Dengue: ED presentation, evaluation, and management

Authors: Morris Aheebwa, MD (EM Resident, Makerere College of Health Sciences, Kampala, Uganda); Shawn Thayer, (EM Resident, University of Missouri-Columbia); Stuart Allen, MD (EM Resident, University of Missouri-Columbia); Jessica Pelletier, DO, MHPE (APD/Assistant Professor of EM/Attending Physician, University of Missouri-Columbia) // Reviewed by: Brit Long, MD (@long_brit); Alex Koyfman, MD (@EMHighAK)

Case

A 25-year-old male rice farmer and occasional trader in Kasese district presents to the ED at Mbarara Regional Referral Hospital in Mbarara city, Uganda, with a two-day history of high-grade fever, initially low-grade five days prior, managed with paracetamol. The day before admission, he reported retro-orbital pain, myalgia, and fatigue. In the ED, the patient was started on IV paracetamol for a temperature of 40°C. Labs could not result the same day, so he was admitted to the internal medicine ward with a provisional diagnosis of possible malaria. On the day after admission, the patient developed a maculopapular rash on his extremities, accompanied by overnight episodes of nausea and abdominal discomfort. Examination by the senior house officer revealed a fever of 38.7°C, mild dehydration, and a slightly reduced platelet count of 180×10³/µL, with a negative malaria test, prompting management for suspected sepsis with a gastrointestinal focus.

By the second day after admission, the fever subsided, but the patient reported worsening abdominal pain, vomiting, and bleeding from the nose and gums. Physical exam showed petechiae, ascites, and a further decreased platelet count of 80×10³/µL. On the fifth day, his condition deteriorated, with melena, profound fatigue, confusion, cold and clammy extremities, blood pressure of 80/50 mmHg, pulse rate of 115 bpm, hematocrit of 50%, and platelets dropping to 20×10³/µL. Abdominal ultrasound confirmed hepatosplenomegaly. In the ICU, blood samples sent to the Uganda Virus Research Institute tested positive for DENV-2. With the timely administration of IV fluids and platelet transfusions, the patient stabilized by the eighth day, with resolving symptoms, improving vital signs, and a rebounding platelet count of 100×10³/µL.

Introduction

Dengue fever is a mosquito-borne viral infection caused primarily by the dengue virus (DENV), transmitted by Aedes aegypti and Aedes albopictus mosquitoes. It presents a significant global public health challenge, with epidemiological patterns influenced by factors such as urbanization, climate change, travel, and inadequate vector control.^1,2 The disease manifests in a spectrum from mild febrile illness to severe dengue, which can be life-threatening.^3,4 Historically, dengue has evolved from sporadic outbreaks in the early 20th century to hyperendemic transmission in many tropical regions today, driven by the globalization of the virus’s four serotypes (DENV-1 to DENV-4).^2,3

Epidemiology

Dengue poses a major global health threat, with approximately 4 billion people at risk across the Americas, Africa, the Middle East, Asia, and the Pacific Islands.⁵ 100-400 million dengue infections occur yearly, though these numbers may be underreported due to asymptomatic and mild cases.⁶ In 2024, the Centers for Disease Control and Prevention (CDC) reported more than 13 million cases of dengue in the Americas and the Caribbean.⁷ There have also been multiple Pacific islands that have declared outbreaks of dengue.⁷ Since the beginning of 2025, the European CDC has reported over 4 million cases and over 2800 deaths from dengue in 101 countries and territories.⁸ From 1990 to 2021, the global incidence of dengue escalated from 26.45 million to 58.96 million cases, accompanied by an increase in related deaths from 14,315 to 29,075.⁹

Dengue is preventable through efforts to limit exposure and habitats suitable for mosquito reproduction and replication. The distribution of infection correlates with Aedes mosquito habitats and is exacerbated by global warming, which may expand ranges northward.^1,2

Dengue is predominantly a disease of tropical and subtropical climates, with over 3.9 billion people at risk of infection across more than 128 countries as of 2013, concentrated in Asia, the Americas, Africa, and parts of Oceania.¹ The Asia-Pacific region bears the heaviest burden, accounting for about 70% of global cases, with hyperendemic transmission in countries like India, Indonesia, Thailand, and the Philippines, where all four serotypes co-circulate and drive frequent outbreaks.^1,10 In the Americas, dengue has resurged since the 1980s, with the highest incidence in Brazil, Mexico, and Colombia, reporting millions of cases annually; the region saw a 30-fold increase in reported cases from 1960 to 2010.² Africa, often underreported due to diagnostic challenges, has emerging foci in East and West Africa.¹¹ Recent cohort studies, such as one in Western Uganda, highlight ongoing underdiagnosis, where dengue accounted for a notable proportion of undifferentiated febrile illnesses in children, suggesting the true burden may be even higher in Africa.¹¹ Europe remains largely spared, though imported cases and limited autochthonous transmission occur in southern regions like France and Italy due to Aedes invasions.² Global estimates indicate dengue causes millions of disability-adjusted life years (DALYs) annually, disproportionately affecting low- and middle-income countries.^1,6

