Volume 17, Number 12—December 2011
Humans as Source of Mycobacterium tuberculosis Infection in Cattle, Spain
To the Editor: Mycobacterium tuberculosis is the main causative agent of tuberculosis in humans. However, little attention has been paid to its transmission from humans to animals. We report M. tuberculosis infections in 3 cattle farms in Spain. The epidemiologic investigation traced humans as the source of infection, with 1 of the strains showing multidrug resistance.
Recent studies have reported isolation of M. tuberculosis in cattle with prevalences of 4.7%–30.8% in African and Asian countries (1–3). In cattle, this infection occurs in countries with the highest incidence of human tuberculosis in the world. In Europe, only 14 cases of M. tuberculosis infection have been described in 3 eastern countries since implementation of eradication programs (4,5). The only reported cases of M. tuberculosis in cattle in western Europe were described in Great Britain and date back to the 1950s (6).
During 2007–2009, three cases of tuberculosis caused by M. tuberculosis were detected in 3 unrelated cattle farms, 2 of them free of tuberculosis (farms 1 and 2). As part of the surveillance system of bovine tuberculosis, a pool of tissue samples from each cow (respiratory lymph nodes and lung) were homogenized with sterile distilled water, and culture was carried out by the BACTEC mycobacteria growth indicator tube 960 system (Beckton Dickinson, Madrid, Spain). Members of the M. tuberculosis complex were identified and genotyped by direct variable repeat spacer olignucleotide typing and mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) typing (7).
M. tuberculosis–infected animals from farms 1 and 3 were detected by the intradermal tuberculin test (Table). The animal without immunologic response (farm 2) was detected because an M. bovis infection was confirmed in the herd, and all animals were slaughtered. Confirmation of infection by culture without immunologic response is rare, although the high sensitivity of the mycobacteria growth indicator tube system could detect a low bacterial load in the initial stages of infection. Recent implementation of liquid systems in animal health laboratories has enabled detection of M. tuberculosis when it is compared with results using only conventional methods. Moreover, no tuberculosis-compatible lesions were observed in the 3 animals, similar to previous studies (6). On the basis of these facts, M. tuberculosis transmission was not detected among cattle in the following intradermal tuberculin tests.
Co-infection with other mycobacteria (M. avium subsp. hominissuis) was found in the same animal from farm 1 (Table). This co-infection suggested the immunocompromised status of the animal and hence a high susceptibility to M. tuberculosis infection. Moreover, M. bovis was isolated from 52% (16/31) of all animals from farm 2 that showed a positive reaction to the intradermal tuberculin skin test, making remarkable the absence of co-infection with M. bovis in the M. tuberculosis–infected animal. Therefore, the lack of M. tuberculosis transmission within this herd contrasts with the M. bovis dissemination.
The veterinary services reported these findings to the National Public Health System, and an epidemiologic investigation was conducted on the cattle farms to determine the source of infection. In all cases, staff of the farms had active tuberculosis (Table). Three different strains were characterized: SIT2537 (octal code 777617777720771), 253533233433236252211423 (farm 1); SIT1564, 3′52334232455457251213423 (farm 2); and SIT58, 254343243232325262213423 (farm 3) (Table). The MIRU-VNTR pattern and spoligotype are shared by Spanish human and cattle isolates from farm 1; SIT2537 is an uncommon profile that has been detected in Brazil and Spain (according to the SITVIT2 database). The human strain showed multidrug resistance to isoniazid, rifampin, and ethionamide. In cattle and human isolates, genes associated with isoniazid and rifampin resistance were studied (8) and rpoB analysis confirmed rifampin resistance (Ser531Leu). In farm 2, the origin of the farm worker was eastern Europe and the cattle isolate showed an SIT1564 profile, which is found only in 6 human isolates in the SpolDB4 database, all from Poland, Bulgaria, and Russia. On farm 3, human and cattle isolates from Spain shared identical spoligotype and MIRU-VNTR patterns. The profile SIT58 is frequent in Spain (9) and other countries with historical links to Spain, mainly the south American countries (79/114 according to SpolDB4).
