Tuesday, August 19, 2014

Over 1,100 "Incidents" (aka escapes) with dangerous "Select Agents" were reported in the US during 2008-2012/ USA Today

Just in case you thought that CDC and federal regulators had things under control regarding research on microorganisms that can be used in bioterrorism, think again.  There were an average of 4 reported escapes each week over the 5 years that ended with 2012.

From USA Today, "The only thing unusual about the CDC's recent anthrax and bird flu lab incidents, Ebright said, is that the public found out about them. 'The 2014 CDC anthrax event became known to the public only because the number of persons requiring medical evaluation was too high to conceal,'  he said."  Here is another excerpt; it is chilling:

More than 1,100 laboratory incidents involving bacteria, viruses and toxins that pose significant or bioterror risks to people and agriculture were reported to federal regulators during 2008 through 2012, government reports obtained by USA TODAY show.
More than half these incidents were serious enough that lab workers received medical evaluations or treatment, according to the reports. In five incidents, investigations confirmed that laboratory workers had been infected or sickened; all recovered.
In two other incidents, animals were inadvertently infected with contagious diseases that would have posed significant threats to livestock industries if they had spread. One case involved the infection of two animals with hog cholera, a dangerous virus eradicated from the USA in 1978. In another incident, a cow in a disease-free herd next to a research facility studying the bacteria that cause brucellosis, became infected due to practices that violated federal regulations, resulting in regulators suspending the research and ordering a $425,000 fine, records show.
But the names of the labs that had mishaps or made mistakes, as well as most information about all of the incidents, must be kept secret because of federal bioterrorism laws, according to the U.S. Department of Agriculture, which regulates the labs and co-authored the annual lab incident reports with the Centers for Disease Control and Prevention...

Sunday, August 17, 2014

Legal Ramifications of Declaring a Public Health Emergency

I noticed that 2 old posts of mine about the laws and regulations governing public health emergencies were getting a lot of attention this week.  I thought I would post them again, as they may soon be relevant here, and are already relevant to Africans faced with quarantines, cordon sanitaires and other legal and physical barriers to contain Ebola.

From the Times of India:
UNITED NATIONS: With more than one million people affected by the current Ebola outbreak in West Africa, the WHO has warned that there is "no early end in sight" to the severe health crisis and called for "extraordinary measures" to stop the transmission of the disease.
The next two posts are mine from January, 2013:

Wednesday, January 9, 2013

State of Emergency: 700 flu cases in Boston this season and 4 elderly deaths/ NY Daily News

Puh-Leeze.  A State of Emergency?  I'd laugh except declaring an emergency gives states new political powers.  Powers designed by CDC and Lawrence Gostin.  Begun by 1999, before the anthrax letters or comparable public health emergencies existed, CDC "called for strengthening the legal foundation for public health practice."

The Model Emergency Health Powers Act was only unveiled 4 weeks after the anthrax letters emergency, a time of confusion when legislators were inclined to approve legal fixes.  Yet good legal arguments can be made that the new powers are unnecessary, unethical and conflict with prior health law. On this issue the Heritage Foundationand I come together.
Under the original Model State Emergency Health Powers Act, upon the declaration of a "public health emergency," governors and public health officials would be empowered to do the following and more:
  • Force individuals suspected of harboring an "infectious disease" to undergo medical examinations.
  • Track and share an individual's personal health information, including genetic information. [The new electronic medical records do this already--Nass]
  • Force persons to be vaccinated, treated, or quarantined for infectious diseases.
  • Preempt existing state laws, rules and regulations, including those relating to privacy, medical licensure, and--this is key--property rights.
  • Control public and private property during a public health emergency, including pharmaceutical manufacturing plants, nursing homes, other health care facilities, and communications devices.
  • Mobilize all or any part of the "organized militia into service to the state to help enforce the state's orders."
  • Ration firearms, explosives, food, fuel and alcoholic beverages, among other commodities. 
"One of the most outspoken opponents of the MSEHPA, on which Article VI of the Turning Point Model is based, is George Annas, who eloquently outlines a few of the most popular objections to the act: (1) bioterrorism is inherently a federal issue, and only secondarily a state issue; (2) the premise that Americans must trade freedom for security in the event of a bioterrorist attack is wrongheaded, as is the presumption that the public and physicians would not cooperate except under threat of law; and (3) the arbitrary use of force by public officials with immunity from liability is incompatible with medical ethics, constitutional principles, and basic democratic values."   See his NEJM article here.

