Blundering Bureaucrats Forgot Cancel Clause in H1N1 Vaccine Contract

Conflicts of Interest, General, Top Stories, Undue Influence

Blundering Bureaucrats Forgot Cancel Clause in H1N1 Vaccine Contract

No Comments 25 February 2010

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Victoria Fletcher
Express
02/24/10

BLUNDERING bureaucrats have spent £200million earmarked for hospital buildings on doses of the swine flu jab that will never be used.

Up to 132 million doses of the vaccine were ordered at the height of the panic over the H1N1 virus in 2009. But earlier this month it emerged that only 13 million doses had been delivered and more than four million were used on patients – three per cent of the total.

Now it is feared the millions of doses still on order cannot be stopped because officials forgot to add a cancel clause to the contract.

Yesterday the Department of Health admitted it had raided the coffers for hospital buildings and equipment – called the capital budget – “to meet existing commitments on pandemic flu”. Officials insisted that no projects had been axed due to the diverted cash.

But last night Shadow Health Secretary Andrew Lansley said it was outrageous that such a simple mistake would cost the NHS and the taxpayer so much money. He said: “Because there was no break clause in the GlaxoSmithKline contract, hundreds of millions will be spent on a vaccine for which the government has no use.”

“Today it has been revealed that the Government will take £200million out of the capital budget to pay for this. Who in the Government is going to take responsibility for this gross mistake in procurement? Which NHS Capital project was cut to pay for this?”

Ministers have refused to say how much money it spent on the swine flu contract with pharmaceutical giants GlaxoSmithKline and Baxter. But other nations have spent up to £9 per dose. Just months after the order for 132 million vaccines was signed providing enough for two jabs per person, it emerged that only one dose was needed to provide protection and that 66 million doses would have been ample.

The swine flu pandemic began to slow in autumn last year, despite Government warnings just months before that up to 65,000 could die in a “worst case scenario”. In fact, only 309 people have died of swine flu and most had underlying health conditions. Only 53 were killed by swine flu alone.

Although 14 million people were advised they should get vaccinated, only 4.5 million have taken up the offer. A bid to vaccinate all under-fives has also failed, with only 500,000 out of three million children having the jab.

And earlier this month, the flu threat faded to such low levels that the Health Department decided to close the National Pandemic Flu Service hotline and website. Most flu experts believe that a second wave of the virus in the spring is also unlikely although a revival next winter could occur.

Last night, a Health Department spokesman said the vaccines had been an “insurance policy”. “We can categorically confirm that no capital projects were cut as a result of the transfer,” he said.

“Ordering a vaccine and antivirals, and communicating how people can protect themselves from the pandemic, has been a worthwhile insurance policy that has undoubtedly saved lives. Every life saved from swine flu is worthwhile.”

In recent weeks, Germany has successfully negotiated a cut in its order for swine flu jabs by 30 per cent. Other countries are still negotiating.

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General, H1N1

Swine Flu Virus Created from Pig Vaccine?

1 Comment 17 September 2009

ISIS Report 16/09/09

The swine flu virus had three parents from two continents and appeared suddenly without warning, evading all routine flu surveillance and quarantine; sequence data suggest it may have been created from a faulty vaccine given to pigs in North America Prof. Adrian Gibbs and Dr. Jean Downie

This report has been submitted to the US FDA and CDC, and to Sir Liam Donaldson, UK’s Chief Medical Officer

MATERIAL ON THIS SITE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPLICIT PERMISSION. FOR PERMISSION, AND REPRODUCTION REQUIREMENTS, PLEASE CONTACT ISIS. WHERE PERMISSION IS GRANTED ALL LINKS MUST REMAIN UNCHANGED


Background

Several papers reporting phylogenetic analyses of the gene sequences of the new pandemic swine-origin H1N1 virus (S-OIV) have been published.  All show that S-OIV inherited its genes from parents that came from two well-known groups of swine flus.  Flu viruses have 8 different genes and in mixed infections sometimes shuffle those genes to form ‘reassortants’ with new combinations of the 8 genes chosen from those of the parents.  Several reports have shown that six of the genes of S-OIV came from a ‘triple-reassortant’ influenza virus (or viruses).  These viruses have been common in North American pigs for more than a decade, and have never been found in Europe.  The other two genes (NA and MP) came from Eurasian ‘avian-like’ viruses common in Europe for longer, but never found in North America.  Both groups of viruses have however been found recently in pigs in SE Asia.

The analyses reveal an unusual feature of the S-OIV genes, which is that none of the genes have been found recently in swine influenzas collected during routine flu surveillance.  The NA gene had not been sampled (identified in samples) for 17 years before it reappeared in S-OIV, and the others, including the MP gene, for around 11 years.  Thus the NA and MP genes were most likely acquired by S-OIV from Eurasian ‘avian-like’ viruses on separate occasions, and therefore S-OIV probably had at least three parents.

We have done further specific analyses to find out which isolates contain the genes that are closest to those of S-OIV.  We find that all are viruses of pigs.  The NA gene of S-OIV is closest to that of European ‘avian-like’ H1N1 influenza viruses sampled in 1991/1993, its MP gene closest to that of H3N2 Asian ‘avian-like’ viruses sampled in 1999, and its other six genes are closest to those of North American H1N2 ‘triple-reassortant’ viruses sampled in 1999/2000.  Note that the dates those isolates were collected agree with the calculated ‘time-line’ leading to S-OIV; NA 17 years ago, all the others 11 years.

In summary, S-OIV is a reassortant with at least three parents.  The parents were sampled over a decade ago, all found in pigs, and in three very distant parts of the world; North America, Europe and SE Asia!!!

