Next Article in Journal
Knowledge, Attitude, and Practices of Healthcare Workers Towards Tuberculosis, Multidrug-Resistant Tuberculosis, and Extensively Drug-Resistant Tuberculosis
Previous Article in Journal
Nasopharyngeal Colonization and Antimicrobial Susceptibility of Bacterial Isolates in Children and Young Adults with Acute, Protracted, and Chronic Cough: A Cross-Sectional Bulgarian Study
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Systematic Review

Tracking the Threat, 50 Years of Laboratory-Acquired Infections: A Systematic Review

by
Esteban Zavaleta-Monestel
1,2,*,
Carolina Rojas-Chinchilla
1,
Adriana Anchía-Alfaro
1,
Diego Quesada-Loría
1,
Jonathan García-Montero
1,2,
Sebastián Arguedas-Chacón
1 and
Georgia Hanley-Vargas
1
1
Research Department, Hospital Clínica Bíblica, San José 10104, Costa Rica
2
Faculty of Pharmacy, Universidad de Ciencias Médicas (UCIMED), San José 10108, Costa Rica
*
Author to whom correspondence should be addressed.
Acta Microbiol. Hell. 2025, 70(2), 11; https://doi.org/10.3390/amh70020011
Submission received: 27 December 2024 / Revised: 5 February 2025 / Accepted: 14 February 2025 / Published: 24 March 2025

Abstract

:
Laboratory-acquired infections (LAIs) pose significant risks to laboratory personnel, public health, and the environment, despite the implementation of biosafety measures. This study provides a comprehensive analysis of global LAIs reported from 1974 to 2024, identifying trends, causes, and pathogen distributions to address gaps in biosafety knowledge. A systematic literature review was conducted using databases such as PubMed, Cochrane, Google Scholar, and the American Biological Safety Association (ABSA). A total of 234 studies meeting strict inclusion criteria were analyzed. Bacterial pathogens accounted for 58.6% of reported incidents, followed by viruses at 36.1%. Procedural errors and accidents were the predominant causes of LAIs, with Brucella spp. being the most frequently reported pathogen, primarily in China. Temporal trends indicated a decline in incidents coinciding with the implementation of international biosafety regulations. However, disparities in incident reporting and compliance remain evident across countries. This study underscores the urgent need for a global regulatory framework, mandatory biosafety audits, a centralized incident database, and standardized training for high-containment laboratory personnel. Enhancing global collaboration, transparency in research, and adherence to ethical standards will further reduce LAI risks and strengthen public health security worldwide.

1. Introduction

Despite global efforts to implement preventative and safety measures, biological materials accidents occur worldwide in laboratories [1]. This highlights the critical importance of biosecurity, a comprehensive set of techniques and protocols designed to prevent the unintentional exposure of personnel and the environment to hazardous pathogens [2]. These pathogens can lead to lethal diseases with pandemic potential [2].
Laboratory-acquired infections (LAIs) represent significant biohazards, posing serious risks not only to the environment but also to public health, particularly for laboratory workers who face exposure through various routes. While LAIs may or may not spread beyond the laboratory environment [3,4], this inherent risk underscores the need for robust biosafety practices [5].
The likelihood of a bio-incident (accidental exposure to a biological agent) is influenced by the level of biosafety implemented within a facility [3,6]. Microbiological laboratories employ a four-tiered biosafety classification system established by the World Health Organization (WHO) to manage the risks associated with various biological agents [7]. Table 1 outlines the different biosafety levels and the types of pathogens permitted for manipulation within each level [7]. As biosafety levels increase, so do the stringency of protocols, including the use of tailored personal protective equipment (PPE), rigorous sterilization, specialized waste management, and customized laboratory designs to ensure containment and safeguard against breaches [7].
Despite these rigorous safety measures, accidents can still occur, with BSL-4 incidents posing the greatest concern due to the extreme dangers associated with the pathogens that are handled [4,8]. Human errors, equipment failures, and a lack of robust safety culture are common contributors to LAIs, highlighting the need for continuous improvement in biosafety measures and compliance [4,8]. Importantly, any bio-incident has the potential to extend beyond the laboratory, posing significant public health risks and potential pandemic threats.
To our knowledge, there are no existing research articles that systematically report and analyze LAIs on a global scale over an extended period, such as the five decades covered in this review (1974–2024). This gap in the literature is critical, since these types of reports are fundamental to understand the incidence of LAIs and identify trends that could inform improvements in biosecurity measures. While there are notable studies on LAIs, they are limited in scope. For instance, Blacksell et al. and Manheim et al. analyzed laboratory-acquired infections worldwide over 21 years and 41 years, respectively. However, their studies include non-peer-reviewed sources such as news reports and blog posts, which may present challenges on the reliability of the data presented [9,10]. Moreover, their studies do not fully address the broader pandemic or epidemic implications of LAIs [9,10].
Similarly, other reports, such as those by Balbontin et al. and Ackelsberg et al., focus on LAIs within specific countries or for individual pathogens, limiting their applicability to global trends [11,12]. Isolated case reports, such as those by Bang et al. and Aebischer et al., provide valuable insights into managing specific incidents but fail to offer a comprehensive global perspective on LAI trends [13,14]. These limitations underscore the need for a systematic, global analysis to better understand LAI patterns, risks, and prevention strategies.
This systematic literature review aims to address these gaps by providing a comprehensive analysis of laboratory accidents involving pathogens reported globally between 1974 and 2024. By examining trends and identifying common causes of LAIs, this study aims to enhance the understanding of global biosafety challenges. Additionally, it evaluates the effectiveness of biosafety measures to inform future efforts in mitigating laboratory-related risks.

