Global Overview of Tuberculosis in Humans and Animals in the Period 2013 - 2022 and Public Health Protection

3.1. Drivers of Zoonotic Emergence

Given the global importance of cattle herd populations and the consumption of meat, milk, and their derived products worldwide, pathogens causing zoonoses in cattle are being studied and classified as potential bioterrorism agents on a daily basis [13]. Of the 24 agents with zoonotic potential in cattle, which represent 53% of the recognized zoonotic pathogens in the bovine species, two pathogens (8%) are Category A (high priority pathogens that pose the greatest risk to national security), 16 pathogens (67%) are Category B pathogens that pose a moderate national security risk, and six (25%) are Category C pathogens, meaning that they have emerged and could be used as biological weapons [14].

Locally, there are zoonoses that are specific to particular regions and animal species, but at the same time, their occurrence and re-occurrence is highly influenced by residents` occupation, habits, and knowledge on the topic.

3.2. Surveillance and Monitoring of Tuberculosis Caused by M. bovis in the EU in Animals

At the EU level, bovine tuberculosis is reported through the Animal Disease Information System (ADIS) and in accordance with the procedure laid down in Directive 2003/99/EC. The reports contain data from surveillance in cattle, part of mandatory national eradication and monitoring programmes implemented in accordance with EU legislation, which allow the assessment of the epidemiological situation and the analysis of trends in the Member States and their zones.

Data on the epizootic situation in the Republic of Bulgaria, in the EU, and at the international level regarding M. bovis are presented in Tables 1 and 2, which track the outbreaks reported by the respective countries when bovine tuberculosis was detected in the period 2013-2022 [15-24].

Results in Table 1 present the number of reported outbreaks of bovine tuberculosis in the Republic of Bulgaria. The number of outbreaks detected in the country is sporadic, and it should be noted that during the entire study period, tuberculosis was reported only in cattle.

Data presented in Table 1 for the period 2013-2022, after subjected to statistical analysis show that there are no significant differences according to the selected criteria (number of reporting MSs with zones under an eradication programme; number of infected herds in zones under an eradication programme), which are monitored annually in the EU by EFSA and ECDC, with the exception of the number of infected herds in areas covered by an eradication programme and the MSs with implemented programmes for animal disease management (t[10] = -10.668, p < 0.05). It is necessary to emphasize that, during the studied period, the number of infected herds decreased significantly (46%), as compared with their number in 2013, when it was 18059; in 2022, it was found that the number had declined by half to 9696.

Regarding the status of countries free of bovine tuberculosis, it can be stated that it is generally improving, since the number of countries with a “disease-free” status has increased in recent years. In 2013, there were 15 countries with “disease-free” status; in 2014, there were 16 countries, followed by three consecutive years (2017-2015) when the number of countries was 18, and from 2018 until the end of the study period, a lasting trend was observed, represented by 17 countries in the EU free of the disease (Table 1).

Data presented in Table 2 show that the largest number of outbreaks of the disease in domestic animals for the studied period was reported on the territory of Asia, followed by an almost equal relative number in the regions of America and Europe, and Africa is the region in which the smallest total number of outbreaks was reported in all years [25].

It is obvious when considering the outbreaks that their total number in all regions for the studied years gradually increased, with the largest increase being observed in Asia (74%), followed by Europe (61%), America (30%), and Africa (10%). The statistical analysis found a significant difference in the prevalence of TB cases between animals registered in Asia and Europe (t[10] = 6.337, p < 0.05) and between the American region and Europe (t[10] = 2.617, p < 0.02).

The total number of TB outbreaks for Europe differs among the research sources used; however, it is important to note that these are not technical errors. The differences stem from the fact that the annual reports of EFSA and ECDC on registered outbreaks and cases of zoonoses include twenty-seven Member States and the United Kingdom (Northern Ireland), while within the global WAHIS database there are included more cases from other countries in the European continent such as Bosnia and Herzegovina, North Macedonia, Russia, Serbia and Ukraine, and others, for which outbreaks in domestic cattle have been reported.

Comparing data on reported outbreaks at the global level through WAHIS, it can be concluded that the overall prevalence of tuberculosis in the European Union is decreasing, considering the cases of bovine tuberculosis caused by M. bovis, M. caprae, or M. tuberculosis. At the same time, registered outbreaks caused by M. bovis worldwide are increasing in all regions, including European countries that are not Member States but have reported positive results for the disease in domestic animals.