The Questions

Where were S-OIV’s genes between the time that they were last sampled and 2008 when they all reappeared in S-OIV?  In which virus or viruses, which host, and when and how did they get together?  It is important for us to try to answer these questions as it might help us avoid similar pandemics in future.

The Theories

There are two theories regarding the origin of S-OIV, as described below.

The “unsampled pig theory”, was published by Gavin Smith and his colleagues in Nature [1]. They suggest that “the progenitor of the S-OIV epidemic originated in pigs”.  The “long unsampled history observed for every segment” of the S-OIV genome “suggests that the reassortment of Eurasian and North American swine lineages may not have occurred recently, and it is possible that this single reassortant lineage has been cryptically circulating rather than two distinct lineages of swine flu”, and that “Movement of live pigs between Eurasia and North America seems to have facilitated the mixing of diverse swine influenzas, leading to the multiple reassortment events associated with the genesis of the S-OIV strain.”  Note that Smith and his colleagues had not realized that their results showed that S-OIV had at least three, not two, parents.

Their theory has three parts. First, S-OIV’s parents reassorted to produce S-OIV at least a decade ago; second, the reassortant has been circulating in untested pigs since then, and third, it entered North America in the live pig trade from Eurasia.

The sequence databases show that during the past decade only the swine influenzas of Europe, North America and SE Asia were collected (and gene sequenced), so Smith and colleagues are correct in concluding that S-OIV, or its parents, could have been circulating undetected in, for example, South America or Africa or much of Asia.  However the parent(s) of S-OIV would require at least two trans-continental trips to get together in one place, and hence this theory requires at least two quarantine failures, probably three.  Is this likely? Given that quarantine has kept the widespread Eurasian avian-like swine viruses out of North America, and the ‘triple reassortant’ swine viruses of North America out of Europe.  Furthermore S-OIV is very infectious for both human beings and pigs, a characteristic that is probably an ‘emergent property’ of the reassortant, not of its parents, therefore it is more likely that the reassortment event producing S-OIV occurred immediately before it first appeared in humans in late 2008, than over a decade ago.  If S-OIV had originated earlier then most likely it would have spread to the human and/or pig populations earlier, and would probably have been found.

The “vaccine theory” was contrasted with the “unsampled pig theory” in a paper we submitted for publication in an academic journal.  We note that influenza viruses survive well in virus laboratories, that laboratories are not subject to routine surveillance, and that there are probably many laboratories in the world where a range of swine influenzas from different sources and continents are kept.  These viruses are used for research, diagnostic tests and for making vaccines.  Thus if laboratory activity was involved in the genesis of S-OIV, this would explain most simply why S-OIV’s genes had escaped surveillance for over a decade, and how viruses last sampled in North America, Europe and Asia could have got together.  Note too that there have been several reports, especially by Deborah Mackenzie in the ‘New Scientist’, about swine influenzas in agribusiness piggeries, and the uncontrolled production of veterinary vaccines, mostly “multivalent” (i.e. containing several different viruses).

So how could a laboratory mistake produce S-OIV?  The simplest scenario is that a multivalent vaccine was not fully sterilized.  Multivalent ‘killed’ vaccines are mixtures of virus particles that have been grown in hen’s eggs and then chemically sterilized.  Such vaccines are widely used in North American piggeries to control influenzas.  Thus S-OIV might have been produced if insufficient sterilant, usually formaldehyde or propiolactone, had been added to the particle mixture.  The live mixture would then infect pigs ‘vaccinated’ with it, and the growing viruses could then reassort to produce S-OIV.

It is significant that one of the North American H1N2 ‘triple reassortants’ closest to S-OIV is probably used in commercial multivalent pig vaccines in North America [2].  This may be the reason why, as the S-OIV pandemic started, there has been no report of an outbreak of S-OIV in a pig farm in the USA, whereas it has been reported from unvaccinated pig herds in other parts of the world; two each in Canada and Australia, and one in Argentina.  It is also relevant that the three likely parents of S-OIV are those one would choose if one were designing a multivalent swine influenza vaccine for international use.

There are historical precedents for laboratories being involved in virus outbreaks, not just foot-and-mouth disease and polio, but also influenza.  For example there was the H1N1 influenza lineage that circulated in the human population for four decades after the 1918 Spanish influenza epidemic but disappeared during the 1957 Asian influenza pandemic and reappeared in 1977.  The H1N1 that reappeared was found to be genetically very close to an H1N1 isolate collected in 1950, indicating that it had probably been held in a laboratory freezer between 1950 and 1977.  There is also the recent incident of a commercial human test vaccine being found to contain live H5N1 virus.

Action plan

So what can be done to distinguish between these two theories, and any others that are proposed?  The phylogenetic patterns in the present gene sequence data do not distinguish between them – more data are needed.

First, samples of all isolates of influenza used in swine vaccines in North America in 2008 must be collected, and their gene sequences determined.  This would immediately check the vaccine theory.  Second, the refrigerators of vets throughout the world, especially those of South and Central America, Asia and Africa, should be checked for samples of swine influenzas collected over the past decade, and the gene sequences of the isolates viruses determined.  Third, the quarantine authorities of North America should discuss, if they have not already done so, whether it is likely that pigs infected with S-OIV or its parents could evade quarantine measures when coming from other parts of the world.

It is important for the relevant authorities to obtain this evidence while the ‘scent’ is still warm – the search for the source of S-OIV must not be relegated to the ‘too hard’ basket, some possibilities can still be checked.  Influenza is a significant and very costly cause of mortality and morbidity in the human population.  If we wish to avoid new outbreaks rather than just minimizing the damage they cause, we must better understand what conditions produce them.

