Epidemiology of Mycobacterium bovis and Mycobacterium tuberculosis in animals: Transmission dynamics and control challenges of zoonotic TB in Ethiopia

Preventive Veterinary Medicine 158 (2018) 1–17

Contents lists available at ScienceDirect

Preventive Veterinary Medicine journal homepage: www.elsevier.com/locate/prevetmed

Epidemiology of Mycobacterium bovis and Mycobacterium tuberculosis in animals: Transmission dynamics and control challenges of zoonotic TB in Ethiopia

T

⁎

Gebremedhin Romhaa, , Gebreyohans Gebrub, Abrha Asefac, Gezahegne Mamod a

Department of Animal Production and Technology, College of Agriculture and Environmental Science, Adigrat University, Adigrat, Ethiopia Department of Animal Sciences, College of Agriculture, Aksum University, Shire, Ethiopia c Department of Geography, College of Social Science, Adigrat University, Adigrat, Ethiopia d Faculty of Veterinary Medicine, Addis Ababa University, Debre Zeit, Ethiopia b

A R T I C LE I N FO

A B S T R A C T

Keywords: Epidemiology Mycobacterium bovis Mycobacterium tuberculosis Geospatial distribution Transmission dynamics Control challenges Ethiopia

Mycobacterium tuberculosis complex is the cause of tuberculosis (TB) in humans and other animals. Specifically, Mycobacterium bovis (M. bovis) and Mycobacterium tuberculosis (M. tuberculosis) are highly pathogenic mycobacteria that may infect different animal species and are the sources of TB in humans. The objective of this paper was to review the epidemiology of M. bovis and M. tuberculosis in animals. The review also highlighted the transmission dynamics of M. bovis and M. tuberculosis in humans and animals and control challenges of zoonotic TB in Ethiopia. The literature review focused on scientific peer-reviewed articles from studies exclusively conducted in Ethiopia that were published from 1998 to 2017. Husbandry system, breed and herd size have significant role in the epidemiology of bovine tuberculosis (BTB) in Ethiopia. The information presented reveals that different strains of M. bovis are widely distributed in domestic animals predominantly in the Ethiopian cattle and the main strain was found to be SB1176. In addition, the isolation of M. tuberculosis from domestic animals in different settings signifies the circulation of the agent between humans and animals in Ethiopia. The life styles of the Ethiopian communities, close contact with domestic animals and/or the habit of consuming raw animal products, are suggested as the main factors for transmission of M. bovis and M. tuberculosis between human and animal which may have impact on the TB control program in human. In Ethiopia, a human TB control program has been widely implemented, however, the role of animal in the transmission of the causative agent has been neglected which could be one of the challenges for an effective control program. This warrants the need for incorporating animal TB control programs using “One Health” approach for effective TB control for both human and animal.

1. Introduction M. tuberculosis complex cause TB in various mammalian hosts but exhibit specific host tropisms (Smith et al., 2006). M. tuberculosis and M. bovis are the major causes of TB. They are highly pathogenic mycobacteria that may infect many animal species and are the sources of TB in humans (Mathema et al., 2006). M. bovis, the main but not exclusive causative agent of bovine tuberculosis (BTB), is a member of the M. tuberculosis complex, which also comprises the important human pathogen, M. tuberculosis, as well as Mycobacterium canettii, Mycobacterium africanum, Mycobacterium pinnipedii, Mycobacterium microti, and Mycobacterium caprae. These species are phylogenetically closely related

mycobacteria sharing more than 99.9% chromosomal identity and they cause TB with similar pathology in various mammalian hosts (Smith et al., 2006). Human TB and BTB share key aspects such as the development of similar lesions and immune responses, which often result in colonization and spread to various organs, mainly to lungs and lymphatic tissues (O’Reilly and Daborn, 1995; Buddle et al., 2005; Cassidy, 2006; Van Rhijn et al., 2008). Recent studies showed that some reactor animals to bovine tuberculin skin test were found infected with M. tuberculosis isolates (Tschopp et al., 2011; Kassa et al., 2012; Ameni et al., 2013). In fact, tuberculin test cannot discriminate M. bovis from M. tuberculosis (De la Rua-Domenech, 2006).

⁎

Corresponding author. E-mail addresses: [email protected] (G. Romha), [email protected] (G. Gebru), [email protected] (A. Asefa), [email protected] (G. Mamo). https://doi.org/10.1016/j.prevetmed.2018.06.012 Received 6 September 2017; Received in revised form 27 June 2018; Accepted 27 June 2018 0167-5877/ © 2018 Elsevier B.V. All rights reserved.

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Fig. 1. Articles retrieval and screening method.

and contact with livestock has been suggested as a risk factor when compared to pulmonary TB (Berg et al., 2015). The epidemiology of BTB has been widely explored in Ethiopia; however, the role of zoonotic TB has been overlooked. The molecular identification of M. tuberculosis and M. bovis in animals and animal products as well as demonstration of M. tuberculosis lymphadenitis TB (cervical lymph node TB) in humans in recent times have brought new insights about the epidemiology and transmission dynamics of M. bovis and M. tuberculosis. Therefore, the objectives of this paper were to review (1) the epidemiology of M. bovis and M. tuberculosis in animals, (2) the transmission dynamics of M. bovis and M. tuberculosis in humans and animals, and (3) control challenges of zoonotic TB in Ethiopia.

In Ethiopia, research on BTB began in the mid-1970s when slaughterhouse studies confirmed the presence of the disease (reviewed in Shitaye et al., 2007). Analysis of nine years of meat inspection records also revealed an increasing incidence of BTB over the years (Demelash et al., 2009). Currently, conventional and molecular epidemiological studies have provided evidence for the widespread distribution of BTB in cattle populations throughout the country (Ameni et al., 2007a; Elias et al., 2008; Berg et al., 2009; Demelash et al., 2009; Biffa et al., 2010a; Tsegaye et al., 2010; Gumi et al., 2012a; Firdessa et al., 2012; Tschopp et al., 2013). The widely spread distribution of TB in livestock, in turn, could be a major obstacle to the country’s livestock export trade due to strict sanitary requirements by the importing countries (Elias et al., 2008; Demelash et al., 2009). It is also suggested that the disease may impact productivity of animals and this is likely linked to economic losses (Tigre et al., 2010; Tschopp et al., 2012). Moreover, studies have indicated that zoonotic TB is as an on-going risk to public health in Ethiopia, as rural dwellers live in close contact with their animals (Berg et al., 2009; Gumi et al., 2012b) as well as due to meat-borne infections as a result of poor meat inspection practices (Biffa et al., 2010b) and consumption of unpasteurized dairy products (Firdessa et al., 2012). On the other hand, studies have also indicated that cattle and other animals can acquire M. tuberculosis from humans (Ameni et al., 2011; Dawson et al., 2012; Kassa et al., 2012), which may have implications in the epidemiology and control of human TB. M. tuberculosis has also widely been isolated from bovine milk (Mariam, 2014) and tissues of different animal species in Ethiopia (Berg et al., 2009; Ameni et al., 2010, 2013; Arega et al., 2013; Aylate et al., 2013; Deresa et al., 2013, Kassa et al., 2012) using different molecular diagnostic methods such as PCR and spoligotyping. Indeed, transmission of M. tuberculosis from humans to other animals has also been suggested (Berg et al., 2009; Ameni et al., 2011; Kassa et al., 2012). On the other hand, M. tuberculosis plays a significant role in TB lymphadenitis (cervical lymph node TB) (Kidane et al., 2002; Firdessa et al., 2013; Berg et al., 2015),

2. Methods A systematic literature review was used to identify publications on the distribution of M. bovis and M. tuberculosis in animals, its (zoonotic) transmission dynamics and control challenges. The literature review focused on scientific peer-reviewed articles from studies exclusively conducted in Ethiopia that were published from 1998 to 2017 and found in PubMed central (PMC) and Web of Science Core Collection (ETH-BIBLIOTHEK). Broad search terms were used to capture the majority of the scientific publications under the scope of this review. Publications that are not from Ethiopia were excluded. Articles, both full length and abstracts, which are available online, were included. However, abstracts without adequate evidence, technical reports, book chapters and review articles were not considered. The review depended on three steps. First, key words and search terms were identified for use in the search process. Second, searching for relevant publications using the search terms and key words was conducted. Third, once we retrieved all the sources, we reviewed and identified the pertinent publications. Publications were considered as eligible if they included at least one of the following three broad themes. (1) Articles that focused on the epidemiology of animal TB and 2

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

breed and local zebu). Seven of them asserted that HF breeds were found to be the most susceptible (Ameni and Erkihun, 2007; Ameni et al., 2003a,b; Ameni et al., 2007b; Elias et al., 2008; Regassa et al., 2008; Firdessa et al., 2012). Firdessa et al. (2012) reported prevalence of tuberculin test positivity; 58, 19 and 0.3% in HF, cross and zebu breeds, respectively. One study conducted on the three breeds kept under the same husbandry system (semi-extensive) found that HF were likely to be more at risk for BTB positivity (22.2%) followed by cross (11.9%) and zebu breeds (11.6%) (Ameni et al., 2007b). Similarly increased severity of pathology was reported in HF slaughtered from strong PPD reactors than the local zebu breed (Ameni et al., 2007b). Using experimental and epidemiological analyses, Vordermeier et al. (2012) provided evidence that zebu breeds are less susceptible than exotic HF breeds. The experiment conducted by infecting calves of both breeds (HF and zebu) using very low infective dose of M. bovis to evaluate the pathology developed after 16 weeks, and visible pathology was scored only from HF calves (Vordermeier et al., 2012). Regarding husbandry system, Ameni et al. (2006) demonstrated in PPD reactors HF cattle that were kept indoors (intensive production system) had shown to produce significantly higher levels of interferon gamma (IFN-ᵞ) than the same breed kept extensively. Other studies also reported that the risk of BTB in Ethiopia is likely to be directly related to husbandry, intensive farming practices driving the increased risk of BTB (Ameni et al., 2007b; Tsegaye et al., 2010; Firdessa et al., 2012). A strong positive correlation was observed between herd size and number of reactor animals (Tsegaye et al., 2010). Higher tuberculin positivity has been recorded in large herd size (Ameni et al., 2003a; Ameni and Erkihun, 2007; Elias et al., 2008; Regassa et al., 2008, 2010; Tsegaye et al., 2010; Firdessa et al., 2012). Increased risk of tuberculin positivity has also been observed in farms with poor sanitation status (Ameni et al., 2003b; Elias et al., 2008; Regassa et al., 2010; Zeru et al., 2014). Moreover, bacteriology, postmortem inspection and molecular typing from tuberculin skin tested cattle, confirmed that mycobacteria infection is more common in intensive dairy farms with large herd size and exotic cattle breeds (e.g. HF) (Ameni et al., 2006, 2007b; Elias et al., 2008; Tsegaye et al., 2010; Firdessa et al., 2012).

those which included tuberculin skin test, abattoir and molecular epidemiology studies as well as pathological evidence. (2) Publications that included the transmission dynamics of M. bovis and M. tuberculosis between animal and human, and among animals. (3) Publications that addressed the control challenges of TB. Based on the exclusion and inclusion criteria, articles were screened as described in Fig. 1. Briefly, titles of the articles (in some cases abstracts) were reviewed in the aforementioned databases manually, and their full length articles or abstracts accessed if it was found relevant. After full text or abstract review, articles were selected based on two perspectives. (1) Regarding the epidemiology, articles were selected only based on their content of evidence/numerical data/such as tuberculin test, pathology or mycobacterial strains. (2) In the case of transmission and control challenges, articles were selected based on evidences to support the research output (especially transmission dynamics), while other articles were considered based on strong author suggestion or research implication. Strains were retrieved from published articles as well as from the respective databases, http://www. Mbovis.org for M. bovis and SpolDB4.0 (http://www.pasteurguadeloupe.fr:8081/SITVITDemo) for M. tuberculosis. Strains of M. bovis and M. tuberculosis were listed (Table 3) and clustering was calculated for each study location (Table 4). Geospatial distributions of M. bovis and M. tuberculosis spoligotypes were generated using Arc GIS version 10.2.1 (Esri, Redlands, California 92373-8100, USA). 3. Review 3.1. Epidemiology of M. bovis and M. tuberculosis in animals in Ethiopia In Ethiopia, the epidemiology of BTB is well studied in animals when compared to other neglected tropical diseases. In this review, both M. bovis and M. tuberculosis have predominantly been found as cause of BTB in animals. Nonetheless, these studies have mainly concentrated on cattle. Few studies have been performed on small ruminants, camel, pig and wildlife. Based on the inclusion and exclusion criteria (see methods), 65 publications were selected and included in this review. Out of these, 49 articles included at least tuberculin test and abattoir survey (Fig. 1). Twenty eight publications were based on tuberculin test (Table 1) while 21 were abattoir studies (Table 2). Additional diagnostic techniques such as culturing and genotyping have been performed on some studies (Tables 1 & 2). Moreover, 15 studies that employed spoligotyping of M.bovis and M.tuberculosis strains were included in this review and presented in Table 3.

3.1.1.2. Other domestic animals. In total, seven articles based on the CIDT test, which include small ruminants, have been reviewed. Two articles focused solely on small ruminants but the remaining 5 articles included other species of animals (Table 1). Based on these studies, PPD reactors in small ruminants occur in low prevalence ranging from 0.6% (2/343) to 7.6% (48/630) (Tschopp et al., 2011; Tafess et al., 2011) (Table 1). Tschopp et al. (2011) reported 1.6%(1/63) goat and 0.6% (2/ 343) sheep PPD reactors in Meskan Gurage zone, while Tafess et al. (2011) reported 7.6% (48/630) prevalence in goats of Adamitulu district, East shewa. On the other hand, Kassa et al. (2012) found 4.3% (81/1884) goats and 1.4% (5/347) sheep PPD reactor animals in three districts of Afar Pastoral Regions of Northeast Ethiopia. In this study, postmortem examination combined with microbiological culture and molecular characterization of the isolate from a strong bovine PPD reactor goat confirmed M. tuberculosis infection in goats which might be transmitted from human (Kassa et al., 2012). Since the Ethiopian pastoral communities have deep rooted and risky traditions of consuming the raw milk of goat and sheep, small ruminants might be playing roles in the zoonotic and reverse zoonosis transmission of TB and needs due consideration. With respect to camel, only 2 CIDT based articles (One of them involved other species of animals) were reviewed which reported 0.4% (2/479) (Gumi et al., 2012a) and 6% (29/480) (Beyi et al., 2014) PPD reactor animals.