2. Materials and Methods

2.1. Study Design

The research team conducted a systematic literature search. The following databases were searched from 1974 to December 2024: PubMed, Cochrane, Google Scholar, and the American Biological Safety Association (ABSA). PubMed was selected for its extensive coverage of biomedical literature. Cochrane was selected due to its specialization in systematic reviews and meta-analyses. Google Scholar was included to capture a broader range of literature across disciplines, including grey literature. Finally, ABSA was included due to its extensive number of reports on LAIs worldwide.
The following keywords were used in the search strategy: “biosafety”, “laboratory-acquired infections”, “laboratory infection”, “LAI”, “laboratory escape”, “pathogen escape”, and “laboratory leak”. The term “biosafety” was included to encompass literature related to minimizing biological risks in which LAIs have been reported. Also, the terms “laboratory-acquired infections”, “laboratory infection”, and “LAI” were selected to directly focus on the primary subject of the study, capturing data specific to infections arising from laboratory setting. Additionally, the keywords “laboratory escape”, “pathogen escape”, and “laboratory leak” were included to incorporate studies addressing breaches were pathogens exited laboratory environments. Finally, Boolean operators (AND, OR, NOT) were used to combine keywords and refine the search.

2.2. Data Extraction

The literature search was conducted individually, the selection process began with an initial assessment of the title and/or abstract, followed by a comprehensive review of the full text for relevant materials. The compiled information was cross-checked amongst the authors for validation. The extracted data was then organized into a table (Table S1) to organize the following extracted variables: causal pathogen, pathogen type, number of cases, number of reported incidents, cause of the incident, country, and date. The cause of the incident was classified according to Table 2. Additionally, information related to the implementation and updates of regulations during this period was also collected.

2.3. Inclusion and Exclusion Criteria

The selection criteria encompassed all articles published or translated into English. The study focused exclusively on LAIs among staff and students working in laboratory environments, such as clinical microbiology laboratories, research laboratories, and animal research facilities. Literature that lacked sufficient details, such as those that did not specify the pathogen, date or country, were excluded. Furthermore, cases involving infected animals not related to laboratory settings or those that could not be definitively classified as LAIs, as well as duplicated records, were also excluded. To avoid redundancy, reviews on LAIs that covered specific countries or time periods, or referenced individual LAI cases, were only included once to ensure unique representation of the data.

2.4. Analysis

A thorough analysis of all summary tables was conducted using Microsoft Excel. This involved cross-tabulating variable data to rank causal pathogens, pathogen classes, case numbers, affected countries, report dates, and event types; the information is available as Table S1. Microsoft Power BI (version 2.116.966.0) and R software (version 4.3.1) were used to enhance data analysis and visualization. These tools allowed the generation of clear and insightful summary figures, providing deeper insights into the patterns and trends observed within the dataset.

3. Results

The previously described search strategy retrieved a total of 2486 results. After combining the results from all sources and deleting duplicates, 1725 unique results were left; these were then screened based on their applicability to the search criteria. This was followed by the elimination of 304 irrelevant results. The full texts for the remaining 1421 results were retrieved to further assess their eligibility according to the established inclusion and exclusion criteria. Finally, 234 studies which contained all the necessary data were chosen to be included in the statistical analysis conducted in the review. The full selection and retrieval process is shown in Figure 1.
As shown in Figure 2, the predominant pathogen type identified in these incidents was bacteria, accounting for 255 incidents, which constituted 58.6% of the total. Viruses followed with 157 incidents (36.1%), while fungi, parasites, and prions were involved in 10 incidents (2.3%), 10 incidents (2.3%), and 3 incidents (0.7%), respectively.
Table 3 shows that among bacterial incidents, the most common causes were procedural errors (38.3%), not stated causes (36.0%), and accidents (22.5%). Multiple causes and intentional incidents accounted for only 2.0% and 0.8% of bacterial cases, respectively. For incidents involving viruses, accidents were the predominant cause (48.7%), followed by non-stated causes (32.1%), procedural errors (18.0%), and multiple causes (1.3%). In cases involving fungi, most causes were not stated (60.0%), followed by accidents (30.0%) and procedural errors (10.0%). Regarding incidents with parasites, accidents were predominant (50.0%), followed by not stated causes (30.0%) and procedural errors (20.0%). Finally, incidents involving prions were primarily due to non-stated causes (66.7%), with accidents accounting for the remaining cases (33.3%).
Table 4 and Table S1 show the distribution of pathogens identified in laboratory-acquired infections from 1974 to 2024. Brucella spp. emerged as the predominant pathogen, constituting 90.6% of the total number of infections with 10,794 confirmed cases. As shown in Table S2, most cases were reported in China, totaling 10,581 cases (98.03%, of all Brucella spp. cases). The United States followed with 57 cases of brucellosis, representing 0.53% of the total cases. Additionally, Turkey reported 42 cases, accounting for 0.39% of the cases.
Anthrax (Bacillus anthracis) was the second most common, with 205 cases, constituting 1.7% of the total number of infections. Table S2 shows that Russia reported the highest number of cases, totaling 177 (86.34%, of all anthrax cases), followed by the United States with 26 cases (12.68%), and the United Kingdom with 2 cases (0.98%).
Coxiella burnetii ranked as the third most prevalent pathogen, contributing 149 cases, which accounted for 1.6% of the total number of infections. These cases were reported exclusively in the United States. Moreover, hemorrhagic fever with renal syndrome virus was the fourth most common pathogen, accounting for 140 cases (1.2%, of the total number of infections), the totality of cases originating in Japan. Moreover, Crimean–Congo hemorrhagic fever (CCHF)-like virus was the fifth most prevalent pathogen, totaling 75 cases (0.6%, of the total number of infections), all originating in Russia.
Moreover, Figure 3 and Table S3 show the distribution of reported cases by country from 1974 to 2024. China has reported the highest number of laboratory-acquired infection cases, totaling 10,630 cases, representing 89.21% of the global total. The United States follows with 473 cases (3.97% of the total), and Russia ranks third with 256 cases (2.15%). Japan and the United Kingdom are fourth and fifth on the list, with 152 cases (1.28%) and 68 cases (0.57%), respectively. Among the countries evaluated in this study, 57.50% (n = 23) reported an incidence of fewer than 10 cases of laboratory-acquired infections. Notably, 32.50% (n = 13) of the studied countries reported only one case.
On the other hand, Figure 4 and Table S4 illustrate the distribution of reported incidents (events) by country from 1974 to 2024. It is important to note that a single event may result in one or more reported cases (such as those shown in Figure 3 and Table S3) due to the exposure of the pathogen to multiple lab personnel or local communities near the source of the LAI. The United States has reported the highest number of incidents, totaling 162, which represents 37.50% of the global total. The United Kingdom follows with 53 incidents (12.27%), and Canada ranks third with 46 incidents (10.18%). China and Japan are fourth and fifth, reporting 19 incidents (4.40%) and 15 incidents (3.47%), respectively. Among the countries evaluated in this study, 80.00% (n = 32) reported fewer than 10 events. Additionally, 32.50% (n = 13) of countries reported only one incident.
Figure 5 shows the number of reported incidents per year from 1974 to 2024, highlighting the introduction of laws and regulations by various regulatory agencies, including the WHO, Centers for Disease Control and Prevention (CDC), and European health authorities. This visualization illustrates the trend of laboratory-acquired infection incidents alongside the implementation of these control and prevention measures, offering a comprehensive view of how these regulations have impacted incident rates over time.

