Impressive data on likely RotaTeq impact; Rotarix ACIP recommendation added

A good amount of news about rotavirus vaccination in the U.S. came out of Atlanta yesterday. First, a CDC report issued as an MMWR Early Release detailed encouraging data on trends regarding the impact of rotavirus. Titled "Delayed onset and diminished magnitude of rotavirus activity -- United States, November 2007-May 2008," the report examines data from clinical laboratories as to the frequency and timing of confirmed rotavirus samples during the rotavirus season currently underway.

In addition to seeing a delay of 2-4 months in the start of this year's rotavirus season, the report states that the number of positive tests for rotavirus was "substantially lower during the 2007-08 rotavirus season than during any of the prevaccine seasons." These trends coincide with increasing use of RotaTeq, Merck's rotavirus vaccine, approved in 2006. (Despite being the most likely explanation, both the report and an accompanying CDC press release acknowledge that the role of the vaccine cannot be stated definitively from these data alone.)

If these changes are, in fact, attributable to RotaTeq, there are also early signs that the benefit of vaccination may extend beyond those vaccinated to the community-at-large. The MMWR piece explains:

"Because the changes in rotavirus activity appear more pronounced than might be attributed to direct protective effects of vaccination alone, the results of this analysis suggest that vaccination of a proportion of the population might offer indirect benefits to unvaccinated children (i.e., herd immunity) by reducing transmission of rotavirus in the community. "

Needless to say, more data will be needed to see whether this positive trend continues in future years, as well as whether the declines in positive tests for rotavirus correspond with decreases in rotavirus-induced hospitalizations and deaths as vaccination programs proceed.

Here's coverage from the Los Angeles Times and the Washington Post, and a press release by Merck touting the positive news.

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In other rotavirus vaccine news, GSK's Rotarix, approved by FDA in April (as we noted previously), was added yesterday by the Advisory Committee on Immunization Practices to its universal recommendation for infants. No preference was stated between the two vaccines by ACIP. Here's a story on the recommendation (technically not official until published in MMWR) by the Associated Press.

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Unrelated to rotavirus, the ACIP also voted to add recommendations for two combination vaccines as options for parents and physicians: Sanofi Aventis' Pentacel (DTaP, polio, Hib) and GSK's Kinrix (DTap, polio), both of which would reduce the total number of injections needed to complete the recommended vaccination series. This Reuters story has more.

Fundraising drive marks latest polio eradication effort

Rotary International, an organization that has been one of the leaders in supporting global polio eradication efforts since the 1980s, announced the start of a $100 million fundraising drive aimed at funding the 'final push' toward eradication. Once complete, the Gates Foundation will match the total, as this Rotary International press release describes. Rotary also launched this website with more information.

Developing-world polio vaccination efforts have been quite successful, as this summary on the website of the Global Polio Eradication Initiative details, but eliminating the final few thousand worldwide cases each year has proven extraordinarly difficult. As we've written about, 2007 saw 1313 confirmed cases of polio, nearly 90% of which in two countries, India and Nigeria. (Some have argued that the current state of tight control of the virus and its spread is sufficient, given the challenges and cost of eradication efforts aimed at the final few thousand global cases.)

Here's coverage of the announcement from CIDRAP News and The Canadian Press.

Perspectives on vaccine safety, exemptions, and autism links

Tuesday's Washington Post included a story about religious and other non-medical exemptions to state vaccine requirements. The article, "Faith lets some kids skip shots," examines the increase in personal belief exemptions by parents to forgo vaccination and its implications on disease rates as seen by the medical community. Interviewed for the story were Paul Offit, Saad Omer, and Barbara Loe Fisher.

This piece appears a few weeks after the cover story of Time magazine titled "The Truth about Vaccines." The story detailed the ongoing worries about alleged links between MMR or other vaccines with increases in autism rates and the response of the medical community to these concerns. Of particular note is the reporter's discussion of research using genetics and genomics to understand individual responses to vaccination. The story included a useful diagram (.pdf) tracing the recent increase in measles cases in the U.S., an increase suspected of being linked to trends in exemptions.

