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.

"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.

Flu vaccine recommendation expanded through age 18

News out of this week's ACIP meeting in Atlanta that the committee voted today to expand its influenza vaccine recommendation to include all children and teenagers up to age 18. Previously, the recommended pediatric population only included children between 6 months and 5 years of age. Here's the CDC announcement about the expanded recommendation; it notes that approximately 30 million children are affected.

Here's coverage from the New York Times, CIDRAP News, and the Associated Press. The AP story reports that of the 36,000 annual influenza deaths in the U.S., only 25-50 occur in the 5-18 population. (Of course, preventing deaths is only one goal of expanded vaccination efforts.)

With some in the medical and public health communities advocating a universal recommendation, i.e., that all Americans receive the vaccine annually, the new recommendations (once fully implemented) will include essentially all Americans under age 18 and over age 50, in addition to a host of specific groups at higher risk of influenza morbidity or mortality.

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Today's announcement follows several weeks of bad news about the severity of the current flu season and issues with this year's vaccine failing to match a significant percentage of the circulating strains. Earlier this month, WHO recommended a wholesale redesign of the composition of the 2008-9 influenza vaccine -- replacing all three strains in the current season's vaccine. Here's the WHO report (pdf) and a CDC Q&A explaining the process by which the annual composition of the vaccine is determined. As is standard practice, the identical three strains were also recommended by the relevant FDA advisory committee at their meeting last week. Here's a related CIDRAP News story.

This link includes the most recent weekly report from CDC on influenza activity in the U.S., just part of the vast amount of information and resources available at its seasonal flu website.

2008 recommended vaccination schedule; Paper on historical changes in disease rates

Last week's issue of MMWR included the recommended vaccine schedule for children and teenagers (i.e., birth to age 18). The familiar color-coded tables incorporate changes made in the joint recommendations of CDC, AAP, and AAFP over the past year. (The updated schedule was also published nearly simultaneously in the journal Pediatrics earlier this month.)

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Speaking of CDC, a paper by a group of researchers at its National Center for Immunization and Respiratory Diseases was published in JAMA in December titled, "Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States."(free abstract; subscription required for full text). From the abstract, here is what the researchers report:

"A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. Endemic transmission of poliovirus and measles and rubella viruses has been eliminated in the United States; smallpox has been eradicated worldwide. Declines were 80% or greater for cases and deaths of most vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, Hib, and varicella. Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively."

A table showing this 'before-and-after vaccines' disease incidence data is a mainstay of Powerpoint presentations by vaccine policy-makers and researchers. While the numbers are impressive, such analyses of historical disease rates are fraught with challenges, particularly when attempting to isolate the impact of a certain variable (such as a vaccine) over many decades. To their credit, the authors of the paper note some of the many other factors that also contributed to the changes in disease rates during the 20th century, such as improvements in health care, standards of living, and many others.

The major decline in disease rates is impressive, and there's no doubt that vaccines play a major part in these successes. However, without being given comparisons to rates of other infectious diseases for which vaccines are not available, the reader of this paper could not be faulted for forgetting that vaccines are part of a much larger story of changes in medicine, health, and disease during the 20th century.

Revised adult immunization schedule released; Hep A news and recommendations

Friday's MMWR included a newly updated adult recommended immunization schedule -- PDF available here. As the introductory material details, changes made to last year's schedule are fairly minor, notwithstanding the addition of zoster vaccine (recommended for adults 55+) and an expanded recommendation for varicella (now recommended for all adults without evidence of immunity).

The same issue of MMWR included updated ACIP recommendations on postexposure prophylaxis for those exposed to Hepatitis A virus. The recommendations address the relative merits of Hep A vaccine versus immune globulin (IG) as a postexposure strategy, the subject of a randomized clinical trial ("Hepatitis A Vaccine versus Immune Globulin for Postexposure Prophylaxis") and an editorial ("Another Success for Hepatitis A Vaccine") in this week's New England Journal of Medicine.

2007 Pediatric & adolescent immunization schedules released

Yesterday, the American Academy of Pediatrics released the 2007 recommended immunization schedules for children, adolescents and catch-up immunization. (As always, the schedules are a joint production of the ACIP, AAP, and American Academy of Family Physicians, but it appears that the AAP website is first to release it publicly.) The new schedule includes, among other changes, the new recommendations for rotavirus and HPV vaccination, as announced in 2006.

The traditional one-page schedule covering all vaccine doses from birth to 18 years had grown increasingly complex and crowded in recent years, a multi-colored sea of bars, shaded boxes, dotted lines, abbreviations, and minuscule print. The chief solution to this problem is the expansion of the single-page schedule to three pages, one for birth-6 years, another for ages 7-18, and a third for catch-up immunization spacing. Many of the more confusing design elements from years past have been eliminated and the fine-print footnotes are now bullet points.

