CDC: Dengue Virus Poses Increased Threat in United States

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Cases of Dengue virus—the most common global arboviral disease—are on the rise.

Dengue cases are on the rise and the virus now poses an increased risk of infections in the United States, according to a CDC Health Alert Network Health Advisory.1

According to the agency, global incidence of dengue virus has been the highest on record in 2024, with many countries reporting “higher-than-usual dengue case numbers.” Countries in the Americas in particular are reporting a record-breaking number of cases recorded between January 1 and June 24 of this year: more than 9.7 million cases, or twice as many as all cases reported in 2023.

Dengue virus is transmitted by infected Aedes mosquitos. | Image credit: witsawat - stock.adobe.com

Dengue virus is transmitted by infected Aedes mosquitos. | Image credit: witsawat - stock.adobe.com

Dengue is the most common global arboviral disease, caused by “4 distinct but closely related dengue viruses.” These viruses are transmitted through the bite of infected Aedes mosquito vectors. After infection, an individually is generally protected against reinfection from that specific dengue virus, but protection from other dengue viruses is only conferred for “several months to years.”

One in 4 dengue virus infections are symptomatic and can be mild or severe in nature. Symptoms typically begin following a 5- to 7-day incubation period (range, 3-10 days) and include fever in conjunction with other nonspecific signs and symptoms: nausea, vomiting, rash, muscle aches, joint pain, bone pain, pain behind the eyes, headache, and/or low white blood cell counts. Dengue virus warning signs—which can predict progression to severe disease—include abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation such as ascites or pleural effusion, mucosal bleeding, lethargy or restlessness, progressive increase of hematocrit, or liver enlargement of 2 cm or more.

Severe disease occurs in 1 in 20 people with symptomatic dengue and is associated with symptoms that include severe bleeding, shock or respiratory distress due to plasma leakage, or end-organ impairment.

Pregnant people, infants aged 1 year or younger, and adults aged 65 years and older, as well as individuals with certain medical conditions, are at an increased risk of developing severe dengue.

READ MORE: Reducing the Misuse of Antibiotics in Malaria and Dengue

Diagnostics tests are available for individuals presenting with symptoms of dengue. All patients should be tested with a reverse-transcription polymerase chain reaction (RT-PCR) or nonstructural protein 1 (NS1) antigen test, as well as with an Immunoglobulin M (IgM) antibody test to confirm dengue infection. While these tests can be used regardless of the date of symptom onset, test sensitivity for both RT-PCT and NS1 antigen tests decrease after the first 7 days. Immunoglobulin G detection via enzyme-linked immunosorbent assay (ELISA) should not be used to diagnose acute dengue; this testing option “does not distinguish between current and previous” dengue virus infection.

Dengue virus treatment include supportive care and “careful volume management,” as there are no approved antiviral medications available for treatment. The most effective interventions to reduce dengue-related morbidity and mortality include appropriate triage, management, and follow-up. A World Health Organization-recommended management strategy can decrease dengue-related mortality from 13% to less than 1%.

In 2019, the FDA approved the dengue tetravalent vaccine, live (Dengvaxia) as the first and only vaccine available in the US for the prevention of dengue disease caused by all 4 dengue virus serotypes.2 The vaccine is indicated for use in children and adolescents aged 9 to 16 years with laboratory confirmed previous dengue virus infections who live in areas, such as American Samoa, Guam, Puerto Rico, and the US Virgin Islands, where dengue is endemic. In 2021, the CDC Advisory Committee on Immunization Practices recommended this vaccine for this patient population.1

However, vaccine manufacturer Sanofi Pasteur elected to stop manufacturing Dengvaxia “citing a lack of demand in the global market to continue production”3 and reassuring the public that the decision “is not driven by quality, safety, or efficacy concerns.”4 Dengvaxia will be discontinued in September 2025 and final doses are set to expire in September 2026.

