Prevention of Laboratory Animal Allergy and Impact of COVID-19 on Prevention Programs in the United States

A National Survey 10-Year Update

Abstract

Objective 

Laboratory animal allergy (LAA) is common and preventable. This study provides a 10-year update on LAA prevention programs in the United States and the effect of COVID-19 on prevention practices.

Methods 

An electronic survey was e-mailed to designated institutional officials at laboratory animal facilities identified by the National Institutes of Health Office of Laboratory Animal Welfare. Results were compared with the prior survey.

Results 

A total of 141 institutions employing 58,224 laboratory animal workers responded. Results were similar to the prior survey with wide variation in practices. Medical surveillance increased (58%–71%), but N95 respirator use decreased (17%–13%). As before, only 25% of institutions knew their LAA incidence and prevalence rates. COVID-19 had a small time-limited effect on personal protective equipment use.

Conclusions 

Universal use of evidence-based practices and improved medical surveillance would provide greater worker protection from LAA.

In Brief

Respiratory allergy and asthma to laboratory animals are common and preventable using engineering, administrative, and work practice controls, along with PPE (including reparatory protection) and tracked using medical surveillance. In this 10-year follow-up national survey of prevention practices, wide variation in practices, controls, and medical surveillance persisted.

CME Learning Objectives

After completing this enduring educational activity, the learner will be better able to:

• Discuss approaches to prevent allergy and asthma from exposure to laboratory animals in research settings
• Summarize the findings of the use of preventive measures in this national survey
• Discuss the implications for the use of control measures and medical surveillance as part of an evidence-based program to prevent laboratory animal allergy

Laboratory animal allergy (LAA) is an important occupational disease that affects the health and livelihoods of people who work in laboratory animal research. Animal allergens may induce dermal allergy, respiratory allergy, asthma, or anaphylaxis.^1–3 Respiratory allergy and asthma are common, potentially debilitating, and require a multifaceted prevention strategy. Cross-sectional studies have reported wide variations in the prevalence of LAA, from 11% to 44%.² Approximately 4% to 22% of symptomatic individuals will eventually develop occupational asthma.² Early detection of occupational asthma is important because continued exposure may result in persistent asthma and permanent disability.³

Animal allergens are generated in routine laboratory practices and pose a serious health risk to workers. The consequences of exposure depend on personal risk factors and degree of exposure.⁴ Whereas an airborne allergen concentration of 5 ng/m³ has been proposed as a safe level, levels below 1 ng/m³ have been shown to induce symptoms of LAA.^4,5 Because there is no known safe level of exposure, engineering controls, administrative controls, safe work practices, and appropriate use of personal protective equipment (PPE), including respiratory protective equipment (RPE), should be organizational priorities to prevent LAA. Occupational medicine professionals play a further role through medical surveillance, LAA diagnosis, and work restrictions.

A national survey of LAA prevention practices in the United States published in 2012 demonstrated that there was a wide variation in practices with no consistent approach across organizations.⁶ Key findings of that survey included that only about one of four organizations required the use of respirators or knew the incidence and prevalence of LAA, while just slightly more than half mandated medical surveillance.⁶

The primary objective of this study was to provide a 10-year update on LAA prevention practices and control programs in animal laboratory research facilities to determine whether practices have changed to increase worker protection. This survey was conducted 2 years after the beginning of the coronavirus disease 2019 (COVID-19) pandemic, which caused workplace disruptions along with a shortage of PPE and RPE. Since there was a concern that changes in prevention practices could have been a result of these challenges, questions were added to the survey to help understand the effect of the pandemic on animal research and LAA prevention practices.

