Vaccine Update for Healthcare Providers

In the Journals

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

Influenza vaccine requirement in young children lowers hospitalization rates

Pre-school children are at risk for severe influenza infections; especially those in child care, where the risk of acquisition is greater. To protect against influenza in this setting, the state of Connecticut passed a law in September 2010 requiring all children between 6 months and 5 years of age who attend licensed preschool or child care facility in the state to receive at least one dose of influenza vaccine each year. Connecticut became the second state – after New Jersey – to implement this policy.

After the regulation was put in place, immunization rates among Connecticut children between 6 months and 5 years of age increased from 67.8 percent during the 2009-2010 season to 84.1 percent during the 2012-2013 season. Among 11 Emerging Infections Program (EIP) sites surveyed, Connecticut had the greatest percentage increase among children ≤ 4 years of age (Hadler JL, Yousey-Hindez K, Kudish K, et al. Impact of requiring influenza vaccination for children in licensed child care or preschool programs—Connecticut, 2012-2013 influenza season. MMWR Morb Mortal Wkly Rep. 2014 Mar 7;63(9):181-5.).

Connecticut’s action lessened the incidence of influenza disease among young children in their state. During the 2007-2008 influenza season, Connecticut was third highest in its incidence of influenza-associated hospitalizations in children ≤ 4 years of age (58.6 per 100,000). During the 2012-2013 season, Connecticut dropped to seventh among states (51.5 per 100,000) and was one of only two states to record a decrease in incidence (12 percent) among children in that age group. Maryland was the other, with a 6 percent decrease.

Not surprisingly, greater immunization rates led to less hospitalization and suffering.


The latest trend in vaccine exemption legislation

In the 1960s, parents in the United States had only one way to legally withhold vaccines for their children: medical exemptions. Beginning in the 1970s, however, parents pushed for other legislation to exempt their children from vaccines, even if there wasn’t a medical contraindication to receiving them. As a consequence, 41 states have religious exemptions to vaccines and 20 states have philosophical exemptions. The results have been predictable. As has been shown in several studies, states or regions with high numbers of vaccine exemptors are more likely to suffer outbreaks of pertussis and measles. Those with lower rates of exemptors suffer lower rates of disease.

To examine recent legislative efforts to expand or restrict exemptions to vaccination, Saad Omer and colleagues examined bills introduced to state legislations between 2009 and 2012 (Omer SB, Peterson D, Curran EA, Hinman A, Orenstein WA. Legislative Challenges to School Immunization Mandates, 2009-2012. JAMA 2014 Feb 12;311(6):620-1). Thirty bills were introduced into the 30 states that didn’t have a personal belief exemption; all were defeated. Five bills were introduced restricting personal belief exemptions in states that already had them; three passed (Washington, California, and Vermont).

The trend is apparent. One can only assume that state legislators — realizing that personal belief exemptions have only increased the risk of disease, suffering, and hospitalizations in their states — have started to push back on legislation aimed at expanding exemptions and adopt legislation intended to restrict them. Children in these states will clearly benefit from this trend.


Intussusception and rotavirus vaccination

In 1999, the simian-human reassortant rotavirus vaccine (RotaShield®) was taken off of the market because it was found to be a rare cause of intussusception, an intestinal blockage. The attributable risk was 10 per 100,000 vaccinees. At the time, it was hard to understand why RotaShield had caused this problem. All existing evidence didn’t support the notion that natural rotavirus infection caused intussusception. So why should a vaccine, which replicates at the intestinal mucosal surface much less efficiently than natural virus, cause a problem that isn’t caused by natural virus?

In 2006, the pentavalent bovine-human reassortant rotavirus vaccine (RotaTeq®) was licensed and recommended for all infants. Since then, about 50 million doses have been administered in the United States. Similarly, in 2008, the monovalent attenuated human rotavirus vaccine (RotaRix®) was also licensed and recommended for universal use; about 10 million doses have now been administered. With millions of children now vaccinated with these two newer rotavirus vaccines, two recent papers have now addressed the question of whether RotaTeq and RotaRix are also rare causes of intussusception.

Yih and coworkers evaluated data from a program called PRISM (Post-Licensure Rapid Immunization Safety Monitoring), which is directed by the Centers for Biologics and Research of the FDA (Yih WK, et al. Intussusception risk after rotavirus vaccination in U. S. infants. New Engl J of Med. 2014 Feb 6;370:503-12). These researchers found that the attributable risk for intussusception following RotaTeq was 1.5 per 100,000 vaccinees (about seven-fold less than that found after RotaShield). The number of children inoculated with RotaRix was too small for adequate evaluation using PRISM.

A second article in the same journal evaluated the risk of intussusception following both RotaTeq and RotaRix using a different data set: the Vaccine Safety DataLink (Weintraub ES, et al. Risk of intussusception after monovalent rotavirus vaccination. New Engl J of Med. 2014 Feb 6;370:513-9). These investigators found that RotaRix was also a rare cause of intussusception with an attributable risk of 5.3 per 100,000 (about half that of RotaShield); RotaTeq was not associated with intussusception in this study.

What do these data teach us? The findings with RotaRix are particularly instructive. RotaRix is a live weakened virus originally obtained from a young boy with rotavirus diarrhea in Cincinnati in 1989. If RotaRix is a rare cause of intussusception, it raises the question of whether natural rotavirus infection is also a rare cause of intussusception. This question can be answered by evaluating the incidence of intussusception in the United States since the introduction of RotaTeq and RotaRix. Because the incidence of natural rotavirus infections has decreased dramatically, we have essentially replaced natural rotavirus with vaccine viruses. The CDC recently presented data showing that the incidence of intussusception has stayed about the same. This means that, in all likelihood, the attributable risk of intussusception following vaccination is about the same as that following natural infection.

If parents are concerned about whether rotavirus vaccination causes intussusception, they should be reassured that it does not appear that rotavirus vaccines have altered the incidence of intussusception in the United States.


H1N1 vaccine and narcolepsy

In 2009, an unusual side effect was observed in a group of European and Scandinavian people who received a swine flu vaccine that contained the adjuvant, squalene. About 1 of every 55,000 people who received the vaccine developed narcolepsy: a disorder characterized by excessive sleepiness during the day, a sudden loss of muscle tone and strength, and rapid eye movement abnormalities.

Several important facts are known about narcolepsy. It’s caused by a loss of the 70,000 neurons in the hypothalamus that make a peptide called hypocretin, which is responsible for wakefulness. Also, the disease is far more common in people who have a particular genetic background (HLA-DQA1).

Alberto De la Herrán-Arita and colleagues at Stanford University School of Medicine appear to have figured out what happened (De la Herrán-Arita AK, Kornum BR, Mahlios J, et al., CD4+ cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy. Sci Transl Med.2013 Dec 18;5(216):216ra176). The Stanford researchers found a peptide on the influenza hemagglutinin that mimics hypocretin. So when people were immunized with the swine flu vaccine, those with HLA-DQA1 were more likely to develop an immune response (T cells) against their own hypocretin than those who didn’t get the vaccine or those who didn’t have that genetic susceptibility.

More research is required. People in the United States, for example, received an unadjuvanted vaccine and didn’t develop narcolepsy. It would be interesting to know whether the same side effect would have occurred in Europe and Scandinavia if their vaccine had not contained squalene as an adjuvant.


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