Last year (winter 2011-12) was the lightest flu season since records started being kept:  basically there was no flu epidemic.  The year before was also light.  That is how influenza works:  some years lighter, some heavier.  The heavier years give us more cross-immunity for future outbreaks.

Anyway, this year is [unsurprisingly] heavier.  One in 25 ER patients has flu.  As a former ER doc, that is something to yawn about.  But I'm not yawning about the emergency powers invoked--to do what, exactly?  From the Daily News:

The City of Boston declared a public health emergency Wednesday as the city and country deal with a historic outbreak of the flu.  The influenza-ravaged city has seen about 700 confirmed cases of the virus since Oct. 1, the unofficial start of the flu season, according to the office of Boston Mayor Thomas Menino, who declared the state of emergency Wednesday morning.

By comparison, Boston saw 70 confirmed cases during last year’s flu season.

The outbreak has so far killed four Boston residents, all elderly, since the season unofficially began.

“This is the worst flu season we’ve seen since 2009, and people should take the threat of flu seriously,” Menino said in a release...

Thursday, January 10, 2013

What Does State of Emergency mean?

What exactly is a "state of emergency"?

According to Association of State and Territorial Health Officials (ASTHO), state declarations "may also identify state rules and regulations that are waived or suspended during the emergency...  They can include:
  • Activation of statutory immunities and liability protections for those involved in response activities.
  • Suspension and waiver of rules and regulations (and statutes, if allowed).
  • Streamlining of state administrative procedures such as procurement requirements." 
Here is an 87 page guide to declared public health emergencies in NY State.  Each state is a little different regarding its legal framework for such emergencies, and municipalities are different as well.  But they are more similar than different.  Page 50 says the following: 
Executive Law §§ 29-a(1) [“Subject to the state constitution, the federal constitution and federal statutes and regulations . . . the governor may by executive order temporarily suspend specific provisions of any statute, local law, ordinance, or orders, rules or regulations, or parts thereof, of any agency during a state disaster  emergency.”]
ASTHO also tells us the following about the federal response:
Federal law imbues designated federal officials with broad powers that allow them to respond to and assist states and localities in responding to emergencies even without a federal emergency declaration ...
Federal emergency declarations activate legal and programmatic responses from federal agencies including: 
  • Activating federal assistance to states in the form of financial, personnel, services, logistical, and technical assistance.
  • Triggering emergency provisions in other laws including Social Security Act Section 1135 waivers and statutory immunities and liability protections, such as the Public Readiness and Emergency Preparedness Act (PREP Act) [which waives liability for manufacturers whose products are used under PREPA, even if they do not work and cause considerable injuries.  Swine flu vaccine was given under PREPA, so US children who developed narcolepsy could not sue the manufacturer.  Anthrax vaccine is given to civilians under PREPA as well.--Nass]
  • Easing regulatory requirements on individuals, organizations, and state and local governments.
Declared public health emergencies provide a potential back door to suspension of democracy.  By declaring frequent, bogus states of emergency for swine flu, flu and the next not-so-dread disease, Americans may be lulled into ignoring the suspensions of the rule of law that may accompany the declarations.  

It's the Patriot Act all over again.  The Patriot Act was enabled by the fog of war.  

Now it's the smog of pestilence that enables the killing of democratic traditions.  In the shadows, the republic is being killed by a thousand cuts.  This is how Hitler did it, too.