Jean Downie and Adrian Gibbs are viologists, they study the evolution of viruses using their gene sequences

References

1.Smith GJD, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M et al. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009, 459, 1123-6.

2.H1N1 Influenza Veterinary Talking Points – 5/5/09, http://www.aasp.org/public/H1N1InfluenzaVeterinaryTalkingPoints-05-05-09.doc

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Autism, General

CONFIDENTIAL – Thimerosal VSD Study Phase I

1 Comment 16 September 2009

H1N1 Experimental Swine Flu Vaccine will have 25 mcg of Thimerosal… (x4 for this flu season = 100 mcg of mercury with the flu shots alone)

– They Know.


CONFIDENTIAL – Thimerosal VSD Study Phase I

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General

Dr. Sherri Tenpenny on Coast to Coast AM TONIGHT!

No Comments 12 August 2009

Dr. Sherri Tenpenny
on Coast to Coast AM
TONIGHT
1-2aEST
10-11pPST

Pandemic Preparedness continues. Vaccine trials are underway and mass vaccination is slated to begin in October, 2009. Countries around the world are gearing up. For example:

> Britain is preparing to vaccinate all school age children

> Greece has ordered 61 million doses of vaccine to vaccinate the entire population, “no exceptions.”

> I have been told that Israel has ordered enough vaccine for the entire country, going against 72% of local physicians who are concerned about the vaccine safety and the mildness of the infection.

This week, the government will discuss the following plans:

Mass Fatality Management Planning
Direct and Activate fatality management operations
Conduct morgue operations
Manage ante-mortem data
Conduct final disposition
Psychological Issues
Unwillingness to follow government orders
Breakdown of public services, utilities and food supply chains

First Responders: Fire Department
Effectively undertake mass vaccinations
Enforce quarantines
Control traffic, evacuation & mass transportation

Law Enforcement Agencies
Control & diffuse social unrest & public disorder
Plan for 30-40 percent drop in labor force
Apprehension, examination and release of travelers

Tonight, Dr. Sherri Tenpenny will be a guest with George Noory on Coast-to-Coast AM radio to discuss Pandemic Preparations and What You Should Do. Tune in from 10-11pPST (1-2aEST) for a full hour of lively discussion.

Check Coast to Coast AM for local listings and times.

 

Go to www.MedicalVoices.org and sign up for twice weekly FREE webinars with Dr Tenpenny and Dr Eisenstein. 

Go to www.PandemicFluOnline.com for daily updates on pandemic planning and what you can do to help others prepare for mass vaccination.

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General, H1N1, News

School-based vaccine clinics planned

No Comments 28 May 2009

School-based vaccine clinics planned

http://www.nujournal.com/page/content.detail/id/507177.html?nav=5009

POSTED: May 27, 2009
By Fritz Busch Journal Staff Writer

NEW ULM – Brown County Public Health Director Karen Moritz gave several doses of good news to Brown County commissioners Tuesday.

Proposed federal funding has been earmarked for more vaccine for children, according to Moritz.

“We are working with the Springfield Medical Center and partnering with American Lung Association to plan school-based, seasonal influenza immunization clinics this fall,” she wrote in her public health update.

Moritz said her department continues to be on alert and hopeful that the H1N1 virus does not become more severe.

The median age of people with confirmed H1N1 cases is about 16 years old. Very few people over age 50 have confirmed cases, according to Moritz.
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Study: Parents who refuse vaccines put children at risk

General, Herd Immunity, News

Study: Parents who refuse vaccines put children at risk

No Comments 28 May 2009

Study: Parents who refuse vaccines put children at risk

http://www.denverpost.com/ci_12448293

The Colorado research found that children who aren’t immunized against whooping cough are 23 times more likely to get it.
By Jennifer Brown
The Denver Post

Posted:05/26/2009 01:00:00 AM MDT

Children whose parents refuse to have them immunized against it are 23 times more likely to get whooping cough, according to a new study that is perhaps the most definitive yet linking vaccine refusal to disease.

The Colorado study, which spanned 12 years and included more than 700 children, is expected to become a weapon in the medical community’s fight against a growing number of parents refusing vaccines for their children.

Immunization programs have been so successful that diseases including polio and measles virtually have been eliminated, shifting concern instead to the safety of vaccines, said Jason Glanz, study author and an epidemiologist with Kaiser Permanente’s Institute for Health Research.

Parents refusing vaccines cite safety concerns as well as ineffectiveness.

“The perception the vaccine doesn’t work isn’t true,” Glanz said. “We showed it clearly does work.”

*** Author Insert

This graph shows the decline in five infectious diseases from 1900 up until 1965, also indicating the years when various vaccines were introduced into public use. Clearly vaccines were introduced well after the Whooping Cough was in decline

This graph shows the decline in five infectious diseases from 1900 up until 1965, also indicating the years when various vaccines were introduced into public use. Clearly vaccines were introduced well after the Whooping Cough was in decline


Continue Reading

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General, News

Managing and Reducing Uncertainty in an Emerging Influenza Pandemic

No Comments 28 May 2009

Managing and Reducing Uncertainty in an Emerging Influenza Pandemic

http://content.nejm.org/cgi/content/full/NEJMp0904380

Published at www.nejm.org May 27, 2009 (10.1056/NEJMp0904380)
Marc Lipsitch, D.Phil., Steven Riley, D.Phil., Simon Cauchemez, Ph.D., Azra C. Ghani, Ph.D., and Neil M. Ferguson, D.Phil.

