Portal de Periódicos da CAPES

An outbreak of tuberculosis due to Mycobacterium bovis infection in a pack of English Foxhounds (2016-2017)

2018; Wiley; Volume: 65; Issue: 6 Linguagem: Inglês

10.1111/tbed.12969

1865-1682

Conor O’Halloran, Jayne C. Hope, Melanie Dobromylskyj, Paul Burr, Kieran McDonald, Shelley Rhodes, Tony Roberts, Richard Dampney, R. de la Rúa-Domènech, Nicholas A. Robinson, Danièlle Gunn‐Moore,

Infectious Diseases and Tuberculosis

Transboundary and Emerging DiseasesVolume 65, Issue 6 p. 1872-1884 ORIGINAL ARTICLEOpen Access An outbreak of tuberculosis due to Mycobacterium bovis infection in a pack of English Foxhounds (2016–2017) Conor O'Halloran, Corresponding Author Conor O'Halloran conor.ohalloran@roslin.ed.ac.uk orcid.org/0000-0002-4921-2907 Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK Correspondence Conor O'Halloran, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, EH25 9RG Midlothian, UK. Email: conor.ohalloran@roslin.ed.ac.ukSearch for more papers by this authorJayne C. Hope, Jayne C. Hope Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UKSearch for more papers by this authorMelanie Dobromylskyj, Melanie Dobromylskyj Finn Pathologists, Diss, Norfolk, UKSearch for more papers by this authorPaul Burr, Paul Burr Biobest Laboratories, Edinburgh, UKSearch for more papers by this authorKieran McDonald, Kieran McDonald Biobest Laboratories, Edinburgh, UKSearch for more papers by this authorShelley Rhodes, Shelley Rhodes Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorTony Roberts, Tony Roberts Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorRichard Dampney, Richard Dampney Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorRicardo De la Rua-Domenech, Ricardo De la Rua-Domenech Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorNicholas Robinson, Nicholas Robinson Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorDanielle A. Gunn-Moore, Danielle A. Gunn-Moore Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UKSearch for more papers by this author Conor O'Halloran, Corresponding Author Conor O'Halloran conor.ohalloran@roslin.ed.ac.uk orcid.org/0000-0002-4921-2907 Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UK Correspondence Conor O'Halloran, Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, EH25 9RG Midlothian, UK. Email: conor.ohalloran@roslin.ed.ac.ukSearch for more papers by this authorJayne C. Hope, Jayne C. Hope Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UKSearch for more papers by this authorMelanie Dobromylskyj, Melanie Dobromylskyj Finn Pathologists, Diss, Norfolk, UKSearch for more papers by this authorPaul Burr, Paul Burr Biobest Laboratories, Edinburgh, UKSearch for more papers by this authorKieran McDonald, Kieran McDonald Biobest Laboratories, Edinburgh, UKSearch for more papers by this authorShelley Rhodes, Shelley Rhodes Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorTony Roberts, Tony Roberts Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorRichard Dampney, Richard Dampney Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorRicardo De la Rua-Domenech, Ricardo De la Rua-Domenech Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorNicholas Robinson, Nicholas Robinson Animal and Plant Health Agency, Addlestone, Surrey, UKSearch for more papers by this authorDanielle A. Gunn-Moore, Danielle A. Gunn-Moore Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, UKSearch for more papers by this author First published: 30 July 2018 https://doi.org/10.1111/tbed.12969Citations: 19AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Mycobacterium bovis can cause tuberculosis (TB) in social mammals including lions, cattle and man, but canine infections are considered rare. In 2016/17 we investigated a M. bovis TB outbreak in a pack of approximately 180 Foxhounds within the bovine TB Edge Area of England. We employed a combination of immunological tests including an interferon gamma release assay (IGRA) and a serological assay (DPP VetTB, Chembio). Test-positive hounds were euthanased and subjected to post-mortem examination (PME). Overall 164 hounds were tested; 97 (59%) responded positively to at least one test. Eighty-five (52%) dogs responded to M. bovis antigens by IGRA while only 21 (12.9%) had detectable serological responses. At PME three hounds (3.1%) had visible lesions (VL) due to M. bovis infection, later confirmed by culture. Samples from 24 non-VL hounds were cultured and M. bovis infection was confirmed in a further three hounds (11%). This study is the first investigation and report of an outbreak of M. bovis TB in a canine species. We establish that, in principle, diagnostic tests used for identifying infected individuals of other species can effectively be used in the dog. Further work is urgently needed to establish the sensitivity and specificity of the testing approach used in this study for future clinical application. 1 INTRODUCTION Mycobacterium (M.) bovis is one of the nine member species of the Mycobacterium tuberculosis complex (MTBC) which are capable of causing tuberculosis (TB), across a broad taxonomy of social mammal including but not limited to humans, lions, elephant and meerkats (Angkawanish et al., 2013; Brosch et al., 2002; Drewe, 2010; Miller et al., 2012; Parsons, Drewe, Gey van Pittius, Warren, & van Helden, 2013). Within this group of pathogens, M. bovis stands out as the least host restricted and thus has significant zoonotic potential (Broughan et al., 2013; Michel et al., 2013; Miller & Olea-Popelka, 2013; Palmer, 2007). Disease in humans due to infection with M. bovis, termed “zoonotic TB” by the World Health Organisation (WHO), is a major global public health priority which resulted in nearly 150,000 cases and at least 12,500 deaths in 2010 worldwide (Ciszewski, Czekaj, Chojnacki, & Szewczyk, 