Sunday, August 10, 2014

Ebola therapeutics from China, Canada, Germany, US: promising but without human testing for Ebola, though the last article suggests already-licensed drugs may be useful

 2014 Jun 12;189C:254-261. doi: 10.1016/j.virusres.2014.06.001. 
A highly immunogenic fragment derived from Zaire Ebola virus glycoprotein elicits effective neutralizing antibody. 
Wang Y1Liu Z1Dai Q2.
In order to produce polyvalent vaccines based on single rVSV vector, we investigated the immunogenicity, antibody neutralizing activity, and antigenic determinant domain of Zaire Ebola's fragment MFL (aa 393-556) that contains furin site and internal fusion loop. Both the recombinant protein and the recombinant plasmid of fragment MFL elicited high levels of antibody, similar to those of Zaire Ebola GP (ZGP). The MFL fragment of ZGP also elicited high levels of neutralizing antibody and induced moderate cellular immune response in mice, as revealed by the proliferation and cytokine secretion of splenocytes. Through the analysis of the induction of neutralizing antibody by pVAX1-based recombinant plasmids that expressed truncated fragments of MFL, we found that the domain containing the internal fusion loop and the furin site was the major contributor of fragment MFL's immunogenicity. Furthermore, the rVSV-based bivalent vaccine expressing Sudan Ebola GP (SGP) and MFL fragment elicited efficient cross-immunity against ZGP and SGP with high levels of neutralizing antibody. Our results indicate that fragment MFL is an effective and novel antigen for the production of neutralizing antibody and polyvalent vaccines of Ebola virus.

 2014 Jun 17;111(24):8873-6. doi: 10.1073/pnas.1316902111. 
Vaccinating captive chimpanzees to savewild chimpanzees.

Infectious disease has only recently been recognized as a major threat to the survival of Endangered chimpanzees and Critically Endangered gorillas in the wild. One potentially powerful tool, vaccination, has not been deployed in fighting this disease threat, in good part because of fears about vaccine safety. Here we report on what is, to our knowledge, the first trial in which captive chimpanzees were used to test a vaccine intended for use on wild apes rather than humans. We tested a virus-like particle vaccine against Ebola virus, a leading source of death in wild gorillas and chimpanzees. The vaccine was safe and immunogenic. Captive trials of other vaccines and of methods for vaccine delivery hold great potential as weapons in the fight against wild ape extinction.

 2014 Jul;107:102-9. doi: 10.1016/j.antiviral.2014.04.014. Epub 2014 May 9. 
Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells.
Antigen presenting cells (APCs), including macrophages and dendritic cells, are early and sustained targets ofEbola virus (EBOV) infection in vivo. Because EBOV activates mitogen-activated protein kinase (MAPK) signaling upon infection of APCs, we evaluated the effect of pyridinyl imidazole inhibitors of p38 MAPK on EBOV infection of human APCs and EBOV mediated cytokine production from human DCs. The p38 MAPK inhibitors reduced viral replication in PMA-differentiated macrophage-like human THP-1 cells with an IC50 of 4.73μM (SB202190), 8.26μM (p38kinhIII) and 8.21μM (SB203580) and primary human monocyte-derived dendritic cells (MDDCs) with an IC50 of 2.67μM (SB202190). Furthermore, cytokine production from EBOV-treated MDDCs was inhibited in a dose-dependent manner. A control pyridinyl imidazole compound failed to inhibit either EBOV infection or cytokine induction. Using an established EBOV virus-like particle (VLP) entry assay, we demonstrate that inhibitor pretreatment blocked VLP entry suggesting that the inhibitors blocked infection and replication at least in part by blocking EBOV entry. Taken together, our results indicate that pyridinyl imidazole p38 MAPK inhibitors may serve as leads for the development of therapeutics to treat EBOV infection.