Approximately 96% of dengue infections are subclinical or present as self-limiting dengue fever (DF), characterized by high fever, headache, myalgia, and rash, which typically resolves within 7–10 days without specific treatment.^1,4 In contrast, severe dengue encompassing DHF (marked by plasma leakage, thrombocytopenia, and hemorrhagic manifestations) and DSS (with hypotensive shock) affects only about 1–5% of symptomatic cases, translating to roughly 500,000 severe episodes globally per year.^4,12 This low progression rate to severity, often linked to secondary infections with heterologous serotypes via antibody-dependent enhancement, results in a case-fatality rate of less than 1% with proper management, but it can exceed 20% in untreated severe cases.^3,12 For instance, in high-burden areas, the ratio of mild to severe dengue can be as high as 500:1, emphasizing that while dengue is ubiquitous in endemic zones, severe outcomes are relatively rare but carry high morbidity and mortality risks, particularly among children and those with comorbidities.^11,12

Table 1. Summary of the prevalence of dengue and severe dengue disease cases.

Pathophysiology

The dengue virus (DENV) is a single-stranded RNA arbovirus in the genus Flavivirus and family Flaviviridae; other members of this family include West Nile virus and yellow fever virus. DENV can be further subdivided into serological groups DENV 1-5 (the 5th serotype, DENV-5, discovered in 2007), with each serotype having multiple subtypes based on endemic regions.¹³ Due to serological differences among DENV subtypes, infection with one serotype confers long-term immunity to that serotype, but not to other serotypes. This immunologic gap leaves those previously infected vulnerable to reinfection with other DENV subtypes.¹⁴ In DENV-endemic areas, multiple serotypes circulate, leading to periodic outbreaks as herd immunity against specific serotypes wanes. Not only does this make natural herd immunity unachievable, but it is also worsened by the ease and speed of international travel, which spreads new subgroups to both endemic and non-endemic areas alike.¹⁵

Like other Flaviviridae, DENV is primarily spread through mosquito vectors. The main culprit is Aedes aegypti; however, Aedes albopictus has also been shown to transmit DENV. These vectors are responsible for a vast majority of DENV cases worldwide; however, other vectors of transmission have been documented. Although relatively rare, important modes of transmission include: vertical transmission (from pregnant mother to fetus),¹⁶ bloodborne transmission via needle stick or blood transfusion,¹⁷ and sexual transmission.¹⁸ There are also reports of the DENV found in the breast milk; however, at this time, there are no confirmed cases of vertical transmission through this route.¹⁹

While DENV infection and progression to DF, severe dengue is still not fully understood and remains an area of active research, it is known to involve multiple organ systems as well as immune and autoimmune processes.²⁰

Once DENV enters the host, it infects local immune cells, typically epithelial macrophages or dendritic cells. Migration of those cells into local lymph tissue initiates systemic dissemination of infected cells throughout the body, and their rupture leads to detectable viremia approximately 24-48 hours prior to clinical signs of infection. From here, DENV infection can take 2 paths: Dengue fever (DF) or severe dengue. DF symptoms can range from asymptomatic to severe. The pathogenesis of DF is complex, multifactorial, and not entirely elucidated; however, research shows that both viral factors and host immune factors play a large role in the severity of disease. This makes it difficult to predict who will develop mild vs. severe DF. The clinical manifestations in DF can be roughly categorized into 3 pathologic areas: endothelial dysfunction, bone marrow suppression, and hepatic damage.²⁰

Endothelial Dysfunction

 DENV induces immune cell activation and the release of inflammatory cytokines, increasing capillary permeability. It also produces Non-Structural protein-1 (NS1), a soluble protein released from the surface of infected cells. NS1 can independently activate immune cells and increase the levels of inflammatory cytokines; it also binds directly to endothelial cells, activating multiple factors that further increase permeability.²⁰ Several studies have demonstrated that high levels of NS1 are correlated with the severity of disease and the development of severe dengue.^21,22

Bone Marrow Suppression

DENV infection is associated with leukocytosis and thrombocytosis, with thrombocytopenia partially explaining the petechiae and gingival bleeding in DF and the hemorrhage in DNF. DENV has been shown to infect multiple bone marrow cell lines via immunohistological staining.²³ Infection of megakaryocytes specifically results in thrombocytopenia, not only through cellular apoptosis, which reduces colony numbers, but also through reduced platelet production in infected cells before cell death.²⁴

Hepatic Damage

Elevations in liver enzymes resulting from hepatocellular damage are common in DENV infections, although acute liver failure is rare²⁵ (seen in 1.6% of patients in a 2015 study with 4,069 participants).²⁶ It appears that liver damage occurs through multiple mechanisms, although most hepatocellular damage is linked to two mechanisms: (1) Direct infection of hepatocytes by DENV,²⁷ and (2) hepatocellular damage caused by high levels of complement activation. The complement system is activated by both the high circulating levels of cytokines in DENV infections, as well as directly activated by circulating NS1.²⁸ This hepatic dysfunction is linked to reduced synthetic functioning and reduced production of coagulation factors. In severe dengue, hepatic damage is also augmented by poor perfusion (i.e., shock liver), further increasing the chance of hemorrhage.²⁶

