Monday, October 27, 2008

Trail of Odd Anthrax Cells Led FBI to Army Scientist: Washington Post

Today's front page Washington Post article by Joby Warrick on the Ivins case appears to present the FBI's side of the story. I will post excerpts from the article and comment (in italics) on its inconsistencies.
Abshire focused her lens on a moldlike clump. Anthrax bacteria were growing here, but some of the cells were odd: strange shapes, strange textures, strange colors. These were mutants, or "morphs," genetic deviants scattered among the ordinary anthrax cells like chocolate chips in a cookie batter...

Ivins, the FBI discovered, had spent more than a year perfecting what agents called his "ultimate creation" -- his signature blend of highly lethal anthrax spores -- and guarded it so carefully that his lab assistants did not know where he kept it...

"It was his ultimate creation," said Jason D. Bannan, an FBI microbiologist assigned to the Amerithrax case. "This was the culmination of a lot of hard work."

Exceptionally pure concentrations of anthrax spores were Ivins's trademark and placed him in an exclusive class...

It was intended for garden-variety animal experiments, but the collection of anthrax spores known as RMR-1029 was anything but ordinary. Ivins, its creator, had devoted a year to perfecting it, mixing 34 different batches of bacteria-laden broth and distilling them into a single liter of pure lethality...

Ames-strain bacteria was essentially identical wherever it was found, the advisers said...

The art of "spore preparation" is a tedious job often relegated to novices and technicians.
Inconsistency: Ivins made exceptionally pure spore preparations, but his "master" prep was full of mutants.

Exaggerations: FBI agents call his flask of Ames anthrax his "ultimate creation," but all it contained was the combined product of 34 separate small production runs at Fort Detrick and Dugway, only some of which Ivins had made. FBI advisers said that Ames was pretty much the same wherever it was found. So the claim of Ivins' flask having special virulence, compared to other Ames batches, is doubtful.

Ivins spent a year perfecting it? How do you "perfect" 34 separate batches when you didn't make all of them? There has been no prior evidence that the flask contained "special" Ames spores, nor does this article report any such evidence.

Furthermore, as is noted in the article, growing anthrax is usually the work of technicians, and does not require advanced skills. Growing spores is not a method of perfecting them. The recipes are widely available in the open literature. Ivins could have spent a year growing the anthrax in the flask, but he would have been accomplishing plenty of other tasks simultaneously.

Unknowingly, Abshire had discovered a key to solving the anthrax case. But it would take nearly six years to develop the technology to allow FBI investigators to use it...
Some of the technology needed to solve the case had not been invented. And the FBI's top science advisers were warning that the effort would fail...
...the bureau had to invent an entirely new investigative field, microbial forensics...
When the FBI later asked Ivins for anthrax spores from his lab, he deliberately bypassed his prize spore collection, agents said, and gave them a false sample...
Inconsistencies: Ivins gave the FBI a sample from the RMR-1029 flask initially, one tube of which was sent to Paul Keim. When FBI complained about the way the sample was prepared, he gave them a pure specimen, rather than the mixture he initially provided, which contained the 4 mutations FBI later focused on. But why would Ivins have done this to fool the FBI, when he gave them RMR-1029 first, and provided both samples before the methodology to track the mutations had even been invented?

And the WP article acknowledges this:

But Ivins could not have known that RMR-1029 contained genetic mutants, in relatively high numbers. A batch of spores like RMR-1029 might be expected to contain, at most, one mutated variant. But Ivins's flask, because of its unusual pedigree, contained five.
Furthermore, FBI obtained voluntary specimens from most scientists; would a guilty party volunteer the specimen used to prepare the letter spores, as Ivins did initially?

For one thing, no one besides Ivins seems to have known where they were kept. The plain, triangle-shaped storage flask was one of many kept in plastic tubs inside a refrigerated storage room in Ivins's restricted lab. It had only a handwritten label -- RMR-1029, shorthand for "reference material received, No. 1029." When spores were needed for experiments, Ivins alone would retrieve them. "His own people who worked with him on a daily basis didn't know which flask it was," Langham said.

Exaggeration: He kept the vial, properly labeled, in the refrigerated storage room where it belonged. Maybe he didn't share its exact location with others because it contained a huge number of highly lethal spores, equal to millions of lethal doses? Isn't that exactly what he should have been doing from a biosafety perspective?

The list of suspects narrowed, officials said, until only one was left: Ivins. Ivins alone created and controlled the distinctive collection of anthrax cells that provided the seeds for the attacks. And he was the undisputed master at manipulating the bacteria into dense concentrations of deadly spores. While graduate school microbiologists could have performed most of the tasks, Ivins had the experience and the "good set of hands" required to achieve a spore preparation of such quality, a government scientist said.
Exaggeration: you need a master to concentrate spores. No: you need a centrifuge, or a filter, and a college student can do it. Good hands not required.