4. Discussion

Despite established pathogen management policies and regulations, laboratory accidents and potential pathogen transfers remain significant concerns [32,33]. This review reveals alarming patterns in incidents of LAIs over the past five decades, highlighting the diversity and complexity of infectious agents, including bacteria, viruses, fungi, parasites, and prions, that laboratory workers interact with daily [4,34].
The identified causal factors shown in Figure 2 underscore the need to improve pathogen handling practices and strengthen laboratory safety protocols [4]. A high proportion of incidents with unspecified causes points to deficiencies in documentation and reporting of critical events, making it difficult to identify patterns and implement effective preventive strategies [31]. Accidents and procedural errors constitute a significant portion of reported incidents, emphasizing the importance of continuous staff training, regular protocol reviews, and audits to reduce these occurrences.
To guide global preparedness for future pandemics, the WHO has established a priority list of pathogens that pose significant risks of outbreaks or pandemics [35]. This list, updated in 2024, aims to direct research efforts toward the development of vaccines, diagnostic tests, and treatments [35,36]. The pathogens identified include high-priority agents such as Mammarenavirus, Vibrio cholerae, Yersinia pestis, Shigella, Salmonella, Klebsiella, Merbecovirus, Sarbecovirus, Orthoebolavirus, influenza viruses, Henipavirus, Bandavirus, Orthopoxvirus, and Alphavirus (Chikungunya and Venezuelan) [35]. These agents are highly transmissible and virulent, with limited available countermeasures, underscoring the importance of research in pandemic readiness. However, this research requires stringent guidelines to prevent LAIs, as laboratories working with these highly virulent pathogens must adhere to robust biosafety protocols.
The need for caution is further highlighted by the risks associated with laboratory work on pathogens with pandemic potential. For instance, Klotz and Merler’s risk analyses on H5N1 demonstrate the challenges of containment following a laboratory escape event [37,38]. Merler et al.’s simulations suggest a non-negligible probability (5–15%) that such events may go undetected, depending on factors such as the pathogen’s reproduction number, transmissibility, and probability of clinical symptom development [38]. These findings underscore the critical need for tailored biosafety measures, especially in high-density urban areas, where the probability of a global event following a breach is significantly higher than in rural settings.
Unfortunately, the risks of pandemics resulting from LAIs are not merely theoretical. Historical examples demonstrate the severe consequences of such events. For example, the 1977–1978 influenza epidemic is hypothesized to have originated from a laboratory incident due to a clinical vaccine trial which used an improperly attenuated live virus [39,40]. This remains the only documented example of a human epidemic resulting directly from research activity [39]. Similarly, post-epidemic SARS outbreaks in 2003 (Singapore) and 2004 (Beijing) were directly tied to laboratory work. In Singapore, a researcher working with attenuated West Nile Virus samples inadvertently became infected with SARS-CoV [41]. In Beijing, live SARS coronavirus experiments led to two initial cases, which went undetected long enough to cause community transmission and infect nine additional people [9,42,43]. Ironically, these laboratories were handling pathogens to prevent the outbreaks they ultimately caused.
The origins of SARS-CoV-2 have also reestablished concerns about laboratory safety. While substantial evidence supports zoonotic emergence through repeated human–animal contact in wildlife trade, the possibility of a laboratory accident has not been completely dismissed [39,44]. Although there is no direct evidence of a lab-origin escape [39], the COVID-19 pandemic serves as a reminder of the potential global implications of a laboratory breach involving pathogens with pandemic potential.
A notable finding in this review is the high incidence of cases associated with Brucella spp., particularly in China, where the 2019 Lanzhou biopharmaceutical factory incident resulted in 10,528 cases of brucellosis [45]. This outbreak, caused by expired disinfectants leading to pathogen aerosolization, underscores the need for stringent BSL-3 biosafety practices and robust international regulatory oversight [45]. Similarly, Bacillus anthracis remains a critical bioterrorism agent, with multiple reported cases in Russia and the United States. U.S. policies, such as the Select Agent Program, demonstrate the effectiveness of strict regulations and rapid response measures in reducing incidents and provide a model for other nations [10,46].
The weaknesses in current pandemic management systems are evident in their fragmented and reactive nature [47]. Inconsistent responses to the COVID-19 pandemic, driven by decentralized approaches and varying levels of preparedness, delayed outbreak identification and containment [48]. This challenge is compounded by outdated surveillance systems and limited integration of advanced technologies for real-time data sharing and analysis [48]. Platforms like FluNet and GLASS face compliance and reporting delays, while promising tools such as artificial intelligence and machine learning remain underutilized [48,49,50]. Investments in these technologies, integrated into a unified global framework, are essential for rapid responses to public health emergencies [51].
Strict adherence to biosafety protocols is particularly crucial in research involving the manipulation of microorganisms with high pandemic potential. Comprehensive risk assessments are necessary to identify and mitigate hazards effectively [52]. Laboratory-acquired infections and documented outbreaks underscore the vulnerabilities in current biosecurity frameworks and the importance of robust training, a culture of safety, and lessons learned from past incidents. Incorporating these lessons into global pandemic preparedness efforts will enhance health security and reduce the risk of accidental releases.
Although Figure 5 suggests a decline in reported LAIs starting in 2021, this trend remains inconclusive due to limitations in reporting. Establishing a standardized global database for laboratory biosecurity, guided by international organizations like the WHO, is essential. Such a framework should emphasize transparency, timely incident reporting, and rigorous monitoring. Adopting a unified governance model, such as the “One Health” approach, and leveraging advanced technologies will enable more resilient systems to prevent and respond to future health crises effectively and equitably [47,48].
A limitation due to underreporting. While countries such as Canada and the United States have implemented systems like LINC (Laboratory Incident Notification Canada) to encourage the reporting of LAIs, challenges persist with underreporting, as well as the accuracy and completeness of reports [53]. These challenges, coupled with the potential for publication bias (where studies with significant or positive findings may be more likely to be published), can significantly impact the true burden and characteristics of LAI events.

