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.

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.

ACIP: FluMist OK for children 2+; 6th seasonal flu vaccine approved

There's news from this week's meeting of the ACIP that the committee's influenza vaccine recommendation for children age 2-5 now includes FluMist. Here's a story from the Associated Press and another from the Wall Street Journal. This is hardly a surprise, in light of the decision by FDA to approve the vaccine for use in the 2-5 age group. (FluMist had previously been approved for 5-49 years olds only.)

In unrelated seasonal influenza vaccine news, we haven't yet noted the FDA approval late last month of Afluria, an injectable vaccine made by the Australian company CSL Biotherapies. The vaccine, licensed for use in adults 18 and older, is now the 6th different influenza vaccine available in the U.S. Here's coverage from CIDRAP News and Forbes.com and a media release from FDA.

New and improved CDC website for vaccines

Last week the CDC launched a new web home for all of its vaccine-related content -- www.cdc.gov/vaccines. Timed with the creation of the National Center for Immunization and Respiratory Diseases, which replaces the National Immunization Program,
the website has many more resources, is better organized, and is a dramatic visual improvement over the former NIP site.

We're still exploring the new site, but there is clearly a great deal of new information in addition to the expected info regarding the ACIP, recommended vaccination schedules, safety, cost/access, and much more. Also prevalent are links to websites of non-CDC (but like-minded) advocates of vaccination.

There's no doubt that the new CDC vaccines site is the premier source for understanding the federal governments' responsibilities, activities, and recommendations on vaccination.

February ACIP Minutes Available

The minutes of the February meeting of the CDC's Advisory Committee on Immunization Practices are now available here. The 96-page report includes discussions of the report this spring of a possible link between RotaTeq and intussusception, an overview of the thimerosal/safety debate, an update on pandemic flu vaccine development, and presentations from Merck and GSK on their HPV vaccines.

As always, very interesting reading for those seeking unfiltered coverage (comparatively speaking) of the latest in federal vaccine policy.

Gardasil round-up: Merck lobbying, ACIP chair comments, Virginia mandate, and more

There continues to be a steady trickle of news about Gardasil, largely centered on the ongoing debate regarding possible state mandates. Rather than attempt to keep up with each day's new op-eds, news stories, and the rest, we've decided to combine several of the most interesting items from the past 10-14 days into a single post. With that, here are some recent items making headlines:

• Perhaps the biggest news from the past few weeks was Merck's decision to stop participating in lobbying efforts for state mandates. Here's one account of the story from late February, courtesy of Reuters. It quotes Merck's Richard Haupt calling the company's activities a "potential distraction." Few would disagree with this assessment, and it is surprising, given the company's extensive and seemingly well orchestrated marketing and education efforts, that it would commit so significant a public relations blunder.

• Since that announcement, there has been no shortage of stories and op-eds more or less making the same point, namely, that the Texas political controversy and Merck's lobbying efforts have obscured the scientific and medical aspects of the vaccine and its potential benefits. That's the thesis of this New York Times editorial, "A Necessary Vaccine," (subscription required) which generated a number of letters in response. Also: a story in today's Times titled "A Vital Discussion, Clouded."

• Sunday's Washington Post also looked at these issues ("Parents Question HPV Vaccine: Push to Mandate Shots Rapidly Creates Backlash") Quoted in this story is ACIP chair Dr. Jon Abramson, who makes clear here and elsewhere that he is no supporter of current attempts to mandate vaccination. Abramson is also featured in this essay by Arthur Allen, "Why It's Too Soon for a Mandatory HPV Vaccine," published in the New Republic Online.

• Also mentioned in the Washington Post story above is the imminent action by Virginia Gov. Tim Kaine to sign legislation making his state the second to mandate HPV vaccination. The requirement would not take effect until 2008 or 2009 and would include the traditional types of exemptions (increasingly referred to in the media, accurately, as an 'opt-out provision'.) More information can be found in this story.
  

Renewed attention to possible rotavirus vaccine link to intussusception

A fairly significant amount of alarm was raised by an FDA statement last week titled "Information on RotaTeq and Intussusception". The statement reports 28 cases of intussusception -- the significant intestinal complication that led to the removal of the first rotavirus vaccine, RotaShield, in 1998 -- in children following administration of RotaTeq.

