The first discussion was on meningococcal vaccine in patients with increased risk of disease, particularly patients with complement deficiency, HIV, or asplenia. Evidence was presented that the recommended one-dose schedule is inadequate to provide protection in these patients. A two-dose vaccination series, 2 months apart, was highly immunogenic. The committee voted and approved this schedule change.
Evidence also was presented that a single dose of meningococcal vaccine at 11 to 12 years of age did not provide adequate protection through college. Studies show the vaccine does not protect for more than 5 years. Cost-effectiveness data for vaccination of adolescents with the current recommendation of a single dose at age 11 to 12 years is the least cost-effective model; a single dose at age 15 years would prevent the greatest number of cases per dose given, and a dose at 11 years with a booster at 16 years would prevent the most number of cases. Since vaccination of adolescents began, the total number of cases in those 11 to 22 years of age during a 4-year period has decreased from 214 (2000–04) to 141 (2005–09) cases—a decrease of 34%. Vaccine effectiveness has been estimated at 78%. In summary, the low incidence of disease and low vaccination coverage have limited the power of these studies. The working group also recognized that this age group presents programmatic difficulties as a result of low number of provider visits and high vaccine cost. The committee, following a great deal of discussion and public comment, voted to keep the first dose at 11 to 12 years of age and to add a booster dose at age 16 or 5 years after the previous dose if they received the vaccine at an older age. Of note, the vote was close: 6 members were for and 5 were against the change.
Hepatitis B vaccination in high-risk adults was discussed. Vaccination coverage is improving but is still below desired levels. It was reported that 75% of health care workers have received only one dose of hepatitis B vaccine and 68% received all three doses. The ACIP working group on hepatitis B vaccination reviewed the incidence of hepatitis in people with diabetes (which is higher than the general population) and came to several conclusions: (1) infection control practices are not sufficient to prevent the disease, (2) seroprevalence of hepatitis B is increased in diabetes, and (3) vaccination is likely to substantially reduce the risk in people with diabetes. One area of concern is the practice of assisted monitoring of blood glucose (AMBG). The settings in which AMBG is performed include nursing homes, assisted-living facilities, hospitals, clinics, senior centers, health fairs, correctional facilities, schools, camps, and shelters. Risk of exposure increases at settings where shared-use monitors and lancet devices are used. Not changing gloves between patients also increases the risk. The working group will continue to discuss the issue surrounding hepatitis B and diabetes. Future discussions will include declining seroprotection and cost effectiveness in older patients, age criteria for vaccination, whether all patients with diabetes should be vaccinated or only certain identified groups, and if titers should be drawn following vaccination.
The incidence of pertussis is increasing. In addition, several outbreaks have occurred around the United States. The California Department of Health received reports of increase in pertussis cases in March 2010. The health department immediately began efforts to increase vaccination rates with tetanus–diphtheria–acellular pertussis (Tdap) vaccine. Intensive education efforts regarding diagnosis, treatment, recommendations for vaccination, and cocooning were put in place to meet their goal of protecting infants. Barriers started to arise concerning availability of Tdap, confusing guidelines about minimal intervals between tetanus–diphtheria (Td) and Tdap, licensing of Tdap for children aged 7 to 9 years, and emergency departments not following Tdap recommendations for wound management. Initially, free vaccine was offered to postpartum women and other infant contacts. In July, recommendations were expanded beyond ACIP recommendations to include women of childbearing age (including during pregnancy), all persons who have contact with infants, persons older than 64 years, underimmunized children aged 7 to 9 years, and wound management (which was an existing ACIP recommendation). The minimal interval between Td and Tdap was eliminated. From March to mid-October, a total of 6,978 cases and 10 infant deaths have been reported. The health department discovered during its investigations that a large pool of susceptible persons in need of vaccination exists. Although most of the young children were immunized, mandates for middle-school vaccination were implemented in September 2010. The investigation is continuing.
Current ACIP recommendations state that an interval of at least 5 years between Td and Tdap is encouraged; however, a shorter interval may be used. This created a barrier to vaccination because of varying physician-recommended intervals. Several postlicensing safety-reporting systems have not reported an increase in adverse events with shorter intervals. Local adverse events were similar to most other vaccines. The working group recommended removing this language by stating that adolescents or adults not vaccinated should be immunized as soon as feasible. ACIP voted to accept the language that adolescents and adults ages 19 to 64 years should receive a single dose of Tdap in place of Td vaccine dose. Also they voted that Tdap can be administered regardless of interval since the last tetanus- or diphtheria-containing vaccine.
Safety and immunogenicity studies of Tdap (Adacel—sanofi pasteur, and Boostrix— GlaxoSmithKline) in patients older than 64 years were presented. The studies showed no difference in the safety profile compared with Td vaccine, no differences in the tetanus and diphtheria immunogenicity, and a robust response to all pertussis antigens in the vaccines. Clinical efficacy studies have not been performed. ACIP voted to approve the recommendation that for all adults older than 64 years, a dose of Tdap may be given in place of a Td vaccine and Tdap should be administered if the person has close contract with an infant younger than 12 months. Clarification will be necessary regarding payment issues and especially if this will be considered a Medicare Part D vaccine, which would make this a pharmacy benefit.
