Vaccine Update for Healthcare Providers

In the Journals

Paul A. Offit, MD, Director, Vaccine Education Center at The Children’s Hospital of Philadelphia

• Long-term effectiveness of varicella vaccine May 2013
• Vaccines and autism April 2013
• Efficacy of influenza vaccine in adults March 2013
• Pertactin-negative variants of Bordatella pertussis in the U.S. Feb. 2013
• Vaccination Site and Risk of Local Reactions in Children 1 Through 6 Years of Age Jan. 2013

Long-term effectiveness of varicella vaccine

In May 2013, Roger Baxter and coworkers reported the long-term effectiveness of varicella vaccine (Baxter R, Ray P, Tran TN, et al. Long-term effectiveness of varicella vaccine: a 14-year, prospective cohort study. Pediatrics 2013 May;131(5):e1389-96). In 1995, the varicella vaccine was first licensed and recommended for universal use in the United States in children 12 months of age or older. In 2006, a second dose of varicella vaccine was recommended for children 4 to 6 years of age.

The authors followed 7,585 children vaccinated in 1995 through 2009. A total of 2,826 of these children also received a second dose of varicella vaccine between 2006 and 2009. Rates of varicella and herpes zoster were determined in these children and compared with rates of disease prior to the introduction of vaccine.

The authors found that the incidence of varicella was 15.9 per 1,000 person years, about ten-fold lower than in the pre-vaccine era. Vaccine effectiveness at the end of the study period was still 90 percent without evidence of waning immunity over time. Most cases of disease in vaccinated children were mild and occurred early after vaccination. No child developed varicella after a second dose. Similarly, rates of herpes zoster infections were lower in vaccinated children than had been observed in the pre-vaccine era, suggesting that varicella vaccine reduces the incidence of shingles.

The authors concluded that one dose of varicella vaccine provided excellent protection against moderate to severe disease, that immunity to the virus did not appear to fade during the 14-year follow-up period and that varicella vaccine might reduce the incidence of zoster as children get older.

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Vaccines and autism

In a paper published in March 2013, Frank DeStefano and colleagues addressed the relationship between vaccines and autism (DeStefano F, Price CS , Weintraub, ES. Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of Autism. J Pediatr. 2013 Mar 29. doi 10.1016/j.jpeds.2013.02.001).

Three hypotheses have evolved during the past 15 years. In 1998, Andrew Wakefield and coworkers claimed that the combination measles-mumps-rubella (MMR) vaccine caused autism: a contention now refuted by 12 well-controlled studies. One year later, concern shifted to thimerosal, an ethylmercury containing preservative used in several vaccines given to infants. Seven studies have now clearly refuted the thimerosal-causes-autism hypothesis. More recently, concern about vaccines and autism settled on the fear that children were receiving too many vaccines too soon.

The first paper to address this issue showed no relationship between the number of vaccines received in the first year of life and the development of autism (Smith MJ, Woods CR. On-time vaccine receipt in the first year does not adversely affect neuropsychological outcomes. Pediatrics. 2010 Jun;125(6):1134-41). The study by DeStefano advances the findings of the previous study in that it looks not only at the number of vaccines received but at the number of immunological components contained in those vaccines. DeStefano and coworkers examined the quantity of antigens received by 250 children with autism spectrum disorder (ASD) and 750 children without ASD. They found no relationship between antigenic burden from vaccines and autism.

Taken together, these studies should reassure concerned parents that although the cause or causes of autism remain unclear, one thing that has become clear is that vaccines aren’t to blame.

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Efficacy of influenza vaccine in adults

In February 2013, investigators at Vanderbilt University in collaboration with the Centers for Disease Control and Prevention (CDC) evaluated the efficacy of influenza vaccine at preventing hospitalizations caused by influenza virus in adults (Talbot HK, Zhu Y, Chen Q, Williams JV, Thompson MG, Griffin MR. Effectiveness of influenza vaccine for preventing laboratory-confirmed influenza hospitalizations in adults, 2011-2012 influenza season. Clin Infect Dis. 2013 Feb 28.). Investigators evaluated adults admitted with acute respiratory disease to one academic and three community hospitals in the Nashville, Tennessee area. Eligibility criteria included an admission diagnosis of pneumonia, influenza, or acute respiratory disease plus at least two of the following: temperature greater than 100oF or less than 96.8oF, new onset of cough, dyspnea, chills, headache, myalgia or sore throat. Patients with symptoms lasting longer than 10 days or having been treated with antivirals were excluded. Diagnosis of influenza virus infection was made by reverse-transcriptase polymerase chain reaction (RT-PCR). Of 191 eligible patients, 21 had confirmed influenza.