While this update is marked improvement over previous versions with respect to comprehensibility, most parents will still be far better served consulting their physician to understand clearly which vaccines are recommended for their children and when.

Update, 1/5/06 -- The latest issue of CDC's MMWR also announces the newly revised schedules.

CDC releases updated "General Recommendations on Immunization"

Every few years, the Advisory Committee on Immunization Practices releases an updated version of its "General Recommendations on Immunization." The new document released Friday is an update to the previous version released in 2002.

As the title suggests, it is a series of recommendations that are not specific to a particular vaccine, addressing issues such as vaccine handling, administration, spacing, contraindications, and vaccination of specific populations (such as pregnant women or those with altered immune systems). Coupled with 200+ references to the medical literature, it's an excellent resource for those looking for a synopsis of a particular topic and directions for further study.

Gardasil provisional ACIP recommendations posted

As shown by the series of announcements in the past six months regarding Merck's rotavirus vaccine, there's a pattern for how ACIP recommendations become official -- first a vote at one of the committee's thrice-annual meetings, then the online posting of recommendations on the ACIP website a few months later, and, finally, publication in MMWR a few months after that. Only then are the recommendations truly 'official', for what that's worth. In the case of RotaTeq, the ACIP vote came on February 21, provisional recommendations were posted in May, and final publication occurred on August 10 (as we noted here).

Using this timetable for comparison, all signs point to Merck's HPV vaccine, Gardasil, being on a faster track. Recall that the ACIP vote took place on June 29 (as we discussed then), but the provisional recommendations are already posted here at the ACIP website, where they've been available for over a week. The only real news from the document is that publication of the official version of the recommendations in MMWR is tentatively slated for November. (Thanks to the Immunization Action Coalition for the heads-up.)

ACOG issues HPV vaccine recommendations

The American College of Obstetricians and Gynecologists announced their recommendations to ob/gyns for HPV vaccination in women age 9 to 26. Not exactly a surprise that the group supports routine vaccination, but it's an important action, as ob/gyns see the vast majority of women in the 'catch-up' immunization group -- age 13 and above. Coupled with efforts by primary care providers, encouragement for vaccination by ob/gyns increases the likelihood of high vaccination rates overall among the large catch-up population. There's ample evidence that official recommendations from professional groups such as this do influence physician practices.

Here's the ACOG press release as well as excerpts from the full recommendations posted yesterday on the ACOG website. The full recommendations will be published in the September issue of Obstetrics and Gynecology.

Rotavirus vaccine recommendations published in MMWR

Back in February, the ACIP recommended Merck's rotavirus vaccine, RotaTeq, for universal administration to infants. While provisional recommendations were posted on the ACIP's website in May (as we discussed here), just yesterday did the recommendations become official upon their publication in MMWR. Here are the full recommendations.

The publication means a few things: 1) The process of insurance companies adding RotaTeq to their list of covered vaccines will likely accelerate over the coming months, and 2) professional groups and individual pediatricians will increasingly recommend vaccination to parents as it becomes a standard part of pediatric care.

Gardasil receives ACIP recommendation for girls 11-26

We're in Atlanta for the summer ACIP meeting, where the biggest news coming out of the CDC is the (not unexpected) action on Gardasil. In short, the ACIP unanimously recommended that all 11-12 year old girls receive the 3-dose series, although vaccination can begin as young as 9, at the physician's discretion. Additionally, a 'catch-up' immunization program was recommended for girls and women through age 26.

Here's the coverage from the New York Times, Associated Press, Los Angeles Times, and Reuters, as well as the press releases from Merck and the CDC. Also of interest is this transcript of a CDC media briefing held this afternoon shortly after the recommendation.

In many respects, today's proceedings were rather anti-climactic, despite a standing-room-only crowd in the meeting auditorium. Coming after four hours of presentations and discussion on HPV vaccines at the February ACIP meeting, there was very little new information presented this morning. The pre-vote discussion was equally subdued, as Gardasil's trial data and FDA indications provided few alternatives beyond the recommendation as approved. That's probably a good thing, as decisions made amid uncertainty or a significant division in opinion would likely mean that things hadn't been thoroughly explored prior to the meeting. Clearly, the committee was well prepared and ready to act.

Personally, we were curious to see whether any of the groups opposing state mandates for HPV vaccination would use the "public comment" time to continue making themselves heard (as the Family Research Council did at the February meeting). Once again, however, no fireworks to report, as all nine public commenters strongly supported the vaccine. Commenters included representatives from the National Coalition for Cancer Survivorship, the Planned Parenthood Federation of America, AmeriChoice, The Balm in Gilead, the American Social Health Association, the Celebrate Life Foundation, Women in Government, and the International RRP ISA Center. Also commenting was Dr. Otis Brawley, a professor at Emory University. While unanimously praising the ACIP's recommendation, several commenters advocated broadening the vaccine's target groups in the future to include boys as well, an action that will surely occur in the not-too-distant future.

