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The Wide World of Vaccines

July 2019

Summer is for Travel: A New Vaccine for Potential Use in Repeated Travelers to the Caribbean? 

Dr. Harrison.jpg            

Christopher J. Harrison, MD, FAAP, FPIDS
 | Director, Infectious Diseases Research Laboratory | Director, Vaccine and Treatment Evaluation Unit | Professor of Pediatrics, UMKC School of Medicine
 
Why should we care that a new live-attenuated dengue vaccine is available to prevent disease due to all four dengue serotypes in patients 9 to 16 years old?1,2 It is currently approved in the U.S. for those living in endemic areas with laboratory-confirmed dengue immunity. 

What? The vaccine is only for those that have already had dengue and have antibody on lab testing? This is the opposite of most vaccines where we need to protect those with no prior infection, which would ordinarily be thought of as inducing protection. Well, dengue acts differently, in a way. Infection does protect from the infecting serotype, but the worst illnesses occur in seropositive patients who get infected a second time with a different serotype than they had during their first dengue infection. Another reason to only vaccinate seropositive patients is that seronegative recipients of this live vaccine often get symptoms very much like wild type dengue fever.  

Primary Dengue Fever       
 
After acquisition via a bite from an infected mosquito (most often Aedes aegypti, see Figure 1 for continental U.S. with this mosquito), there is a 4 to 10-day incubation. With initial primary infection there are then 2 to 7 days of acute symptoms. In children under 15 years old, there may be a prodrome (mottling of skin and facial flushing) followed often by a self-limited febrile illness, which may include severe headache and myalgias, retro-orbital pain, arthralgias, altered taste, adenopathy and vomiting. Leukopenia, thrombocytopenia and elevated AST and ALT are common with primary infection. Untreated dengue fever has a mortality rate of ~3% versus <1% if supportive treatment is provided. Hydration is key in supportive management and patients should avoid aspirin, ibuprofen or Naprosyn, which may affect hemostasis themselves. 

Figure 1. Range of Aedes aegypti in continental U.S.

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Severe Dengue (dengue hemorrhagic fever and/or dengue shock syndrome) 

Severe dengue starts similar to dengue fever, but soon after deffervescence, there can be loss of vascular integrity and onset of hemorrhagic signs/symptoms including easy bruising/bleeding and/or GI bleeding or hematuria. Severe abdominal pain, persistent vomiting and febrile seizures may also occur. The 24 hours after onset of severe symptoms is frequently critical, particularly if untreated, as recalcitrant shock may occur. Combinations of abdominal pain, vomiting, restlessness, pallor, tachypnea, tachycardia, narrow pulse pressure, dizziness/lightheadedness and decreased consciousness raise concern for impending shock and circulatory failure. Untreated severe dengue has a mortality as high as 20% versus 2 to 5% if treated.

The Vaccine: Dengvaxia® 

This live-attenuated vaccine is given as doses at 0, 6 and 12 months. It is ~76% effective in 9 to 16-year-olds who had a previous, laboratory-confirmed infection. This age was chosen because youths are most likely to be seropositive and at greatest risk of severe symptoms.   

Vaccine Adverse Effects        
 
Headache, muscle pain, joint pain, fatigue, injection site pain and low-grade fever occur, but in trials the frequency was: headache (40%); injection site pain (32%); myalgia (29%); and malaise (25%), and was similar in placebo recipients. 

Geography             
 
Nearly all of the infrequent, but reported dengue cases in the continental U.S. have been in travelers infected elsewhere, particularly in the heartland (no cases in Missouri and one in Kansas last year). Figure 2.3 Small local dengue outbreaks most recently occurred in Texas (2013); Florida (2013); and Hawaii (2015), per the CDC.4        

The disease often occurs in American Samoa, Puerto Rico, Guam, U.S. Virgin Islands, Latin America, Southeast Asia and the Pacific Islands. However, there is little doubt that most continental U.S. cases go unrecognized. It takes a high index of suspicion to distinguish dengue fever from other nonspecific viral illnesses. The patient’s travel history is the key factor.  

Figure 2. States and territories reporting dengue cases, United States, 2019 (as of June 5, 2019). 

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Is There Anything Heartland Providers Can Do? 
 
If your patients have traveled previously to areas endemic for dengue and are planning to travel there again, discuss whether they had a compatible illness during or soon after their travel. Antibody testing can then be obtained to confirm previous infection. While the likelihood of prior infection is small, if positive, they may be at risk for subsequent infection. A visit to a travel clinic four to six weeks before the repeat travel may be useful to consider, not only for dengue vaccine, but also for other travel-related vaccines and advice.5
 
References

1. JAMA. 2019;321(21):2066. doi:10.1001/jama.2019.6886. 

2. https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-dengue-disease-endemic-regions. 

3. https://www.cdc.gov/dengue/areaswithrisk/in-the-us.html. 

4. https://www.cdc.gov/dengue/statistics-maps/index.html. 

5. https://www.cdc.gov/dengue/prevention/plan-for-travel.html.