A Searchable Laboratory-Acquired Infection Database

Abstract

Published peer-reviewed accounts of laboratory-acquired infections (LAIs) are difficult to track and assess due to several underlying factors. Reports of LAI in peer-reviewed journals are recognized as “goal posts” for biosafety programs and may contain invaluable information for proactive steps to take to prevent a potential incident in the laboratory. Objectively reviewing published studies enhances prevention efforts and reinforces training by providing examples of LAI and associated procedures. In an effort to make this information more accessible, ABSA International has developed an online searchable database of peer-reviewed published LAIs. This article presents the questions included in the repository and discusses the need for consistency in the data being collected for LAIs. In addition, this article presents historical information leading up to the development of these questions, as well as the formalization of the online database of published LAIs.

Pike and Sulkin recognized the importance of laboratory-acquired infections (LAIs) >50 years ago,^1,2 and >20 years ago, Sewell discussed the importance of biosafety as it relates to LAI. ³ In 2005, in a letter to the American Society for Microbiology (republished in Applied Biosafety), Bavoil stated, “Indifference is however the main factor in the rise of LAIs, particularly that from federal agencies, such as the [Centers for Disease Control and Prevention (CDC) and US Department of Agriculture], whose function is to safeguard the health of the public, researchers included.” ⁴ Data are not available on the rate of LAI occurrence for most laboratory activities. One notable exception is when select agents or toxins are involved, as entities are required to report possible and known occupational exposures to the Federal Select Agent Program.^5,6 Biosafety professionals have further called for the creation of a LAI database for years. For example, in 2013, Byers wrote, “There is no national or international registry that records critical information about LAI exposures, and publications vary in the level of detail provided.” ⁷

Health care providers, hospitals, clinics, diagnostic laboratories, and other medical facilities are required to report certain infectious diseases and conditions (also known as notifiable diseases) to federal, state, or local agencies. ⁸ A subset of these notifiable diseases must be reported to the CDC. Just as regulations differ from one place to another, reporting requirements also vary. In the case of notifiable diseases, the responsibility to report falls to a health care provider and not the patient.

This presents one of the first differences between an LAI and a notifiable disease. In the event of a notifiable disease, a patient is generally seeking medical care, and if an infectious disease on the notification list is discovered, it is subsequently reported by a medical professional. However, an LAI may never be reported, or if it is, it may not be linked to the laboratory. ⁹ An LAI may also occur with pathogens not included on a state’s list of notifiable diseases. This is especially true for exotic or emerging diseases, such as Zika virus, which was not included in the CDC’s list of notifiable pathogens just a few years ago. ¹⁰ In addition, a laboratory worker may be afraid to report an LAI to his or her employer out of fear of reprisal.

The collection and dissemination of LAI information are vital to biosafety professionals because having examples of LAIs is critical to effectively training individuals working with biohazards. As a result, the ABSA International Publications Committee launched a professional service project in October 2016 to collect significant data from published LAIs. The project was the culmination of years of effort to promote the importance of these known LAIs.

Nearly 2 years prior to the October 2016 release, Karen Byers, biosafety officer at the Dana Farber Cancer Institute, contacted Partha Krishnan, safety advisor at Yale University, and David Gillum, institutional biosafety officer at Arizona State University, to seek advice on what software program should be used to create an LAI website that could be easily searchable on a specific set of criteria. This conversation sparked an extensive dialogue regarding the best approach for capturing the data, including the questions to be asked, the best technology to use, and how to find an official online repository for the information. In a short time, a demonstration site was created through a Drupal form on the website owned and operated by the Arizona Biosafety Alliance, an affiliate of ABSA International.

The draft Arizona Biosafety Alliance LAI submission form was provided to the Publications Committee in March 2015. The members of the committee immediately supported the idea of an online LAI database and agreed that the time commitment for entering articles and verifying information would be minimal. Bruce Whitney, cochair of the Publications Committee, described the system as a “living review article” with members constantly updating and verifying the data.

When presented to the ABSA International Council, there was significant discussion regarding whether there were legal issues with presenting this information in a condensed format. Questions included whether legal counsel had been contacted regarding liability issues, such as the protection of information and the full approval and knowledge of the institution where the incident occurred. There was also concern that anyone having an LAI would go to the site and enter the details of his or her LAI. To remedy this concern, legal implications were avoided by limiting data entry to peer-reviewed and published journal articles. Using published LAIs also eliminates concerns regarding liability due to malicious posting of false information and privacy concerns. It also minimizes any potential consequences to biosafety and biosecurity professionals and their respective institutions. Finally, a disclaimer was added to the form, which stated that the LAI database was not intended to replace institutional, local, state, or federal reporting requirements.

