Laboratory-acquired infections and pathogen escapes worldwide between 2000 and 2021: a scoping review.

Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Foot and Mouth Disease Virus.

Introduction: Foot and mouth disease (FMD) is a highly contagious infection of cloven-hoofed animals. The Biosafety Research Road Map reviewed scientific literature regarding the foot and mouth disease virus (FMDV). This project aims to identify gaps in the data required to conduct evidence-based biorisk assessments, as described by Blacksell et al., and strengthen control measures appropriate for local and national laboratories. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections: the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: The available data regarding biosafety knowledge gaps and existing evidence have been collated. Some gaps include the need for more scientific data that identify the specific safety contribution of engineering controls, support requirements for showering out after in vitro laboratory work, and whether a 3- to 5-day quarantine period should be applied to individuals conducting in vitro versus in vivo work. Addressing these gaps will contribute to the remediation and improvement of biosafety and biosecurity systems when working with FMDV.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Crimean Congo Haemorrhagic Fever Virus and Lassa Virus.

Introduction: Crimean Congo Hemorrhagic Fever (CCHF) virus and Lassa virus (LASV) are zoonotic agents regarded as high-consequence pathogens due to their high case fatality rates. CCHF virus is a vector-borne disease and is transmitted by tick bites. Lassa virus is spread via aerosolization of dried rat urine, ingesting infected rats, and direct contact with or consuming food and water contaminated with rat excreta. Methods: The scientific literature for biosafety practices has been reviewed for both these two agents to assess the evidence base and biosafety-related knowledge gaps. The review focused on five main areas, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: There is a lack of data on the safe collection and handling procedures for tick specimens and the infectious dose from an infective tick bite for CCHF investigations. In addition, there are gaps in knowledge about gastrointestinal and contact infectious doses for Lassa virus, sample handling and transport procedures outside of infectious disease areas, and the contribution of asymptomatic carriers in viral circulation. Conclusion: Due to the additional laboratory hazards posed by these two agents, the authors recommend developing protocols that work effectively and safely in highly specialized laboratories in non-endemic regions and a laboratory with limited resources in endemic areas.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Zoonotic Avian Influenza and Mycobacterium tuberculosis.

Introduction: The Biosafety Research Road Map reviewed the scientific literature on a viral respiratory pathogen, avian influenza virus, and a bacterial respiratory pathogen, Mycobacterium tuberculosis. This project aims at identifying gaps in the data required to conduct evidence-based biorisk assessments, as described in Blacksell et al. One significant gap is the need for definitive data on M. tuberculosis sample aerosolization to guide the selection of engineering controls for diagnostic procedures. Methods: The literature search focused on five areas: routes of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination methods. Results: The available data regarding biosafety knowledge gaps and existing evidence have been collated and presented in Tables 1 and 2. The guidance sources on the appropriate use of biosafety cabinets for specific procedures with M. tuberculosis require clarification. Detecting vulnerabilities in the biorisk assessment for respiratory pathogens is essential to improve and develop laboratory biosafety in local and national systems.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Mpox/Monkeypox Virus.

Introduction: The virus formerly known as monkeypox virus, now called mpoxv, belongs to the Orthopoxvirus genus and can cause mpox disease through both animal-to-human and human-to-human transmission. The unexpected spread of mpoxv among humans has prompted the World Health Organization (WHO) to declare a Public Health Emergency of International Concern (PHEIC). Methods: We conducted a literature search to identify the gaps in biosafety, focusing on five main areas: how the infection enters the body and spreads, how much of the virus is needed to cause infection, infections acquired in the lab, accidental release of the virus, and strategies for disinfecting and decontaminating the area. Discussion: The recent PHEIC has shown that there are gaps in our knowledge of biosafety when it comes to mpoxv. We need to better understand where this virus might be found, how much of it can spread from person-to-person, what are the effective control measures, and how to safely clean up contaminated areas. By gathering more biosafety evidence, we can make better decisions to protect people from this zoonotic agent, which has recently become more common in the human population.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in Human and Veterinary Laboratories.

