Dengue Fever (ไข้เลือดออก)
- ICD-10:
- A90 Dengue fever [classical dengue]
- A91 Dengue haemorrhagic fever
- ICD-11:
- 1D2Z Dengue fever, unspecified
- 1D20 Dengue without warning signs
- 1D21 Dengue with warning signs
- 1D22 Severe dengue
Key points
- Arboviral illness due to four dengue virus serotypes (DENV-1–4) transmitted by Aedes mosquitoes.
- Three phases: febrile → critical (at defervescence; plasma leakage risk) → recovery.
- Warning signs predict progression to severe dengue: abdominal pain/tenderness, persistent vomiting, mucosal bleed, lethargy/restlessness, clinical fluid accumulation, hepatomegaly ≥2 cm, rising haematocrit with rapid fall in platelets.
- Laboratory confirmation by NS1/RT-PCR in days 0–5; IgM/IgG serology after day 5.
- Management is supportive with meticulous fluid therapy; avoid NSAIDs/aspirin and unnecessary IM injections.
Overview
Dengue fever is an acute systemic viral infection caused by dengue virus (genus Flavivirus). Clinical manifestations range from subclinical infection to severe dengue with shock, severe bleeding, or organ impairment. Secondary infection with a heterologous serotype increases the risk of severe disease via immunopathological mechanisms.
Epidemiology
Dengue is endemic in >100 countries with cyclical epidemics in tropical and subtropical regions, particularly South/Southeast Asia, the Western Pacific, and the Americas. Incubation is typically 4–10 days. All ages are affected; in hyperendemic settings, children and adolescents bear a substantial burden. Urbanisation, water storage practices, and climatic factors (rainfall/temperature) drive transmission dynamics.
Microbiology
Dengue virus is an enveloped, positive-sense, single-stranded RNA virus. Four closely related serotypes (DENV-1–4) are antigenically distinct. Transmission is primarily via the bite of infected Aedes aegypti and Aedes albopictus. Humans are the principal amplifying host during viraemia. Uncommon routes include vertical transmission and blood products.
Vector competence, diurnal biting behaviour, and peri-domestic breeding (containers, tyres, construction sites) are central to spread. Integrated vector control—source reduction, larviciding, and adulticiding—remains essential.
Pathophysiology
Key points
- Primary infection yields durable, serotype-specific immunity with transient cross-protection to others.
- Antibody-dependent enhancement (ADE) during secondary infection augments viral entry into Fcγ-receptor–bearing cells.
- Endothelial dysfunction and cytokine-mediated capillary leak cause haemoconcentration, effusions, and shock.
- Bone marrow suppression and immune-mediated destruction lead to thrombocytopenia and bleeding.
- Critical phase begins around defervescence and lasts ~24–48 h; close monitoring is vital.
Following inoculation, DENV replicates in dendritic cells and monocytes/macrophages. Secondary infection with non-neutralising antibodies facilitates ADE, increasing viraemia and inflammatory mediators (TNF-α, IL-6, IL-8). Resultant endothelial glycocalyx disruption increases vascular permeability. Coagulopathy arises from platelet dysfunction, consumption of coagulation factors, and hepatic involvement.
Clinical Presentation
Typical course: Febrile phase (2–7 d) with high fever, headache, retro-orbital pain, myalgia/arthralgia, rash; Critical phase (24–48 h around defervescence) with plasma leakage; Recovery phase with reabsorption of extravasated fluid and convalescent rash.
| Sign & Symptom | Pathogenesis | Frequency (+ to ++++) | Specificity (+ to ++++) |
|---|---|---|---|
| High fever, severe headache, retro-orbital pain, myalgia | Viraemia, cytokinaemia | ++++ | + |
| Nausea/vomiting, abdominal pain | Visceral inflammation; early plasma leakage | +++ | ++ |
| Rash (“islands of white in a sea of red”) | Immune-mediated dermal vascular changes | ++ | ++ |
| Mucosal bleed, petechiae | Thrombocytopenia, platelet dysfunction, coagulopathy | ++ | +++ |
| Warning signs (lethargy, hepatomegaly, rising Hct with falling platelets) | Capillary leak and hepatic involvement | ++ | ++++ |
| Shock, severe bleeding, organ dysfunction | Profound plasma leakage; DIC; multi-organ injury | + | ++++ |
Investigation
Clinical suspicion in an epidemiological context is supported by laboratory confirmation. Early testing (days 0–5) prioritises virological methods; later testing relies on serology. Serial haematocrit and platelet counts guide fluid therapy. Point-of-care ultrasound (pleural effusion, gallbladder wall oedema, ascites) is useful during the critical phase.