METHODS

A cross-sectional survey study was undertaken to document current LAA prevention practices and the effect of COVID-19 on animal research. As with the original study, potential survey participants were identified through a Freedom of Information Act request for all listed designated institutional officials at laboratory animal care facilities from the National Institutes of Health (NIH) Office of Laboratory Animal Welfare. A contact list of 881 officials was provided. Participants were questioned about their current (May 2022) LAA prevention practices. An online survey using Qualtrics software asked questions that had been included in the earlier survey on the following topics:

1. The total number of employees exposed to laboratory animal allergens
2. Administrative controls
3. Engineering controls
4. Use and availability of PPE
5. Recommended hygiene practices
6. Medical surveillance
7. LAA diagnostic criteria
8. Prevalence and incidence of LAA
9. Restrictions for workers diagnosed with LAA

To study the impact of the COVID-19 pandemic, questions were added on the following topics:

1. Overall use of research animals and number of people working with them
2. Use of PPE and, specifically, use of respirators (excluding surgical masks)
3. Budget for safety equipment and engineering controls
4. Attention paid by management to animal allergen exposures
5. Training on use of PPE

Aside from the questions pertaining to COVID-19, the survey questions were essentially identical to that of the original study. The only substantive changes were the addition of choices, “HEPA-filtered shavers,” and “HEPA-filtered vacuums” to the list of engineering controls.

The results from this survey were compared with the national survey published in 2012.⁶ For that study, 1,033 contacts were identified. For unclear reasons, many organizations known to conduct research with laboratory animals were not included on the current list of designated contacts provided by the NIH. Consequently, it was not possible to provide a comparison of results by sector.

The study protocol was reviewed by the Duke University Institutional Review Board and determined to be research not involving human subjects.

RESULTS

Online surveys were distributed via email to the 881 contacts provided by the NIH Office of Laboratory Animal Welfare. The survey was accessed by 185 recipients (22%) and completed for 141 institutions (17%). Two responses were not included in the analysis because they came from institutions that worked exclusively with animals not associated with LAA. In the prior study, contact information was provided for 1,033 institutions, and responses were collected from 198 (19%).

Of the responding institutions, the number of employees working with animals ranged from 1 to 5,000. The distribution of respondents was similar to respondents for the 2012 study, with organizations of 15 to 99 laboratory animal workers being the most common (35%), followed by those with 100 to 499 workers (27%) (Supplemental Digital Content, Supplementary Table 1, https://links.lww.com/JOM/B266). The responding institutions represented 58,224 laboratory animal workers. Within an institution, LAA prevention practices were mostly uniform for all the institution's facilities.

Overall, the distribution of responses to all questions was similar for the 2012 and 2022 study.

EXPOSURE CONTROL

Administrative Controls

Reported rates of the use of administrative controls remained largely unchanged, aside from an increase in training workers on LAA (82%–92%). At most institutions, work with research animals was conducted in a dedicated animal facility (96%). However, a significant proportion (58%) of institutions also allowed for work to be conducted outside of the animals' dedicated facilities. Most institutions restricted access to animal rooms (92%). Further restrictions on the handling and disposal of contaminated PPE in animal facilities were employed by most (84%) of the institutions. Showering out upon leaving (17%) was the least commonly reported requirement (Supplemental Digital Content, Supplementary Table 2, https://links.lww.com/JOM/B267).

Work Practice Controls

Work practices were mostly unchanged from the 2012 results. Handwashing remained the most common reported practice (95%), followed by limiting animal density (60%) and designing processes to reduce animal handling (58%). The use of wet preparation for shaving, a practice that reduces exposure but can also chill animals, decreased (20%–13%) (Supplemental Digital Content, Supplementary Table 3, https://links.lww.com/JOM/B268). It is possible that some institutions substituted high-efficiency particulate air (HEPA)–filtered shavers, although this equipment was only used by 9% (Supplemental Digital Content, Supplementary Table 4, https://links.lww.com/JOM/B269).

Engineering Controls

Various engineering control methods can remove or reduce animal allergens. Multiple types of engineering controls were utilized by almost all institutions reporting their use. Increased rates of use were reported for separately ventilated cages (65%–76%), biologic safety cabinets (74%–86%), and downdraft tables (37%–49%). High-efficiency particulate air–filtered vacuums were used by 39%. The use of robotic equipment was uncommon, reported by only 4% of institutions (Supplemental Digital Content, Supplementary Table 4, https://links.lww.com/JOM/B269).

