Zoonotic tuberculosis

In humans, symptoms of tuberculosis caused by M. bovis and M. caprae are considered clinically and radiographically indistinguishable from those caused by M. tuberculosis ( Spickler, 2019 ). Not all individuals infected with M. bovis or M. caprae develop tuberculosis disease, but the risk increases in individuals with:

• A weakened immune system
• Concurrent infections (co-morbidities)
• Degenerative conditions
• Malnutrition and poor living conditions

Tuberculosis is considered an occupational disease, and individuals in close contact with animals are considered more at risk, such as:

• Farmers
• Veterinarians
• Slaughterhouse workers

Tuberculosis is a chronic disease with a long incubation period, ranging from weeks to years. Mycobacteria can persist inactive in the body for a variable amount of time, before eventually causing symptoms and becoming infective for other people. After the initial infection and relative treatment, the bacteria can remain latent, without causing any symptoms, and can reactivate if the immune system is weakened ( Spickler, 2019 ).

Host immune status and the bacterial entry route determine the disease course. Progression is generally slow and debilitating. General symptoms include:

• Loss of appetite
• Weight loss
• Lethargy
• Weakness
• Low-grade fluctuating fever

In the respiratory form (pulmonary tuberculosis), symptoms include:

• Persistent moist cough, occasionally with blood-streaked sputum
• Chest pain
• Weakness
• Fever at night
• Night sweats

Gastrointestinal involvement can cause more general signs, such as:

• Vomiting
• Diarrhoea

Extrapulmonary tuberculosis can affect any part of the body and symptoms are site-related:

• Nodular skin lesions
• Ocular disorders
• Abortion and infertility
• Signs of central nervous system involvement

Even after successful treatment, post-tuberculosis lung disease affecting the large and small airways may develop in individuals exposed to particular factors such as:

• Multiple tuberculosis re-infections
• Drug-resistant mycobacteria
• Delayed diagnosis
• Smoking (possibly)

Individuals affected by post-tuberculosis lung disease, exhibiting symptoms such as breathlessness and chronic cough, have reduced life expectancy, an increased risk of recurrent tuberculosis infections, and might suffer from psycho-social complications ( Allwood et al., 2021 ).

If untreated, tuberculosis can lead to death in about half of infected patients within five years, with most fatal outcomes occurring within the first 18 months ( EFSA AHAW Panel, 2017 ). According to the WHO, the global proportion of people affected by tuberculosis who died from the disease in 2021 was 15% ( WHO Global Tuberculosis Report, 2022 ).

In animals, including cattle and goats, the disease occurs with an insidious onset. Clinical manifestations can take from a few months to years to appear. In addition, after the initial infection, the bacteria may remain latent for years before reactivating during periods of stress or in old age, or persist dormant for a lifetime ( EFSA AHAW Panel, 2017 ). Shorter incubation periods have also been reported. When infected with M. bovis or M. caprae, animals may show:

• Weight loss and reduced appetite
• Low-grade fluctuating fever
• Enlarged and palpable superficial lymph nodes
• Respiratory symptoms, such as moist, intermittent cough and dyspnoea
• Weakness
• Alternating diarrhoea and constipation

Importantly, the disease course may vary across different mammal species. As an example, M. bovis infection has shown greater  pathogenicity  in goats than M. caprae and M. tuberculosis ( Bezos, 2015 ).

In infected cattle and goats, mycobacteria can colonise the mammary glands through the bloodstream. While this colonisation may lead to so-called “tuberculous mastitis” in cattle, mastitis is not usually observed in goats. Nevertheless, the bacteria can be secreted in milk and thereby contaminate food products, posing a risk of infection to humans ( EFSA, 2004 ).

In Europe, the disease is rare in domestic animals due to statutory surveillance in affected Member States.

However, tuberculosis caused by M. bovis has significant socio-economic and public health impacts in low-income countries, where livestock is the primary source of people's subsistence, and where close contact between animals and humans is common.

Economic losses are mainly due to the costs of animal disease eradication programmes, which include periodic diagnostic testing, movement restriction and culling measures. In addition, financial losses result from the treatment of infected people and lost work time. A long, intensive course of treatment of infected individuals (from 6 to 9 months) with several first-line antibiotics is usually required, which could be prolonged by the presence of multidrug resistance of certain M. bovis and M. caprae strains ( EFSA AHAW Panel, 2017 ).

Depending on population densities, some  species  may act as  reservoirs  or  hosts  for the disease. The main reservoirs of M. bovis and M. caprae in the EU are domestic and wild animals.

Domestic animals:

• Bovines (cattle, buffaloes and bison)
• Goats
• Sheep
• Pigs
• Camelids (including alpacas, llamas and camels)

Wild animals:

• Wild boars (Sus scrofa)
• Eurasian badgers (Meles meles)
• Deer (Cervus elaphus)

The European badger (Meles meles), wild boar (Sus scrofa), and deer (Cervus elaphus) are considered important reservoirs of M. bovis, and possibly also M. caprae, in some zones of the EU. For example, wild boars are a source of M. bovis in parts of the Iberian Peninsula, with occasional  spillover  to cattle.

