Abstract
BackgroundBovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen.MethodsMycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis isolates were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes.ResultsMycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR = 2.7,p = 0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients with available HIV status, the odds of isolating M. bovis from HIV patients (2/119) was 3.3 higher relative to non-HIV patients (4/774). Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p<0.0001, OR = 124.4,95% CI = 30.1–508.3). Two (13.3%) of the M. bovis isolates were INH resistant due to the S315T mutation in katG whereas one (6.7%) was RIF resistant with Q432P and I1491S mutations in rpoB. M. bovis from Ghana resolved as mono-phyletic branch among mostly M. bovis from Africa irrespective of the host and were closest to the root of the global M. bovis phylogeny. M. bovis-specific amino acid mutations were detected among MTBC core genes such as mce1A, mmpL1, pks6, phoT, pstB, glgP and Rv2955c. Additional mutations P6T in chaA, G187E in mgtC, T35A in Rv1979c, S387A in narK1, L400F in fas and A563T in eccA1 were restricted to the 5 clinical M. bovis from Ghana.ConclusionOur data indicate potential zoonotic transmission of bTB in Ghana and hence calls for intensified public education on bTB, especially among risk groups.
Highlights
Among the Mycobacterium tuberculosis complex (MTBC), Mycobacterium bovis is the main causative agent of TB in cattle and sheep, albeit with the widest host range among other mammals including wildlife and humans [1]
Direct contact with livestock or their unpasteurized products was significantly associated with bTB (p
We identified 41 M. bovis restricted amino acid mutations among 32 core-genes of the 5 clinical M. bovis from Ghana when compared to 257 M. africanum (Maf) [27] and 20 global M. tuberculosis complex (MTBC) genomes [41]
Summary
Among the Mycobacterium tuberculosis complex (MTBC), Mycobacterium bovis is the main causative agent of TB in cattle and sheep, albeit with the widest host range among other mammals including wildlife and humans [1]. M. bovis associated TB is a re-emerging global problem affecting both livestock and humans alike. Human-to-human transmission of M. bovis is mostly rare [5], human bTB is considered a zoonotic chronic disease characterized by lung infections and their draining lymph nodes as granulomatous necrotizing inflammatory disease [6,7]. BTB among immunocompromised people and children are mostly extrapulmonary or disseminated affecting other organs other than the lungs and their draining lymph nodes. A lack of knowledge or negligence of the dangers associated with being in close contact with livestock or wildlife and their unpasteurized products is apparent among some individuals who are constantly in direct contact with animals [10]. Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDRTB and disseminated disease makes it imperative to understand the biology of the pathogen.
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