Dengue Fever

Dengue is the commonest arboviral infection of humans and a perennial NEET PG favourite from Medicine and Microbiology. Master the WHO 2009 case classification, the diagnostic window for NS1 versus serology, the warning signs that herald plasma leakage, and the fluid-replacement protocol — these are the points examiners hammer year after year.

Definition & overview

Dengue is an acute systemic, vector-borne viral illness caused by the dengue virus (DENV), a single-stranded positive-sense RNA Flavivirus (family Flaviviridae). There are four antigenically distinct serotypes — DENV-1, 2, 3, 4. Infection by one serotype confers lifelong homotypic immunity but only transient (months) cross-protection against the others; subsequent secondary infection by a heterotypic serotype is the classic setting for severe disease.

The principal vector is the female Aedes aegypti mosquito (a daytime feeder, breeds in clean stagnant water in/around homes), with Aedes albopictus as a secondary vector. The virus is also the cause of yellow fever's "cousin" diseases and shares a vector with chikungunya and Zika.

High-yield: Aedes aegypti is a day-biter (peak biting early morning and late afternoon) that breeds in clean, stagnant domestic water — the basis of source-reduction control. Contrast with Anopheles (malaria, night-biter, breeds in clean water) and Culex (filariasis/JE, night-biter, dirty water).

Pathophysiology — why secondary infection is dangerous

The hallmark of severe dengue is increased vascular permeability causing plasma leakage (not consumptive bleeding alone). Two interlinked mechanisms are tested:

1. Antibody-Dependent Enhancement (ADE): Pre-existing non-neutralising (sub-neutralising) antibodies from a prior infection bind the new heterotypic serotype and, via Fcγ receptors, enhance viral entry into monocytes/macrophages → higher viral load → exaggerated cytokine release.
2. Cytokine storm: Activated T cells and infected monocytes release TNF-α, IL-2, IL-6, IL-8, and notably the viral NS1 protein, which directly disrupts the endothelial glycocalyx → capillary leak, haemoconcentration, hypoproteinaemia, and serosal effusions (pleural effusion, ascites).

Thrombocytopenia results from bone-marrow suppression, immune-mediated platelet destruction, and platelet consumption. Coagulopathy (mild DIC) and capillary fragility together produce bleeding.

High-yield: The proximate cause of dengue shock is plasma leakage → hypovolaemia, not haemorrhage. This is why fluid resuscitation — not platelet transfusion — is the cornerstone of management.

Pathophysiology flow: Secondary heterotypic infection → ADE + cytokine storm (TNF-α, IL-6, NS1) → endothelial glycocalyx damage → plasma leakage → haemoconcentration + effusions → hypovolaemic shock (DSS).

Clinical features — the three phases

Dengue is classically biphasic/triphasic. Recognising the phases is examined directly.

Phase	Timing	Key features
Febrile	Day 1–3 (lasts 2–7 d)	Sudden high fever, severe retro-orbital pain, myalgia/arthralgia ("break-bone fever"), facial flushing, maculopapular rash, positive tourniquet test, mild haemorrhage
Critical	Day 3–7 (around defervescence)	Plasma leakage window (24–48 h); warning signs appear; risk of shock, effusions, bleeding; platelets fall, haematocrit rises
Recovery / Convalescent	Day 7–10 onward	Reabsorption of fluid, rising platelets, characteristic "isles of white in a sea of red" confluent rash; risk of fluid overload from over-transfusion

Classic febrile-phase signs: biphasic ("saddleback") fever, petechiae, the convalescent rash, and intense bone/joint pain. The tourniquet (Hess) test is positive when ≥10–20 petechiae appear in a 2.5 cm² (1-inch) square after the BP cuff is inflated to midway between systolic and diastolic for 5 minutes.

High-yield: Beware the paradox of defervescence — the patient is most at risk of shock when the fever settles (day 3–7), as this coincides with peak plasma leakage. Do not be falsely reassured by a falling temperature.

WHO 2009 classification (the one to memorise)

The older 1997 DF/DHF/DSS scheme is replaced for clinical use by the WHO 2009 revised classification, which is the most frequently tested framework.