3.1.1. Comparative intradermal tuberculin (CIDT) test and other diagnostic methods In total, 28 publications which included CIDT test were selected and reviewed. Twenty publications exclusively focused on cattle. Two articles merely focused in small ruminant while one article considered only in camels. However, five publications were found to include two or more than two species of animals. Some publications employed additional diagnostic tests including molecular tools (Table 1). 3.1.1.1. Cattle. A total of twenty five publications were reviewed. Twenty publications focused only on cattle while 5 publications involved other species of animals (Table 1). According to our reviewed findings, the prevalence of tuberculin test positivity ranged from 0.3% in local breeds (zebu) when kept in a traditional or smallholder production system (Tschopp et al., 2013) to 48% in exotic (Holstein Friesian, HF) when kept under intensive production system (Ameni et al., 2007a) (Table 1). In Ethiopia, it is very common to keep HF and zebu breeds under intensive and extensive farms, respectively, and most studies have been conducted on these breeds being reared in different husbandry systems. Among the selected articles, only eight articles were based on comparative studies on different cattle breeds (HF, HF and zebu cross

3.1.2. Pathological detection The selected abattoir studies included in this review are based on detailed post mortem inspection. In total, 27 articles which include 21 from abattoir and 6 PPD reactors, of different species of animals, were selected and considered for this review to evaluate tuberculous lesion. 3

4 Cattle Cattle Camel Goats Goat and sheep Cattle Cattle Cattle Cattle Camel Cattle Cattle Goats

Addis Ababa & its surroundings Filtu district/Somali region

Arsi/Oromyia

Humera/Tigray

Mekelle/Tigray Dire dawa and Somali Bahr dar city/Amhara

Awash Fentalle (Afar), and Fentalle (Oromiya)

Fiche/Oromiya

Afar

Cattle Cattle Goats Goat and sheep Cattle

Addis Ababa Holeta & Slalle/Oromiya Adami Tulu Jiddo Kombolcha/Oromiya Meskan district/SNNPR

Meskan, Woldia and Bako-Gazer

Goats wildlife Cattle

499: 4 (0.8) 499: 17 (3.4)a 186:0 ND 5377: 57 (0.9) 5377: 238 (4)a 1132: 386 (34.1) NA 630:48 (7.6) 406:0 406: 3 (0.41)a 1214: NA (1.6) 1214: NA (6.8)a 2956:NA (32.3) 421: 10 (2) 479: 2 (0.4) 518: 1 (0.2) 2231: 10 (0.5) 2231: 86 (3.8)a 2033: 36 (1.8) 2033: 96 (4.7)a 584: 2 (0.3) 584:7 (1.2)a 484: 32 (6.6) 484: 42 (8.7)a 480: 54 (11.3) 480: 29 (6.0) 788:10 (1.27) 788: 28 (3.55)a 220: 2 (0.9)a 551:4 (0.7)a

Cattle

Hawassa/SNNPR Welega, Awash, Babille (Harari), Bale Mountains and South Omo Hamer South Omo/ SNNPR

788: 188 (23.9) 763:60 (7.9) 735: 31 (4.2) 320:5 (1.6) 500: 240 (48) 5424: 732 (13.5) 524: 58 (11) 1869:443 (23.7) 1041: 169 (16) 425:27 (6.4) 170:1 (0.9) 203:1 (0.5) 413: 48 (11.6) ND

Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle Cattle Goat Sheep Cattle Wildlife,*

Debre zeit and Addis Ababa Wuchale-Jida District/central Ethiopia Fitche Town/ Oromiya Boji district/Oromiya Holeta/Oromiya Holeta&Selalle/Oromiya Adama/Oromiya Addis Ababa Fitche/Oromyia Arsi-Negelle/Oromiya

Tuberculin test (> 4 mm) Total: Positive (%)

Hosts

Study area

NS ND

ND ND

ND

ND

ND ND ND

ND

ND

ND ND ND

24 : 16 (66.7)

e

36 :16 (44)

c

34 :31 (91.2) ND ND ND 5c,d: 5 (100)

31:31 (100) ND ND ND 5: 5 (100)

ND

ND c

11:11 (100) 52: 52 (100) ND 1:1 (100)

11 :11 (100) NA NA 1:1 (100)

c

ND 48c: 24 (50) ND

ND 24:24 (100) ND

ND

ND

60b: 11 (18) ND ND ND 16b:1 (6.3) 89c:29 (32.5)

ND ND ND ND NA ND ND ND ND ND ND ND ND 29: 17 (58.6)

m-PCR Total: Positive (%)

NA 24b: 0 (0) 15b: 0 (0) ND 20c: 17 (85) 145c: 81 (56) 44b:16 (36.4)

Culture Total: Positive (%)

ND ND

ND ND

ND ND ND

4 : 4 (100) ND ND

ND n

ND

5: 3/2

31/0 ND ND ND 1r: 0/1

ND

11: 8/3 37:31/6 ND 1r: 0/1

ND 0 ND

ND

ND ND ND ND 41:1/0 ND 9: 6/3 ND 7:5/2 ND ND ND 1: 1/0 0

MTC: M.bovis/ MTB

ND ND

ND ND ND

ND

ND

11

0 ND ND ND 4

ND

0 15 ND 0

ND 24 ND

ND

ND ND ND ND 0 ND 2 ND 4 ND ND ND ND 17

NTMs

Isolation of mycobacteria

ND

ND

36 : 25 (69)

n

36 : 34 (94.4) ND ND ND 5n: 5 (100)

n

ND

ND ND ND ND

ND 33ϕ: 9(27) ND

ND

NA ND ND ND ND 153n: 145 (95) 11h: 11 (100) 141k: 12 (8.5) ND ND ND ND ND 87:20 (23)ϕ

Others Total: Positive (%)

(continued on next page)

Tschopp et al. (2015)

Zeru et al. (2014) Beyi et al. (2014) Nuru et al. (2015)

Romha et al. (2013)

Tschopp et al. (2013)

Ameni et al. (2013)

Kassa et al. (2012)

Firdessa et al. (2012) Gumi et al. (2012a)

Tsegaye et al. (2010) Ameni et al. (2011) Tafess et al. (2011) Tschopp et al. (2011)

Tschopp et al. (2010c)

Tschopp et al. (2010b)

Regassa et al. (2010) Tschopp et al. (2010a)

Kiros (1998) Ameni et al. (2003a) Ameni et al. (2003b) Laval and Ameni (2004) Ameni et al. (2007a) Ameni et al. (2007b) Ameni and Erkihun (2007) Elias et al. (2008) Regassa et al. (2008) Ameni et al. (2010)

Reference

Table 1 Skin test reactor animals using CIDT test (cervical) and isolation of the causative agent using culture, multiplex polymerase chain reaction (m-PCR) and other diagnostic techniques from animals, Ethiopia.

G. Romha et al.

Preventive Veterinary Medicine 158 (2018) 1–17

Preventive Veterinary Medicine 158 (2018) 1–17

NA: Not Available; ND: Not Done; MTC: Mycobacterium Tuberculosis Complex; MTB: Mycobacterium Tuberculosis; NTM: Non-Tuberculous Mycobacterium; SNNPR: Southern Nations, Nationalities and Peoples Regional State. a Result is recorded at cut-off > 2 mm. b Milk sample from bovine PPD positive animals. c tissue samples from bovine PPD positive slaughtered animals. d Only from goats. e 24 isolates obtained from tissues of 16 cattle. h Pyrazinamidase test and TCH susceptibility test. k Their milk is tested for acid-fast bacteria. n Slaughter PPD positive animals to detect tuberculous lesion. r Isolatesare from goats. * The study conducted on 28 different wildlife animal species. ϕ Rapid serology test.

ND ND ND ND ND ND ND ND ND ND Cattle Cattle Afar Region and Awash National Park Holeta & Bishoftu/Oromiya

2550:141 (5.5) 720:119 (16.5)

NTMs MTC: M.bovis/ MTB

Hosts Study area

Table 1 (continued)

Tuberculin test (> 4 mm) Total: Positive (%)

Culture Total: Positive (%)

m-PCR Total: Positive (%)

Others Total: Positive (%)

Isolation of mycobacteria

Reference

Dejene et al. (2016) Endalew et al. (2017)

G. Romha et al.

The vast majority have been conducted on cattle (Tables 2 and 3). 3.1.2.1. Cattle. In total, 17 articles (13 abattoir based and 4 sacrificed PPD reactor cattle) were reviewed for pathological detection and characterization in cattle. Prevalence of tuberculous lesion, ranging from 3.5 to 10.2%, have been reported in cattle slaughtered in different abattoirs brought from different agro-ecology and husbandry systems (Shitaye et al., 2006; Berg et al., 2009; Demelash et al., 2009; Ameni et al., 2010; Gumi et al., 2012b) (Table 2). In Ethiopia, cattle brought to abattoir to be slaughtered are predominantly of zebu breeds kept under traditional farming system by subsistence farmers. In such a type of farming system, tracing back of the geographical origins of the study animals was difficult (Teklu et al., 2004; Berg et al., 2009) due to the absence of animal certification. Hence, to investigate epidemiological (environmental) risk factors which could contribute for the existence of BTB was impossible rather we tried to characterize the pathology of sacrificed PPD reactor cattle, for example, the impact of intensification on the severity of pathology. It was indicated that the severity of the pathology depends on breed and husbandry system. Both the prevalence and severity of pathology have been found higher in HF than in zebu cattle, and cattle managed intensively/kept in-door were more at risk than cattle kept in pasture (Ameni et al., 2006, 2008; Biffa et al., 2012). Tuberculous lesions were predominantly found in the respiratory tract in animals reared under intensive management (Ameni et al., 2007a; Tsegaye et al., 2010; Ameni et al., 2011; Firdessa et al., 2012) while the digestive system more likely to be found afflicted in traditional husbandry system (Ameni et al., 2007b; Ameni et al., 2011). 3.1.2.2. Other domestic animals. In camel, six studies based on gross pathological detection conducted in Dire Dawa, Addis Ababa and other abattoirs were reviewed, and tuberculous-like lesion prevalence of 4.5–12.3% were reported (Mamo et al., 2009, 2011; Gumi et al., 2012b; Zerom et al., 2013; Kasaye et al., 2013; Beyi et al., 2014) (Table 2). In fact, camels slaughtered in the abattoirs were brought from different pastoral and agro-pastoral regions of Ethiopia. Based on tuberculous lesion detected in abattoirs, highest prevalence rates were observed in camel than any other species of animals (Table 2). For example, difference in prevalence were recorded in cattle (1%), goats (4.4%) and camels (11.7%) kept in the same husbandry system (pastoralist and agro-pastoralists) (Gumi et al., 2012b). Three abattoir based articles which include goat, mainly conducted at Mojo export abattoir were reviewed, and the prevalence of tuberculous-like lesion ranging from 3.5 to 4.4% were reported (Hiko and Agga,2011; Gumi et al., 2012b; Deresa et al., 2013). In Ethiopia, intensive farming of small ruminants is not being practiced. Therefore, goats and sheep which has been brought to slaughterhouse, were of local breeds, kept under extensive production systems, either in mixed crop–livestock or in pastoral and agro-pastoral production systems, and were purchased from different local markets (Table 2). Recently, one study reported that 5.8% of the inspected pigs had tuberculous like lesion based on gross pathology (Arega et al., 2013) (Table 2). Two studies detected tuberculous lesions in sacrificed PPD reactor goats and isolated M. tuberculosis (Tschopp et al., 2011; Kassa et al. (2012). 3.1.3. Molecular epidemiology Conventional diagnostic tools such as culture and biochemical tests have been used to identify mycobacterial species infecting animals (Kiros, 1998; Ameni and Erkihun, 2007; Regassa et al., 2008) despite their low discrimination ability. Currently, using molecular techniques, considerable strains of M. bovis (Ameni et al., 2007a; Biffa et al., 2010a; Mamo et al., 2011; Firdessa et al., 2012; Mekibeb et al., 2013), M. tuberculosis (Tschopp et al., 2011; Kassa et al.,2012; Arega et al., 2013; Deresa et al., 2013), and both M. bovis and M. tuberculosis (Berg et al., 2009; Ameni et al., 2010; Gumi et al., 2012b; Ameni et al., 2013) have been identified from tuberculoid tissues of abattoir slaughtered and 5

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Table 2 The detection of tuberculous lesion using detailed abattoir inspection, and isolation of mycobacteria using culture, multiplex polymerase chain reaction (m-PCR) and other diagnostic techniques from animals, Ethiopia. Study area

Hossana/SNNPR Addis Ababa Addis Ababa, Gonder, Woldiya, Gimbi, Butajira, and Jinka Pastoral area of Somali and Oromia Addis Ababa, Adama, Hawassa, Yabello, Melge-Wondo Kombolcha/Amhara Hawassa/SNNPR Nekemte/Oromiya Central Ethiopia/Oromiya Pastoralist of Afar & Oromiya Negelle/Oromia Negelle/Oromiya, and Filtu/Oromiya & Somali Addis Ababa &Bishoftu Woldyia/Amhara Oromiya, Somali & Amhara Borena, Kereyu and Minijar Addis Ababa Humera/Tigray Eastern Pastoralists Mekelle/Tigray Dire dawa and Somali Bahir Dar Abattoir

Hosts

Cattle

m-PCR Total: Positive (%)

Tuberculous lesion Culture Total: Positive (%) Total: Positive (%)

751:34 (4.5)

34: 6 (17.6) 32: 1 (3.1)ϕ

ND

Others Total: Positive (%)

ND 1

Isolation of mycobacteria Reference

MTC: M.bovis/ MTB

NTMs

7: 7/0

ND

Teklu et al. (2004)

b

1524:171 (11)

34: 4 (11.8) 135: 119 (88.5)

34 :3 (8.8) ND

4:0 66: 58/8

0 53

Shitaye et al. (2006) Berg et al. (2009)

Camel 276:14 (5.1) Cattle 3322: 337 (10.2)

14:4 (28.6) 406a:105 (25.9)

ND 105: 48 (45.7)

ND ND

4:4/0 45: 45/0

ND 0

Mamo et al. (2009) Biffa et al. (2010a)

Cattle Cattle Cattle goats Camel Cattle Camel goats Pig Cattle Goat Camel Cattle Cattle Camel Cattle Camel Cattle

57: 27 (47) ND ND 65:20 (30.8) 91:31 (34) 50: 36 (72) 81:3 (4) 76:9 (11.8) 49:15 (30.6) NA 78a: 11 (14) 21a: 4 (19) 25: 6 (24) 34:12 (35.3) 36: 22 (61) 49:29 (59.2) 33: 10 (30.3) 96:17 (17.7)

