Supporting advancement of lab animal welfare and scientific integrity in developing countries: ACURET Cage Consortium (ACCON) Project

Abstract

Research involving animals remains an essential tool to increase our understanding of how human and animal bodies work; how diseases affect them and the safety assessment of chemicals, such as pesticides, for their possible effects on human health or the environment; and how diseases can be prevented or treated via developing and testing medicines and vaccines for humans or animals. To achieve high quality science based on animal manipulations and experimentations from developing countries, adequate welfare of the lab animals needs to become sine qua non for all concerned.

ACURET.ORG is in the forefront of promoting humane animal care and use for scientific purposes in developing countries, with focus on Africa, seeking to aid and facilitate aspects of Institutional Lab Animal programmes in addition to its training and education programmes in the last 11 years since its inception and incorporation eight years ago. ACURET has embarked upon a project tagged ‘ACURET Cage Consortium Project’, the provision of re-usable ‘open-top’ cages for mice and rats in place of the many varied artificial housing materials being used to hold such animals in many facilities in Africa. ACURET is seeking old but functional cages and accessories, still ‘fit for purpose’; other animal husbandry and research equipment, as donations from institutions and industry for distribution to institutions in Africa who require them to improve their lab animal welfare programme.

With a phased funding support from Laboratory Animal Ltd., ACURET will be responsible for the collection of donated items from locations, re-package them for sea-shipping to NIMR in Lagos, from where they will be distributed to successful applying institutional animal facilities, on a ‘first come, first served’ basis.

At the heart of the ACURET Cage Consortium Project is the enablement of researchers in Africa to engage in the essence of their research when the welfare of the laboratory animals they care for and use has been affirmed. Ultimately, we anticipate that the project will support raising the bar on Africans skilled in humane animal care and use for scientific purposes in developing countries.

Keywords

Cages animal husbandry lab animal welfare lab animal medicine conventional plastic open cages IVCs rats mice developing countries ACURET

Introduction

The use of animals in experimentation is common in Africa,^1–5 as it occurs in western countries where mice and rats make up approximately 95% of all laboratory animals, with mice the most commonly used animal in biomedical research.⁶ Mice are a commonly selected animal model for a variety of reasons, including small size (facilitating housing and maintenance); short reproductive cycle and lifespan; generally mild-tempered and docile; wealth of information regarding their anatomy, genetics, biology and physiology; and the possibility for breeding genetically manipulated mice and mice that have spontaneous mutations.^6,7

The crisis of reproducibility and validity has become a challenge to the current animal research paradigm, making it essential to apply the highest standards in animal welfare, including animal husbandry and care,⁸ with discussions surrounding evaluation of the predictive value of animal models of disease^9,10 in addition to implementation of Animals in Research: Reporting In Vivo Experiments (ARRIVE)^8–12 and Planning Research and Experimental Procedures on Animals: Recommendations for Excellence (PREPARE)^13,14 guidelines to improve the reporting quality of animal studies.

The use of laboratory mice in contemporary biomedical research is constantly increasing in research, education and testing, especially genetically modified mice, which serve as model organisms for functional studies of human diseases. These animals are housed in an environment which can significantly influence their behaviour and welfare, acting as a potential confounding factor for those studies in which they are utilized.⁸ The housing environment of laboratory animals has been demonstrated to have a significant influence on the behaviour, physiology, pathology and brain development of the animals housed within, thereby potentially impacting upon the comparability and reproducibility of the data generated.^15–17

One important aspect of the housing environment is the design of the cage itself, and the way it is managed. Traditionally, ‘open’ (conventional) cages are ventilated by the room ventilation system in which they are located.¹⁵ Open cages risk exposure of the animals to microorganisms present in the room and an increased exposure to potential allergens for human workers within the same environment. Animal allergens constitute a serious health risk in laboratory animal facilities. For this reason, and to maintain adequate ventilation, low relative humidity and reduced concentrations of ammonia and CO₂ in the cages, Individually Ventilated Cage (IVC) systems have been developed that aim to ameliorate these problems.^18–22 However, very few Institutions in Africa breed and use transgenic mice, hence the use of the open cages is still efficient and cost effective.

Housing environment of laboratory animals

Conventional (open-top) caging

There are strict international rules on what type of cage you can put the animals in, and how many animals you can have in one cage. In this housing paradigm standard cages fitted with a wire bar lid, absent of filter top, are placed directly onto a rack or shelf and the cage interior is directly open to the room environment (Figure 1).¹⁵ While this methodology is low cost and efficient, the biosecurity risk is significantly high, as there is no protection afforded against cage-to-cage spread of microorganisms and potential rodent pathogens. This type of caging practice is still commonly used within a true barrier setting, where robust biocontainment practices are in place at the room level. Another scenario where this type of caging practice is still used is in infectious disease research where the quick spread of pathogens from cage-to-cage is necessary.