Specific test
- RT-PCR (reference standard, days 0–5): Detects DENV RNA and serotype; highest specificity and early sensitivity.
- NS1 antigen (days 0–5): Rapid/ELISA assays; sensitivity varies by serotype and immune status; useful when PCR is unavailable.
- IgM/IgG serology (from day ≥5): IgM appears after day 5; high IgG with low/absent IgM suggests secondary infection; paired sera improves accuracy.
- Viral isolation: Research/confirmation only; not routine.
- Tourniquet test: Supportive in resource-limited settings; not diagnostic alone.
- Thrombocytopenia: often <100×109/L.
- Haemoconcentration: Hct rise >20% from baseline or population mean.
- Leucopenia with neutropenia; relative lymphocytosis.
- Mild–moderate transaminitis: AST usually > ALT.
- Urinalysis: haematuria/proteinuria may occur.
- Imaging (US/CXR): pleural effusion, gallbladder wall thickening, ascites.
- Other: lactate for shock assessment; coagulation profile if bleeding.
Diagnosis criteria (Dx)
WHO clinical classification:
- Dengue without warning signs-fever with nausea/vomiting, rash, aches/pains, positive tourniquet, leucopenia.
- Dengue with warning signs-any warning sign, warrants close observation/admission.
- Severe dengue-severe plasma leakage (shock/respiratory distress), severe bleeding, or severe organ involvement (e.g., AST/ALT >1000, myocarditis, encephalopathy).
Diffential diagnosis (DDx)
| Disease | Signs & symptoms | Lab finding | Specific test for ruleout | Other |
|---|---|---|---|---|
| Malaria | Fever, chills, anaemia, splenomegaly | Thrombocytopenia; haemolysis | Thick/thin smear or RDT | Travel to endemic area; periodic fever |
| Chikungunya | High fever with severe arthralgia/arthritis | Platelets often normal | RT-PCR/serology | Debilitating joint pain predominates |
| Leptospirosis | Fever, myalgia, conjunctival suffusion, jaundice | Leucocytosis; renal/hepatic dysfunction | MAT/PCR | Exposure to contaminated water/animals |
| Enteric fever (Typhoid) | Step-ladder fever, abdominal pain, relative bradycardia | Leucopenia; elevated LFTs | Blood/stool/bone marrow culture | Rose spots; GI predominance |
| COVID-19/Influenza | Fever, myalgia, respiratory symptoms | Lymphopenia | RT-PCR/antigen testing | Respiratory tract signs dominate |
Treatment
There is no licensed specific antiviral. Care is supportive with careful, goal-directed fluid therapy tailored to haemodynamic status and serial haematocrit/urine output. Acetaminophen (paracetamol) for analgesia/antipyresis. Avoid NSAIDs/aspirin due to bleeding risk. Blood products are reserved for clinically significant haemorrhage or severe thrombocytopenia with bleeding. Early recognition of the critical phase and timely escalation reduce mortality to <1% in well-resourced settings.
Pharmacology
| Agent | Indication | Typical adult dosage (normal renal/hepatic function) | Notes |
|---|---|---|---|
| Paracetamol | Fever/pain | 500–1000 mg PO q6–8h (max 3–4 g/day) | Avoid combination with hepatotoxins; no NSAIDs/aspirin. |
| Oral rehydration solution | Mild dehydration | Small frequent volumes guided by losses | Continue during febrile and recovery phases. |
| Isotonic crystalloid (e.g., Ringer’s lactate, 0.9% NaCl) | Plasma leakage; compensated shock | Titrated boluses/infusions per clinical response and Hct | Use standard dengue fluid charts; frequent reassessment. |
| Packed red cells / platelets | Significant bleed / severe thrombocytopenia with bleed | Per institutional transfusion thresholds | Not indicated for low platelets alone without bleeding. |
Guideline
The World Health Organization (WHO) published comprehensive dengue guidelines in 2009, subsequently reaffirmed in 2024. These guidelines categorise patients into three groups for clinical decision-making: Group A (ambulatory cases without warning signs), Group B (cases with warning signs or comorbidities requiring hospital observation), and Group C (severe dengue requiring emergency management). The classification is designed to simplify triage and ensure early recognition of severe disease.
