Charles H. Mayo, MD, one of the famed Mayo brothers wrote, “Today the only thing that is permanent is change.” That might have been a hundred years ago, but it’s certainly still the situation with influenza and its prevention nowadays. This coming fall for 2018-2019 clinicians will once again have changes to the recommendations that will affect their practice and their patients.
Change is inevitable with influenza prevention because of the annual genetic drift and sometime shift across the influenza strains. Every year experts survey global influenza occurrence, the genetic characterization of circulating strains, the antigenic characterization of those infections, and the candidate vaccine viruses available to determine what strains to recommend to influenza vaccine manufacturers. This year the Food and Drug Administration’s Vaccines and Related Biologic Products Advisory Committee recommended that the 2018–19 trivalent vaccine to be used in the United States contain two A strains, including the A/Michigan/45/2015 (H1N1)pdm09-like virus, representing no change from last season, and the A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, which is new this season, chosen because the resulting egg-propagated vaccine virus is more similar to the circulating virus, as well as B/Colorado/06/2017-like virus (B/Victoria line), which is new this season, as there is an increasing circulation of a B/Victoria line strain with antigenic drift.
More and more influenza vaccines are made as quadrivalent vaccines with two B strains. These theoretically offer benefits to children who suffer more with B strain influenza infections. The benefit is wider coverage of possible circulating strains. This year the Food and Drug Administration’s Vaccines and Related Biologic Products Advisory Committee recommended the quadrivalent influenza vaccine strains also include the B/Phuket/3073/2013-like virus (B/Yamagata) strain, which was the same last year. While the quadrivalent influenza vaccines offer theoretical advantages to the trivalent vaccine for children, the Advisory Committee on Immunization Practices (ACIP) does not state a preference of the quadrivalent vaccine over the trivalent vaccine, even for children.
The live attenuated influenza vaccine or LAIV, known by the brand name FluMist, will be this season as before only available as a quadrivalent rather than trivalent vaccine.
New this year is the reinstating of the ACIP recommendation for LAIV. The last two seasons (2016-2017 and 2017-2018) the ACIP has not recommended the vaccine. While before the pandemic of 2009-2010, LAIV performed favorably to the injected influenza vaccines for children and equally as well for adults, the ACIP reviewed post-pandemic performance of LAIV and concluded that it could not recommend LAIV given problematic performance, primarily for the pandemic H1N1 strain still circulating. It appears that the LAIV H1N1 vaccine strain did not replicate in the nasal epithelial cells as well as the pre-pandemic H1N1 strain. Thus for two years while the Food and Drug Administration continued to license the vaccine, the ACIP did not recommend its use. This year, however, the ACIP met in February and reviewed evidence presented by the manufacturer that showed improved immunogenicity. The manufacturer had made a substantive change in the strain used in the vaccine representing the pandemic H1N1 strain. The A/Slovenia strain used appears to replicate better as it was more immunogenic in children producing higher antibodies in children than the 2015-2016 strain. The term immunogenicity refers to the vaccine’s ability to produce protective antibodies. We lack efficacy data, however, comparing the vaccine against no vaccine or against the inactivated, injected forms with its ability to actually prevent disease rather than just make antibodies. Of note, the FDA licenses all influenza vaccines each year on just antibody production or immunogenicity and does not require or expect efficacy data.
Surprisingly, the American Academy of Pediatrics (AAP) chose to limit its recommendation of the LAIV this coming season to be used only if no other option was available. It did this due to the lack of efficacy data for this new form of LAIV. In previous years the AAP along with the American Academy of Family Physicians, the American College of Physicians, and the American College of Obstetricians and Gynecologists harmonized their recommendations for the flu vaccines as well as other vaccines to reduce confusion and help advance vaccine delivery. This decision may likely cause confusion for pediatricians recommending flu vaccine as they are faced with two different official recommendations for their patients.
The previous restrictions to LAIV all apply except the past contraindication for those with egg allergies. The ACIP now permits the use of any egg-based influenza vaccine to be given to egg allergic individuals but holds that those with serious egg allergies (anaphylaxis) should receive their vaccine in a medical setting. The vaccine is indicated only for children 2 years and older and adults 49 years and younger. LAIV shared contraindications and precautions with the inactivated influenza vaccine and has some additional special contraindications and precautions. Table 1 lists the contraindications and precautions for both the IIV and the LAIV.
The injected inactivated influenza vaccines vary in the ages indicated. Table 2 lists all the vaccines available in 2018-2019 and reflects the complexities with regard to the dosing. Fluzone has a lower dose for children 6 months through 35 months of age whereas Flulaval and Fluarix do not.
Clinicians will also have once again non-chicken-egg based vaccines, including the recombinant influenza vaccine (RIV) and the cell-cultured based inactivated influenza vaccine (ccIIV). The RIV and ccIIV are only indicated for those 18 years and older. The ACIP permits the administration of RIV in non-medical settings to those 18 years and older even if they had severe egg allergies. A recent study shows RIV offers no additional protection against the flu than the IIVs do.
Children under age 9 years still need 2 doses 4 weeks apart of the influenza vaccine the first season that they begin the series. For those who only received one lifetime dose in any previous season, they need two doses this season. For those who received two doses last season or in previous seasons but not necessarily in the same year, they only need one dose even if the forms of those vaccines differed.
Clinicians should work to offer the flu vaccine to their patients by the end of October or the beginning of November. While many infants born in 2018 will not be old enough to start the two dose flu vaccine series at that time, they will eventually become old enough during the season. Clinicians should continue to offer the flu vaccine throughout the season until their vaccines have expired or until the end of June. Minnesota often has outbreaks at school and long term care facilities in May as it did this year and experts have pointed out that the flu viruses continue to circulate year round.
To download a one-pager listing the contraindications and precautions for both the IIV and the LAIV as well as a listing of vaccines available in 2018-2019, visit http://mnaap.org/immunizationshelpfulresources.htm