Mycobacterium tuberculosis is recognized as the main cause of human tuberculosis worldwide, yet for more than 25 years, various studies have suggested that it may be underestimated as a cause of zoonotic tuberculosis in humans [26]. The World Organization for Animal Health recognizes bovine tuberculosis as an important zoonosis [27], while the Food and Agriculture Organization has identified it as an important infectious disease and prioritizes control [28], which should be implemented in humans, animals, and their interactions through national and international measures.

3.3. Surveillance and Monitoring of Tuberculosis Caused by M. bovis in the EU in Humans

Results from the analysis of the epidemiological situation in the Republic of Bulgaria, in the EU, and at the international level regarding the reported cases of TB detected in humans during the period 2013 - 2022 are presented in Tables 3 and 4. Data have been collected from ECDC annual reports extracted from TESSy from EU/EEA countries for the period 2013-2022, with the corresponding numbers and rates of TB cases per 100,000 population. For 2022, all reporting countries had comprehensive surveillance systems. Confirmed cases required either a positive culture or both detection of acid-fast bacilli by microscopy and detection of M. tuberculosis complex by nucleic acid amplification testing, communicated by the competent authorities (Table 3).

In 2013, 64,821 cases of tuberculosis were reported from EU/EEA countries; in 2014, their number decreased significantly by 11%, then in two consecutive years (2015 and 2016) they increased until 2017, when a permanent trend of decreasing the number of people infected with TB was established (Table 3). Comparing the relative number of people infected from EU/EEA countries during the studied period, it can be concluded that a permanent trend of decreasing the overall prevalence of tuberculosis is established, since the percentage of decrease is 44%. The total number of people infected with tuberculosis in the Republic of Bulgaria in the studied period is in line with the established trend of decreasing newly diagnosed cases from EU/EEA countries, as a 59% decrease was observed, comparing the 1932 cases reported in 2013 to the 792 human cases in 2022 [29].

The notification rate per 100,000 population in EU/EEA countries was 8.0 in 2022, reflecting a continued decline since the initiation of enhanced Tuberculosis (TB) surveillance in Europe in 1996. The notification rate for the EU/EEA in 2013 was 12.7 per 100,000, marking a temporary interruption in the otherwise consistent decrease observed since 2002. From 2013 to 2022, notification rates across countries showed significant variability, ranging from 3.4 in Iceland to 83.4 per 100,000 in Romania in 2013, and from 2.9 in Liechtenstein to 48.1 per 100,000 in Romania in 2022.

Regarding Bulgaria, the notification rate fluctuated from 26.6 per 100,000 in 2013 to 11.1 per 100,000 in 2022, demonstrating a clear downward trend. Despite this, the rate remained average compared to other EU/EEA countries. Romania consistently reported the highest notification rates across all years and countries studied, with values ranging from 83.4 in 2013 to 48.1 per 100,000 in 2022. In 2013, the notification rates were higher than the EU/EEA average in Bulgaria, Estonia, Latvia, Lithuania, Portugal, and Romania, while in 2022, only Lithuania and Romania exceeded the EU/EEA average (Table 3).

Tuberculosis was the leading cause of death before the COVID-19 pandemic emerged globally, as the incidence of the zoonosis increased by 3.6% between 2020 and 2021, which was observed in all WHO regions except Africa, reversing around 2% annual declines over most of the previous two decades, as reported by the WHO [30].

In 2022 and 2023, the highest number of newly diagnosed tuberculosis cases were registered since the WHO began collecting data from all countries and regions in the mid-1990s, with 7.5 million and 8.2 million cases, respectively. It could be argued that this surge appeared related to disruptions in health services caused by the COVID-19 pandemic in the preceding two years, noting that global access to tuberculosis diagnosis and treatment has now been restored [31].

Data presented in Table 4 show that despite the established steady trend of decreasing cases of people with tuberculosis in Europe and the United States [32], at the global level, the registered cases are increasing by 27%, reaching record levels [33]. The disease remains persistent and widespread throughout the world despite the joint efforts and collaboration by individual governments. Statistically, there is a significant difference between the registered TB cases in the human population between Bulgaria and the EU/EEA countries (t[10] = -13.739, p < 0.05) and the EU/EEA TB cases and those notified at the global level (t[10] = -36.594, p < 0.05), likely due to the common health policies introduced.

3.4. Policy Frameworks

In order to ensure high standards of animal and public health in the EU and to limit the emergence and spread of transmissible animal diseases, including zoonoses, which have a negative impact on animals, food safety, livestock farmers, and the economy, Regulation (EU) 2016/429 [34] was published and entered into force in 2021. This Regulation replaced 30 other acts of European law implementing rules on disease prevention and control applicable to various categories of diseases.

