HPV Roundup: Gardasil safety worries, Cervarix FDA delays, more on mandates

There's been a flurry of media coverage this week about possible safety issues related to Gardasil. It appears that the attention was initiated by this report released by Judicial Watch, the conservative watchdog group. Like its previous reports alleging numerous deaths and illnesses caused by vaccine, this Judicial Watch report is based on unconfirmed submissions to VAERS, the government's clearinghouse for reports of possible vaccine-related adverse events. Reports to VAERS -- widely described as a 'hypothesis-generating mechanism' -- are later examined by government officials to determine what, if any, role a vaccine may have had in the reported condition.

Numerous other outlets have raised questions about Gardasil's safety in the past few days, most notably this CBS News story by Sharyl Attkinson, the media member who is increasingly at the forefront of reporting on alleged vaccine risks. Other media outlets examining the topic include CNN and WebMD.

In the meantime, officials from CDC and FDA have assured the public that the vaccine remains safe and effective and that reports of possible adverse events will continue to be investigated. Merck responded similarly yesterday, noting the limitations of reports made to VAERS.

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Meanwhile, it appears that the U.S. head-to-head battle between Gardasil and GSK's Cervarix will most likely be delayed until late 2009. Last week, the Wall Street Journal and Reuters, among others, reported the GSK announcement of its timetable for submitting additional trial data requested by FDA. Here is the GSK press release. It notes that Cervarix is already approved in 67 countries, including the E.U., but it's no secret that the U.S. market is by far the most lucrative, as Merck's sales figures from earlier this year illustrated.

From a business standpoint, this is decidedly good news for Merck, as it extends its head start in the U.S. (The news has not all been good, however, as it was announced late last month that Merck's application to expand the indication for Gardasil for women through age 45 will face additional scrutiny and delays. Here's a story from Reuters and the Merck press release.)

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In other news, two papers have recently been published in academic journals on HPV mandates (joining a growing literature on this topic -- including papers by Schwartz, et al., Colgrove, and Zimmerman.) One paper, "Assessing Mandatory HPV Vaccination: Who Should Call the Shots?" (Javitt, et al.) appears in the Summer 2008 issue of the Journal of Law, Medicine & Ethics (subscription required). In short, the authors conclude, "...Mandating HPV vaccination at the present time would be premature and ill-advised."

Also, the May 2008 Harvard Law Review published a paper titled "Toward a 21st Century Jacobson v. Massachusetts (pdf), alluding to the 1905 case that is widely seen as the foundation for state public health powers. The authors argue that a distinction should be drawn between vaccines that are 'medically necessary' (such as smallpox) and those that are 'practically necessary' (such as hepatitis B and HPV, for which other preventive measures are available but not widely used). The paper suggests that current law and policy fail to acknowledge the implications of this distinction.

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.

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.

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.
  

Journal roundup: Racial disparities and school requirements, Parental comprehension, MMR media coverage, and more

As we do periodically, here are some papers of note published recently in the medical literature. (Most require a subscription in order to view the full text.)

• "Effect of a School-Entry Vaccination Requirement on Racial and Ethnic Disparities in Hepatitis B Immunization Coverage Levels Among Public School Students" (Pediatrics, Vol. 121, No. 3); Included in an issue with several papers on vaccination, this study analyzes racial/ethnic differences in Hepatitis B vaccination status among adolescents in Illinois before and after the establishment of a school-entry requirement. The authors conclude, "There was a dramatic decrease in the disparity of hepatitis B vaccination coverage between white and black or Hispanic students. School-entry requirements effectively increased hepatitis B vaccination coverage levels regardless of race or ethnicity and should be considered for other recently recommended adolescent vaccines."

• "Parents' vaccination comprehension and decisions" (Vaccine, Vol. 26, No. 12, 1595-1607); Based on a series of in-depth interviews with parents, the researchers report on the attitudes and mental frameworks that shape feelings about vaccination. They conclude that the parents were generally favorably toward vaccination, but "many had limited understanding of how [vaccination] works, making them potentially vulnerable to misinformation (or disinformation)."

• "Media Coverage of the Measles-Mumps-Rubella Vaccine and Autism Controversy and Its Relationship to MMR Immunization Rates in the United States" (Pediatrics, Vol. 121, No. 4); This paper published by our colleagues at Penn and The Children's Hospital of Philadelphia examines changes in U.S. vaccination rates in the wake of papers published in the scientific literature suggesting a link between MMR vaccine and autism compared to mainstream media coverage of the same controversy. The authors conclude, "There was a significant increase in selective MMR nonreceipt that was temporally associated with the publication of the original scientific literature, suggesting a link between MMR and autism, which preceded media coverage of the MMR-autism controversy."