5. Conclusions

The study underscores the importance of strengthening pathogen management practices, improving regulatory compliance, and fostering global collaboration. To address these challenges, the establishment of a global regulatory framework for BSL-3 and BSL-4 laboratories is recommended, with oversight by an international body, to ensure uniform biosafety standards. The implementation of mandatory accreditation programs and routine biosafety audits is necessary to assess compliance and identify areas for improvement. The development of a centralized database for transparent reporting and analysis of laboratory incidents is essential for mitigating repeat risks. Standardized training curricula for high-containment laboratory personnel, supported by international knowledge exchange, can further enhance safety practices. Transparency in dual-use research should be ensured through rigorous ethical oversight by international committees. These measures present a structured approach to improving laboratory safety, reducing the risk of laboratory-acquired infections, and strengthening global public health security.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/amh70020011/s1, Table S1: Dataset Tracking the Threat: 50 Years of Laboratory Acquired Infections; Table S2: Laboratory-acquired infection case distribution by country for the most frequently reported pathogens; Table S3: Case number of laboratory-acquired infections per country from 1974 to 2024; Table S4: Event number of laboratory-acquired infections per country from 1974 to 2024.

Author Contributions

Conceptualization, E.Z.-M.; methodology, E.Z.-M., C.R.-C., J.G.-M. and G.H.-V.; formal analysis, D.Q.-L. and C.R.-C.; investigation, C.R.-C., J.G.-M. and G.H.-V.; data curation, D.Q.-L.; writing—original draft preparation, C.R.-C., J.G.-M., G.H.-V. and S.A.-C.; writing—review and editing, E.Z.-M.; visualization, A.A.-A.; supervision, E.Z.-M.; project administration, E.Z.-M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

The original data presented in the study are openly available as Table S1 in the Supplementary Materials Section.