Severe Dengue

Severe dengue has distinct differences in pathogenesis, with the two main differences being (1) increased vascular permeability and (2) hemorrhage. These manifestations can be so severe that they lead to shock (DSS) and cardiovascular collapse. While not entirely understood, this difference in pathogenesis appears to be largely due to DENV non-neutralizing antibodies, leading to antibody-dependent enhancement (ADE). The presence of these non-neutralizing antibodies explains why severe dengue occurs almost entirely in individuals with prior DNEV infection or in infants born to mothers previously infected and now immune to DENV.²⁹

After an initial DENV infection, a variety of antibodies are produced; these antibodies also cross the placenta into the fetal circulation. While these antibodies confer immunity to the same DENV serotype, they provide only partial protection against other serotypes. These antibodies bind but do not neutralize newly produced DENV virions, forming a virion-antibody complex that underlies ADE.³⁰ This DENV-antibody complex shows increased activation of and entry into immune cells. This enhanced activation and infection of immune cells result in multiple cascading effects that worsen the disease course. Increased immune cell activation elevates cytokine levels, leading to endothelial dysfunction and platelet destruction.¹³ Increased infection of immune cells also results in both direct leukopenia due to cell lysis and a higher viral titer. This increased virion number increases infection of bone marrow progenitor cells, worsening leukopenia and thrombocytopenia.³⁰ The increased infectivity produced by ADE is likely the cause of elevated NS1 found in severe dengue patients. NS1 binds to and activates Toll-Like Receptor-4 (TLR4) on multiple cell types. Binding immune cells increases cytokine production. Binding with endothelial cells increases glycocalyx permeability. Both of these interactions lead to increased vascular leakage.³¹ NS1 also binds to TLR4 on platelets, increasing platelet activation, apoptosis, and clearance by phagocytic cells, further worsening thrombocytopenia.²⁴ These factors all increase the level of acute liver injury acquired during DENV infection; the resultant liver injury further reduces hepatic synthetic function, further worsening vascular leak and coagulopathy.²⁵

Clinical Presentation

Dengue begins abruptly after a typical incubation period of 5–7 days, and the course follows three phases: febrile, critical, and recovery.³²

The febrile phase is characterised by 2-7 days of fever, which can be biphasic (i.e., there is resolution of the fever between spikes). Other symptoms vary widely and include severe headache, retro-orbital pain, myalgia and arthralgia, macular or maculopapular rash, and minor hemorrhagic manifestations, including petechiae, ecchymoses, purpura, epistaxis, gingival bleeding, hematuria, or a positive tourniquet test.³² The tourniquet test is a physical exam finding that increases suspicion for dengue. A blood pressure cuff is inflated on the patient’s arm to the midway point between systolic and diastolic blood pressure, left inflated for 2 minutes, and then the petechiae are counted. More than 10 petechiae in a square inch is suggestive of dengue.³³

The critical phase of dengue begins when the fever breaks and lasts 24 to 48 hours, with most people returning to baseline normal. This is also when severe dengue sets in, and patients develop the plasma leakage found with severe dengue. Severe dengue can develop over the course of hours. As severe dengue sets in, the body initially maintains adequate circulation by narrowing the pulse pressure, with diastolic blood pressure rising. When patients develop plasma leakage, the fluid can accumulate in normal locations and cause hypoproteinemia or hemoconcentration. Patients can initially hide their compensation, but once hypotension develops, blood pressure rapidly declines, which can quickly be followed by shock and death despite adequate resuscitation. Patients with severe dengue can develop hemorrhagic complications, including hematemesis, hematochezia, menorrhagia, and melena. Other manifestations, which are less common, include encephalitis, hepatitis, myocarditis, and pancreatitis.³²

The recovery phase of dengue begins when plasma leakage slows, and the body begins to reabsorb the effusions that have occurred. With reabsorption of effusions, the patient’s clinical condition improves, hemodynamics stabilize, and diuresis starts. With the influx of fluid, cell counts can be diluted, but this corrects over time. Patients may present with a rash that desquamates and is intensely pruritic.³² 

For suspected dengue, dengue should be included in the differential diagnosis for patients with fever who live in or have recently traveled to dengue-endemic areas. Other common symptoms include severe headache, retro-orbital pain, myalgia and arthralgia, and a macular or maculopapular rash. History and physical exam findings are crucial for guiding concern for dengue.³⁴

Diagnostic Testing

Laboratory diagnosis of dengue can be confirmed by Nucleic Acid Amplification Testing (NAAT), RT-PCR, IgM antibody testing, or NS1 Antigen testing. With NAAT, no further testing is needed because a positive result is certain. Unfortunately, NAAT testing can be falsely negative if a patient is tested too early, before the virus has had enough time to reach detectable levels in the body. After 1 week, the preferred testing is IgM antibody testing. Positive NAAT or NS1 antigen confirmation indicates a confirmed test.³⁴

For each subsequent dengue infection, IgG is the dominant immunoglobulin, which can become present at the 10-month mark from the first infection with detectable IgG antibodies lasting throughout life in some patients.³²