Introduction: Lack of evidence-based information regarding potential biological risks can result in inappropriate or excessive biosafety and biosecurity risk-reduction strategies. This can cause unnecessary damage and loss to the physical facilities, physical and psychological well-being of laboratory staff, and community trust. A technical working group from the World Organization for Animal Health (WOAH, formerly OIE), World Health Organization (WHO), and Chatham House collaborated on the Biosafety Research Roadmap (BRM) project. The goal of the BRM is the sustainable implementation of evidence-based biorisk management of laboratory activities, particularly in low-resource settings, and the identification of gaps in the current biosafety and biosecurity knowledge base. Methods: A literature search was conducted for the basis of laboratory design and practices for four selected high-priority subgroups of pathogenic agents. Potential gaps in biosafety were focused on five main sections, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Categories representing miscellaneous, respiratory, bioterrorism/zoonotic, and viral hemorrhagic fever pathogens were created within each group were selected for review. Results: Information sheets on the pathogens were developed. Critical gaps in the evidence base for safe sustainable biorisk management were identified. Conclusion: The gap analysis identified areas of applied biosafety research required to support the safety, and the sustainability, of global research programs. Improving the data available for biorisk management decisions for research with high-priority pathogens will contribute significantly to the improvement and development of appropriate and necessary biosafety, biocontainment and biosecurity strategies for each agent.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-SARS-CoV-2.

Introduction: The SARS-CoV-2 virus emerged as a novel virus and is the causative agent of the COVID-19 pandemic. It spreads readily human-to-human through droplets and aerosols. The Biosafety Research Roadmap aims to support the application of laboratory biological risk management by providing an evidence base for biosafety measures. This involves assessing the current biorisk management evidence base, identifying research and capability gaps, and providing recommendations on how an evidence-based approach can support biosafety and biosecurity, including in low-resource settings. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections, including the route of inoculation/modes of transmission, infectious dose, laboratory-acquired infections, containment releases, and disinfection and decontamination strategies. Results: There are many knowledge gaps related to biosafety and biosecurity due to the SARS-CoV-2 virus's novelty, including infectious dose between variants, personal protective equipment for personnel handling samples while performing rapid diagnostic tests, and laboratory-acquired infections. Detecting vulnerabilities in the biorisk assessment for each agent is essential to contribute to the improvement and development of laboratory biosafety in local and national systems.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Bacillus anthracis and Brucella melitensis.

Introduction: Brucella melitensis and Bacillus anthracis are zoonoses transmitted from animals and animal products. Scientific information is provided in this article to support biosafety precautions necessary to protect laboratory workers and individuals who are potentially exposed to these pathogens in the workplace or other settings, and gaps in information are also reported. There is a lack of information on the appropriate effective concentration for many chemical disinfectants for this agent. Controversies related to B. anthracis include infectious dose for skin and gastrointestinal infections, proper use of personal protective equipment (PPE) during the slaughter of infected animals, and handling of contaminated materials. B. melitensis is reported to have the highest number of laboratory-acquired infections (LAIs) to date in laboratory workers. Methods: A literature search was conducted to identify potential gaps in biosafety and focused on five main sections including the route of inoculation/modes of transmission, infectious dose, LAIs, containment releases, and disinfection and decontamination strategies. Results: Scientific literature currently lacks information on the effective concentration of many chemical disinfectants for this agent and in the variety of matrices where it may be found. Controversies related to B. anthracis include infectious dose for skin and gastrointestinal infections, proper use of PPE during the slaughter of infected animals, and handling contaminated materials. Discussion: Clarified vulnerabilities based on specific scientific evidence will contribute to the prevention of unwanted and unpredictable infections, improving the biosafety processes and procedures for laboratory staff and other professionals such as veterinarians, individuals associated with the agricultural industry, and those working with susceptible wildlife species.

The Biosafety Research Road Map: The Search for Evidence to Support Practices in the Laboratory-Shigella spp.

Introduction: Shigella bacteria cause shigellosis, a gastrointestinal infection most often acquired from contaminated food or water. Methods: In this review, the general characteristics of Shigella bacteria are described, cases of laboratory-acquired infections (LAIs) are discussed, and evidence gaps in current biosafety practices are identified. Results: LAIs are undoubtedly under-reported. Owing to the low infectious dose, rigorous biosafety level 2 practices are required to prevent LAIs resulting from sample manipulation or contact with infected surfaces. Conclusions: It is recommended that, before laboratory work with Shigella, an evidence-based risk assessment be conducted. Particular emphasis should be placed on personal protective equipment, handwashing, and containment practices for procedures that generate aerosols or droplets.

Global Veterinary Diagnostic Laboratory Equipment Management and Sustainability and Implications for Pandemic Preparedness Priorities1.

Substantial investments into laboratories, notably sophisticated equipment, have been made over time to detect emerging diseases close to their source. Diagnostic capacity has expanded as a result, but challenges have emerged. The Equipment Management and Sustainability Survey was sent to the Veterinary Services of 182 countries in mid-2019. We measured the status of forty types of laboratory equipment used in veterinary diagnostic laboratories. Of the 68,455 items reported from 227 laboratories in 136 countries, 22% (14,894/68,455) were improperly maintained, and 46% (29,957/65,490) were improperly calibrated. Notable differences were observed across World Bank income levels and regions, raising concerns about equipment reliability and the results they produce. Our results will advise partners and donors on how best to support low-resource veterinary laboratories to improve sustainability and fulfill their mandate toward pandemic prevention and preparedness, as well as encourage equipment manufacturers to spur innovation and develop more sustainable products that meet end-users' needs.