After several months, legal counsel determined that the information could be summarized through the online form and made into a searchable database as long as the original publication was referenced and the original article was not plagiarized. The formal request to the ABSA International Council included a commitment from the Publications Committee to carefully review each entry in the database. As a method to ensure quality control, the Publications Committee voted that only designated ABSA International personnel would be permitted to enter data from published articles into the system.

Why Is an LAI Database Needed?

The Belgian Biosafety Association’s list of publishable LAIs is useful, up-to-date, and easily accessible. ¹¹ However, it is not a searchable database. Searches for LAIs may also be conducted through PubMed, ScienceDirect, Google Scholar, and the websites of individual journals (eg, Emerging Infectious Disease, New England Journal of Medicine, Morbidity and Mortality Weekly Report), as well as some subscription services, such as Scopus. With these services, individual biosafety professionals are required to perform a literature search for each LAI or associated procedure. The results may not necessarily be on point for their current need, and a variable percentage of the referenced papers would not be accessible. The references may not even be relevant to biosafety programs. In addition, some of the references would show up as “accidental infection,” “occupational infection,” and so on, which would lead to the time-consuming activity of multiple searches and checking every abstract for relevance. Having a searchable database of usable “lessons learned” references from peer-reviewed scientific journals is needed.

One of the problems encountered when doing literature searches for LAIs is that the keyword search may miss important articles. Articles with titles such as “Isolation and Partial Characterisation of a New Strain of Ebola Virus,” ¹² “Vibrio parahaemolyticus Infectious for Both Humans and Edible Mollusk Abalone,” ¹³ “Echo 11 Conjunctivitis,” ¹⁴ or “Seoul Virus and Hantavirus Disease, Shenyang, People’s Republic of China” ¹⁵ may be missed. In addition, some of the papers that do appear on a literature search for LAIs are not specifically related to an actual LAI, so sorting through various queries can take a long time. This database is intended to shorten the amount of time that it takes biosafety professionals to discover useful and relevant LAIs to share with others to demonstrate the need for practical and appropriate biosafety precautions. Also, since information from each peer-reviewed LAI publication is “sorted” through the same questionnaire, this allows for a biosafety professional to run a query—for example, a list of all LAIs involving work with Dengue virus.

LAI Questions

Early discussion regarding the specific questions to be asked for an LAI database involved an evaluation of 2 published articles. The first involved the transmission of HIV through droplets, ¹⁶ and the second involved a laboratory transmission of buffalopox virus. ¹⁷ These 2 articles served as a guide in identifying standardized extractable data pertinent to the preventative efforts and procedures, engineering and administrative controls, personal protective equipment, safety equipment, and other aspects about the LAI. The questions developed by the team are included in the online LAI database and shown in Table 1.

Table 1.

Laboratory-Acquired Infection Questionnaire.

