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Diagnostics and the challenge of antimicrobial resistance: a survey of UK livestock veterinarians’ perceptions and practices

Background This paper explores the current role and place of diagnostic tests in the treatment of farm animal disease. With the growing focus on reduced reliance on antibiotic medicines in both animal and human patient care, attention is increasingly being focused on the practice, the technology and the function of diagnostic tests and how these can support responsible antimicrobial use. Emerging diagnostic technologies offer the possibility of more rapid testing for bacterial disease, while food chain actors and others are increasingly seeking to make diagnostic tests mandatory before the use of critically important antibiotics. Method This paper reports the findings of a recent large-scale online survey of UK farm animal veterinarians (n=153) which investigated current veterinary diagnostic practice with particular attention to the relationship between diagnostic test use and antibiotic treatment. Results Results revealed a range of factors that influence veterinary diagnostic practice and demonstrate the continuing importance of clinical observation and animal/herd knowledge in the selection of antibiotic treatment. Conclusion The findings identify a considerable ambivalence on the part of farm animal veterinarians regarding the current and future uses of rapid and point-of-care diagnostic tests as a means of improving clinical diagnosis and addressing inappropriate antibiotic medicine use.


INTRODUCTION
Reducing unnecessary and inappropriate use of antibiotics in farm animal production has become a key objective to combatting the emergence and transmission of antimicrobial resistance (AMR) [1,2,3]. To date, attention has largely focused on two approaches. The first approach has been to contest particular rationales for using antibiotics in agriculturewhether these are to stimulate growth promotion (a use banned in the EU since 2006) or to prophylactically guard against the development and spread of endemic disease amongst herds and flocks. The second approach has been to reduce the prescription of particular classes of antibiotics, notably fluoroquinolones, higher order cephalosporins and colistin, considered critically important for human health [4,5].These strategies have already begun to achieve marked reductions in antibiotic use within veterinary medicine in the UK [6,7] . A third approach, which has arguably attracted less attention within the various policy and professional communities until recently, is one that focuses more specifically upon the processes, technologies and practices of veterinary diagnosis as a means to achieve responsible and more accurate antibiotic use. The Review on Antimicrobial Resistance, led by Jim O'Neill, identified the need for better diagnostic tests 'to ensure better-targeted and more appropriate veterinary prescribing' [8], arguing that more rapid tests would allow farmers and veterinarians to intervene in a more timely manner to identify bacterial infection and to prevent disease spread. Others too have identified rapid and point-of-care diagnostic tests as a means to confirm primary disease agents and enable appropriate treatment decisions [9,10]. The European Commission Guidelines for the prudent use of antibiotics in veterinary medicine [11 p23] strongly recommends the use of rapid diagnostic tests as an effective way to reduce antibiotic use in farm animal production. Most recently, in a significant shift to market-driven forms of regulation, the UK's Red Tractor assurance and certification scheme now requires veterinarians on participant farms to only use Highest Priority Critically Important Antimicrobials (HPCIAs) as a last resort and only when supported by sensitivity testing and/or diagnostic testing [12]. However, while there has been significant recent growth in research exploring the development of rapid diagnostics in human medicine (for example to test for toxicology, sensitivity and cardiometabolic and infectious diseases: [13,14,15,16], there is relatively little empirical research looking at the role of rapid tests, and diagnostic practices in general, within contemporary veterinary decision-making in achieving responsible antibiotic use [17]. The aim of the current study was therefore to investigate current diagnostic practices amongst UK veterinary surgeons and the opportunities and barriers that might exist for new and current rapid and point-of-care tests to contribute to reducing antibiotic use on farms.

Participants
An online questionnaire was developed in autumn 2018 and made available to all livestock veterinarians with membership of the British Veterinary Association (BVA) in November/December 2018. A draft online version of the survey was initially piloted and tested using selected veterinarians from the cattle, pig and poultry sectors (16 veterinarians) and academic veterinarians from a veterinary school (4 veterinarians). The questionnaire was then refined, formatted and made available to the target population using Qualtrics software interface (Qualtrics, Provo). Before data collection, ethical approval was granted by the University of Exeter Geography Ethics Committee (approval reference number eCLESGeo000069v.3.0). Respondents' participation was voluntary and anonymous. The online questionnaire was also advertised on social media (e.g. Twitter) and within the Veterinary Record. When the questionnaire was closed, 190 veterinarians had responded.

