Introduction: Tuberculosis is a major global public health problem resulting in considerablernmorbidity and mortality. According to 2012 World Health Organization report, an estimated 8.6rnmillion people developed tuberculosis and1.3 million died from the disease (including 320 000rndeaths among Human Immunodeficiency Virus (HIV) positive people). Ethiopia is one of thernhighest tuberculosis burden countries in the world, which ranks 8th amongst the 22 highrntuberculosis burden countries. In Ethiopia, it was also estimated that about 41% of tuberculosisrncases were HIV positive. The transmission of Mycobacterium tuberculosis from humans tornhumans is well known globally; however, little is known about the transmission ofrnMycobacterium tuberculosis complex species between humans and animals, in particular cattle.rnBovine tuberculosis is endemic in Ethiopia. Intimacy of cattle and humans in rural farmingrncommunities may transmit Mycobacterium bovis to humans. However, there is little informationrnabout the possible transmission of tuberculosis between humans and cattle in Ethiopia. Therncontribution of Mycobacterium tuberculosis to bovine reactivity is also unknown. Althoughrnbovine tuberculosis is a known zoonosis, it is mainly a disease of cattle. Humans could berninfected by consuming raw milk and, to some extent, by inhaling droplet nuclei. Cattle owned byrntuberculosis patients revealed higher bovine tuberculosis tuberculin skin test result and this mightrnbe due to the possible infection of cattle with Mycobacterium tuberculosis. The causative agentrnresponsible for the infection in both populations could be identified using molecular techniques.rnThis research work aimed to investigate the role of cattle in the occurrence of pulmonaryrntuberculosis in humans at a rural community in Ethiopia.rnMethods: The study used both cross-sectional and case-control designs in Northeast andrnNorthwest parts of the Amhara Region. A cross-sectional study was employed to determine thernpresence of bovine tuberculosis among cattle owned by presumptive pulmonary tuberculosisrncases. A comparative cross-sectional study was conducted on 124 cattle owned by householdsrnwith confirmed pulmonary tuberculosis and 381cattle owned by households without tuberculosisrnto determine the likelihood of bovine tuberculosis among livestockâ€™s in the two groups. A casecontrolrnstudy was conducted on 35 households with at least one pulmonary tuberculosis case andrn105 households without tuberculosis to determine the risk of bovine tuberculosis in humans.rnXIXrnBesides, laboratory based deletion typing and spoligotyping that was carried out forrnMycobacterium tuberculosis isolated from acid fast bacilli confirmed pulmonary tuberculosisrnpatients. A comparative cervical intradermal tuberculin skin test was conducted on all the studyrnsubjects (cattle) using bovine and avian purified protein derivatives as an antigen. Based on thernskin test reaction measurement, the cattle were categorized as negative, doubtful and positive, ifrnthe measured difference between the bovine and avian injection site is below 1, 1- 4 and >4, orrn2, respectively. All sputum samples collected from presumptive tuberculosis casesrnas well as tuberculosis confirmed human patients were cultured on Lowenstein-Jensen mediumrn(tubes containing glycerol and sodium pyruvate) and polymerase chain reaction, deletion typing,rnspoligotyping and single nucleotide polymorphism were performed for positive culture findingsrnto identify the Mycobacterium tuberculosis strains involved for human tuberculosis infection.rnClosed questionnaires and forms were used to collect the required data.rnResults: Of the 124 sputum samples collected from presumptive tuberculosis cases 4/124 (3.2%)rnwere culture positive. Polymerase Chain Reaction using region of difference-9 as a marker hasrnconfirmed that 2/4 (50%) were found to be Mycobacterium tuberculosis while the rest werernatypical Mycobacterial species.rnOf the 381 cattle tested 5/381 (1.31%) were found to be tuberculin positive (prevalence of 1.31%rnwith 95% CI: 0.2.0, 2.5) and 10/381 (2.63%) (Prevalence of 2.63% with 95% CI: 1.0, 4.2) werernpositive for the test according to a cutoff value > 4mms and > 