The Advisory Committee on Immunization Practice (ACIP) met in Atlanta, GA, on October 24–25, 2012. Complete minutes of the meeting will be posted at www.cdc.gov/vaccines/acip/index.html.
Pertussis outbreaks in the United States continue. This year, 32,645 cases have been reported as of October 12, 2012, with 16 deaths. Washington State has reported 4,300 cases in 2012. The highest incidence has been in 10-year-old children. This raises concerns regarding early waning of protection from pertussis vaccination (diphtheria–tetanus–acellular pertussis [DTaP]) at 5 to 6 years of age. It appears that those vaccinated with diphtheria–tetanus–whole-cell pertussis (DTwP; discontinued in 1999) had a longer duration of protection than those vaccinated with DTaP. Recent changes in pertussis epidemiology may be a result of the switch from DTwP to DTaP. Initial protection from DTaP is excellent, but immunity appears to wane rapidly.
The tetanus–diphtheria–acellular pertussis (Tdap) vaccine was recently recommended for all pregnant women (after 20 weeks' gestation) if not previously vaccinated. In addition to protecting the mother, antibody transfer to the infant protects it following birth. Analysis models by CDC proposed a 33% decrease in pertussis cases if the mother is vaccinated during pregnancy compared with 20% for vaccine administered postpartum.
Tdap vaccination rates are 78% in adolescents (2011) but only 8% in adults (2010) and 2.6% in pregnant women (2012). Infant cases and deaths in infants whose mothers had already received Tdap have been reported. Evidence was presented showing that pertussis antibodies levels fall rapidly after Tdap vaccination in adults. Also, placental transport has been shown to decrease after about 2 months in infants. In addition, rates of adverse effects from Tdap following differing intervals from tetanus–diphtheria vaccine did not show any differences. More serious events, such as Arthus reactions (immune complex-mediated hypersensitivity with local tissue necrosis) and excessive swelling, were rare but resolved within a few days if they occurred. Also, only about 5% of women have more than four children; therefore, vaccination during every pregnancy would not be more than two to three doses for most women.
ACIP voted to recommend administration of Tdap during all pregnancies. Routine repeat doses of Tdap in all adults will be discussed at the February 2013 ACIP meeting.
Four FDA-approved meningococcal vaccines are now available: one quadrivalent polysaccharide (meningococcal polysaccharide vaccine [MPSV4]; Menomune—Sanofi Pasteur); two conjugated quadrivalent vaccines (Menactra—Sanofi Pasteur and Menveo—Novartis), both with serotypes ACYW-135; and a combination (Menhibrix—GlaxoSmithKline; FDA approved in June [combination of Hib and meningococcal type C and Y, conjugated]). Menhibrix is FDA indicated in infants at age 2, 4, 6, and 12 months. Safety and immunological studies were presented to show the data leading to FDA approval.
A GRADE (Grading of Recommendations, Assessment, Development, and Evaluation; description available at www.cdc.gov/vaccines/acip/recs/GRADE/about-grade.html) analysis was presented to analyze whether HibMenCY should be recommended routinely for all infants.
ACIP has not recommended routine infant immunizations in the past because of the low incidence of disease in infants. Menactra has been FDA approved and ACIP recommended for high-risk infants (i.e., two-dose series administered between 9 and 23 months).
The working group concluded that the data do not support routine infant vaccination at this time. Targeting high-risk infants is consistent with current ACIP recommendations, including those for infants with complement deficiencies and asplenia (including sickle cell disease). Although Menhibrix should not be used as a travel vaccine, it could be used for community outbreaks if types C and Y are the identified serotype. If Menhibrix is used, the complete four-dose series must be administered.
The measles–mumps–rubella (MMR) vaccine working group has been updating the ACIP recommendations that were last published in 1998. Since that time, measles and rubella have been eliminated but several large outbreaks of mumps have occurred. Some changes to the recommendations have been published, including the interval to avoid pregnancy following rubella vaccination (2001), updated mumps vaccine requirements (2006), and evidence of immunity for health care personnel (2011).
Mumps vaccine was licenses in 1967, and the two-dose series was recommended in 1989. Several mumps outbreaks have occurred during the previous few years, and many of the involved cases had completed the two-dose series. During one of the outbreaks, a third dose was administered, resulting in a significant decrease in attack rates. However, the outbreak was already in a decline when administration of the third dose had started. CDC stated that data are insufficient to recommend for or against a third dose of MMR during mumps outbreaks.
Acceptable evidence of immunity is to be changed to add laboratory confirmation of disease and remove physician diagnosis of mumps and measles.
As mentioned in the last ACIP report, wild measles has mostly disappeared from the population and U.S. immune globulins levels of antibody against measles are decreasing. The maximal dose of IGIM (immune globulin for intramuscular administration) is not adequate for measles prevention in most people—even doubling the dose would only give minimal antibody concentrations. IGIV (immune globulin for intravenous administration) may need to be used to get an adequate dose. New language was developed to make recommendations for several high-risk groups on what to do if exposed to measles.
ACIP voted to approve the new additions to the recommendations.
