Q1 LONG ANSWER 10M ★ High-yield

Discuss the pathogenesis, clinical features, warning signs, investigations and management of dengue fever.

General Medicine · Final Professional

Aetiology

Dengue is caused by the dengue virus, a single-stranded RNA flavivirus with four serotypes (DENV 1–4), transmitted by the daytime-biting *Aedes aegypti* mosquito (and *Ae. albopictus*). It breeds in clean stagnant water in domestic containers — coolers, tyres, flower pots, overhead tanks — which is why dengue is an urban and peri-urban disease and why source reduction is the mainstay of control.

Infection with one serotype confers lifelong immunity to that serotype only, and short-lived cross-immunity to the others. India is hyperendemic, with all four serotypes circulating.

Pathogenesis of Severe Dengue

Two mechanisms explain why the second infection is often the dangerous one:

1. Antibody-dependent enhancement (ADE) — non-neutralising antibodies from a previous infection with a different serotype bind the new virus and facilitate its uptake into macrophages via Fc receptors, increasing viral load.

2. Cytokine storm — massive release of TNF-α, IL-6, IL-8 and VEGF causes endothelial dysfunction and increased capillary permeability, leading to plasma leakage into the pleural and peritoneal cavities — the central event in severe dengue.

Thrombocytopenia results from marrow suppression, immune-mediated destruction and platelet consumption; bleeding results from thrombocytopenia, platelet dysfunction, vasculopathy and coagulopathy.

CLINICAL PEARL

The killer in dengue is PLASMA LEAKAGE, not bleeding or the platelet count. Deaths occur from hypovolaemic shock due to capillary leak, and are almost entirely preventable with careful fluid management. A patient with a platelet count of 10 000 who is well perfused is far safer than one with a count of 60 000 who is leaking and shocked. Fixating on the platelet count — and transfusing platelets rather than assessing perfusion — is the commonest and most dangerous error in dengue management.

Clinical Course — Three Phases

Phase	Timing	Features
Febrile	Days 1–3	Sudden high fever, severe headache, RETRO-ORBITAL PAIN, severe myalgia and arthralgia ("breakbone fever"), flushed face, macular rash, nausea, vomiting. Positive tourniquet test
Critical	Days 3–7, as the fever SETTLES	The dangerous phase. Defervescence coincides with plasma leakage — this is when shock, effusions and severe bleeding occur. Warning signs appear here. Lasts 24–48 hours
Recovery	Days 7–10	Reabsorption of extravasated fluid — risk of fluid overload and pulmonary oedema if fluids are continued. Confluent "isles of white in a sea of red" rash with intense itching; bradycardia; profound fatigue

WHO Classification and Warning Signs

Dengue without warning signs — fever with two of: nausea/vomiting, rash, aches and pains, positive tourniquet test, leucopenia.

Dengue WITH warning signs — the signals that a patient is entering the critical phase and needs admission:

Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation — ascites, pleural effusion
Mucosal bleeding
Lethargy or restlessness
Liver enlargement > 2 cm
Rising haematocrit with a rapidly falling platelet count

Severe dengue — any of:

1. Severe plasma leakage → shock (dengue shock syndrome) or respiratory distress from fluid accumulation

2. Severe bleeding

3. Severe organ involvement — AST/ALT ≥ 1000, impaired consciousness, myocarditis, renal failure

Dengue shock syndrome: rapid weak pulse, narrow pulse pressure (≤ 20 mmHg), cold clammy extremities, prolonged capillary refill, restlessness, oliguria. Note that blood pressure is maintained until late — narrowing of the pulse pressure precedes hypotension and is the earlier warning.

Investigations

Test	Useful when	Comment
NS1 antigen	Days 1–5 (early)	Detects viral antigen; the test of choice in the first few days
IgM ELISA (MAC-ELISA)	From day 5 onwards	Confirms recent infection; may cross-react with other flaviviruses
IgG	Rising titre; high early IgG suggests secondary infection	—
RT-PCR	Days 1–5	Serotyping; specialised laboratories
Haematocrit — serial, twice daily	The single most important monitoring test — a rise of ≥ 20% indicates significant plasma leakage	Falls with bleeding or after fluid replacement
Platelet count — serial	Falls in critical phase	Does NOT determine severity or the need for transfusion
CBC	Leucopenia is characteristic and early	Rising haematocrit with falling platelets is the classic pairing

Other: liver function (transaminases are usually raised — very high levels indicate severe disease), renal function and electrolytes, coagulation profile, chest X-ray (right lateral decubitus for pleural effusion) and ultrasound abdomen (ascites, gall bladder wall oedema — a sensitive early sign of leakage), ECG and echocardiography if myocarditis is suspected.

Management

The whole of management is careful fluid therapy guided by clinical perfusion and haematocrit.

Group A — dengue without warning signs, able to drink and pass urine: manage at home with oral fluids (ORS, coconut water, rice water, fruit juice — not plain water alone), paracetamol only, rest, and mosquito protection. Give clear written warning signs and review daily during the critical phase.

Group B — warning signs, or co-morbidity, or social circumstances: admit. Give isotonic crystalloid, titrated to maintain perfusion and urine output, with serial haematocrit and vital signs, reducing the rate as the patient improves.

Group C — severe dengue: manage in high-dependency or intensive care with rapid isotonic crystalloid boluses for shock, reassessment after each bolus, colloid for refractory shock, and blood transfusion for significant bleeding. Correct acidosis, calcium and glucose. Monitor haematocrit before and after each bolus — a falling haematocrit with continuing shock means bleeding, and requires blood, not more crystalloid.

Critical principles:

AVOID: aspirin, NSAIDs and intramuscular injections — they increase bleeding risk. Use paracetamol only.
Platelet transfusion is NOT indicated by the count alone — it is given only for active significant bleeding, or before an invasive procedure. Prophylactic transfusion at arbitrary thresholds is ineffective, wasteful and potentially harmful, yet remains widespread practice in India.
Stop or slow fluids in the recovery phase — continuing them causes pulmonary oedema, a well-recognised iatrogenic cause of death.
Monitor for expanded dengue syndrome — myocarditis, encephalitis, hepatitis, acute kidney injury, Guillain–Barré syndrome.

Prevention

Vector control is the mainstay: source reduction (weekly emptying and scrubbing of water containers, covering tanks, disposing of tyres and discarded containers), larvicides, space spraying during outbreaks, personal protection with repellents and full-sleeved clothing, and community participation — dengue control fails without it. Vaccines exist but their deployment is limited by serostatus-dependent efficacy.

NEEDS VERIFICATION

Fluid regimens (volumes and rates by weight and phase) and transfusion thresholds — confirm against the current National Guidelines for Clinical Management of Dengue Fever before printing figures.

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