Figure 1.

A comparison of types of cages. (With permission from the publisher.¹⁵)

The advantages to conventional (open-top) caging include: (a) low cost; (b) ease of use; and (c) ability to quickly transmit pathogens from cage to cage.

The disadvantages to conventional (open-top) caging include: (a) high biosecurity risk; (b) inability to contain microorganisms and pathogens; and (c) effective primarily in a true barrier setting.

In spite of the benefits of IVCs and risk associated with open-top cages in lab animal housing, many facilities in developing countries are not yet ready to use IVCs owing to poor resources and lack of efficient systems and infrastructures such as electricity and water supply. One must consider a variety of factors in deciding upon the most appropriate rodent housing system to use. The weight placed on any of these factors is specific to each institution and its resources as well as research programmes. While some generalizations can be made, none would assure or exclude the use of any system for housing rodents destined to be used in research. For this reason, keeping to traditional open-top cages for rodents is still appropriate and humane housing for rats and mice in many African institutions. The challenges associated with IVCs will become an additional burden if introduced now. Therefore, in utilizing open-top cages, a minimal requirement for the building becomes essential, in the holding room for instance; ventilation, humidity, temperature and lights, when using a conventional open caging system. When entering a holding room, staff should wear appropriate personal protective equipment (clean cotton suits and shoes, disposable gloves, bonnets and face masks); cages and water bottles should be changed weekly either on mobile stainless-steel tables or in class II cage-changing stations.

Other types of caging systems for rodents include isolators and metabolic cages^23,24 and disposal cages.^25,26 Isolators are specialized caging systems that are used in cases where bioprotection of the animals needs to be very high, for example, very valuable immunocompromised animals, germ-free animals, and gnotobiotics. Metabolic cages allow the researcher to collect information about the animal by collecting samples from the cages. The most commonly used metabolic caging designs house the rat or mouse in a Plexiglas or glass cylinder with a wire mesh floor. All faeces and urine are collected over a period, generally 24 h.

All animals deserve an environment adequate to promote their well-being, either prescribed by legislation or based upon professional judgement. Given the importance of potential welfare influences of cage size on the animals themselves, there is a growing trend and expectation that welfare science should inform regulatory decision-making.^15,16

Refinement almost always results in benefits to both welfare and science²⁷ with majority application involving improvement of project design, euthanasia method and housing and husbandry.²⁸ Refinements in husbandry and optimization of sanitization protocols improve animal wellbeing and help standardize the microenvironment, contributing to research reproducibility. Refinement is a legal and ethical requirement, yet refinements may not always be implemented.²⁷ There are numerous obstacles to the implementation of refinement, which may be real or perceived. Either way, in order to take refinement forward, it is important to coordinate the approach to refinement, validate the science behind refinement, ensure there is adequate education and training in new techniques, improve liaison between users and make sure there is feedback on suitability of refinements for use. Overall, refinement requires a coordinated ongoing process of critical appraisal of practice and active scrutiny of resources for likely improvements.²⁷ The ACCON Project is an implementation of refinement in how housing and husbandry can benefit animal welfare and scientific quality in developing countries.

THE ACCON Project

Inception

ACURET.ORG is a multinational, interdisciplinary chartered organization of professionals, promoting humane animal care and use for scientific purposes in developing countries, mostly in Africa. ACURET was conceived in 2011 in Ilorin, Nigeria, incorporated with CAC Abuja, Nigeria in 2014 and governed by a Board of Trustees (www.acuret.org), geared toward re-orienting the minds of those who use animals in developing countries to take responsibility for their welfare.

To encourage these practices, which are greatly influenced by cultural, religious, socioeconomic and political factors in many African countries, ACURET.ORG seeks to aid and facilitate aspects of Institutional Lab Animal Programmes. The first of these is the provision of re-usable traditional ‘open-top’ cages for mice and rats, in place of the many varied artificial housing materials being used to hold such animals in many facilities in Africa. This is with anticipation for consideration for animal size versus floor space, to reduce overcrowding and enhance enrichment for their socio-behavioural benefits. It will also support proper animal distribution in breeding processes and avoid animals becoming cannibalistic.

With these plastic cages, better husbandry protocols will become the order of the day, enabling regular bedding exchange and easy manual washing. These cages will also provide for proper separation of food, limit contamination of same and allow water to be available ad libitum. Many offerings currently place the food and water in wide rim bowls within the cages, with the result that animals climb into the bowls to feed, followed by contamination, spillage and wetting of the bedding. Add to that the ammonia from their urine; animals eventually stop feeding, a situation that has significant impact upon their physiology and the data obtainable for any kind of manipulation using these kinds of animal husbandry.

