The Advisory Committee on Immunization Practice (ACIP) met in Atlanta, GA, on February 23–24, 2011. Complete minutes of the meeting will be published on the CDC National Center for Immunization and Respiratory Diseases (NCIRD) website.
An epidemic of pertussis has been reported in the United States, with most of the reported cases in California. A total of 9,225 cases have been reported in California, with 10 neonatal deaths.
Because pertussis can be spread by health care personnel (HCP), use of the tetanus—diphtheria—acellular pertussis (Tdap) vaccine in HCP was presented. Serologic conversion to pertussis among HCP was reported to be approximately 1.3–3.6%. Transmission from patient to HCP and HCP to patient is well documented. Currently, 60–72% of hospital employees are vaccinated and the overall HCP vaccination rate is reported to be 15.9%. However, these studies were performed following a pertussis outbreak, so the numbers are probably lower today. The efficacy of Tdap has been reported to be 65–92%. Stronger language in the recommendations was approved by the committee, which included removal of time intervals since last tetanus—diphtheria vaccine, inclusion of HCP 65 years or older, and suggestion of providing vaccination for free.
A study of postexposure prophylaxis (PEP) with antibiotics in vaccinated HCP was presented. Of HCP without and with PEP following exposure, 90% and 97.6%, respectively, did not develop pertussis—a significant difference. Of note, these findings came from a small study of 86 people; therefore, the results are not entirely conclusive. Wording in the recommendation was added to recommend PEP for HCP with unprotected exposure to pertussis if they are likely to expose at-risk patients.
Pregnant women were excluded from Tdap licensing studies. A few old studies showed that adverse events in pregnant women were not different compared with nonpregnant women, pregnancy outcomes were not affected, and the vaccine was immunogenic in pregnant women. These studies used whole-cell diphtheria—tetanus—pertussis (DTwP) vaccines, and protective efficacy was demonstrated. However, no Tdap studies have been done and the immune response in infants of pregnant women has not been adequately evaluated. Pregnancy registries by GlaxoSmithKline and Sanofi Pasteur currently have very small numbers, but earlier studies using DTwP showed some protection in infants. Recent studies on Tdap, though data are limited, show that Tdap is safe for mothers and newborns and that antibodies develop in fetuses. Whether this will interfere with infants' ability to respond to DTaP vaccination at a later time is unclear. ACIP will await further studies before making a decision.
In June 2009, the last Japanese encephalitis (JE) vaccine recommendation was published. Two vaccines are available at this time. JE-Vax (Research Foundation for Microbial Diseases of Osaka University) is no longer being produced, and the remaining doses expire in March 2011. Ixiaro (Intercell) was approved in March 2009 for patients 17 years or older. JE-Vax is the only vaccine approved for children.
In addition, limited data are available at this time regarding the need for a booster dose of Ixiaro. It is currently given in a two-dose series at 0 and 28 days. Three clinical trials on antibody persistence have been performed since licensing. Persistence at 12 months ranged from 58% to 83% post–first dose. A new trial on a booster dose at 15 months after the two-dose primary series resulted in 100% seroprotection that remained over the next 12 months. Wording in the package insert was changed to recommend a booster dose at 15 months if continued exposure to JE virus occurs. No evidence for a second booster dose is available at this time. ACIP voted to include wording to state that if exposure potential continues after 1 year, a booster dose may be given (a permissive recommendation).
Pediatric studies also are under way with Ixiaro; however, it will take several years before they are completed. Until that time, travelers need to take precaution to avoid mosquito bites.
Immunization of health care personnel
Changes in the published document (recommendation last published in 1997) were presented. The definition of health care personnel was broadened to include anyone working in the health care setting. In addition, recommendations for serological testing for select vaccines will be clarified. This document will reflect the many changes that have occurred over the years. It will not change policy passed by ACIP previously.
Vaccines and febrile seizures
Based on reports of an increase in febrile seizures with CSL Biotherapies' influenza vaccine (Fluvax) in Australia, other vaccines were reviewed. Febrile seizures in general occur in about 2–5% of children aged 6–60 months. Febrile seizure following vaccination is a fairly common event mentioned in package inserts of most childhood vaccines. One vaccine that caused a substantial increase in febrile seizures was DTwP; however, DTaP has not been associated with an increase. Measles–mumps–rubella vaccine also was associated with an increased risk (range 25–156/100,000 individuals) based on three studies.
In April 2010, Australia reported an increase in febrile seizures with CSL Biotherapies' influenza vaccine with a cluster on day 1 postvaccination in children younger than 5 years. The rate was estimated to be an increase of up to 9 per 1,000. The United States suspended the use of Afluria (CSL Biotherapies) in children younger than 9 years.
Following a review of data from the Vaccine Adverse Event Reporting System (VAERS) and Vaccine Safety Datalink project, no increase in febrile seizures was seen with influenza vaccine. However, a slight increase was seen in the 2010–11 season with the concomitant administration of the trivalent inactivated influenza virus vaccine and pneumococcal 13 conjugate vaccine. Clinically, the rate is nonsignificant compared with the febrile seizures caused by other factors.
The working group will continue to follow associations between vaccines and febrile seizures.
Influenza activity of the northern hemisphere is showing a mixture of H1N1, H3N2, and type B. Since October 1, 2010, percentages of activity of 13% H1N1, 54% H3N2, and 33% type B have been reported in the United States. The viruses continue to be susceptible to neuraminidase antivirals and resistant to adamantine antivirals. The greatest number of cases has been reported in February 2011. A total of 55 pediatric deaths have been reported thus far for the 2010–11 influenza season. In conclusion, activity remains high at this time, the circulating virus matches vaccine strains well, and all three strains continue to circulate.
