Questioning the decision to bring two live, infected, and contagious US citizens home for treatment of their Ebola is not simply fear mongering or hysteria: there is a perfectly rational risk-averse calculation that can be made without raising one’s blood pressure and calling down the end of the world.
In fact, a simple review of the documented risk of accidental infection by medical professionals and even highly secure government bio-hazard facilities should leave one with ample reason to remain skeptical of the decision to treat these people on American soil.
Hint: we’ve already had a professional virologist exposed to Ebola in a US Biosafety Level 4 laboratory, a Russian scientist has actually died from exposing herself to Ebola in a similar lab, a German scientist who stuck herself with an Ebola laced needle, and a researcher in the UK gave himself an Ebola/Marburg-like hemorrhagic fever while processing samples from African patients.
In 2004, a virologist at USAMRIID was working in a BSL-4 laboratory with mice that had been infected 2 days before with a mouse-adapted variant of the Zaire species of Ebola virus (ZEBOV) (2). The virulence and infectious dose of this variant of ZEBOV are unknown in humans; wild-type virus has a case-fatality rate of up to 90% (3).
The person had been following standard procedure, holding the mice while injecting them intraperitoneally with an immune globulin preparation. While the person was injecting the fifth mouse with a hypodermic syringe that had been used on previous mice, the animal kicked the syringe, causing the needle to pierce the person’s left-hand gloves, resulting in a small laceration. The virologist immediately squeezed the site to force the extravasation of blood. After decontamination of the blue suit in the chemical shower, the injured site was irrigated with 1 liter of sterile water and then scrubbed with povidone-iodine for 10 minutes.
In terms of exposure risk, the needle was presumed to be contaminated with virus-laden blood, although it was suspected that low levels of virus were present on the needle. The animals had not yet manifested signs of infection, and much contamination may have been removed mechanically when the needle pierced the gloves. The local decontamination of the site also reduced potential for infection.
USAMRIID medical, scientific, and executive staff concluded that the person with potential exposure warranted quarantine in the MCS. Contact plus airborne precautions (gown, gloves, N95 mask, eye protection) were used, with a plan to upgrade to BSL-4 precautions for signs or symptoms of illness. These extra precautions were instituted while the patient was asymptomatic for several reasons: 1) the timing of initial clinical manifestations with regard to potential for shedding virus were not known for this specific isolate in human infection; 2) there was interest in ensuring all infection control procedures were being followed appropriately in advance of clinical illness; and 3) there was interest in reducing any potential confounders, such as a caregiver transmitting a febrile respiratory infection to the patient, which might lead to unnecessary procedures or additional isolation. The person was monitored for routine vital signs; daily laboratory studies (coagulation studies, blood counts, chemistries, viral isolation, D-dimer) and regular physician assessments were performed.
Over the next several days, discussions were held with several internationally recognized filovirus experts regarding potential treatments or postexposure prophylaxis options. Local and state public health officials were also notified. The consensus opinion was that there was no safe, readily available source of immune plasma and little evidence existed to support its use. Emergency investigational new drug (IND) protocols were established for treatment with recombinant nematode protein (rNAPc2) and antisense oligomers, with the intention to consider implementation only if the patient demonstrated evidence of infection.
Ultimately, none of the 5 mice had confirmed viremia at the time of the incident. The patient did not become ill or seroconvert and was discharged after 21 days. The story received national and local media attention (4,5).
This case was ideal, a form of the virus that might not be infectious to humans, the virus had not been established in the mice at the time of the accident, and the exposure site was small. The details of the Russian accident mere months following the US accident are not as detailed but the result is decidedly worse:
A Russian scientist at a former Soviet biological weapons laboratory in Siberia has died after accidentally sticking herself with a needle laced with ebola, the deadly virus for which there is no vaccine or treatment, the lab’s parent Russian center announced over the weekend.