The last Tdap issue discussed was regarding children aged 7 to 10 years who are undervaccinated. A single dose of Tdap is recommended for these children. If the child has not received any vaccine, then one dose of the series should be Tdap followed by the completion of the series with Td. ACIP voted to approve Tdap in this age group.
Further guidance on revaccination with Tdap will be forthcoming.
Data regarding HPV vaccine safety based on several safety-monitoring systems were presented. No adverse reaction concerns or patterns have been identified through the Vaccine Adverse Event Reporting System (VAERS) and a Vaccine Safety Datalink (VSD) Rapid Cycle Analysis study conducted by CDC. They confirmed no increase in risk for Guillain-Barré syndrome, seizures, syncope, appendicitis, stroke, venous thromboembolism, and allergic reactions. Monitoring will continue.
Coverage of HPV in adolescent girls continues to be low. Data from the National Immunization Survey for teens aged 13 to 17 years indicated that only 44% had been given one dose and 27% completed all three doses. Barriers identified included financing, provider recommendations, and acceptance by parents.
Multiple issues were discussed about HPV vaccine in male patients. Although the vaccine continues to be safe and effective, controversy exists regarding its cost effectiveness and in what groups it should be recommended.
Hepatitis B vaccine is not being distributed by Merck except for the dialysis product, and GlaxoSmithKline has a strong supply of the vaccine. Diphtheria–tetanus–acellular pertussis (DTaP)–inactivated poliovirus vaccine (IPV) (Kinrix—GlaxoSmithKline) combination vaccine is not available, but the individual vaccine components are in good supply. Zoster vaccine is available for ordering; however, providers will still experience back orders. Both Merck and GlaxoSmithKline will not be distributing hepatitis A vaccine for the remainder of 2010. When hepatitis A vaccine will be available is not known. Details of shortages may be found at www.cdc.gov/vaccines/vac-gen/shortages/default.htm.
Multiple changes were made to the schedule this year based on new ACIP recommendations. Because of changes made at the meeting discussed here, the schedule will not be published until February 2011. The schedule may appear on the CDC website before being published in MMWR. Details of changes will be published with the schedule.
The largest change in the adult schedule is the universal influenza. Changes in the appearance of the schedule have made it easier to use. Also, because changes were made to recommendations at this meeting, the publication also will be delayed. Details will be published with the schedule.
Two issues concerning rotavirus vaccine have occurred to cause concern since last year: porcine circovirus contamination and risk of intussusception (IS).
GlaxoSmithKline reported that the prelicensure clinical trials showed no increase in IS in the first 31 days and in a subset of these children followed for 1 year. A postmarketing study in Mexico is currently ongoing. Because of a higher rate of IS in Mexico, a study was designed to assess a temporal association following rotavirus vaccine (Rotarix—GlaxoSmithKline) administration. Interim analysis of this study during a 1-year period with more than 1 million infants under surveillance showed a temporal association between IS and vaccine within the first 31 days after the first dose. This was not seen following the second dose. This temporal increased risk does not indicate an overall increased risk of IS.
An additional study by CDC was performed in Mexico and Brazil. These locations were chosen because of the high birth cohort (5.6 million combined). This study demonstrated a short-term risk of IS after dose 1 in Mexico, peaking on days 4 and 5 following vaccination. No increase was seen in Brazil. During this time period, a significant decline in rotavirus disease occurred.
Additional reports from VAERS, VSD, and Merck for rotavirus vaccine (RotaTeq—Merck) revealed no evidence of an increase in IS in the United States; however, the amount of vaccine administered is low, making it difficult to determine a problem with a small incidence, such as IS.
Additional presentations were made from Australia. No increased risk of IS was seen with RotaTeq; however, a slight increase in relative risk following the first dose of Rotarix was observed. Authorities will continue to monitor the situation.
Merck also reported on a study of porcine circovirus (PCV) in its rotavirus vaccine. PCV type 2 DNA was discovered in several lots of bulk rotavirus, although no evidence of infectious PCV was detected. The source was determined to be irradiated trypsin, which is used to cleave the cells from the media. No antibodies to PCV2 were found in serum samples of vaccine recipients of Rotateq tested. This information has been presented to regulatory agencies worldwide.
Rotavirus vaccination has demonstrated a significant decrease in deaths, hospitalizations, emergency department visits, and clinic visits. Based on these studies, CDC supports the finding that the benefits outweigh the risks.
Current circulating influenza virus includes all three strains (H1N1, H3N2, and B) contained in the vaccine; however, incidence of disease is declining in the southern hemisphere, where the influenza season is ending. Recently circulating viruses were tested at CDC and are similar to the vaccine components. Also, the circulating viruses are susceptible to the neuraminidase inhibitor antivirals and resistant to the adamantanes. Very little influenza is circulating in the United States currently. Total vaccine production projection for this season is 160 to 165 million doses, with approximately 139 million doses distributed as of October 15, 2010. This total is greater than the influenza doses distributed in any previous season (114 million doses distributed last year). Safety monitoring will be the same as last season. Based on reports of febrile convulsions caused by Afluria (CSL) last season, monitoring for seizures will be closely followed.
The next meeting will be February 23–24, 2011, in Atlanta, GA.
Stephan L. Foster, PharmD, FAPhA
Professor and Vice Chair
University of Tennessee College of Pharmacy
APhA Liaison Representative to the Advisory Committee on Immunization Practices (ACIP)