Childhood and adolescent immunization schedule
The proposed childhood and adolescent immunization schedule was introduced for 2013. No major changes in content were made outside of those occurring at the ACIP meeting described here. Numerous edits were made to wording and formatting to improve clarity. Several options were presented to a focus group of providers. The providers liked combining the 0-to-6-years and 7-to-18-years schedules into one schedule with only one set of footnotes. The catch-up schedule was not changed. Also, a proposed high-risk table was evaluated and a suggested format was chosen. To combine the two schedules, the colors had to be harmonized. A decision was made to defer the high-risk table until 2014 to further discuss the format.
Adult immunization schedule
Proposed changes to the adult immunization schedule included (1) incorporating changes in Tdap recommendations (remove hash bar for age >65 years), (2) adding a bar for PCV13 (13-valent pneumococcal conjugate vaccine) vaccine, (3) removing the purple bar for MMR for those born before 1957 (because they are considered immune), and (4) correcting the PPSV23 (23-valent pneumococcal polysaccharide vaccine) bar (i.e., changing from yellow to purple for men who have sex with men). Also, several changes were made to the footnotes. A name change from TIV (trivalent influenza vaccine) to IIV (inactivated influenza vaccine) will be made since quadrivalent vaccine will be available next year.
The next steps are to make revisions based on changes from this meeting; obtain CDC clearance; harmonize with the American Academy of Family Physicians, American College of Physicians, American Congress of Obstetricians and Gynecologists, and American College of Nurse-Midwives; and submit to Morbidity and Mortality Weekly Report. The revised schedule is expected to be published in early February 2013. ACIP voted to approve this schedule.
Japanese encephalitis vaccine
The Japanese encephalitis (JE) vaccine is licensed for patients 17 years or older. The working group has been activated to review safety and efficacy of this vaccine in children younger than 17 years. Presentation to ACIP is expected in February 2013.
Hepatitis B virus vaccine
The goal of the workgroup is to ensure hepatitis B virus (HBV) protection for health care personnel (HCP) who received vaccination without postvaccination serologic testing. Also the hepatitis working group has been discussing options for HCP who had HBV vaccine in the remote past (including at birth) without serology.
The number of total estimated cases of HBV in the United States is about 35,000 per year, and approximately 800,000 individuals have chronic HBV. HBV infections in HCP have declined, with 10 reported cases in 2010; however, the actual number of cases was estimated to be 263. This decline is a result of vaccination and Occupational Safety and Health Administration standard improvements. Approximately 74% of HCP with patient exposure have completed the vaccine series. Acute HBV has been shown to occur in those who are unvaccinated or nonresponders. HBV vaccine coverage in HCP is not optimal.
Serological titers are useful for determining protection if performed 1 to 2 months following completion of the vaccine series. However, titers wane over months to years, making it impossible to identify responders (90%) or nonresponders (10%). Individuals entering the health care workforce who received the HBV vaccine years earlier are expected to have low titers. Multiple proposals to deal with this issue were presented at the previous ACIP meeting.
Data were presented on studies performed on long-term protection when vaccine given at birth. In six studies followed for approximately 20 years, protection against acute and chronic HBV infection was proven. Subclinical infection was uncommon but did occur. Vaccine nonresponders remained susceptible to acute and chronic infection. Limitations to these studies included small sample sizes, most participants receiving plasma-derived vaccine (not recombinant, which is used now), and varying exclusion criteria, schedules of vaccination, and definitions.
The workgroup discussed two approaches: preexposure evaluation for protection or postexposure assessment and management. Preexposure testing involves drawing titers, and if antibody to the hepatitis B surface antigen (anti-HBs) levels are 10 mIU/mL or greater, patients are considered protected. If anti-HBs levels are lower than 10 mIU/mL, one dose of HBV vaccine should be administered and the patient retested in 1 to 2 months. If titers remain low, then two additional doses should be given followed by serologic titers. If titers still remain low, then postexposure management will be necessary. If titers are 10 mIU/mL or greater, then postexposure management is not necessary.
Postexposure management consists of assessment for anti-HBs titers and the source of hepatitis B surface antigen. Based on these results, HCP will be provided vaccination or hepatitis B immune globulin.
The workgroup made no recommendations on the approach and are seeking guidance from ACIP. It was suggested that both approaches are effective and that no preference would be made. No decision was rendered at the meeting.
Human papillomavirus vaccine
Although no new policy issues are being discussed, efficacy for prevention of oral human papillomavirus (HPV) infection and vaccine uptake was discussed.
HPV causes more oropharyngeal (OP) cancers among men, and the incidence may surpass cervical cancer by 2020. The prevalence of oral HPV type 16 in the United States is 1% and is the primary serotype found in OP cancer, with estimates of 12% to 72%. Most studies on vaccine effectiveness do not include OP HPV prevention. A randomized blinded trial in women was performed in Costa Rica using hepatitis A vaccine (n = 2,910) as a control against HPV 16/18 vaccine (n = 2,924). HPV testing using cervical and oral specimens was performed during a 4-year period. The vaccine efficacy against infection was 93% against HPV; however, the prevalence was very low (1 in HPV group vs. 15 in placebo group).
