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Dengue - PSM Exam Oriented Notes

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1. AGENT FACTORS

• 4 serotypes: DEN-1, DEN-2, DEN-3, DEN-4 (all can cause DHF/DSS)
• Immunity to one serotype does NOT protect against others (no cross-immunity)
• Secondary infection with a different serotype → risk of DHF/DSS (antibody-dependent enhancement)

• First infection → cross-reactive non-neutralizing antibodies
• Second infection (different serotype) → antibody-dependent enhancement (ADE) → increased viral load → plasma leakage
• DENV-1 → DENV-2 sequence: 500-fold risk of DHF vs primary infection
• DENV-3 → DENV-2: 150-fold risk
• DENV-4 → DENV-2: 50-fold risk

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2. VECTOR FACTORS

• Day-biting mosquito (peak activity: early morning and late afternoon)
• Breeds in clean, stagnant water in and around houses (peridomestic)
• Breeds in: water storage containers, flower pots, discarded tyres, coolers, overhead tanks
• Does NOT breed in dirty/polluted water (unlike Culex)
• Eggs can survive desiccation for months
• Short flight range (~50-100 m)
• Predominantly urban; found below 1000 m altitude

• Base of pyramid: majority of cases are asymptomatic (subclinical)
• Middle: classical dengue fever (DF)
• Top: DHF → DSS (smallest proportion)

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3. HOST FACTORS

1. Infants and elderly
2. Obesity
3. Pregnancy
4. Peptic ulcer disease
5. Women in menstruation or with abnormal bleeding
6. Use of NSAIDs/aspirin/ibuprofen/corticosteroids

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4. ENVIRONMENTAL FACTORS

• Tropical and subtropical regions; urban and semi-urban areas
• Peridomestic water storage (key risk factor)
• Lack of sanitation, crowding
• Spreading to rural areas now
• Associated with rainy season

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5. CLINICAL MANIFESTATIONS

Dengue Syndrome Classification

Dengue Virus Infection
├── Asymptomatic (majority)
└── Symptomatic
    ├── Classical Dengue Fever (DF)
    ├── Dengue Haemorrhagic Fever (DHF) without shock
    └── Dengue Haemorrhagic Fever with shock (DSS)

A. Classical Dengue Fever

• Sudden onset: high fever (39-40°C), chills, severe headache, myalgia, arthralgia ("breakbone fever")
• Within 24 hours: retro-orbital pain (on eye movement/pressure), photophobia
• Biphasic fever curve (saddle-back pattern): fever → remission → second febrile phase
• Rash in 80% cases - appears during remission or 2nd febrile phase:
  • Early: diffuse flushing, mottling on face/neck/chest
  • 3rd-4th day: maculopapular or scarlatiniform rash (chest/trunk → extremities, rarely face)
  • May be followed by desquamation
• Extreme weakness, anorexia, altered taste, constipation
• Fever lasts ~5 days (rarely >7 days); recovery usually complete
• Case fatality: exceedingly low

B. Dengue Haemorrhagic Fever (DHF) - Three Phases

• High fever, flushing, erythema
• Myalgia, arthralgia, headache
• Mild haemorrhagic manifestations

• Plasma leakage → haemoconcentration, effusions
• Thrombocytopenia (platelets <100,000/cu.mm)
• Warning signs: abdominal pain, persistent vomiting, mucosal bleeding, lethargy, rapid breathing, liver enlargement >2 cm, rising haematocrit + rapid platelet fall

• Reabsorption of leaked fluids
• Risk of fluid overload → pulmonary oedema, CHF if excessive IV fluids given

C. Dengue Shock Syndrome (DSS) / Severe Dengue

• Pulse pressure ≤20 mmHg (in children) = compensated shock
• Signs of poor perfusion: cold extremities, delayed capillary refill, rapid pulse
• In adults: pulse pressure ≤20 mmHg indicates more severe shock

1. Plasma leakage → shock/fluid accumulation ± respiratory distress
2. Severe bleeding
3. Severe organ impairment (liver failure, encephalopathy, cardiomyopathy)

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6. CLINICAL DIAGNOSIS CRITERIA

Probable Dengue Fever

• Headache
• Retro-orbital pain
• Myalgia
• Arthralgia/bone pain
• Rash
• Haemorrhagic manifestation
• Leucopenia (WBC <5000/cu.mm)

DHF Criteria (ALL four must be present)

1. Fever - acute onset, high, 2-7 days, sometimes biphasic
2. Haemorrhagic tendencies - positive tourniquet test, petechiae/ecchymoses/purpura, bleeding from mucosa/GI/injection sites, or haematemesis/melaena
3. Thrombocytopenia - platelet count ≤100,000/cu.mm
4. Evidence of plasma leakage - haematocrit rise ≥20% above baseline, or ≥20% drop after treatment, OR signs of plasma leakage (pleural effusion, ascites, hypoproteinaemia)

Tourniquet Test (Rumpel-Leede test)

• Inflate BP cuff to midpoint between systolic and diastolic for 5 minutes
• Positive: >10-20 petechiae per 1 sq inch (2.5 cm²)
• Reflects capillary fragility

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7. GRADING OF DHF (WHO Classification)

• Grades I & II = DHF
• Grades III & IV = DSS (Dengue Shock Syndrome)