27:27 (100) ND ND ND 31: 21 (68) 36: 28 (77.8) 3: 3 (100) 9: 9 (100) 10: 6 (60) ND 8: 5 (62.5) ND 6: 6 (100) 12: 4 (33.3) 22: 18 (81.8) 29: 4 (13.8) ND 17:15 (88.2)

ND 14b: 4 (28.6) ND NA ND 50:36 (72)c 81:3 (4)d 76:9 (11.8)c 15:10 (66.7)c NA 11:8 (73%)c ND 6:6 (100%) ND ND ND ND ND

27: 25/2 ND ND 20: 18/2 2: 2/0 24: 24/0 1: 0/1 0 5: 0/5 12: 9/3 3: 0/3 4: 4/0 6: 6/0 ND 3: 0/3 2: ND 10:4/6 0

0 ND ND ND 18 4 1 9 1 ND 1 ND 0 4 15 2 ND 14

Ameni et al. (2010) Regassa et al. (2010) Tigre et al. (2010) Hiko and Agga (2011) Mamo et al. (2011) Gumi et al. (2012b)

Cattle Cattle

984:34 (3.5) 32,779:1524 (4.7)

1138: 57 (5) 1,023: 11 (1.1) 940:48 (5.1) 1536: 65 (4.2) 906: 91 (10) 5250: 50 (1) 694: 81 (11.7) 1744:76 (4.4) 841: 49 (5.8). 1029: 63 (6.1) 1990: 69 (3.5) 420:19 (4.5) 500: 25 (5) 582:34 (5.8) 293: 36 (12.3) 768: 49 (6.4) 398: 33 (8.3) 2846:79 (2.8)

Arega et al. (2013) Aylate et al. (2013) Deresa et al. (2013) Kasaye et al. (2013) Mekibeb et al. (2013) Romha et al. (2013) Zerom et al. (2013) Zeru et al. (2013) Beyi et al. (2014) Nuru et al. (2017)

MTC: Mycobacterium Tuberculosis Complex; MTB: Mycobacterium Tuberculosis; NTM: Non-Tuberculous Mycobacterium; SNNPR: Southern Nations, Nationalities and Peoples Regional State Region. 1 Examination of tissues by IS6110 PCR detected the presence of IS6110 specific for MTC. ϕ From animals not having tuberculous lesion. a More than one samples were taken from some animal from different TB suspected tissue/organs. b Subject to histopathological examination. c Acid fast positive. d Could be M. africanum.

Table 3 Number of isolates, spoligotype patterns and the number of new strains reported of M. bovis and M. tuberculosis from animal tissues in different studies from different settings in Ethiopia. Study area

Hosts

Samplea

M. bovis strains Total isolates: Spoligotype/ new

M. tuberculosis strains Total isolates: Spoligotype/ new

Sample collected

Reference

Holeta/Oromiya Addis Ababa, Gonder, Woldiya, Gimbi, Butajira, and Jinka Kombolcha/Amhara Addis Ababa, Adama, Hawassa, Yabello, MelgeWondo Addis Ababa Pastoralist of Afar & Oromiya Meskan district/SNNPR Addis Ababa & its surroundings Negelle/Oromiya, and Filtu/Oromiya & Somali

Cattle Cattle

500 32,779

41: 1/1 58:7/4

0 8:6/1

Tuberculin reactor Abattoir

Ameni et al. (2007b) Berg et al. (2009)

Cattle Cattle

1138 3322

26: 6/3 45(341): 12/6

2:1/0 0

Abattoir Abattoir

Ameni et al. (2010) Biffa et al. (2010a)

Cattle Camel Goat Cattle Cattle Camel Goat Cattle Pig Goat Cattle Camel

1132 906 406b 2956 5250 694 2231b 2033 841 1990 500 293 58736

8: 3/0 2: 2/1 0 31:4/0 24: 6/2 0 0 3: 1/0 0 0 6: 3/1 0 243 (233):45/18

3: 2/0 0 1:1/0 0 0 1:1/0 1: 1/0 2: 2/0 5: 3/2 3: 3/2 0 3: 3/2 29:23/7

Tuberculin reactor Abattoir Tuberculin reactor Tuberculin reactor Abattoir

Tsegaye et al. (2010) Mamo et al. (2011) Tschopp et al. (2011) Firdessa et al. (2012) Gumi et al. (2012b)

Tuberculin reactor Tuberculin reactor Abattoir Abattoir Abattoir Abattoir

Kassa et al. (2012) Ameni et al. (2013) Arega et al. (2013) Deresa et al. (2013) Mekibeb et al. (2013) Zerom et al. (2013) 15 studies

Afar region Fiche/Oromiya Addis Ababa & Bishoftu Oromiya, Somali & Amhara Addis Ababa Eastern Pastoralists Total 1 a b

45 spoligotypes were identified but the authors considered identical spoligotypes from the sameanimal as one. Either tuberculin tested or post mortem examined animals. Include sheep. 6

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Table 4 Geospatial distribution of M. bovis and M. tuberculosis spoligotype pattern isolated from sacrificed PPD reactor and abattoir slaughter animals, Ethiopia (-, indicates the absence of mycobacterial spoligotype patterns and isolate). Geographical isolation: Specific location/ Region/type of studya

Hosts

Sample

strains

Reference

M. bovis

M. tuberculosis

Spoligotype pattern

No. of isolates

Spoligotype patterns

No. of isolates

Holeta/Oromiya/Field

Cattle

500

SB1176

41

–

–

Addis Ababa/abattoir

Cattle

2800

–

Cattle

14314

–

–

Woldiya/Amhara/abattoir

Cattle

4338

SIT59

1

Gimbi/Oromiya/abattoir

Cattle

3250

Butajira/SNNPR/abattoir

Cattle

4606

SIT149 SIT1 New1 SIT1742

1 2 1 1

Jinka/SNNPR/abattoir

Cattle

3471

SIT1688

2

Kombolcha/Amhara/abattoir

Cattle

1138

SIT262

2

Melge-Wondo/SNNPR/abattoir Hawassa/SNNPR/abattoir Yabello/Oromiya/abattoir

Cattle Cattle Cattle

3322 (sample size not available for each specific location)

–

–

Addis Ababa/abattoir

Cattle

–

–

Adama/Oromiya/abattoir

Cattle

–

–

Addis Ababa/Field

Cattle

1132

SIT149 SIT121

2 1

Tsegaye et al. (2010)

Akaki/Addis Ababa/abattoir

Camelc

906

Meskan district/SNNPR/Field

Goat

406

4 1 1 2 8 1 7 3 2 2 2 8 1 2 1 10 1 1 1 13 4 2 4 2 1 1 1 1 1 9 2 4 1 3 1 1 1 3 1 1 1 1 5 1 2 1 1 –

–

Gonder/Amhara/abattoir

SB0134 SB0133 SB1489 SB1477 SB1176 SB0134 SB1476 SB1176 SB0133 SB1176 SB0133 SB1476 SB1477 SB1476 SB1176 SB0133 SB1488 SB1477 SB1476 SB1176 SB0133 SB0912 SB1490 SB1491 SB1492 SB0133 SB1176 SB1265 SB01517 SB1176 SB1517 SB0133 SB0134 SB0912 SB1520 SB1518 SB1519 SB1176 SB0912 SB1521 SB1522 SB1468 B1176 B0134 SB0133 SB0133 SB1953 –

– – SIT837

– – 1

Addis Ababa & its surroundings/Field

Cattle

2956

–

Cattle

5250

–

–

Filtu/ Somali/abattoir Amibara districts/Afar/Field Fiche/Oromiya/Field

Camel Goats Goat Cattle

694 1744 2231 2033

13 5 12 1 17 2 2 3 – – – 3

–

Negelle/Oromiya,/abattoir

B1176 SB0133 SB0134 SB1477 SB0133 SB1942 SB1983 SB0933 – – – B1176

Mamo et al. (2011) Tschopp et al. (2011) Firdessa et al. (2012)

Addis Ababa & Bishoftu/abattoir

Pig

841

–

–

SIT 149 – SIT149 SIT149 SIT53 SIT1088 SIT1195 New2

1 – 1 1 1 2 1 2

Ameni et al. (2007b) Berg et al. (2009)

Ameni et al. (2010)

Biffa et al. (2010a)

Gumi et al. (2012b)

Kassa et al. (2012) Ameni et al. (2013) Arega et al., 2013

(continued on next page)

7

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Table 4 (continued) Geographical isolation: Specific location/ Region/type of studya

Hosts

Sample

strains

Reference

M. bovis

M. tuberculosis

Spoligotype pattern

No. of isolates

Spoligotype patterns

No. of isolates

SIT53 New3 New4 –

1 1 1 –

Deresa et al. (2013)

SIT 21 New5 New6 18

1 1 1 29

Zerom et al. (2013)

Modjo/Oromiya/abattoir

Goatb

1990

–

–

Addis Ababa/Abattoir

Cattle

500

Jigiga/Somali/abattoir

Camel

293

SB1176 SB1477 SB0133 New –

2 2 1 1 –

58736

24

233

Dire Dawa/abattoir Total

Mekibeb et al. (2013)

15 studies

a Samples were collected from two types of studies in the original studies; 1) Abattoir study- tuberculous lesions were collected from slaughtered animals in abattoir, and 2) Field study - based on tuberculin test and strong reactor animals were slaughtered to sample tuberculous lesion. b Originated mainly from Arsi, Borana, Jimma, Somali and South Wello. c SB0133 from Borena and SB1953 from Metahara and Awash area camel; New1, Not available; New2, octal value 777,767,777,777,771; New3,octal value 03,777,540,003,171; New4, octal value 777,757,777,560,771; New5,octal value 73,357,776,763,671; New 6, octal value 773,357,777,763,661.

Fig. 2. Geospatial distribution of M. bovis and M. tuberculosis spoligotype isolated from tissues of PPD reactor animals, Ethiopia.

8

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Fig. 3. Geospatial distribution of M. bovis and M. tuberculosis spoligotype isolated from tissues of abattoir slaughtered animals, Ethiopia.

have been brought to abattoir from extensive husbandry systems (croplivestock mixed farming and pastoralists). However, we tried to indicate their origin based on the evidence documented in the original papers and the information we received from authors (Table 4). The high isolation frequency of SB1176 (M. bovis) demonstrates dominance of this spoligotype as a major cause of BTB in Ethiopian cattle (Ameni et al., 2007b; Berg et al., 2009; Biffa et al., 2010a; Firdessa et al., 2012; Mekibeb et al., 2013). Likewise, several new spoligotypes of M. bovis have been reported recently from different production settings in the country (Ameni et al., 2007a; Berg et al., 2009; Ameni et al., 2010; Biffa et al., 2010a; Mamo et al., 2011; Mekibeb et al., 2013) (Table 3). M. bovis and M. tuberculosis species have not been identified from Ethiopian wildlife. Moreover, according

sacrificed PPD reactor animals (cattle, camels and goats) (Table 3). These studies have showed wide distribution of different strains of M. bovis and M. tuberculosis in animals in various regions across the country (Figs. 2, 3). Strains from sacrificed strong PPD reactor animals were located in their geographical isolation (Fig. 2). However, the geographical origins of the study animals brought to abattoir could not be traced thereby locating the precise isolation settings of each mycobacterial strain was difficult. Instead, we located the strains based on abattoir where they were isolated (Fig. 3). This is because most local (regional) abattoirs were supplied from the nearby settings with small area coverage except Addis Ababa abattoir, which covers a larger geographical area due to high demand for meat products in the capital (Table 3). It was difficult to locate the origin of camels and goats as they 9

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Table 5 Clustering of M. bovis and M. tuberculosis spoligotype pattern based on specific study, Ethiopia (-, indicates the absence of Clustered and orphan mycobacterial isolates). Mycobacterial species

Spoligotype patterns

Hosts

Total isolates

Orphan

Cluster size

Reference

Mycobacterium bovis

SB1176 SB0134 SB0133 SB1489 SB1477 SB1176 SB1476 SB1488 SB1176 SB0133 SB0912 SB1490 SB1491 SB1492 SB1176 SB1517 SB1265 SB0133 SB0134 SB0912 SB1520 SB1518 SB1468 SB1519 Sb1421 SB1522 B1176 B0134 SB0133 SB0133 SB1953 B1176 SB0133 SB0134 SB1477 SB0133 SB1942 SB1983 SB0933 SB1176 SB1176 SB1477 SB0133 New 24 strains

Cattle Cattle

41 64

– 8

41 2–10

Ameni et al. (2007a) Berg et al. (2009)

Cattle

26

1

2–13

Ameni et al. (2010)

Cattle

36

12

2–8

Biffa et al. (2010a)

Cattle

8

1

2–5

Tsegaye et al. (2010)

Camel

2

2

–

Mamo et al. (2011)

Cattle

31

1

5–15

Firdessa et al. (2012)

Cattle

24

–

2–17

Gumi et al. (2012b)

Cattle Cattle

3 6

– 2

3 2

Ameni et al. (2013) Mekibeb et al. (2013)

233

27

2–41

Cattle

8

4

2

Berg et al. (2009)

Cattle Cattle

2 3

– 1

2 2

Ameni et al. (2010) Tsegaye et al. (2010)

Cattle

2

2

–

Ameni et al. (2013)

Camel Goat Goat Pig

1 1 5

1 1 1

– – 2

Gumi et al. (2012b) Tschopp et al. (2011) Kassa et al. (2012) Arega et al. (2013)

Goat

3

3

–

Deresa et al. (2013)

Camel

3

3

–

Zerom et al. (2013)

29

17

2

Totala Mycobacterium tuberculosis

Totala a

SIT59 SIT149 SIT1 New1 SIT1742 SIT1688 SIT262 SIT149 SIT121 SIT149 SIT53 SIT 149 SIT837 SIT149 SIT1088 SIT1195 New2 SIT53 New3 New4 SIT 21 New5 New6 18 strains

Total clustering = 206/233 and 12/29 for M.bovis and M.tuberculosis, respectively (NB, total clustering = clustered isolates/total isolates).