Group A — Outpatient care: Patients without warning signs, with reliable access to healthcare, and the ability to maintain oral hydration can be managed as outpatients. Key components include oral fluids, paracetamol for fever, and counselling regarding warning signs that necessitate immediate reassessment. Daily follow-up during the febrile period is recommended until recovery is established.
Group B — Admission and close monitoring: Any patient with warning signs, pregnancy, infancy, advanced age, comorbidities (diabetes, renal or cardiovascular disease), or social vulnerability should be hospitalised. Intravenous fluid therapy may be required if oral intake is inadequate or if warning signs progress. Monitoring should include vital signs every 1–4 hours, strict input/output charting, and haematocrit/platelets every 6–12 hours. Early ultrasound (gallbladder wall oedema, pleural effusion, ascites) can aid recognition of plasma leakage.
Group C — Severe dengue: This group includes patients with shock (dengue shock syndrome), severe bleeding, or severe organ impairment (hepatic, cardiac, neurologic). Immediate resuscitation is required. Initial therapy consists of rapid intravenous crystalloid bolus (10–20 mL/kg over 15–30 minutes) with reassessment. Haematocrit guides subsequent management: if rising, continue fluids cautiously; if falling with instability, consider bleeding and transfuse packed red cells. Colloids may be used in refractory shock. Platelets and fresh frozen plasma are reserved for life-threatening haemorrhage or invasive procedures; prophylactic transfusion for low platelet counts is not indicated.
Fluid Management Guideline
Careful fluid therapy is the cornerstone of dengue management. The aim is to maintain effective circulation while avoiding fluid overload, particularly during the recovery phase when vascular permeability normalises. The WHO guidelines emphasise judicious, titrated intravenous (IV) crystalloid therapy, guided by frequent clinical and laboratory reassessment.
General principles:
- Use isotonic crystalloids (Ringer’s lactate or 0.9% normal saline) as first-line fluids.
- Monitor vital signs, capillary refill, urine output (≥0.5 mL/kg/h), and mental status.
- Serial haematocrit measurements are critical to distinguish plasma leakage from bleeding.
- Avoid hypotonic fluids, excessive maintenance volumes, and routine colloid use.
- Adjust fluid rates every 1–2 hours based on clinical response and laboratory trends.
Management by severity:
1. Dengue with warning signs (but no shock)
- Begin IV fluids if oral intake inadequate or persistent vomiting present.
- Suggested rate: 5–7 mL/kg/h of isotonic crystalloid for 1–2 h, then reduce to 3–5 mL/kg/h for 2–4 h, then 2–3 mL/kg/h depending on improvement.
- Continue to reassess: if clinical improvement and stable Hct, taper fluids gradually over 24–48 h.
- If deterioration or rising Hct, escalate to shock protocol.
2. Dengue shock syndrome (compensated/decompensated shock)
- Initial resuscitation: 10–20 mL/kg isotonic crystalloid over 15–30 minutes.
- Reassess after bolus:
- If improvement (BP stabilises, capillary refill <2 s, urine output improves, Hct decreases/stabilises): continue 5–10 mL/kg/h, then taper as patient stabilises.
- If persistent shock with rising Hct: repeat crystalloid bolus, up to two cycles.
- If persistent shock with falling/low Hct: suspect bleeding → transfuse packed red cells (10 mL/kg).
- If shock not corrected after two crystalloid boluses: consider colloids (dextran, starch, albumin) under specialist supervision.
3. Recovery phase
- Occurs ~24–48 h after critical phase, marked by stabilisation of vital signs, improving urine output, and subsiding warning signs.
- Vascular permeability normalises; extravasated fluid reabsorbs.
- Reduce IV fluid rate to avoid overload (1–2 mL/kg/h, then switch to oral hydration as tolerated).
- Monitor for pulmonary oedema, effusions, and heart failure, especially in children and elderly.
Key monitoring:
- Haematocrit: Rising Hct = ongoing plasma leakage; falling Hct + unstable vitals = bleeding.
- Urine output: Goal ≥0.5 mL/kg/h indicates adequate perfusion.
- Clinical parameters: BP, pulse pressure, capillary refill, mental status, respiratory rate.
Example Doctor Order
Ward admission — Dengue with warning signs
- Diagnosis: Dengue fever with warning signs (day __ of illness).
- Activity: Bed rest; fall/bleeding precautions.
- Monitoring: Vitals q2h; I&O chart; Hct/CBC q6–12h; capillary glucose q6h.
- Fluids: RL/NS titrate per protocol to clinical/Hct response.