Acknowledgments

The authors extend their gratitude to Richard H. Ebright for his guidance and mentorship throughout the development and writing of this article.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Appelt, S.; Jacob, D.; Rohleder, A.-M.; Bråve, A.; Björndal, Å.S.; Di Caro, A.; Grunow, R. Assessment of Biorisk Management Systems in High Containment Laboratories, 18 Countries in Europe, 2016 and 2017. Eurosurveillance 2020, 25, 2000089. [Google Scholar] [CrossRef] [PubMed]
  2. Beeckman, D.S.; Rüdelsheim, P. Biosafety and Biosecurity in Containment: A Regulatory Overview. Front. Bioeng. Biotechnol. 2020, 8, 650. [Google Scholar] [CrossRef] [PubMed]
  3. Petts, D.; Wren, M.; Nation, B.; Guthrie, G.; Kyle, B.; Peters, L.; Mortlock, S.; Clarke, S.; Burt, C. A Short History of Occupational Disease: 1. Laboratory-Acquired Infections. Ulst. Med. J. 2021, 90, 28. [Google Scholar]
  4. Peng, H.; Bilal, M.; Iqbal, H.M. Improved Biosafety and Biosecurity Measures and/or Strategies to Tackle Laboratory-Acquired Infections and Related Risks. Int. J. Environ. Res. Public Health 2018, 15, 2697. [Google Scholar] [CrossRef]
  5. Gao, W.; Wu, Z.; Zuo, K.; Xiang, Q.; Zhang, L.; Chen, X.; Tan, F.; Liu, H. From Biosafety to National Security: The Evolution and Challenges of Biosafety Laboratories. Laboratories 2024, 1, 158–173. [Google Scholar] [CrossRef]
  6. Coelho, A.C.; García Díez, J. Biological Risks and Laboratory-Acquired Infections: A Reality That Cannot Be Ignored in Health Biotechnology. Front. Bioeng. Biotechnol. 2015, 3, 56. [Google Scholar] [CrossRef]
  7. Microbe, T.L. Searching for SARS-CoV-2 Origins: Confidence versus Evidence. Lancet Microbe 2023, 4, e200. [Google Scholar] [CrossRef]
  8. Willemarck, N.; Van Vaerenbergh, B.; Descamps, E.; Brosius, B.; Dai, C.; Leunda, A.; Baldo, A. Laboratory-Acquired Infections in Belgium; Technical report; Flemish Agency for Care and Health, Biosafety and Biotechnology Unit: Brussels, Belgium, 2015. [Google Scholar]
  9. Blacksell, S.D.; Dhawan, S.; Kusumoto, M.; Le, K.K.; Summermatter, K.; O’Keefe, J.; Kozlovac, J.P.; Almuhairi, S.S.; Sendow, I.; Scheel, C.M.; et al. Laboratory-Acquired Infections and Pathogen Escapes Worldwide between 2000 and 2021: A Scoping Review. Lancet Microbe 2024, 5, e194–e202. [Google Scholar] [CrossRef]
  10. Manheim, D.; Lewis, G. High-Risk Human-Caused Pathogen Exposure Events from 1975–2016. F1000Research 2021, 10, 752. [Google Scholar] [CrossRef]
  11. Balbontin, N.; Gauthier, A.; Abalos, C.; Davis, A.N.; Lister, M. Canadian Laboratory Incidents with Human Pathogens and Toxins: An Overview of Reports, 2016–2022. Can. Commun. Dis. Rep. 2024, 50, 144–152. [Google Scholar] [CrossRef]
  12. Ackelsberg, J.; Liddicoat, A.; Burke, T.; Szymczak, W.A.; Levi, M.H.; Ostrowsky, B.; Hamula, C.; Patel, G.; Kopetz, V.; Saverimuttu, J.; et al. Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017. J. Clin. Microbiol. 2020, 58, e01096-19. [Google Scholar] [CrossRef] [PubMed]
  13. Bang, E.; Oh, S.; Chang, H.E.; Shin, I.S.; Park, K.U.; Kim, E.S. Zika Virus Infection During Research Vaccine Development: Investigation of the Laboratory-Acquired Infection via Nanopore Whole-Genome Sequencing. Front. Cell. Infect. Microbiol. 2022, 12, 819829. [Google Scholar] [CrossRef]
  14. Aebischer, O.; Meylan, P.; Kunz, S.; Lazor-Blanchet, C. Lymphocytic Choriomeningitis Virus Infection Induced by Percutaneous Exposure. Occup. Med. 2016, 66, 171–173. [Google Scholar] [CrossRef]
  15. Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. PLoS Med. 2021, 18, e1003583. [Google Scholar] [CrossRef] [PubMed]
  16. WHO. Biorisk Management. In Laboratory Biosecurity Guidance; WHO: Geneva, Switzerland, 2006. [Google Scholar]
  17. National Research Council; Policy and Global Affairs; Development, Security, and Cooperation; Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology. Biotechnology Research in an Age of Terrorism; National Academies Press: Washington, DC, USA, 2004; p. 10827. ISBN 978-0-309-08977-7. [Google Scholar]
  18. Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction. Main Page. Available online: https://legal.un.org/avl/ha/cpdpsbbtwd/cpdpsbbtwd.html (accessed on 18 July 2024).
  19. European Commission. EU Animal Health Strategy 2007–2013. Available online: https://food.ec.europa.eu/animals/animal-health/eu-animal-health-strategy-2007-2013_en (accessed on 18 July 2024).
  20. Executive Order 13486 Working Group on Strengthening the Biosecurity of the United States. Available online: https://www.phe.gov/s3/law/boards-committees/biosecurity-wg/Pages/default.aspx (accessed on 18 July 2024).
  21. Federal Select Agent Program. Available online: https://www.selectagents.gov/overview/history.htm (accessed on 18 July 2024).
  22. World Health Organization. Guidelines for the Collection of Clinical Specimens during Field Investigation of Outbreaks; WHO: Geneva, Switzerland, 2000. [Google Scholar]
  23. Laboratory Biorisk Management. CWA 15793. Available online: https://internationalbiosafety.org/wp-content/uploads/2019/08/CWA-15793-English.pdf (accessed on 18 July 2024).
  24. World Health Organization. Laboratory Biosafety Manual, 3rd ed.; World Health Organization: Geneva, Switzerland, 2004; ISBN 978-92-4-154650-8. [Google Scholar]
  25. Laboratory Biosafety Manual Fourth Edition. Available online: https://www.who.int/publications/i/item/9789240011311 (accessed on 18 July 2024).
  26. European Commission. National Action Plans. Available online: https://food.ec.europa.eu/plants/pesticides/sustainable-use-pesticides/national-action-plans_en (accessed on 18 July 2024).
  27. Presidential Policy Directive 2 (SGP-2). National Strategy to Counter Biological Threats. Available online: https://irp.fas.org/offdocs/ppd/ppd-2.pdf (accessed on 18 July 2024).
  28. World Health Organization. Public Health Response to Biological and Chemical Weapons: WHO Guidance, 2nd ed.; Robinson, J.P., Ed.; World Health Organization: Geneva, Switzerland, 2004; ISBN 978-92-4-154615-7. [Google Scholar]
  29. Goldson, S.L.; Frampton, E.R.; Ridley, G.S. The Effects of Legislation and Policy in New Zealand and Australia on Biosecurity and Arthropod Biological Control Research and Development. Biol. Control. 2010, 52, 241–244. [Google Scholar] [CrossRef]
  30. UN Security Council Resolution 1540 (2004)—UNODA. Available online: https://disarmament.unoda.org/wmd/sc1540/ (accessed on 25 November 2024).