• "On message, off target: Official advice on vaccination is too often poorly transmitted" (Nature, Vol. 452, No. 128); An editorial published in response to press reports noting presumptive Republican presidential nominee John McCain's sympathy toward arguments suggesting a link between vaccines and autism. The editors argue that new, enhanced communication strategies from CDC and other agencies are necessary to counter allegations of vaccine safety concerns.

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.

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.

Study reports no link between thimerosal and neuropsychological outcomes

In what is sure to mark a new round in the debate regarding the impact of thimerosal in vaccines, a paper published in the latest issue of the New England Journal of Medicine reaches the following conclusion:

"Our study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years."

The paper by CDC's William Thompson and (many) colleagues -- "Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years" -- is available for free at the NEJM website. The study compared children's performance on a battery of neuropsychological tests to their total exposures to thimerosal during vaccination as infants. The paper repeatedly states that autism was not a focus of this study, but there's little doubt that the findings here will find their way into the vaccines and autism debate, even despite efforts from CDC officials at today's teleconference to emphasize this distinction.

Tomorrow, we'll link to some of the media coverage that this news will surely receive -- it was already prominently featured on several of the national evening news broadcasts tonight. For now, here's coverage from the Associated Press, US News & World Report, and Reuters.

The New England Journal also published two related perspectives on thimerosal and vaccines. Paul Offit writes in "Thimerosal and Vaccines -- A Cautionary Tale" (free full text),

"The thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public; otherwise, the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned."

Stephen Sugarman also contributes a piece titled "Cases in Vaccine Court -- Legal Battles over Vaccines and Autism."

Autism advocates and proponents of a link between thimerosal and autism are already raising questions about the researchers, the study and its conclusions (despite the standards required for publication in the world's premier medical journal). For examples, here are statements from Autism Speaks and SafeMinds (which calls the study 'wrong').

More to come...

Seasonal flu: Record supply expected; FluMist approved for 2-4 year olds; Data shows low coverage in past

In what is becoming an annual tradition, CDC announced last week that a record supply of seasonal influenza vaccine is expected to be available for the approaching flu season. Once again, however, barring a massive increase in the number of Americans seeking the vaccine, millions of doses will very likely go unused.

As this AP story reports, current estimates are for 132 million doses to be available this year, an increase over last year's total of 121 million doses (itself a record). Despite the vaccine being recommended for 218 million Americans, 18 million doses were not used last year and were destroyed. Here's more coverage from CIDRAP News and the Washington Post.

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Last Wednesday, FDA approved FluMist -- the only flu vaccine that is administered nasally -- for use in children between the ages of 2-5. Previously, the vaccine had been approved for those age 5-49. Here's the FDA announcement, coverage from CIDRAP News, and a particularly detailed story from the Washington Post.

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Last week's MMWR included several papers detailing flu vaccination coverage in recent seasons. Here's state-by-state data of adults 18 and older, children age 6-23 months, and early data on children age 6-59 months (reflecting the new ACIP recommendation of June 2006). The editorial notes for all three papers explain that the observed vaccination rates are well below CDC goals.

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In related news, CDC announced a new-and-improved seasonal influenza website available at www.cdc.gov/flu/. The site contains extensive information for health professionals and the general public about the virus, prevention, and treatment.

CDC National Immunization Survey Results Released

On Friday, the latest issue of MMWR included the 2006 data from the National Immunization Survey, the most reliable source for information on vaccination rates nationwide. MMWR (pdf) includes two reports. One looks at children age 19-35 months (the traditional study population of NIS since its inception in 1994). The other surveys teenagers age 13-17 years (a new 'spin-off' study appropriately dubbed NIS-Teen).

In the infant/toddler population, the news appears to be quite good. Based on a sample of over 21,000 children, 77% had received the full recommended series of vaccinations in 2006, a slight (though statistically insignificant) increase over 2005's figure of 76.1%. This year's data moves closer to the Healthy People 2010 goal of 80% coverage for the recommended series.

That said, there is a great variation in vaccination rates among states and clear differences among races and socioeconomic status. 73.9% of African-American children have received the complete series of recommended vaccinations, compared to 77.9% of white children and 77.4% of Hispanic children.