Basic lab findings include thrombocytopenia and leukopenia. Plasma leakage during the critical phase of dengue infection can cause hemoconcentration and is commonly observed in laboratory testing. A severe dengue case can also be classified as such by elevated transaminases >1000, per the WHO classification.³²

Treatment

As DENV infections can range in severity from asymptomatic to hypovolemic/hemorrhagic shock, the strategy in the treatment of these patients varies based on presentation and anticipated clinical course. However, maintaining the widely accepted algorithmic approach, ABCDE (Airway, Breathing, Circulation, Disability, Exposure) has been shown to assist in the early recognition and treatment of time-critical diagnoses, interventions, and improve patient outcomes. Therefore, discussing the concerns when treating DF/severe dengue with this algorithm, prior to specific treatment recommendations for DENV infection, is warranted.³⁵

Airway: Severe forms of DENV may cause hemorrhagic bulla on mucosal surfaces.  Vomiting, oropharyngeal bleeding, lethargy, or reduced level of consciousness are all commonly reported in DENV infections and may require clearance with suctioning or placement of a definitive airway.³⁶

Breathing: Although uncommon, severe dengue can directly affect breathing through pulmonary edema secondary to vascular leakage or pulmonary hemorrhage secondary to thrombocytopenia and coagulopathy.³⁷ Vomiting and reduced level of consciousness may also impact a patient’s respiratory status. Breathing may also be affected by concomitant bacterial infections (such as pneumonia, which may or may not be secondary), which occur in up to 44% of deaths due to DENV infection.³⁸

Circulation: Severe dengue infections specifically impact circulation through endothelial dysfunction, leading to vascular leak and hemorrhage secondary to thrombocytosis and hepatic synthetic dysfunction. Volume expansion with crystalloid is the recommended first-line treatment with specific guidelines on transfusion of blood products.

Disability: Altered mental status/reduced level of consciousness may be present and can result from multiple etiologies. These include: low cerebral perfusion secondary to shock, cerebral edema secondary to vascular leak, hepatic encephalopathy due to acute liver injury, or direct cerebral infection with DENV.

Exposure: Exposing a patient and thoroughly examining their skin may uncover petechia/purpura or signs of gastrointestinal bleeding. These signs increase suspicion of hemorrhage, even in the absence of overt signs of shock.

Recommendations for Treatment and Hospitalization³⁹

There are no specific treatments for DENV infection at this time. While several novel treatments are currently being researched, the mainstay of treatment remains supportive care and homeostatic maintenance.

Current WHO guidelines divide DENV infections into three categories.

Non-severe disease: Individuals who do not have warning signs of worsening clinical status, are tolerating oral intake, and do not have other risk factors for acute decompensation. These patients are appropriate for outpatient management.

• Oral hydration is the primary treatment for these patients to prevent dehydration. Patients can be instructed to monitor their urine output as a measure of hydration, aiming for 4-6 urinations per day.
• Pain and fevers can be managed with oral acetaminophen (paracetamol). Standard doses apply and should be adjusted for children and for patients with renal/hepatic dysfunction. NSAIDs are not recommended due to the potential bleeding risk.
•  Corticosteroids were previously recommended; however, they are NOT currently recommended, given their high adverse effect profile and low improvement rates in non-severe DENV infection. Patients already being treated with corticosteroids for other reasons may be continued based on risk-benefit analysis.

Dengue with warning signs:³⁹ Persistent abdominal pain or vomiting, bleeding from mucosal membranes, hepatomegaly, or progressive elevation of hematocrit, minimal reduction in mental status.

Severe dengue: dyspnea, hypotension, signs of poor perfusion or end-organ damage such as AKI, ALI, significant change in level of consciousness, as well as any pregnant patient.

These patients require hospitalization and inpatient treatment, ranging from general floor management to critical care/ICU admission. The most critical portion of treatment in these patients is the management of hypovolemic shock.^38-40

