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Dengue Fever - PSM Exam Oriented 15 Marker

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Introduction

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1. Causative Agent (Etiology)

• Virus: Dengue virus - a single-stranded RNA virus belonging to family Flaviviridae, genus Flavivirus
• Serotypes: 4 distinct serotypes - DEN-1, DEN-2, DEN-3, DEN-4
  • Immunity to one serotype does not protect against others
  • Secondary infection with a different serotype is associated with severe dengue (DHF/DSS) due to antibody-dependent enhancement (ADE)
• Recent emergence of a 5th serotype (DEN-5) has been reported

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2. Epidemiology (Problem Statement)

• Global burden: ~3.9 billion people in 128 countries are at risk
• 390 million dengue infections per year; 96 million manifest clinically
• Reported cases rose from <0.5 million in 2010 to 4.2 million in 2019
• ~500,000 DHF cases require hospitalization annually; 90% are children <5 years
• Case fatality rate: ~2.5% (can be reduced to <1% with proper management)
• India: Category A country (major public health problem); hyperendemic with all 4 serotypes; Delhi 1996 outbreak was landmark event
• Endemic regions: Tropical and subtropical countries; SE Asia and Western Pacific most severely affected

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3. The Dengue Syndrome (Clinical Classification)

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4. Host, Agent & Environment (Epidemiological Triad)

• All ages susceptible; children more severely affected
• Secondary heterologous infection - more severe (ADE theory)
• Immunocompromised - at higher risk

• Four serotypes; DEN-2 and DEN-3 associated with severe disease
• Simultaneous circulation of multiple serotypes (hyperendemicity) = worse outbreaks

• Urban and semi-urban areas with stagnant water
• Tropical/subtropical climate (temperature 16-40°C)
• Monsoon and post-monsoon season peak in India (July-November)
• Unplanned urbanization, poor sanitation, water storage in containers

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5. Mode of Transmission

• Vector: Aedes aegypti (primary); Aedes albopictus (secondary)
• Bite pattern: Day-biting mosquito (peak at dawn and dusk)
• Aedes aegypti breeds in clean, stagnant water in artificial containers (flower pots, coolers, tyres, overhead tanks)
• Transovarial transmission (vertical transmission in mosquito) maintains the virus between seasons
• No direct human-to-human transmission
• Rare routes: blood transfusion, organ transplant, needle-stick

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6. Incubation Period

• 3-14 days (usually 4-7 days)
• Intrinsic IP (in human): 3-14 days
• Extrinsic IP (in mosquito): 8-12 days

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7. Clinical Features

Phase 1 - Febrile Phase (Days 1-3)

• Sudden onset high fever (39-40°C), "saddleback" biphasic fever
• Severe headache, retroorbital pain
• Myalgia, arthralgia - "breakbone fever"
• Flushed face, injected conjunctiva
• Early rash (macular/maculopapular)
• Positive tourniquet test (Rumple-Leede test)

Phase 2 - Critical Phase (Days 4-6)

• Defervescence (fever comes down) - most dangerous period
• Plasma leakage - pleural effusion, ascites, hemoconcentration
• Rising haematocrit (>20% increase)
• Thrombocytopenia (platelets <100,000/mm³)
• If plasma leakage is severe: shock (DSS)
• Warning signs: abdominal pain, persistent vomiting, bleeding, liver enlargement, restlessness, rapid breathing

Phase 3 - Recovery Phase (Days 7-10)

• Reabsorption of leaked fluid
• Bradycardia, characteristic convalescent rash (white islands in sea of red)
• Risk of fluid overload if excess IV fluids given

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8. WHO 2009 Classification

• Abdominal pain/tenderness
• Persistent vomiting
• Clinical fluid accumulation
• Mucosal bleeding
• Lethargy/restlessness
• Liver enlargement >2 cm
• Platelets rapidly declining / rising haematocrit

• Severe plasma leakage with shock (DSS)
• Severe bleeding
• Severe organ impairment (liver, CNS, heart, kidneys)

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9. WHO Criteria for DHF (Classic 4 Criteria)

1. Fever - acute onset, high-grade, lasting 2-7 days
2. Haemorrhagic tendency - positive tourniquet test, petechiae, ecchymosis, epistaxis, gum bleeding, hematemesis
3. Thrombocytopenia - platelet count ≤100,000/mm³
4. Plasma leakage - haematocrit rise ≥20% above average, or drop ≥20% after treatment; pleural effusion, ascites, hypoproteinemia