10

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

been found as the major cause of TB in cattle kept under extensive husbandry systems and with other domestic animals (Tables 1 & 2). Based on these evidences, the existence of a high possibility of cattle to cattle transmission of M. bovis, specifically, among intensive farming can be speculated. Some studies have tried to discover the entry routes of mycobacterium species in cattle depend on pathology and isolation of the causative agent. Based on these results, it can be suggested that the transmission routes of mycobacterium species in intensive and extensive husbandry systems are respiratory (Ameni et al., 2007a; Tsegaye et al., 2010; Ameni et al., 2011; Firdessa et al., 2012) and digestive system (Ameni et al., 2007b, 2011), respectively.

to the reviewed articles, mycobacterium species have not been isolated from sheep. It was believed that M. tuberculosis complex species are the causative agent for the development of tuberculous/granulomatous lesions in the predilection tissues of these mycobacteria (reviewed in Kiran et al., 2016). However, in this review, the frequency of non-tuberculous mycobacteria (NTM) isolation rate from tuberculous lesions was found to be more than one third (37%) of the total isolated mycobacteria species even though varied among the study settings (Tables 1 & 2). The isolation rate of NTM from tuberculous lesions likely to be high in cattle kept extensively (Berg et al., 2009; Ameni et al., 2011, 2013; Romha et al., 2013; Zeru et al., 2013). The isolation of NTM was also common from tuberculous lesion in other animals reared under extensive husbandry systems; goat (Gumi et al., 2012b; Kassa et al., 2012), camel (Mamo et al., 2011; Gumi et al., 2012b; Zerom et al., 2013) and wildlife (Tschopp et al., 2010a, b) (Tables 1, 2). This indicates the role of NTM in causing of tuberculous lesions or pathology.

3.1.4.2. Human to animal. In this review, adequate evidences were not found to hypothesize the transmission of M. bovis from human to animals. However, the isolation of M. tuberculosis from bovine milk (Ameni and Erkihun, 2007; Regassa et al., 2008; Mariam, 2014) and tissues of different animal species such as bovine (Berg et al., 2009; Ameni et al., 2010, 2013; Arega et al., 2013; Aylate et al., 2013), caprine (Kassa et al., 2012; Deresa et al., 2013), camel (Gumi et al., 2012b; Zerom et al., 2013) and pig (Arega et al., 2013) could likely justify the possible transmission of M. tuberculosis from human to animals. It had been observed that tuberculin positivity was found to be three times higher in cattle owned by farmers with TB as compared to those owned by farmers with no active TB (Regassa et al., 2008). Ameni et al. (2011) isolated M. tuberculosis, SIT149, from cattle in central Ethiopia, a strain commonly isolated in human in the area.

3.1.4. Transmission dynamics of M. bovis and M. tuberculosis 3.1.4.1. Animal to animal. A total of 24 M. bovis and 18 M. tuberculosis spoligotypes were isolated from 15 studies that employed spoligotyping (Tables 4, 5). Total clustering of M. bovis and M. tuberculosis were 88.4% (206/233) and 41.4% (12/29), respectively. In cattle, higher isolation frequency was seen in M. bovis than M. tuberculosis (Table 5). In M. bovis, the highest frequency was observed in SB1176 with 41 isolates per specific study, while maximum frequency for M. tuberculosis was only two (Table 4). In fact, M. tuberculosis strains such as SIT149, SIT53 and SIT37 have frequently been isolated in humans and SIT149 has been found to be dominant (Gumi et al., 2012b; Mihret et al., 2012; Ameni et al., 2013; Firdessa et al., 2013; Garedew et al., 2013a). For example, in central Ethiopia it has been reported that 26.2% (34/130) (Ameni et al., 2013) and 19.8% (19/96) (Garedew et al., 2013a) of the M. tuberculosis isolates, were SIT149. Similarly in cattle, the highest frequency was observed in SIT149. Nevertheless, in contrast to humans, maximum isolation frequency of M. tuberculosis in cattle per specific study was two (Table 4). On the other hand, of the total M. bovis strains isolated in the country, about 105 were SB1176 (Table 5). All the publications included in this review showed that SB1176 was isolated only from cattle. In Holeta farm where tuberculin positivity was found 48%, only SB1176 has been isolated from 17 sacrificed PPD reactor cows with 41 isolates, and it was suggested that the farm appears to be infected with this strain (Ameni et al., 2007a). The same study demonstrated that the reduction of PPD reactor prevalence from 48% to 1% in four consecutive tuberculin test and segregation rounds within nineteen months (Ameni et al., 2007a). This is because when the number of contacts with TB patients increases, transmission of M. bovis increases (Ameni et al., 2007b). The majority (more than 70%) of SB1176 isolates were collected from Addis Ababa and its surroundings (Table 4) (Ameni et al., 2007a; Biffa et al., 2010a; Tsegaye et al., 2010; Firdessa et al., 2012; Mekibeb et al., 2013) where intensive husbandry systems, keeping HF and cross breed, are being practiced. In this area, it was identified that animals have frequently been purchased and/or sold among farms (Firdessa et al., 2012) which could facilitate the circulation of this strain. In Ethiopia, mixing of different species of animals (e.g., cattle and goat) is common in rural areas in which an extensive husbandry system (crop-livestock mixed farming and pastoralists) is being practiced. Intensification is commonly practiced in large cities and towns in which contacts with other domestic animals and wildlife is hardly present. Nowadays, even though high productive exotic and cross breed animals have been traded from the urban areas around the capital to the rural areas where dairy cattle numbers are still relatively low (Firdessa et al., 2012). These breeds are still mostly being kept indoors and may have less contact with other domestic animals and with no exposure to wildlife. Indeed, except the two M. bovis strains (SB1953 and SB0133) isolated from camels (Mamo et al., 2011), M. tuberculosis and NTM have

3.1.4.3. Animal to human. Recently, it was indicated that M. bovis is not the major cause of human TB lymphadenitis in Ethiopia (Kidane et al., 2002; Abebe et al., 2012; Biadglegne et al., 2013, 2015; Firdessa et al., 2013; Berg et al., 2015) although the transmission of M. bovis from animal to human was suggested. The suggestion was supported through isolation of M. bovis from human (Gumi et al., 2012b; Firdessa et al., 2013; Nuru et al., 2017) as well as considering the risky socio-cultural conditions and practices such as the habit of consumption of raw meat and milk (Ameni et al., 2010; Mengistu et al., 2015; Nuru et al., 2017). Other factors being suggested are, the presence of less protected livestock (industries) workers (Etter et al., 2006; Biffa et al., 2010b) and the existence of close contacts between animals and humans in the Ethiopian society due to low awareness (Ameni and Erkihun, 2007; Tschopp et al., 2011; Gumi et al., 2012b; Firdessa et al., 2012). However, studies have subsequently confirmed that the majority of extra pulmonary TB (EPTB) was due to M. tuberculosis (Kidane et al., 2002; Garedew et al., 2013b; Firdessa et al., 2013). Moreover, zoonotic M. tuberculosis (including other factors) has contributed a significant role in human TB lymphadenitis and M. bovis was excluded to be a major factor (Firdessa et al., 2013; Berg et al., 2015) which appear to support the transmission of M. tuberculosis from cattle to humans. 4. Discussion 4.1. Epidemiology of M. bovis and M. tuberculosis 4.1.1. Distribution In Ethiopia, the epidemiology of BTB is well studied as compared to other neglected tropical diseases. Nonetheless, these studies have mainly concentrated on cattle. This might be due to the fact that cattle have been found as the main host of M. bovis (Amanfu, 2006; Smith et al., 2006; Thoen et al., 2006; Rodwell et al., 2010; Müller et al., 2013; Lopes et al., 2016). In this review, we addressed some risk factors that could be considered imperative for the occurrence of BTB, and mainly related to human activities. The practice of intensification has been suggested as one of the driving factors for the existence of high prevalence of BTB in cattle (Ameni et al., 2007a; Tsegaye et al., 2010; Firdessa et al., 2012). A comparative study has been done by Ameni et al. (2006) on HF cattle 11

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

In Ethiopia, neither M. bovis nor M. tuberculosis has been identified from wildlife. However, Greater kudu has been suggested as a maintenance host for the causative agent of BTB in the Afar Region and Awash National Park, and indicated to be a risk for cattle in the area (Dejene et al., 2016). In Great Britain, the badger has contributed a great role in the epidemiology of M. bovis (Cheeseman et al., 1989; Delahay et al., 2000; Woodroffe et al., 2005). In Spain, the isolation of M. bovis from red deer and European wild boar, which had no contact for about two decades with livestock, indicated the importance of wildlife as maintenance host for M. bovis (Gortazar et al., 2005, 2008). M. bovis has been identified in nine geographically distinct wildlife populations in North American and Hawaii (Miller and Sweeney, 2013). The importance of wildlife in the epidemiology of M. bovis has also reported in African countries such as Zambia (Hangombe et al., 2012) and Tanzania (Katale et al., 2017). However, in Ethiopia, M. tuberculosis was reported to cause TB in animals; cattle (Ameni and Erkihun, 2007; Regassa et al., 2008; Mariam, 2014; Berg et al., 2009; Ameni et al., 2010; Ameni et al., 2013; Aylate et al., 2013), goats (Kassa et al., 2012; Deresa et al., 2013), camels (Gumi et al., 2012b; Zerom et al., 2013) and pigs (Arega et al., 2013). Similar results have been reported in other countries that M. tuberculosis posed TB in different animal species; cattle (Liebana et al., 1995; Mishra et al., 2005; Prasad et al., 2005; Romero et al., 2011; Araújo et al., 2014;), horses (Lyashchenko et al., 2012), and elephants (Lyashchenko et al., 2006).

kept one group under extensive and another group under intensive farming systems. The study confirmed that HF cattle kept under intensive farming system had more PPD reactors and produced high level of IFN−ᵞ and more sever pathology. According to Ameni et al. (1999), the sensitivity and specificity of skin tuberculin test in Ethiopia was determined to be 90.9% and 100%, respectively. Density of cattle was explained to be a significant risk factor for BTB in Belgium (Humblet et al., 2010). The highest incidence of BTB is generally observed in areas where intensive farming is practiced (Cosivi et al., 1998) because of the closer proximity of animals to each other and the increased contacts and interactions between them (Humblet et al., 2010). Cubicle housing (Griffin et al., 1993), high milk production (Barlow, 1997) and overcrowding (Ameni et al., 2006) have also been reported as stressful factors in intensive farming systems. In developing countries, HF cattle are increasingly imported in order to improve milk production and are usually kept under intensive husbandry systems which exacerbate the incidence of BTB in areas where intensive dairy systems are practiced (Cosivi et al., 1998). Recent studies reported that exotic (HF) breed has been found more susceptible than local (zebu) breeds as evaluated using different diagnostic methods (elaborated in Sec. 3.1.1) (Ameni et al., 2003a, b; Ameni et al., 2007a, b; Ameni and Erkihun, 2007; Regassa et al., 2008, 2010; Firdessa et al., 2012; Vordermeier et al., 2012). Epidemiologically, it was reported that European/exotic breeds were more susceptible to BTB than zebu in Iran (as reviewed in Tadayon et al., 2013) and Eritrea (Omer et al., 2001). It was also genetically proven that the genomic regions suggestively associated with BTB susceptibility in HF breeds were on Bos taurus autosomes (BTA) 22 (Finlay et al., 2012), BTA 13 (Bermingham et al., 2014), BTA6 (Kassahun et al., 2015) and BTA 23 (Richardson et al., 2016; Raphaka et al., 2017). Increased risk of tuberculin positivity has been reported in large herd (Ameni et al., 2003a; Ameni and Erkihun, 2007; Elias et al., 2008; Regassa et al., 2008, 2010; Tsegaye et al., 2010; Firdessa et al., 2012) and where there has been a poor sanitation status (Ameni et al., 2003b; Elias et al., 2008; Regassa et al., 2010; Zeru et al., 2014). Herd size has been reported as one of the major risk factors for the occurrence of BTB in different countries; USA, northeastern Michigan (Kaneene et al., 2002), Ireland (Olea-Popelka et al., 2004), Tanzania (Cleaveland et al., 2007) and New Zealand (Porphyre et al., 2008). This is because the more cattle present on a farm, the higher the chance that one of them can acquire the infection (Humblet et al., 2009). Sanitation status might be associated with spreading of slurry on grazing areas without having prior storage (Griffin et al., 1993), or with accumulation of slurry in the pen which could be conducive for the persistence of the organism for long periods of time. Clustering of M. bovis strains based on spoligotype ranged from 66.7% (Biffa et al., 2010a) to 100% (Ameni et al., 2007a). Specifically, SB1176 displayed the highest isolation frequency at country level and per specific study as well. The majority (more than 70%) of SB1176 isolates were collected from Addis Ababa and its surroundings (Table 4) (Ameni et al., 2007a; Berg et al., 2009; Biffa et al., 2010a; Tsegaye et al., 2010; Mekibeb et al., 2013; Firdessa et al., 2012) where animals have frequently been purchased or sold among farms of this area. In and around Addis Ababa, the prevalence of PPD reactor and tuberculous lesions suspected cattle (from abattoir) were relatively high (Tables 1 & 2). Similar results have been reported from other countries (Supply et al., 2003; Guerra-Assuncao et al., 2015) which suggested that in settings of high prevalence, the genetic diversity of sampled strains is usually low. Despite the fact that only two spoligotypes of M. bovis have been isolated from Ethiopian camels (Mamo et al., 2011), studies in other countries have reported that other domestic animals have their own role in the epidemiology of M. bovis: pigs (Di Marco et al.,2012; Muwonge et al., 2012; Bailey et al., 2013), horses (Sarradell et al., 2015; Hlokwe et al., 2016); camels (Narnaware et al., 2015) and goats (Gutierrez et al., 1995, 1997; Cadmus et al., 2009; Higino et al., 2011).