  31. World Health Organization. WHO Guidance on Implementing Regulatory Requirements for Biosafety and Biosecurity in Biomedical Laboratories: A Stepwise Approach; World Health Organization: Geneva, Switzerland, 2020; ISBN 978-92-4-151626-6. [Google Scholar]
  32. Ali, K.; Meyer, E.; Kabir, F. Biorisk Management, Laboratory Acquired Infections and Clinical Containment, Volume II. Front. Public Health 2024, 12, 1368828. [Google Scholar] [CrossRef] [PubMed]
  33. Vennis, I.M.; Boskovic, M.; Bleijs, D.A.; Rutjes, S.A. Complementarity of International Instruments in the Field of Biosecurity. Front. Public Health 2022, 10, 894389. [Google Scholar] [CrossRef]
  34. Joseph, T. Management System Approach for Addressing Biosafety and Biosecurity of Emerging Pathogens in a Biosafety Level-3 Core Facility. Appl. Biosaf. 2021, 26, 210–220. [Google Scholar] [CrossRef]
  35. WHO. Pathogens Prioritization: A Scientific Framework for Epidemic and Pandemic Reserach Preparednesss; WHO: Geneva, Switzerland, 2024. [Google Scholar]
  36. Mallapaty, S. The Pathogens That Could Spark the Next Pandemic. Available online: https://nature.proxyucr.elogim.com/articles/d41586-024-02513-3 (accessed on 24 January 2025).
  37. Klotz, L.C.; Sylvester, E.J. The Consequences of a Lab Escape of a Potential Pandemic Pathogen. Front. Public Health 2014, 2, 116. [Google Scholar] [CrossRef]
  38. Merler, S.; Ajelli, M.; Fumanelli, L.; Vespignani, A. Containing the Accidental Laboratory Escape of Potential Pandemic Influenza Viruses. BMC Med. 2013, 11, 252. [Google Scholar] [CrossRef]
  39. Holmes, E.C.; Goldstein, S.A.; Rasmussen, A.L.; Robertson, D.L.; Crits-Christoph, A.; Wertheim, J.O.; Anthony, S.J.; Barclay, W.S.; Boni, M.F.; Doherty, P.C.; et al. The Origins of SARS-CoV-2: A Critical Review. Cell 2021, 184, 4848–4856. [Google Scholar] [CrossRef] [PubMed]
  40. Rozo, M.; Gronvall, G.K. The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate. mBio 2015, 6, e01013-15. [Google Scholar] [CrossRef] [PubMed]
  41. Lim, P.L.; Kurup, A.; Gopalakrishna, G.; Chan, K.P.; Wong, C.W.; Ng, L.C.; Se-Thoe, S.Y.; Oon, L.; Bai, X.; Stanton, L.W.; et al. Laboratory-Acquired Severe Acute Respiratory Syndrome. N. Engl. J. Med. 2004, 350, 1740–1745. [Google Scholar] [CrossRef]
  42. Parry, J. Breaches of Safety Regulations Are Probable Cause of Recent SARS Outbreak, WHO Says. BMJ 2004, 328, 1222. [Google Scholar] [CrossRef] [PubMed]
  43. Liang, W.-N.; Zhao, T.; Liu, Z.-J.; Guan, B.-Y.; He, X.; Liu, M.; Chen, Q.; Liu, G.-F.; Wu, J.; Huang, R.-G.; et al. Severe Acute Respiratory Syndrome—Retrospect and Lessons of 2004 Outbreak in China. Biomed. Environ. Sci. 2006, 19, 445–451. [Google Scholar] [PubMed]
  44. WHO. WHO-Convened Global Study of Origins of SARS-CoV-2: China Part; COVID-19: Animal-Human Interface and Food Safety; WHO: Geneva, Switzerland, 2021. [Google Scholar]
  45. Pappas, G. The Lanzhou Brucella Leak: The Largest Laboratory Accident in the History of Infectious Diseases? Clin. Infect. Dis. 2022, 75, 1845–1847. [Google Scholar] [CrossRef]
  46. CDC. Bioterrorism and Anthrax: The Threat. Available online: https://www.cdc.gov/anthrax/bioterrorism/index.html (accessed on 18 July 2024).
  47. Khorram-Manesh, A.; Brukle, F.M., Jr.; Goniewicz, K. Pandemics: Past, Present, and Future: Multitasking Challenges in Need of Cross-Disciplinary, Transdisciplinary, and Multidisciplinary Collaborative Solutions. PHRP 2024, 15, 267–285. [Google Scholar] [CrossRef]
  48. Khorram-Manesh, A.; Goniewicz, K.; Burkle, F.M. Unleashing the Global Potential of Public Health: A Framework for Future Pandemic Response. J. Infect. Public Health 2024, 17, 82–95. [Google Scholar] [CrossRef]
  49. Ward, R.J.; Mark Jjunju, F.P.; Kabenge, I.; Wanyenze, R.; Griffith, E.J.; Banadda, N.; Taylor, S.; Marshall, A. FluNet: An AI-Enabled Influenza-Like Warning System. IEEE Sens. J. 2021, 21, 24740–24748. [Google Scholar] [CrossRef]
  50. WHO. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report: 2022; Global Antimicrobial Resistance and Use Surveillance System (GLASS); WHO: Geneva, Switzerland, 2022. [Google Scholar]
  51. Syrowatka, A.; Kuznetsova, M.; Alsubai, A.; Beckman, A.L.; Bain, P.A.; Craig, K.J.T.; Hu, J.; Jackson, G.P.; Rhee, K.; Bates, D.W. Leveraging Artificial Intelligence for Pandemic Preparedness and Response: A Scoping Review to Identify Key Use Cases. NPJ Digit. Med. 2021, 4, 1–14. [Google Scholar] [CrossRef]
  52. AlShammari, W.; Alhussain, H.; Rizk, N.M. Risk Management Assessments and Recommendations Among Students, Staffs, and Health Care Workers in Educational Biomedical Laboratories. Risk Manag. Healthc. Policy 2021, 14, 185–198. [Google Scholar] [CrossRef] [PubMed]
  53. El Jaouhari, M.; Striha, M.; Edjoc, R.; Bonti-Ankomah, S. Healthcare-Associated Infections & Antimicrobial Resistance: Laboratory-Acquired Infections in Canada from 2016 to 2021. Can. Commun. Dis. Rep. 2022, 48, 303. [Google Scholar] [PubMed]
Figure 1. Process of literature selection according to PRISMA flow chart, adapted from Page et al. [15].
Figure 1. Process of literature selection according to PRISMA flow chart, adapted from Page et al. [15].
Amh 70 00011 g001
Figure 2. Distribution of relative proportion of laboratory-acquired infection (LAI) cases caused by various pathogen types. Each segment is color coded by pathogen type (bacteria, virus, fungus, parasite, and prion) and labeled with corresponding case count and percentage.
Figure 2. Distribution of relative proportion of laboratory-acquired infection (LAI) cases caused by various pathogen types. Each segment is color coded by pathogen type (bacteria, virus, fungus, parasite, and prion) and labeled with corresponding case count and percentage.
Amh 70 00011 g002
Figure 3. Case number of laboratory-acquired infections, for each geographical country from 1974 to 2024. This world map provides a global view of the reported cases of LAIs, categorized by country. Countries are color-coded based on the number of documented cases: lighter shades represent fewer cases (1–10), while darker shades indicate higher case counts (101–1000+).
Figure 3. Case number of laboratory-acquired infections, for each geographical country from 1974 to 2024. This world map provides a global view of the reported cases of LAIs, categorized by country. Countries are color-coded based on the number of documented cases: lighter shades represent fewer cases (1–10), while darker shades indicate higher case counts (101–1000+).
Amh 70 00011 g003
