Friday, November 29, 2013

BMC Medicine: Containing Laboratory Escape Of Pandemic Viruses


BSL-4 Lab Worker - Photo Credit –USAMRIID



# 8017


While nobody really knows how the H1N1 influenza virus – absent in the human population for 20 years – managed to spark a pseudo-pandemic in 1977,  many researchers suspect it escaped a lab in either Russia or China in the mid-1970s.  Genetically, it was very similar to a strain that had circulated 2 decades earlier, something that would be difficult to occur in the wild, but might well  be explained had the virus been stored in a lab freezer (see EID Journal article Influenza Pandemics of the 20th Century Edwin D. Kilbourne).


The evidence is only circumstantial, so we may never know the truth of the matter.


With the rise of `Gain of Function’  (GOF) research – which aims to enhance the virulence, host range, or transmissibility of dangerous pathogens so that we may better understand their pandemic potential – biosecurity experts have warned that an accident at a BSL-3 or BSL-4 lab could have global ramifications (see mBio: The H5N1 Biosafety Level Debate).


While most researchers involved in this sort of work call the risks both manageable, and negligible, the truth is - lab accidents have occurred in the past, and despite very strict bio-safety rules and procedures, they are likely to happen again in the future. 


In 2009, the United States GAO issued a 104 page report (HIGH-CONTAINMENT LABORATORIES : National Strategy for Oversight Is Needed ) that looked at four high-profile biosecurity breeches {see below), and examined the risks of future lab accidents.


  • Alleged insider misuse of a select agent and laboratory;
  • Texas A&M University’s (TAMU) failure to report to CDC exposures to select agents in 2006
  • Power outages at CDC’s high-containment laboratories in 2007 and 2008
  • The release of foot-and-mouth disease virus in 2007 at the Pirbright facility in the U.K.


The GAO described the risks going forward (bolding mine):


Four highly publicized incidents in high-containment laboratories,  as well as evidence in scientific literature, demonstrate that (1) while laboratory accidents are rare, they do occur, primarily due to human error or systems (management and technical operations) failure, including the failure of safety equipment and procedures, (2) insiders can pose a risk, and (3) it is difficult to control inventories of biological agents with currently available technologies. Taken as a whole, these incidents demonstrate failures of systems and procedures meant to maintain biosafety and biosecurity in high-containment laboratories. For example, they revealed the failure to comply with regulatory requirements, safety measures that were not commensurate with the level of risk to public health posed by laboratory workers and pathogens in the laboratories, and the failure to fund ongoing facility maintenance and monitor the operational effectiveness of laboratory physical infrastructure.



At one of the most secure BSL-4 facilities in the world – USAMRIID (U.S. Army Medical Research Institute of Infectious Diseases) - their safety record is exceedingly good  . . .  but it is not perfect.  This (bolding mine) from their website:


In order to properly assess safety performance over time, USAMRIID compares the number of incidents to the number of times employees entered BSL-3 and BSL-4 laboratories in a given year.  It is important to note that in every incident from 2010-2012, no symptoms were reported and there were no signs of illness.

For instance, in 2012, USAMRIID had 20,402 entries into BSL-3 laboratories. During that time, there were 9 safety incidents within those laboratories; 2 were Potential Biological Exposures (PBE).  A PBE means that some risk of exposure to infectious agents and/or toxins may have occurred, resulting in Occupational Health staff placing the personnel involved on precautionary medical surveillance.  No illness or disease occurred in either case. The 2012 incident rate for BSL-3 laboratories was 0.044 percent.

Looking at BSL-4 laboratories, USAMRIID had 9,154 entries during 2012, with a total of 30 incidents including 6 Potential Biological Exposures (PBE).  A PBE means that some risk of exposure to infectious agents and/or toxins may have occurred, resulting in Occupational Health staff placing the personnel involved on precautionary medical surveillance.  In every case, no illness or disease occurred.  The 2012 incident rate for BSL-4 laboratories was 0.328 percent.


In 2011 CIDRAP NEWS published a report called:


Report: 395 mishaps at US labs risked releasing select agents

By Robert Roos

Sep 28, 2011 (CIDRAP News) – US government laboratories had 395 incidents that involved the potential release of select agents between 2003 and 2009, though only seven related infections were reported, according to a new National Research Council (NRC) report.