Infection with M. bovis and M. caprae can also occur in other susceptible domestic and wild mammals, such as:

Domestic animals:

• Dogs
• Cats
• Horses

Wild animals:

• Red foxes
• Minks
• Ferrets

In Europe, where the  prevalence  of the infection in cattle is low, the disease in domestic animals other than ruminants is a very rare event.

Mycobacterium caprae has also been found sporadically in zoo animals such as tigers, camels, dromedaries and American bison, demonstrating that transmission is possible among these species. Cases of tuberculosis caused by M. caprae are fewer than those caused by M. bovis in both domestic and wild animals. Due to the additional molecular tests needed, these numbers are likely underestimated since diagnosis of M. caprae is not routinely performed.

In the environment, mycobacteria are somewhat resistant. They can stay vital in soil, feed, faeces and other materials, especially in cold, dark and moist conditions. However, the importance of mycobacteria survival in soil with regard to disease spreading is still unclear ( Spickler, 2019 ).

Mycobacterium bovis and M. caprae can infect humans through indirect and direct routes.

Indirect:

• Ingestion of contaminated raw/non-heat-treated or non-filtrated milk and derived dairy products

Direct (less common):

• Animal-to-person by inhalation of droplets from infected animals through coughing or sneezing
• Person-to-person by inhalation of droplets from infected individuals through coughing or sneezing
• Direct contact with cutaneous penetration (occupational risk)

In particular, consumption of contaminated raw milk or milk not subjected to adequate heat treatment (such as pasteurisation and ultra-high temperature) or filtration treatment, to kill or remove the mycobacteria, along with derived dairy products, such as soft cheese, remains the main way to contract tuberculosis from animals.

Zoonotic tuberculosis in humans has been reduced since the introduction of pasteurisation.

Elderly or immunosuppressed individuals are more likely to contract zoonotic tuberculosis due to a weaker immune system.

Regarding animals, the routes of transmission are similar to those in humans.

Direct:

• Animal-to-animal by inhalation of droplets due to close contact with infected animals
• Person-to-animal by inhalation due to close contact between an infected person and susceptible animals (anthropozoonosis)

Indirect:

• By ingestion of mycobacteria in milk by young animals
• By ingestion of feed or water contaminated with urine and faeces containing MTBC bacilli

Among domestic animals, transmission via inhalation is the most important route of transmission.

Bacteria can be inhaled from droplets generated by coughing or sneezing animals or from infected dust particles in the air. Animals housed in stables and barns, as seen in intensive systems, are at a higher risk due to close contact. Generally, a higher concentration of microorganisms is required to establish an infection via ingestion than inhalation ( Spickler, 2019 ). 

In the European context, contact between wild and domestic animals is rare, and indirect transmission is the most frequent. Bacteria belonging to the Mycobacteria tuberculosis complex have been identified in waterholes and other water points, which are shared between domestic and wild animals. Here, environmental contamination (water, mud or  fomites ) can be higher, especially during the dry season. In Europe, the most important system of host-sharing Mycobacteria tuberculosis complex bacilli is the cattle-deer-wild boars system ( EFSA AHAW Panel, 2017 ).

Localisation of live Mycobacterium bacilli in meat is rare, and there is no scientific evidence that it can constitute a hazard for humans. Moreover, the safe consumption of meat is ensured by detecting infected animals at the early stages of infection through periodic in-life controls and excluding carcasses affected by general tuberculosis from human consumption during post-mortem veterinary inspections ( EFSA AHAW Panel, 2017 ).

• In 2023, the percentage of zoonotic tuberculosis cases among the total number of tuberculosis cases in humans in European Union countries was 0.35%. There were 138 confirmed cases of human tuberculosis due to Mycobacterium bovis or Mycobacterium caprae, corresponding to a European Union notification rate of 0.04 cases per 100,000 population. This resulted in 6.1% decrease in notification in the European Union compared with 2022.
• In 2023 and 2022, the number of cases of human tuberculosis due to M. bovis or M. caprae in the European Union remained higher than during the pandemic years 2020 and 2021. In 2023, the number of human cases among the 25 Member States exceeded the number of cases reported in 2019.
• In 2023, the M. bovis and M. caprae case notification rate was 0.03 cases per 100,000 among European Union Member States with disease-free status and 0.05 cases per 100,000 in European Union Member States with non-disease-free status for the bovine population.
• The majority of M. bovis and M. caprae cases in humans (48.6%) were of European Union origin (native cases and/or cases originating from other Member States).
• In bovine animals, in 2023, the overall prevalence of tuberculosis (0.57%) due to M. bovis or M. caprae decreased slightly compared with the previous year (0.61%), and the number of infected cattle herds in the European Union decreased from 9845 to 8821 herds.
• Similar to previous years, the distribution of infected herds was heterogeneous and spatially clustered, with national herd-level prevalence ranging from <0.01% (Austria, Germany, Poland, Romania) to 7.2% (the United Kingdom (Northern Ireland)).
• Seventeen Member States had disease-free status in 2023. Ten Member States, along with the United Kingdom (Northern Ireland), were under an eradication programme, of which three Member States (Italy, Portugal and Spain) had disease-free status zones.
• In the disease-free status zones, a total of 162 cattle herds (0.02%) were reported to be infected with the Mycobacterium tuberculosis complex, 13 more than in 2022, confirming that infection occurs rarely in these areas.
• In the zones under an eradication programme 8659 cattle herds (1.5% of the total) tested positive for M. tuberculosis complex in 2023, a 10.7% decrease from the 9696 herds reported in 2022. The United Kingdom (Northern Ireland) (7.2%), Ireland (4.8%) and Spain (3.2%) were the only countries with prevalence higher than 1%. No positive herds were reported by Bulgaria, Cyprus or Malta. Over the last decade (2014–2023), the total number of positive cattle herds in eradication programme zones decreased by 49.4%, largely due to the withdrawal of the United Kingdom from the European Union in 2020. 