• Grade I: Fever + positive tourniquet test
• Grade II: Grade I + spontaneous bleeding
• Grade III: Grade II + circulatory failure (DSS)
• Grade IV: Profound shock, undetectable BP/pulse (DSS)

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10. Laboratory Diagnosis

• Leucopenia (WBC <5,000/mm³)
• Thrombocytopenia
• Rising haematocrit (hemoconcentration)

• Suspected case: Acute febrile illness + ≥2 of: headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leukopenia
• Probable case: Suspected + positive IgM/IgG serology
• Confirmed case: Isolation of virus, or fourfold IgG rise, or detection of dengue genome by PCR, or detection of NS1 antigen

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11. Treatment (Management)

• Adequate rest, oral fluids (ORS, coconut water, juices)
• Paracetamol for fever (NO aspirin, ibuprofen, NSAIDs - risk of bleeding)
• Watch for warning signs

• IV fluid therapy - isotonic crystalloids (Normal saline / Ringer's lactate)
• Rate titrated to urine output (0.5-1 mL/kg/hr)
• Monitor HCT, platelet, BP

• Aggressive fluid resuscitation
• Blood transfusion for severe bleeding
• Platelet transfusion only if active bleeding + platelet <20,000

• Avoid: Aspirin, NSAIDs, steroids, antibiotics (unless bacterial co-infection), intramuscular injections
• Platelet transfusion is NOT recommended prophylactically

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12. Prevention and Control

A. Vector Control (Most Important)

• Remove/destroy artificial water containers (flower pots, used tyres, coolers)
• Cover overhead tanks
• Change water in flower vases weekly
• Drain/fill water collections around houses

• Gambusia fish (larvivorous) in ponds and tanks
• Bacillus thuringiensis israelensis (Bti) - biological larvicide

• Larviciding: Temephos (Abate) - 1 mg/L in drinking water containers; pyriproxyfen
• Adulticiding: Pyrethrum or malathion space spraying during outbreaks (ULV spraying)
• DDT has no effect (Aedes rests indoors on dark surfaces - DDT not effective)

• Insect repellents (DEET-based)
• Protective clothing (long-sleeved shirts, long pants)
• Mosquito nets (permethrin-treated)
• Window/door screens

B. Surveillance

• Disease surveillance: Case reporting, sentinel surveillance hospitals (521 identified in India)
• 14 Apex Referral Laboratories in India
• Entomological surveillance: Stegomyia (Breteau) index, Container index, House index

C. Vaccine

• Dengvaxia (CYD-TDV) - first approved dengue vaccine (Sanofi Pasteur)
  • Tetravalent live attenuated chimeric vaccine
  • Approved in several countries (Philippines, Brazil, etc.)
  • NOT recommended for seronegative individuals (increases risk of severe dengue in those with no prior exposure)
  • WHO position: Recommended only in settings where seroprevalence is >70% in target age group, or with pre-vaccination screening
• TAK-003 (Qdenga) - newer vaccine (Takeda); approved in several countries including EU (2022); currently under review for India

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13. National Programme (Government of India)

• Dengue is covered under National Vector Borne Disease Control Programme (NVBDCP)
• Mid-term plan (2011-2016) for prevention and control with components:
  1. Surveillance (disease + entomological)
  2. Case management
  3. Vector management
  4. Outbreak response
  5. Capacity building
  6. BCC (Behavioural Change Communication) / IEC
  7. Inter-sectoral coordination
  8. Monitoring and supervision
• IgM Capture ELISA kits provided free through National Institute of Virology (NIV), Pune
• NS1 antigen ELISA kits introduced for early diagnosis (detects from Day 1)
• Contingency grant provided to states during outbreaks

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14. Recent Advances (Important for Exams)

• WHO 2009 Classification replaced the older 1997 classification (DF/DHF/DSS)
• NS1 antigen test is the most important early diagnostic test
• Dengvaxia controversy (2017 Philippines scandal) - vaccine given to seronegative children caused severe dengue - reinforces need for pre-vaccination screening
• Wolbachia-infected Aedes aegypti release - emerging vector control strategy (blocks dengue virus replication in mosquito)

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Quick Summary (Memory Aid for Exams)

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