Scientists and officials said the accident had raised concerns about safety and secrecy at the State Research Center of Virology and Biotechnology, known as Vector, which in Soviet times specialized in turning deadly viruses into biological weapons. Vector has been a leading recipient of aid in an American program to help former Soviet scientists and labs convert to peaceful research.
Although the accident occurred May 5, Vector did not report it to the World Health Organization until last week. Scientists said that although Vector had isolated the scientist to contain any potential spread of the disease and there was no requirement that accidents involving ebola be reported, the delay meant that scientists at the health agency could not provide prompt advice on treatment that might have saved her life.
The earliest documented case of oopsy-poopsy Ebola infection comes from the UK in 1976:
In November 1976 an investigator at the Microbiological Research Establishment accidentally inoculated himself while processing material from patients in Africa who had been suffering from a haemorrhagic fever of unknown cause. He developed an illness closely resembling Marburg disease, and a virus was isolated from his blood that resembled Marburg virus but was distinct serologically. The course of the illness was mild and may have been modified by treatment with human interferon and convalescent serum. Convalescence was protracted; there was evidence of bone-marrow depression and virus was excreted in low titre for some weeks. Recovery was complete. Infection was contained by barrier-nursing techniques using a negative-pressure plastic isolator and infection did not spread to attendant staff or to the community.
A virologist working in the BSL-4 laboratory pricked herself in the finger during a mouse experiment on 12 March 2009. The syringe contained ZEBOV from culture supernatant that had been concentrated by ultracentrifugation and mixed 1:1 with incomplete Freund’s adjuvant for immunization of mice. The material was injected into the animal before the accident happened. When the laboratory worker tried to recap the needle, it penetrated the cap laterally and subsequently all 3 gloves. The puncture site on the skin was visible, but it did not bleed. The wound was disinfected after leaving the laboratory.
The virologist was not hospitalized for several days.
The patient voluntarily agreed on being hospitalized on 13 March. The responsible public health authorities, infectious disease specialists, and virologists considered the risk of virus transmission during the incubation period extremely low, as available epidemiological evidence indicates that Ebola virus is spread by ill or deceased patients through direct contact with infectious body fluids [1–3].
Ultimately the patient never developed symptoms of Ebola and it’s not documented that the accident lead to an actual sufficient exposure. But what’s greatly troubling is that the accident caught the BL-4 community with their pants down regarding what to do in such a case:
One may ask why the team in Hamburg chose this ad hoc procedure and not activated a defined operational plan to manage the patient. The Bernhard Nocht Institute followed a general operational plan for the management of accidental laboratory exposures, which included agreements with the Infectious Diseases Unit at the University Medical Center. Both virologists and clinicians in Hamburg had been aware of experimental treatment options as published in the literature.
However, like other BSL-4 facilities or infectious diseases units, which do not work on filovirus vaccines and therapeutics in NHPs or have contributed to field missions in filovirus outbreaks, they lacked the personal experience with this matter, the access to unpublished data, and the link to suppliers of investigational drugs and vaccines for making a choice among the different options. While a comprehensive set of general recommendations for the management of accidental laboratory exposures in BSL-3 and BSL-4 laboratories is available , there are no pathogen-specific recommendations for medical treatment of a case, especially for filoviruses. The BSL-4 laboratory community should consider establishing such recommendations.
Now we have a form of Ebola that is very human-infectious, in fact it’s infected more people this year than in any other year, ever. And we’re not dealing with the simple containment of mice, we’re dealing with the force and uncertainty of humans who might very well be dying. Namely, the challenges one faces in a traditional medical setting in addition to the much more routine and controlled environment in a laboratory (hint: medical professionals face even higher rates of accidental infection than lab workers).
Additionally we’re also very much facing a situation where Ebola will be handled more often by more researchers and other medical professionals on US soil than ever before. Ebola accidents are likely rare because the mere handling of Ebola is rare.
Other types of laboratory-acquired infections are not rare, especially for viruses and bacteria that are handled more often than Ebola.