 2014 Aug;22(8):456-463. doi: 10.1016/j.tim.2014.04.002. Epub 2014 Apr 30. 
Post-exposure therapy of filovirus infections.
Filovirus infections cause fatal hemorrhagic fever characterized by the initial onset of general symptoms before rapid progression to severe disease; the most virulent species can cause death to susceptible hosts within 10 days after the appearance of symptoms. Before the advent of monoclonal antibody (mAb) therapy, infection of nonhuman primates (NHPs) with the most virulent filovirus species was fatal if interventions were not administered within minutes. A novel nucleoside analogue, BCX4430, has since been shown to also demonstrate protective efficacy with a delayed treatment start. This review summarizes and evaluates the potential of current experimental candidates for treating filovirus disease with regard to their feasibility and use in the clinic, and assesses the most promising strategies towards the future development of a pan-filovirus medical countermeasure.

 2014 Aug;69(8):2123-31. doi: 10.1093/jac/dku091. Epub 2014 Apr 7.

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties.


We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds.


We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant.


The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry.

Friday, August 8, 2014

International Travel: 679 people per day enter the US from Nigeria/ NY Times

According to the NYT, there are "243,000 international travelers to United States airports each day... including an average of 679 from Nigeria and 145 from the other three countries, (Liberia, Guinea and Sierra Leone) according to the C.D.C."

Medicins Sans Frontieres Ebola Updates: more detail than I have found anywhere else

This is the site where you will get up to date information on the Ebola outbreak from MSF, which is providing the most detailed information from Liberia, Sierra Leone and Guinea.

Ebola Opinion / Nass

Despite an estimated 69% death rate, Medicins Sans Frontiers (Doctors Without Borders or MSF) doctors and nurses have not come down with the disease.  MSF has 676 staffers working on the ground in Africa.  CDC has 31 to help with case-finding, but none treating victims.  WHO says it has 141 people in West Africa sent to help manage the epidemic.

An Aug 7 Congressional hearing was told that "the international community was comfortable in allowing [only] 2 relief agencies (private NGO charities, MSF and Samaritan's Purse) to provide all of the clinical care for Ebola victims in 3 countries" until 2 Americans became ill (at 1:11).  Truly, this is disgraceful.

Ebola is not the world's first or only high-mortality viral hemorrhagic fever.  We do know how to manage these infections safely.  But it requires intense attention to detail.  Staff must be very well trained, and very careful.  They will make mistakes if they are overworked. They needs lots of equipment too: materials to isolate patients, deal with body wastes safely, and huge numbers of gowns, gloves, goggles, boots, etc.

Ebola may possibly be "airborne"but that is not as ominous as it sounds.  C. diff (Clostridium difficile) is a bacterium that forms a spore. Explosive diarrhea sends C. diff airborne--but Americans are not dying of it in droves.  Pneumonia is caused by airborne viruses and bacteria, but most of those exposed do not get sick.  Some become immune. My guess is that this occurs very rarely with Ebola.

When a disease is new, or rare, we only hear about the worst cases--at first.  Later, when serologic sampling is performed, we learn that many more people were exposed, did not become ill or experienced mild disease, and recovered, often with long-lasting immunity. Then we learn that the mortality rate is actually much lower than at first thought.

The Washington Post reporting 4 cases in Lagos (population 20 million) today tells me that there are or soon will be hundreds or thousands of cases in Lagos.  Controlling the outbreak in one of the world's largest cities, made up of miles of slums and without a sewerage system is going to cost plenty:  not the 10 or 100 million dollars being collected for the entire outbreak.  Compared to the billions spent on the 2009 swine flu, which was milder than most seasonal flu, what on earth has led to the six month delay by the world's rich nations to seriously try and control this outbreak?  (This Ebola outbreak was first noted in West Africa between December 2013 and March 2014.
 The lack of interest shown in it till recently makes one wonder about population control.

The birth rate in Africa is over 5 births per female, more than twice that of the rest of the world. According to The Economist:

In 1970, there were 360m Africans and they amounted to a tenth of the world’s population. If fertility were to drop roughly in line with Asia’s 1970-2000 trajectory, there would be 2.1 billion Africans by 2050. If it continues on its current path, there will be 2.7 billion—a quarter of the global population then. Africa’s population will almost triple in 40 years.
According to UN predictions reported in the Washington Post in late 2013 (see below), Africa will have 4 billion people by 2100, approaching the predicted population of all Asia.