But what may have seemed at first glance to be a major announcement about the vaccine's safety was clarified later in the statement...

"Intussusception can occur spontaneously in the absence of vaccination. Of the reported 28 cases of intussusception, the number that may have been caused by the vaccine, or occurred by coincidence, is unknown."

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"The number of intussusception cases reported to date after RotaTeq administration does not exceed the number expected based on background rates of 18-43 per 100,000 per year for an unvaccinated population of children ages 6 to 35 weeks (CDC, unpublished data)."

In other words, there's no reason to be alarmed about the number of cases reported to date, but the statement, not unsurprisingly, did just that. This AP story by Andrew Bridges originally did not include any information about the background rate, likely contributing to the Alliance for Human Research Protection (and others, no doubt) misinterpreting the FDA item. "Merck rotavirus vaccine linked to 28 reports of life-threatening effect," is how the AHRP item describes the announcement, not at all what the FDA said.

CDC promptly released a statement attempting to clear up confusion. Among the 'key facts' they list:

• "We are not surprised by the number of reported intussusception cases following RotaTeq vaccination."
• "Intussusception, a form of bowel obstruction, occurs spontaneously in the absence of vaccination."
  
• "This notice does not mean there is a problem with the RotaTeq vaccine."

There's been no detectable coverage of this topic in the media since the initial FDA statement last week. It will, however, be discussed at this week's meeting of the ACIP, the agenda for which can be viewed here.

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.

Shingles vaccine recommended for adults 60+

We'd be remiss not to mention the biggest development out of this week's ACIP meeting, namely, the recommendation that all adults age 60 and over receive a single dose of Merck's new shingles vaccine, Zostavax. Here's the CDC press release, the Merck press release, and an AP story (courtesy of the Washington Post).

Also useful is this site assembled by the NIP with numerous resources about the painful condition formally known as herpes zoster and the new vaccine against it. Zostavax was licensed by the FDA in May and is the latest in a series of new vaccines introduced by Merck during the past year, though it's safe to say that this news hasn't received a hundredth of the attention that went to Gardasil in June.

ACIP: June minutes and October agenda

The folks at the Immunization Action Coalition pointed out that the full minutes from the June 2006 meeting of the CDC Advisory Committee on Immunization Practices are now available here. The 96-page PDF is the next best thing to attending the meeting yourself, as it provides comprehensive coverage of everything that took place. In June, of course, the major news was the recommendation vote for Merck's HPV vaccine, Gardasil. For those interested in the data that informed the ACIP's recommendation, the report is invaluable.

Also on the ACIP website is a draft agenda for the group's next meeting, scheduled for October 25-26. The most notable item is a scheduled vote on a recommendation for Merck's shingles vaccine, Zostavax, for use in adults.

Rotavirus inventors to receive CHOP gold medal

As this front-page story in today's Philadelphia Inquirer reports, the three researchers responsible for the discovery of what ultimately became Merck's new rotavirus vaccine, RotaTeq, will receive the "Gold Medal" from the Children's Hospital of Philadelphia. As even the brief outline in the Inquirer story suggests, the story of RotaTeq could be a case study for the difficulties of developing new vaccines -- the work leading to this year's FDA licensure and ACIP recommendation extends all the way back to research conducted in 1980.

Congratulations to Paul Offit, Stanley Plotkin, and Fred Clark on this latest honor. (For the record, Offit and Plotkin are friends and colleagues who have contributed their insights and expertise in various ways to the development of the Ethics of Vaccines Project.)

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.)

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.

June ACIP presentations available online

We neglected to mention that the slides from speakers at June's ACIP meeting were posted online in the last few weeks. For those looking for details, data, references, and scientific sophistication well beyond anything available in the media (for understandable reasons), these are great resources, particularly regarding Merck's HPV vaccine, the main item on the June agenda.

The files available include several presentations on Gardasil (safety and efficacy data from Merck, cost-effectiveness analyses, recommendation details, etc.), as well as the many other topics the committee considered, including a new recommendation for varicella vaccination, updates on influenza, mumps, rotavirus, avian flu, and much more.