The Time cover story was likely motivated -- at least in part -- by the case of Hannah Poling which received significant attention this spring. In March, CDC acknowledged that vaccines Poling had received had exacerbated an underlying genetic condition related to mitochondria (a cellular component) leading to symptoms resembling those of autism. The case has been viewed by proponents of the vaccine-autism link as a 'smoking gun,' but CDC officials and others have noted that Poling's diagnosis and condition are exceptional and do not speak to a more general connection between vaccines and autism. The case was the subject of a commentary in the New England Journal of Medicine last month by Paul Offit that focused on the confusion surrounding many aspects of the decision.

Finally, returning to exemptions and their consequences, the New York Times' Ethicist column -- an often light-hearted Q&A on ethical dilemmas -- featured this question last weekend:

"My daughter’s play group consists of children ranging in age from infancy to 4 years old. One mother revealed that she does not vaccinate her son. After much frank but cordial discussion and opinions from pediatricians — some thought she endangered our vaccinated kids; others did not — she felt pressured to leave the group. Did the group behave ethically?"

Based on pediatricians' opinions that the unvaccinated child did not pose a significant threat to her vaccinated playmates (a view that is not held by all in the medical community), 'The Ethicist' concludes that the other parents were wrong to exclude the unvaccinated child.

Discussing HPV with teens; Overlooking genital warts; New data on South Asian HPV prevalence

A potpourri of recent publications on various aspects of HPV vaccination:

• "Genital warts: Mountains or molehills?" (Lancet Infectious Diseases, Vol. 8, No. 5, 277-278 -- free abstract) -- Co-authored by Sarah Hull and our own Art Caplan, this commentary focuses on genital warts, protection for which is included Merck's Gardasil but not in GSK's Cervarix. The authors discuss how the additional benefit provided by Gardasil may factor in to debates over pricing and the market battle between the two products sure to occur in the U.S. in the years ahead.

• "Informing adolescents about human papillomavirus vaccination: What will parents allow?" (Vaccine, Vol. 26, No. 18, 2203-2210) -- A study by British researchers Vallely, et al., this paper reports on a study using an informational film to improve adolescents' knowledge about HPV, cervical cancer, and HPV vaccinations. The key messages of the film were: 1) HPV causes cervical cancer, 2) HPV is sexually transmitted, 3) Condoms may not fully protect against HPV, and 4) HPV vaccination protects against cervical cancer. A post-screening test revealed improved knowledge regarding the information presented in the film. The adolescents' parents found the messages of the film acceptable.

• "A meta-analysis of human papillomavirus-type distribution in women from South Asia: Implications for vaccination" (Vaccine, Vol. 26, No. 23, 2811-2817) -- One of the unanswered questions regarding the use of HPV vaccines in the developing world is the extent of protection provided by the cervical cancer-causing HPV strains (16 and 18) included in the vaccine. In the U.S., these strains account for approximately 70% of cervical cancer cases. Studies examining the prevalence of these strains in other parts of the world have generally found them to be less common by as much as 10%. This paper, by Bhatla et al, examines nine previously published studies from India. The researchers conclude that HPV 16/18 vaccines could provide over 75% protection against invasive cervical cancer. While an encouraging finding, it is important to note that this data is largely the product of a mathematical estimate, and it does not speak to the challenges of implementing a large-scale vaccination program in India or elsewhere.
  

Examining future lessons of HIV vaccine trials

A recent issue of Vaccine included a paper that asked this question: "What can HIV vaccine trials teach us about future HIV vaccine dissemination?" (Newman, et al. Vaccine 26 (2008), 2528-2536 -- free abstract).

Based on focus groups conducted in the Los Angeles area, the researchers map the common barriers between participants' willingness to participate in vaccine trials and the acceptability of a hypothetical vaccine. In both cases, common themes emerged, including fear of vaccine-induced infection, false positives to HIV tests and associated consequences, side effects, partial vaccine efficacy, AIDS stigma, and mistrust of government, among others.