2mms, respectively. About 67%rn(6/9) of the individuals who owned bovine tuberculosis positive cattle had the habit of drinkingrnraw milk. Of the 10 positive cattle, five of them resided in lowland (Kola) areas (1300-1500rnmeters above sea level). However, none of the owners of tuberculin positive cattle were found tornbe tuberculosis positive.rnUsing >2mm as a cutoff value for the diagnosis of bovine tuberculosis, the study revealed that anrnoverall apparent prevalence of 23.6% and individual cattle apparent prevalence of 8.7% forrnbovine tuberculosis in the study area with an odds of nearly three times (AOR= 2.90, 95% CI:rn1.50, 5.54) higher bovine tuberculosis among cattle owned by households with tuberculosis. Thernfindings indicated that 49.3% and 61.4% were having the habit of drinking raw milk and eatingrnXXrnuncooked meat, respectively. More than three fourth of the study subjects did not know thernbenefit of boiling milk. About 70.7% knew there is chance of disease transmission from animalsrnto humans. Of the total respondents participated in a case - control study, 78.6% did not isolaterntheir sick cattle and 87.1% kept the sick cattle with them.rnAmong the TB cases, 31.4% reported sharing the living room with their cattle as compared tornonly 9% of controls. It was also disclosed that 42.9%, 37.1% and 14.3% of the cases sharedrnutensils, gave their urine to cattle and urinate on a cattle feed, respectively, as compared torn36.2%, 27.6% and 4.8% of the controls. Based on >2mms as a cutoff value bovine tuberculosisrnwas recorded in 48.6% of the cases and 15.2% of controls, more than 8 times higher for casesrn(AOR=8.32, 95% CI; 2.82, 24.60).rnIn total, 70 acid fast bacilli positive sputum samples were collected in the study areas. The age ofrnsubjects ranged from 18 to 63 years with a mean age of 35.7 + 13.24 years. Of the total 70 acidrnfast bacilli positive sputum samples, 50/70 (71.4%) were culture positive, from which 37.1 andrn31.5% had the habit of drinking unboiled milk and eating uncooked meat, respectively.rnUsing deletion typing all the isolates were identified as Mycobacterium tuberculosis.rnSpoligotyping revealed 94% (47/50) interpretable patterns and three lineages namely; East-rnAfrica-Indian (57.4%), Euro-American-African (38.3%) and Ethiopian (lineage-7) 2/50 (4.3%).rnLineage 7 was registered only in North Wollo Zone. In this study 8 clusters (with cluster sizernranging from 2 to 8), 8 unique and 10 new patterns were recorded. Shared International Typesrn(SIT) (21, 25, 26, 35, 53, 109, 149 and 289) were found as clusters among which SIT 25 (7) andrnSIT 289 (8) were the predominant ones.rnConclusion: About 3.2% (4/124) of sputum samples collected from individuals with chronicrncough were culture positive, of whom 50% (2/4) were found to be Mycobacterium tuberculosisrnby polymerase chain reaction. The findings indicate that bovine tuberculosis is a threat inrnEthiopia and implicated possible transmission of tuberculosis between humans and cattle wherernhuman pulmonary tuberculosis cases could serve as a possible source of Mycobacteriumrntuberculosis infection to cattle. House sharing was found as a contributing factor in bovinernXXIrntuberculosis test reaction. Therefore, mechanisms should be developed to create awareness.rnSeparate houses for cattle should be constructed to minimize the risk of cross infections andrnfurther study regarding the possible infection of cattle with Mycobacterium tuberculosis thusrnrecommended. Similarly, households with bovine tuberculosis had a higher chance of gettingrnpulmonary tuberculosis. It is, therefore, necessary to investigate whether the pathogenrnresponsible is Mycobacterium tuberculosis or Mycobacterium bovis and appropriate measuresrnshould be taken to prevent spread of tuberculosis in both humans and livestock. This study alsornrevealed that 3 Mycobacterium tuberculosis lineages, namely; the ancient, intermediate andrnmodern were identified. Besides, considerable clustering, which indicates current tuberculosisrntransmission was also reported in the study areas.rnKey words: bovine/cattle, bovine tuberculosis, cough, households, human TB, lineage, NorthrnGondar /Wollo, risk, skin test, Spoligotyp, tuberculosis, typing, Ethiopia.