A well-designed program for eradicating bovine tuberculosis helps to detect M. tuberculosis infection by immune response or by bacteriologic culture. The use of liquid systems and results of epidemiologic studies (Spanish Database of Animal Mycobacteriosis, mycoDB.es) (S. Rodríguez, unpub. data) are recommended for prompt confirmation of the M. tuberculosis complex infection and for enhancing the sensitivity of culture. In addition, the Spanish Ministry of Environment, Rural and Marine Affairs has reinforced the need to improve cooperation between human and animal health systems to minimize the risk for M. tuberculosis complex transmission from animals to humans or vice versa and to control infection in all susceptible animal species (10).
We thank L. Carbajo, J. Carpintero, E. Fernández, and L.M. Álvarez for their continuous encouragement; F. Lozano, N. Moya, A. Gutiérrez, J. Gimeno, A. Penedo, A. Menéndez, C. Martínez, and J.A. Anguiano for technical help; R. Daza and M.S. Jiménez for providing the human strains and related data; Nalin Rastogi for comparison of spoligotyping results with the SITVIT2 proprietary database; and M. Gilmour for careful revision of the manuscript.
This research was funded by project TB-STEP FP7-KBBE-2007-212414 of the European Union and by the Spanish Ministry of the Environment, and Rural and Marine Affairs and partially by Fondo de Investigaciones Sanitarias (FIS S09/02205). B.R. received a research contract funded by Comunidad de Madrid (IV regional framework program of research and technological innovation 2005−2008).
- Fetene T, Kebede N, Alem G. Tuberculosis infection in animal and human populations in three districts of western Gojam, Ethiopia. Zoonoses Public Health. 2011;58:47–53.PubMed doi:10.1111/j.1863-2378.2009.01265.x.
- Chen Y, Chao Y, Deng Q, Liu T, Xiang J, Chen J, Potential challenges to the Stop TB Plan for humans in China; cattle maintain M. bovis and M. tuberculosis. Tuberculosis (Edinb). 2009;89:95–100.
- Prasad HK, Singhal A, Mishra A, Shah NP, Katoch VM, Thakral SS, Bovine tuberculosis in India: potential basis for zoonosis. Tuberculosis (Edinb). 2005;85:421–8.
- Pavlik I, Trcka I, Parmova I, Svobodova J, Melicharek I, Nagy G, Detection of bovine and human tuberculosis in cattle and other animals in six central European countries during the years 2000–2004. Vet Med Czech. 2005;50:291–9 [cited 2011 Oct 24]. http://www.vri.cz/docs/vetmed/50-7-291.pdf
- Pavlik I, Ayele WY, Parmova I, Melicharek I, Hanzlikova M, Körmendy B, Mycobacterium tuberculosis in animal and human population in six Central European countries during 1990−1999. Vet Med Czech. 2003;48:83-89 [cited 2011 Oct 24]. http://www.vri.cz/docs/vetmed/48-4-83.pdf
- Lesslie IW. Tuberculosis in attested herds caused by the human type tubercle bacillus. Vet Rec. 1960;72:218–24.
- Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rüsch-Gerdes S, Willery E, Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis. J Clin Microbiol. 2006;44:4498–510.
- Romero B, Aranaz A, de Juan L, Álvarez J, Bezos J, Mateos A, Molecular epidemiology of multidrug-resistant Mycobacterium bovis isolates with the same spoligotyping profile as isolates from animals. J Clin Microbiol. 2006;44:3405–8.
- García de Viedma D, Bouza E, Rastogi N, Sola C. Analysis of Mycobacterium tuberculosis genotypes in Madrid and identification of two new families specific to Spain-related settings. J Clin Microbiol. 2005;43:1797–806.
- Ministerio de Medio Ambiente y Rural y Marino. Discussion conference about the eradication of bovine tuberculosis [in Spanish]. Santander, 2010 Jun 29−30, Spain [cited 2011 Oct 24]. http://www.mapa.es/es/ganaderia/pags/eventos_presidencia/jornada_tuberculosis_bovina.htm