The accidents, including animal bites, needle sticks, and other mishaps, are mentioned briefly in an NRC report on the plans for a risk assessment for an Army biodefense lab to be built at Ft. Detrick in Frederick, Md.

"The Centers for Disease Control and Prevention (CDC) reports 395 cases of potential release events at national laboratories working with select agents," the report says.

"Seven LAIs [laboratory-acquired infections] were reported to CDC; four infections involved Brucella melitensis, two involved Francisella tularensis, and one involved an unspecified Coccidioides species," it continues. "CDC plans to publish an analysis of these events." The report does not list the outcomes of the infections.

(Continue . . . )

All of which serves as prelude to a report that was published yesterday in BMC Medicine, that models the ability of a research lab to detect and contain a potentially dangerous biosecurity breech, once it has occurred.


Containing the accidental laboratory escape of potential pandemic influenza viruses

Stefano Merler, Marco Ajelli, Laura Fumanelli and Alessandro Vespignani

BMC Medicine 2013, 11:252  doi:10.1186/1741-7015-11-252

Published: 28 November 2013

Abstract (provisional)


The recent work on the modified H5N1 has stirred an intense debate on the risk associated with the accidental release from biosafety laboratory of potential pandemic pathogens. Here, we assess the risk that the accidental escape of a novel transmissible influenza strain would not be contained in the local community.


We develop here a detailed agent-based model that specifically considers laboratory workers and their contacts in microsimulations of the epidemic onset. We consider the following non-pharmaceutical interventions: isolation of the laboratory, laboratory workers' household quarantine, contact tracing of cases and subsequent household quarantine of identified secondary cases, and school and workplace closure both preventive and reactive.


Model simulations suggest that there is a non-negligible probability (5% to 15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all. We find that the containment depends on the timely implementation of non-pharmaceutical interventions and contact tracing and it may be effective (>90% probability per event) only for pathogens with moderate transmissibility (reproductive number no larger than R0 = 1.5). Containment depends on population density and structure as well, with a probability of giving rise to a global event that is three to five times lower in rural areas.


Results suggest that controllability of escape events is not guaranteed and, given the rapid increase of biosafety laboratories worldwide, this poses a serious threat to human health. Our findings may be relevant to policy makers when designing adequate preparedness plans and may have important implications for determining the location of new biosafety laboratories worldwide.

(Continue . . . . )

From a press release via Northeastern University, we get additional background on this research.  Follow the link to read it in its entirety, as I’ve only included an excerpt:


The potential pandemic

November 28, 2013 by Angela Herring


The results of the sim­u­la­tion sug­gest a 5–15 per­cent chance that an acci­dental escape would not be detected, espe­cially in the case of very trans­mis­sible viruses and those where symp­toms are not imme­di­ately spotted. In addi­tion, they found that con­tain­ment would depend on the struc­ture and den­sity of the local pop­u­la­tion sur­rounding a facility.


“Most BSL labs are in big urban areas,” Vespig­nani explained. “In those areas we show that the prob­a­bility of not con­taining the out­break is three to five times larger than what it would be in iso­lated areas.”


While the prob­a­bility of acci­dental release is extremely low—there’s only 0.3 per­cent chance of a virus escaping one of these labs each year—even a single event can trans­late into a vast public health emer­gency, said Ste­fano Merler, one of the researchers who is based at the Kessler Foun­da­tion. More­over, the number of BSL3 and 4 lab­o­ra­to­ries is increasing, cre­ating a greater com­bined risk the world over.

(Continue . . . )



While there are only a few dozen BSL-4 labs around the world, there are literally thousands of BSL-3 capable labs. Admittedly, few are conducting GOF research, but even the release of an un-enhanced pathogen could potentially produce a huge impact.


Although many researchers can justifiably point out their lab’s exemplary safety record, the standards set and met in labs around the world can vary substantially.  And even the finest biosecurity methods can be thwarted by deliberate `bad acts’ by staff.  


Whether researchers doing this sort of research like to admit it it, the risks of seeing an accidental release from one of these labs is far from zero. While a .3% chance of release from any given lab works out to be roughly one every 100 years, with hundreds of of BSL-3 and BSL-4 labs around the world, the odds of seeing an accident in any given year somewhere in the world go up substantially.


And if today’s BMC Medicine study is correct, containment – particularly of a high R0 pathogen (highly infectious) – is far from guaranteed.

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