The authors conclude that these parallels provide a valuable opportunity to use HIV vaccine clinical trials to study issues related to acceptability of an approved vaccine. They write:

"...Rigorous sociobehavioral research conducted in conjunction with HIV vaccine trials, in addition to facilitating informed enrollment in safe and ethically conducted trials, may provide an empirical basis for targeted sociobehavioral interventions to ensure the effectiveness of future HIV vaccines in controlling the epidemic."

From CDC: Zoster recommendations, measles outbreak, post-vaccine fainting, and more

Several items of note have been released by CDC in recent weeks, including:

• "Prevention of Herpes Zoster: Recommendations of the Advisory Committee on Immunization Practices" -- The publication making official the recommendations regarding the use of Merck's zoster vaccine, Zostavax. In short, routine vaccination of all persons age 60 and older is advised, except for those with specific contraindications.

• "Measles--United States, January 1-April 25, 2008" -- A report on the unexpectedly large number of measles cases confirmed in the U.S. in the early months of the 2008. Of the 64 cases, 63 occurred in people who were unvaccinated or were of undocumented vaccination status. The report notes that a large number of the cases occurred in children whose parents had received philosophical exemptions from vaccine requirements.

• "Syncope After Vaccination--United States, January 2005-July 2007" -- The arrival of newly recommended adolescent vaccines has led to an increase in fainting, particularly among 11-18 year old females, CDC reports. One fatality has been confirmed as a result of a head injury caused by a fainting-induced fall. The report reiterates a previous recommendation to observe patients for 15 minutes following vaccination to reduce the risk of falls and injuries caused by fainting.

• NCIRD Annual Report -- The 2008 annual report of the National Center for Immunization and Respiratory Diseases -- the administrative home of most of CDC's vaccination-related activities -- was released last month. Of interest to those interested in the breadth of CDC's immunization activities, it its own words.
  

No evidence of RotaTeq-intussusception link observed

Students of contemporary vaccine history are likely familiar with the story of RotaShield, a vaccine against rotavirus licensed in 1998 but withdrawn a year later following the apparent correlation between it and intussusception, a potential life-threatening bowel obstruction.

The clinical testing of RotaTeq, the Merck vaccine licensed in 2006, showed no such link, yet alarms were raised by a 'public health notification' titled "Information on RotaTeq and Intussusception" issued by FDA in February 2007. Despite its title, the announcement did not suggest that intussusception rates among vaccinees were any greater than what could be expected in the general population.

This month's issue of Pediatrics examines the topic in much greater detail, in a paper from CDC and FDA researchers titled, "Postlicensure Monitoring of Intussusception After RotaTeq Vaccination in the United States, February 1, 2006, to September 25, 2007". Based primarily on VAERS reports, the study concludes that there is no association between RotaTeq and intussusception.

Information about general trends in intussusception rates -- independent of a connection to vaccines -- appeared in a paper in the May issue of Pediatrics: "Trends in Intussusception Hospitalizations Among US Infants, 1993–2004: Implications for Monitoring the Safety of the New Rotavirus Vaccination Program".

"Science Progress" on Vaccine Policy

Our colleague Jonathan Moreno, also a Senior Fellow at the Center for American Progress, directs a project there on science and technology policy called "Science Progress." The project, consisting thus far of a web magazine and blog, celebrates its inaugural print edition this Friday. Last month, it published an interview with Dr. Saad Omer of Johns Hopkins, best known for his work on non-medical exemptions to vaccine requirements.

An excerpt from the interview:

SP: What do you think is most important for people who are both working in the public health community, people who are policymakers, people who might be hearing about this issue, and for parents to take away from this whole conversation in the public sphere at the moment?

Omer: One thing that people should realize is that we know that vaccines have some side effects. And we should acknowledge that, everyone who is involved. However, the risk and benefit calculus for all vaccines that are out there, based on our current knowledge, heavily favors not only getting your child vaccinated, but also getting them vaccinated according to the specified schedule.