Dengue Vaccine: What Pharmacists Need to Know
The FDA approved the first vaccine for dengue disease in May 2019.
Although COVID-19 is not completely behind us, prepandemic life is starting to make a comeback. With stay-at-home orders being lifted and the Northern Hemisphere shifting to warmer weather, more people are venturing outside. Although many of us are relishing this newfound freedom, so too are the mosquitoes, ticks, and fleas, anxiously awaiting the opportunity to feast on exposed skin and spread disease. Indeed, the World Health Organization reports that globally, vector-borne diseases account for more than 17% of all infectious diseases, with dengue being the most prevalent viral infection.1 In 2019, there were 5.2 million cases of dengue reported across 129 countries,2 including several US territories.3
There are no effective antiviral treatments available against dengue, and up until recently, there was no available prophylaxis. In May 2019, however, the FDA approved the first vaccine for dengue disease, Dengvaxia (Sanofi Pasteur).3 The vaccine will be available in the United States this year (2022); however, its use comes with restrictions.4 This article provides information on the vaccine and eligible individuals who can receive it.
OVERVIEW OF DENGUE
Dengue is an infection caused by a virus transmitted through infected mosquitoes, primarily female Aedes aegypti, and Aedes albopictus to a lesser extent. There are 4 viral serotypes: DENV-1, DENV-2, DENV-3, and DENV-4.2
Dengue affects approximately 100 million to 400 million people each year and continues to be a growing public health concern.2 Although rare in the continental United States,5 territories of American Samoa, Puerto Rico, and the US Virgin Islands, and freely associated states, including the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau are considered dengue-endemic.4
Most cases of dengue are asymptomatic or mild, but some cases can be severe with flu-like symptoms such as2:
- High fever (104°F)
- Muscle and joint pain
- Pain behind the eyes
- Swollen glands
If an individual has just returned from traveling in any of these regions and presents with many of these symptoms, dengue should be suspected. Severe dengue usually presents 3 to 7 days after illness onset; symptoms, which can be fatal, include plasma leaking, fluid accumulation, respiratory distress, bleeding, and organ failure. Severe dengue infection remains a leading cause of illness and death in some Asian and Latin American countries.2 Those with first dengue infections generally experience mild or no symptoms; however, subsequent infections can lead to a more severe form of the disease.3 Approximately 95% of hospitalized patients with dengue have a subsequent infection, underscoring the need for greater prevention.
Dengvaxia is a live-attenuated chimeric tetravalent vaccine.6 It is made using recombinant DNA technology; sequences encoding the premembrane and envelope proteins of the yellow fever 17D backbone were exchanged with the homologous sequences encoding for dengue virus serotypes 1, 2, 3, and 4.6,7 Before Dengvaxia, the CDC’s Advisory Committee on Immunization Practices (ACIP) had no recommendations regarding vaccines to prevent dengue.7 With the approval of Dengvaxia, the ACIP has recommended the vaccine for individuals aged 9 to 16 years who live in an area where the virus is endemic and have had a previous dengue infection with a confirmed laboratory test (positive dengue reverse transcription-polymerase chain reaction [RT-PCR] test result or positive dengue nonstructural protein 1[NS1] antigen test or positive results on both anti-dengue virus immunoglobulin G tests in a 2-step testing algorithm).7,8
Because of the cross-reactivity of dengue with other flaviviruses than can be circulating in dengue-endemic areas (eg, Zika virus), a single positive anti-dengue virus immunoglobulin M test result is not sufficient proof of dengue virus infection for vaccination.8 An acute dengue diagnosis can be made using blood or serum collected no more than 7 days after symptom onset to detect viral RNA through nucleic acid amplification tests, viral antigens by enzyme-linked immunosorbent assay (ELISA) or rapid diagnostic tests, or immunoglobulin M antibodies via serologic testing.7 It is important to note that if a person not previously infected with dengue receives Dengvaxia, the vaccine could act like a first dengue infection (without actually infecting the person) and a subsequent infection could lead to the severe form of the disease.9 Health care professionals should confirm prior dengue infection before proceeding with the vaccine series. A prevaccination checklist is available from the CDC (Figure).10
Vaccine Formulation, Safety, and Efficacy
Dengvaxia is a lyophilized powder that needs to be reconstituted with the supplied diluent (0.4% NaCl). Three doses (0.5 mL each) are given 6 months apart.6