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8. LABORATORY DIAGNOSIS

1. Haematological: Serial platelet count + haematocrit (rise in Hct + fall in platelets = hallmark of DHF)
2. NS1 Antigen: Detectable from Day 1 up to Day 6 of illness; both primary and secondary infection; commercial kits available; does NOT differentiate serotypes
3. IgM (MAC-ELISA): Detectable after Day 5; indicates recent infection
4. IgG ELISA/HIA: Primary vs secondary infection (IgG rise in secondary)
5. RT-PCR: 1-2 days; detects and differentiates serotypes
6. Viral isolation: Mosquito/cell culture; takes ≥1 week

• Primary infection: high IgM, low IgG
• Secondary infection: low IgM, high IgG (IgG rises first)

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9. MANAGEMENT

Dengue Fever (DF) - Management

• Rest, oral fluids (oral rehydration)
• Paracetamol for fever (NEVER aspirin/NSAIDs - risk of bleeding + Reye's syndrome)
• Monitor for warning signs
• Outpatient management adequate

DHF Grades I & II - Management

• Oral rehydration; monitor haematocrit
• If cannot tolerate oral fluids → IV crystalloids (Normal saline or Ringer's lactate)
• Monitor platelet + haematocrit every 4-6 hours
• Volume replacement algorithm: Hct rising + clinical deterioration → increase IV rate; Hct falling + stable → decrease IV rate

DHF Grades III & IV (DSS) - Management

• Immediate IV fluid resuscitation - crystalloid 10-20 ml/kg/hour
• If no improvement → colloid (Dextran 40/haemaccel) or fresh whole blood (10-20 ml/kg/hour)
• Oxygen to all patients in shock
• Monitor ABCS: Acidosis, Bleeding, Calcium (Na⁺ & K⁺), Sugar

Platelet Transfusion Indications

• NOT given prophylactically even at <20,000/cu.mm
• Give at: <10,000/cu.mm prophylactically
• Prolonged shock with coagulopathy
• Systemic massive bleeding

Red Cell / Whole Blood Transfusion

• Blood loss ≥10% of total blood volume
• Refractory shock despite fluids with declining Hct
• 10 ml/kg at a time

Discharge Criteria

1. Afebrile for ≥24 hours (without antipyretics)
2. Return of appetite
3. Visible clinical improvement
4. Good urine output
5. Minimum 2-3 days after recovery from shock
6. No respiratory distress from effusions
7. Platelet count >50,000/cu.mm

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10. EPIDEMIOLOGY - GLOBAL & INDIA

• ~3.9 billion people in 128 countries at risk
• ~390 million infections/year; 96 million clinically manifest
• Cases rose from <0.5 million (2010) to 4.2 million (2019)
• 500,000 with DHF require hospitalization annually
• ~90% of DHF cases in children <5 years
• Case fatality: ~2.5% in DHF
• During epidemics: infection rate 40-90% among non-immune

• Hyperendemic: all 4 serotypes circulating
• Leading cause of hospitalization/death in children

• Dengue first major outbreak: Delhi, 1996
• 2015 Delhi: worst outbreak since 2006 (>15,000 cases)
• Highest burden states: Maharashtra, Kerala, Punjab, Karnataka

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11. CONTROL MEASURES

A. Mosquito/Vector Control

• Source reduction (removing breeding sites - most important)
• Covering water storage containers
• Biological control: Gambusia affinis (larvivorous fish), Bacillus thuringiensis israelensis (Bti)
• Chemical: Temephos (abate) - organophosphate larvicide
• Ovitrap surveillance to monitor vector density

• Space spraying with insecticides (malathion fogging)
• Pyrethroid-based indoor residual spraying

• Repellents, long sleeves/clothing
• Bed nets (though Aedes bites during day!)
• Wire mesh screens on windows

B. Vaccine - CYD-TDV (Dengvaxia)

• Developed by Sanofi Pasteur; approved December 2015
• Tetravalent, live-attenuated (chimeric yellow fever 17D backbone)
• Schedule: 3 injections of 0.5 ml subcutaneous; at 0, 6, 12 months
• WHO recommendation (2016): only for seropositive individuals (previously infected)
• Concern: Vaccinating seronegative individuals → acts like "first infection" → risk of severe dengue on subsequent natural infection

C. National Programme (India)

• 521 sentinel surveillance hospitals with laboratory support (endemic states)
• 14 Apex Referral Laboratories (backed by NIV Pune)
• IgM capture ELISA kits provided free of cost by National Institute of Virology (NIV), Pune
• NS1 ELISA kits: detect from Day 1; IgM ELISA: detect after Day 5

1. Surveillance - disease and entomological
2. Case management - lab diagnosis + clinical management
3. Vector management - environmental, chemical, personal protection, legislation
4. Outbreak response - epidemic preparedness, media
5. Capacity building - training, HR, operational research
6. BCC - IEC, social mobilization
7. Inter-sectoral coordination - Urban development, rural dev, panchayati raj, transport, education
8. Monitoring and supervision

• Reduce dengue mortality by ≥50% by 2020
• Reduce dengue morbidity by ≥25% by 2020
• Estimate true burden of disease by 2015

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12. KEY ONE-LINERS FOR MCQs

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13. WARNINGS SIGNS OF DENGUE (High-yield)

1. Abdominal pain or tenderness
2. Persistent vomiting
3. Clinical fluid accumulation (ascites, pleural effusion)
4. Mucosal bleed
5. Lethargy / restlessness
6. Liver enlargement >2 cm
7. Lab: rapid rise in Hct + concurrent rapid decrease in platelet count

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