Personal Protective Equipment

While no notable changes in mandatory PPE use rates were observed between surveys, institutions again reported significant variation in the rates of use. Although inadequate to protect against allergens, surgical mask use, which does not provide protection from allergens, increased from 43% to 59%. Most institutions (~90%) used gloves and uniforms. Mandatory use of respirators remained limited and declined slightly, with N95 respirators used by 13% of institutions, powered air-purifying respirators by 5%, and cartridge air-purifying respirators by 2% (Supplemental Digital Content, Supplementary Table 5, https://links.lww.com/JOM/B270). While mandatory PPE rates changed little, the availability of optional PPE increased for some workers. More than three fourths of the institutions had some form of optional respiratory protection available (Supplemental Digital Content, Supplementary Table 6, https://links.lww.com/JOM/B271). Modest increases were seen in availability of shoe and clothing covers. Whereas the use of hair covers increased, it remained below 50%. For tasks that generate high levels of allergens, such as cage cleaning and washing, only about 40% of institutions mandated respiratory protection, an increase from 2012 (Table 1; Supplemental Digital Content, Supplementary Table 7, https://links.lww.com/JOM/B296). There was no substantial difference in the use of PPE by task between organizations that reported knowing the incidence of LAA (Table 2) or when compared with the prior survey (Supplemental Digital Content, Supplementary Table 7, https://links.lww.com/JOM/B296).

TABLE 1 - Mandatory PPE Used to Reduce Exposure to Animal Allergens (Responses Are Not Mutually Exclusive)

Mandatory PPE Required Only for Specific Tasks (2022)	Cage Cleaning	Cage Washing	Animal Care	Dosing	Surgery	Necropsy
N95 air-purifying respirators	28.5	26.0	15.4	9.8	11.4	13.8
Cartridge air-purifying respirators	4.1	4.1	3.3	2.4	1.6	2.4
Powered air-purifying respirators	7.3	8.1	4.1	2.4	2.4	5.7
Surgical masks*	46.3	39.8	49.6	46.3	69.1	54.5
Shoe covers	45.5	43.9	51.2	37.4	52.8	43.9
Uniforms/clothing cover	80.5	78.0	82.1	70.7	75.6	71.5
Hair covers	42.3	42.3	40.7	30.9	53.7	36.6
Gloves	81.3	77.2	85.4	79.7	82.9	80.5
None	1.6	1.6	1.6	1.6	1.6	1.6

*Surgical masks are not actually PPE but were included to capture this common practice.

TABLE 2 - Among Institutions With Known LAA Incidence, Mandatory PPE Used to Reduce Exposure to Animal Allergens (Responses Are Not Mutually Exclusive)

Mandatory PPE Required Only for Specific Tasks Among Organizations With Known LAA Incidence (2022)	Cage Cleaning	Cage Washing	Animal Care	Dosing	Surgery	Necropsy
N95 air-purifying respirators	34.5	27.6	13.8	17.2	13.8	13.8
Cartridge air-purifying respirators	3.4	0	3.4	3.4	0	3.4
Powered air-purifying respirators	6.9	0	0	0	0	3.4
Surgical masks*	51.7	48.3	51.7	51.7	62.1	58.6
Shoe covers	58.6	55.2	69.0	58.6	65.5	58.6
Uniforms/clothing cover	82.8	79.3	82.8	69.0	72.4	65.5
Hair covers	37.9	37.9	48.3	34.5	44.8	34.5
Gloves	86.2	86.2	93.1	89.7	93.1	86.2
None	3.4	3.4	3.4	3.4	3.4	3.4

*Surgical masks are not actually PPE but were included to capture this common practice.

Medical Surveillance

From 2012 to 2022, the use of mandatory preplacement assessments increased from 76% to 83%. Mandatory LAA medical surveillance for all workers increased from 58% to 71% (Supplemental Digital Content, Supplementary Table 8, https://links.lww.com/JOM/B273). Larger organizations were more likely to conduct medical surveillance (Fig. 1). Among those conducting medical surveillance, clinical examinations were conducted by about half of the respondents, whereas the routine use of allergen testing was uncommon (Supplemental Digital Content, Supplementary Table 9, https://links.lww.com/JOM/B274). Surveillance findings continued to be reviewed almost entirely with individual employees. Although about 25% of institutions reported data on the incidence and prevalence of LAA, analysis of group surveillance data was performed by only 5%.