• Intravenous fluids: Crystalloid (e.g., normal saline [NS] or Lactated Ringer’s [LR]) infusion is the preferred volume expander. Hypovolemia in DENV patients is largely due to endovascular dysfunction resulting in fluid leakage from capillary beds. Multiple studies have investigated the use of colloid-containing fluids to recover some of the patients’ extravasated plasma into circulation. However, colloid has not been shown to be superior to crystalloid. Additionally, colloid fluid has a higher side-effect profile than crystalloid, is significantly more expensive, and is more difficult to obtain in resource-poor areas (where severe DENV infections are more likely to occur).^38-40
  • The end goal of fluid resuscitation is improvement in peripheral perfusion. There are multiple measures that can be utilized, depending on patient factors, clinician comfort, and available resources. These include but are not limited to: IVC ultrasound, capillary refill time, passive leg raise, serial lactate measurements, improved tachycardia, and/or hypotension. In monitoring changes in perfusion, clinicians should not rely on a single variable, but rather multiple patient factors.^38-40
  • Studies have not shown a clinical difference in the use of NS vs LR in DENV patients. However, specific patients may benefit from one fluid vs another, for example, those with hyper/hyponatremia.⁴⁰
• Blood Products: There is no current role for prophylactic platelet transfusion in the majority of severe DENV patients. Thrombocytopenia and hemorrhage are well-known consequences of severe DENV infection. However, multiple studies have shown that platelet transfusion does not reduce the risk of hemorrhage, does not improve bleeding when present, does not reduce bleeding progression, or increase clot strength in these patients.^38-40
• There is a subset of patients whom platelet transfusion may be beneficial: planned procedures where bleeding is expected, platelet count < 10,000/microliter (10×103), and those with significant hemorrhage.^38-40
• Patients with significant hemorrhage should also be treated with PRBCs or a whole blood transfusion.^38-40
• Due to hepatic dysfunction in these patients, thrombocytosis is not the only coagulopathy they may have. Hemorrhaging patients should be tested and treated with FFP, cryoprecipitate, or vitamin K if indicated.
• Whenever feasible, localized hemorrhage control with hemostatic agents, packing, pressure, etc, should be attempted.³⁸
• Patients on antiplatelet therapy prior to infection had no significant change in clinical outcomes, regardless of whether antiplatelet therapy was continued or discontinued.⁴¹
• Corticosteroids have also not been shown to improve patient outcomes in severe DENV and may increase the risk of gastrointestinal bleeding.
• Acetaminophen (paracetamol) remains the recommendation for fever and pain reduction.
• Immunoglobulin infusion is not recommended as studies have not shown consistent benefit, and it may be implicated in increased bleeding events. It is only recommended in patients who develop complications that are known to respond favorably, such as Guillain-Barré.³⁹

Special Populations

• Pregnancy – Pregnant patients develop severe DENV infection at significantly higher rates than the general population. Physiological changes during pregnancy may obscure early signs of disease progression. As such, it is recommended that all pregnant patients, especially those near term, be hospitalized and closely observed during infection. Delivery should be delayed if possible, but if delivery is imminent, platelet transfusion and aggressive prevention of post-partum hemorrhage are indicated.³⁸
• Breastfeeding – Current guidelines recommend continued breastfeeding regardless of DENV infection, as the benefits of breastfeeding greatly exceed the low risk of transmission.¹⁶
• Diabetic patients have an increased risk of developing DKA/HHS during DENV infection. This is likely to worsen extant hypovolemia and should be treated aggressively.³⁸

Prognosis

In mild DF, the prognosis is generally excellent, with most patients experiencing a biphasic febrile illness lasting 5 to 7 days, after which they fully recover without any lasting effects. Supportive care, such as staying hydrated and receiving analgesics, is usually all that is needed.^3,11 Most of these patients return to regular activities within 1 to 2 weeks, although some may experience fatigue for a few weeks after the illness.^1,4

On the contrary, severe dengue poses a serious risk if not promptly recognized and managed, often requiring hospitalization for fluid replacement and monitoring. Severe dengue significantly amplifies morbidity through prolonged hospitalization for 5 to 10 days and intensive care needs in 1 to 5% of cases.^10,12 The critical period usually occurs between days 3 and 7 after fever subsides and is characterized by warning signs such as abdominal pain, persistent vomiting, mucosal bleeding, lethargy, and hepatomegaly.¹¹ With appropriate medical intervention, such as IV and potential blood transfusions, recovery is possible, and long-term effects are uncommon, though some patients may experience prolonged fatigue or, infrequently, organ dysfunction.^3,4,12 Certain factors can worsen the prognosis, and these include children younger than 5 years, pregnancy, obesity, and underlying conditions like diabetes or hypertension.^12,42

Overall, the mortality rate from dengue is relatively low, but it increases significantly in severe cases that are not properly treated. The global case-fatality rate (CFR) for dengue is estimated to be under 1% with effective treatment. However, it can soar above 20% in severe cases that go unmanaged, often leading to complications like shock, organ failure, or bleeding.^3,12 The WHO stresses that early detection and fluid treatment can help lower the CFR to under 1%.^4,42 Recent statistics indicate that there were over 12,000 dengue-related fatalities in 2024 and more than 3,000 in early 2025, coinciding with a significant rise in cases, including 14.6 million recorded in 2024.4 In outbreaks in the U.S., such as in Puerto Rico in 2024, the mortality rate was 0.2% among reported cases, with severe dengue affecting 4.2%.⁴² Cases linked to travel in the U.S. had an even lower mortality rate of less than 1% from 2010 to 2018, highlighting the importance of access to healthcare.⁴² In areas with limited resources, the impact of dengue can be much worse, resulting in higher rates of illness and death without timely intervention.⁴

Infection Prevention and Control

Dengue fever is a serious global health issue caused by the DENV, which is spread by Aedes mosquitoes. It affects between 50 and 100 million people worldwide each year.³ Since there’s no specific antiviral treatment available, prevention and control efforts focus on reducing mosquito populations and protecting individuals from bites.⁴ Below, various measures will be discussed that can be taken both on an individual basis and within communities, along with updates on vaccine developments.