The early phases of an epidemic present decision makers with predictable challenges1 that have been evident as the current novel influenza A (H1N1) virus has spread. The scale of the problem is uncertain when a disease first appears but may increase rapidly. Early action is required, but decisions about action must be made when the threat is only modest — and consequently, they involve a trade-off between the comparatively small, but nearly certain, harm that an intervention may cause (such as rare adverse events from large-scale vaccination or economic and social costs from school dismissals) and the uncertain probability of much greater harm from a widespread outbreak. This combination of urgency, uncertainty, and the costs of interventions makes the effort to control infectious diseases especially difficult.

Plans for addressing influenza pandemics define a graded series of responses to emerging pandemic viruses, ranging from very limited interventions to stringent measures such as closing schools and other public venues, encouraging people to work at home, and using antiviral drugs for treatment and prophylaxis. Such grading of responses is based on the pandemic’s severity; for example, the United States’ Pandemic Severity Index is calibrated to the case fatality ratio (www.pandemicflu.gov/plan/community/community_mitigation.pdf). Mild responses are prescribed for a strain resembling seasonal influenza, which kills perhaps 0.1% of those infected, with higher rates in the very young and elderly, whereas stringent measures are envisioned for a very severe pandemic with a case fatality ratio of 2% or more and deaths concentrated in the middle age groups.

This approach makes sense in theory, but in practice, decisions have had to be made before definitive information was available on the severity, transmissibility, or natural history of the new H1N1 virus. The United States, for example, passed the 1000-case mark on May 4, and the second death was reported on May 5. Crudely speaking, the case fatality ratio thus appeared to be 0.2%, near the upper end of the range for seasonal influenza, and superficially, this statistically uncertain estimate seems remarkably accurate given the data available on May 27, by which point there were 11 deaths and 7927 confirmed cases (a case fatality ratio of 0.14%).

However, two principal sources of uncertainty critically affect severity estimates. The proportion of severe cases is overestimated in settings where many mild cases are not reported or tested, a situation that is becoming more common as public health officials become unable to test a large fraction of suspected cases. In contrast, severity estimates are biased downward when they are calculated as simple ratios of numbers of deaths to numbers of cases, because there is a delay between the onset of illness and death. During the 1918 influenza pandemic, the mean time from symptom onset to death was 8 to 9 days,2 whereas the number of cases was doubling about every 3 days. With a similar delay, today’s deaths would reflect the state of the epidemic three doublings ago, when there were about one eighth the number of cases there are now. If modern therapies have extended the time between onset and death, the censoring bias will be even more pronounced. Such uncertainty has made it impossible to assess severity confidently.

Moreover, several other factors suggest that it is premature to dismiss concerns about severity. First, this virus tends to infect relatively young, healthy people, and it caused a high hospitalization rate of 2% in the United States even before testing shifted to emphasize severe cases.3 Second, the much higher proportion of people likely to be infected in a pandemic (because of limited immunity to the new strain) will mean substantially higher levels of severe outcomes than usual. A virus that is fatal in “only” 0.15% of cases but infects twice the typical number of people would cause about three times as many deaths as typical influenza, or more than 100,000 deaths in the United States. Moreover, this “mild” illness will almost certainly take a more severe toll in less wealthy countries, as infectious diseases routinely do. The Northern Hemisphere may see a decline in transmission over the summer, but the 1918 pandemic demonstrated that sustained spring and summer transmission is possible for a novel influenza strain, and the Southern Hemisphere is entering its influenza season now. The Southern Hemisphere, at least, and possibly the entire world, is likely to see a substantial epidemic of this virus in the next few months, with attack rates exceeding those in a typical influenza season, before significant quantities of vaccine become available.

Paradoxically, uncertainty about this infection’s characteristics is likely to increase further as the Northern Hemisphere’s summer progresses. The low specificity of clinical signs and symptoms, combined with changes in reporting practices, will make it difficult to interpret apparent incidence trends at the national level. Without reliable incidence measures, it is impossible to track the epidemic’s growth rate, which makes estimates of transmissibility highly uncertain and subject to biases because of changes in the probability of detection. School absences, a crude measure of epidemic spread, will become less informative once most schools are closed for the summer. Without good incidence estimates, estimates of severity will continue to suffer from an uncertain denominator. The effectiveness of control measures will be difficult to assess without accurate measures of local incidence. When a vaccine becomes available, appropriate targeting of limited supplies will require knowledge of levels of preexisting immunity, age-specific severity estimates, and other quantities that depend on reliable measures of the incidence of mild and severe disease.

If we could be sure that the infection would remain mild in most cases, these uncertainties would be similar to those we tolerate in a normal influenza season, although the numbers affected would probably be larger. But historically, pandemic viruses have evolved between seasons,4,5 and the current strain may become more severe or transmissible in the coming months. Thus, decision makers in both hemispheres could again face uncertainty about the characteristics of a possibly evolving virus in the coming half-year.

There is a brief window of opportunity to take measures to reduce the uncertainty. Serologic studies in the tropics during the Northern Hemisphere summer and at higher latitudes in both hemispheres will permit estimation of the extent of spread of mild infection. If transmission wanes in the north, a late-summer serologic survey will provide baseline information about population immunity that will aid in both vaccine targeting and interpretation of patterns of illness in the fall.