It should be noted that several opponents of state mandates, while not vocal at today's meeting, are quoted in some of the news stories linked above.

With licensure and a recommendation secured this month, the fate of Gardasil now depends on a variety of financing programs to make the vaccine available and affordable to all who should receive it, a comprehensive education program for parents and physicians alike, and the actions of all 50 state departments of health, whose decisions regarding school-entry mandates will impact greatly the degree of vaccine uptake and, thus, the overall benefit of the vaccine for society. Stay tuned.

Provisional rotavirus recommendations expected within a month

This afternoon, the National Immunization Program hosted a live netconference titled "Current Issues in Immunization". Among the topics covered in the one-hour session were revisions to the General Recommendations on Immunization, the document updated every few years that provides general guidance of immunization practices in the U.S. The revisions, addressing particulars of simultaneous administration of multiple vaccines and the impact of altered immunocompetence on vaccination recommendations, were discussed in detail at the February ACIP meeting.

Also presented was an update on the recently licensed and recommended rotavirus vaccine, Merck's RotaTeq. CDC's Dr. Umesh Parashar gave an overview of rotavirus epidemiology worldwide and in the U.S., contrasted RotaTeq with RotaShield (Wyeth's failed vaccine of 1998-99), and offered an update on the current status of the ACIP recommendation approved in February that all infants receive the vaccine at 2, 4, and 6 months.

According to Dr. Parashar, the ACIP recommendation is currently undergoing final clearance from the CDC and HHS. These required approvals are expected within the next month, at which point provisional recommendations will be posted online here. Recommendations do not become official until printed in the Morbidity and Mortality Weekly Report (MMWR), a step expected to occur sometime in fall 2006.

Still, federal government vaccination recommendations remain only recommendations unless individual states act to require the vaccine as a condition of school or day care attendance. These mandates are widely expected for RotaTeq, but require actions by state departments of health or (in some cases) legislatures. Mandates for rotavirus vaccination are not expected to be nearly as contentious as those for HPV vaccines in the months and years ahead.

Society for Adolescent Medicine position on HPV and other teen vaccines

This is a few weeks old, but the March issue of the Journal of Adolescent Health included this position paper on adolescent immunization from the Society for Adolescent Medicine. (free PDF).

The paper addresses several vaccines administered to teenagers and outlines some of the general challenges that adolescent immunization programs face. HPV vaccines receive significant attention, with respect to the science, cost-effectiveness, and behavioral concerns the vaccine raises among many. On the latter, here's what they write...

"Data indicate that parents will support the use of a vaccine to prevent sexually transmitted infections (STIs) including HPV, especially after receiving education and an understanding of the potential outcomes of the disease. In addition, provider acceptability is important to parents and their adolescent children. Thus, health care professionals need to educate themselves, parents and patients with the goal of promoting the health and well-being of patients regardless of the transmission routes of infection and disease. Vaccination does not preclude the use of other methods to prevent disease, including significant educational initiatives. Even with significant educational efforts aimed at behavioral change, adolescents still engage in health-risk behaviors. Just as with any other health prevention strategy, it makes the most sense to protect all youth--including our most vulnerable youth--with all prevention strategies available, including education and vaccination."

GSK rotavirus vaccine approved by EU

Rotarix, the GSK rotavirus vaccine, received EU approval Monday. Forbes, among other places, had the details.

While GSK's vaccine is out in front on the international stage, it's yet to be licensed in the United States. RotaTeq, the rotavirus vaccine from Merck, was licensed by the FDA in December. As was widely reported last week, CDC's Advisory Committee on Immunization recommended routine vaccination with RotaTeq for all newborns at 2, 4, and 6 months. Here's the Washington Post story.

For those confused by news accounts of vaccines in development, similar products from competing manufacturers, and the maze of regulatory steps required in the U.S., the American Academy of Pediatrics has a very useful table on its website that provides the trade name, target, manufacturer, age range, licensure status, and AAP/ACIP recommendations (if any) for vaccines recently approved or currently in the approval process. The page is updated regularly and is a great resource. A link has been added on the right of the page.

NY Times Calls for Further Expansion of Flu Vaccine Recommendations

Responding to ACIP's recommendation earlier this week calling for flu vaccination for 2-5 year olds, the New York Times this weekend suggested expanding the recommendation ever further, increasing the production capacity potentially necessary if or when a pandemic arrives...

"Our only qualm is to wonder whether even more children should be vaccinated to protect us all from the flu bugs circulating in elementary, middle and high schools. The advisory committee seems to have limited its recommendation at least in part because of concerns that the troubled vaccine industry may not be able to meet a much higher demand. But in the long run, it would make sense to ramp up production capacity and vaccinate virtually everyone as a prelude to preparing for mass vaccinations should an influenza pandemic strike."