The Impact of Air Inflow and Interfering Factors on the Performance of Microbiological Safety Cabinets.

Introduction: The operator protection factor (OPF) of four biological safety cabinets (BSCs) has been measured under standard and suboptimal conditions. Methods: The OPF for one BSC1, two BSC2, and an acid-fast bacilli staining station (AFBSS) was measured using the potassium iodide method for in situ testing of BSCs (CEN12469) over a range of inflow velocities under standard conditions and with common interfering factors (fans, opening doors, and walk pasts). Results: The BSC1 and the AFBSS gave a high level of protection under standard test conditions at all airflows (down to 0.3 and 0.38 m/s, respectively). During interfering processes, the BSC1 and AFBSS gave a high level of protection (OPF >105) at the specified inward airflow. At lower airflows, there was a predictable deterioration in performance. There was a significant difference in performance between the two BSC2s tested, with one model passing all tests under all interfering conditions at all airflows. The second BSC2 failed the standard test at the lowest airflow and provided poor levels of protection (OPF <105) in all tests carried out with interfering processes. Conclusion: Although BSC2s are capable of giving a high level of performance, this is design dependent and the BSC1 and AFBSS give a more predictable level of performance due to their simpler design. In environments where BSC certification is not possible, they may provide more robust and sustainable primary containment.

Microbial Aerosols Generated from Standard Microbiological Laboratory Procedures.

Background: Modern microbiology laboratories are designed to protect workers and the environment from microbial aerosols produced during microbiological procedures and accidents. However, there is only limited data available on the aerosols generated from common microbiology procedures. Methods: A series of common microbiological procedures were undertaken with high concentration spore suspensions while air samplers were operated to sample the aerosols generated. Surface contamination from droplets was visualized using sodium fluorescein within the suspension. A total of 36 procedures were studied using different sample volumes (0.1-10 mL) and two spore suspension titers (107 and 109 colony forming units [cfu]/mL). Results: The aerosol concentrations generated varied from 0 to 13,000 cfu/m3. There was evidence to suggest that titer, volume, and poor use of equipment were significant factors in increased aerosol generation from some of the procedures. A risk assessment undertaken using the data showed that any aerosol generated from these processes would be contained within a correctly operating biological safety cabinet. Therefore, with these procedures, the operator and the environment would not require any additional protective measures such as respiratory protective equipment or a negative pressure laboratory to prevent aerosol exposure or release. Conclusions: Aerosol generation from common laboratory processes can be minimized by reducing sample volumes and concentrations if possible. Training laboratory staff in good microbiological techniques would further mitigate aerosols generated from common laboratory processes.

Dopant activation process in Mg-implanted GaN studied by monoenergetic positron beam.

A process for activating Mg and its relationship with vacancy-type defects in Mg-implanted GaN were studied by positron annihilation spectroscopy. Mg+ ions were implanted with an energy of 10 keV, and the Mg concentration in the subsurface region (≤ 50 nm) was on the order of 1019 cm-3. After the Mg-implantation, N+ ions were implanted to provide a 300-nm-deep box profile with a N concentration of 6 × 1018 cm-3. From capacitance-voltage measurements, the sequential implantation of N was found to enhance the activation of Mg. For N-implanted GaN before annealing, the major defect species were determined to Ga-vacancy related defects such as divacancy. After annealing below 1000 °C, the clustering of vacancies was observed. Above 1200 °C annealing, however, the size of the vacancies started to decrease, which was due to recombinations of vacancy clusters and excess N atoms in the damaged region. The suppression of vacancy clustering by sequential N-implantation in Mg-implanted GaN was attributed to the origin of the enhancement of the Mg activation.

Self-formed compositional superlattices triggered by cation orderings in m-plane Al1-xInxN on GaN.