2015; Dürr et al., 2013; Olea-Popelka et al., 2017). In addition, the lack of diagnostic discrimination between M. tuberculosis and M. bovis in most human mycobacterial reference laboratories (MRLs) means that the true mortality and morbidity caused by zoonotic TB is possibly underestimated (Dürr et al., 2013; Olea-Popelka et al., 2017). Discriminating between TB caused by different species of the MTBC is challenging as all member species share identical sequences across the 16s rRNA gene and 99.5% sequence homology across the remainder of the genome (Brosch et al., 2002). The most discriminating features between the species at the nucleotide level are genomic deletions, termed regions of difference (RD; Teo, Cheng, Jureen, & Lin, 2013). These have been shown to encode a variety of different virulence factors, for example, RD-1 is present on all MTBC mycobacteria other than M. bovis Bacillus-Calmette-Guérin (BCG) and M. microti and encodes for the immunodominant proteins and key virulence factors; early secreted antigenic target-6 KDa (ESAT-6) and culture filtrate protein-10 KDa (CFP-10) (Gao et al., 2004; Guinn et al., 2004; Junqueira-Kipnis et al., 2006). The human burden of disease is highest across Africa, South-East Asia and the Western Pacific. In South Africa, dogs have been shown to become infected with M. tuberculosis, as diagnosed using human interferon gamma release assays (IGRA), when exposed to high risk humans, that is, those with active TB disease (Parsons, Warren, Ottenhoff, Gey van Pittius, & van Helden, 2012). Similarly, African wild dogs (Lycaon pictus) have been found to be infected with M. bovis, presumptively from hunting exposure (Ayele, Neill, Zinsstag, Weiss, & Pavlik, 2004). In the UK, however, the significance of M. bovis in companion animals is largely limited to domestic cats, were frequent diagnoses are made (Broughan et al., 2013; Gunn-Moore, 2014; Pesciaroli et al., 2014; Rocha et al., 2017). Canine incidence of TB in the UK is currently considered to be rare, and almost all reported cases are limited to individual sporadic infection or small numbers of epidemiologically unrelated cases (Ellis et al., 2006; Gay et al., 2000; Liu, Weitzman, & Johnson, 1980; Park, Lim, Kwon, Bae, & Park, 2016; Parsons et al., 2012; Pesciaroli et al., 2014; Posthaus et al., 2011; Shrikrishna, de la Rua-Domenech, Smith, Colloff, & Coutts, 2009; Snider, 1971; Szaluś-Jordanow et al., 2016; Van Der Burgt, Crawshaw, Foster, Denny, & Schock, 2009). Between the end of 2016 and July 2017, a large outbreak of M. bovis infection occurred in a kennel of working Foxhounds within the Edge Area of England; which is a buffer zone of intermediate bovine TB incidence separating the High and Low bovine TB Risk Areas and subject to additional surveillance and controls for this disease. This report describes the clinical features of the outbreak, the testing approach taken and the epidemiological aspects of the spread of disease as they are currently understood. Work to evaluate the testing approach further is currently ongoing and will be published separately. We go on to explain the new statutory controls which have been implemented in England as a result of this incident to minimize the low risk of spreading TB through the feeding of fallen stock to hounds in registered kennels. 2 OUTBREAK INVESTIGATION 2.1 Index case The hunt kennel where this outbreak occurred is situated in the south of England, UK, and housed up to 180 working Foxhounds ranging in age from juvenile puppies ( PPDA bias, neither of these were responsive to ESAT-6/CFP-10. Retrospective investigation revealed that one of these dogs was a hound which had been retired from the affected pack due to age-related poor performance only a few weeks prior to Case 0 becoming clinically sick. The second was a terrier dog, used as a “cutting room scrap dog” that is, it was regularly close to the preparation of carcasses before they were fed to the hounds. In total, 13 bitches were sent from the affected kennel to one of two other kennels for breeding purposes, (groups B and C); both of these kennels are in the High Risk Area (HRA) of endemic bTB of England. Seven of these bitches were still away at the other kennels at the time of testing (i.e., group B), where they were assessed by IGRA and DPP VetTB test assay (as outlined above; Sections 2.2.1 and 2.2.2) and found to be negative on both tests. Six bitches had been off site for breeding purposes in the 18 months preceding the outbreak and returned to the kennels before the first case occurred (i.e., group C). Only three of these animals were still alive at the time of the outbreak; one was found to be IGRA positive (PPDB > PPDA) but was DPP VetTB test-negative and had no visible lesions at PME. The remaining two live hounds were test negative by both assays. The reason for, and timing of, euthanasia or death of the three untested hounds is not known as it was not recorded by kennel staff. 2.2.4 Post-mortem examination of test positive animals and subsequent mycobacterial culture During the course of the outbreak, from December 2016 until July 2017, a total of eight hounds became clinically unwell (Table 1). All hounds displayed similar clinical signs to Case 0 including acute onset anorexia, lethargy, polyuria and polydipsia. Only one of these hounds was subjected to IGRA testing ante mortem and was found to be responsive to the antigen cocktail of ESAT-6/CFP-10, the remainder had to be euthanased for welfare reasons before samples could be obtained. Table 1. Results of post-mortem investigations compared to ante mortem test results Initial screening tests DPP positive DPP “at risk” DPP negative Total IGRA positive 4 5 76 86a IGRA negative 7 5 66 78 Total 11 10 142 164 Repeat tests Culture positive Culture negative Culture n