4.1.2. Transmission of M. bovis and M. tuberculosis 4.1.2.1. Animal to animal. The ability of M. bovis to infect a wide variety of species can be attributed to the different routes of transmission by which M. bovis can be transmitted from animal to animal (Thoen et al., 2006) and probably because of the adaptive nature of the bacteria (Waters et al., 2015). Based on spoligotyping, higher clustering was observed in M. bovis strains than M. tuberculosis (Table 4). Specifically, the high isolation frequency of SB1176 in and around Addis Ababa was due to the movement of cattle as elaborated in Section 4.1.1 which indicates transmission of the strain among these dairy farms. Clustering is the evidence of recent transmission between and among the given communities (Small et al., 1994; Bauer et al., 1998; Borgdorff et al., 1998; Yang et al., 1998), and location/area contributes a significant role in its existence (commonly appears in geographically confined population) (Vynnycky et al., 2003; Verver et al., 2004; Oelemann et al., 2007). Low genetic diversity of M. bovis strains indicated on-going local transmission events (due to high transmission rate) (Supply et al., 2003; Guerra-Assuncao et al., 2015). SB1176 has also been isolated from other settings a long distance from Addis Ababa, for instance, Woldiya, Gonder and Butajira (Berg et al., 2009) and Kombolcha (Ameni et al., 2010). This might be due to the trading of high productive exotic and cross breed animals from the urban around the capital to the rural areas (Firdessa et al., 2012) and may become a sources of infection therein. So far, only two spoligotypes of M. bovis (SB1953 and SB0133) have been isolated from camels. SB0133 has been isolated from camels of Borena pastoralists (Mamo et al., 2011). This strain has also been isolated with high frequency from cattle of Borena pastoralists (South-East Ethiopia) (Gumi et al., 2012b). In Spain (Gutierrez et al., 1997), Brazil (Higino et al., 2011), South Korea (Je et al., 2015) and Tanzania (Katale et al., 2015), transmission of M. bovis among different species of animals has been indicated. Recently, it was suggested that Greater kudu could be a risk for cattle reared under extensive farming around the Afar Region and Awash National Park (Dejene et al., 2016). The circulation of M. bovis among wildlife, and between wildlife and cattle was also reported in North America (Miller and Sweeney, 2013) and in Ireland (Biek et al., 2012). SB0133 was isolated from buffaloes (Syncerus caffer) and African civet (Civettictis civetta) in Tanzania (Katale et al., 2017). In Ethiopia, This spoligotype was identified from pastoral cattle (Gumi et al., 2012b) and camels (Mamo et al., 2011) which needs further investigation on its interspecies transmission ability. The high 12

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

percent of cervical lymphadenitis cases in children (Cosivi et al., 1995) associated to the consumption of infected milk (Thoen et al., 2006). In 2011, the EPTB reported in Ethiopia was 33%, one of the highest proportions in the world (WHO, 2011). It has always been claimed that M. bovis would be the possible cause of this high EPTB occurrence. It was suggested that the risk of transmission of the disease to humans is potentially high (Boukary et al., 2011). Two strains of M. bovis (SB0133 and SB0303) were isolated from humans in South-Eastern pastoralists of Ethiopia, and SB0133 was found dominant in cattle of the area (Gumi et al., 2012b). Kidane et al. (2002) identified 6 isolates (6/40, 15%) of M. bovis from human FNA samples in Butajira, southeastern Ethiopia. In Nigeria, M. bovis strains have been isolated from livestock traders (Adesokan et al., 2012). Likewise, M. bovis with identical MIRU-VNTR has been identified in Zambia (Malama et al., 2014). M. bovis strains have also been isolated from human in other countries (Rodwell et al., 2010; Torres-Gonzalez et al., 2013; Sanou et al., 2014; Chan and Mpe, 2015). The isolation of M. bovis strains from human may support its transmission from animal to human. Moreover, recent studies have suggested the transmission of M. tuberculosis from animals to humans and caused EPTB in humans (Firdessa et al., 2013; Berg et al., 2015). M. tuberculosis strains have been identified from animal tissues (Table 3) and pooled milk (Mariam, 2014). Close contacts between humans and animals in rural areas of Ethiopia is very common (Kassa et al., 2012; Tschopp et al., 2013), and consumption of unpasteurized (raw) milk (Tschopp et al., 2011, 2013) and raw meat (Etter et al., 2006; Biffa et al., 2010b) has not been avoided. Individuals who are occupationally exposed to livestock and other animals are also less protected due to inadequate facilities and low level of awareness (Etter et al., 2006; Biffa et al., 2010b; Kassa et al., 2012; Tschopp et al., 2013; Aylate et al., 2013). Like that of M. bovis, these factors could also facilitate the transmission of M. tuberculosis from animal to human. M. tuberculosis were isolated from livestock traders in Nigeria (Adesokan et al., 2012), and meat handlers were being considered a risk group in the same country (Hambolu et al., 2013). In humans it has been reported that among the 35 PCR-positive cases of tuberculous lymphadenitis, 29 (82.9%) were caused by M. tuberculosis and six (17.1%) were caused by M. bovis (Kidane et al., 2002). Likewise, other studies have identified that majority of EPTB were due to M. tuberculosis (Garedew et al., 2013b; Firdessa et al., 2013). A community based study has identified that contact with livestock is being as a risk factor for tuberculous lymphadenitis when compared to pulmonary TB (Berg et al., 2015).

isolation frequency of M. bovis strains (especially SB1176 and SB0133) might indicate that intra-species transmission of M. bovis seems to be more significant especially in areas where intensifications are practiced (Ameni et al., 2007a; Berg et al., 2009; Tsegaye et al., 2010; Firdessa et al., 2012; Mekibeb et al., mekibeb et al., 2013). In Spain, the interspecies and intra-species transmission of M. bovis has been reported with the latter being predominant (Gortazar et al., 2008). It has been suggested that individuals with a history of significant contacts with TB cases (Denholm et al., 2012; Dobler, 2013), can have 5 to 10% lifelong risk of developing TB following primary infection (Barnett et al., 1971; Styblo, 1985), and one TB patient can infects 13 persons per year on average (Styblo and Meijer, 1980). This might result in high isolation frequency of M. tuberculosis strains. For instance, relatively high isolation frequency of SIT149 was reported in central Ethiopia (Ameni et al., 2013; Garedew et al., 2013a) (see Section 3.1.4 subsection animal to animal transmission). In contrast to M. bovis strains, the review found low isolation frequency of M. tuberculosis isolates (Table 5) which could appear to backing that cattle to cattle transmission of M. tuberculosis may be minimal. In Spain, in a farm infected with both M. bovis and M. tuberculosis, it has been reported that the isolation of M. bovis and M. tuberculosis from 52% (16/31) and 3.2% (1/31) of the animals, respectively which eventually indicated the lack of transmission of M. tuberculosis within the herd contrasts to the spreading of M. bovis (Romero et al., 2011). 4.1.2.2. Human to animal. Since cattle are the primary host of M. bovis, to estimate the level of transmission of M. bovis from human to animal is difficult. However, human to cattle transmission of M. tuberculosis can be addressed, and nowadays, it has frequently been reported in Ethiopia. In settings where farm members with high-burden of TB and in close contact with their animals, human-to-cattle transmission of M. tuberculosis is reported (Ameni et al., 2011). The isolation of M. tuberculosis in pastoral goats from Afar Regional state of Ethiopia (Kassa et al., 2012) suggested a transmission of the causative agent from human to goats and this could be associated with the existence of close contact with their animals. This is supported by a study conducted in Spain that isolated M. tuberculosis from three unrelated cattle farms which had staff members of the farm with active TB. In each farm, an animal and a human TB case, caused by M. tuberculosis, were identified. Cattle and human strains isolated from each farm, shared identical mycobacterial interspersed repetitive unit–variable-number tandem repeat (MIRU-VNTR) (Romero et al., 2011). Likewise, in India, Prasad et al., (2005) demonstrated mixed infection (with both M. bovis and M. tuberculosis) in 8.7% and 35.7% of human and animal samples, respectively which indicated the transmission of mycobacteria from cattle to human and vice versa. In rural areas; therefore, the possible risk of human-to-animal transmission of M. tuberculosis could be occurred where animals live in close contact with tuberculous humans (Shitaye et al., 2006; Berg et al., 2009; Ameni et al., 2011; Tschopp et al., 2011; Kassa et al., 2012) and through the practice of spitting traditional medicines such as tobacco juice as identified in Ameni et al. (2011). Moreover, M. tuberculosis has been suggested to be transmitted to cattle through different routes including ingestion of feed contaminated with infected sputum and/or urine from infected farmers (Ameni et al., 2013). Pigs have been found infected with M. tuberculosis (Arega et al., 2013) where they might be exposed to contaminated feed with human shedding (Mohamed et al., 2009). Human to cattle transmission of M. tuberculosis had been demonstrated by the isolation of the same strains from cattle and farm worker who suffered from pulmonary TB in farms where all animals tested on the farm were negative to bovine tuberculin during the previous routine TB testing (Ocepek et al., 2005).

4.2. Control challenges of zoonotic TB in human in Ethiopia Most industrialized countries have been successful in controlling or eradicating BTB from domestic animals by programs that restrict animal movements as well as test-and-slaughtering policies. The situation may be fundamentally different in developing countries. For example, in most African countries, BTB is highly prevalent, but effective disease controls including regular milk pasteurization and slaughterhouse meat inspection, are largely absent (Ayele et al., 2004). As reviewed in this paper, in addition to the wide distribution of M. bovis in the Ethiopian cattle, the isolation of M. tuberculosis isolates from domestic animals in different settings may suggest the circulation of the agent between animals and humans. In fact, similar spoligotype patterns of M. tuberculosis have been isolated from farmers and their cattle (Ameni et al., 2013). The potential control challenges of zoonotic TB in human are summarized as follows: 1 Nowadays, national TB control program strategy, incorporating directly observed treatment short course (DOTS) in Ethiopia (Ministry of Health Ethiopia (MOH, 2008) has been practicing exclusively on human, neglecting the disease in animals, even though it seems difficult for the program to be effective without the taking part of animal health professionals. The DOTS strategy existing in human

4.1.2.3. Animal to human. So far, cattle to human transmissions of M. tuberculosis have not been observed (as reviewed in Michel et al., 2009). It was believed that M. bovis had been responsible for more than fifty 13

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

2

3

4

5

6

2012; Firdessa et al., 2012). The low standard of hygiene in the production farms (Kiros, 1998; Shitaye et al., 2006) might support the existence of mycobacterial species and their transmissions.

will not directly impact the control of BTB (Firdessa et al., 2012) as BTB is a neglected tropical zoonotic disease which is underestimated and has not been receiving scientific attention and resources as compared to its impacts (Olea-Popelka et al., 2017; WHO/FAO/OIE, 2017). Likewise, advanced laboratory tools required to diagnose zoonotic TB are frequently unavailable, and the disease is resistant to pyrazinamide, one of the four essential medications used in the current standard first-line anti-TB treatment regimen (WHO, FAO and OIE, 2017). In Ethiopia, based on the detection of tuberculous lesions, condemnation of carcasses totally or partially is a standard practice for the control of zoonotic TB infections at abattoirs. Detection of tuberculous lesions in slaughterhouses takes place by observation of the visible tuberculous lesions in infected cattle using routine abattoir inspection protocols. However, this method has low sensitivity and is insufficient to detect the majority of TB lesions at the gross pathology level and subsequently infected meat can get approved for human consumption (Teklu et al., 2004; Biffa et al., 2010b; Aylate et al., 2013). The quality of such practices may vary from place to place and/or abattoir to abattoir (Biffa et al., 2010b) as well as from person to person. Moreover, it was estimated that more than half of slaughtered animals each year are illegally processed in backyard system without undergoing proper meat inspection, thus posing a great health risk to the consumers (Biffa et al., 2010b). In Ethiopia, official slaughter supplies only 28% of the total carcass, and the rest 72% comes from backyard slaughter. This indicates that the problem of TB could not be solved even with very efficient control on the official slaughter (Etter et al., 2006). Zoonotic TB among abattoir workers in Ethiopia has never been highlighted as occupational disease; therefore, it remains unknown to the public. Although undefined, inhalation exposure during slaughter procedures and ante-mortem inspection when infected carcasses are opened might have epidemiological role in the zoonotic transmission of TB among the abattoir workers in Ethiopia (Biffa et al., 2010b). Zoonotic TB risk assessment using meta-analysis has been done in Ethiopia (Etter et al., 2006) which indicated that the risk of releasing an infected carcass in to the food chain was high and the meat inspection was insufficient to offer consumers a great guarantee of safety of cattle meat. It had been reported that BTB in cattle follows subclinical presentation and most TB infected cattle seem apparently healthy, but they show an immunological response to tuberculin (Collins, 2006; Ameni et al., 2007a; Firdessa et al., 2012). This might be difficult to detect the diseased animals by the owners and/or experts to take measures wherever possible, and such asymptomatic animals could be potential disseminators of the agent (Menin et al., 2013). In Spain, Romero et al. (2011) also isolated M. tuberculosis from three cattle farms with no TB compatible lesions. Long standing risky feeding practices such as eating of raw meat and drinking of raw milk and very common close contact of animals with humans in most rural areas (Etter et al., 2006; Shitaye et al., 2006; Ameni et al., 2011; Tschopp et al., 2011; Kassa et al., 2012) have not, so far, been avoided in Ethiopia especially in the rural areas. These conditions are considered as main potential risk factors that favor the spreading of zoonotic TB between human and cattle (Berg et al., 2015), which could also hinder the control program. Unrestricted movement of animals could make it difficult to control the disease. To increase the financial well-being of farmers, significant number of high productive exotic and cross breed animals are likely to be traded from the urban to the rural areas. However, without any control strategy the risk of spreading BTB by such movements is high and may create new hot-spots of BTB in other parts of the country (Firdessa et al., 2012). Because the higher the contact among herds, the larger the chance of acquiring BTB infection (Dejene et al., 2016). Intensification of dairy herds by itself is being suggested likely to cause the spread of BTB (Alvarez et al.,

This systematic review study has its own limitations. (1) In abattoir studies, locating the specific geographical isolation of M. bovis and M. tuberculosis was difficult due to the absence of the practice of animal certification especially in extensive farming systems. Such types of problems were felt in the original papers of abattoir studies in which case strains were mapped based on abattoir where they were isolated as depicted. (2) Transmission dynamics were not tracked based on DNA fingerprint change through annual analysis of cluster frequency in subsequent years since data of majority studies included in this review were not based on long-term follow-up studies. 3) It would be interesting to evaluate grouping/clustering or diversity of the isolated strains using MIRU-VNTR technique since it offers higher level of discrimination than spoligotyping. However, most studies included in this review did not employ this technique.