Exaggeration: "Ivins alone controlled the distinctive concentration of anthrax cells..." But everyone he gave a sample to from that flask also controlled the same distinctive concentration of anthrax cells. That is why FBI received multiple matching samples from other scientists.
"When you go to the true experts and ask them how many people can develop [anthrax spores] into something with this purity and this concentration, they shake their heads," said Montooth, the lead Amerithrax investigator. "Some will say there are perhaps six. Others will say maybe a dozen."

Misleading: the spore purity was a result of the spores having been washed thoroughly after they were grown. When experts say only 6-12 people could have produced similar spore preparations, they are referring to the special features of the dry, weaponized spores, not to the fact the spore preparation was concentrated or lacking in debris. It remains uncertain whether Ivins could have produced such dry spores, and it is doubtful that the spores in the flask, in liquid medium, had the same concentration as the dry letter spores.

But drying the spores turned out to be no obstacle at all, FBI scientists said. It required only one more step, using a common laboratory machine known as a lyophilizer. Ivins had one in his lab.

"Because he grew spores on a daily basis, he was in a position to make [the powder], and no one would be the wiser," Montooth said.

Misleading: The lyophilizer reportedly available to Ivins would have required many runs to dry the volume of spores used in the letters, thus taking a longer time than was available between 9/11 and the letter attacks. It would also be more visible to colleagues, some of whom have said he could not have done it without being detected.

Thursday, October 23, 2008

ACIP opens door to anthrax shots for first responders

Robert Roos * News Editor

Oct 23, 2008 (CIDRAP News) – The federal Advisory Committee on Immunization Practices (ACIP) has opened the door to voluntary anthrax vaccination for first responders, revising an 8-year-old recommendation against that step.

The committee, meeting yesterday, said the risk of anthrax exposure for emergency responders is low but "may not be zero," and therefore first-responder agencies may want to offer the vaccine on a voluntary basis, according to information supplied by the Centers for Disease Control and Prevention (CDC) today.

The CDC routinely adopts the ACIP's recommendations.

Anthrax vaccination—which currently involves six doses over 18 months, followed by annual boosters—is required for US military personnel serving in the Middle East and other high-risk areas. Nearly 2 million service members have been vaccinated under the program, according to ACIP reports.

However, a number of military members have complained of negative side effects from the shot, and a lawsuit by several of them interrupted mandatory vaccinations for about 2 years starting in October 2004. Another lawsuit against the program is still in the courts.

Allowing the option
The new recommendation adopted by the ACIP does not actively encourage anthrax shots for first responders. It states:

"Emergency and other responders, including police departments, fire departments, hazardous material units, government responders, the National Guard and others, are not recommended for routine pre-event anthrax vaccination. However, the committee recognized that while the risk of exposure for first responders to anthrax is low it may not be zero. Therefore, first responder units may choose to offer their workers pre-event vaccination on a voluntary basis. The vaccination program should be carried out under the direction of a comprehensive occupational health and safety program."

In 2000 the ACIP recommended against "pre-event" anthrax shots for first responders, and that stance was reaffirmed when the committee revisited the issue after the anthrax attacks of late 2001, according to an online summary of the June 2008 ACIP meeting. The reasons for reconsidering that recommendation included a growing supply of the vaccine and new data suggesting a change in the vaccine's safety profile, plus interest from some first-responder groups, according to comments made at that meeting.

Interest from emergency responders
A change in the recommendation for first responders was proposed at the June meeting by an ACIP subcommittee called the Anthrax Vaccine Workgroup. The panel's work was described by Jennifer G. Wright, DVM, MPH.

"Post-event vaccination in combination with antibiotics is an effective intervention following exposure to B[acillus] anthracis spores, but the workgroup felt that pre-event vaccination could offer additional protection beyond that afforded by antibiotics and post[exposure] vaccination by providing early priming of the immune system," the meeting summary states. "Some respondent organizations have stated that their members would be more willing to respond to a bioterrorism event if they were vaccinated prior to the occurrence of the event."

Dr. Richard Besser, director of the CDC's Coordinating Office for Terrorism Preparedness and Emergency Response, commented at the June meeting that a number of emergency response agencies had indicated interest in preemptive anthrax immunization for their workers, but the existing negative recommendation was seen as an impediment.

Also at that meeting, the CDC's Nancy Messonier said that the workgroup's intent in proposing a change was "to open the door, knowing that the vaccine is commercially available and that first responder groups are at liberty to call the manufacture to obtain the vaccine themselves," the meeting summary states.

The FDA-licensed vaccine, called anthrax vaccine adsorbed (AVA) (Biothrax), is made by Emergent BioSolutions Inc. Current annual production capacity is 8 million to 9 million doses, up from about 2 million in 2002, the June meeting report says. A new manufacturing facility that is being tested will eventually boost production to as many as 30 million to 35 million doses, it says.

"The workgroup felt that at the current time, vaccine supply was sufficient to support vaccination for a large group of individuals," the report states. It says the nation may have as many as 3 million first responders, depending on how the term is defined.

The work group concluded that the risk of anthrax exposure for first responders through a bioterrorism event is "undefinable," the summary states. However, the group concluded that the available data suggest that the vaccine is safe and effective.

