Our findings confirm that M. bovis disease remains rare among humans in England, Wales, and Northern Ireland. Over the study period, the annual rate of M. bovis disease and the proportion of culture-confirmed TB cases with M. bovis identified as the cause displayed a small but statistically significant increase; annual case numbers for the past 10 years were similar to those for the early 1990s (4). Although speciation has improved from the use of strain typing results (19,20), this improvement is unlikely to account for all of the increase identified. Although the previous study by Jalava et al. (4) and our study overlap by 2 years, our results benefit from improved matching (17) between case notification and culture results from 2002 on, thereby providing improved accuracy for reporting annual case numbers.

We identified, unlike previous studies (4,5), that although the number of M. bovis patients not born in the United Kingdom remained low and fluctuated over time, the annual number of cases in this group increased slightly over time. Our finding may be confounded by better recording of place of birth but is not unexpected given the increase during this period in the overall number of TB patients not born in the United Kingdom (13). Similar to previous findings (5), our findings indicate that most M. bovis patients not born in the United Kingdom lived in urban areas, specifically London. These patients originated mostly from low-income countries where TB incidence is high and therefore are at higher risk for human-to-human transmission and animal-to-human transmission because of limited detection of M. bovis in animals and less frequent milk pasteurization (24). Thus, infection was probably acquired before arrival in the United Kingdom and less likely to be related to exposure to risk factors while in the United Kingdom. Unfortunately, speciation is not routinely conducted in many high TB burden, low-income countries (16), so it is difficult to identify in which countries incidence of M. bovis is high and whether the trends in country of birth for M. bovis patients not born in the United Kingdom reflect the global incidence of the disease (24,25).

We identified a decrease over time in the proportion of UK-born patients >65 years of age and a decrease in the median age, although neither was statistically significant. Previously, most cases in UK-born patients were the result of reactivation of infection acquired before the large rollout of pasteurization (by the 1960s) (4), when M. bovis incidence was higher. Given the length of time that widespread pasteurization has been in place, progressively fewer cases among the older population are expected as the cohort exposed before pasteurization decreases. It was unexpected that, despite this decrease, the number of M. bovis cases occurring in the UK-born population did not reduce over the study period. Instead, the number and proportion of younger UK-born patients increased slightly. Numbers remain small, and it is not possible to yet detect any change in exposures; however, in recent years, the media have reported increased public demand for unpasteurized milk, which, if contaminated, could result in more human infections.

No data are available to quantify unpasteurized milk production or consumption within England, Wales, and Northern Ireland. However, results from a 2012 survey of adult consumer attitudes about unpasteurized milk (26) showed that 33% of respondents had consumed unpasteurized milk but only 3% currently consumed unpasteurized milk. Although the proportion who had ever consumed unpasteurized milk was highest among older age groups (18–24 years, 31%; 25–44 years, 28%; 45–64 years, 38%; >65 years, 40%), the proportion of current consumers was higher among younger age groups (18–24 years, 7%; 25–44 years, 4%; 45–64, 1%; >65, 1%). It is possible that increased consumption of unpasteurized milk, as reported by the media, is contributing to the small increase in M. bovis cases and may contribute to a change in demographics of patients over time. Although we do not have evidence to confirm, this hypothesis could be explored further through a formal observation study. The time between unpasteurized milk consumption and onset of TB disease among the M. bovis patients in our cohort emphasizes that the effects of current unpasteurized milk consumption may not be observed for many years.

The results of combining routine 24-loci MIRU-VNTR typing of M. bovis from humans with epidemiologic data provide evidence of only occasional human-to-human M. bovis transmission; despite extensive follow-up of the 57 clustered cases, only 2 instances of 2 cases being epidemiologically linked were found. Only 1 prior occurrence of MIRU-VNTR–confirmed (using 15-loci typing) human-to-human transmission of M. bovis in the United Kingdom has been documented (5,27); it occurred before the rollout of routine prospective 24-loci MIRU-VNTR typing. There are also few examples of human-to-human M. bovis transmission in countries other than those included in this study (28,29), suggesting that such transmission is rarely identified. Overall, the proportion of clustering among M. bovis cases (49%) was slightly lower than that of the overall proportion among all TB cases (56%) observed in England (13).