Figure 4. Laboratory-acquired infection reported incidents, for each geographical region for the period from 1974 to 2024. This world map provides a global view of the reported incidents of LAIs, categorized by country. Countries are color-coded based on number of documented cases: lighter shades represent fewer cases (1–5), while darker shades indicate higher case counts (11–101+).
Figure 4. Laboratory-acquired infection reported incidents, for each geographical region for the period from 1974 to 2024. This world map provides a global view of the reported incidents of LAIs, categorized by country. Countries are color-coded based on number of documented cases: lighter shades represent fewer cases (1–5), while darker shades indicate higher case counts (11–101+).
Amh 70 00011 g004
Figure 5. Chronological overview of the number of reported laboratory-acquired incidents and regulations from 1974 to 2024. (a) Biological and Toxin Weapons Convention (WHO). (b) The term “biosecurity” was used for the first time. (c) Guidelines for clinical specimen collection during outbreak field investigation (WHO/CDS/CSR/EDC). (d) Public health response to biological and chemical weapons (WHO). (e) Fink report: National Research Council of the National Academies USA. (f) United Nations Security Council Resolution 1540. (g) WHO laboratory biosafety manual. (h) Biological risk management: laboratory biosafety guidance (WHO/CDS/EPR). (i) Biosecurity as a key element in the European Union’s Animal Health Strategy. (j) Biosecurity in the European Centre for Disease Prevention and Control (ECDC) national plan. (k) Executive Order (EO) 13486, Strengthening Laboratory Biosafety in the United States. (l) Presidential Policy Directive 2 (SGP-2), National Strategy to Counter Biological Threats. (m) Executive order 13546, optimizing the safety of selected biological agents and toxins in the United States. (n) Laboratory Biohazard Management Standard CWA 15793. (o) WHO guidance on implementing regulatory requirements for biosafety and biosecurity in biomedical laboratories. (p) Biosafety in the laboratory manual, 4th edition WHO Biosafety in the Laboratory [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31].
Figure 5. Chronological overview of the number of reported laboratory-acquired incidents and regulations from 1974 to 2024. (a) Biological and Toxin Weapons Convention (WHO). (b) The term “biosecurity” was used for the first time. (c) Guidelines for clinical specimen collection during outbreak field investigation (WHO/CDS/CSR/EDC). (d) Public health response to biological and chemical weapons (WHO). (e) Fink report: National Research Council of the National Academies USA. (f) United Nations Security Council Resolution 1540. (g) WHO laboratory biosafety manual. (h) Biological risk management: laboratory biosafety guidance (WHO/CDS/EPR). (i) Biosecurity as a key element in the European Union’s Animal Health Strategy. (j) Biosecurity in the European Centre for Disease Prevention and Control (ECDC) national plan. (k) Executive Order (EO) 13486, Strengthening Laboratory Biosafety in the United States. (l) Presidential Policy Directive 2 (SGP-2), National Strategy to Counter Biological Threats. (m) Executive order 13546, optimizing the safety of selected biological agents and toxins in the United States. (n) Laboratory Biohazard Management Standard CWA 15793. (o) WHO guidance on implementing regulatory requirements for biosafety and biosecurity in biomedical laboratories. (p) Biosafety in the laboratory manual, 4th edition WHO Biosafety in the Laboratory [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31].
Amh 70 00011 g005
Table 1. Laboratory biosafety levels and associated microorganisms.
Table 1. Laboratory biosafety levels and associated microorganisms.
Safety LevelDescription of Permissible Microorganisms
Biosafety Level 1 (BSL-1)Agents unlikely to cause disease in healthy adults that pose minimal laboratory exposure and infection risk.
Biosafety Level 2 (BSL-2)Agents that may cause moderate human disease and can result in severe illness or death through exposure via inhalation, ingestion, or skin absorption.
Biosafety Level 3 (BSL-3)Agents that can cause serious or fatal human disease through inhalation, ingestion, or skin absorption.
Biosafety Level 4 (BSL-4)Agents that cause extremely dangerous and fatal human diseases through airborne transmission.
Table 2. Definitions of LAI causes.
Table 2. Definitions of LAI causes.
CauseDefinition
Procedural errorImproper selection or use of personal protective equipment (PPE) or primary containment devices, inadequate training, incorrect techniques or procedures, or mishandling of specimens.
AccidentUnintended exposure to a pathogen despite adherence to adequate safety procedures through incidents such as cuts from glass shards, animal bites, needlestick injuries, or splashes and spills.
IntentionalDeliberate actions carried out with the intent to cause harm due to the intentional misuse of biological agents to compromise safety or security.
Not statedThe cause of the LAI is not mentioned or specified in the literature.
Multiple causes A specific cause is not reported, but rather a combination of several factors that triggered the incident.
Table 3. Percentage of reported incidents by type of pathogen (bacteria, virus, fungus, parasite, and prion) and associated cause (accident, procedural error, multiple causes, not stated, intentional, or unknown).
Table 3. Percentage of reported incidents by type of pathogen (bacteria, virus, fungus, parasite, and prion) and associated cause (accident, procedural error, multiple causes, not stated, intentional, or unknown).
BacteriaVirusFungusParasitePrion
Accident22.5%48.7%30.0%50.0%33.3%
Procedural error38.3%18.0%10.0%20.0%-
Multiple causes2.0%1.3%---
Not stated36.0%32.1%60.0%30.0%66.7%
Intentional0.8%----
Unknown0.4%----
Table 4. Distribution of most common laboratory-acquired infections, classified by pathogen.
Table 4. Distribution of most common laboratory-acquired infections, classified by pathogen.
Pathogen Total Case NumberPercentage (%)
Brucella spp.10,79490.6%
Anthrax (Bacillus anthracis)2051.7%
Coxiella burnetii1491.6%
Hemorrhagic fever with renal syndrome virus 1401.2%
CCHF-like virus750.6%
Salmonella spp.700.6%
West Nile virus550.5%
SARS-CoV-2540.5%
SARS-CoV340.3%
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Zavaleta-Monestel, E.; Rojas-Chinchilla, C.; Anchía-Alfaro, A.; Quesada-Loría, D.; García-Montero, J.; Arguedas-Chacón, S.; Hanley-Vargas, G. Tracking the Threat, 50 Years of Laboratory-Acquired Infections: A Systematic Review. Acta Microbiol. Hell. 2025, 70, 11. https://doi.org/10.3390/amh70020011