Fewer adverse events
Through June 2008, 4,705 reports of adverse events associated with anthrax vaccination of military personnel were filed with the government's Vaccine Adverse Event Reporting System, the report says. That represents a rate of 61.1 reports per 100,000 doses, as compared with 117 reports per 100,000 doses of smallpox vaccine. About 10% of the reports described "serious" adverse events.

The report also said that in February the ACIP looked at data showing a decrease in local adverse events when the vaccine was given intramuscularly rather than by the standard subcutaneous route. That was an apparent reference to interim findings in a CDC study, which were reported in the Oct 1 Journal of the American Medical Association (JAMA; see link to news story below).

The JAMA report said people who were vaccinated intramuscularly had fewer injection-site reactions after four doses than those who received subcutaneous shots. It also said those who received three intramuscular shots in the first 6 months had about the same immune response as those who received the standard four subcutaneous shots, suggesting that dose reduction may be possible.

Discussion at the June ACIP meeting pointed out the challenges that would be posed by any effort to vaccinate large numbers of first responders, given the number and timing of doses involved. These include determining who would administer the vaccine, tracking recipients to keep them on schedule, providing liability coverage, monitoring adverse events, and caring for those who experience adverse events.

Postexposure protection
At yesterday's meeting, the CDC reported, the ACIP also made a recommendation on postexposure protection against anthrax: 60 days of antimicrobial treatment in combination with three doses of vaccine. Vaccine should be offered within 10 days of exposure.

"Anthrax vaccine is not licensed for children and has not been studied in children," the CDC update said. "However, postexposure anthrax vaccination in children potentially exposed to anthrax may be considered on an event-by-event basis in conjunction with 60 days of antibiotics."

The recommendation on postexposure prophylaxis includes pregnant women. "Pregnancy is neither a precaution nor a contraindication. Pregnant women should receive vaccine and antibiotics if they are exposed to inhalation anthrax," the CDC said.

See also:

Minutes of June 2008 ACIP meeting, including discussion of anthrax vaccine

Oct 6 CIDRAP News story "Trial offers hope for shortening anthrax-shot series"

Oct 2 CIDRAP News story "To blunt anthrax attack, mail carriers to get antibiotics"

Monday, October 20, 2008

CDC: 1-2% of anthrax vaccinees may die or become disabled...but consider expanding vaccinations

CDC published a report October 1 on its very expensive, 43 month-long trial of anthrax vaccine, but inexplicably discussed only the first 7 months and only 65% of the subjects. No explanation was given for why only partial data were provided in this important paper.

Bloomberg may provide the reason; the selected data discussed in the paper do not explore the 229 serious adverse events that occurred. But the selected data will be used to support new recommendations for expanding vaccinations to civilians that CDC's Advisory Committee will consider on October 22, 2008:
"After seven months, all the groups showed a comparable immune response, leading the researchers to say the three doses of the vaccine are "non-inferior.'' The CDC's Advisory Committee on Immunization Practice may make new recommendations on use of BioThrax that take the study's findings into account, said Curtis Allen, a CDC spokesman."
Yet other CDC officials told GAO in 2007 that 1-2% of vaccinees might have severe adverse events leading to disability or death.

Sunday, October 19, 2008

Congressman Holt Asks National Academy of Science to investigate holes in FBI's anthrax letters case

Representative Rush Holt, Chairman of the House Select Intelligence Oversight Panel of the House Committee on Appropriations, and a Representative whose constituents were directly affected by the anthrax attacks, has requested that the National Academy of Science also answer the following questions, should it elect to undertake an independent review of the FBI's scientific methods and conclusions in the Amerithrax case. His October 16, 2008 letter raises a number of important points, including the following:
"Are any of the FBI’s scientific findings inconsistent with the FBI’s conclusions?

Are there any scientific tests that the FBI has not done that might refute their conclusions?

Did the FBI follow all accepted evidence-gathering, chain of possession, and scientific analytical methods? Is it possible that any failure to do so could have affected the FBI’s conclusions?

Is it scientifically possible to exclude multiple actors or accessories?"

Saturday, October 18, 2008

Congressional Research Service Legal Report on PREPA

The Public Readiness and Emergency Preparedness Act, also known as Division C of P.L. 109-148 (2005) limits liability with respect to pandemic flu and other public health countermeasures. A Congressional Research Service Report for Congress by Henry Cohen, Legislative Attorney notes the following:

1. The ONLY circumstance in which a shielded person could be held liable for a death or serious injury requires that the action was done "intentionally to achieve wrongful purpose" and "knowingly" --disregarding a high probability of harm.
2. However, the HHS Secretary "shall promulgate regulations...that further restrict the scope of actions or omissions by a covered person that may qualify as 'willful misconduct.'" In other words, HHS is directed to raise the bar even higher on lawsuits than the bill has already done.
3. And no matter how bad the misconduct, federal employees have a special protection: under no circumstances will you be able to bring action "against a federal employee."

There is more: mandatory sanctions for lawyers who bring frivolous claims, for instance. It's antidemocratic provisions are astonishing.