At the individual level, preventing mosquito bites and minimizing personal risk factors are key. It is important to apply insect repellent containing ingredients such as DEET, picaridin, or oil of lemon eucalyptus to any exposed skin, especially at dawn and dusk when Aedes aegypti and Aedes albopictus mosquitoes are most active.⁴ Wearing long-sleeved shirts, long pants, socks, and closed shoes can significantly reduce skin exposure.³ In areas where mosquitoes are common, sleeping under insecticide-treated nets is advisable, particularly during the day, as these mosquitoes tend to bite indoors.¹²

In households, taking proactive measures such as installing fine-mesh screens on windows and doors, and eliminating standing water in places like flower vases or buckets, can help prevent mosquito breeding.2 For individuals with existing health conditions, such as hypertension or diabetes, conditions that can raise the risk of severe complications by up to 60%, it’s crucial to seek medical attention early if symptoms like fever, headache, or malaise appear. This can help prevent severe dengue.⁴³ Moreover, in cases of suspected infections, individuals are encouraged to report them promptly through integrated disease surveillance systems (IDSR) to enable timely action.^44,45

Community-level strategies focus on controlling mosquito populations and educating the public to curb the spread of diseases such as dengue. Integrated vector management includes strategies such as modifying the environment by covering water storage containers, ensuring proper waste disposal, and eliminating stagnant water in drains and construction sites.⁴ To prevent outbreaks, products such as temephos or biological agents such as Bacillus thuringiensis israelensis, a process known as larviciding, can be applied to breeding areas, alongside adulticiding methods such as space spraying with malathion.³

Mobilizing the community through health education initiatives raises awareness of dengue symptoms and prevention strategies, encouraging practices such as weekly “source reduction” efforts.¹² In regions heavily affected by dengue, such as Southeast Asia and the Americas, where outbreaks surged after 2010,¹⁰ collaboration across different sectors, especially with urban planning to improve drainage systems, is crucial.² Additionally, using surveillance systems such as the IDSR enables early detection, allowing community health workers to relay information to national health organizations.⁴⁶ The Ugandan Ministry of Health emphasizes the One Health approach, which combines human, animal, and environmental health strategies to tackle zoonotic risks in peri-urban areas.⁴⁴

Currently, there is no universal vaccine that completely prevents dengue fever, but significant advancements have been made in vaccine development.  The initial licensed dengue vaccine, CYD-TDV (Dengvaxia), was approved in several countries but faced limitations due to an increased risk of severe disease in seronegative individuals. Its use and production were discontinued in the market and are no longer recommended by the WHO.^47,48

The live attenuated tetravalent vaccine TAK-003 (Qdenga®), developed by Takeda, is currently the sole WHO-recommended vaccine for preventing dengue. As of 2025, the WHO endorses Qdenga for use in children aged 6 to 16 years in regions with a high dengue transmission prevalence. The vaccine is given as a two-dose regimen with a minimum interval of 3 months between doses and can be administered regardless of prior dengue infection, although its efficacy is greater in seropositive individuals.^47,49 Long-term results from Phase III studies indicate a sustained overall efficacy of about 61% against virologically confirmed dengue and 84% against hospitalized dengue over multiple years, although this varies by serotype.⁴⁹

Alternative vaccines, like the single-dose Butantan-DV, have demonstrated encouraging results in Phase III trials, showing about 80% efficacy; however, it is not yet broadly accessible or endorsed by the WHO as of 2025.⁴⁹ While vaccines play an essential role in preventing the disease, they should complement other control methods aimed at reducing mosquito populations rather than serve as standalone solutions. This emphasizes the importance of pre-vaccination screening.¹⁰

In summary, combating the spread of dengue requires a comprehensive approach that includes personal protective measures, community insect vector management (IVM), and targeted vaccination. Given the likelihood of increased dengue cases due to urbanization and climate change,² effective strategies will necessitate ongoing monitoring and public education efforts.⁴

Pearls and Pitfalls

• DENV is an arboviral disease transmitted by Aedes mosquitoes; half of the world’s population is at risk of infection.
• Typical dengue symptoms include fever, retro-orbital pain, myalgias, arthralgias, and fatigue.
• Most dengue infections are asymptomatic or mild, but severe dengue is a potentially fatal disease involving hemorrhagic complications, multi-organ failure, shock, and death.
• A positive tourniquet test can raise clinical suspicion for dengue infection.
• Diagnosis can involve a combination of NAAT (where available), PCR, and immunoassays.
• Treatment involves supportive care.
• IPC involves the prevention of mosquito bites.
• TAK-003 (Qdenga®) is the only vaccine approved for prevention of dengue infection, and it is only approved in children 6-16 years of age in high-risk regions.

