 onwards |
| Dengue IgG | Later; indicates past infection |
| PCR | Gold standard |
Imaging
- CXR: Pleural effusion
- USS: Ascites, gallbladder thickening
Classification & Staging
WHO Classification (2009)
| Category | Features |
|---|---|
| Dengue without warning signs | Fever + typical features |
| Dengue with warning signs | As above; close monitoring |
| Severe dengue | Shock, severe bleeding, organ impairment |
Management
General Principles
- No specific antiviral
- Supportive care
- Close monitoring for warning signs
- Careful fluid management
Outpatient (No Warning Signs)
- Oral rehydration
- Paracetamol for fever (avoid NSAIDs, aspirin)
- Daily review until afebrile 48h
- Return precautions for warning signs
Inpatient (Warning Signs or Severe)
The WHO "Group B" and "Group C" Protocol.
1. The Logic of Fluids
- Goal: Maintain perfusion, NOT normalise BP immediately.
- Risk: Fluid Overload (Pulmonary Oedema) is common and fatal in the recovery phase.
- Type: Crystalloid (0.9% Saline or Ringer's Lactate). Avoid Dextrose.
2. The Regime (Step-Down Protocol)
- Start: 5-7 ml/kg/hour for 1-2 hours.
- Re-assess: Vital signs + HCT (Haematocrit).
- Improved: Reduce to 3-5 ml/kg/hr for 2-4 hours.
- Stable: Reduce to 2-3 ml/kg/hr.
- Goal: STOP fluids within 48 hours of defervescence.
- Not Improved (Shock):
- Bolus 10-20 ml/kg over 15 mins.
- Consider Colloid if unresponsive (controversial).
- Check HCT:
- High HCT: Need more fluid (Leakage ongoing).
- Low HCT: BLEEDING (Internal haemorrhage) -> Transfuse Blood.
3. Monitoring Metrics
- Pulse Pressure: Narrowing (e.g., 100/90 = 10mmHg) is the EARLIEST sign of shock.
- Urine Output: Target 0.5 ml/kg/hr.
- HCT: The "Leakingometer".
Severe Dengue:
| Phase | Approach |
|---|---|
| Febrile | Oral/IV maintenance |
| Critical (plasma leakage) | IV crystalloid; start 5-7 mL/kg/hr; titrate to HCT and BP |
| Recovery (fluid reabsorption) | Reduce/stop IV fluids; avoid overload |
Monitoring:
- Vital signs hourly
- HCT every 4-6 hours
- Urine output
Severe Dengue:
- IV fluids, colloids if needed
- Blood transfusion if significant bleeding
- ICU for shock
Avoid
- NSAIDs, aspirin (bleeding risk)
- IM injections
- Excessive IV fluids (pulmonary oedema in recovery phase)
Medical Discharge Criteria
When is it safe to go home?
- Afebrile: For 48 hours (without antipyretics).
- Clinical Improvement: Appetite returned, visible rash (recovery rash).
- Platelets: Rising trend (usually >50).
- Haematocrit: Stable without IV fluids.
- No Respiratory Distress: (No pleural effusion).
Complications
Severe Dengue
- Dengue shock syndrome
- Severe haemorrhage
- Organ failure (liver, CNS)
- Death (0.1-2% of severe cases)
Other
- Myocarditis
- Encephalitis
- Post-infectious fatigue
Pregnancy & Dengue
A Double Risk.
- Maternal: Increased risk of severe bleeding during labour (if thrombocytopenic).
- Fetal: Risk of vertical transmission (neonatal dengue), preterm birth, low birth weight.
- Management: Conservative. Avoid delivery during critical phase if possible.
Occupational Health
- Risk: Lab workers handling samples.
- Needlestick: Standard protocol. No oscillation prophylaxis.
- Notification: Notifiable disease in many jurisdictions.
Historical Context
Why "Breakbone"?
- 1789: Benjamin Rush described "Bilious Remitting Fever" in Philadelphia.
- The Name: "Dengue" may come from Swahili "Ka-dinga pepo" (seizure caused by an evil spirit) or Spanish "Denguero" (fastidious - referring to gait).
- WWII: Massive spread due to troop movements in the Pacific.
Prognosis & Outcomes
Prognosis
- Most recover fully within 1-2 weeks
- Severe dengue mortality under 1% with treatment
- Up to 20% mortality if untreated severe disease
Post-Recovery
- Fatigue may persist weeks
- Lifelong immunity to same serotype (but not others)
Evidence & Guidelines
Key Guidelines
- WHO Guidelines for Dengue Prevention and Control
- PHE/UKHSA Dengue Guidelines
Key Evidence
- Careful fluid management reduces mortality in severe dengue
- Avoid NSAIDs
Evidence Base Summary
- Cochrane Review (2014): Colloids vs Crystalloids in Shock. No difference in mortality. Crystalloids (Saline/Ringers) are cheaper and safer (less allergic reactions).
- DENCO Study (2009): Defined the modern "Warning Signs" classification, replacing the old "DHF/DSS" system which was too rigid.
- Wolbachia Trials (2021): The gold standard for vector control evidence (77% efficacy).
Patient & Family Information
What is Dengue Fever?
Dengue is a viral infection spread by mosquito bites. It causes high fever, headache, and severe muscle and joint pain ("breakbone fever").
Symptoms
- Sudden high fever
- Severe headache
- Pain behind the eyes
- Muscle and joint pain
- Rash
Warning Signs (Seek Urgent Help)
- Severe abdominal pain
- Persistent vomiting
- Bleeding from gums or nose
- Feeling very tired or restless
Treatment
- Rest and fluids
- Paracetamol (avoid ibuprofen/aspirin)
- Hospital admission if severe
Prevention
Fight the Bite.
- DEET: 50% DEET repellent on exposed skin (safe in pregnancy and kids >2 months).
- Clothing: Long sleeves, trousers, permethrin-treated clothes.
- Habitat: Remove standing water (flower pots, tyres) where Aedes breed.
- Nets: Aedes bite in the DAY, but nets help for daytime naps (especially babies).
Travel Advice
- Risk Assessment: Check ongoing outbreaks (e.g., CDC/FitForTravel).
- Insurance: Ensure coverage for hospitalization (Dengue can mean 1 week in hospital).
- Vaccine: Consider Qdenga for long-term travellers to endemic zones.
Resources
References
Primary Guidelines
- WHO. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control. 2009.
Key Reviews
- Simmons CP, et al. Dengue. N Engl J Med. 2012;366(15):1423-1432. PMID: 22494122
- Wilder-Smith A, et al. Dengue. Lancet. 2019;393(10169):350-363. PMID: 30696575