An accompanying CDC press release somewhat awkwardly explains the disparity this way:

"Children who live below the poverty level are less likely to be vaccinated than children who live at or above the poverty level. Because a substantial percentage of black children lived below the poverty level, coverage for black children overall was low compared with white children. Therefore, even though the 2006 survey found that black, non-Hispanic children had lower vaccination rates than white, non-Hispanic children for the series of routine vaccines, at [sic] the difference was likely related to socioeconomic status and household income rather than race."

As for teenagers, the NIS-Teen data was not as encouraging, as none of the recommended vaccines for this age group had coverage levels meeting the Healthy People 2010 goals. The accompanying editorial note and CDC press release point to the relative newness of several of the new recommendations for teenagers. Both look to the data as evidence for continued education of parents and health care providers about the benefits of these vaccines.

Seasonal flu: Benefits of childhood vaccination; '06-'07 flu season wrap-up

Among the many vaccine-related contributions to the latest issue of Pediatrics (dated September 1) is a paper titled "Childhood Influenza: Number Needed to Vaccinate to Prevent 1 Hospitalization or Outpatient Visit." (free abstract; subscription required for full text). The authors seek to evaluate the potential benefit of influenza vaccination of children ages 6-59 months following the ACIP decision last year to add this group to those for whom the vaccine is recommended annually.

Determining the "number needed to treat" is a common tool of epidemiologists and those interested in the cost-effectiveness of medical treatments. The methods and results of this study don't lend themselves well to summary, but here is the authors' one-sentence conclusion:

"With 1 outpatient visit being prevented through vaccination of [fewer than] 50 children, influenza vaccination can reduce influenza-attributable medical visits in children significantly, even in years with modest vaccine efficacy."

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Speaking of influenza vaccination, a report in MMWR in mid-August wrapped up the 2006-07 flu season and previewed the vaccine composition for the upcoming 07-08 season.

The report notes that the 2006-07 season was comparatively mild relative to the 3 flu seasons that preceded it, as mortality and pediatric hospitality rates were all below those of recent year.

The influenza vaccine for the upcoming season will include two of the same strains in last year's vaccine, with FDA advisers opting to include one different influenza A component. (Each season's vaccine includes two influenza A and one influenza B components.

MMWR: Flu recommendations and polio eradication update

Several interesting items related to vaccination appear in today's issue of MMWR. Among them:

-- A revision to the ACIP document "Prevention and Control of Influenza," an expansive review of all aspects of seasonal flu vaccination guidance and related data. Notable in this updated version is additional encouragement aimed at promoting influenza vaccination of health care workers as well as information on the composition of the 2007-08 vaccine.

-- A report on worldwide progress toward polio eradication, as of May 2007. The number of polio-endemic countries remains at four (Pakistan, Afghanistan, Nigeria, and India) with the vast majority of the 1,997 cases reported in 2006 occurring in Nigeria (1,123) and India (676). Global vaccination coverage stands at 78%, a number that is well over 90% in the Americas but far lower in Nigeria (39%) and India (58%). Those interested in polio eradication should visit our previous posts about polio, which include several items discussing the merits and challenges associated with pursuing eradication.

JAMA and Slate on vaccine-related replacement disease

A common question asked about vaccines that target specific variants of a pathogen (such as HPV, pneumococcus, or meningococcus) is how great the likelihood is that 'replacement disease' may occur. Simply stated, this phenomenon describes the emergence of new serotypes or subtypes not included in a vaccine becoming more prevalent as those that are included in the vaccine are eliminated.

A paper in JAMA this spring suggested replacement disease may be occurring among recipients of Prevnar, Wyeth's pneumococcal conjugate vaccine. (Four doses of the vaccine are recommended for all U.S. infants.) The paper was the basis for a commentary by Arthur Allen ("Fear of Replacement: What if a vaccine kills off one strain of a disease—but makes room for another?") that appeared in Slate late last month.

Ben Kleifgen, working at the Penn Center for Bioethics this summer, summarizes both items:

"In the JAMA paper, CDC’s Arctic Investigations Program observed an increase in pneumococcal infections in Native Alaskans receiving Prevnar. Of particular concern to researchers is the fact that the infections are largely from serotype 19A, a highly virulent but previously quite rare strain. Allen wonders if the threat of replacement disease may discourage further vaccine development, although the situation may not be that bleak. There is evidence that the new strain may be on the rise worldwide, unrelated to the use of Prevnar. In addition, Wyeth and GSK are both working on new pneumococcal vaccines that will cover 19A."