References

1. Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013;496(7446):504-507. doi:10.1038/nature12060 
2. Murray NEA, Quam MB, Wilder-Smith A. Epidemiology of dengue: past, present and future prospects. Clin Epidemiol. 2013;5:299-309. doi:10.2147/CLEP.S34440 
3. Ligon BL. Dengue fever and dengue hemorrhagic fever: a review of the history, transmission, treatment, and prevention. Semin Pediatr Infect Dis. 2005;16(1):60-65. doi:10.1053/j.spid.2004.09.013 
4. World Health Organization, Special Programme for Research and Training in Tropical Diseases, eds. Dengue: Guidelines for Diagnosis, Treatment, Prevention, and Control. New ed. World Health Organization; 2009. 
5. Centers for Disease Control and Prevention (CDC). Areas with Risk of Dengue.; 2025. Accessed December 23, 2025. https://www.cdc.gov/dengue/areas-with-risk/index.html 
6. World Health Organization (WHO). Dengue.; 2025. Accessed August 30, 2025. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue 
7. Centers for Disease Control and Prevention (CDC). Current Dengue Outbreak.; 2025. Accessed December 23, 2025. https://www.cdc.gov/dengue/outbreaks/2024/index.html 
8. European Centre for Disease Prevention and Control. Dengue Worldwide Overview. European Union; 2025. Accessed September 2, 2025. https://www.ecdc.europa.eu/en/dengue-monthly 
9. Zhang WX, Zhao TY, Wang CC, et al. Assessing the global dengue burden: Incidence, mortality, and disability trends over three decades. Mang’era C, ed. PLoS Negl Trop Dis. 2025;19(3):e0012932. doi:10.1371/journal.pntd.0012932 
10. Guo C, Zhou Z, Wen Z, et al. Global Epidemiology of Dengue Outbreaks in 1990–2015: A Systematic Review and Meta-Analysis. Front Cell Infect Microbiol. 2017;7:317. doi:10.3389/fcimb.2017.00317 
11. Boyce RM, Collins M, Muhindo R, et al. Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness. BMC Infect Dis. 2020;20(1):835. doi:10.1186/s12879-020-05568-5 
12. Sanyaolu A. Global Epidemiology of Dengue Hemorrhagic Fever: An Update. J Hum Virol Retrovirology. 2017;5(6). doi:10.15406/jhvrv.2017.05.00179 
13. Roy SK, Bhattacharjee S. Dengue virus: epidemiology, biology, and disease aetiology. Can J Microbiol. 2021;67(10):687-702. doi:10.1139/cjm-2020-0572 
14. Wahala WMPB, De Silva AM. The Human Antibody Response to Dengue Virus Infection. Viruses. 2011;3(12):2374-2395. doi:10.3390/v3122374 
15. Gwee XWS, Chua PEY, Pang J. Global dengue importation: a systematic review. BMC Infect Dis. 2021;21(1):1078. doi:10.1186/s12879-021-06740-1 
16. Centers for Disease Control and Prevention (CDC). How Dengue Spreads.; 2025. Accessed December 23, 2025. https://www.cdc.gov/dengue/transmission/index.html 
17. Ohnishi K. Needle-stick dengue virus infection in a health-care worker at a Japanese hospital. J Occup Health. 2015;57(5):482-483. doi:10.1539/joh.14-0224-CS 
18. Grobusch MP, Van Der Fluit KS, Stijnis C, et al. Can dengue virus be sexually transmitted? Travel Med Infect Dis. 2020;38:101753. doi:10.1016/j.tmaid.2020.101753 
19. Barthel A, Gourinat AC, Cazorla C, Joubert C, Dupont-Rouzeyrol M, Descloux E. Breast Milk as a Possible Route of Vertical Transmission of Dengue Virus? Clin Infect Dis. 2013;57(3):415-417. doi:10.1093/cid/cit227 
20. Puerta-Guardo H, Glasner DR, Harris E. Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability. Kuhn RJ, ed. PLOS Pathog. 2016;12(7):e1005738. doi:10.1371/journal.ppat.1005738 
21. Ghetia C, Bhatt P, Mukhopadhyay C. Association of dengue virus non-structural-1 protein with disease severity: a brief review. Trans R Soc Trop Med Hyg. 2022;116(11):986-995. doi:10.1093/trstmh/trac087 
22. Libraty DH, Young PR, Pickering D, et al. High Circulating Levels of the Dengue Virus Nonstructural Protein NS1 Early in Dengue Illness Correlate with the Development of Dengue Hemorrhagic Fever. J Infect Dis. 2002;186(8):1165-1168. doi:10.1086/343813 
23. Rothwell SW, Putnak R, La Russa VF. Dengue-2 Virus Infection of Human Bone Marrow: Characterization of Dengue-2 Antigen-Positive Stromal Cells. Am J Trop Med Hyg. 1996;54(5):503-510. doi:10.4269/ajtmh.1996.54.503 
24. Khazali AS, Hadrawi WH, Ibrahim F, Othman S, Nor Rashid N. Thrombocytopenia in dengue infection: mechanisms and a potential application. Expert Rev Mol Med. 2024;26:e26. doi:10.1017/erm.2024.18 
25. Juneja D, Jain R, Nasa P. Dengue induced acute liver failure: A meta summary of case reports. World J Virol. 2024;13(1). doi:10.5501/wjv.v13.i1.91457 