Questionnaire structure
The questionnaire has been included as supplementary material (Appendix 1). It had four sections and was comprised of 25 questions in total. The first section asked for participant demographics, followed by a series of questions on current use of diagnostic tests. This 'Sometimes (25-50%)' 'Rarely (<25%)' and 'Never (0%)' was used to categorise frequencies and respondents' decisions to undertake a diagnostic test (Figure 1). A similar five-point scale was also used to evaluate the degree of agreement to statements regarding the use of rapid diagnostic tests with responses ranging from 'strongly agree' to 'strongly disagree'.

Data entry, management and analysis
Data imported from the Qualtrics software were initially processed through MS Excel (Microsoft, Redmond) and collated into a form suitable for descriptive analysis. Subsequent data cleaning reduced the number of fully usable responses to 153 (largely following the removal of partially answered questionnaires). Some individual questions remained unanswered in the retained questionnaire returns, meaning that the number of responses per question was at times less than the total number of respondents. Qualitative text analysis, following an inductive coding method [18]

General Respondent Information
Of the respondents to the survey, 54% identified as female and 42% identified as male veterinarians. The largest group of respondents (27%) graduated between 2014 and 2018 with a further 17% graduating between 2009 and 2013. In total, almost half of respondents graduated within the last 10 years. In terms of their work environment, more than half of respondents (53%) worked in practices of between 1 and 5 full-time veterinarians; the remainder worked in practices of variable but larger size. Geographically, a large number of respondents were from the South West of England (26%) and Wales (19%), possibly reflecting areas of high livestock and farm density.
The largest single group of respondents (37%) worked for independent veterinary practices, while 20% worked for corporate veterinary practices. The remainder were either selfemployed (15%) or had a range of different occupations including government veterinarians, academic veterinary scientists and consultants, pharmaceutical company and zoo veterinarians, retired veterinarians and Scottish Veterinary Investigation Officers.
The bulk of respondents referred to themselves in generic terms as 'farm vets' or 'mixed practice vets' (Table 1), though well over half (63%) of these spent the majority of their working time with cattle (dairy of beef). Few of the respondents identified themselves specifically as pig or poultry veterinarians ( Table 1). As the last available RCVS survey of the veterinary profession [19] has shown, pig and poultry work is today a relatively minor component of current veterinary working time.
Although evidence suggests that the proportion of overall veterinary input to farms has decreased in recent years [19], responses to this survey showed that on-farm work, whether routine (including checking fertility, performing castrations, dehorning, blood sampling and monitoring the health of farm animals), preventative (preventative medicine and treatment; herd, flock or group health planning advisory services and consultancy) or reactive (emergency services and therapeutic treatment), accounted for an estimated two thirds of respondents' professional workload.

Diagnostic Testing
Survey results revealed that, most of the time, veterinarians prescribe antibiotics without a specific diagnostic test (whether undertaken on-site or in a laboratory). The majority of respondents (70%) reported prescribing most antibiotic treatments over the last year without undertaking a diagnostic test. To understand the circumstances when a test would and would 1 'Other' included animal scientists and aquaculture consultants, veterinary nutritionists, veterinary investigation officers, pathologists, small ruminant veterinarians, sheep veterinarians, veterinarians working for the Veterinary Medicines Directorate, game bird veterinarians, a government veterinarian, and companion animal and equine veterinarians. not be used for a variety of conditions (including both those that are relevant to and those that have little relation to antibiotic use), respondents were asked to estimate the relative frequency with which certain factors were taken into account in their decision to undertake a diagnostic test when confronted with the possibility of animal illness (Figure 1).

Figure 1
Proportions (%) of responses of UK veterinarians rating (from 'never' to 'always') the frequency with which certain factors influence their decision to undertake a diagnostic test suggests that diagnostic tests are predominantly used as a 'rule in' mechanism and much less as a 'rule out' mechanism.
The need, or the requirement, to monitor for endemic or subclinical disease presence is also revealed as a common consideration with 52% of respondents claiming this is 'always' or 'often' a factor in their use of diagnostic tests. Current widely-practiced veterinary testing and monitoring regimes for endemic or subclinical diseases such as Bovine Tuberculosis (bTB), Johne's disease and Bovine Viral Diarrhoea (BVD) undoubtedly account for a significant proportion of these considerations. To explore this in greater depth, veterinary surgeons were asked to identify the diagnostic tests they used most frequently. Amalgamating the responses into four 'target' categories (Table 2), tests were almost equally divided between those undertaken to rule-in (confirm) or rule-out (exclude) a specific or named infectious agent (such as Tuberculosis or Johne's disease) and those carried out in response to a broader clinical indication (such as mastitis, lameness due to infection causes, scour or respiratory disease). To monitor the health status of farm animals, veterinarians also recorded undertaking tests in response to observed nutritional and metabolic states including hypocalcaemia and ketosis. In certain cases, respondents also employed diagnostic tests for antibiotic residues.