Emergent Biosolutions Hits New 52-Week High On Positive Outlook

Mayur Pahilajani - iStockAnalyst Writer
New York, NY
Shares of Emergent Biosolutions Inc (NYSE: EBS) topped 52-week mark after the bell on Friday as investors gained confidence in the company after the Rockville-based biotech's profitable anthrax treatments won emergency protection.

On October 9, the firm announced that the vaccine Biothrax and its Anthrax Immune Globulin, both have been included as covered countermeasures to a public health emergency under the Public Readiness and Emergency Preparedness Act.

The U.S. Department of Health and Human Services (HHS) said in a declaration, which will remain in effect until December 31, 2015, that there is a credible risk that the threat of exposure to anthrax and the resulting disease constitutes a public health emergency.

"This PREP Act declaration is further evidence of the U.S. Government’s commitment to our efforts to develop a portfolio of medical countermeasures to address the threat to public health posed by the use of anthrax as a weapon of biological warfare," Daniel J. Abdun-Nabi, president of Emergent BioSolutions, said in a statement.

The measure came after the company gained a new multi-year contract with the U.S. HHS to supply additional doses of its anthrax vaccine. The contract is valued in the range of between $364 million to $404 million. Under the agreement, the company will supply HHS with the second order of 14.5 million doses of Biothrax vaccine. The first order of 19.75 million doses of the vaccine is currently being delivered, which will provide the company with $448 million...

Emergency declarations smooth way for vaccine makers

The Kansas City Star
Sure, the economy is causing a crisis, but what about anthrax? How about smallpox?

In a little noticed move, federal officials this month have declared a series of public health emergencies relating to potential weapons of biological terror.

On Oct. 1, Health and Human Services Secretary Mike Leavitt declared an anthrax public health emergency. On Oct. 10, he declared health emergencies for smallpox, radiation sickness from the detonation of a nuclear device and poisoning from botulinum toxins, the active ingredient of Botox.

There’s no clear evidence that terrorists have managed to weaponize anthrax or stolen large caches of Botox from cosmetic surgeons in Beverly Hills.

But by declaring these public health emergencies, HHS has granted manufacturers of anti-terrorism drugs and vaccines and others involved with the products protection from lawsuits if the drugs were to cause unfortunate side effects....

In a letter to Frist and Hastert, Sen. Ted Kennedy and 20 other members of Congress called the measure “a stealth provision to shield manufacturers from responsibility for making faulty drugs and vaccines.”

While terrorists would like to have biological weapons, they don’t have the sophisticated technology yet to make them, said R. Gregory Evans, director of the Institute for Biosecurity at St. Louis University... But someday, terrorists may develop such weapons, Evans said, which makes countermeasures like vaccines and drugs “absolutely necessary.”

“It probably does need some liability protection to get companies to develop vaccines that may never be used,” he said. “The profit margins associated with things like this are very little.” (See post above--Nass)

Health and Human Services is not invoking the law in response to any immediate threat, said William Raub, science adviser to Leavitt.

We don’t believe there’s anything imminent,” he said. “We’ve tried to be careful to not instill fear in people, (but) if we wait until the day of an event, valuable time is lost … and people could die...”

Friday, October 17, 2008

U.S. Limits Anthrax Vaccine Liability--Global Security Newswire

Elaine Grossman
Global Security Newswire Oct. 17, 2008
WASHINGTON - The U.S. Health and Human Services Department early this month moved to shield government, industry and business officials from lawsuits filed by those who have received the anthrax vaccine (see GSN < > , Sept. 5, 2007).

Health and Human Services Secretary Michael Leavitt established legal immunity for public and private officials who oversee the production or distribution of the anthrax vaccine by declaring a "public health emergency" due to the risk of a bioterrorism attack. He said the emergency began on Oct. 1 and would run through Dec. 31, 2015.

U.S. law provides protection from lawsuits to individuals responsible for selected countermeasures, including antibiotics, during a declared emergency. Under the Public Readiness and Emergency Preparedness Act, which President George W. Bush signed into law in December 2005, a health and human services secretary's emergency declaration can limit financial risk for government program planners and the manufacturers or distributors of pharmaceutical countermeasures. One exception to this immunity would be willful misconduct on the part of covered individuals. The ramifications, in this instance, could be to prevent individuals who have received one or more anthrax inoculations from taking grievances to court, based on claims that the vaccine caused severe adverse reactions or did not work. The anthrax vaccine has proven particularly controversial following reports of serious adverse events, including some deaths, among U.S. recipients (see GSN < > , Nov. 21, 2005).

In addition, there are some doubts about the vaccine's efficacy in protecting people from developing anthrax after breathing in spores during a biological attack. A 2003 lawsuit - based on lapses in the Food and Drug Administration's drug-approval process for the vaccine - temporarily shut down the Defense Department's compulsory anthrax shots program. Mandatory inoculations resumed in 2006 for personnel whose assignments are judged to put them at heightened risk of exposure to anthrax (see GSN < > , Dec. 16, 2005).

Leavitt's declaration < > was published in the Federal Register and quietly heralded at the end of a two-page news release < > devoted largely to another anthrax-related initiative (see GSN < > , Oct. 2).