Info on Kawasaki disease added to RotaTeq label

A colleague from CDC alerted us to this announcement regarding a change to the label of RotaTeq, Merck's rotavirus vaccine recommended to all infants at 2, 4, and 6 months. Here's the first paragraph of the CDC statement:

"The Food and Drug Administration (FDA) approved today a revised label for RotaTeq, a rotavirus vaccine manufactured by Merck and Co., Inc., to include information on reports of Kawasaki disease occurring before and after the vaccine’s licensure in February 2006. FDA has not made any changes to its indications for use of RotaTeq nor has it issued new or revised warnings or precautions. Likewise, the Centers for Disease Control and Prevention (CDC) has not made any changes in its recommendations regarding the use of RotaTeq. Healthcare providers and parents should remain confident in using RotaTeq in infants."

Here's the FDA release and a related story from Reuters (the only media outlet to have reported on this item as of now.)

General info on Kawasaki disease can be found here and here. It's a rare and poorly understood inflammatory condition that affects 4,000 American children annually.

The "label" referred to in the announcements above is actually this document, an 11-page, single-spaced, data-laden product insert unlikely to top the reading lists of most parents (or pediatricians, for that matter).

The FDA statement notes, "The cases reported to date are not more frequent than what could be expected to occur by coincidence," a statement that could also describe its announcement in February regarding intussusception reports among recipients of RotaTeq.

Similar to that earlier occasion, this announcement was seemingly made so that providers and parents may be vigilant in looking for symptoms of Kawasaki disease, in case a connection to the vaccine does exist. However, calling attention to severe conditions for which no evidence suggests a vaccine link may create undue confusion and worry among parents still told to vaccinate their children with RotaTeq. Admittedly, it is a difficult balance that must be weighed by policy-makers, but one that merits further study.

Gardasil: CDC response on safety/efficacy; survey on parental support for mandates

The weekly news update from the Immunization Action Coalition alerted us to this CDC Q&A released last week titled "CDC Questions and Answers Concerning the Safety and Efficacy of Gardasil." The three-page document outlines the current status regarding safety monitoring, known safety concerns, the potential need for boosters, and the ongoing necessity of Pap screening.

It seems likely that the fact sheet was this breathless press release from JudicialWatch.org asserting (based on VAERS reports) that "three deaths were related to the vaccine." The CDC fact sheet clearly explains how and why this statement is a misinterpretation of VAERS data, reaching conclusions that are no possible from that information alone. Not surprisingly, a search of Google News suggests that the press release garnered virtually no attention from the print media. While safety concerns linked to Gardasil could still surface, there's no evidence at present to suggest such a connection.

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One other item related to Gardasil: The headline from a survey released by a group at the University of Michigan C.S. Mott Children's Hospital reads: "Majority of U.S. Parents Not in Favor of State HPV Vaccine Mandates." The report is available here, and here is coverage from CBS News and the Washington Times.

However, the headline -- while likely shrewdly written to generate the media coverage sampled above -- is very misleading. The report's own data (Table 1 in the report) lists 26% of parents disagreeing with an HPV mandate, 44% of parents agreeing, and a very significant 30% as 'neutral.'

Therefore, the same data could also carry the headline, "76% of parents not opposed to HPV mandate," which would actually more accurately capture the large percentage of respondents with no opinion for or against a mandate.

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.

New data on HPV prevalence; conflicting thoughts on relevance to vaccine debate

Last week's JAMA paper by Dunne, et al., -- "Prevalence of HPV Infection Among Females in the United States" -- garnered a significant bit of media attention. An accompanying editorial, "Estimating the Population Prevalence of HPV," by Weller and Stanberry, makes a point of examining the implications of this data to HPV vaccination policy, specifically cost-effectiveness calculations. (Free abstracts; subscription required for full text).

Here's some of the coverage of the paper by the popular press: Associated Press, Dallas Morning News, Washington Times, and Washington Post.

The data has provided ammunition for both sides of the vaccine mandate debate. Proponents of vaccination (and mandates, specifically) are pointing to the surprisingly high prevalence of HPV, of all types, in women: 24.8%

Those on the other side note the study's findings that the specific HPV types included in Gardasil are present in only 3.4% of females. To critics of mandates, this suggests that it is unnecessary to vaccinate all young girls when only a small percentage of females have the specific strains included in the vaccine. However, these numbers do not change the overall facts regarding cervical cancer incidence and mortality.

If anything, the ways in which the Dunne, et al., paper's findings have been used and will continue to be used in the Gardasil debate offer a valuable lesson of the potential dangers of using statistics in isolation to advance a policy argument.