5. Conclusion M. bovis is widely distributed in Ethiopian cattle. It has also been detected in camels using molecular tools. In addition, the isolation of M. tuberculosis isolates from cattle, camel, small ruminant and pigs in different settings of the country may suggest the circulation of the agent between animals and humans. The importing of exotic breeds and movement/trading of these animals among farms and across regions (actually this is a government strategy) without setting control strategy, increased the risk of BTB. Molecular identification of M. tuberculosis in animals and animal products as well as demonstration of M. tuberculosis in lymphadenitis (cervical lymph node TB) in humans in recent times have brought new insights in the epidemiology and transmission dynamics of zoonotic TB. The habit of eating raw meat and unpasteurized (or raw) milk as well as the absence of effective meat inspection may exacerbate the transmission from animal to human. The existence of close contact in rural areas might also be a risk for potential transmission of M. tuberculosis from human to animal, and these animals may become a source of infection for human TB. This warrants the integration of the TB control program (only in humans) with the veterinary sector to control the disease in animals too. Therefore, it is high time to put in to effect the concept of “One Health’’ so that the human and animal health subsectors can cooperate to control TB cost effectively. Moreover, the national TB control programs in Ethiopia should also consider implementing effective strategies such as surveying zoonotic TB cases among the risky communities such as the pastoralists to have improved evidences, consistently with the recently launched roadmap for tackling zoonotic tuberculosis (WHO/OIE/FAO, 2017). Standardization of meat inspection protocols in abattoirs (in line with international sanitary requirements), enhanced training and competency testing of meat inspectors, control backyard slaughters and raising public awareness are recommended as essential and cost-effective interventions to improve meat inspection service and subsequently protect consumers’ health (Etter et al., 2006; Biffa et al., 2010b). Moreover, the test and slaughter strategy to reduce the incidence of BTB in animals is economically unaffordable currently in Ethiopia. Alternatively, tuberculin skin testing (early screening) and segregation might be applicable. Control strategies such as sound animal management and movement control (Firdessa et al., 2012), could be feasible in Ethiopia if applicable in a sustained manner. Furthermore, government should encourage and create incentives for farmers who strictly follow the TB control program such as certifying each animal as being free of TB and create market linkage for their products that could lead them to better economic values.

14

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Competing interest

Barnett, G.D., Grzybowski, S., Styblo, K., 1971. The current risk of contracting evolutive tuberculosis, in Saskatchewan, according to the state of previous tuberculin tests and x-ray image. Bull. Int. Union Tuberc. 45, 55–79. Bauer, J., Yang, Z., Poulsen, S., Andersen, A.B., 1998. Results from 5 years of nationwide DNA fingerprinting of Mycobacterium tuberculosis complex isolates in a country with a low incidence of M. tuberculosis infection. J. Clin. Microbiol. 36, 305–308. Berg, S., Firdessa, R., Habtamu, M., Gadisa, E., Mengistu, A., et al., 2009. The burden of mycobacterial disease in Ethiopian cattle: implications for public health. PLoS One 4, e5068. Berg, S., Schelling, E., Hailu, E., Firdessa, R., Gumi, B., et al., 2015. Investigation of the high rates of extrapulmonarytuberculosis in Ethiopia reveals no single driving factor and minimal evidence for zoonotic transmission of Mycobacterium bovis infection. BMC Infect. Dis. 15, 112. Bermingham, M.L., Bishop, S.C., Woolliams, J.A., Pong-Wong, R., Allen, A.R., McBride, S.H., et al., 2014. Genome-wide association study identifies novel loci associated with resistance to bovine tuberculosis. Heredity 112, 543–551. Beyi, A., Gezahegne, K., Mussa, A., Ameni, G., Ali, M., 2014. Prevalence of bovine tuberculosis in dromedary camels and awareness of pastoralists about its zoonotic importance in Eastern Ethiopia. J. Vet. Med. Anim. Health 6, 109–115. Biadglegne, F., Tesfaye, W., Sack, U., Rodloff, A.C., 2013. Tuberculous lymphadenitis in Northern Ethiopia: in a public health and microbiological perspectives. PLoS One 8, e81918. Biadglegne, F., Merker, M., Sack, U., Rodloff, A.C., Niemann, S., 2015. Tuberculous lymphadenitis in Ethiopia predominantly caused by strains belongingto the Delhi/ CAS lineage and newly identified Ethiopian clades of the Mycobacterium tuberculosis complex. PLoS One 10, e0137865. Biek, R., OHare, A., Wright, D., Mallon, T., McCormick, C., et al., 2012. Whole genome sequencing reveals local transmission patterns of Mycobacterium bovis in sympatric cattle and badger populations. PLoS Pathog. 8, e1003008. Biffa, D., Skjerve, E., Oloya, J., Bogale, A., Abebe, F., Dahle, U., Bohlin, J., Djønne, B., 2010a. Molecular characterization of Mycobacterium bovis isolates from Ethiopian cattle. BMC Vet. Res. 6, 28. Biffa, D., Bogale, A., Skjerve, E., 2010b. Diagnostic efficiency of abattoir meat inspection service in Ethiopia to detect carcasses infected with Mycobacterium bovis: implications for publichealth. BMC Public Health 10, 462. Biffa, D., Bogale, A., Godfroid, J., Skjerve, E., 2012. Factors associated with severity of bovine tuberculosis in Ethiopian cattle. Trop. Anim. Health Prod. 44, 991–998. Borgdorff, M.W., Nagelkerke, N., van Soolingen, D., dehaas, P.E.W., Veen, J., van Embden, J.D.A., 1998. Analysis of tuberculosis transmission between nationalities in the Netherlands in the period 1993–1995 using DNA fingerprinting. Am. J. Epidemiol. 14, 187–195. Boukary, A.R., Thys, E., Abatih, E., Gamatie, D., Ango, I., et al., 2011. Bovine tuberculosis prevalence survey on cattle in the rural livestock system of Torodi, Niger. PLoS One 6, e24629. Buddle, B.M., Wedlock, D.N., Denis, M., Skinner, M.A., 2005. Identification of immune response correlates for protection against bovine tuberculosis. Vet. Immunol. Immunopathol. 108, 45–51. Cadmus, S.I., Adesokan, H.K., Jenkins, A.O., van Soolingen, D., 2009. Mycobacterium bovis and M. tuberculosis in goats, Nigeria. Emerg. Infect. Dis. 15, 2066–2067. Cassidy, J.P., 2006. The pathogenesis and pathology of bovine tuberculosis with insights from studies oftuberculosis in humans and laboratory animal models. Vet. Microbiol. 112, 151–161. Chan, H.H.Y., Mpe, J., 2015. A rare cause of pulmonary tuberculosis. Clin. Correspondence 128, 81–83. Cheeseman, C.L., Wilesmith, J.W., Stuart, F.A., 1989. Tuberculosis: the disease and its epidemiology in the badger, a review. Epidem. Inf. 103, 113–125. Cleaveland, S., Shaw, D.J., Mfinanga, S.G., Shirima, G., Kazwala, R.R., Eblate, E., Sharp, M., 2007. Mycobacterium bovis in rural Tanzania: risk factors for infection in human and cattle populations. Tuberculosis 87, 30–43. Collins, J.D., 2006. Tuberculosis in cattle: strategic planning for the future. Vet. Microbiol. 112, 369–381. Cosivi, O., Meslin, F.X., Daborn, C.J., Grange, J.M., 1995. Epidemiology of Mycobacterium bovis infection in animals and humans, with particular reference to Africa. Rev. Sci. Technol. 14, 733–746. Cosivi, O., Grange, J.M., Daborn, C.J., Raviglione, M.C., Fujikura, T., et al., 1998. Zoonotic tuberculosis due to Mycobacterium bovis in developing countries. Emerg. Infect. Dis. 4, 59–70. Dawson, K.L., Bell, A., Kawakami, P.R., Coley, K., Yates, G., Desmond, M., Collins, M.D., 2012. Transmission of Mycobacterium orygis (M. tuberculosis Complex Species) from a tuberculosis patient to a dairy cow in New Zealand. J. Clin. Microbiol. 50, 3136–3138. De la Rua-Domenech, R., 2006. Human mMycobacterium bovis infection in the United Kingdom: incidence, risks, control measures and review of the zoonotic aspects of bovine tuberculosis. Tuberculosis (Edinb.) 86, 77–109. Dejene, S.W., Heitkönig, I.M.A., Prins, H.H.T., Lemma, F.A., Mekonnen, D.A., Alemu, Z.E., et al., 2016. Risk factors for bovine tuberculosis (bTB) in Cattlein Ethiopia. PLoS One 11, e0159083. https://doi.org/10.1371/journal.pone.0159083. Delahay, R.J., Langton, S., Smith, G.C., Clifton-Hadley, R.S., Cheeseman, C.L., 2000. The spatio-temporal distribution of Mycobacterium bovis (bovine tuberculosis) infection in a high-density badger population. J. Anim. Ecol. 69, 428–441. Demelash, B., Inangolet, F., Oloya, J., Asseged, B., Badaso, M., Yilkal, A., Skjerve, E., 2009. Prevalence of bovine tuberculosis in Ethiopian slaughter cattle based on postmortem examination. Trop. Anim. Health Prod. 41, 755–765. Denholm, J.T., Leslie, D.E., Jenkin, G.A., Darby, J., Johnson, P.D., Graham, S.M., et al., 2012. Long-term follow-up of contacts exposed to multidrug-resistant tuberculosis in Victoria, Australia, 1995–2010. Inter. J. Tuberc. Lung Dis. 16, 1320–1325.

The authors have declared that they have no competing interests. Authors’ contributions GR conceived and planned the review study; GR, GG & GM searched and organized the published materials; GR drafted the manuscript; AA prepared the map; GR, GG, GM & AA edited and approved the manuscript. Acknowledgement The authors would like to acknowledge Professor Gobena Ameni for his intellectual contribution in the development of this review. References Abebe, G., Deribew, A., Apers, L., Abdissa, A., Deribie, F., et al., 2012. Tuberculosis lymphadenitis in Southwest Ethiopia: a community based cross-sectional study. BMC Public Health 12, 504. Adesokan, H.K., Jenkins, A.O., van Soolingen, D., Cadmus, S.I.B., 2012. Mycobacterium bovis infection in livestock workers in Ibadan, Nigeria: evidence of occupational exposure. Int. J. Tuberc. Lung Dis. 16, 1388–1392. Alvarez, J., Perez, A.M., Bezos, J., Casal, C., Romero, B., et al., 2012. Eradication of bovine tuberculosis at a herd-level in Madrid, Spain: study of within-herd transmission dynamics over a 12 year period. BMC Vet. Res. 8, 100. Amanfu, W., 2006. The situation of tuberculosis and tuberculosis control in animals of economic interest. Tuberculosis 86, 330–335. Ameni, G., Erkihun, A., 2007. Bovine tuberculosis on small-scale dairyfarms in Adama Town, central Ethiopia, and farmer awareness of the disease. Rev. Sci. Tech. Off. Int. Epiz. 26, 711–719. Ameni, G., Miorner, H., Roger, F., Tibbo, M., 1999. Comparison between comparative tuberculin and gamma-interferon tests for the diagnosis of bovine tuberculosis in Ethiopia. Trop. Anim. Health Prod. 32 (5), 267–276. Ameni, G., Amenu, K., Tibbo, M., 2003a. Bovine tuberculosis: prevalence and risk factor assessment in cattle and cattle owners in Wuchale-Jida District, Central Ethiopia. Int. J. Appl. Res. Vet. Med. 1, 17–25. Ameni, G., Belay, M., Medhin, G., 2003b. A preliminary study on bovine tuberculosis in stallholder farms and its zoonotic implication to owners in Fitche Town, Central Ethiopia. Sudan J. Vet. Res. 18, 37–46. Ameni, G., Aseffa, A., Engers, H., Young, D., Hewinson, G., Vordermeier, M., 2006. Cattle husbandry in Ethiopia is a predominant factor affecting the pathology of bovine tuberculosis and gamma interferon responses to mycobacterial antigens. Clin. Vaccine Immunol. 13, 1030–1036. Ameni, G., Aseffa, A., Sirak, A., Engers, H., Young, D.B., Hewinson, G.R., Vordermeier, M.H., Gordon, S.V., 2007a. Effect of skin testing and segregation on the incidence of bovine tuberculosis, and molecular typing of mycobacterium bovis in Ethiopia. Vet. Rec. 161, 782–786. Ameni, G., Aseffa, A., Engers, H., Young, D., Gordon, S., Hewinson, G., Vordermeier, M., 2007b. High prevalence and increased severity of pathology of bovine tuberculosis in Holsteins compared to Zebu breeds under field cattle husbandry in Central Ethiopia. Clin. Vaccine Immunol. 14, 1356–1361. Ameni, G., Aseffa, A., Engers, H., Young, D., Gordon, S., Hewinson, G., Vordermeier, M., 2008. A comparative study on the epidemiology and immunopathology of bovine tuberculosis in Bos indicus and Bostaurus cattle in Ethiopia. Ethiop. J. Health Dev. 22, 132–134. Ameni, G., Desta, F., Firdessa, R., 2010. Molecular typing of Mycobacterium bovis isolated from tuberculosis lesions of cattle in north eastern Ethiopia. Vet. Rec. 167, 138–141. Ameni, G., Vordermeier, M., Firdessa, R., Aseffa, A., Hewinson, G., Gordon, S.V., Berg, S., 2011. Mycobacterium tuberculosis infection in grazing cattle in central Ethiopia. Vet. J. 188, 359–361. Ameni, G., Tadesse, K., Hailu, E., Deresse, Y., Medhin, G., et al., 2013. Transmission of Mycobacterium tuberculosis between farmers and cattle in Central Ethiopia. PLoS One 8, e76891. Araújo, C.P., Osório, A.L.A.R., Jorge, K.S.G., Ramos, C.A.N., Filho, A.F.S., et al., 2014. Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR. Braz. J. Microbiol. 45, 633–640. Arega, S., Conraths, F.J., Ameni, G., 2013. Prevalence of tuberculosis in pigs slaughtered at two abattoirs in Ethiopia and molecular characterization of Mycobacterium tuberculosis isolated from tuberculous-like lesions in pigs. BMC Vet. Res. 9, 97. Ayele, W.Y., Neill, S.D., Zinsstag, J., Weiss, M.G., Pavlik, I., 2004. Bovine tuberculosis: an old disease but a new threat to Africa. Int. J. Tuberc. Lung Dis. 8, 924–937. Aylate, A., Shah, S.N., Aleme, H., Gizaw, T.T., 2013. Bovine tuberculosis: prevalence and diagnostic efficacy of routine meat inspection procedure in Woldiya municipality abattoir north Wollo zone, Ethiopia. Trop. Anim. Health Prod. 45, 855–864. Bailey, S.S., Crawshaw, T.R., Smith, N.H., Palgrave, C.J., 2013. Mycobacterium bovis infection in domestic pigs in Great Britain. Vet. J. 198, 391–397. Barlow, N.D., 1997. A simulation model for the spread of bovine tuberculosis within New Zealand cattle herds. Prev. Vet. Med. 32, 57–75.

