Introduction
Dengue is the most important arboviral infection affecting humans worldwide. It is caused by any of four antigenically distinct but closely related dengue virus serotypes, DENV-1 to DENV-4, which are enveloped, single-stranded positive-sense RNA viruses in the genus Flavivirus within the family Flaviviridae. Transmission is primarily by Aedes aegypti and, to a lesser extent, Aedes albopictus. Unlike many other flaviviruses, humans can develop sufficient viremia to sustain an urban mosquito–human–mosquito transmission cycle.
For clinical practice, dengue should be considered in any patient with acute febrile illness who lives in, or has recently traveled to, an area with dengue risk, particularly if headache, retro-orbital pain, myalgia, arthralgia, rash, leukopenia, or thrombocytopenia are present. Clinicians should not wait for diagnostic confirmation before initiating appropriate monitoring and supportive care when dengue is suspected.
Epidemiology
Dengue is endemic in more than 100 countries and now poses risk across much of the tropics and subtropics, with expansion into new geographies driven by urbanization, human mobility, climate-related vector spread, and health system pressures. WHO estimates that about 100–400 million infections occur annually, although reported cases capture only a fraction of the true burden. Reported disease has risen sharply: WHO recorded 14.6 million cases and more than 12,000 deaths globally in 2024, the highest number reported in a single year to date.
The old statement that dengue causes “10,000 deaths every year from dengue hemorrhagic fever” is now too narrow and not fully accurate. Modern reporting uses the broader category of severe dengue rather than relying on the older DHF/DSS terminology alone, and recent mortality figures vary by year and outbreak intensity.
Virology, transmission, and incubation
Transmission usually follows the bite of an infected Aedes mosquito. After feeding on a viremic human, the mosquito typically requires an extrinsic incubation period of roughly 8–12 days before it can transmit virus efficiently. In humans, the incubation period is usually 4–10 days after the infective bite, though broader ranges are sometimes reported. Patients are typically infectious to mosquitoes from shortly before fever onset through the early febrile phase, when viremia is highest.
Humans are the principal amplification host in urban transmission cycles. Vertical transmission can occur in pregnancy and around delivery, and clinicians should consider neonatal dengue in infants born to mothers with dengue late in pregnancy or peripartum. Dengue in pregnancy has been associated with fetal loss, prematurity, and low birth weight.
Pathogenesis and immunopathology
Dengue pathogenesis is driven by both viral factors and host immune responses. Following inoculation into the skin, virus infects dendritic cells, monocytes, macrophages, and other susceptible cells. Severe disease is thought to arise from a combination of high viral burden, endothelial dysfunction, inflammatory mediator release, complement activation, coagulopathy, and immune phenomena including antibody-dependent enhancement during some secondary heterotypic infections. Cross-reactive but non-neutralizing antibodies may facilitate viral entry into Fc receptor-bearing cells, increasing viral replication and inflammatory injury.
A prior dengue infection increases the risk of severe dengue with subsequent infection by a different serotype, although severe disease can also occur in primary infection. Infection with one serotype generally provides long-term protection against that same serotype, while cross-protection against other serotypes is temporary.
Clinical course
Dengue classically progresses through three phases.
1. Febrile phase
This phase usually lasts 2–7 days and is characterized by abrupt fever, severe headache, retro-orbital pain, myalgia, arthralgia, nausea, vomiting, and rash. Minor mucosal bleeding may occur. Leukopenia is common. The traditional “saddleback” fever pattern can occur, but it is neither sensitive nor specific enough to be diagnostically useful.
2. Critical phase
The critical phase commonly begins around defervescence, often on illness days 3–7. This is the period when increased capillary permeability and plasma leakage may develop. Warning signs typically emerge as the fever starts to fall, not necessarily while fever is still high. This is the key window for close reassessment, because patients can deteriorate rapidly despite appearing transiently improved.
3. Recovery phase
If the patient survives the leakage phase, reabsorption of extravascular fluid follows over the next 24–48 hours or longer. Hemodynamics stabilize, urine output improves, appetite returns, and hematocrit falls. During recovery, excessive IV fluid administration given earlier may manifest as pulmonary edema or heart failure, especially in older adults and those with renal or cardiac comorbidity.
Current classification
For modern clinical practice, WHO and CDC use the 2009-style severity framework rather than relying primarily on the older labels “dengue fever,” “dengue hemorrhagic fever,” and “dengue shock syndrome.” Patients should be classified as: dengue without warning signs, dengue with warning signs, or severe dengue.