You cannot control urban Ebola without a sanitation system and access to clean water. These require huge investments and lots of time. Time may be running out to stop this outbreak without huge numbers of deaths in Africa, and tremendous dislocations globally.

UPDATE:  Just learned there are cases in Conakry, Monrovia and other large urban areas. MSF says the situation in Monrovia is catastrophic.

Monday, August 4, 2014

Of several potential Ebola vaccines, here is one

This 2008 article (available free in full text here) described a very promising Ebola vaccine from USAMRIID:

Sunday, August 3, 2014

Many unlicensed, experimental Ebola treatments and vaccines exist: Dr. Brantly can give informed consent to use them

Since Ebola first was identified in 1976, there have been at least a dozen outbreaks and at least 5 strains have been identified. Serologic tests for Ebola have been available since 1977.

The US did not ignore Ebola.  It posed a threat as a natural illness, and posed a different threat as a potential biological warfare agent.  The US government, and especially USAMRIID at Fort Detrick in Frederick, MD have worked on approaches to Ebola for decades.

Dr. Brantley, now in the US, will benefit from these potential treatments, and he will also provide serum samples to improve diagnostics and therapies for this specific strain of Ebola. Bringing an Ebola-infected doctor back to the US is really a win-win for him and for American understanding of Ebola.

I have been curious why we have not heard of these therapies being tried on an experimental basis in Africa, nor have we heard about Ebola vaccine trials there (yet).  CDC staff have advised on case identification and isolation, but have not been "on the ground" working in areas where there are Ebola cases to be treated.

It is rather a bizarre situation that private charities like MSF and Samaritan's Purse are doing the clinical heavy lifting, when this outbreak has a potential to kill millions and spread widely.  When will we see WHO, CDC and other national health entities on the ground?

Here are just a few press releases about promising experimental Ebola therapeutics developed at USAMRIID:

Experimental Ebola Treatment Protects Some Primates Even After Disease Symptoms Appear

Ebola Antibody Treatment, Produced in Plants, Protects Monkeys from Lethal Disease 

Novel “Antisense” Therapies Protect Primates from Lethal Ebola and Marburg Viruses

Post-Exposure Antibody Treatment Protects Primates from Ebola, Marburg Viruses

Gene-Specific Ebola Therapies Protect Nonhuman Primates from Lethal Disease


Friday, July 18, 2014

Inspector General Reports: Biosecurity at Multiple Agencies (including CDC and NIH) a Joke/ USAToday

From USAT:

... CDC has not responded to USA TODAY's requests, under the Freedom of Information Act, filed in June 2012, for records involving lab safety and security incidents at the lab complex.
The latest set of "restricted" inspector general audits covered six federal entities conducting research on potential bioterror germs. Additional audits looked at how the agents are shipped and compliance at labs run by a sampling of universities and state, local and private labs.
For security reasons, the IG's office removed the names of the government agencies, universities and private firms that were running the labs. The specific germs or toxins were also withheld.
Among the reports' findings:
• An August 2009 report cites an undisclosed federal lab for not always restricting access to bioterror agents to approved individuals; failing to maintain complete records of who had accessed the specimens and not ensuring that individuals working with the specimens received proper training. In some cases, the agency had failed to cancel the electronic "swipe cards" and biometric access rights of people no longer authorized to be in the areas. "The Laboratory's access records showed that the three individuals entered select agent areas a total of 35 times after their access rights were terminated," the report notes.
• A June 2006 summary report examining labs at 15 universities found weaknesses at 11 of them. Three had incomplete inventory records. One university told auditors it "could not verify inventory records because it lacked qualified personnel to safely perform this function." Six universities were cited for issues that could have allowed unapproved individuals to access areas where specimens were stored, including one university where unapproved individuals could have generated keys for themselves and others.
A January 2008 summary report about issues at state, local, private and commercial labs, which was sent to Julie Gerberding, the CDC's director at the time, found problems at all of them that "could have compromised the ability to safeguard select agents from accidental or intentional loss." The issues included not adequately restricting access to approved individuals, insufficient security plans and lack of documented training. Although the eight entities had agreed with auditors' recommendations for corrections, the IG noted that six months had passed and CDC lab inspectors still hadn't documented corrections and submitted reports to auditors.
An April 2009 audit sent to the CDC's acting director at the time, Richard Besser, found problems in the transfer of specimens between undisclosed labs and failures by labs to ensure that only approved individuals received the packages. "Allowing unapproved individuals to handle select agents increased the risk that the agents could be lost or stolen, thereby potentially posing a severe threat to public health and safety," the auditors wrote. Yet CDC's lab inspectors were not adequately monitoring or enforcing requirements that labs protect against loss or theft during such transfers. Of 24 entities where auditors found unauthorized individuals accepting delivery of specimen packages, CDC inspectors had cited only four of them. CDC spokesman Tom Skinner said this week the agency has strengthened its inspection process since the report was written.
• A December 2009 audit involved a federal agency that described itself in an attached response letter as "the Nation's premier biomedical research institution." The National Institutes of Health has used that phrase in online publications to describe itself. Violations cited in the report included failure to maintain accurate and current inventory records. "The laboratory did not conduct a physical count until apprised of our audit in October 2008, at which time the laboratory determined that it had seven vials of select agents that were not recorded in the inventory records," auditors wrote. The types of germs in the vials, which the report said dated from the 1960s, were redacted from the report. The agency in its response said auditors had overstated the potential consequences of their findings. Auditors wrote that they disagreed. The NIH press office, in a statement, said it was not able to confirm that the report is about its agency.
All of the reports about federal entities involve agencies that are part of HHS, according to the letterhead of agency response letters that had the specific agency name removed. HHS officials did not respond to USA TODAY's interview request about the IG reports, and referred all questions to the CDC. In addition to the CDC, the two other federal agencies involved in the forgotten smallpox vials — the FDA and NIH — are also part of HHS...

What happened to the last safety czar you appointed? Asked who this was, the CDC Director didn't know/ Reuters

I am posting the entire Reuters story below. Is it funny, pathetic, or both?
CDC Director Tom Frieden promised Congress to appoint a senior official to oversee lab security in a 2012 letter responding to a Congressional inquiry. Asked about this person at the House Energy and Commerce Oversight and Investigations Hearing on Wednesday (at 1 hr 25 minutes), Frieden could not recall who had been appointed.  The next day, CDC spokesman Skinner said the official was appointed in March 2013, and that the official was Joseph Henderson.
One problem:  Henderson had been sitting next to Frieden at the witness table the day before.  It seems he didn't know he was the appointee, or he would have presumably informed Frieden and the committee. Will Frieden get another chance to spout happy talk to Congress? Watch his performance at the hearing, where he probably pissed off every member of the subcommittee with his canned non-answers.  (He sounded like a slightly impatient teacher explaining the same thing over and over to slow children, never ever expanding beyond his brief, initial comments. OTOH, there may have been good reasons why Frieden desperately avoided veering from his script.)