To my knowledge there isn’t some easily accessible database of accidents and accidental infections that’s available to the public, but when the US Government decided to expand and renovate their High Containment Facilities at USAMRIID (Fort Detrick, Maryland) to replace and augment the one built in 1969, they had to file an Environmental Impact Statement which was reviewed by the National Academy of Sciences. The information therein is troubling.
For one thing, the review found that USAMRIID’s application was dubious in it’s own assessment of risk. Basically the Government is bullshitting the public about the actual risks.
“The maximum credible event analysis (required by the EIS) involved simulation of biological aerosol releases from Biosafety Level (BSL)-3 and BSL-4 laboratories. In the scenarios, Coxiella burnetii (requiring BSL-3 containment) and Ebola Zaire virus (requiring BSL-4 containment) were released to the surrounding environment from an exhaust stack after vials in a centrifuge leaked and air filters failed to filter the pathogens. The EIS estimates that ground concentrations would be insignificant and would not pose a hazard to the nearby community.
However, the committee was unable to verify this prediction, because the modeling performed in support of the scenarios was not transparent, could not be reproduced, and was incomplete.
Specifically, the data and parameterizations used in in the computerized simulation scenarios were not provided in the EIS and the model software (Hazard Prediction and Assessment Capability model) is a closed-source system not available for independent review. The committee attempted to verify the calculations using common alternative models. The committee’s calculations indicated the potential for significantly higher doses of infectious agents following puff releases than was described in the EIS.
The EIS contained no documentation of an indivisual’s risk of infection under the prescribed conditions or any description of the effect of population density and population size on the number of cases expected for any of the pathogens of interest. Furthermore, the scenarios only considered exposures beyond the Fort Detrick fence line, with no consideration of exposure to USAMRIID workers or other people on the base.”
The review had access to USAMRIID’s records on laboratory-acquired infections, and that last bit (no consideration of USAMRIID worker infection) is damning because USAMRIID does not have a clean bill of health regarding laboratory-acquired infections.
In the 14 years between 1989 and 2002, USAMRIID had 234 exposure/illness incidents with 5 confirmed laboratory-acquired infections: Glanders (BL-3), Q fever (BL-3), Vaccinia (BL-2/3), Chikungunya (BL-3) and Venezuelan Equine Encephalitis (BL-3).
“Between 1943 and 1969, the Offensive Biological Warfare Research Program logged 452 diagnosed infections, for an average of 16 laboratory acquired infections per year.”
The rate of infections from the implicated diseases has dropped since due to vaccination of laboratory workers against Tularemia, Q fever, and Venezuelan Equine Encephalitis. None of these vaccines are given to the public on a routine basis.
Even more troubling, at least two USAMRIID employees in recent years were infected with deadly agents and did not notify USAMRIID or seek treatment from the specially provided clinics on base!
“Since 2000 (reported in 2010), there have been two known cases in which [exposed and infected] USAMRIID workers failed to seek medical attention at the SIP clinic and also appeared to have failed to disclose that they were USAMRIID employees to the off-base physicians from whom they sought medical care. These failures delayed prompt diagnosis and treatment, and have raised community concerns about the potential for secondary transmission (that is, infection of others through contact).”
And the situation just gets worse when we consider that all of the above are in laboratory environments, not treating infectious patients in a medical setting.
“Common risks to [laboratory] workers are needle or sharps-stick accidents, inadvertent aerosol generation that leads to inhalation or ocular/mucosal exposure, and contact with infected laboratory animals.”
Trying to put a number on the actual rates of laboratory-acquired infections is difficult because of no systematic reporting.
In a 2002–2004 survey of clinical laboratory directors who participate in ClinMicroNet, an online forum sponsored by the American Society of Microbiology, 33% of laboratories reported the occurrence of at least 1 laboratory-associated infection.
Even so, what data we do have is troubling.
An estimated 500,000 workers are employed in laboratories in the United States . These workers are exposed to a variety of pathogenic microorganisms that may put them at risk of infection. However, the precise risk posed to individual laboratory workers after an exposure is difficult to determine, in part because of a lack of systematic reporting.
