Nabila Ismail, PharmD

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.

 In 2019, there were 5.2 million cases of dengue reported across 129 countries,

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).

 The vaccine will be available in the United States this year (2022); however, its use comes with restrictions.

This article provides information on the vaccine and eligible individuals who can receive it.

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.

Dengue affects approximately 100 million to 400 million people each year and continues to be a growing public health concern.

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.

Most cases of dengue are asymptomatic or mild, but some cases can be severe with flu-like symptoms such as

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.

 Those with first dengue infections generally experience mild or no symptoms; however, subsequent infections can lead to a more severe form of the disease.

 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.

 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.

 Before Dengvaxia, the CDC’s Advisory Committee on Immunization Practices (ACIP) had no recommendations regarding vaccines to prevent dengue.

 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).

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.

 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.

 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.

 Health care professionals should confirm prior dengue infection before proceeding with the vaccine series. A prevaccination checklist is available from the CDC (Figure).

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.

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%).

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.

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.

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.

 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.

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

Articles

The FDA approved the first vaccine for dengue disease in May 2019.

Dengue Vaccine: What Pharmacists Need to Know

My name is Nabila Ismail, PharmD, but you may know me online as Dose of Travel. I started traveling in my early college days and started blogging about the journey. Now, I’ve visited 40 countries, mostly solo, and I’m passionate about empowering others to travel more. I love storytelling, discussing travel medicine, and talking about diversity in travel.

Here’s how my travel story began and how Dose of Travel came about.

All throughout high school and the beginning of college, I felt like something was missing. I was craving an adventure that I hadn’t yet experienced. One day, right before my Chemistry 101 final, I decided that I wanted to be an au pair in Madrid, Spain. A few months prior, I had visited my best friend during her gap year where she was an au pair in Belgium. Having seen the experiences, freedom, and the stories she had to share, I knew I wanted to feel the same way.

I spent my summer living in Madrid and caring for 3 children under the age of 6. That summer changed everything for me, as I learned more about myself than I had that entire year in college.

I wish I could put the feelings into words to describe what that summer meant for me. I found the experience to be liberating, educational, and a breath of fresh air. This adventure was only the start and led to so many others.

From that moment, I started documenting my travels on Instagram. I had a blog, I loved arts and crafts, and really valued creativity so I started sharing my stories on Instagram with photos—nothing to rave home about now, they were most definitely on an iPhone 3.

Each stretch of vacation time I had, I started planning a trip. Since I was a full-time student, I found ways to go abroad with minimal finances but maximal experiences. Here are a few ways I traveled, I even wove in pharmacy in some of my experiences:

I was an au pair twice. After Spain, I went on to be an au pair in wine country outside of Verona, Italy, for another 3 months before the start of pharmacy school. Being an au pair awards you free housing, food, and a small stipend in exchange for caring for children and teaching them your language. It means even exchange, so it’s meant to be an exchange of culture and experiences.

You can choose to go through an agency where you will have to pay a hefty fee, but it may be worth it. I chose not to and took the risk. I loved both of my experiences, but it may not be for everyone.

Being an au pair is a great way to get a better understanding of culture and have an authentic experience. It’s also really easy to meet other au pairs and become friends with them.

As a pharmacy student, I took a big liking to public and global health, which came in handy because there was the potential for travel. I spent a lot of my time hanging out in the School of Public Health and we had an office in another building dedicated to my university’s global efforts and projects.

I joined a hackathon at school and, luckily, my team won. I stayed working on that project and had the opportunity to go to Uganda to get hands-on experience. I spent 2 weeks during my spring break as a pharmacy student working on something really important to me.

I eagerly waited for my fourth year of pharmacy school because it meant that I could leave Buffalo and explore new places. Having the opportunity to do an international rotation was really important to me so I factored that in when selecting a school.

I was the only one in my class to do a rotation in Zimbabwe. It was a global health elective and I had a lot of freedom to design the 6 weeks the way I wanted. My interests were really diverse, I was fascinated to learn about pharmacy practice, health care in general, HIV/AIDS, psychiatry, and non-profit work. 

The bulk of my time was spent in HIV/AIDS clinics, in which I had lots of hands-on experience with patients. I had the opportunity to visit the UNICEF compound, visit a mental health clinic, go to a pharmaceutical company, visit labs, and even the FDA of Zimbabwe called Medicines Control Authority of Zimbabwe.

This trip not only satiated the travel bug in me but I truly believe made me a better pharmacist. I was able to practice motivational interviewing, provide cultural-competent care, and view pharmacy and health care on a global level.

After that enriching experience in Zimbabwe, I had an off block (I planned it that way!) and I set out on yet another solo journey.

I spent 4 months solo backpacking throughout Africa with a 65L bag, taking local transport, staying at hostels, and eating street food. I saw one of the most spectacular waterfalls—Victoria Falls—saw the Big 5 while on safari in Tanzania, woke up to zebras grazing outside of my tent, wandering the colorful streets of Bo Kaap in Cape Town, going on a game drive in Chobe National Park in Botswana, and so much more.

I’ve also backpacked through Europe and Southeast Asia. Having visited Thailand, Cambodia, Czech Republic, and Hungary to name a few.

During the summers, winter and spring breaks, and long weekends, I was jet-setting across the globe. When I was in school, my Instagram and blog fell quiet because I wasn’t traveling. I started to document my journey to pharmacy school with my experience and tips.

It was mostly a way for me to have my creative outlet but I had no idea that there were people interested in knowing more. As I progressed in school, I started to think about the career I wanted afterwards so I began interviewing pharmacists in unique roles and adding that to my blog.

I began to realize that I was inspiring 2 different audiences, those in pharmacy and those who were interested in travel. Nine years after my first trip, I have no intention of stopping my travels. I’m always planning my next one and since I work remotely now, I’m able to weave travel into my schedule more and more these days.

I’ve started to combine my interests more so these days, continuing with public and global health, learning more about travel medicine, and discussing health and travel as we maneuver through a pandemic.

If you’re interested in knowing more about how I travel, what I do now, and want more tips, please feel free to follow me @doseoftravel.

Pharmacist combines storytelling, travel medicine, and discussions about diversity in travel.