This analysis also presents findings consistent with those previously reported (4). Although the proportion of cases among the older UK-born population seems to be decreasing, over the study period this group accounted for most cases. Our comparative analysis confirmed that the demographic profile of M. bovis patients differs from that of M. tuberculosis patients. The consumption of unpasteurized milk remained the most frequently reported exposure, and M. bovis patients were more likely than M. tuberculosis patients to work or have worked in agricultural and animal-related occupations. These findings are reassuring and show that M. bovis disease is still largely limited to those with recognized risk factors for infection. Few incidents involving animal-to-human transmission on farms (1,30,31) and a single incident of M. bovis transmission from a pet to its owners 32,33) have occurred during the study period. Most animal-to-human transmission remains sporadic, and implementation of additional specific interventions beyond those currently in place (1,2) would be difficult.

A high proportion of UK-born patients lived in rural areas, especially across the South West and Midlands of England, where M. bovis incidence among cattle is high (Figure 3, panel B). Most of these patients reported consumption of unpasteurized milk or contact with animals. However, human patients without such exposures and who reside in these areas where M. bovis cattle incidence is high should continue to be monitored and thoroughly investigated to ensure that lesser known exposures are not missed.

Similar to our study, a study in the Netherlands identified that the highest proportion of M. bovis cases occurred in the older native population (50%), followed by the foreign-born population (40%) (34). In comparison with our study, studies from the United States found that being foreign born (in particular, being of Hispanic ethnicity) and younger were independently associated with M. bovis when compared with M. tuberculosis (35,36). The difference in demographic characteristics of M. bovis patients in the United States and in England, Wales, and Northern Ireland may be explained by the fact that M. bovis in cattle or wildlife is not frequently reported in the United States (37,38) but is more common in neighboring Mexico (39,40). Thus, the epidemiology of human M. bovis in England, Wales, and Northern Ireland continues to be driven by the past and, to some extent, present prevalence of disease in cattle. Given advances in molecular techniques, improved understanding of animal-to-human transmission will require linking the genotyping results from animals with M. bovis infection in England, Wales, and Northern Ireland with data from humans.

Globally, zoonotic TB should be tackled, and the needs of those affected by M. bovis disease, namely those in animal-related occupations and those consuming unpasteurized milk from infected animals, should be addressed. The implementation of methods to identify M. bovis where culture is not possible have been highlighted as essential (16,41,42). Although findings from England, Wales, and Northern Ireland cannot be extrapolated even to other high-income countries, much less to high TB burden, low-income countries, our study does illustrate the value of monitoring M. bovis disease and the data required to do so.

Our study does have some limitations. The exposure questionnaires return rate was 89%, and some responses were missing, which could lead to some error in the estimation of exposures; in addition, nonresponders were more likely to be urban dwellers. Our comparison of M. bovis and M. tuberculosis patients was limited because exposure questionnaire information was only collected for M. bovis patients; therefore, animal-related exposures, travel to countries with high TB incidence, and contact with human TB patients could not be included in the analysis. In addition, patients not born in the United Kingdom, most of whom belong to Indian subcontinent ethnic groups, are more likely missed in analysis because a higher proportion have exclusively extrapulmonary disease (43), for which culture confirmation is lower. Approximately 60% of TB cases in England, Wales, and Northern Ireland are culture confirmed; therefore, the estimated M. bovis incidence presented in this article is probably an underestimate. The proportion of TB cases culture confirmed over time has remained relatively stable (44), so underascertainment should not affect changes in the number or proportion of TB cases caused by M. bovis.

In conclusion, we found that M. bovis disease continues to account for a small number and low proportion of total TB cases in England, Wales, and Northern Ireland. The proportion of culture-confirmed TB cases caused by M. bovis has increased slightly, and the age of UK-born patients has decreased. The reasons are not fully understood, and trends should continue to be monitored. For most patients, exposure to risk factors for M. bovis acquisition (e.g., unpasteurized milk consumption, farm work, or contact with a human TB patient) were known. The current control measures in place to prevent animal-to-human spread seem to be effective; such spread occurs in a few isolated incidents and sporadic events. However, to increase understanding of M. bovis transmission in England, Wales, and Northern Ireland, we recommend strengthening collaboration between animal and human health, including linking genotyping results.