15

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Kassa, G., Abebe, F., Worku, Y., Legesse, M., Medhin, G., Bjune, G., Ameni, G., 2012. Tuberculosis in goats and sheep in afar pastoral region of Ethiopia and isolation of Mycobacterium tuberculosis from goat. Vet. Med. Int. 2012 (869146) 8 pages. Kassahun, Y., Mattiangeli, V., Ameni, G., Hailu, E., Aseffa, A., Young, D.B., Hewinson, R.G., Vordermeier, H.M., Bradley, D.G., 2015. Admixture mapping of tuberculosis and pigmentation-related traits in an African-European hybrid cattle population. Front. Genet. 6, 210. Katale, B.Z., Mbugi, E.V., Siame, K.K., Keyyu, J.D., Kendall, S., et al., 2015. Transboundary and emerging diseases. Isolation and potential for transmission of Mycobacterium bovis at human–livestock–wildlife interface of the Serengeti ecosystem, Northern Tanzania. Transbound Emerg. Dis. 64, 815–825. Katale, B.Z., Mbugi, E.V., Siame, K.K., Keyyu, J.D., Kendall, S., et al., 2017. Isolation and potential for transmission of mycobacterium bovis at human–livestock–wildlife interface of the Serengeti ecosystem, Northern Tanzania. Transbound Emerg. Dis. 64, 815–825. Kidane, D., Olobo, O.J., Habte, A., Negesse, Y., Abraham Aseffa, A., et al., 2002. Identification of the causative organism of tuberculous lymphadenitis in Ethiopia by PCR. J. Clin. Microbiol. 40, 4230–4234. Kiran, D., Podell, B.K., Chambers, M., Randall, J., Basaraba, Rb., 2016. Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: a review. Semin. Immunopathol. 38, 167–183. Kiros, T., 1998. Epidemiology and Zoonotic Importance of Bovine Tuberculosis in Selected Sites of Eastern Shewa Ethiopia. MSc Thesis. Faculty of Veterinary Medicine, Addis Ababa University, Addis Ababa, Ethiopia and FreieUniversitat, Berlin, Germany. Laval, G., Ameni, G., 2004. Prevalence of bovine tuberculosis in zebu cattle under traditional animal husbandry in Boji district of western Ethiopia. Rev. Méd. Vét. 155, 494–499. Liebana, E., Aranaz, A., Mateos, A., Vilafranca, M., Gomez-mampaso, E., Tercero, J.C., Alemany, J., Suarez, G., Domingo, M., Dominguez, L., 1995. Simple and rapid detection of Mycobacterium tuberculosis complex organisms in bovine tissue samples by PCR. J. Clin. Microbiol. 33, 33–36. Lopes, P.H., Akweongo, P., Wurapa, F., Afari, E., Sackey, S., Ocansey, D., Nyarko, K.M., 2016. Bovine tuberculosis surveillance system evaluation, Greater-Accra Region, Ghana, 2006–2011. Pan Afr. Med. J. 25 (Supp. 1), 10. Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Olsen, J.H., Ball, R., et al., 2006. Tuberculosis in elephants: antibody responses to defined antigens of Mycobacterium tuberculosis, potential for early diagnosis, and monitoring of treatment. Clin. Vaccine Immunol. 13, 722–732. Lyashchenko, K.P., Greenwald, R., Esfandiari, J., Lecu, A., Waters, W.R., et al., 2012. Pulmonary disease due to Mycobacterium tuberculosis in a horse: zoonotic concerns and limitations of antemortem testing. Vet. Med. Int. 2012 (642145) 6 pages. Malama, S., Johansen, B.T., Muma, J.B., Munyeme, M., Mbulo, G., et al., 2014. Characterization of Mycobacterium bovis from humans and cattle in Namwala District, Zambia. Vet. Med. Int. 2014 (187842) 7 pages. Mamo, G., Kassaye, A., Sanni, M., Ameni, A., 2009. A cross sectional study of camel tuberculosis in Ethiopia. Bull. Anim. Health Prod. Afr. 57, 13–20. Mamo, G., Bayleyegn, G., Sisay, T., Legesse, M., Medhin, G., 2011. Pathology of camel tuberculosis and molecular characterization of its causative agents in pastoral regions of Ethiopia. PLoS One 6, e15862. Mariam, S., 2014. Identification and survival studies of Mycobacterium tuberculosis within laboratory-fermented bovine milk. BMC Res. Notes 7, 175. Mathema, B., Kurepina, N.E., Bifani, P.J., Kreiswirth, B.N., 2006. Molecular epidemiology of tuberculosis: current insights. Clin. Microbiol. Rev. 19, 658–685. Mekibeb, A., Fulasa, T.T., Firdessa, R., Hailu, E., 2013. Prevalence study on bovine tuberculosis and molecular characterization of its causative agents in cattle slaughtered at Addis Ababa municipal abattoir, Central Ethiopia. Trop. Anim. Health Prod. 45, 763–769. Mengistu, A., Enquselassie, F., Mulatu, F., Hailu, E., Demissew Beyene, D., 2015. Tuberculosis infection in cattle and cattle owners in North Eastern parts of Ethiopia. Biol. Med. 7, 4. Menin, A., Fleith, R., Reck, C., Marlow, M., Fernandes, P., et al., 2013. Asymptomatic cattle naturally infected with Mycobacterium bovis present exacerbated tissue pathology and bacterial dissemination. PLoS One 8, e53884. Michel, A.L., Borna Muller, B., van Helden, P.D., 2009. Mycobacterium bovis at the animal–human interface: a problem, or not? Vet. Microbiol. 140, 371–381. Mihret, A., Bekele, Y., Aytenew, M., Assefa, Y., Abebe, M., Wassie, L., Loxton, G.A., Yamuah, L., Aseffa, A., Walzl, G., Howe, R., 2012. Modern lineages of Mycobacterium tuberculosis in Addis Ababa, Ethiopia: implications for the tuberculosis control programe. Afr. Health Sci. 12, 339–344. Miller, R.S., Sweeney, S.J., 2013. Mycobacterium bovis (bovine tuberculosis) infection in North American wildlife: current status and opportunities for mitigation of risks of further infection in wildlife populations. Epidemiol. Infect. 141, 1357–1370. Ministry of Health Ethiopia (MOH), 2008. Tuberculosis, Leprosy andTB/HIV Prevention and Control Programme Manual. Addis Ababa, Ethiopia. . Mishra, A., Singhal, A., Chauhan, D.S., Katoch, V.M., Srivastava, K., et al., 2005. Direct detection and identification of Mycobacterium tuberculosis and Mycobacterium bovis in bovine samples by a novel nested PCR assay: correlation with conventional techniques. J. Clin. Microbiol. 43, 5670–5678. Mohamed, A.M., Abou El-Ella, G.A., Nasr, E.A., 2009. Phenotypic and molecular typing of tuberculous and nontuberculous Mycobacterium species from slaughtered pigs in Egypt. J. Vet. Diagn. Invest. 21, 48–52. Müller, B., Dürr, S., Alonso, S., Hattendorf, J., Laisse, C.J.M., ParsonsS, D.C., van Helden, P.D., Zinsstag, J., 2013. Zoonotic Mycobacterium bovis–induced tuberculosis in humans. Emerg. Infect. Dis. 19, 99–908. Muwonge, A., Johansen, T.B., Vigdis, E., Godfroid, J., Olea-Popelka, F., Demelash Biffa,

Deresa, B., Conraths, F.J., Ameni, G., 2013. Abattoir-based study on the epidemiology ofcaprine tuberculosis in Ethiopia using conventional and molecular tools. Acta Vet. Scand. 55, 15. Di Marco, V., Mazzone, P., Capucchio, M.T., Boniotti, M.B., Aronica, V., et al., 2012. Epidemiological significance of the domestic black pig (Sus scrofa) in maintenance of bovine tuberculosis in sicily. J. Clin. Microbiol. 50, 1209–1218. Dobler, C.C., 2013. What do we know about the outcomes of tuberculosis contact investigations in NSW? N.S.W. Public Health Bull. 24, 34–37. Elias, K., Hussein, D., Asseged, B., Wondwossen, T., Gebeyehu, M., 2008. Status ofbovine tuberculosis in Addis Ababa dairy farms. Rev. Sci. Tech. Off. Int. Epiz. 27, 915–923. Endalew, M.A., Gelalcha, B.D., GobenaAmeni, G., 2017. Bovine tuberculosis prevalence, potential risk factors and its public health implication in selected state dairy farms, Central Ethiopia. World Vet. J. 7, 21–29. Etter, E.M.C., Ameni, G., Roger, F.L.M., 2006. Tuberculosis risk assessment in Ethiopia: safety of meat from cattleslaughtered in abattoirs. Proceedings of the 11th International Symposium on Veterinary Epidemiology and Economics. Available at. www.sciquest.org.nz. Finlay, E.K., Berry, D.P., Wickham, B., Gormley, E.P., Bradley, D.G., 2012. A genome wide association scan of bovine tuberculosis susceptibility in Holstein-Friesian dairy cattle. PLoS One 7, e30545. Firdessa, R., Tschopp, R., Wubete, A., Sombo, M., Hailu, E., et al., 2012. High prevalence of bovine tuberculosis in dairy cattle in Central Ethiopia: implications for the dairy industry and public health. PLoS One 7, e52851. Firdessa, R., Berg, S., Hailu, E., Schelling, E., Gumi, B., Erenso, G., et al., 2013. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg. Infect. Dis. 19, 460–463. Garedew, L., Mihret, A., Mamo, G., Abebe, T., Firdessa, R., Bekele, Y., Ameni, G., 2013a. Strain diversity of mycobacteria isolated from pulmonary tuberculosis patients at Debre Birhan Hospital, Ethiopia. Int. J. Tuberc. Lung Dis. 17, 1076–1081. Garedew, L., Mihret, A., Ameni, G., 2013b. Molecular typing of mycobacteria isolated from extrapulmonary tuberculosis patients at Debre Birhan Referral Hospital, Central Ethiopia. Scand. J. Infect. Dis. 45, 512–518. Gortazar, C., Vicente, J., Samper, S., Garrido, J.M., Fernandez-De-Mera, I.G., Gavın, P., et al., 2005. Molecular characterization of Mycobacterium tuberculosis complex isolates from wild ungulates in South-Central Spain. Vet. Res. 36, 43–52. Gortazar, C., Torres, M.J., Vicente, J., Acevedo, P., Reglero, M., et al., 2008. Bovine tuberculosis in Donana biosphere reserve: the role of wild ungulates as disease reservoirs in the last Iberian lynx strongholds. PLoS One 3, e2776. Griffin, J.M., Hahesy, T., Lynch, K., Salman, M.D., McCarthy, J., Hurley, T., 1993. The association of cattle husbandry characteristics, environmental factors and farmer characteristics with the occurrence of chronic bovine tuberculosis in dairy herds in the Republic of Ireland. Prev. Vet. Med. 17, 145–160. Guerra-Assuncao, J.A., Crampin, A.C., Houben, R.M.G.J., Mzembe, T., Mallard, K., et al., 2015. Large-scale whole genome sequencing of M. tuberculosis provides insights in to transmission in a high prevalence area. ELife 2015 (4), e05166. Gumi, B., Schelling, E., Firdessa, F., Erenso, G., Biffa, D., et al., 2012a. Low prevalence of bovine tuberculosis in Somali pastoral livestock, southeast Ethiopia. Trop. Anim. Health Prod. 44, 1445–1450. Gumi, B., Schelling, E., Berg, S., Firdessa, R., Erenso, G., et al., 2012b. Zoonotic transmission of tuberculosis between pastoralists and their livestock in South-East Ethiopia. Ecohealth 9, 139–149. Gutierrez, M., Samper, S., Gavigan, J., Marin, J.F.G., Martin, C., 1995. Differentiation by molecular typing of Mycobacterium bovis strains causing tuberculosis in cattle and goats. J. Clin. Microbiol. 33, 2953–2956. Gutierrez, M., Samper, S., Jimenez, M.S., van Embden, J.D.A., Marin, J.F.G., Martin, C., 1997. Identification by spoligotyping of a caprine genotype in Mycobacterium bovis strains causing human tuberculosis. J. Clin. Microbiol. 35, 3328–3330. Hambolu, D., Freeman, J., Taddese, H.B., 2013. Predictors of bovine TB risk behaviour amongst meat handlers in Nigeria: a cross-sectional study guided by the health belief model. PLoS One 8, e56091. Hangombe, M.H., Munyeme, M., Nakajima, C., Fukushima, Y., Suzuki, H., Matandiko, W., Ishii, A., Mweene, A.S., Suzuki, Y., 2012. Mycobacterium bovis infection at the interface between domestic and wild animals in Zambia. BMC Vet. Res. 8, 221. Higino, S.S.D., Pinheiro, S.R., de Souza, G.O., Dib, C.C., Rosário, T.R., et al., 2011. Mycobacterium bovis infection in goats from the northeast region of Brazil. Braz. J. Microbiol. 42, 1437–1439. Hiko, A., Agga, G., 2011. First-time detection of mycobacterium species from goats in Ethiopia. Trop. Anim. Health Prod. 43, 133–139. Hlokwe, T.M., Sutton, D., Page, P., Michel, A.L., 2016. Isolation and molecular characterization of Mycobacterium bovis causing pulmonary tuberculosis and epistaxis in a Thoroughbred horse. BMC Vet. Res. 12, 179. Humblet, M.F., Boschiroli, M.L., Saegerman, C., et al., 2009. Classification of worldwide bovine tuberculosis risk factorsin cattle: a stratified approach. Vet. Res. 2009 (40), 50. Humblet, M.F., Gilbert, M., Govaerts, M., Fauville-Dufaux, M., Walravens, K., Saegerman, C., 2010. New assessment of bovine tuberculosis risk factors in Belgium based on nationwide molecular epidemiology. J. Clin. Microbiol. 48, 2802–2808. Je, S., Ku, B.K., Jeon, B.Y., Kim, J.M., Jung, S.C., Cho, S.N., 2015. Extent of Mycobacterium bovis transmission among animals of dairy and beef cattle and deer farms in South Korea determined by variable-number tandem repeats typing. Vet. Microbiol. 176, 274–281. Kaneene, J.B., Bruning-Fann, C.S., Granger, L.M., Miller, R., Porter-Spalding, A., 2002. Environmental and farm management factors associated with tuberculosis on cattle farms in northeastern Michigan. J. Am. Vet. Med. Assoc. 221, 837–842. Kasaye, S., Molla, W., Ameni, G., 2013. Prevalence of camel tuberculosis at Akaki abattoir in Addis Ababa, Ethiopia. Afr. J. Microbiol. Res. 7, 2184–2189.