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.

Updates on measles epidemics in U.S. and worldwide

A few items of note regarding measles outbreaks during the past few years:

• We've written several times about the 2005 measles outbreak in Indiana that sickened 34 (such as here and here). This AP story from late last month confirms what was widely speculated to be the cause of the outbreak: a 17-year old unvaccinated girl who traveled to a Romanian orphanage as part of a church mission trip, according to CDC.

• Farther from home, PLoS Medicine published yesterday a paper with the provocative (but accurate) title: "Unacceptably high mortality related to measles epidemics in Niger, Nigeria, and Chad," looking at mortality rates in three epidemics in 2004 and 2005. Accompanying the paper is an editorial titled "Measles still has a devastating impact on unvaccinated populations." To those close to global vaccination programs, the title will likely seem laughably obvious, but the paper is a noble effort to draw attention to the continued suffering caused by a completely preventable disease.
  

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.

HPV: favorable data for male vaccination; VFC action; CDC shift in research focus

A paper published in the November issue of the journal Pediatrics includes new data from Merck on some of their ongoing trials of Gardasil in different populations. It's a highly technical paper with an equally complex title: "Comparison of the Immunogenicity and Reactogenicity of a Prophylactic Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine in Male and Female Adolescents and Young Adult Women." (free abstract; subscription required for full-text).

To summarize, the paper reports the results of trials examining whether the vaccine's response in 10-15 year olds mirrors what's been shown in older females (16-23 year-olds). The short answer is that it does generate a comparable ('noninferior,' in scientific jargon) immune response in younger populations. Good news. The most interesting finding from the perspective of potential ethical issues is the comparison of data between 10-15 year old boys versus girls. Boys had a nearly identical response to the vaccine as their female counterparts did as well as a virtually identical safety profile between genders. As the paper's authors (all of whom are employees or consultants of Merck, critics might note, despite that being an obvious result of a Merck trial) note:

"Our findings in boys lend support for implementation of gender-neutral immunization using this vaccine for the purpose of preventing the widespread morbidity and mortality from anogenital cancer, as well as dysplastic cervical and external genital lesions, in the general population."

Speaking of Gardasil, news earlier this week that the vaccine has officially been added to the federal government's Vaccines for Children program, ensuring its availability to uninsured children age 18 or under. Here's a brief story from UPI.

One final related item: a story from Wednesday's Washington Post, "CDC Shifts Vaccine-Data Focus," reports on the decision to refocus intensive data-collection activities on immunization in 22 major cities on teenagers rather than young children. The move is a result of multiple new vaccines recommended for adolescents, including vaccines against HPV, meningococcus, and tetanus/diphtheria/pertussis (Tdap).

From MMWR: childhood & 65+ vaccination rates, 2006-07 adult schedule, and Menactra safety update

A great deal of news on vaccines and vaccination efforts has appeared in recent issues of the CDC's Morbidity and Mortality Weekly Report. Here are some items of note:

• "Childhood Influenza Vaccination Coverage -- United States, 2004-05 Influenza Season" and "Influenza and Pneumococcal Vaccination Coverage Among Persons >65 Years -- United States, 2004-05." With flu cases starting (very slowly) to appear, these two pieces offer some data on the effectiveness of efforts to vaccinate two populations at higher risk of influenza-related complications. For children, the headline is that young children (19-35 months) had a substantially higher vaccination rate in the 04-05 season than for the previous year -- likely attributable to stronger ACIP recommendations. However, the overall percentage of fully vaccinated children in this age group was still very low (17.8%). For 65+ adults, the reverse phenomenon is true: both flu and pneumococcal vaccination rates are over 60%, but flu vaccination rates in 2005 were 4% lower than a year earlier. (The MMWR story notes that all of these numbers are well below the goal of 90% included in Healthy People 2010.)

• Better news can be found in this report, "Vaccination Coverage Among Children Entering School, 2005-2006 School Year." Compiling the latest data available, a editorial note accompanying the report explains, "More than half of reporting states indicate that they have already reached the Healthy People 2010 goal of >95% coverage for each of the vaccines recommended by the Advisory Committee on Immunization Practices (ACIP); the remaining states are making progress toward this goal."

• The 2006-2007 Recommended Adult Immunization Schedule, approved by the ACIP at their June meeting, has been published. Particularly because of efforts made at simplifying the schedule's design, the document is a great source for a general overview of recommended vaccinations in the 18+ population.

