H1N1 roundup: international vaccine supply, nasal vaccine first in US, and more

Several H1N1 vaccine-related items in the news over the past few days:

• President Obama announced Thursday that the US would share 10 percent of its H1N1 vaccine globally, working with WHO. As this Associated Press story reports, the announcement is part of a joint effort by several western countries to improve access to H1N1 vaccine in the developing world. Here is the press statement from the White House, as well as a statement from WHO praising the announcement. This Washington Post story has more.

• Speaking of WHO, this Associated Press story published Friday reports that recent WHO projections of H1N1 vaccine production are "substantially less" than previous forecasts. Supply shortages further complicate the already-enormous challenge of large-scale vaccination against H1N1 influenza in the developing world. (A UN report leaked to the UK newspaper The Guardian presents a particularly ominous forecast of the impact of H1N1 flu in developing countries without a coordinated global assistance effort.)

• Here in the U.S., CDC announced Friday afternoon that 3.4 million doses of MedImmune's nasal spray vaccine (known as FluMist in its seasonal flu variety) will be the first H1N1 vaccine available. These doses should be available by early October, followed by the other (injected) vaccines throughout the month and beyond.
  

• Finally, Flu.gov, the U.S. government website launched several years ago as PandemicFlu.gov, completed a redesign and expansion on Friday. Billed as a 'one stop' for information on both seasonal and H1N1 influenza, the site summarizes its newly added features here.
  

Fundraising drive marks latest polio eradication effort

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

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

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

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.

Draft of federal pandemic flu vaccine allocation plan released

Late last week, a document titled "Draft Guidance on Allocating and Targeting Pandemic Influenza Vaccine" was posted at PandemicFlu.gov. The plan, far more elaborate than any released to date, offers a detailed scheme of how limited vaccine doses should be allocated. (Interesting, nowhere in the 31-page document do the words "ration" or "rationing" appear.)

The specifics of the draft plan are difficult to summarize, but, generally, the plan identifies four categories of individuals, based on their occupations: 1) homeland and national security, 2) health care and community support services, 3) critical infrastructure, and 4) general population (everyone else). Within each category, there are multiple levels of priority (e.g., in 'critical infrastructure,' EMS workers receive priority over postal personnel). Finally, five 'tiers' of priority are identified according to severity of a potential pandemic.

Among the "general population" -- a group that includes nearly 280 million Americans -- pregnant women and children receive first priority, and the estimated 121 million healthy 19-64 year olds are last in line.

The release of this draft plan is timed with a request for comments. The request notes a specific interest in comments on "the extent to which the guidance is likely to lead to fair and ethical allocation and targeting of pandemic influenza vaccine across the population."

Here's coverage of the report's release from CIDRAP News, USA Today, and the Associated Press. Several of the stories correctly note the major logistical questions that remain as to how to implement a national vaccination strategy and ensure the process is conducted fairly.

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In related news, a WHO announcement last week projects a major increase in pandemic influenza vaccine supply. Here's a story on the announcement from Reuters and a particularly interesting story from the Canadian Press about potential drawbacks of such a surge in worldwide capacity.

Hitting the bull's eye for pandemic flu vaccine development

In this month's Lancet Infectious Diseases, a commentary by Sambhara, Bridges, and Poland offers an update on progress toward pandemic influenza vaccine development in the wake of the licensure of Sanofi Pasteur's pre-pandemic vaccine this spring.

The title of the short commentary sums up the authors' assessment: "H5N1 vaccine hits the target, but not the bull's eye." (free abstract). Complementing this metaphor is a graphic which illustrates the specific areas that need to be addressed to produce the "ideal pre-pandemic vaccine." Such a vaccine would be safe (of course), require a single dose with a small amount of antigen, provide long-lasting immunity, and be stable (i.e., capable of remaining potent even if stored for some time).

Given that the Sanofi Pasteur vaccine licensed in April falls far short of these goals, the authors advocate directing research efforts toward these aims in particular.

Speaking of pandemic influenza research, WHO posted on their website late last week a series of tables summarizing the impressive number of vaccine candidates for which clinical trials are underway. As the tables show, while H5N1 is properly commanding the overwhelming majority of attention of late, it is not the only influenza strain with pandemic potential that has attracted the interest of researchers.

With respect to pandemic planning in the U.S., another update was issued late last week by HHS secretary Michael Leavitt. Here's the full report as well as coverage from CIDRAP News. In a brief section on vaccines, the report states that the current pre-pandemic stockpile includes sufficient doses for 6 million people, with a 5-year goal of building enough capacity to produce vaccine for all Americans within six months of 'the' pandemic virus' first appearance.

GSK gives to WHO bird flu vaccine stockpile; cell-based seasonal flu vaccine approved in EU

Some influenza-related goings-on this week:

• Yesterday, GSK announced via press release its plan to donate to WHO 50 million doses of its pre-pandemic avian influenza vaccine. WHO responded with a press release of its own, noting some of the many, many still-to-be-answered questions regarding if, when, and how such a stockpile would be used. Here's the AP story on the announcement. While a nice corporate gesture, vaccine doses for 25 million people -- delivered over 3 years, no less -- seems like a drop-in-the-bucket in the event that anything even resembling the estimates of policy-makers comes to fruition. Also, we've discussed the many uncertainties regarding the value of pre-pandemic vaccines previously, but suffice it to say, the benefit of such vaccines is uncertain today, much less three years from now in light of the viral mutation that would precede a pandemic in humans. All that said, this news can be seen as a good start, one could say, but by no means a major step in preparedness.