Follow-up on ACIP Gardasil recommendation

Following up on last Thursday's post on the ACIP recommendation of Gardasil, here's a sampling of reaction in newspapers around the country:

• Both the Detroit Free Press and Press of Atlantic City ran 'local reaction' stories about the ACIP recommendation, surveying views from parents and physicians in their communities. Though some reservations are expressed -- both those unique to HPV as well as those common across all vaccines (i.e., safety) -- the vast majority of opinions in the story are positive.

• Two editorials specifically address the ACIP recommendation -- "A cancer vaccine triumph" (Chicago Tribune) and "Cancer prevention: Protect our girls" (Seattle Post-Intelligencer). Both pieces praise the recommendation (as the headlines would suggest), while postponing discussion of possible state mandates. The Tribune editorial ends this way:

  "But please, let's remember, this is a cancer vaccine. It's not a surrogate for the abstinence debate. Everyone is best served if this public discussion is about the safety, efficacy and cost-effectiveness of the new vaccine--and that's all."

Finally, the CDC website on HPV has been updated to reflect the Gardasil licensure and ACIP recommendation.

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.

"Merck's vaccine victory not yet complete"

So notes a story on TheStreet.com, the financial news and opinion site, that looks ahead to this week's ACIP actions on Gardasil and subsequent decisions that will be made at the state level. We agree wholeheartedly with the gist of the story, particularly because it quotes at length an earlier post from this very site.

As expected, HPV vote tops June ACIP agenda

Prior to the Memorial Day weekend, the first (public) draft of the agenda for the June 29-30 meeting of the CDC Advisory Committee on Immunization Practices was released. As usual, a wide range of topics are slated to be covered in the two days, but attention will overwhelmingly be directed at the first item on the agenda, the recommendation vote for Merck's HPV vaccine, Gardasil. (Technically, this assumes FDA licensure early next month, but all signs suggest this is all but a sure thing.)

The expected ACIP actions next month follow nearly four hours of presentations and discussions on HPV vaccines at the group's last meeting in February. The minutes for that meeting recently surfaced on the ACIP website, and are well worth reading for those interested in data galore on all aspects of HPV vaccines -- from Merck and GSK's research data, to cost-effectiveness studies, to analyses of possible behavioral consequences of vaccination, and more.

It's worth repeating that while the ACIP recommendation is very significant, the ultimate decision as to whether HPV vaccination will be mandated as a condition of school attendance is the responsibility of each state. Since that appears to be the key point of contention for critics of the vaccine, the federal actions expected in the next month will likely only mark the start of months of deliberation, lobbying, and scrutiny centering on each state's department of health.

A final 'program note': we'll be in Atlanta for the meeting and will be posting extensively here on the discussions and decisions that take place.

"The face that helped alter the nation's flu policy"

While RFK Jr. decries last month's ACIP recommendation to expand flu vaccination to include children between 6 months and 5 years (yes, because of thimerosal), today's Washington Post presents the sad story of the family of a 4-year old girl who died from influenza, prompting her parents to advocate for wider vaccination. An excerpt...

"As he waited his turn at the microphone, in an Atlanta auditorium filled with doctors and scientists, Gary Stein wondered whether what he had to say would make much difference. These were the experts, he realized, the people who spend a lifetime studying viruses and vaccines. They already knew all the facts, the statistics.

Still, they didn't know 4-year-old Jessica.

So Stein began talking, as a father who once had a little girl with hair the color and shimmer of champagne, a child who loved dress-up and Barbies and who was as healthy as they come until the day in January 2002 when she caught the flu. Less than 72 hours later, she was dead. Stein thought he could get through the main points of his remarks without stumbling. But as he stood before the federal Advisory Committee on Immunization Practices, explaining how his Falls Church family had been devastated, he choked up."

Very sad, but a must-read. Reading it side-by-side with RFK Jr.'s piece, it's hard to believe both authors are discussing the same decision by the same group about the same vaccine. (Without wading too far into the murky depths of the thimerosal debate, it's worth noting that central to earlier arguments about its safety were concerns about the total amount of thimerosal administered from all vaccines together. Now that flu vaccine is the only pediatric product containing it, the position seems to be that any thimerosal is unacceptable.)

One can assume that Jessica's story alone did not persuade ACIP to change the flu vaccine recommendation, but, amid debates and controversies, it reminds all of us of the real-life consequences of infectious diseases and immunization policy.