Serologic surveys represent snapshots of the population rather than real-time measures of incidence. Additional surveillance is needed to quantify the incidence of mild and severe infection in nearly real time. Surveillance for nonspecific indicators, such as visits to health care providers for influenza-like illness or hospitalization for pneumonia, can provide an indication of the total disease burden but cannot determine causation. Such surveillance should be combined with routine testing of a systematic sample of patients to estimate the total burden of H1N1-attributable disease. In combination with serologic surveys, such surveillance would allow public health officials to estimate the proportions of infections leading to mild and severe illness and to determine how they vary with age and other risk factors. Detailed outbreak investigations in households and schools would elucidate transmission dynamics and inform recommendations on containment measures. Although cases detected by routine surveillance are subject to case-ascertainment bias, secondary cases in a household or a school outbreak constitute an unbiased sample that can be used to estimate illness severity. Household-transmission studies also provide information on age-specific susceptibility profiles while controlling for levels of exposure.

Augmenting traditional surveillance systems to measure the new virus’s spread should be a high priority. Since the measures outlined above are expensive and require substantial infrastructure, they are practical for only a limited number of sentinel sites. To extend the range of surveillance, nontraditional approaches may be important. Web-based incidence surveys may be practical if there are adequate incentives to respond and adequate privacy assurances. Daily school absences should be tracked according to grade and school and made available for real-time analysis. Use of mobile phones for repeated surveys of large population samples may be another method for real-time surveillance in areas where more traditional approaches are impossible or too expensive. Though such approaches cannot discern the cause of illness, they compensate with greater coverage and speed of data availability. The value of these approaches will be greatest if they are also conducted in areas where more traditional surveillance is also under way, so that their relationship to validated measures of virologically confirmed incidence can be calibrated.

International cooperation will be crucial, not only to enhance capacity for surveillance in the tropics and the Southern Hemisphere but also to monitor changes in antigenicity, severity, transmissibility, and antiviral resistance that may be reflected in a fall wave in the Northern Hemisphere. Many approaches suggested here to improve awareness of the epidemic during the Northern Hemisphere’s fall can be applied more immediately in the tropics and the Southern Hemisphere during the upcoming influenza seasons there.

Surveillance systems and our understanding of the dynamics of infectious-disease transmission have improved substantially since the 1968 influenza pandemic. These improvements can be used to support policymakers in managing the current pandemic. If new data-collection systems capable of reducing key uncertainties are to be implemented in time for the autumn, international and intersector cooperation leveraging the expertise of the university and private sectors must be combined with rapid enhancement of traditional, government-sponsored surveillance.

Public communication of risk and uncertainty will be critical. It has been suggested that the existing criteria for moving to World Health Organization pandemic phase 6 (sustained transmission in multiple geographic regions) should be modified to incorporate a judgment that the world’s population is at increased risk. We would argue against conflating assessments of transmissibility and severity in this subjective way, which risks adding to the confusion faced by decision makers and the public. Rather, the global extent of a pandemic should be described objectively and should be just one factor in decisions about how to respond.

As we adjust our mitigation policies, there will be a continuing need to make decisions without definitive estimates of severity. For example, the decision to move from production of vaccine for seasonal influenza to that for pandemic influenza will need to be made in the next month or two. Similarly, the United States will need to decide soon whether to use adjuvanted vaccines to protect more people with a given amount of antigen, although such vaccines are not currently licensed in the United States. As always, however, the main losers from delays in such decisions are likely to be developing countries, which will have less access to vaccine while probably suffering the greatest clinical impact from this new pandemic virus.

Dr. Lipsitch reports receiving consulting fees from the Avian/Pandemic Flu Registry (Outcome Sciences). Dr. Cauchemez reports receiving consulting fees from Sanofi Pasteur. No other potential conflict of interest relevant to this article was reported.

Source Information

Dr. Lipsitch is a professor of epidemiology at the Harvard School of Public Health, Boston. Dr. Riley is an assistant professor in the Department of Community Medicine, Li Ka Shing Faculty of Medicine, and the School of Public Health, University of Hong Kong — both in Hong Kong. Dr. Cauchemez is a research fellow, and Drs. Ghani and Ferguson professors, at the Medical Research Council Centre for Outbreak Analysis and Modeling, Department of Infectious Disease Epidemiology, Imperial College London, London.

This article (10.1056/NEJMp0904380) was published on May 27, 2009, at NEJM.org.

References

Neustadt RE, Fineberg H. The epidemic that never was: policy-making and the swine flu affair. New York: Vintage Books, 1983.
Brundage JF, Shanks GD. Deaths from bacterial pneumonia during 1918-19 influenza pandemic. Emerg Infect Dis 2008;14:1193-1199. [CrossRef][ISI][Medline]
Update: novel influenza A (H1N1) virus infections — worldwide, May 6, 2009. MMWR Morb Mortal Wkly Rep 2009;58:453-458. [Medline]
Andreasen V, Viboud C, Simonsen L. Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. J Infect Dis 2008;197:270-278. [CrossRef][ISI][Medline]
Viboud C, Grais RF, Lafont BA, Miller MA, Simonsen L. Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic. J Infect Dis 2005;192:233-248. [CrossRef][ISI][Medline]

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General, News

Merck Settles Clean Water Act Violations at its Montgomery County, Pennsylvania Pharmaceutical Plant

No Comments 22 May 2009

Merck Settles Clean Water Act Violations at its Montgomery County, Pennsylvania Pharmaceutical Plant

http://www.justice.gov/opa/pr/2007/December/07_enrd_1000.html

FOR IMMEDIATE RELEASE
THURSDAY, DECEMBER 13, 2007
WWW.USDOJ.GOV

Merck Settles Clean Water Act Violations at its Montgomery County, Pennsylvania Pharmaceutical Plant

WASHINGTON—Merck, the global pharmaceutical research company, has agreed to resolve violations of federal and state water pollution control regulations arising from spills including a June 2006 spill at its pharmaceutical plant outside of Philadelphia, announced Pat Meehan, U.S. Attorney for the Eastern District of Pennsylvania, Ronald J. Tenpas, Acting Assistant Attorney General for the Justice Department’s Environment and Natural Resources Division, the Environmental Protection Agency, and the Pennsylvania Department of Environmental Protection.