FIGURE 1: Medical surveillance for LAA is more likely to be conducted by organizations with larger animal research workforces.

Work Restrictions

No significant changes in institutional work restriction policies for employees with LAA were observed. Slightly more than half of employers considered excluding or restricting workers with nonasthma LAA from working with animals. Roughly one third of employers allowed for continued work with restrictions. Less commonly, workers were excluded from working with the species to which they were allergic (7%) or from any type of work with animals (0.8%) (Supplemental Digital Content, Supplementary Table 10, https://links.lww.com/JOM/B275).

As compared with the 2012 survey, employers again were more likely to exclude work or impose restrictions on workers with LAA asthma in their work with animals. Slightly less than two thirds of employers considered excluding or restricting these workers depending on the severity of their disease. Workers with asthma were excluded entirely from work with all animals at 5% of institutions and from working with the specific species to which they were allergic by 16% (Supplemental Digital Content, Supplementary Table 11, https://links.lww.com/JOM/B276).

Definition of Respiratory LAA

The definition of respiratory LAA was based on symptoms in nearly all institutions. While the use of a clinical examination to establish the diagnosis changed a little (72%–66%), reliance on RAST and skin prick testing decreased (Supplemental Digital Content, Supplementary Table 12, https://links.lww.com/JOM/B277).

Prevalence and Incidence of LAA

As with the previous study, three fourths of institutions were unaware of LAA prevalence and incidence rates. When stratified by organizational size, knowledge of prevalence and incidence rates was more commonly known among small organizations (<15 workers) when compared with larger organizations (Fig. 2). Overall, nearly a quarter of institutions knew their LAA prevalence and incidence rates. Among those who provided information on prevalence, the rates ranged from 0% to 15%, with a mean of 2.8%. Incidence rates ranged from 0% to 5%, with a mean of 0.33%. In the 2012 survey, prevalence rates ranged from 0% to 75%, and incidence rates ranged from 0% to 18%.

FIGURE 2: Knowledge of LAA prevalence and incidence by size of workforce.

COVID-19 IMPACT

Workforce

During the early stage of the COVID-19 pandemic, from March to May of 2020, about one third of institutions substantially reduced the use of animals and the number of workers involved in animal research. About 5% temporarily stopped the use of animals for research, while a similar percentage increased research (Supplemental Digital Content, Supplementary Table 13, https://links.lww.com/JOM/B278, Supplementary Table 14, https://links.lww.com/JOM/B279).

Compared with before the pandemic, at the time of the survey in April 2022, the use of animals for research continued or increased in three fourths of institutions and was decreased substantially in only 2.5%. Similarly, the number of employees working with animals remained unchanged or increased for about 80% of institutions and was decreased substantially in only 2.5% (Supplemental Digital Content, Supplementary Table 15, https://links.lww.com/JOM/B280, and Supplementary Table 16, https://links.lww.com/JOM/B281).

PPE Use and Supply

During the COVID-19 pandemic, only 12% of institutions reported temporary limitations in the use of PPE (Supplemental Digital Content, Supplementary Table 17, https://links.lww.com/JOM/B282). Three fourths of institutions reported no change in respirator use (Supplemental Digital Content, Supplementary Table 18, https://links.lww.com/JOM/B283). Most (87%) felt that their safety budget was adequate, and 11% felt that their budget was inadequate but that it had also been inadequate before the pandemic (Supplemental Digital Content, Supplementary Table 19, https://links.lww.com/JOM/B284). Management's attention to prevention practices and PPE use remained unchanged for 80% of institutions and increased for 15% of institutions (Supplemental Digital Content, Supplementary Table 20, https://links.lww.com/JOM/B285). Training on proper use of PPE increased for almost a quarter and was unchanged for the rest (Supplemental Digital Content, Supplementary Table 21, https://links.lww.com/JOM/B286).