26. Yeh CY, Lu BZ, Liang WJ, et al. Trajectories of hepatic and coagulation dysfunctions related to a rapidly fatal outcome among hospitalized patients with dengue fever in Tainan, 2015. PLoS Negl Trop Dis. 2019;13(12):e0007817. doi:10.1371/journal.pntd.0007817 
27. Marianneau P, Cardona A, Edelman L, Deubel V, Desprès P. Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death. J Virol. 1997;71(4):3244-3249. doi:10.1128/jvi.71.4.3244-3249.1997 
28. Martina BEE, Koraka P, Osterhaus ADME. Dengue Virus Pathogenesis: an Integrated View. Clin Microbiol Rev. 2009;22(4):564-581. doi:10.1128/CMR.00035-09 
29. Kurane I. Dengue hemorrhagic fever with special emphasis on immunopathogenesis. Comp Immunol Microbiol Infect Dis. 2007;30(5-6):329-340. doi:10.1016/j.cimid.2007.05.010 
30. Halstead SB. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns. Crowe Jr. JE, Boraschi D, Rappuoli R, eds. Microbiol Spectr. 2014;2(6):2.6.30. doi:10.1128/microbiolspec.AID-0022-2014 
31. Modhiran N, Watterson D, Muller DA, et al. Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity. Sci Transl Med. 2015;7(304). doi:10.1126/scitranslmed.aaa3863 
32. Centers for Disease Control and Prevention (CDC). Clinical Features of Dengue.; 2025. Accessed January 2, 2026. https://www.cdc.gov/dengue/hcp/clinical-signs/index.html 
33. Centers for Disease Control and Prevention (CDC). Tourniquet Test. Accessed September 2, 2025. https://www.cdc.gov/dengue/training/cme/ccm/Tourniquet_Test_F.pdf 
34. Centers for Disease Control and Prevention (CDC). Clinical Testing Guidance for Dengue.; 2025. Accessed January 2, 2026. https://www.cdc.gov/dengue/hcp/diagnosis-testing/index.html 
35. Thim T, Krarup NHV, Grove EL, Rohde CV, Løfgren B. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. Int J Gen Med. 2012;5:117-121. doi:10.2147/IJGM.S28478 
36. Hasan S, Jamdar SF, Alalowi M, Al Ageel Al Beaiji SM. Dengue virus: A global human threat: Review of literature. J Int Soc Prev Community Dent. 2016;6(1):1-6. doi:10.4103/2231-0762.175416 
37. Marchiori E, Hochhegger B, Zanetti G. Pulmonary manifestations of dengue. J Bras Pneumol Publicacao Of Soc Bras Pneumol E Tisilogia. 2020;46(1):e20190246. doi:10.1590/1806-3713/e20190246 
38. Tejo AM, Hamasaki DT, Menezes LM, Ho YL. Severe dengue in the intensive care unit. J Intensive Med. 2024;4(1):16-33. doi:10.1016/j.jointm.2023.07.007 
39. World Health Organization (WHO). WHO Guidelines for Clinical Management of Arboviral Diseases: Dengue, Chikungunya, Zika and Yellow Fever.; 2025. Accessed December 23, 2025. https://iris.who.int/server/api/core/bitstreams/634a55a5-327e-459b-a633-0650fe8ad6c9/content 
40. Tayal A, Kabra SK, Lodha R. Management of Dengue: An Updated Review. Indian J Pediatr. 2023;90(2):168-177. doi:10.1007/s12098-022-04394-8 
41. Chia PY, Htun HL, Leo YS, Lye DC. Safety of temporary interruption of antiplatelet therapy in dengue fever with thrombocytopenia. J Infect. 2021;82(2):270-275. doi:10.1016/j.jinf.2020.10.038 
42. Rodriguez DM, Madewell ZJ, Torres JM, et al. Epidemiology of Dengue — Puerto Rico, 2010–2024. MMWR Morb Mortal Wkly Rep. 2024;73(49):1112-1117. doi:10.15585/mmwr.mm7349a1 
43. Md-Sani SS, Md-Noor J, Han WH, et al. Prediction of mortality in severe dengue cases. BMC Infect Dis. 2018;18(1):232. doi:10.1186/s12879-018-3141-6 
44. Republic of Uganda Ministry of Health. National Technical Guidelines for Integrated Disease Surveillance and Response, Third Edition.; 2012. Accessed December 22, 2025. https://library.health.go.ug/leadership-and-governance/guidelines/national-technical-guidelines-integrated-disease-surveillance 
45. Republic of Uganda Ministry of Health. National Technical Guidelines for Integrated Disease Surveillance and Response, Third Edition.; 2021. Accessed December 22, 2025. https://www.afro.who.int/publications/third-edition-national-guidelines-integrated-diseases-surveillance-and-response 
46. World Health Organization (WHO). WHO African Region, 3rd Edition.; 2019. Accessed December 23, 2025. https://www.afro.who.int/publications/technical-guidelines-integrated-disease-surveillance-and-response-african-region-third 
47. World Health Organization (WHO). Vaccines and Immunization: Dengue.; 2025. Accessed September 2, 2025. https://www.who.int/news-room/questions-and-answers/item/dengue-vaccines 
48. Wilder-Smith A, Ooi EE, Horstick O, Wills B. Dengue. The Lancet. 2019;393(10169):350-363. doi:10.1016/s0140-6736(18)32560-1
49. Khan MB, Yang ZS, Lin CY, et al. Dengue overview: An updated systemic review. J Infect Public Health. 2023;16(10):1625-1642. doi:10.1016/j.jiph.2023.08.001