It is to ameliorate this situation that ACURET.ORG is seeking every support and assistance to develop and establish what we refer to as the ACURET Cage Consortium (ACCON) Project.

Rationale for the ACCON Project by ACURET.ORG

There is poor investment in lab animal research infrastructure in many developing countries. The result is the unwholesome housing that lab animals are subjected to and the poor quality of science being generated from animal-based experimentations from many Africa countries. The overall goal is an excellent opportunity to ‘demonstrate what is appropriate attitude, practice, tools et cetera, in laboratory animal welfare in the same breath that we expose the inappropriate ways currently exhibited by many in developing countries with a hoping for an attitudinal change’.

The specific goals of the project are:

To stimulate institutional investment for quality assurance through the free distribution of cages to as many facilities applying within the available resources of the consortium, after they would have witnessed the difference and benefit of proper housing from the ACCON Project.

To serve as an opportunity for engaging local mechanical welders in the design and fabrication of steel racks for the sizes and shape of cages obtained as prototype by applying facilities.

To expose Responsible Officials to the properties and features of acceptable minimum standard rodent housing with a view towards informed decision-making where the opportunity avails itself for their selection and purchase.

The project

The ACCON Project will operate in phases (Figure 2):

Figure 2.

Schematic illustration of an overview of the ACCON Project.

Seek, locate and collect used, redundant and unwanted yet functional rodent plastic cages of varying shapes, sizes and designs from different institutions, manufacturers and sellers of such products globally. These will be complete cages with metal mesh covers and water bottles, including record labels.

Request that supporting and participating institutions send their contributory cages to a designated location.

ACURET.ORG will be responsible for collecting from the designated locations, cleaning, packaging and shipping all collected cages to Africa.

ACURE.ORG will be responsible for distribution of the cages based upon predetermined criteria and protocol, needs and requirement of applications from Institutional Lab Animal facilities in Africa.

Duration of the ACCON Project

The project will run for two years (2023–2025) in the first instance, after which it will evaluate the process and progress, challenges and benefits considered, and the impact of the project on humane care and use of lab animals in Africa; and a decision will be taken at that point based upon the success of the project.

Responsibilities, implementation and cost implications of the project

Phase I: aggregation of 3000 cages

An ACURET team composed of ACURET members, affiliate members and international members will manage the project under the chair of the ACURET Principal.

The team will be responsible for seeking and soliciting linkages and support through calls, adverts and direct communications and making contacts on behalf of Cage Consortium Collaboration.

Each supporting and participating institution will be encouraged to be responsible for delivering the cages to the designated collection point.

Phase II: with the aggregation of each batch of 3000 cages

ACURET.ORG will be responsible for sanitation, packaging and shipping of collected cages to designated location in Africa – Nigeria Institute of Medical Research, Lagos (storage).

Phase III: distribution across Africa

ACURET.ORG will be responsible for distributing the cages to needing facilities in Africa based upon a determined process.

ACURET will be responsible for return appreciation to all supporting and participating Institutions.

ACCON Project Management Team

Name Affiliation

Francis-Adelade GO Fakoya ACURET.ORG,

Lagos, Nigeria

(Chair)

Tom Aire SGU, St, George’s, Grenada

‘Femi Odesanmi OAU, Ile-Ife, Nigeria

Julius Haruna Charles Rivers Laboratories,

Montreal, Canada

Otimize Y Masogbor ITR Inc. Quebec, Canada

Oluwagbemiga Aina NIMR, Lagos, Nigeria

Olaide Kareem Salako NIMR, Lagos, Nigeria

Idongesit Owen-Ode ACURET.ORG, Lagos,

Nigeria

Current state of the project

Collectibles

Thus far, we have pledges of over 60 racks, 2000 cages and accessories and bedding waste disposal machines for collection. All items will be collected (Table 1) and packaged for sea transportation from Chelmsford, UK to Lagos, Nigeria. Currently, we are holding items collected in a Safestore in Chelmsford (Figure 3) until we receive sufficient items to fill a 20 foot container, which will then be shipped to Lagos.

Table 1.

List of current donors to the ACCON project.

Institution	Location	Country
University of Nottingham,	Nottingham	UK
Nottingham Trent University	Nottingham	UK
King’s College London	Franklin Wilkins Building, London	UK
King’s College London	Denmark Hill, London	UK

ACCON Project has pledges that will be collected from the listed institutions.

ACCON: ACURET Cage Consortium.

Figure 3.

Photo collage of some collected cages and accessories for the ACURET Cage Consortium Project in storage. Chelmsford, Essex, UK.