AMA Style

Zavaleta-Monestel E, Rojas-Chinchilla C, Anchía-Alfaro A, Quesada-Loría D, García-Montero J, Arguedas-Chacón S, Hanley-Vargas G. Tracking the Threat, 50 Years of Laboratory-Acquired Infections: A Systematic Review. Acta Microbiologica Hellenica. 2025; 70(2):11. https://doi.org/10.3390/amh70020011

Chicago/Turabian Style

Zavaleta-Monestel, Esteban, Carolina Rojas-Chinchilla, Adriana Anchía-Alfaro, Diego Quesada-Loría, Jonathan García-Montero, Sebastián Arguedas-Chacón, and Georgia Hanley-Vargas. 2025. "Tracking the Threat, 50 Years of Laboratory-Acquired Infections: A Systematic Review" Acta Microbiologica Hellenica 70, no. 2: 11. https://doi.org/10.3390/amh70020011

APA Style

Zavaleta-Monestel, E., Rojas-Chinchilla, C., Anchía-Alfaro, A., Quesada-Loría, D., García-Montero, J., Arguedas-Chacón, S., & Hanley-Vargas, G. (2025). Tracking the Threat, 50 Years of Laboratory-Acquired Infections: A Systematic Review. Acta Microbiologica Hellenica, 70(2), 11. https://doi.org/10.3390/amh70020011

Article Metrics

Back to TopTop