Question	Instructions	Example
1a. Date of LAI/exposure?	Please enter the date of the LAI or exposure. If not known, please leave blank. If multiple LAI, please enter in the next question. (format: DD/MM/YYYY)
1b. Dates of LAI/exposure?	If multiple LAIs, please enter the date of each exposure in DD/MM/YYYY format.
2. Location where LAI/exposure occurred (eg, city and country)?	Please list the location (eg, city and country) where the incident occurred. If not known, please indicate “Unknown” in this field.	South Korea
3. Occupations of affected personnel?	Please list the occupations of the individuals who had the LAI/exposure. If not known, please indicate “Unknown” in this field.	Technician in research laboratory
4. Ages of affected personnel?	Please list the ages of the individuals who had the LAI/exposure (at the time of the incident). If not known, please indicate “Unknown” in this field.	30
5. Agents involved?	Enter the name of the agents involved. If not known, please indicate “Unknown” in this field.	Dengue
6. BSL for work being performed?	Please select the appropriate BSL for the work being performed at the time of the LAI/exposure?	BSL-2
7. In what setting did the LAI/exposure occur?	Please briefly describe the setting where the incident occurred (eg, clinical laboratory, research laboratory, animal holding room, field study).	Research laboratory
8. Device or equipment involved?	Please list any devices or equipment contributing to the LAI/exposure? If not known, please indicate “Unknown” in this field.	Needlestick
9. Procedure being performed?	Please briefly describe the procedure being performed or actions being taken at the time of the LAI/exposure. If not known, please indicate “Unknown” in this field.	Incident occurred during filtration of a virus stock for infection of mosquito cells with DENV-2
10. How did the LAI/exposure occur?	Please briefly describe how the LAI or exposure occurred. If not known, please indicate “Unknown” in this field.	A capped needle was removed from a 10-mL syringe, and Dengue virus was drawn up in the syringe from a 50-mL tube. A disposable filter was attached to the syringe, and the preparation was filtered. Repetition of the process led to lower levels in the 50-mL tube, so the filter was removed, and the needle was uncapped and reattached to draw the virus into the syringe. To remove the needle, recapping was attempted and resulted in the needlestick. This is the first Dengue transmission by needlestick in a research laboratory, and this open-access article has images of how the incident occurred.
11. What PPE was worn at the time of LAI/exposure?	Please select the PPE being worn at the time of the LAI/exposure. Select all that apply: face shield, safety glasses, laboratory coat, wraparound gown, full-body suit, single pair of protective gloves, double pair of protective gloves, powered air-purifying respirator, N95 respirator, full-face respirator, half-mask respirator, other PPE, unknown
12. What engineering controls were being used at the time of the LAI/exposure?	Please list any engineering controls that were being used at the time of the LAI/exposure. Select all that apply: biological safety cabinet, laminar flow cabinet, chemical fume hood, safety centrifuge cup, enclosed container, other engineering control, unknown	Biological Safety Cabinet
13. What follow-up procedures were taken?	Please describe any follow-up procedures, if any, that were taken after the LAI/exposure. If not known, please indicate “Unknown” in this field.	The authors recommend changing the WHO manual language from “minimize using syringes and needles” to “syringes and needles must not be used when in a situation where there use is not directly indicated.” Recapping was prohibited, but the authors noted the lack of a sharps container for disposal. First aid kits will be provided and monitored.
14. What actions may have been taken to prevent exposure?	Please describe any actions that may have been taken to prevent exposure. If not known, please indicate “Unknown” in this field.	The investigation revealed that the syringe alone or a pipette should have been used to suction virus. An explicit SOP may have prevented the use of a needle. The authors recommend reinforcement of biosafety measures.
15. What postexposure prophylaxis was provided?	Please list any postexposure prophylaxis (eg, actions taken to prevent infection or spread of disease). If not known, please indicate “Unknown” in this field.	The technician washed the wound with running water. There is no postexposure prophylaxis for Dengue virus. The technician continued to work in the research laboratory where all 4 serotypes were handled until the assay she did herself, daily, became positive on day 10; symptoms began on day 9. The authors refer to literature indicating that infection with a second serotype could result in a more severe outcome, and they believe that exposed staff should not continue to work until a definite diagnosis is made. The individual who had the LAI was reassigned to prevent a secondary infection and, possibly, severe dengue infection.
16. To which agency was the LAI/exposure reported?	To which agency/group was the incident reported? Please select all that apply: the LAI was not reported; the institution where the incident occurred; local governmental agency (eg, city or county health department); state governmental agency (eg, state public health laboratory); federal government agency (eg, CDC, OSHA); other governmental agency; other nongovernmental agency; unknown	Federal government
17. References	Please enter published references regarding the LAI/exposure.	Lee C, Jang EJ, Kwon D, et al. 2016. Laboratory-acquired Dengue virus infection by needlestick injury: a case report, South Korea, 2014. Ann Occup Environ Med. 2016;28:16.
Submitted by:	Name of person who submitted the article	Partha Krishnan, PhD, RBP
Data entry by:	Name of person who entered the data into the system	Karen Byers, MS, RBP, CBSP

Abbreviations: BSL, biological safety level; CDC, Centers for Disease Control and Prevention; DENV-2, Dengue virus type 2; LAI, laboratory-acquired infection; OSHA, Occupational Safety and Health Administration; PPE, personal protective equipment; SOP, standard operating procedure; WHO, World Health Organization.

LAI Searchable Database

The culmination of this research and collaboration was the creation of an online data entry and search page integrated within the ABSA International website. To reach the LAI database, visit the ABSA International website and click on the Members Only link. Once logged into the site, users can search within several fields of applicable information (see Table 1 for an example of the information that is searchable in the database). The data are intended to supplement risk assessment practices, provide ideas for training, promote future LAI reporting, and offer a key resource for biosafety professionals. It is of note that limiting access to the LAI database to current ABSA members may be a significant hindrance to the larger scientific community by impeding timely access to this information and ability to use it in safety plans. To address this issue, ABSA International should offer the LAI database as an open-access online database to reach a broader audience.

Conclusion

The ABSA International online LAI database is a great tool for biosafety professionals, serving as a “one-stop shop” for details associated with each published LAI in a quick and easily accessible format. This living database will grow over time, especially if more ABSA International members become involved in reviewing published LAIs. A future initiative would be to integrate this information into the ABSA International risk group app for smartphones, giving users the ability to learn about the risks and any published LAIs associated with the agent in question within the same application. One motivational currency to assist in this effort is to grant continuing maintenance credits for reviewing and entering data from published LAIs. If individuals are interested in assisting with this service project, please contact [e-mail].