The categorization of infectious animal diseases in Commission Implementing Regulation (EU) 2018/1882 [35] is based on the disease profile, the extent of its impact on animal and public health, animal welfare, and the economy, as well as the availability and effectiveness of diagnostic tools and measures for prevention and control of reported outbreaks. In view of these criteria, various rules for disease prevention and control have been laid down in accordance with Article 9 of Regulation (EU) 2016/429 - reporting of the occurrence or suspicion of a disease, surveillance and eradication of a certain disease, and measures related to the movement of animals and products of animal origin within the Union and their introduction into the Union [36, 37].

Mycobacterium bovis is one of the eight zoonotic agents that are reported by Member States each year under Directive 2003/99/EC [38]. The Directive and Regulation (EC) No 2160/2003 [39] lay down the requirements for the control of systems for monitoring zoonoses at different stages of the production of food of animal origin [40].

Although tuberculosis is a zoonotic disease, it has long been neglected, and this requires ongoing efforts to address the effects of Mycobacterium bovis on the health and well-being of humans and animals with joint measures. In response to the need, a World Health Organisation (WHO) Technical Advisory Group on Tuberculosis in Geneva in June 2016 endorsed ten priorities forming a roadmap for proportionate actions and the engagement of governments, various stakeholder groups, and academia. They quantified reducing the risk of transmission of tuberculosis from animals to humans, improving access to early diagnosis, monitoring, strengthening laboratory capacity, and promoting intersectoral collaboration [41].

Given that healthy animals provide people with safe food, efforts to reduce the reservoir of M. bovis infection in animals, including livestock and wildlife, should be a priority for every national government everywhere.

3.5. Implementation Challenges

Public health protection involves strategies to prevent and control diseases, among which zoonoses pose a great health threat to both humans and animals. Bringing zoonoses under control requires joint efforts and approaches, including hygiene practices, animal health management, and environmental control.

Globally, ranking next to HIV and AIDS, tuberculosis is one of the leading diseases that cause death worldwide, and as such, it is one of the main problems among the poorest in the world, which deepens the existing inequalities between different social groups in societies [42].

According to the Global Strategy for Tuberculosis, approved by the World Health Assembly on 19 May 2014, tuberculosis is a major global public health problem affecting millions of people, mainly in low- and middle-income countries [43], but is also a constant threat to high-income countries, where poor and vulnerable groups also live. Another aspect of the global nature of the disease is the increasing development and spread of drug resistance in times of increasing mobility, financial and social crises, leading to a scarce range of new technologies for the diagnosis, treatment, and prevention of tuberculosis [44, 45]. Under joint investigation, the WHO and the World Bank state in the Global Monitoring Report on Universal Health Coverage that globally, around 4.5 billion people—representing more than half of the world’s population—lack full access to essential health services. In addition, increased health costs force the poorest and most vulnerable groups in society to forgo essential care, which can lead to death [46].

The strategy, developed by the World Health Organization, the European Respiratory Society, and governmental and non-governmental experts from over 30 countries, aims to offer strategic guidance to governments and their partners in implementing measures to reduce tuberculosis-related deaths by 95% and the incidence of tuberculosis by 90% by 2035, compared to 2015 levels. This target is defined by a global incidence of fewer than 100 cases per million population [42].

The WHO TB strategy showed improved results in global TB incidence rate, as it was observed to decrease by 2020, while in three consecutive years of global TB incidence increase (in 2021, 2022, and 2023), the incidence rate returned to 2019 levels [47]. Given the new trend of increasing incidence, the targets set in the WHO strategy remain recommendable, rather than achievable.

Given the results of this study of a 27% increase in registered human cases globally, reaching record levels, with the exception of Europe and the USA, and the increased total number of outbreaks in all regions Asian region (74%), Europe (61%), Americas (30%) and Africa (10%), it is necessary to initiate a comprehensive discussion on the set goals, the used guidelines and measures to implement the strategy related to reduce tuberculosis-related deaths by 95% and the incidence of tuberculosis by 90% by 2035, compared to 2015 levels. A timely change in the applied measures and a general consensus from all national governments is needed to improve veterinary and health services to ensure and promote equal access to them for all people and animals in the context of the conclusion of the Global Monitoring Report from 2023 that globally, half of the world’s population lacks full access to essential health services.