- Antipyresis: Paracetamol 500 mg PO q6h PRN fever (≤4 g/day).
- Avoid: NSAIDs/aspirin; IM injections; unnecessary venepuncture.
- Labs: CBC, Hct, LFTs, PT/INR, aPTT, electrolytes, creatinine; NS1/PCR or IgM (per day of illness).
- Imaging: POCUS chest/abdomen if dyspnoea or abdominal pain.
- Education: Return precautions; counselling on oral hydration.
Physician:__________________ License:_________ Date:________ Time:_______
ICU admission — Severe dengue with shock
- Airway/Breathing: O2 facemask to maintain SpO2 ≥94%.
- Circulation: IV access x2; crystalloid bolus(es) per protocol with reassessment (MAP, HR, capillary refill, Hct, lactate, urine output).
- Transfusion: PRC/FFP/platelets only if clinically indicated (major bleed, coagulopathy with bleed) per institutional thresholds.
- Monitoring: Arterial line if persistent shock; foley catheter; strict I&O.
- Labs: CBC/Hct q2–4h; coagulation profile; ABG/VBG; type & screen.
- Consults: Anaesthesia/critical care; transfusion medicine.
Physician:__________________ License:_________ Date:________ Time:_______
Disclaimer: Examples for educational purposes only; not patient-specific prescriptions.
Prognosis
Most patients recover within 1–2 weeks. Mortality is low when severe cases are recognised early and managed with protocolised fluids; poor prognostic factors include persistent shock, severe bleeding, organ failure (hepatic/renal/CNS), pregnancy, extremes of age, and comorbidity. Convalescent fatigue and transient hair loss may occur. Arrange follow-up to ensure platelet recovery and resolution of effusions.
Prevention
Primary prevention relies on integrated vector control (source reduction, container management, larval control, community engagement) and personal protection (repellents containing DEET/picaridin/IR3535, long sleeves, window screens). Vaccination with TAK-003 (Q-denga) may be considered by national programmes for children aged 6–16 years in settings with high transmission intensity per WHO (2-dose series, 3 months apart). Programme decisions should consider local sero-epidemiology, cost-effectiveness, and logistics.
Conclusion
- Think dengue in any acute febrile illness in endemic/travel contexts.
- Critical phase begins at defervescence—monitor Hct/urine output closely.
- Use RT-PCR/NS1 early; serology after day 5.
- Fluids save lives; avoid NSAIDs/aspirin.
- Escalate promptly for shock/bleeding/organ dysfunction.
- Prevention: vector control + context-appropriate vaccination policies.
- Education and follow-up reduce complications and readmissions.
Quiz (USMLE OSCE)
Frequently Asked Questions (FAQ)
Should platelets be transfused for low counts alone?
No. Prophylactic transfusion is not recommended for thrombocytopenia without bleeding. Reserve blood products for clinically significant haemorrhage or procedures with high bleeding risk, following institutional thresholds.
Can NSAIDs be used for pain control?
Generally avoid NSAIDs/aspirin due to bleeding risk and potential renal effects during plasma leakage. Use paracetamol within safe daily limits.
When should patients return for reassessment?
At defervescence or the onset of any warning sign; sooner if unable to maintain oral intake, oliguria, or bleeding develops. The 24–48 h critical window requires the closest monitoring.
Who is eligible for dengue vaccination?
WHO recommends programme use of TAK-003 (Q-denga) in children 6–16 years in settings with high transmission intensity. National policies vary; check local guidance.
References
- World Health Organization. Dengue and severe dengue — Fact sheet. Updated 21 Aug 2025.
- Tayal A, et al. Management of Dengue: An Updated Review. J Family Med Prim Care. 2022;11:7682–7690 (PMC9793358).
- CDC. Dengue Case Management Pocket Guide. May 2024.
- WHO. Position paper on dengue vaccines (TAK-003). Wkly Epidemiol Rec. May 2024.
- CDC. Yellow Book: Dengue. 2025 edition.
- WHO. Dengue: Guidelines for diagnosis, treatment, prevention and control. 2009.
- ICD-11 MMS (v2025-01). Block 1D62 Dengue; codes 1D62.0–1D62.2.
- Singh RK, et al. Updates in the Management of Dengue Shock Syndrome. 2023 (PMC10631559).
- WHO Q&A. Dengue vaccines. Updated 10 Apr 2025.
- Reuters. WHO prequalifies Takeda’s dengue vaccine Qdenga. 15 May 2024.
Author & Review
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Teerawat Suwannee MD
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