Current available data are limited to retrospective and voluntary postal surveys, anecdotal case reports, and reports about selected outbreaks with specific microorganisms.
Laboratory workers frequently become unwittingly infected through hitherto unexpected modes of transmission. This was illustrated by the first laboratory-acquired case of severe acute respiratory syndrome (SARS) coronavirus, which occurred ∼4 months after the end of the SARS epidemic . A 27-year-old microbiology graduate student in Singapore, who was working with a nonattenuated strain of West Nile virus, was evaluated for flulike symptoms. The patient denied any exposure to SARS and had no travel history. He was discharged from the emergency department but returned 5 days later because of persistent fever. Because Singapore remained in a heightened state of alert for SARS, a polymerase chain reaction assay was performed with a sputum specimen and returned a positive result for SARS coronavirus. Additional epidemiologic investigation revealed that the laboratory where he worked was also involved in research on SARS coronavirus and that one of the cell cultures of West Nile virus was contaminated with the same infecting strain of SARS coronavirus. Although this case represents an exceptional event, it serves to highlight the inherent risk posed to laboratory workers by virtue of their occupation.
There have even been notable outbreaks of viral hemorrhagic fevers, much like Ebola, due to exposures outside of clinical (BL-4) settings.
Viral agents transmitted through blood and bodily fluids cause most of the laboratory-acquired infections in diagnostic laboratories and among health care workers . Although the viral hemorrhagic fevers incite the most fear and dominate the imagination of the media and public, the viruses responsible are rare causes of laboratory infection [3, 4]. However, there is always the possibility that an agent not previously seen may be encountered. This occurred in 1967, when 31 workers were infected while handling tissue specimens from African green monkeys, with 7 deaths resulting . The causative agent was named Marburg virus, after the town in Germany where most cases occurred.
It should be obvious that Ebola infections in the laboratory are rare because working with Ebola is rare. But it’s going to become a lot less rare now that two fresh Ebola sources have entered the country and any number of people and organizations will likely get samples of the virus and come into contact with those samples that would not have done so otherwise.
But we aren’t just shipping in two vials of Ebola, two samples for laboratory use, we’re shipping in two living but infectious human beings into a heightened but no less problematic hospital setting.
Hospital situations offer many more risks. Just consider for a second the sheer volume of Ebola infected bodily fluids that are present in an entire human versus in a small petri dish. And consider how much harder it is to draw fluids or inject fluids into a live human versus transfer solutions between sealed vials or working with rats.
When we look at hospital-acquired infections the numbers get even worse.
“Of the common blood-associated viruses, hepatitis B virus (HBV) is the most common cause of laboratory-acquired infection . The incidence of HBV infection among all health care workers in the United States is estimated to be 3.5–4.6 infections per 1000 workers, which is 2–4 times than the level for the general population .”
Consider that, like before, we don’t even know about all or even most of the hospital-acquired illnesses because there’s no central or mandated reporting, but even so we still have continuing evidence that professionals who know the risks and the precautions are still getting themselves infected.
During 2005–2006, there were 802 confirmed cases of acute hepatitis C reported to the Centers for Disease Control and Prevention, with 5 occupational exposures (1.5%) to blood . However, there are few data on the incidence of hepatitis C among laboratory workers, and only single case reports in surveys have been performed in the United States and the United Kingdom [8-10].
And it’s not just more common diseases. Most doctors will never see a case of HIV, but a non-trivial number of professionals have acquired the disease in the course of their work, 75% in clinical settings and 25% in laboratory settings.
Data on occupational transmission of HIV from the period 1981–1992 revealed a total of 32 health care workers in the United States with occupationally acquired HIV infection; 25% of these health care workers were laboratory workers.
So accidents happen all the time and highly trained and experienced virologists working with huge budgets in cutting edge labs have already screwed up, infected themselves with Ebola, and died.
This is not a hypothetical.
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