• In seasonal flu news, the EU approved a cell-based vaccine by Novartis, likely to be the first marketed flu vaccine produced without the use of eggs. Here's the AP story, courtesy of the Washington Post, and the Novartis press release. The story notes that the vaccine will not be available throughout the EU until the 2008-09 flu season and that U.S. approval will be sought next year. In light of the well-rehearsed problems with egg-based flu vaccine production (most notably the 2004 shortage), this may prove to be a major moment in flu vaccine development.

WHO and state reports on ethics and pandemic flu planning

The folks at CIDRAP News report in this story that the WHO plans to issue a report in January on ethical issues associated with pandemic flu planning. Among the topics to be explored: access, the ethics of quarantine and related actions, health-care worker responsibilities, and international collaboration. All are important topics will ethical aspects that merit attention alongside the relevant science and public health considerations.

Speaking of WHO, yesterday's New York Times included an editorial, "Preparations for a Flu Pandemic," that questions the current pace of pandemic planning, particularly vaccine development and supply issues that are certain to complicate mass vaccination efforts.

Thinking about limited vaccine supply and the ethics of allocating those doses, a number of scholars and organizations have offered ethical perspectives on how best to do so. (The most notable: the Emanuel/Wertheimer essay in Science back in May, which we wrote about here.) This week, the Minnesota Center for Health Care Ethics released a very interesting report titled "Allocating Pandemic Influenza Vaccines in Minnesota." Growing out of a multi-disciplinary working group of state-wide stakeholders, the report offers a different model for prioritizing specifics groups than the current HHS plan. While the report is written for Minnesotans in particular, the discussion of ethical concerns and priorities is relevant everywhere. The report is well worth reading for anyone interested in the ethical priorities that will influence these difficult decisions.

The Minneapolis Star-Tribune wrote a story ("A Tough Call Awaits if a Killer Flu Breaks Out," October 23) on the report that includes a few quotes from us, among others.

Bird flu mutation impacting vaccine planning

As always, CIDRAP News is on top of all things avian flu-related. This story from Friday covers the WHO announcement of the most recent data on avian flu mutation and the specific strains that are recommended targets of future vaccine development. Here's the WHO document.

The CIDRAP story offers a nice analysis of the relevant policy and planning ramifications of the science-laden WHO document. Here's an excerpt, featuring comments from Dr. Michael Osterholm:

"Many experts who follow the ongoing analysis of the H5N1 virus sequences are alarmed at how fast the virus is evolving into an increasingly more complex network of clades and subclades, Osterholm said. The evolving nature of the virus complicates vaccine planning. He said if an avian influenza pandemic emerges, a strain-specific vaccine will need to be developed to treat the disease."

That the virus will continue to evolve has long been known, as has the fact that vaccines developed in advance of a pandemic are likely to be increasingly less effective as time passes. For those hoping that a vaccine currently in development would be the vaccine, this news confirms that such hopes are unrealistic. The vaccines in the pipeline today are based on clade 1 strains of the virus, while most recent human cases have been caused by clade 2 strains, according to the WHO report. While it remains unclear how effective "older" vaccines will be against the eventual pandemic strain (if one develops at all), nearly all continue to agree that the most effective vaccine can only be developed after a human pandemic begins.

The WHO document cited here provides our most specific knowledge to date of the virus' pattern of mutation, information needed to develop effective vaccines. It also makes mention of the potential to develop region-specific vaccines if the virus' mutation proceeds in such a way in the months and years ahead.

Update: China to release avian flu samples to WHO

Last week, we wrote about the unwillingness of Chinese health authorities to share their collected isolates of avian flu with the world community, potentially impeding work toward an effective vaccine in advance of a pandemic ("Chinese secrecy stalls bird flu vaccine").

Today, news that China has appeared to reverse course, agreeing to release approximately 20 live animal samples of the virus in the coming weeks. Voice of America, among others, has the story...

"World Health Organization officials say they expect China to deliver around 20 bird flu virus samples from animals soon. Their announcement Wednesday follows a long standoff in which Beijing had refused to turn over the samples that health officials say could help in the global battle against the disease.

WHO officials have been negotiating for months, trying to get the Chinese Ministry of Agriculture to hand over the live animal samples. Health officials say the dispute has resulted from Chinese academics not wanting to give up their research, partly out of concern that they and their country might not get credit for it."

It's anyone's guess at the moment how beneficial these samples (and hopefully those China agrees to share in the future) will be for efforts to track the virus' mutation, but there's no doubt that this is a positive development.

Encouraging news about worldwide measles vaccination

From ABCNews.com:

"A global immunization drive has cut measles deaths by nearly half during the last six years, the World Health Organization and United Nations Children's Fund said Friday.

Deaths from measles dropped from 871,000 in 1999 to an estimated 454,000 in 2004, according to the UNICEF and WHO report, marking a 48 percent decrease in fatalities suffered from one of the most contagious diseases known."

A tremendous achievement, and a testament to the effectiveness of sound public health interventions and robust vaccination campaigns. Still, the potential exists for even greater victories over measles in the years ahead. Putting these global numbers in context, according to this CDC data, the total number of measles cases (not deaths) in the U.S. in 2005 was a mere 63, thanks to 40 years of vaccination.