Among the activities now afforded liability protection are those "related to developing, manufacturing, distributing, prescribing, dispensing, administering and using anthrax countermeasures in preparation for, and in response to, a potential anthrax attack," the HHS news release states. "This includes entities, such as large 'big-box' retail stores, retail pharmacies, and other private sector businesses, that help to deliver and distribute medicines." Health and Human Services argued the legal shield is essential to guarantee that countermeasures are there if U.S. citizens need them. "Providing liability protection to all involved in such efforts will help ensure their full participation and bolster response efforts," according to the news release. "Preparedness is a shared responsibility that must involve all sectors of society, including the private sector, community groups, families and individuals," Leavitt stated in the release. "We are using the authorities available to us to do all we can to support preparedness at all levels."

The move comes as a pivotal advisory group convened by the U.S. Centers for Disease Control and Prevention prepares to decide whether state and local health officials should consider giving anthrax vaccines to as many as 3 million civilian first responders nationwide (see GSN < > , Oct. 16).

Millions of U.S. military personnel have already received the vaccines since the Pentagon's shots program began in 1997, but the law prohibits service members or their families from holding the government liable for injury or death. Now that the population of vaccine recipients could expand to include millions of civilians - who normally do have a right to take medical injury claims to court - federal response planners and government contractors might be growing nervous about their potential legal vulnerability, according to vaccine critics. "There are people still getting ill from side effects and from the vaccine," John Michels, an attorney in litigation targeting the Pentagon's inoculation program, told Global Security Newswire this week. "When they expand this vaccine from the military population to a civilian population, they're going to have people who sue."

Emergent BioSolutions of Rockville, Md. - the nation's only manufacturer of an FDA-approved anthrax vaccine - recently announced < > that Health and Human Services had ordered 14.5 million doses of its BioThrax vaccine, worth as much as $404 million. The company is already under a $448 million contract to produce 18.8 million doses of the vaccine. The vaccine regimen calls for six shots over an 18 month period, plus annual boosters.

Michels said commercial interests appear to be playing a role in the legal immunity issue. He questioned whether there had been any bona fide escalation in the anthrax threat sufficient to justify the declaration of an emergency. "We have no indications [now] ... that we're much more likely to be attacked by anthrax," Michels said. "But [government officials] see the writing on the wall. They see ... an erosion of [lawsuit] immunity for vaccine manufacturers as a result of widespread civilian use."

Meryl Nass, a bioterrorism expert who has been highly critical of federal handling of anthrax vaccine issues, accused Leavitt of taking more interest in protecting bureaucrats from legal action than in protecting the public from health threats. "How do you decide there is an emergency when there is no evidence of one?" she asked in e-mailed comments last week. Noting the HHS secretary's designation of "governmental program planners" as among those afforded legal immunity by the declaration, Nass asserted that the agency "designates an emergency as a means to protect itself."

Leavitt's declaration, though, states that "targeted liability protections for anthrax countermeasures" are "based on a credible risk that the threat of exposure to [anthrax] and the resulting disease constitutes a public health emergency." The document does not offer additional details on the nature or level of threat. A request that Health and Human Services elaborate on the basis for the public health emergency declaration went unanswered at press time.

(But see previous post for admission by Homeland Security Department's Secretary Chertoff that there is absolutely no evidence of any emergency--Nass)

Chertoff tells Leavitt: No Emergency, No Problem

In a particularly Kafka-esque memorandum, Department of Homeland Security Secretary Chertoff wrote to Department of Health and Human Services Secretary Mike Leavitt on September 23, 2008 and said bluntly that he had no evidence for an anthrax emergency... however, there exists a non-negligible risk there may someday be one, so feel free to invoke the provisions of the PREPA Act.

Read it and weep.

Thursday, October 16, 2008

DHHS Likely Repeating its Mistakes with Anthrax Contracts

October 23, 2007:
GAO says HHS has announced that it will issue another rPA anthrax vaccine proposal but has not formally reviewed what went wrong with the VaxGen contract. "They may repeat their mistakes in the absence of a corrective plan," the report says.

CDC Panel May Advise Anthrax Shots for First Responders

Elaine Grossman
Global Security Newswire: Oct. 16, 2008

WASHINGTON - A U.S. government advisory panel next week could recommend that state and local public health officials consider administering anthrax vaccines to as many as 3 million first responders nationwide, Global Security Newswire has learned. The panel, convened by the Centers for Disease Control and Prevention, would leave it to regional and local authorities to determine whether the risks of biological terrorism - weighed against the potential benefits of a controversial inoculation - justify vaccinating emergency personnel.

In an anthrax attack, victims could inhale tiny airborne particles capable of infecting them with a highly fatal disease. The 2001 mailings that targeted congressional and media offices, launched just days after the Sept. 11 terrorist strikes, killed five people and sickened another 17 (see GSN < > , Oct. 1).