Dengue without warning signs
Typical febrile illness with compatible symptoms but no evidence of warning signs or severe organ involvement. These patients may be suitable for outpatient care if oral intake is adequate, social circumstances are safe, and follow-up is reliable.
Dengue with warning signs
Warning signs include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy or restlessness, liver enlargement, and a rising hematocrit with falling platelet count. These patients require close observation and often hospital-based management, especially near defervescence.
Severe dengue
Severe dengue is defined by severe plasma leakage leading to shock or respiratory distress, severe bleeding, or severe organ involvement such as severe hepatitis, myocarditis, encephalopathy, or other major end-organ dysfunction. Pulse pressure narrowing, cool peripheries, delayed capillary refill, altered mental status, oliguria, and rising lactate should raise concern for impending or established shock.
Clinical features relevant to physicians
Common presenting features include acute fever, severe headache, retro-orbital pain, myalgia, arthralgia, rash, nausea, vomiting, and malaise. A transient macular or maculopapular rash may appear early, followed later by a more diffuse rash during recovery. Mild bleeding manifestations such as epistaxis, gingival bleeding, petechiae, or menorrhagia can occur. Persistent fatigue after acute illness is well recognized and may last for weeks.
The older tourniquet test is no longer central to diagnosis in modern practice. It may still be described in older literature, but laboratory confirmation and structured clinical assessment are preferred.
Warning signs and when to escalate care
Patients require urgent reassessment or admission if warning signs appear, especially around defervescence. Particular concern is warranted in infants, pregnant patients, older adults, and patients with obesity, diabetes, renal disease, cardiovascular disease, immunosuppression, or poor access to follow-up. Pregnancy deserves special caution because normal physiological changes can obscure hemoconcentration and early shock, and vertical transmission can occur.
Laboratory findings
Typical laboratory abnormalities include leukopenia, thrombocytopenia, and rising hematocrit from hemoconcentration. Mild to moderate aminotransferase elevation is common, and AST often exceeds ALT. Hyponatremia and hypoalbuminemia may reflect capillary leak and systemic inflammation. Coagulation abnormalities can occur, but isolated thrombocytopenia is not by itself an indication for platelet transfusion. A rising hematocrit together with a falling platelet count is more clinically useful than the platelet count alone as a marker of evolving plasma leakage.
The statement “platelet count <20,000/mm³ is a warning sign” is outdated if interpreted in isolation. Very low platelets increase bleeding risk, but current triage depends on the overall clinical picture: hemodynamics, bleeding, plasma leakage, organ dysfunction, and hematocrit trend matter more than a single platelet threshold.
Diagnosis
Clinical suspicion
Dengue remains a clinical diagnosis initially, especially in endemic settings and in returning travelers with compatible illness. However, laboratory confirmation is strongly recommended when available because clinical overlap with chikungunya, Zika, malaria, leptospirosis, typhoid, rickettsioses, influenza, and other febrile illnesses is substantial.
Recommended testing by illness day
Current guidance recommends testing based on time from symptom onset.
During the first 0–7 days of illness, order either NAAT plus IgM, or NS1 antigen plus IgM. A positive NAAT confirms acute dengue and usually provides serotype information; a positive NS1 also supports current or very recent infection. A negative NAAT or NS1 does not exclude dengue. After day 7, IgM becomes the main test, although some patients may remain positive by NAAT or NS1 beyond day 7.
Interpretation
A positive NAAT or NS1 is confirmatory for acute infection. A single positive IgM generally supports presumptive recent dengue, but interpretation is complicated by timing and possible flavivirus cross-reactivity. Paired serology showing seroconversion or a change from negative to positive IgM increases confidence. In vaccinated patients or regions with multiple flaviviruses, interpretation can be more complex, and local public health or reference laboratory input may be needed.
The older fixed sensitivity/specificity figures quoted for NS1 are too context-dependent to present as universal values. Test performance varies by assay platform, serotype, illness day, and whether infection is primary or secondary. Timing remains one of the strongest determinants of diagnostic yield.
Management
General principles
There is still no approved specific antiviral therapy for routine clinical use. Management is supportive, and outcomes depend heavily on early recognition of warning signs, judicious fluid therapy, and prompt treatment of shock and hemorrhage. NSAIDs such as ibuprofen and aspirin should be avoided because they may worsen bleeding risk; paracetamol/acetaminophen is preferred for fever and pain.
Outpatient management
Patients without warning signs, with stable hemodynamics, preserved urine output, and adequate oral intake may be managed as outpatients with oral rehydration, antipyretics, and daily or more frequent reassessment during the critical period. They should receive explicit return precautions for abdominal pain, persistent vomiting, bleeding, dizziness, lethargy, dyspnea, reduced urine output, or inability to maintain hydration.