16

Preventive Veterinary Medicine 158 (2018) 1–17

G. Romha et al.

Mycobacterium tuberculosis in a high tuberculosis incidence area. Mol. Microbiol. 47, 529–538. Tadayon, K., Mosavari, N., Feizabadi, M.M., 2013. An epidemiological perspective on bovine tuberculosis spotlighting facts and dilemmas in Iran, a historically zebudominant farming country. Iran. J. Microbiol. 5, 1–13. Tafess, K., Dawo, F., Sori, T., Ameni, G., 2011. Prevalence of caprine tuberculosis in midrift valley area of Oromia, Ethiopia. Afr. J. Microbiol. Res. 5, 1473–1478. Teklu, A., Asseged, B., Yimer, E., Gebeyehu, M., Woldesenbet, Z., 2004. Tuberculous lesions not detected by routine abattoir inspection: the experience of the Hosanna municipal abattoir, Southern Ethiopia. Rev. Sci. Tech. Off. Int. Epiz. 23, 957–964. Thoen, C., Lobue, P., de Kantor, I., 2006. The importance of Mycobacterium bovis as a zoonosis. Vet. Microbiol. 112, 339–345. Tigre, W., Gudeta, T., Regassa, F., 2010. Preliminary study on bovine tuberculosis in Nekemte municipality abattoir, Western Ethiopia. Bull. Anim. Heal. Prod. Afr. 58, 323–327. Torres-Gonzalez, P., Soberanis-Ramos, O., Martinez-Gamboa, A., Chavez-Mazari, B., Barrios-Herrera, M.T., et al., 2013. Prevalence of latent and active tuberculosis among dairy farm workers exposed to cattle infected by Mycobacterium bovis. PLoS Negl. Trop. Dis. 7, e2177. Tschopp, R., Berg, S., Argaw, K., Gadisa, E., Habtamu, M., Schelling, E., Young, D., Aseffa, A., Zinsstag, J., 2010a. Bovine tuberculosis in Ethiopian wildlife. J. Wildl. Dis. 46 (3), 753–762. Tschopp, R., Aseffa, A., Schelling, E., Berg, S., Hailu, E., et al., 2010b. Bovine tuberculosis at the wildlife-livestock-human interface in Hamer Woreda, South Omo, Southern Ethiopia. PLoS One 5, e12205. Tschopp, R., Schelling, E., Hattendorf, J., Young, D., Aseffa, A., et al., 2010c. Repeated cross-sectional skin testing for bovine tuberculosis in cattle kept in a traditional husbandry system in Ethiopia. Vet. Rec. 167, 250–256. Tschopp, R., Bobosha, K., Aseffa, A., Schelling, E., Habtamu, M., et al., 2011. Bovine tuberculosis at a cattle-small ruminant human interface in Meskan, Gurage region, Central Ethiopia. BMC Infect. Dis. 11, 318. Tschopp, R., Hattendorf, J., Roth, F., Choudhoury, A., Shaw, A., et al., 2012. Cost estimate of bovine tuberculosis to Ethiopia. Curr. Top. Microbiol. Immunol. 365, 249–268. Tschopp, R., Abera, B., Sourou, S.Y., Guerne-Bleich, E., Aseffa, A., Wubete, A., Zinsstag, J., Young, D., 2013. Bovine tuberculosis and brucellosis prevalence in cattle from selected milk cooperatives in Arsi zone, Oromia region, Ethiopia. BMC Vet. Res. 9, 163. Tschopp, R., Bekele, S., Moti, T., Young, D., Aseffa, A., 2015. Brucellosis and bovine tuberculosis prevalence in livestock from pastoralist communities adjacent to Awash National Park, Ethiopia. Prev. Vet. Med. 120, 187–194. Tsegaye, W., Aseffa, A., Mache, A., Mengistu, Y., Berg, S., Ameni, G., 2010. Conventional and molecular epidemiology of bovine tuberculosis in dairy farms in AddisAbaba City, the capital of Ethiopia. J. Appl. Res. Vet. Med. 8, 143–151. Van Rhijn, I., Godfroid, J., Michel, A., Rutten, V., 2008. Bovine tuberculosis as a model for human tuberculosis: advantages over small animal models. Microbes Infect. 10, 710–715. Verver, S., Warren, R.M., Munch, Z., Vynnycky, E., van Helden, P.D., Richardson, M., van der Spuy, G.D., Enarson, D.A., Martien Borgdorff, W.M.W., Behr, M.A., Beyers, N., 2004. Transmission of tuberculosis in a high incidence urban community in South Africa. Intern. J. Epidemiol. 33, 351–357. Vordermeier, M., Ameni, G., Berg, S., Bishop, R., Robertson, B.D., et al., 2012. The influence of cattle breeds on susceptibility to bovine tuberculosis in Ethiopia. Comp. Immunol. Microbiol. Infect. Dis. 35, 227–232. Vynnycky, E., Borgdorff, M.W., van Soolingen, D., Fine, P.E.M., 2003. Annual Mycobacterium tuberculosis infection risk and interpretation of clustering statistics. Emerg. Infect. Dis. 9, 176–183. Waters, W.R., Hope, J.C., Hamilton, C.A., Palmer, M.V., McNair, J., et al., 2015. In: Mukundan, H. (Ed.), Immunopathogenesis of Mycobacterium bovis Infection of Cattle in Tuberculosis, Leprosy and Mycobacterial Diseases of Man and Animals: The Many Hosts of Mycobacteria. WHO, OIE, FAO and The Union, 2017. The Roadmap for Zoonotic Tuberculosis. A Call to Action. Available online at. (Accessed 29 November 2017). http://apps.who.int/ iris/bitstream/10665/259229/1/9789241513043-eng.pdf?ua=1. Woodroffe, R., Donnelly, C.A., Johnston, W.T., Bourne, F.J., Cheeseman, C.L., et al., 2005. Spatial association of Mycobacterium bovis infection in cattle and badgers Meles Meles. J. App. Ecol. 42, 852–862. World Health Organization, 2011. Global Tuberculosis Control: World Health Organization Report 2011. Yang, Z., Barnes, P.F., Chaves, F., Eisenach, K.D., Weis, S.E., Bates, J.H., Cave, M.D., 1998. Diversity of DNA fingerprints of Mycobacterium tuberculosis isolates in the United States. J. Clin. Microbiol. 36, 1003–1007. Zerom, K., Tessema, T., Mamo, G., Bayu, Y., Ameni, G., 2013. Tuberculosis in dromedaries in eastern Ethiopia: Abattoir-based prevalence and molecular typing of its causative agents. Small Rumin. Res. 109, 188–192. Zeru, F., Romha, G., Ameni, G., 2013. Gross and molecular characterization of Mycobacterium tuberculosis complex in Mekelle town municipal abattoir, Northern Ethiopia. Glob. Vet. 11, 541–546. Zeru, F., Romha, G., Berhe, G., Mamo, G., Sisay, T., Ameni, G., 2014. Prevalence of bovine tuberculosis and assessment of cattle owners' awareness on its public health implication in and around Mekelle, Northern Ethiopia. J. Vet. Med. Anim. Health 6, 159–167.

D., Skjerve, E., Djønne, B., 2012. Mycobacterium bovis infections in slaughter pigs in Mubende district, Uganda: a public health concern. BMC Vet. Res. 8, 168. Narnaware, S.D., Dahiya, S.S., Tuteja, F.C., Nagarajan, G., Nath, K., Patil, N.V., 2015. Pathology and diagnosis of Mycobacterium bovis in naturally infected dromedary camels (Camelus dromedarius) in India. Trop. Anim. Health Prod. 47, 1633–1636. Nuru, A., Mamo, G., Teshome, L., Zewdie, A., Medhin, G., Pieper, R., Ameni, G., 2015. Bovine tuberculosis and its risk factors among dairy cattle herds in and around Bahir Dar City, Northwest Ethiopia. Ethiop. Vet. J. 19, 27–40. Nuru, A., Zewdie, A., Mohammed, T., Wondale, B., Teshome, L., Getahun, M., Mamo, G., Medhin, G., Pieper, R., Ameni, G., 2017. Nontuberculosis mycobacteria are the major causes of tuberculosis like lesions in cattle slaughtered at Bahir Dar Abattoir, northwestern Ethiopia. BMC Vet. Res. 13, 237. Ocepek, M., Pate, M., Zolnir-Dovc, M., Poljak, M., 2005. Transmission of Mycobacterium tuberculosis from human to cattle. J. Clin. Microbiol. 43, 3555–3557. Oelemann, M.C., Fontes, A.N.B., da Silva Pereira, M.A., Bravin, Y., Silva, G., Degrave, W., Carvalho, A.C., Brito, R.C., Kritski, A.L., Suffys, P.N., 2007. Typing of Mycobacterium tuberculosis strains isolated in Community Health Centers of Rio de Janeiro City, Brazil. Mem. Inst. Oswaldo Cruz. 102, 455–462. O’Reilly, L.M., Daborn, C.J., 1995. The epidemiology of Mycobacterium bovis infections in animals and man: a review. Tuberc. Lung Dis. 76, 1–46. Olea-Popelka, F.J., White, P.W., Collins, J.D., O’Keeffe, J., Kelton, D.F., Martin, S.W., 2004. Breakdownseverity during a bovine tuberculosis episode as a predictor of future herd outbreaks in Ireland. Prev. Vet. Med. 63, 163–172. Olea-Popelka, F., Muwonge, A., Perera, A., Dean, A.S., Mumford, E., et al., 2017. Zoonotic tuberculosis in human beings caused by Mycobacterium bovis-a call for action. Lancet Infect. Dis. 17, e21–e25. https://doi.org/10.1016/S1473-3099(16)30139-6. Omer, M.K., Skjerve, E., Woldehiwet, Z., Holstad, G., 2001. A cross-sectional study of bovine tuberculosis in dairy farms in Asmara, Eritrea. Trop. Anim. Health Prod. 33, 295–303. Porphyre, T., Stevenson, M.A., McKenzie, J., 2008. Risk factors for bovine tuberculosis in New Zealand cattle farms and their relationship with possum control strategies. Prev. Vet. Med. 86, 93–106. Prasad, H.K., Singhal, A., Mishra, A., Shah, N.P., Katoch, V.M., et al., 2005. Bovine tuberculosis in India: potential basis for zoonosis. Tuberculosis (Edinb.). 85, 421–428. Raphaka, K., Matika, O., Sánchez-Molano, E., Mrode, R., Coffey, M.P., et al., 2017. Genomic regions underlying susceptibilityto bovine tuberculosis in Holstein-Friesian cattle. BMC Genet. 18, 27. Regassa, A., Medhin, G., Ameni, G., 2008. Bovine tuberculosis is more prevalent in cattle owned by farmers with active tuberculosis in central Ethiopia. Vet. J. 178, 119–125. Regassa, A., Tassew, A., Amenu, K., Megersa, B., Abunna, F., Mekibib, B., Macrotty, T., Ameni, G., 2010. A cross-sectional study on bovine tuberculosis in Hawassa town and its surroundings, Southern Ethiopia. Trop. Anim. Health Prod. 42, 915–920. Richardson, I.W., Berry, D.P., Wiencko, H.L., Higgins, I.M., More, S.J., McClure, J., Lynn, D.J., Bradley, D.G.A., 2016. Genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23. Genet. Sel. Evol. 48 (1). Rodwell, C.T., Kapasi, J.A., Moore, M., Milian-Suazoe, F., Harris, B., et al., 2010. Tracing the origins of Mycobacterium bovis tuberculosis in humans in the USA to cattle in Mexico using spoligotyping. Int. J. Infect. Dis. 14 (S3), e129–e135. Romero, B., Rodríguez, S., Bezos, J., Díaz, R., Copano, M.F., et al., 2011. Humans as source of Mycobacterium tuberculosis infection in cattle, Spain. Emerg. Infect. Dis. 17, 2393–2395. Romha, G., Ameni, G., Berhe, G., Mamo, G., 2013. Epidemiology of mycobacterial infections in cattle in two districts of Western Tigray Zone, northern Ethiopia. Afr. J. Microbiol. Res. 7, 4031–4038. Sanou, A., Tarnagda, Z., Kanyala, E., Zingué, D., Nouctara, M., et al., 2014. Mycobacterium bovis in Burkina Faso: epidemiologic and genetic Links between human and cattle isolates. PLoS Negl. Trop. Dis. 8, e3142. Sarradell, J.E., Alvarez, J., Biscia, M., Zumarraga, M., Wunschmann, A., Armien, A.G., Perez, A.M., 2015. Mycobacterium bovis infection in a horse with granulomatous enterocolitis. J. Vet. Diagn. Invest. 27, 203–205. Shitaye, J.E., Getahun, B., Alemayehu, T., Skoric, M., Treml, F., Fictum, P., Vrbas, V., Pavlik, I., 2006. A prevalence study of bovine tuberculosis by using abattoir meat inspection and tuberculin skin testing data, histopathological and IS6110 PCR examination of tissues with tuberculous lesions in cattle in Ethiopia. Vet. Med. 11, 512–522. Shitaye, J.E., Tsegaye, W., Pavlik, I., 2007. Bovine tuberculosis infection in animal and human populations in Ethiopia: a review. Vet. Med. 52, 317–332. Small, P.M., Hopewell, P.C., Singh, S.P., Paz, A., Parsonnet, J., Ruston, D.C., Schecter, G.F., Daley, G.F., Schoolnik, G.K., 1994. The epidemiology of tuberculosis in San Francisco: a population-based study using conventional and molecular methods. N. Engl. J. Med. 330, 1703–1709. Smith, N.H., Gordon, S.V., de la Rua-Domenech, R., Clifton-Hadley, R.S., Hewinson, R.G., 2006. Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis. Nat. Rev. Microbiol. 4, 670–681. Styblo, K., 1985. The relationship between the risk of tuberculosis infection and the risk of developing infectious tuberculosis. Bull. Int. Union Tuberc. 60, 117–119. Styblo, K., Meijer, J., 1980. Increase in the annual level of tuberculosis in a country with a low occurrence: measurement of the increase expecting to see if the existing program of mass radiographic examinations was interrupted. Bull. Int. Union Tuberc. 55, 3–8. Supply, P., Warren, R.M., Banuls, A.L., Lesjean, S., Van Der Spuy, G.D., et al., 2003. Linkage disequilibrium between minisatellite loci supports clonal evolution of

17