The CDC panel decision, slated for release at an Oct. 22 meeting in Atlanta, could reverse a nearly 8-year-old recommendation against pre-exposure vaccinations for first responders. By contrast, U.S. military personnel operating in assignments considered at risk of exposure to anthrax attack have been subject to mandatory inoculation for several years (see GSN < > , Sept. 5, 2007). While the compulsory program was suspended at one point under court order, the Defense Department has administered millions of shots since the late 1990s.

The CDC Advisory Committee on Immunization Practices said in December 2000 that it could not recommend anthrax shots for civilian first responders as a matter of national policy because "the risk of exposure cannot be calculated." Even if the threat were considered higher in one city or another, the panel concluded that precautionary vaccines were unnecessary. For emergency personnel who enter an attack site, "studies suggest an extremely low risk for exposure related to secondary aerosolization of previously settled [anthrax] spores," the group wrote at the time. If a first responder were exposed to anthrax, the "initiation of prophylaxis should be considered with antibiotics alone or in combination with vaccine," the panel concluded. Post-exposure treatment with these drugs is standard for unvaccinated patients.

In 2002, the panel updated other aspects of its anthrax vaccine recommendations but refrained from changing its guidance for first responders. However, at a meeting in Atlanta four months ago, a working group convened by the advisory committee said the full panel should alter its 2000 statement. "Post-event vaccination in combination with antibiotics is an effective intervention following exposure to [anthrax] spores, but the workgroup felt that pre-event vaccination could offer additional protection beyond that afforded by antibiotics and post-vaccination by providing early priming of the immune system," according to a CDC summary of the review group's presentation to the panel. In addition, some first-responder organizations "have stated that their members would be more willing to respond to a bioterrorism event if they were vaccinated prior to the occurrence of the event," working group member Jennifer Gordon Wright told the committee, according to the meeting summary. "The workgroup felt that implementing a recommendation for pre-event vaccination of first responders would be difficult, but it may have a positive impact on first-responder preparedness," she reportedly said.

If embraced by the expert panel next week, the new statement would read: "Groups for whom potential contact with aerosolized anthrax is a reasonable expectation based on occupation and duties (e.g. first responders expected to be called to the scene of a bioterrorism event) and for whom a calculable risk is not available may consider pre-event vaccination on the basis of an estimated risk benefit and in the context of an occupational health and safety program."

A Host of Challenges

Among the challenges facing any mass inoculation effort for first responders would be finding a method of tracking a complicated anthrax shot regimen for millions of personnel who might come and go from their jobs, according to the June meeting minutes. The schedule for the existing vaccine calls for six priming shots over an 18-month period, followed by annual boosters. Recent medical research suggests that fewer shots might be needed to establish immunity, but the official regimen has not yet changed (see GSN < > , Oct. 1).

Another hurdle could be organizing a vaccine campaign in the absence of any single organization representing the first-responder community nationwide, according to the June meeting summary. "There are multiple types of first responders and defining this group can be difficult," Wright told the CDC panel.

Litigation pending in federal court could pose another complication for state and local officials who might contemplate setting out a requirement that their first responders take the anthrax shots. Two attorneys who in 2004 won a 16-month injunction against the Pentagon's initial mandatory vaccine effort filed a second lawsuit in late 2006, challenging the science behind a 2005 Food and Drug Administration decision allowing the drug to be used for protection against an attack (see GSN < > , Oct. 28, 2004). They argue that the vaccine has been proven only in the prevention of anthrax contracted through the skin or digestive system, but has not been shown to work against a more serious form of inhaled anthrax posed by biological weapons.

The second case is now on appeal following a federal judge's move to dismiss it in late February (see GSN < > , March 3). If the lawsuit moves forward in the U.S. Court of Appeals, "it would affect the current thinking of CDC and FDA" regarding the advisability of giving the vaccine to millions of first responders, said Mark Zaid, plaintiffs' co-counsel in both legal actions. The CDC advisory panel's working group reported in June that "available vaccine efficacy data suggested that the vaccine is effective and provides protection against inhalation anthrax." However, Zaid said state and local authorities should think twice before requiring the shots for emergency personnel, in the absence of a substantial threat. "It would be virtually unprecedented in modern times to mandate any vaccination on civilian populations without the clear existence of a current outbreak of disease," he told GSN yesterday.

Critics of the vaccine have alleged that officials at the Centers for Disease Control and Prevention - an arm of the U.S. Health and Human Services Department - have underemphasized the risk of severe adverse reactions carried by the anthrax vaccine. For example, a new CDC study of the anthrax vaccine's safety and efficacy logged 229 "serious adverse events" - including seven deaths - in 186 out of 1,563 volunteer participants receiving inoculations since May 2002. Such instances might include events that are life-threatening, require hospitalization or surgical intervention or cause significant disability or birth defects. Results were published in the Oct. 1 issue of the Journal of the American Medical Association.

However, the researchers concluded that just nine of these serious events - none resulting in death - were "possibly related" to the vaccine. Analysis of the research data will remain "double-blind" through next year, meaning the medical investigators and patients do not know which participants received anthrax inoculations and which received a placebo, according to CDC officials.