In Puerto Rico, where dengue has been declared a public health emergency, the American Academy of Pediatrics (AAP) Puerto Rico Chapter is working in conjunction with the CDC and the Puerto Rico Department of Health to continue vaccinating children with Dengvaxia while it remains available.4

“Amid the challenges of climate change, the burden of dengue fever is escalating, particularly impacting children aged 9 to 16 who face a heightened risk of severe infection,” said Gredia Huerta-Montanez, MD, FAAP, immediate past president of the AAP Puerto Rico Chapter and a member of the AAP Council on Environmental Health and Climate Change Executive Committee.4 “Vaccination, alongside measures to prevent mosquito bites and control breeding sites, could play a crucial role in preventing this illness.”

Prior to its approval in the United States, Sanofi faced significant challenges in other countries where the vaccine had been marketed since 2015. In 2017, the company announced labeling updates limiting use of the vaccine to individuals who have been previously exposed to dengue virus; this updated was based on the results of a new analysis which demonstrated antibody-dependent enhancement, “a dengue phenomenon that makes repeat infections more severe and can cause severe illness after vaccination in those who haven’t been previously exposed to the virus.”5

The labeling change was anticipated to cause a $120 million fourth quarter loss for the company.5

Other dengue virus vaccines have faced approval challenges. In 2023, Takeda elected to withdraw its application for vaccine candidate TAK-003, a dengue tetravalent vaccine, live, attenuated, from the FDA.6 The agency had requested additional data not captured in the phase 3 TIDES clinical trial (NCT02747927) that supported the application. TAK-003, known elsewhere as Qdenga, is approved for use in Europe, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand. Earlier this year, Takeda announced a strategic partnership with Biological E. Limited to accelerate Qdenga access in countries to the tune of up to 50 million doses of Qdenga per year.7

Following the worst of the COVID-19 pandemic, dengue cases saw a global resurgence: more than 4.6 million cases and 4000 deaths were reported in the Americas in 2024.1 Disease transmission peaks during warm, wet months in tropical and subtropical regions, and cases are anticipated to continue increasing along with the rise in global temperatures. These rising temperatures are also poised to potentially expand the range of Aedes mosquitos, as well as impact the other factors facilitating viral transmission including quicker viral amplification in the mosquito, increased vector survival, and changes in mosquito reproduction and biting rates.

The CDC suggests that health care providers maintain a high suspicion for dengue virus among patients presenting with fever and recent travel to areas with frequent or continuous dengue transmission. FDA-approved dengue tests should be on-hand, and treatment should not be delayed while waiting for test results. Counsel patients around best practices to prevent mosquito bites, as well as how to recognize dengue symptoms and when medical attention should be sought.

READ MORE: Infectious Disease Resource Center

References
  1. Increased risk of dengue virus infections in the United States. CDC Health Alert Network. June 25, 2024. Accessed June 26, 2024. https://emergency.cdc.gov/han/2024/han00511.asp
  2. First FDA-approved vaccine for the prevention of dengue disease in endemic regions. FDA. News release. May 1, 2019. Accessed June 26, 2024. https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-dengue-disease-endemic-regions
  3. Dengue vaccine. CDC. Updated May 14, 2024. Accessed June 26, 2024. https://www.cdc.gov/dengue/hcp/vaccine/index.html
  4. Jenco M. AAP, CDC working to vaccinate children in Puerto Rico against dengue while vaccine remains available. AAP News. April 12, 2024. Accessed June 26, 2024. https://publications.aap.org/aapnews/news/28617/AAP-CDC-working-to-vaccinate-children-in-Puerto
  5. Soucheray S. Sanofi restricts dengue vaccine but downplays antibody enhancement. University of Minnesota CIDRAP. December 1, 2017. Accessed June 26, 2024. https://www.cidrap.umn.edu/dengue/sanofi-restricts-dengue-vaccine-downplays-antibody-enhancement
  6. Liu A. Updated: Takeda yanks FDA filing for dengue vaccine, citing data disagreement with regulator. Fierce Pharma. June 11, 2023. Accessed June 26, 2024. https://www.fiercepharma.com/pharma/takeda-yanks-fda-application-dengue-vaccine-citing-data-collection-disagreement
  7. Takeda and Biological E. Limited collaborate to accelerate access to dengue vaccine endemic areas. News release. Takeda. February 26, 2024. Accessed June 26, 2024. https://www.takeda.com/newsroom/newsreleases/2024/collaboration-to-accelerate-access-to-dengue-vaccine/
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