Inpatient management
Patients with warning signs, inability to tolerate oral fluids, significant comorbidity, pregnancy, social concerns, or severe dengue should be admitted. The cornerstone is careful isotonic crystalloid therapy tailored to clinical status and ongoing reassessment. WHO’s 2025 guideline suggests crystalloids rather than colloids when IV fluid therapy is required in severe arboviral disease. Capillary refill time and lactate are recommended adjuncts to guide fluid management, and passive leg raise may help if the need for additional fluid is uncertain in shock.
Shock
In compensated or hypotensive shock, urgent fluid resuscitation is required, with close reassessment of pulse pressure, capillary refill, urine output, mental status, lactate, hematocrit, and respiratory status. A rising hematocrit with shock suggests ongoing plasma leakage and need for further volume replacement; falling hematocrit with unstable hemodynamics may indicate major hemorrhage and the need to evaluate for blood transfusion.
Blood products
Routine prophylactic platelet transfusion is not recommended in severe dengue patients with thrombocytopenia who are not bleeding. WHO’s 2025 guideline specifically suggests against prophylactic platelet transfusion for platelet counts below 50,000/µL in the absence of active bleeding. Platelets and other blood components should be reserved for clinically significant bleeding or procedure-specific indications. Packed red cell transfusion is indicated when major hemorrhage is suspected or confirmed.
Corticosteroids and immunoglobulins
Current WHO guidance suggests against systemic corticosteroids for both non-severe and severe arboviral disease, and against immunoglobulins for severe disease. These interventions should not be used routinely for dengue.
Special populations
Pregnancy
Pregnant patients with dengue need lower thresholds for admission and multidisciplinary management. Maternal infection can be transmitted to the fetus during pregnancy or around delivery, and adverse outcomes include fetal death, low birth weight, and preterm birth. Hemodynamic assessment may be more challenging because normal pregnancy alters heart rate, blood pressure, and hematocrit.
Neonates
Neonates exposed late in gestation may present within the first two weeks of life, often in the first week. Illness ranges from mild fever and thrombocytopenia to severe dengue with shock or hemorrhagic manifestations.
Vaccination
The original vaccine section is outdated. Dengue vaccination policy has changed.
WHO’s current position focuses on TAK-003 (Qdenga). WHO recommends programmatic use in children aged 6–16 years in settings with high dengue transmission intensity, as a 2-dose schedule given 3 months apart. WHO does not currently recommend programmatic use in low-to-moderate transmission settings, and it does not recommend routine programmatic use in children under 6 years because efficacy is lower in that age group.
For travelers, recommendations vary by country. In the UK, JCVI guidance is more conservative: Qdenga is recommended only for selected people aged 4 years and older with previous dengue infection who are traveling to risk areas or have occupational exposure. UK guidance specifically notes that Qdenga is not recommended for seronegative individuals because of insufficient data and a theoretical risk related to later DENV-3 or DENV-4 exposure.
In contrast, the CDC Yellow Book states that there are currently no dengue vaccines recommended for travelers in the United States.
Prevention
Prevention still relies primarily on vector control and bite avoidance. For clinicians, this means advising patients to use effective repellents, wear long sleeves, stay in screened or air-conditioned rooms, and reduce domestic mosquito breeding sites by eliminating standing water. Because Aedes mosquitoes bite mainly during daytime, bed nets alone are insufficient unless used by febrile patients or those resting during the day. Patients with suspected dengue should also minimize mosquito exposure during the first week of illness to reduce onward transmission.
Related viruses
Other important mosquito-borne flaviviruses include yellow fever, Zika, Japanese encephalitis virus, and West Nile virus. Tick-borne encephalitis virus is also a flavivirus, but it is tick-borne rather than mosquito-borne. Hepatitis C virus should not be listed under “other flaviviral diseases” in this context because although it belongs to the broader family Flaviviridae, it is in a different genus and is not an arboviral flavivirus.
Practical take-home points for physicians
Dengue is a dynamic illness, and the most dangerous period is often defervescence rather than peak fever. The most useful bedside tasks are serial clinical assessment, trend-based interpretation of hematocrit and platelets, early recognition of warning signs, and careful fluid titration. Severe thrombocytopenia alone should not drive management. Do not use NSAIDs routinely. Do not give prophylactic platelets without bleeding. Use modern severity classification rather than relying on DHF/DSS terminology alone.