HPV vaccination estimates according to the 2011 National immunization Survey are summarized in Table 1.
It was suggested that improved communication and strength of recommendations is needed, both for parents and for boys and girls. Safety monitoring is ongoing, but no increased risk has been demonstrated.
Since the release of rotavirus vaccines in 2006 (RotaTeq—Merck) and 2008 (Rotarix—GlaxoSmithKline), vaccine effectiveness studies have not been performed. The effectiveness of both vaccines was recently evaluated using data from 2009 to 2011. RotaTeq was 84% effective and Rotarix 70% effective; however, neither was statistically significant because of the limited number of cases and wide confidence intervals. One other study in five hospitals showed RotaTeq to be 91% effective and Rotarix 88% effective. In conclusion, both vaccines are highly effective, though Rotatrix needs further monitoring because it has not been on the market as long as RotaTeq. Also, no evidence of waning of immunity exists for either vaccine.
The hepatitis A vaccine VAQTA (Merck) is now available. MMRV (measles–mumps–rubella–varicella) vaccine also is available. Pentacel (DTaP, inactivated poliovirus, and Haemophilus influenzae type b—Sanofi Pasteur) and Daptacel (DTaP—Sanofi Pasteur) supplies are reduced; however, supply of GlaxoSmithKline's DTaP vaccines (Infanrix and Kinrix) is sufficient.
Influenza season is on the horizon. Thus far, only 140 positive samples of influenza have been seen as of October 13. An outbreak of H3N2 variant (H3N2v) influenza occurred this past summer, totaling 306 cases. Of the cases, 98% involved swine exposure (mostly at state fairs), and only 15 person-to-person transmissions were confirmed. This H3N2v outbreak appears to be very rare but will continue to be monitored. In general, the illness is short and few cases require hospitalization. However, the H3N2v outbreak did result in one death.
Last year, the vaccine strains did not change and it was the second season with universal influenza vaccination recommendations. The influenza coverage for children was about the same as the previous season (51.5%). The adult rate was 1.7 percentage points lower in adults 18 years or older (38.8%). HCP influenza rates were slightly higher (63%). The vaccination rate for pregnant women was 43%. Approximately 20% of vaccinations were given in pharmacies or stores.
The effectiveness of LIAV compared with TIV for healthy children was compared using GRADE criteria. A total of 22 randomized trials were included in the initial evaluation; however, 3 trials were included in the analysis. This review showed that LIAV provided greater relative protection than TIV against culture-confirmed influenza in healthy younger children. Data were not sufficient in older children. There will not be a recommendation on preference of LIAV over IIV (inactivated influenza vaccine). Further reviews on safety, supply, and relative cost are needed.
In the 2013–14 influenza season, several quadrivalent inactivated vaccines (QIVs) will be available. Two lineages of influenza B viruses circulate every year (both are circulating currently). A quadrivalent vaccine (FluMist—MedImmune) has been approved by FDA that includes both lineages of the B virus (B/Yamagata and B/Victoria). During the previous 10 seasons, the B vaccine strain only matched the circulating strains five times. One consideration CDC looked at was the amount of resources needed to produce QIV and whether this takes away from resources available for TIV. This depends on uptake of vaccine and the amount of circulating type B strains. They concluded that if TIV supply was similar to demand during 2002–05, fewer doses of QIV being produced could have led to fewer people being vaccinated.
MedImmune presented the new FluMist quadrivalent vaccine. They stated that the transition from TIV will not affect supply. Studies showed that QIV immunogenicity met noninferiority endpoints, demonstrated higher immune responses to B strains, had a favorable safety profile, and is expected to have the same efficacy/effectiveness profile as TIV but with a broader coverage of B strains.
Sanofi Pasteur’s quadrivalent Fluzone vaccine is expecting FDA action on its application in June 2013 and distribution in fall 2013 if the product is available. Safety was demonstrated and antibody responses were noninferior to TIV.
GlaxoSmithKline also has submitted license applications for two QIV vaccines (Fluarix and FluLaval). Both are submitted for patients 3 years or older. Safety and antibody response results were the same as those seen for other QIVs. FDA review is expected for Fluarix by December 2012 and for FluLaval at some point in 2013.
The Vaccines for Children program proposed renaming TIV (trivalent influenza vaccine) as IIV (inactivated influenza vaccine), and ACIP voted to approve.
Novartis presented on a novel cell culture inactivated vaccine. It demonstrated immunogenicity, efficacy, and safety data similar to egg-derived TIV. Novartis stated that this is an alternative to egg-based production methods and that its vaccine is under FDA review for individuals 18 years or older.
The next meeting will be February 20–21, 2012, in Atlanta, GA.
Stephan L. Foster, PharmD, FAPhA
Professor and Vice Chair
College of Pharmacy
University of Tennessee Health Sciences Center
APhA Liaison Representative to the Advisory Committee on Immunization Practices (ACIP)
CAPT (Ret) U.S. Public Health Service