Antibiotic residues
Note: The free-text responses which described the diagnostic tests that the respondents used most frequently were coded by three authors who are also veterinarians, with the aim of identifying the diagnostic targets of the rapid tests as perceived by the respondents. The responses included both clinical indications for performing a test, and infectious agents as test targets. Some degree of overlap is therefore inevitable. However, the responses provide valuable insight into the most common clinical indications and infectious agents that trigger diagnostic testing.
In looking at the specific characteristics of different diagnostic tests that are valued by veterinarians (Figure 2

Figure 2
Characteristics of diagnostic tests considered important by veterinarians.

Using rapid and point-of-care diagnostic tests
Rapid and point-of-care diagnostic tests 2 are not a universal feature of contemporary farm animal veterinary practice. Respondents to this survey were fairly evenly divided between those that did not use these types of diagnostic tests or used them rarely (42%) and those used these types of diagnostic tests sometimes or often (58%). For the latter, their value lay chiefly in the speed with which treatment decisions could not only be confirmed but also, and crucially, which could be justified and defended to the farmer. Respondents were asked to indicate their level of agreement with a series of statements regarding the use of rapid diagnostic tests ( Figure 3). There was a high proportion of 'disagree' responses (62%) to the statement that veterinarians 'need more rapid diagnostic tests for the diseases they commonly encounter'. However, 61% of respondents agree that there is a 'need for more on-farm tests' as current lab-based tests are time-consuming. According to one respondent (Respondent S015 2019): 'It takes too long to wait for a culture and sensitivity report from a laboratory … farmers want an instant decision when discussing treatments for a sick animal.' Critically, as stated by one respondent, future rapid diagnostics could help to 'differentiate viral and bacterial causes of animal diseases such as pneumonia' (Respondent S110 2019).
Yet this interest was also accompanied by concern over certain practicalities of current rapid diagnostic tests.

Figure 3
Would you agree or disagree with the following statements regarding the use of rapid diagnostic tests?.
The equivocal nature of these responses suggests that opinion is relatively divided on the current and future use of rapid, on-farm and point-of-care tests. The open-ended responses hint at differences across production sectors, though the numbers involved are too small to achieve statistical significance. Nevertheless, some veterinarians were more in favour of rapid tests because they were seen as providing a valid addition to the repertoire of diagnostics within the cattle sector, while others noted that rapid diagnostic tests were not 'readily

available and economically viable to conduct bacteria tests on pig and poultry sectors'
(Respondent S124 2019). Finally, when asked to identify any bacterial diseases and farm animal infections for which 'new, good and reliable diagnostic tests were still needed', veterinarians prioritised (in terms of numbers of times mentioned) the following: bTB (21 respondents), Johne's disease (16 responses), mastitis (13 respondents), pneumonia (12 respondents), Mycoplasma-related diseases (10 respondents) and salmonella (7 respondents). Less frequently mentioned, reflecting the distribution of veterinary specialisms captured in the survey as mentioned above, but nonetheless useful to note here, were ileitis and swine dysentery in pigs and E. coli in poultry.

Diagnosis and antibiotic treatment decision making
Veterinarians were asked to consider the relationship between diagnostic testing and antibiotic prescription. Diagnostic tests were not generally used to confirm the prior choice of an antibiotic treatment once it had been prescribed (38% claimed this was never the case over the last year and a further 36% stated this happened in only a few cases). Moreover, few veterinarians routinely undertook a susceptibility test before an antibiotic treatment decision (57% responded 'rarely' and 28% 'never').
Although survey responses displayed considerable variation with respect to the use and relative advantages (or disadvantages) of pen-side and point-of-care diagnostic tests, responses were notably more unified in their agreement with the statement that more readily available rapid diagnostic tests would help in achieving more sustainable use of antibiotics: 92% of respondents selected 'yes' or 'sometimes'. As stated by one respondent: 'If we can prove the disease on farm by using rapid diagnostics, we can pinpoint the best antimicrobial at that time and save waiting for failure treatment' (Respondent S028 2019).
Finally, veterinarians were asked, 'When treating the farmed species with which you work the most, what proportion of antibiotic treatment courses were prescribed over the last 12 months for the following reasons: to treat sick animals, to prevent the spread of disease or to reduce the likelihood of disease.' The most common use of antibiotics was for Option 1, the treatment of sick animals (74% answering 'most' or 'all' treatment courses). Options 2 and 3 were rarely cited as a reason for antibiotic use; 52% indicated they had never used antibiotic treatments to reduce the likelihood of a disease occurring or developing over the last 12month period, whilst (8%) indicated they had never used antibiotics to prevent the spread of a disease already present in the flock or herd.