In one of the most comprehensive remediation settlement agreements for the Eastern District of Pennsylvania, Merck will pay $10 million to put into place systems that will prevent future dangerous discharges at their facility. Merck will spend approximately $9 million for extensive environmental projects. A consent decree requires Merck to pay $1,575,000 in penalties and civil damages for past violations divided as follows: $750,000 to the United States; $750,000 to the Commonwealth of Pennsylvania; $75,000 to the Pennsylvania Fish and Boat Commission.

“Perhaps more than anything else, this settlement says to every company that discharges dangerous chemicals as part of its operations that it is accountable to the environment and the community,” said U.S. Attorney Meehan. “Because when you get right down to it, no one should have to wonder, when they walk into the kitchen for a glass of water, if what they are about to drink is going to make them or their children sick.”

“Merck’s actions led to an extensive fish-kill and caused the Philadelphia Water Department to temporarily shut down its drinking water operations,” said Acting Assistant Attorney General Tenpas. “This settlement ensures that Merck will take steps to prevent future illegal discharges including installing an early warning system to protect drinking water.”

The Merck facility, a pharmaceutical plant located in West Point, Pa., houses pharmaceutical and vaccine research as well as the manufacturing of pharmaceutical products and vaccines. The facility consists of approximately 400 acres, 110 buildings employing approximately 8,500 employees. Merck discharges pollutants from this facility to the Upper Gwynedd Township Publicly Owned Treatment Works (UGT POTW). The treated effluent is discharged into the Wissahickon Creek, a tributary of the Schuylkill River.

The federal court complaint, filed today, along with the settlement papers, alleges that Merck violated the Clean Water Act with several discrete discharges that caused numerous pass through and interference violations at the UGT POTW:

-On June 13, 2006, Merck discharged potassium thiocyanate (KSCN) that reacted with the chlorination at UGT POTW and after discharge caused extensive fish kills in the Wissahickon Creek on June 14th and 15th; also causing the Philadelphia Water Department to close its Schuylkill River drinking water intake on June 14th and 15th; and causing PA DEP to issue health advisories to ban all recreational uses on the Wissahickon Creek for the period June 14, 2006, through July 10, 2006.

-On Aug. 8 and 9, 2006 Merck discharged a large batch of spent substrate used for vaccine production which when treated at UGT POTW caused extensive foam discharge into the Wissahickon Creek.

-On Aug. 16, 2006, Merck discharged a large amount of cleaning agents that when treated at UGT POTW caused extensive foam discharge into the Wissahickon Creek.

The proposed consent decree includes interim measures undertaken already to: prevent discharges without pre-approval; create a tracking system for waste handling; create a task force to assess the system throughout the facility, and impose increased testing and assessment tools for waste stream. The decree contains Merck’s commitment to long term remedial measures including: a prevention program; an enhanced wastewater management program; and a chemical management accountability system for the facility. The estimated costs of these measures are in excess of $10 million.

“The resolution of this case and its special projects will bring both short and long-term environmental benefits to the community and the Wissahickon,” said Donald S. Welsh, EPA’s mid-Atlantic regional administrator. “When you consider that the source of 40 percent of Philadelphia’s drinking water is just downstream of this facility, these improvements and Merck’s environmental accountability has implications extending beyond the boundaries of its facility.”

The proposed consent decree also includes extensive environmental projects designed to improve the water quality and/or protect the Wissahickon as a source of drinking water. Merck has committed to: restoration of a segment of the Wissahickon Creek to improve the water quality of this key tributary of the Schuylkill River; creation of a wetlands on a 10 acre parcel of property adjacent to the creek; purchase and installation of an aquatic bio-monitoring system that monitors fish activity to give the Philadelphia Water Department an early warning system regarding materials in the Wissahickon Creek that may constitute a threat to the drinking water; the purchase and installation of an enhanced Automated Dissolved Oxygen Controls at the Upper Gwynedd Treatment Plant.

Each supplemental environment project, or SEP, is designed to improve water quality and/or protect the Wissahickon as a source of drinking water.

In addition the decree calls for Merck to contribute $4.5 million toward the purchase of a parcel of land adjacent to the creek that will have restricted use and open space easements in perpetuity.

The proposed consent decree is subject to a 30 day public comment period and final court approval. The case was handled by Assistant U.S. Attorney Margaret L. Hutchinson for the U.S. Attorney’s Office for the Eastern District of Pennsylvania. Martha Blasberg, Supervisory Counsel, PADEP, represented the Commonwealth of Pennsylvania. The matter was investigated by EPA Region III Water Protection Division, PADEP and the Pennsylvania Fish and Boat Commission.

###

07-1000

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General, News

Flu shots on tap for health care workers

No Comments 22 May 2009

Flu shots on tap for health care workers

http://www.crainsnewyork.com/article/20090522/FREE/905229982

May 22, 2009 11:16 AM

By Barbara Benson

Published: May 22, 2009 – 11:16 am

The state Department of Health is proposing mandatory flu vaccines for all health care workers in the state. The new rule would apply not just to staff, but to anyone who potentially comes into direct contact with patients. That includes contract workers, students and volunteers.