Category	Criteria
Dengue without warning signs	Fever + ≥2 of: nausea/vomiting, rash, aches/pains, leukopenia, positive tourniquet test (± lab-confirmed dengue, with travel/residence in endemic area)
Dengue with warning signs	Above plus any warning sign (see mnemonic) — admit and observe
Severe dengue	Any of: (1) Severe plasma leakage → shock (DSS) or respiratory distress from effusion; (2) Severe bleeding; (3) Severe organ involvement — AST/ALT ≥1000, impaired consciousness, myocarditis, hepatitis

Warning signs — mnemonic "ABCD-LMP":

• Abdominal pain / tenderness
• Bleeding (mucosal)
• Clinical fluid accumulation (ascites, pleural effusion)
• Drowsiness / lethargy / restlessness
• Liver enlargement >2 cm
• Mucosal bleed + persistent Vomiting
• Platelet rapid fall with rising haematocrit

High-yield: A rising haematocrit with a simultaneously falling platelet count is the single most reliable laboratory marker of impending plasma leakage and the trigger to escalate monitoring and fluids.

Diagnosis & investigation of choice

Diagnostic strategy is time-dependent — match the test to the day of illness.

Test	Detects	Optimal window	Notes
NS1 antigen	Viral non-structural protein 1	Day 1–5 (early/febrile)	First marker positive; investigation of choice in first 5 days; high specificity
RT-PCR / viral isolation	Viral RNA	Day 1–5	Most specific; serotyping; reference labs
IgM (MAC-ELISA)	Acute antibody	From ~day 5, peaks 2 wk	Indicates recent infection; rises after NS1 falls
IgG	Past/secondary	Late primary / early secondary	Early high IgG = secondary infection (ADE risk)

Diagnostic flow: Day 1–5 → send NS1 antigen (± RT-PCR). Day ≥5 → send IgM serology. A high IgG appearing early with IgM suggests secondary infection and warrants closer watch for severe dengue.

Supportive labs: leukopenia (early), thrombocytopenia (<150,000; severe <100,000), raised haematocrit (≥20% rise = significant leak), transaminitis (AST > ALT, unlike viral hepatitis), hypoalbuminaemia. Ultrasound/chest X-ray detects plasma leakage early — gallbladder wall oedema, ascites, right-sided pleural effusion.

High-yield: NS1 antigen is the investigation of choice in the first 5 days; IgM after day 5. A ≥20% rise in haematocrit (or ≥20% fall after fluids) defines significant plasma leakage.

Management — fluids first, platelets rarely

There is no specific antiviral; management is supportive and risk-stratified by WHO category.

Group A — Dengue without warning signs (outpatient): Oral fluids, paracetamol for fever, rest. Strict advice on warning signs and daily review with CBC/haematocrit.

Group B — With warning signs / co-morbidity (admit): Isotonic crystalloids — 0.9% normal saline or Ringer lactate. Start 5–7 mL/kg/h × 1–2 h → 3–5 mL/kg/h × 2–4 h → 2–3 mL/kg/h, titrating to haematocrit, urine output (≥0.5 mL/kg/h), and vitals.

Group C — Severe dengue / DSS (ICU):

• Compensated shock: crystalloid bolus 5–10 mL/kg over 1 h, reassess.
• Hypotensive shock: crystalloid 10–20 mL/kg over 15–30 min; if no response and HCT still high, repeat; switch to colloid if HCT remains high despite crystalloid.
• A falling haematocrit with persisting shock signals occult haemorrhage → transfuse whole blood/packed cells, not more crystalloid.

High-yield: AVOID aspirin, NSAIDs (ibuprofen, diclofenac), and IM injections — they worsen bleeding/gastritis and platelet dysfunction. Use paracetamol for fever. (Aspirin in children also risks Reye syndrome.)

High-yield: Prophylactic platelet transfusion is NOT recommended based on count alone. Transfuse platelets only for active significant bleeding, or by local protocol when platelets <10,000–20,000 with bleeding risk. Bleeding in dengue is driven by leakage/coagulopathy, not just thrombocytopenia.

Resuscitation flow (DSS): Assess shock → crystalloid bolus → reassess HCT & vitals → if HCT ↑ & still shocked → second bolus/colloid → if HCT ↓ & still shocked → blood transfusion → taper fluids once stable to avoid fluid overload in recovery phase.