Approximately 163 million doses of vaccine have been produced. Current vaccination coverage is as follows:
Pharmacists or pharmacies have given about 12% of all vaccines, and this does not account for vaccines given in supermarkets, grocery stores, and superstores, which also were administered by pharmacists primarily.
ACIP recommendations for use of antivirals in influenza were recently published in Morbidity and Mortality Weekly Report. These recommendations include information and guidance on indications for those in high-risk groups, dosing of antivirals, and duration of treatment.
Anaphylaxis to eggs is very rare in influenza vaccination, with four reports of death occurring between 1990 and 2005. New recommendations by the National Institute of Health, American Academy of Allergy Asthma & Immunology, and American Academy of Pediatrics suggest giving the vaccine in two steps (10% and 90%); however, data on this method are limited.
The recommended strains for the 2011–12 vaccine are the same as those present in the current vaccine. The FDA Vaccine and Related Biologic Products Advisory Committee met on February 25, 2011, and confirmed this recommendation.
The clinical presentation and complications of herpes zoster disease were discussed. A recent study by Tseng et al. published in the January 12 JAMA was performed in a large Kaiser Permanente Population and showed a vaccine effectiveness of 55%, similar to the Shingles Prevention Study. The same authors also presented a safety study from the Vaccine Safety Datalink Program that included patients aged 50–59 years. The conclusion reached showed that zoster vaccine is generally safe and well tolerated. A small increase occurred in the risk of vaccine site reactions and generalized allergic-type reactions (rash), with an elevated risk of local reactions in the group aged 50–59 years.
VAERS data on zoster vaccine were presented for the years 2006–10. Over time, the incidence of reports to VAERS has decreased. The most commonly reported adverse drug events were herpes zoster disease, injection site reactions, pain, and rash. No unexpected patterns were observed, and monitoring will continue. The surveillance is difficult because of the high prevalence of comorbid conditions in this age group.
A similar trial to the Shingles Prevention Study was performed by Merck among patients aged 50–59 years. A total of 22,439 patients were enrolled, with 11,211 receiving zoster vaccine and 11,228 receiving placebo. Results of confirmed zoster were 30 in the vaccine group and 99 in placebo group (69.8% vaccine effectiveness). For those who developed zoster, a 73% relative reduction in pain severity was reported compared with placebo. An increase in injection site adverse reactions occurred with vaccine compared with placebo (72.8% vs. 41.5%). The incidence of serious adverse effects was similar between the two groups.
Human papillomavirus vaccine
Human papillomavirus (HPV) is responsible for 96% of cervical cancers, 93% anal cancers, 36% penile cancers, and 63% oropharyngeal cancers. This results in an estimated 10,200 cervical cancers, 4,600–5,100 anal cancers, and 34,000 oropharyngeal cancers. Currently, the highest incidence of anal cancer occurs in HIV-infected men who have sex with men (MSM; 37/100,000) compared with cervical cancer (8/100,000). These findings indicate that anal HPV is more common than expected. Cost-effectiveness models of HPV vaccination demonstrated that vaccination in men may not be cost effective if the vaccination rate among women is high. Male vaccination cost effectiveness ranges from $24,000 to $192,000 per quality-adjusted cost year. Many factors are involved in these calculations, including coverage of women, type of disease being prevented (e.g., cancer by location, warts), duration of disease, duration of protection, number of doses, cost of vaccine, cancer trends, sexual orientation of male, and many others. In conclusion, male vaccination becomes less cost effective as female vaccination improves; however, at current levels of female coverage, vaccinating men would be cost effective. Cost of the vaccine is a major determinant in these calculations. The vaccine would be more cost effective if MSM were identified and vaccinated; however, this is not realistic. The ACIP HPV working group continues to discuss these issues.
Diabetes and hepatitis also were discussed. The incidence of hepatitis B was significantly higher among adults with diabetes aged 23–59 years compared with those without diabetes in this age group. For those older than 60 years, the difference was not significant. The working group will continue to seek estimates of hepatitis B vaccine coverage, cost-effectiveness analysis, and infection control initiatives.
Pneumococcal conjugate vaccine in adults
A new indication for 13-valent pneumococcal conjugate vaccine (PCV13) in adults 50 years or older is being proposed. The morbidity and mortality caused by pneumococcal disease in this age group continues to be high despite use of the current nonconjugated vaccine (23-valent polysaccharide vaccine [PSV23]). In addition, the rate of vaccination, particularly in high-risk groups, remains low.
Pfizer has performed a study in 1,100 patients randomized to get PSV23 or PCV in patients aged 50–64 years. Antibiotic response of the PCV13 was robust and noninferior to PSV23, but the data have not been published and are not available at this time.
Efficacy trials of pneumococcal diseases are difficult and expensive to perform. Pneumococcal pneumonia is relatively rare and difficult to culture. As a result, other markers of disease and efficacy of vaccine have been developed. One such marker is the enzyme-linked immunosorbent assay, which is used to measure anti-pneumonia immunoglobulin G (IgG) antibodies. No consensus currently exists regarding the level of anti-pneumonia IgG antibodies that correlates with protection, and this function declines with age. Another lab marker is opsonophagocytic killing (OPK) activity, which measures an antibody against pneumococcal capsular polysaccharide function; however, no studies are available correlating OPK assay with protection. Assays against each of the serotypes in vaccine must be measured.
Some studies have shown that prior receipt of PSV23 may blunt the response to PCV7. This blunting does not appear to occur if the PCV 13 is given before the PSV23. Also, fewer serotypes are present in PCV13. More information is needed before ACIP will make new recommendations.
Computer modeling also was presented for the use of PCV in adults to demonstrate the potential use of this vaccine. More information will be forthcoming.
The next meeting will be June 22–23, 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)