• One final item provides an update on reports of cases of Guillain-Barre Syndrome (GBS) among recipients of Menactra, Sanofi Pasteur's meningococcal vaccine. (We've written previously about this story in April.) A total of 17 cases have been reported with a suspected link to Menactra vaccination. As the report explains, analysis of these cases suggests a slightly increased risk of GBS among Menactra recipients, but the risk of meningococcus itself is among the reasons why no change in the current recommendation is being made at this time.
  

CDC Weekly Flu Update

We've added a link at the right to the CDC's Weekly Influenza Update. For those interested in tracking the flu season, the page includes week-by-week updates on the number of seasonal flu cases identified, the specific flu strains isolated, geographical variation, mortality, and more.

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.

CDC report on 2005 infant vaccination coverage

The National Immunization Survey is an annual effort by the CDC to evaluate coverage rates in infant populations (19-35 months) across the country. The telephone survey has several limitations and many critics, but it remains the best available, most comprehensive source of data on the success of vaccination programs nationwide.

In this week's MMWR, the 2005 data and discussion has been published. The report doesn't lend itself well to summary here, but suffice it to say that it is an excellent starting point for those looking for data of the scope of U.S. vaccination efforts in infants.

'06 flu vaccine supply might set records

During our Labor Day publishing hiatus, good news came from CDC that the total supply of flu vaccine for the upcoming flu season may reach an all-time high. The headline is that more than 100 million doses are expected to be available by late fall, a number that could reach as high as 115 million if a new vaccine from ID Biomedical (part of GSK) is licensed in the near future, as is anticipated. Either estimate would easily surpass the previous all-time high of 83 million doses administered in a single season.

Here's the detailed CDC press release as well as the related news story from CIDRAP. Between the impressive supply forecasts and the expected arrival of a fifth vaccine, signs suggest that at least some lessons were learned from the Chiron-induced flu vaccine shortage of 2004. The next challenge will be working to ensure that those 100+ million doses are administered, particularly to those groups identified as high-risk populations.

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.

CDC: 2005-06 flu season mild; vaccine an ideal match

Last week's MMWR included a report on the flu season that concluded last month. It noted that this year was milder than the past several flu seasons and that the three flu strains selected for the '05-'06 vaccine matched the predominant strains isolated throughout the season. As the selection of viral strains to be included in the next year's vaccine is by no means an error-proof process, WHO should be lauded for their work.

The University of Minnesota's CIDRAP has a story of its own on the CDC report.

CDC update on Midwest mumps outbreak

Yesterday, the MMWR website posted a dispatch with an update on the mumps outbreak in the Midwest followed by a discussion of possible causes.

Through 2 May, 2,597 cases have been reported, 57% of which coming from Iowa. Fortunately, no more than 25 hospitalizations can be attributed to mumps among these cases, with no deaths.

Among the possible causes for the outbreak discussed in an accompanying editorial note are: 1) the close quarters of college dormitories, 2) the absence of 2-dose MMR vaccination requirements for college attendance in 8 of the 11 states affected, 3) delayed recognition of mumps by younger physicians with limited exposure (so to speak) to it or physicians not initially suspecting mumps among vaccinated patients, both leading to more time for transmission to occur, and 4) the long-known fact that the vaccine is less than 100% effective at preventing disease.

CDC fact sheet/Q&A on HPV vaccines

Likely of interest to many visitors to this site is a fact sheet recently posted by CDC on HPV vaccines. There's not much in the way of new information, but the site concisely covers most of the basic questions that might be missed by many amidst the more specific controversy surrounding the vaccine's arrival and implementation.

CDC update on global polio eradication efforts

The latest MMWR reports on progress made over the past 15 months in the quest to eradicate polio worldwide. Among the details included:

• The number of polio-endemic countries now stands at 4 (Afghanistan, India, Nigeria, and Pakistan), down from 6 as recently as February 2006 (Egypt and Niger have been dropped from the list.)
• India and Pakistan are moving closer to eradication, with a 50% decrease in cases over the past year.
• Nigeria remains the primary nation of concern (as we've written about previously). 41% of cases worldwide (799 of 1,948) occurred in Nigeria, and 94% of global cases were caused by viruses originating in northern Nigeria.
• Worldwide infant vaccination levels are estimated at 80%, but are much lower (as expected) in polio-endemic countries. The number is only 39% in Nigeria overall, and lower still in provinces with higher rates of polio transmission.

Today's report comes a month after an extended feature in the New York Times on polio eradication efforts, which we previously discussed here.