DISCUSSION

In this 10-year follow-up to a national survey of LAA prevention practices, results are strikingly similar to those from the earlier survey with only small differences across most categories. Institutions continue to report a wide variation in practices with inconsistent use of preventive approaches. Whereas there was a small (approximately 10%) increase in the use of medical surveillance and some engineering controls (separately ventilated cages, biological safety cabinets, and downdraft tables), there were no changes in the use of other controls and respirator use decreased. Some variation in practice was anticipated given differences in represented industries, animal species, organizational sizes, and facilities design. However, it is likely that many of these practices have persisted because of individual and institutional preferences.

There are several possible explanations for the observed variation in practice and the lack of significant progress in worker protection for 10 years. Along with the need to protect workers, there is an appropriate focus on the protection of animals from infection. However, some of the laboratory animal science literature on the use of PPE in animal facilities that may influence practice does not address the importance of also reducing allergen exposure.^7–9

It is possible that some institutions consider their preventive efforts to be sufficient but lack data to fully evaluate their programs, as most respondents (~75%) were unaware of the incidence and prevalence of LAA at their institution and only 5% reviewed medical surveillance findings on a group basis. Of those reporting prevalence rates, they were substantially below those found in the published literature with a prevalence of 0% often reported.¹⁰ This is unexpected because many technicians, scientists, and veterinarians have developed LAA as students or in working for other organizations.² Folletti et al¹⁰ found that LAA rates were not decreasing for 25 years in a 2008 review. Although the respondents reported rates could be accurate, they are more likely to be underestimates. One reason for the possible discrepancy may be that many medical surveillance programs now use online questionnaires on which workers may be less likely to indicate health concerns. Employees may report health concerns more fully when meeting in-person with an occupational health professional.

Variation in practice may also be due to the lack of an official LAA prevention regulation. Although National Institute of Occupational Safety and Health (NIOSH) published an Alert in 1998 on asthma associated with laboratory animal work with recommendations for prevention and subsequently updated their website to incorporate allergy, there is no Occupational Safety and Health Administration (OSHA) standard addressing LAA.¹¹ However, there is a large evidence base with numerous publications that supports best practice recommendations.^12–24

The use of administrative, engineering, and work practice controls along with PPE (including respiratory protection) has long been recommended for minimizing exposure to laboratory animal allergens.^2,4,12 As no known safe level of allergen concentration exists, organizations should strive to maintain allergen concentrations as low as feasible.

Programs that reduce exposure can prevent allergy.^13–16 Larese Filon et al¹⁵ demonstrated a reduction in sensitization from 25.6% in 2001 to 2004 to 8.2% in 2013 to 2016 through a comprehensive prevention effort in a university setting among a workforce of 467 for 16 years. Key elements of their program included limiting facilities access, wet cleaning practices, use of local exhaust ventilation, HEPA-filtered room ventilation, dust-free bedding, and mandated use of high efficiency PP3 respirators (similar to N99).¹⁵ A 10-year study of a LAA prevention program at a pharmaceutical company showed that a comprehensive prevention program, including mandatory respirator use, reduced the development of symptomatic first allergy to animals to zero or near zero, although this level of protection did not prevent the development of additional allergies to new animal species among those with allergy to at least one species.^13,14

Among respondents, there was wide variation in use of administrative practices, work practices, and engineering controls. Although nearly all organizations continued to restrict access to animal facilities, other containment procedures such as the limiting of animal use to dedicated facilities, showering out after a shift, and providing separate lockers for clean clothes were much less common. These practices are important considerations in LAA prevention programs because they potentially protect coworkers who do not handle animals from exposures.¹⁷

In addition to limiting exposure by animal and nonanimal handling employees, institutions should also take action to protect against take home exposures. Children of laboratory animal workers have been found to be sensitized to laboratory animals to which they otherwise would not have been exposed.¹⁸ The transfer of animal allergens to a worker's hair is a documented source of paraoccupational exposure.^19,20 Krop et al¹⁹ detected animal allergens on laboratory animal workers' mattresses secondary to allergens brought home on exposed workers' hair. Hair nets were shown to be effective in limiting the spread of animal allergens to workers' homes. However, only two of five institutions reported the mandatory use of hair coverings in both surveys.