The proposal, which is still in draft form, would apply to everyone working in hospitals, diagnostic and treatment centers, certified home health agencies, long-term home health care programs, AIDS home care programs, licensed home care services agencies, and hospices. A separate rule is pending in the Legislature that applies to nursing home workers.

The state health department’s move is an acknowledgment that voluntary flu vaccination efforts don’t work. But it wasn’t clear if the regulation would be implemented before any vaccination for the H1N1 flu virus is manufactured.

Although the CDC has recommended flu shots for health workers since 1981, voluntary participation is extremely low among New York health workers, at a mere 40%.

But at least one study showed that while 23% of health care personnel had serologic evidence of a flu infection, most of those—59% in fact—could not recall having symptoms. Nonetheless, the potential for spreading infection among elderly and weak patients is high.

According to DOH data, 5,179 employees in hospitals and nursing homes were sickened by either suspected or confirmed flu infections between 2000 and 2007, while more than 19,000 hospital patients and nursing home residents fell into that category.

Under the proposed regulations, the only people who would be exempt from getting a flu vaccination by Nov. 30 of each year would be those who had a medical reason for avoiding the shot.

All health facilities would have to offer the free shots, and DOH didn’t specify who would pay for them. Most likely, the facilities would.

The facilities also would be responsible for documenting in personnel files all information relating to the vaccination, including the date, dose, manufacturer, lot number, place of vaccination, and any reactions to the shot. By May 1 each year, the health care industry would report to DOH the number of people vaccinated by profession.

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General, News

ATS 2009: Second Wave of H1N1 Flu Feared in the Fall

No Comments 21 May 2009

ATS 2009: Second Wave of H1N1 Flu Feared in the Fall

http://www.medscape.com/viewarticle/703113

by Kristina Rebelo

May 20, 2009 (San Diego, California) — In a special panel session here at ATS 2009: the American Thoracic Society International Conference, experts and public-health officials discussed the current situation and ways hospitals can prepare for a potential second wave of infections in the fall.

The novel influenza A (H1N1) virus “sneaked in the door while health authorities who should have known better were busy closing windows,” said Carol J. Cardona, DVM, PhD, ACPV, from the Department of Population Health and Reproduction, and professor in the School of Veterinary Medicine, University of California, Davis, to an overflow crowd of thoracic and critical-care physicians.

“This virus has followed the pattern of all historic pandemics, and we’ve missed some precursors out there and we’ve missed some signals,” Dr. Cardona said. She is a virologist and an expert in determining how disease-causing agents damage their hosts. Dr. Cardona’s segment of the presentation was entitled “Swine Flu: Molecular Clues to the Origin, Transmission, and Pathogenesis of the Virus.”

Failure to Detect Precursors

Dr. Cardona said she anticipates mutations in the virus. “Expect to see stepwise changes over time and incremental changes over time in influenza A viruses.” She pointed out that there is opportunity for reassortment between and among viruses that will result in the generation of new antigenically novel strains filtered through poultry and pigs to humans. “You have several segments from one, then another, and then a third, for a triple reassortment; this results in big leaps in the genome,” she said, referring to the origins of H1N1.

“We’re providing ample opportunity with animals being raised quickly in large groups, where you have many, many generations. It’s an efficient way to raise food and an effective way to spread viruses,” Dr. Cardona said. “It is the replicative properties of influenza virus hemagglutinin [HA] subtype diversity mutants with altered receptor-binding properties that underlie virulence and spread. The viruses come together and reassert into pathogens that can infect humans. The disease outcomes are influenced by host immunity; viruses with novel HAs can evade host immunity and cause these diseases.”

Dr. Cardona explained that there are no antibodies to H1N1 influenza, which is why it has spread so rapidly. “And that’s the unusual thing about this virus: we failed to detect precursors and we failed to find it in swine.” She said that the H1N1 influenza has the ability to spread quickly. “It could happen within a few days, the mutation in animals, and infect other species,” she said, pointing out the recent swine herd in Canada where, earlier this month, a traveler carried the new H1N1 virus from Mexico to Canada, infecting his family along with a herd of swine, according to Canadian health officials.

Also on the panel was Rear Admiral Kenneth G. Castro, MD, acting chief/science officer of the Centers for Disease Control and Prevention Emergency Operation Center, who told attendees that because this H1N1 influenza is spread from person to person, it’s beginning to prepare for a pandemic. “This is what we are preparing for and worrying about,” he said. The title of his presentation was “Human Cases in the United States of Swine Influenza.”

He predicted that we have not seen the last of this H1N1 influenza: “Clearly, this virus has readily spread across the [United States] at a time we’re no longer experiencing influenza. The criteria for this virus have nothing to do with the severity problem in pandemic planning. This is very likely to be circulating and you can expect to see it again when our virus season occurs.”

Dr. Castro pegged the number of confirmed or probable cases in the United States at 5469, with 6 deaths (as of May 20, 7 deaths; a 44 year-old man in St. Louis who had visited Mexico died) in 48 states and the District of Columbia. Only Wyoming and West Virginia have had no confirmed cases. The median age is 17 years (range, 1 month – 87 years); 63% of those afflicted had an underlying medical condition at the time of illness onset. The average stay in a hospital is 4 days, with a median stay of 5 days (range, 2 – 31 days); 24% were admitted to the hospital’s intensive care unit (ICU).

He described the clinical presenting characteristics as fever, cough, shortness of breath, and sore throat, with 52% of presentations having abnormal findings of bilateral infiltrates consistent with pneumonia; 31% also had asthma or diabetes. Of the population presenting to hospitals, 66% were treated with antivirals and 85% were treated with 1 to 7 antibiotics (overlapping), with a median of 3. “Everything has been thrown into the equation to try to treat these hospitalized patients,” Dr. Castro said.