Until the serious-event data can be correlated with an understanding of which patients actually received the anthrax vaccine, an empirical analysis of the drug's safety in this study cannot be done, according to Meryl Nass, a longtime critic of the U.S. government's handling of the vaccine. An internist who has consulted with the U.S. government on bioterrorism issues, Nass questioned how CDC researchers could have concluded that just nine of the 229 serious adverse events might have been connected to the vaccine. In e-mail comments sent to GSN last week, she accused the agency of "glossing over" the severe reactions potentially related to the vaccine and of offering few details about them.

The working group's June presentation to the CDC advisory group identified vaccine safety as a possible issue for consideration in treating first responders, but voiced confidence in the research findings. "While the workgroup [members] believe the vaccine is safe, rare adverse events do occur and a serious adverse event is not a small matter, regardless of whether it is vaccine-associated," Wright told the panel, according to the CDC minutes.

The government advisory panel "has been given a one-sided picture from the working group at the CDC," Nass said in an interview this week. She rued the fact that few, if any, of the advisory panel's current members took part in the committee's debate nearly eight years ago, which resulted in its initial guidance against mass inoculations for first responders. This year, Nass said, the committee has heard nearly no critical perspectives about the safety and efficacy of the anthrax vaccine, and the group might similarly be unaware of skepticism about biowarfare threats facing the United States. The CDC panel has scheduled just five minutes of public comment about the issue during its upcoming meeting, she said.

A review of the committee's membership shows that none of the advisory panel's 15 voting members sat on the group in 2000, so there is little track record on which to base projections about how it will decide the issue this time. Eight liaisons from medical associations and industry organizations, "ex officio" members and others associated with the Advisory Committee on Immunization Practices served in similar roles in 2000, but none of them have a vote. Of the voting advisory panel members, several voiced support at the June meeting for making what they termed a "reasonable" change in the group's guidance regarding anthrax shots for first responders.

One of them, Jonathan Temte - a faculty member at the University of Wisconsin's School of Medicine and Public Health in Madison - said "allowing smaller [state and local] groups to consider their own risks is a very worthwhile approach," according to the CDC summary. Others expressed a degree of concern. For example, Franklyn Judson - a professor at the University of Colorado Health Sciences Center in Denver - said he would support the new statement but thought "practically it would do little at the local level," the summary states. Another, Ciro Sumaya of Texas A&M Health Center in College Station, "was uncomfortable with the wording" in the statement about assessing a risk-benefit tradeoff, adding that "there should be some type of algorithm to make risk determinations that can be useful to the practitioner and at the local level," according to the CDC minutes.

Wednesday, October 15, 2008

Bogus Anthrax 'State of Emergency' Protects Drugmakers, Not Public

Excerpts from Wired Blog:

The emergency was declared earlier this month by the Department of Health and Human Services, and will last until 2015. Whether it will protect public health is debatable, but it will certainly protect makers of faulty anthrax vaccines.

The act is supposed to be invoked when the Secretary of Homeland Security has determined "that there is a domestic emergency, or a significant potential for a domestic emergency, involving a heightened risk of attack with a specified biological, chemical, radiological, or nuclear agent or agents."

But as Homeland Security chief Michael Chertoff explains, none of these conditions are met: there's neither emergency nor heightened risk of attack nor "credible information indicating an imminent threat of an attack." But that doesn't matter. "These findings are not necessary to make a determination," Chertoff wrote. It's enough that anthrax was declared a threat four years ago, and that "were the government to determine in the future that there is a heightened risk of an anthrax attack ... that determination would almost certainly result in a domestic emergency."

In other words, there could be an emergency someday — so we might as well declare an emergency now.

Friday, October 10, 2008

Anthrax Letters and Pandemic Flu Fears Led to Legislation that Removed Citizen Protections for Vaccine Injuries; Anthrax Emergency Just Declared

The Public Readiness and Emergency Preparedness Act (PREPA), passed by the United States Congress and signed into law in December, 2005, is a controversial tort liability shield intended to protect vaccine manufacturers from financial risk in the event of a declared public health emergency. The Act does not specify any criteria for determining the existence of an emergency. PREPA removes the right to a jury trial for persons injured by a covered vaccine, unless a plaintiff can provide clear evidence of willful misconduct that resulted in death or serious physical injury. A notice was issued regarding Potential Eligibility for Compensation in December 2007, but it applies only to avian flu vaccine, and has not been funded.

CDC has asked its Advisory Committee on Immunization Practices to vote on recommending anthrax vaccine for civilian first responders (up to three million people) on October 22, 2008. The vaccine has only been used by the Defense Department in the past, under a mandatory and controversial program. DHHS announced another purchase of 14 million doses of anthrax vaccine on October 1, 2008, in addition to approximately 25 million doses already stockpiled.

DHHS issued a Declaration under the Public Readiness and Emergency Preparedness Act on October 1, 2008, declaring a public health emergency for anthrax. No discussion of why there is an emergency was provided. Not only did the declaration shield anthrax vaccine manufacturers and doctors who use the vaccine from liability for injuries that might arise: the declaration explicitly shielded "government program planners" who might recommend anthrax vaccine or other anthrax countermeasures.