Immiscible semiconductors are of premier importance since the source of lighting has been replaced by white light-emitting-diodes (LEDs) composed of thermodynamically immiscible InxGa1-xN blue LEDs and yellow phosphors. For realizing versatile deep-ultraviolet to near-infrared light-emitters, Al1-xInxN alloys are one of the desirable candidates. Here we exemplify the appearance and self-formation sequence of compositional superlattices in compressively strained m-plane Al1-xInxN films. On each terrace of atomically-flat m-plane GaN, In- and Al-species diffuse toward a monolayer (ML) step edge, and the first and second uppermost < [Formula: see text]> cation-rows are preferentially occupied by Al and In atoms, respectively, because the configuration of one In-N and two Al-N bonds is more stable than that of one Al-N and two In-N bonds. Subsequent coverage by next < [Formula: see text]> Al-row buries the < [Formula: see text]> In-row, producing nearly Al0.5In0.5N cation-stripe ordering along [0001]-axis on GaN. At the second Al0.72In0.28N layer, this ordinality suddenly lessens but In-rich and In-poor < [Formula: see text]>-rows are alternately formed, which grow into respective {0001}-planes. Simultaneously, approximately 5-nm-period Al0.70In0.30N/Al0.74In0.26N ordering is formed to mitigate the lattice mismatch along [0001], which grow into approximately 5-nm-period Al0.70In0.30N/Al0.74In0.26N {[Formula: see text]} superlattices as step-flow growth progresses. Spatially resolved cathodoluminescence spectra identify the emissions from particular structures.

Photocatalytic NO removal over calcium-bridged siloxenes under ultraviolet and visible light irradiation.

Ca-Bridged siloxenes (Ca-siloxenes) composed of two-dimensional siloxene planes with Ca bridging were prepared and their photocatalytic properties for nitrogen oxide (NO) removal were investigated. Ca-Siloxenes were synthesized via a solid-state metathesis reaction using TaCl5 to extract Ca from CaSi2 with different Cl2/Ca molar ratios of 0.25, 1.25 and 2.5 (CS0.25, CS1.25 and CS2.5, respectively) in an attempt to control the extent of Ca extraction. Ca-Siloxenes have a wide optical absorption band from the visible to ultraviolet region with absorption edges of 1.5, 2.9, and 3.1 eV for CS0.25, CS1.25, and CS2.5, respectively. Ca-Siloxenes exhibited photocatalytic activity for NO removal under irradiation with visible (λ > 400 nm (<3.10 eV)) and ultraviolet light (λ > 290 nm (<4.28 eV)). The photocatalytic activity was particularly improved by mixing the Ca-siloxene with acetylene black as a conductive material, which might have inhibited the recombination of photogenerated electrons and holes. The mixture of Ca-siloxene and acetylene black exhibited improved photocatalytic activity in the presence of 1O2 as one of the active oxygen species formed under ultraviolet light irradiation.

Photocatalytic activity of silicon-based nanoflakes for the decomposition of nitrogen monoxide.

The photocatalytic decomposition of nitrogen monoxide (NO) was achieved for the first time using Si-based nanomaterials. Nanocomposite powders composed of Si nanoflakes and metallic particles (Ni and Ni3Si) were synthesized using a simple one-pot reaction of layered CaSi2 and NiCl2. The synthesized nanocomposites have a wide optical absorption band from the visible to the ultraviolet. Under the assumption of a direct transition, the photoabsorption behavior is well described and an absorption edge of ca. 1.8 eV is indicated. Conventional Si and SiO powders with indirect absorption edges of 1.1 and 1.4 eV, respectively, exhibit considerably low photocatalytic activities for NO decomposition. In contrast, the synthesized nanocomposites exhibited photocatalytic activities under irradiation with light at wavelengths >290 nm (<4.28 eV). The photocatalytic activities of the nanocomposites were confirmed to be constant and did not degrade with the light irradiation time.

Defect-Resistant Radiative Performance of m-Plane Immiscible Al1-x Inx N Epitaxial Nanostructures for Deep-Ultraviolet and Visible Polarized Light Emitters.

Planar vacuum-fluorescent-display devices emitting polarized UV-C, blue, and green light are demonstrated using immiscible Al1-x Inx N nanostructures grown in nonpolar m-directions. Despite the presence of high concentration of nonradiative recombination centers, the Al1-x Inx N nanostructures emit polarized light with the luminescence lifetimes of 22-32 ps at 300 K. This defect-resistant radiative performance suggests supernormal localized characteristics of electron-hole pairs.

Pulse capture without carrier absorption in dynamic Q photonic crystal nanocavities.

We develop a gallium arsenide (GaAs) photonic crystal nanocavity device capable of capturing and releasing a pulse of light by dynamic control of the Q factor through free carrier photoexcitation. Unlike silicon-based devices where the performance of this dynamic optical control is limited by absorption from free carriers with nanosecond-order lifetimes, the short carrier lifetime (∼ 7 ps) of our equivalent GaAs devices enables dynamic control with negligible absorption losses. We capture a 4 ps optical pulse by briefly cycling the Q factor from 40,000 to 7900 and back just as the light couples to the nanocavity and confirm that the captured energy can be subsequently released on demand by a second injection of free carriers. Demonstrating dynamic control with negligible loss in a GaAs nanophotonic device also opens the door to dynamic control of cavity quantum electrodynamics with potential application towards quantum information processing.