Complications

• Dengue shock syndrome (DSS) — narrow pulse pressure (≤20 mmHg), cold clammy peripheries, hypotension.
• Plasma-leak sequelae — pleural effusion, ascites, pulmonary oedema (especially iatrogenic from over-transfusion in recovery phase).
• Severe haemorrhage — GI bleed, menorrhagia, intracranial bleed.
• Expanded dengue syndrome — myocarditis, acute liver failure / fulminant hepatitis, encephalitis/encephalopathy, acute kidney injury, ARDS.
• Dengue myocarditis and acalculous cholecystitis are increasingly tested.

High-yield: Fluid overload during the recovery (reabsorption) phase is a leading iatrogenic complication — stop/reduce IV fluids once the patient is haemodynamically stable and haematocrit normalises, as reabsorbed fluid can precipitate pulmonary oedema.

Key differentials

Disease	Distinguishing clues
Chikungunya	Same Aedes vector; severe, persistent symmetrical arthralgia; rash common; thrombocytopenia & shock uncommon
Malaria	Periodic chills/rigors, splenomegaly; peripheral smear/RDT positive; relative thrombocytopenia but no plasma leak
Enteric fever	Stepladder fever, relative bradycardia, rose spots, Widal/blood culture
Leptospirosis	Conjunctival suffusion, jaundice + AKI (Weil's), myalgia (calf), exposure to water
Zika	Aedes-borne; mild, conjunctivitis, congenital microcephaly; milder course
Scrub typhus	Eschar, regional lymphadenopathy, responds to doxycycline

Prevention & vaccine

Control rests on vector source reduction (eliminate domestic breeding sites, larvivorous fish, larvicides, personal protection). The licensed tetravalent vaccine CYD-TDV (Dengvaxia) is recommended only for seropositive individuals (prior dengue) because seronegative recipients may experience ADE-like severe disease on natural infection — a high-yield public-health caveat. Newer vaccines (e.g., TAK-003/Qdenga) are emerging.

Recently asked / exam angle

• NS1 vs IgM timing — "Which test on day 3 of fever?" → NS1 antigen. "Which after day 5?" → IgM ELISA. Repeatedly examined.
• WHO 2009 warning signs — identify the patient with abdominal pain + persistent vomiting + rising HCT as dengue with warning signs requiring admission.
• HCT–platelet relationship — a single-best-answer on the most reliable early marker of plasma leakage → rising haematocrit with falling platelets.
• Drug to avoid — aspirin/NSAIDs prohibited; paracetamol is the antipyretic of choice; no IM injections.
• Platelet transfusion — image/clinical vignette testing that prophylactic transfusion by count alone is wrong; transfuse only for active bleeding.
• Fluid management — crystalloid first; the trick of falling HCT in persistent shock = bleeding → transfuse blood.
• Vector facts — Aedes aegypti, day-biter, clean stagnant water; rule-out vs Anopheles/Culex.
• Dengvaxia caveat — give only to seropositive individuals.
• Expanded dengue — myocarditis/hepatitis/encephalopathy as severe-dengue organ criteria (AST/ALT ≥1000).
• Convalescent rash — "isles of white in a sea of red."

Rapid revision

1. Cause: DENV, a Flavivirus with 4 serotypes; vector Aedes aegypti, a day-biter breeding in clean stagnant water.
2. Severe disease classically follows secondary heterotypic infection via antibody-dependent enhancement (ADE).
3. Core lesion of severe dengue = plasma leakage from capillary permeability (NS1- and cytokine-driven), causing hypovolaemic shock.
4. Phases: febrile (day 1–3) → critical/leakage (day 3–7, at defervescence) → recovery.
5. NS1 antigen = test of choice day 1–5; IgM from day 5; early high IgG = secondary infection.
6. Rising haematocrit + falling platelets = best early marker of plasma leakage; ≥20% HCT rise is significant.
7. WHO 2009: without warning signs / with warning signs / severe dengue.
8. Warning signs = abdominal pain, persistent vomiting, fluid accumulation, lethargy, hepatomegaly >2 cm, mucosal bleed, HCT rise with platelet fall.
9. First-line fluid = isotonic crystalloid (NS / Ringer lactate); colloid/blood if refractory; falling HCT in shock = haemorrhage → transfuse blood.
10. Avoid aspirin, NSAIDs, IM injections; antipyretic = paracetamol.
11. No prophylactic platelet transfusion by count alone — only for active bleeding.
12. Dengvaxia (CYD-TDV) only for seropositive individuals; watch for fluid overload in the recovery phase.