In this survey, work practices of limiting animal cage density, reducing animal handling, and room cleaning procedures that minimize exposure remained the most common work practices and were used by roughly two thirds of institutions. These work practices are important components in any LAA mitigation plan. Thulin et al²¹ found that interventions such as limiting cage density, using automated cleaners, and using central ventilated vacuums led to significant decreases in airborne allergen exposure. However, despite their effectiveness, the reported use of these evidence-based work practices has not increased since the initial survey.

Individually ventilated cages (IVCs) offer protections for both the animals and workers by providing separated controlled environments and reducing aeroallergen levels. As demonstrated by Renström et al,²² the introduction of IVCs led to 30- and 50-fold reductions in allergen levels when compared with traditional open cages. These reductions in allergens are associated with lower rates of symptomatic workers. Schweitzer et al⁵ reported a symptomatic worker rate of 45.9% in rooms with the highest allergen concentrations (2.3 ± 0.4 ng/m³), compared with 12.9% symptomatic workers in the rooms with the lowest concentrations (0.14 ± 0.02 ng/m³) that used IVCs. It is encouraging that adoption of IVCs increased to 76% of institutions compared with 65% in the prior survey. Although IVCs are very effective when sealed, respiratory protection should be used whenever unsealed IVC systems are operated at positive pressure or when opened for cleaning.²³

Great variations in mandatory and optional PPE use persisted. Although controls may be effective in reducing allergen concentrations, adequate protection may require additional PPE and RPE. Respiratory protective equipment should be mandatory unless the use of controls can be shown to reduce allergen concentrations to safe levels. Mandatory RPE use rates were low and decreased from the prior survey. This was not due to the temporary shortage of respirators early in the COVID-19 pandemic. When stratified by task, PPE practices varied significantly between institutions. These differences remained even for higher-risk tasks such as cage washing and cleaning that are typically associated with higher exposure, findings that are similar to the earlier survey.

Mandatory participation in medical surveillance rates increased among institutions. However, surveillance findings continued to be reviewed only on an individual basis. Group surveillance allows organizations to track preimplementation and postimplementation LAA prevention program's measures and annual progress. However, as in the last survey, only a quarter of the institutions knew the prevalence or incidence of LAA.

Given the significant challenges and PPE supply shortages early in the COVID-19 pandemic, questions were added to the survey to explore the effects on PPE use for the laboratory animal workforce. There was little perceived effect of the pandemic on reported PPE use with some increase in safety-related behaviors. Work with laboratory animals also increased.

Limitations

This study had several limitations. The response rate was acceptable for a survey distributed by email at 17%, but this limits the generalizability as a nationally representative sample. Participants who were willing to respond may have a more extensive LAA prevention program in place than nonresponders, and so responses from these participants may reflect higher rates of controls and lower rates of LAA.

To keep the questionnaire brief, several topics were not explored. These include data on the use of industrial hygiene sampling to monitor allergen exposure, measurement of endotoxins (which can contribute to respiratory symptoms²⁵), and efforts to prevent secondary LAA (allergy to additional species after developing LAA to one species), which can develop in settings that protect against the development of primary LAA.¹⁴

CONCLUSION

Laboratory animal workers are at risk for LAA and occupational asthma. Laboratory animal allergy is preventable through a comprehensive program that reduces or eliminates animal allergen exposures. In this 10-year update to a national survey of prevention practices, there continues to be great variation in prevention practices with no significant changes in control measures or PPE use rates. Most institutions are not tracking the incidence or prevalence of LAA, without which they may not be aware of the need to implement additional LAA prevention practices, and workers may not be adequately protected. Universal use of evidence-based practices and improved medical surveillance would provide greater worker protection from LAA.