Sunday, October 5, 2008

Emergent Biosolutions wins $364M anthrax vaccine award

This week DHHS contracted to buy 14.5 million more doses of EBS' anthrax vaccine. It has already purchased about 25 million doses for a civilian stockpile. This supply may be where the vaccine for first responders will come from. GAO reported in 2007 on the large losses DHHS will incur when the anthrax vaccine outdates; vaccinating first responders may be a way of rotating vaccine stocks.

NAS Study May Fail to Settle Anthrax Case: Science Magazine

The October 3 article by Yudhijit Bhattacharjee (below) discusses the FBI's request to NAS. How can the National Academy of Sciences answer whether the scientific work would meet evidentiary standards in a court of law? They are scientists, not lawyers.

The Federal Bureau of Investigation (FBI) has provided the U.S. National Academy of Sciences (NAS) with a list of 15 questions that it wants the academy to consider in its review of the scientific evidence in the FBI's case against Bruce Ivins, the Army microbiologist implicated in the anthrax letter attacks of 2001. Besides asking whether the genomic analysis carried out to trace the source of the anthrax was valid, the questions address aspects such as the source of silicon found in the spores and whether the attacker needed specialized equipment to grind the spores into an easily dispersible powder.

But even before the academy frames the scope of the study and seeks approval from its governing board, members of Congress and bioterrorism experts are voicing concerns that a purely scientific review won't counter skepticism that Ivins, working solo, was the perpetrator of the attacks. One expert calls the FBI's request "a nice little jujitsu move" to deflect attention from nonscientific questions about the investigation, such as how the FBI ruled out all the other individuals who had access to RMR-1029, the flask of anthrax under Ivins's control. Last week, those concerns prompted Representative Rush Holt (D-NJ) to introduce legislation proposing a commission--similar to the one that investigated the 11 September 2001 terrorist strikes--that would review all the evidence in the case.

Since Ivins committed suicide on 29 July, FBI officials have unsealed court documents that detail part of the scientific evidence linking the anthrax in the letters to the flask under Ivins's control at the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Maryland. By requesting the NAS study, the FBI is essentially subjecting that evidence to peer review in lieu of a jury trial. The last question on the FBI's 15 September list is whether "testimony regarding the methods used to link the mailed anthrax to RMR 1029" would meet evidentiary standards in a court of law.

Gregory Koblentz, a biodefense researcher at George Mason University in Fairfax, Virginia, says even for a scientific review, the questions posed by the FBI don't go far enough. He and Alan Pearson of the Center for Arms Control and Non-Proliferation in Washington, D.C., want the academy to ask more probing questions about the science as well as undertake a broader investigation; they are submitting their suggestions to NAS. For example, says Pearson, referring to a question on the FBI's list, it isn't pertinent to ask whether "Bacillus anthracis samples dried with a rudimentary methodology can pose an inhalation hazard resulting in pulmonary anthrax. Of course they can. The question is whether [this method] can produce anthrax like that found in the letter."

"Our aim here is to lay out the facts gathered in this investigation and be as transparent as we can," says FBI spokesperson Paul Bresson. "That is all we can do and all we can control. As we have stated previously, we would have preferred to have brought this case to trial."

JAMA: CDC Spins the results of its multicenter trial of EBS's licensed anthrax vaccine

1. Omitting one dose, and injecting the vaccine deeper into muscle was widely reported to reduce adverse effects. But only brief local reactions at the skin are reduced, as one might expect with a deeper shot. The occurrence of the more consequential systemic adverse events was "not significantly influence[d]" by route of administration.

2. Women continued to have signficantly higher local and systemic event rates (approximately double the systemic adverse event rate of men) as has been reported in 4 previous studies since 2001.

3. Immunogenicity was assessed by using a measure relatively unique to anthrax vaccine: the geometric mean concentration and geometric mean titre of anti-PA antibody, as well as a fourfold rise in titre. In several animal models, antibody titres have not corresponded with survival rates following anthrax exposure. There is still no direct measure of efficacy in humans for this vaccine, in any published literature or manufacturer submission, although required by FDA regulations. (The FDA's Animal Rule, which includes ways to use substitute animal data for this requirement, has not been used to license this vaccine.)

4. There were 229 serious adverse events reports (including 7 deaths) filed with VAERS during the study, and a number of people were withdrawn from the study at the direction of the principal investigator due to adverse events. Yet the Data Safety Monitoring Board rated only seven subjects' adverse events as possibly related to the vaccine. The problem with this is that there is still no standard to tell us the kinds of reaction caused by anthrax vaccine; the package insert fails to provide this information, and one goal of this study originally was to learn about the reactions by comparing the vaccinated and placebo groups. That has not been done.

5. Despite the fact that this report provides no meaningful data to suggest EBS' anthrax vaccine is either safe or effective, the study is being used by CDC to ask its Advisory Committee on Immunization Practices to make a new recommendation for anthrax vaccine use in civilian first responders at its next meeting on October 22, 2008.