Shipping to Lagos

Shipping is contingent upon filling a 20 foot container (cost effective, instead of piecemeal shipping of materials). Items will be packed for safe shipping by sea and loaded into a 20 foot container that will eventually serve as a storage container in Lagos for subsequent cycles of the project in the future.

Distribution of donated materials

Items will be distributed freely on a ‘first come, first served’ basis to requesting institutions in developing countries through an application and selection process based upon determined criteria by the ACURET Board of Trustees. The application process is an open, transparent opportunity for eligible Institutions in any developing country. This will be published on the ACURET website along with the application form. The form will be reviewed by an ACURET selection panel that will make recommendations for approval to the ACURET Board of Trustees.

Eligibility guidelines are designated to promote institutional humane animal care and use programmes for scientific purposes that will boost lab animal welfare. These demonstrable conditions are sine qua non for participation in the project. A project participatory fee will be applied for all successful institutions. This fee, which is nowhere near comparable to the cost of the project deliverables, is necessary to sustain the project to enable shipping and handling as we receive more donations in the future, providing opportunities for more Institutions.

What next?

As part of the monitoring and evaluation programme following allocation of cages and accessories to institutions, ACURET will initiate a series of coordinated visits to the institutions gifted and subsequently to all other institutions that invite or indicate an interest in the process. The objective of the visits will include enlisting such sites as registered animal research facilities under African Consortium of Research Animal facilities. Visits will involve observations of the range of different species and their housing, handling and care, along with surgical sites, storage rooms, offices and libraries. They will also include meetings and conversations with various staff at the sites. While it is anticipated that not every institution will be willing to open their doors or allow their animals and facilities to be visited for concerns of being judged and assessed, efforts will be made to create cordial interactive ambience with the staff, the technicians, investigators and management staff who can discuss the animal care and use programmes at the institutions, for instance, the interaction between the people and the animals, how staff members behave when they enter an animal room and how the animals respond, amongst others.

Anticipated outcomes of the visits

A database of engaging and participating research facilities across the continent for exchange of ideas, personnel, training and project collaboration, and networking and conferencing;

Harmonization of performance standard in lab animal welfare under resource constraint conditions.

Raising the bar on Africans skilled in humane animal care and use for scientific purposes has been a target of ACURET.ORG since 2017, with the formation of its Directorate of Forum, Training and Education. We anticipate that this project will ignite and galvanize further efforts to mitigate some of the challenges facing lab animal welfare and animal-based research in developing countries, in particular, poor research infrastructure, a technology and skill gap, as well as a mind-set inherent within the environment.

In conclusion

We at ACURET hope you will take inspiration from this short piece to support our efforts across developing countries to promote and advance lab animal welfare and scientific integrity as we seek to enhance and enrich the housing and animal husbandry of lab animals that are completely dependent upon us.

We implore anyone involved with animals in laboratories — technicians, veterinarians, scientists, institutional officials, enrichment specialists, IACUC members, and inspectors and their respective institutions – to pledge and donate cages and other research facilities to this consortium project instead of trashing them (Figure 4). Thank you to those who have pledged their support, helping us to move the bar ever higher in animal husbandry. To those who are not there yet, we do not underestimate the task before you in trying to facilitate change, but such change is warranted.

Figure 4.

How can I join?

Ultimately, these are contributions of scientific or technological resources that result in humane experimentation and/or improved animal care practices intended to upgrade animal facilities, develop administratively centralized programmes of animal care, and enable institutions to comply with guidelines and policies related to the care and use of laboratory animals.

This is about not only global best practice standards, but an evidence-based modality that before now was hindered by limitations of resource constraint. These cages will help boost the physiological and behavioural expressions of research animals, offering high yield validity and reproducibility of the data generated in the care and use of these animals. The result is a high degree translational potential from animal-based experimentations.

ACURET will acknowledge your company’s/institution’s contributions to the ACCON Project.

Footnotes

Animal use approval

This work does not involve any animal use.

Acknowledgements

ACURET wishes to appreciate the support and efforts of Mr Andrew Marr, Facility Manager at Nottingham Trent University, Nottingham, UK, whose ingenious networking and communications led to these initial pledges being collected. Alison Ritchie at University of Nottingham; Mike Williams and Jolene Hammonds at King’s College London, respectively. I thank the DG/CEO of NIMR, Lagos, Prof. BL Salako, for partnering to host the 20 foot container within the NIMR premise for safety and security. Finally, I thank the Board of Trustees for approving the project concept and Prof. Tom Aire, Chair of the ACURET Board of Trustees, for evaluating the application process and form.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Laboratory Animal Ltd (grant number LP501 2022).

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