The Vanderbilt investigators found that influenza vaccine effectiveness was 71.4 percent for all adults and 76.8 percent for adults 50 years of age and older. These results stand in contrast to results of vaccine efficacy recently published by the CDC (CDC, “Interim adjusted estimates of seasonal influenza vaccine effectiveness—United States, February 2013,” Morbidity and Mortality Weekly Report (2013) 62:119-123). According to CDC data, vaccine effectiveness was 56 percent overall with the following breakdown by age: 58 percent for 6 month to 17-year-olds; 46 percent for 18- to 49-year-olds; 50 percent for 50- to 64-year-olds, and 9 percent for those 65 years of age and older. However, CDC data were based on protection against outpatient visits whereas the Vanderbilt data were based on protection against hospitalization. According to these two sets of data, influenza vaccine is better at preventing more severe disease.

Although the influenza vaccine is imperfect, it remains to best tool we have to prevent severe and occasionally fatal influenza virus infections.

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Pertactin-negative variants of Bordatella pertussis in the U.S.

On February 7, 2013, the New England Journal of Medicine published an article titled, “Pertactin-Negative Variants of Bordetella pertussis in the United States” (Queenan AM, Cassiday PK, Evangelista A. N Engl J Med. 2013 Feb 7;368(6):583-4). In this report, researchers at St. Christopher’s Hospital for Children in Philadelphia examined 12 isolates of B. pertussis obtained from children admitted to their hospital. They found that 11 of the 12 isolates no longer contained pertactin, a structural protein associated with bacterial virulence. Two of the three DTaP vaccines used in the United States (ACEL-IMUNE® and Infanrix®) contain pertactin. Also, both Tdap vaccines, Boostrix® and Adacel®, contain pertactin. It is possible that these pertactin-negative isolates are the result of selective pressure exerted by widespread vaccination with pertactin-containing vaccines.

The more important question, however, is what does this mean. The authors concluded, “Although much attention has been given to the waning immunity associated with the introduction of acellular vaccines, another factor contributing to the outbreaks may be the adaptation of B. pertussis to vaccine selection pressure.” To date, however, pertactin-negative isolates are a microbiological finding in search of clinical relevance. First, pertactin-negative strains, which have been isolated in Japan, France and Finland, have not been shown to be at the center of outbreaks in those countries. Second, pertactin-negative strains have not been found to be associated with outbreaks in the United States. Therefore, there remains no evidence to support the concern that pertussis outbreaks in the United States or elsewhere are associated with anything other than waning immunity caused by acellular vaccines, which are clearly less effective albeit safer than the whole-cell vaccines.

It would have been of value to have had data that pertactin-negative strains were clinically relevant before publication. Otherwise, the media will latch on to this finding as potentially important without evidence to suggest that it as anything other than a curiosity.

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Vaccination Site and Risk of Local Reactions in Children 1 Through 6 Years of Age

In February 2013, Lisa Jackson and coworkers, working with data from the Vaccine Safety Datalink, published a study examining local site reactions following intramuscular (IM) injections of the hepatitis A, influenza, and diphtheria-tetanus-acellular pertussis (DTaP) vaccines (Jackson L ., Peterson D, Nelson JC, et al. “Vaccination Site and Risk of Local Reactions in Children 1 Through 6 Years of Age,” Pediatrics 2013 Jan 14; 131:283-289). The authors wanted to know whether children were more likely to develop local injection site reactions if they were inoculated in the arms as compared with their thighs. The Advisory Committee on Immunization Practices (ACIP) currently recommends that IM immunizations be administered in the arm muscle (deltoid) for children 3 years of age and older and in the anterolateral thigh muscle (quadriceps) for toddlers 12 through 35 months of age.

The authors performed a retrospective, cohort study of 1.4 million children who received 6 million IM vaccines between 2002 and 2009. They found that local reactions were greater after IM inoculation of DTaP in the arm than in the leg in children 12 to 35 months of age and in children 3 to 6 years of age; however, the difference in the older group was not statistically significant. Injection site reactions following both influenza and hepatitis A vaccines were uncommon, and there were no differences between arm and leg inoculation.

These data support the ACIP recommendation for IM inoculations in the thighs of younger children.

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