He recommended that patients with any early signs of influenza stay home, and he pointed out that closing schools was no guarantee that students wouldn’t assemble at local malls.

Second Wave Likely

Also on the panel was Christian E. Sandrock, MD, MPH, deputy health officer of Yolo County in Sacramento, California, and assistant clinical professor, Division of Pulmonary and Critical Care Medicine, University of California, Davis, School of Medicine. He told the audience: “With regard to what may happen in the Southern Hemisphere in the next few months, I get to be intensely prophetic or the village fool.” His presentation was entitled “H1N1 2009: Should We Be Concerned About a Second ‘Wave’?”

He compared previous worldwide pandemic patterns that occurred in the twentieth century — the 1918, 1957, 1968/1969, and 1977 (in children) pandemics that represented 3 different antigenic subtypes of the influenza A virus (H1N1, H2N2, and H2N2) — to this current swine-origin influenza A (H1N1) virus first detected in April 2009.

“The 1 difference in pattern is that this current virus is widespread, around the world to multiple continents, and we’re heading toward a second wave. We’re moving in that direction,” he said, “and the second wave is very likely.”

Dr. Sandrock said there is no vaccine that will protect against the virus, but he said that if populations are old enough to have experienced the 1968 strain, for instance, they may have a host-adapted MHC I primed T-cell response with epitopes, [which] is appropriate for viral clearance [and] may confer some protection and result in a mild to moderate disease, where the host would just “feel crummy.” Dr. Sandrock added that patients who present with asthma and a fever should not be written off but should be screened for influenza.

When asked how quickly he thought the current virus would mutate, he called that the “million-dollar question.” Dr. Sandrock noted that “it takes a while for the virus to mutate and spread, but once it’s up and going, we’ll see a surge in the numbers and deaths.”

Lewis Rubinson, MD, PhD, assistant professor of medicine, pulmonary and critical care medicine, Harborview Medical Center in Seattle, Washington, gave a segment entitled, “Swine Flu: What if the Critical Care Need Increases?” He said that the goals of the ICU in this era of phase 5 are to keep the hospital staff safe. “One of the hardest things for providers is how to integrate into the hospital but not take it over; there’s nothing worse than having a leader working alone.”

(The World Health Organization [WHO] raised the worldwide pandemic alert level to phase 5 on April 29; phase 5 is a “strong signal that a pandemic is imminent”; however, there is a current debate at the WHO World Health Assembly in Geneva, Switzerland, as to whether the WHO should raise the alert level to phase 6, which would indicate that a pandemic is under way. US Secretary of Health and Human Services Kathleen Sebelius said in Geneva that the United States is already taking phase 6 measures.)

Risk Stratification and Prophylaxis

Dr. Rubinson warned that triaging could get very confusing if coordination and integration within the rest of the institution are not on board. “When you have groups operating independently, you can lose control of the system,” he said. “You don’t have convalescent homes evacuating patients to emergency rooms.” Dr. Rubinson said that hospitals needed to have standardized decision-making in place. “Maybe we should start thinking about risk stratification and prophylaxis at this point in time — the key interventions should take place in cases where patients might not survive if we do not provide them.”

He suggested that hospitals start looking around at items most frequently used in their ICUs and get stocked up now. “Even if you’re a behemoth, you will be competing with all the other behemoths for supplies, and if you run out of something like corticosteroids or ventilator circuits, you’re in trouble.” Dr. Rubinson noted that even if this virus “fizzles out,” stockpiled supplies will eventually be used.

He said it might get to the point that entire hospitals will be converted to ICU care, because institutions cannot care for ill patients in tents that are not equipped with liquid oxygen systems. He suggested that acute respiratory distress syndrome and asthma would be the predominant conditions of presenting patients. “Despite excellent care, people are still dying and until recently there were no good data to predict just how sick people would be; these are sick people who will require a full-court press of what we can provide.”

Rounding out the group was Guillermo Dominguez-Cherit, MD, who heads up the ICU in the Department of Critical Care Medicine, Instituto Nacional de Ciencias Medicas y Nutrición in Mexico City, Mexico, whose presentation was entitled “Caring for Critically Ill Patients in Mexico City Infected with Swine Flu.” He informed attendees that as of May 4, 2009, there were a total of 3646 cases, with 70 deaths as of May 18, 2009. He described life in Mexico since April 17, when the Minister of Health closed schools and took other extreme measures. He showed slides of empty streets and business centers. “You can imagine the impact on the economy,” he said.

Staffing in Mexico’s hospitals had been an issue, with some employees refusing to come to work, final-year nursing students were being used to staff ICUs, and they were recruiting physicians from other departments, such as anesthesia and surgery, to help care for the influenza patients, Dr. Dominguez-Cherit said.

He added that at least half of all hospitalized patients had 2 or more comorbidities, and 78% had bilateral infiltrates on presentation. Other symptoms were respiratory distress, fever (100%), diarrhea, conjunctivitis, vomiting, coryza, weakness, and myalgias. The time from the first symptom to admittance to a medical facility was 6 days, and once in the hospital, the time to ICU admittance was 1.6 days, with an average hospital stay of 9.5 days. The locations of deaths within medical facilities were the ICU and the emergency department.

Dr. Dominguez-Cherit suggested that a global plan be in place so that action could be quickly taken to combat the anticipated influx of disease.

ATS 2009: American Thoracic Society International Conference: Special Session. Presented May 19, 2009.

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