Here is the Reuters story
(Reuters) - U.S. lawmakers investigating repeated safety lapses at government laboratories questioned Thursday whether the U.S. Centers for Disease Control and Prevention was up to the task of fixing the problem, given similar promises to remedy such breaches in 2012.
The CDC is under scrutiny for a June incident, in which more than 80 lab workers may have been exposed to live anthrax bacteria that was mistakenly sent out of a high-security lab on its Atlanta campus. Federal investigators have since reported dozens of other infractions at CDC labs that handle deadly pathogens such as anthrax and avian flu.
A House Energy and Commerce subcommittee is investigating the incident and the CDC's response. Committee members are weighing the possibility of imposing new outside oversight on CDC labs and crafting national lab safety standards that would be administered by a single government body.
On Thursday, Committee Chairman Fred Upton made public a 2012 letter from CDC Director Dr Thomas Frieden saying the agency had put a senior official in charge of lab security and was soliciting advice from outside experts in biosecurity.
"We have designated a senior official who will report directly to the CDC Director regarding concerns or complaints related to safety at CDC's laboratories," Frieden said in the letter from September 2012 that was addressed to Upton.
Two years later, those measures did not appear to prevent a new round of safety breaches, including the anthrax incident.
Last week, Frieden said the CDC had appointed Dr. Michael Bell to be in charge of lab safety issues and would convene a panel of outside experts to advise the agency.
“These measures sound very similar to the corrective actions Dr. Frieden outlined last Friday to address the current lab crisis," Upton said. "Why should we believe this time that things will be different?”
Frieden testified on Wednesday at a hearing of the Energy and Commerce Subcommittee on Oversight and Investigations.
When asked about the senior official put in charge of lab security in 2012, Frieden was unable to name the appointee or describe the official's duties.
"I will have to get back to you about that to get you the name and the details of what was done pursuant to that letter," he told Representative Gregg Harper, a Mississippi Republican.
CDC spokesman Tom Skinner said on Thursday that CDC official Joseph Henderson was named to the position around March 2013, and that the role included a broader portfolio of responsibilities. Henderson, currently director of the Office of Safety, Security and Asset Management, sat next to Frieden at the witness table during the subcommittee hearing.
"When that letter was written in September 2012, there may have been a person designated in an acting role. Joe was hired full time seven months later in 2013," Skinner said.

Monday, July 14, 2014

CDC says there were 269 separate, reported incidents of lost or escaped 'select agent' microbes in 2010/ Reuters

Not to put too fine a point on it, but today's Reuters story has even more bad news on safety at our highest containment labs:
According to a 2012 report by CDC scientists, there were 16 incidents of lost or escaped microbes from select-agent labs in 2004, meaning everything from misplaced samples to an infected researcher walking out the door harboring a virus. That rose to 128 in 2008 and 269 in 2010.
There is some good news.  In light of all this, CDC Director Tom Frieden has proposed reducing the number of high containment labs in the US, and at CDC.  Sounds like a great idea! Also from the Reuters story:
    In the wake of disclosures that top government labs mishandled anthrax, smallpox and avian flu, U.S. health authorities are considering the once unthinkable: cutting the burgeoning number of labs working with the planet's most dangerous microbes.
    When the U.S. Centers for Disease Control and Prevention last week unveiled a report documenting multiple safety breaches at its labs, its director for the first time suggested the country turn back the rapid-fire proliferation of such research units, which have tripled in little more than a decade to at least 1,500. 
    "One of the things that we want to do is reduce the number of laboratories that work with dangerous agents to the absolute minimum necessary," said CDC Director Dr Thomas Frieden. "Reduce the number of people who have access to those laboratories to the absolute minimum necessary. Reduce the number of dangerous pathogens we work with." 
    His remarks may vindicate the views of a small group of biosafety and biosecurity experts who see that as the only way to protect dangerous viruses and bacteria from both lab accidents and thefts.... 
UPDATE:  US Government purges more than half the members of an NIH biosafety advisory board, including several anthrax experts.  Guess the executive branch has its own ideas about the kind of advice it wants, and feared it might not be forthcoming from this group.  See email sent to the 11 members here.

CDC scientists' lack of understanding of anthrax is shocking and terrifying

The WaPo has published the full text of the CDC report on its anthrax mishap last month, with mention of a number of other, almost identical mishaps...one even from the same lab... in which highly virulent, live bacteria, including anthrax, H5N1 avian flu and Clostridium botulinum were transferred to other labs, on the assumption they were benign strains or had been killed.

However, the report deemphasizes a critical safety breech:  that multiple lab personnel failed to appreciate the differences between anthrax spores and vegetative organisms.  It further minimizes the risk from live spores.

The report repeatedly states that the procedure used to inactivate anthrax would have worked for vegetative forms of anthrax.  The report admits the procedure did not completely kill spores.

There's an understatement.  Vegetative, growing anthrax bacteria can be killed by almost anything, including flying through the air. They cannot be used as a weapon due to their fragility.  