The safety of Dengvaxia was assessed in 9 randomized, placebo-controlled, multicenter clinical trials. A total of 19,102 individuals (aged 9-16 years) received at least 1 dose of Dengvaxia and 9484 received placebo. Common adverse reactions were headache (40%), injection site pain (32%), malaise (25%), asthenia (25%), and myalgia (29%).6
Vaccine efficacy was studied in 2 randomized, observer-blind, placebo-controlled, multicenter studies. The first trial was conducted in 20,869 individuals (aged 9-16 years) from 4 Latin American countries and Puerto Rico. The second trial was conducted in 10,275 participants (aged 2-14 years) from 5 Asian-Pacific countries. Participants were monitored for symptomatic virologically confirmed dengue (VCD) starting on day 0. VCD was defined as an acute febrile illness with temperatures of at least 38 °C on at least 2 consecutive days verified by a dengue RT-PCR or dengue NS1 ELISA antigen test. Efficacy against VCD was assessed from 28 days following dose 3 for a period of 12 months.6
The efficacy analysis of Dengvaxia was limited to participants who were seropositive for dengue at baseline and who received all 3 doses of the vaccine. Among those enrolled in the first study, Dengvaxia was associated with an 80.6% (95% CI, 50.7%-93.2%) efficacy rate in preventing symptomatic VCD. Similarly, in the second study, Dengvaxia demonstrated an efficacy rate of 77.2% (95% CI, 18.3%-94.9%). Of note, the studies were not designed to assess the efficacy of Dengvaxia in the individual dengue serotypes.6
THE FUTURE OF VACCINES FOR GLOBAL PUBLIC HEALTH
The development and approval of a dengue vaccine is a critical step in combatting this global public health challenge. Although not indicated as a travel vaccine, the availability of Dengvaxia in the United States to those who qualify may be important as travel increases and travelers may be exposed to diseases regional to their destination. Indeed, the market for travel vaccines is expected to explode in the upcoming years, with estimates of US $5.91 million by 2028.11 It is an exciting time for new vaccine technology and pharmacists will be at the helm to educate patients and health care colleagues on all the latest vaccines.
ABOUT THE AUTHOR
Nabila Ismail, PharmD, is a pharmacist and engagement marketing manager at GoodRx in Los Angeles, California. She is also the founder and creator behind Dose of Travel, LLC. You can find her sharing travel content from the 40+ countries she's been to and find her work in Forbes, Fodors, Travel and Leisure, and more! You can follow her at @doseoftravel on Instagram.
1. Fact sheet. Vector-borne diseases. World Health Organization. March 2, 2020. Accessed May 5, 2022. https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases
2. Fact sheet. Dengue and severe dengue. World Health Organization. January 10, 2022. Accessed May 1, 2022. https://www.who.int/en/news-room/factsheets/detail/dengue-and-severe-dengue
3. First FDA-approved vaccine for the prevention of dengue disease in endemic regions. News release. United States Food and Drug Administration. May 01, 2019. Accessed May 1, 2022. https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-denguedisease-endemic-regions
4. For healthcare providers: a dengue vaccine can protect your patients. Centers for Disease Control and Prevention. Last reviewed: December 16, 2021. Accessed May 6, 2022. https://www.cdc.gov/dengue/vaccine/hcp/index.html
5. Shepard DS, Undurraga EA, Halasa YA, Stanaway JD. The global economic burden of dengue: a systematic analysis. Lancet Infect Dis. 2016;16(8):935- 941. doi:10.1016/S1473-3099(16)00146-8
6. Dengvaxia. Prescribing information. Sanofi Pasteur, Inc; 2019. Accessed May 1, 2022. https://www.fda.gov/media/124379/download
7. Paz-Bailey G, Adams L, Wong JM, et al. Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021. MMWR Recomm Rep. 2021;70(6):1-16. doi:10.15585/mmwr.rr7006a1
8. Laboratory testing requirements for vaccination with Dengvaxia dengue vaccine. Centers for Disease Control and Prevention. Last reviewed May 10, 2022. Accessed May 25, 2022. https://www.cdc.gov/dengue/vaccine/hcp/testing.html
9. Vaccine eligibility & recommendations. CDC website. Last reviewed: December 20 , 2021. Accessed May 12, 2022. https://www.cdc.gov/dengue/vaccine/hcp/eligibility/index.html
10. Dengvaxia pre-vaccination checklist. Centers for Disease Control and Prevention. Updated December 10, 2021. Accessed May 6, 2022. https://www.cdc.gov/dengue/resources/DVBD_FS_Vaccination_Checklist-508.pdf
11. Travel vaccines market forecast to 2028 - COVID-19 impact and global analysis by product (hepatitis a, hepatitis b, meningococcal vaccines, DPT, yellow fever, typhoid, Japanese encephalitis, measles mumps & rubella, rabies, polio, influenza, varicella & shingles, cholera, and others) and application (domestic travel and outbound travel). The Insight Partners. Published March 2022. Accessed May 6, 2022. https://www.theinsightpartners.com/reports/travel-vaccines-market