DISCUSSION
Current arguments around achieving more sustainable antibiotic use in both humans and animals frequently point to the need to reduce unnecessary or inappropriate treatment. For many [8,[20][21][22][23], a key mechanism for achieving this is better and faster diagnostic tests, not only to ensure that the medicines deployed are appropriately targeted to bacterial pathogens but also to justify decisions to employ those medicines, particularly in cases where critically important antibiotics are deemed necessary to protect animal or herd/flock health. In the light of such arguments, the present study sought to identify current approaches amongst farm animal veterinarians to both diagnostic tests generally as well as rapid and point-of-care tests in particular in the context of their relationship to antibiotic use. Three key points emerged from the survey.
Firstly, for many of the more commonly encountered farm animal diseases or infections, specific diagnostic tests were not considered necessary nor are they regularly used, even when the subsequent treatment involves antibiotics. Most veterinarians appeared confident in their clinical observation and expertise, often drawing upon previous pathologies or prior test results within known herds and flocks to make subsequent treatment decisions [24,25].
Certain endemic and production diseases are common, and tests, when used, are generally there to confirm (rather than exclude) a diagnosis. Such confirmation can be useful to the veterinarian not only in justifying subsequent treatment costs to the farmer but also as a basis for encouraging the implementation of animal management measures to reduce the spread or occurrence of infection.
Secondly, the survey revealed a number of mixed, and, in places, contradictory, approaches to the use and future development of pen-side and point-of-care diagnostic tests.
Respondents would like to see more rapid and point-of-care tests made available to shorten the time between test result and treatment (as previously described by Griffioen and others [17] to confirm particular diseases such as mastitis, and to easily differentiate between bacterial and non-bacterial infections. Many felt strongly that rapid tests have a place in achieving more sustainable use of antibiotics, but few used them regularly. Many also acknowledged concerns regarding their sensitivity, specificity and ease-of-use.  [27,28] and although the number of self-identified pig and poultry veterinarians was relatively small compared to cattle veterinarians, their number is consistent with estimates of the proportion of time spent on these species within the veterinary profession [19]. Responses to this survey indicated that those describing themselves as 'farm' or 'mixed practice' veterinarians covered a suitable range of species and experiences.

Limitations
This online survey used a sampling frame of BVA members and others who engaged through social media. The study population represented only a small proportion of the veterinary profession of the UK despite collaboration with a national and well-subscribed body along with efforts to recruit respondents as widely as possible. Geographical bias is also likely to have occurred due to overrepresentation of cattle veterinarians, many of whom are located in South West England. Early career veterinary surgeons were also over-represented, which might have added to responses about unfamiliarity with diagnostic tests. To address these limitations, further studies are being conducted to offer triangulation with this survey data through in-depth interviews with veterinarians at different levels of seniority and geographical spread.

CONCLUSION
This exploratory study offers insights into veterinarians' attitudes and approaches to diagnostic procedures and the use of diagnostic tests in the treatment of farm animal illness and disease within the context of growing societal and professional concern over the use of antibiotics in farm animal veterinary medicine. The study shows that diagnostic tests are far from universally used in determining disease, with many farm animal veterinarians preferring to rely on their own observational and clinical skills and experience in making treatment decisions. This is specifically shown to be the case for treatments involving antibiotics.
Moreover, where antibiotics are used, it is generally for therapeutic treatment rather than prophylaxis or metaphylaxis. Finally, this study reveals a varied set of attitudes and approaches to the use of point-of care tests and identifies generalised patterns of using rapid diagnostic technologies across cattle, pig and poultry sectors in the UK. Despite the potential for rapid diagnostics to support sustainable antibiotic use in livestock -as identified in the O'Neill report -the results presented indicate that this is not standard practice at present.