But spores are an entirely different matter.  There are very few things that kill anthrax spores, which can live for hundreds of years. That is why it was so difficult and expensive to decontaminate buildings contaminated with them.  An area harboring anthrax spores remains dangerous for the foreseeable future.  Scotland's Gruinard Island, where anthrax was tested during World War 2, was off limits to humans for 45 years, until it was decontaminated by being bathed in formaldehyde.

At CDC, an inactivation procedure was used on anthrax spores that was developed for vegetative, growing Brucella bacteria, yet was expected to inactivate spores.  This fact alone is astounding.  It shows complete lack of understanding of what the scientists were dealing with.  The report says its scientists had "inadequate knowledge of the peer-reviewed literature" on anthrax.  I would say they knew nothing about how to work with anthrax and are lucky they are still alive. They did not understand what they were doing, and should be reassigned away from select agents.

Even after 24 hours in a chemical bath, not all spores were killed.  Four colonies grew from an estimated 50,000 put on a plate.  Based on this, CDC's report claims there was no problem, as not enough spores (only about 1 in 10,000) might have lived to cause trouble.

However, only an estimated 50,000 spores were plated.  But how many were transferred to other labs? That number is never provided.  Bruce Ivins kept 1 trillion spores per ml (milliliter) in his flask at Fort Detrick. Fermenters produce one billion organisms per ml.  Most experiments require many orders of magnitude more than were plated. A reasonable guess might be that 10 billion spores were transferred.  At the given rate of inactivation, a million anthrax spores would have remained viable. According to the NY Times:
Over the next few days, scientists in two other labs where breathing equipment was not used agitated the bacteria and sprayed them with compressed gas, which could have blown spores into the air.
Could have blown spores into the air?  Clearly, these procedures did release spores into the air. Luckily for the scientists, it usually takes thousands of spores to cause infection.  But the occasional person (consider nonagenarian Ottilie Lundgren in Connecticut) may succumb to just a few spores.

The litany of mistakes that were made, detailed in the report's Findings, is breathtaking.  Lack of understanding of anthrax. Lack of SOPs. Lack of appropriate experimental design. Failure to follow CDC's own protocols, where they existed. Lack of supervision. Lack of timely communication when the incident was discovered, including identifying employees who may have been exposed so they could receive prophylaxis. (See page 16 of the Report.)  However, I disagree that it was highly unlikely that staff were exposed to anthrax:  they were, more likely, simply not exposed to enough anthrax spores, along with receiving prophylactic antibiotics, to induce disease.

Good recommendations are made to prevent a repeat in this report.  However, as the NY Times notes below, CDC has failed repeatedly to correct the very same problems identified in the report.  Decades ago, Fort Detrick lost two employees at its research facility to anthrax.  Many of us think it simply isn't possible for thousands of labs to perform this type of work safely.  It needs a tremendous degree of attention, care, and a paranoid mindset.  I would not trust myself to do it.  

It is slow working in a moon suit with a self-contained breathing apparatus.  You don't get to do blockbuster science this way. 

Have lower caliber scientists been shunted to the labs that perform this type of work, when what is required are the highest caliber, in order to do it safely?

UPDATE:  USDA's investigation of CDC finds even more bloopers and blunders, including failure to secure one of the labs that received the live anthrax.  People continued to transit the area for days after the mistake was discovered.  The CDC clinic failed to see exposed workers for up to 5 days, and advised some to check themselves for anthrax.  Anthrax was kept in an unlocked hall fridge; elsewhere, anthrax had gone missing.

2nd UPDATE:  Congressional memo with comments on USDA's APHIS report

Congress will be investigating with a hearing July 16.  From the Times:

Several experts on biosecurity noted that the inspector general’s office of the Department of Health and Human Services sent official complaints to the C.D.C. in 2008, 2009 and 2010 about undertrained lab personnel and improperly secured shipments.
Both Dr. Frieden and his predecessor, Dr. Julie L. Gerberding, replied in letters over their signatures that the problems would be fixed.