For more information on Zoonotic tuberculosis reported in humans, animals and food in the EU and other reporting countries in 2023 and in previous years, refer to the  2023 EU One Health Zoonoses Report , to the online  dashboard on Zoonotic tuberculosis , and to the online  dashboard on foodborne outbreaks  published by EFSA.  

The map on the right shows the status of countries, by 05/06/2023, as regards infection with Mycobacterium tuberculosis complex (M. bovis, M. caprae and M. tuberculosis) (MTBC), in accordance with  Commission Implementing Regulation (EU) 2021/620 .

For a more up-to-date version of the map, please visit the " Surveillance, eradication programmes and disease-free status " webpage of the European Commission. 

The prevention of infections with M. bovis and M. caprae relies on a comprehensive “farm-to-fork” approach.

• Testing and culling infected animals in countries or zones under eradication programmes.
• Using personal protective equipment (PPE), such as disposable masks and rubber gloves, for farmers, operators and veterinarians during handling of potentially infected animals.
• Implementing  biosecurity  measures to reduce direct and indirect contact between domestic and wild animals.
• Organising continuous biosecurity training for farm managers and farm workers.

• Applying proper pasteurisation (or other heat or filtration treatment) of milk intended both for direct consumption and for the production of derivatives.
• Using PPE, such as disposable rubber gloves, lab coats, or aprons, for personnel handling live or dead animals, such as farmers, slaughterhouse workers and veterinarians.
• Conducting regular and proper official controls by competent authorities, such as post-mortem inspection of the carcass.
• Organising continuous  food safety  training for food business operators.

• Performing regular and proper official controls by competent authorities.
• Ensuring that milk is from farms and animals that are subject to official controls.

• Avoiding the consumption of raw milk or milk that has not undergone adequate heat or filtration treatment, and/or cheese and other derived dairy products, in and from  enzootic  areas.
• Boiling raw drinking milk before consumption when purchased from an automatic distribution system for raw milk and/or direct purchase from farmers.

The " Five Keys to Safer Food " were developed by WHO to educate consumers and food handlers on the safe handling of food.

 _{Click on the plus sign in the right-hand panel for more information on each element.}  

Data on Mycobacterium bovis and Mycobacterium caprae are collected across the entire food chain.

Surveillance in humans

•  Commission Implementing Decision (EU) 2018/945  provides case definitions for a range of communicable diseases, including zoonotic tuberculosis.
•  Regulation (EU) 2022/2371  establishes rules on relevant cross-border threats to health, including epidemiological surveillance, monitoring, early warning, and response actions.
• ECDC collects, analyses and disseminates data on human cases ( ECDC’s Surveillance Atlas of Infectious Diseases ) in compliance with Regulation (EU) 2022/2371 and uses indicator-based surveillance data to produce its  Annual Epidemiological Reports .  

Surveillance in food and feed

• In accordance with  Directive 2003/99/EC , Member States are required to monitor and report on bovine tuberculosis at the most appropriate stage of the food chain.
• No harmonised monitoring for M. bovis or M. caprae contamination in food or feed has been established in the EU.

Surveillance in animals

•  Regulation (EU) 2016/429  (the Animal Health Law) lays down rules for the prevention and control of animal diseases transmissible to animals or humans. The EU has specific legislation covering several animal diseases according to their potential social and economic impact, including infection with Mycobacterium tuberculosis complex (M. bovis, M. caprae, M. tuberculosis, (MTBC)). This includes notification obligations, diagnostic methods and measures to be applied in case of suspicion and confirmation of disease. Commission Implementing  Regulation (CIR) (EU) 2020/2002  lays down reporting rules for Member States for infection with MTBC in animals.
• Following Regulation (CIR) (EU) 2020/2002, Member States must notify the  EU Animal Diseases Information System (ADIS) , managed by the European Commission, of all cases of MTBC in bovine (cattle, buffaloes and bison), caprine, ovine and other animal species.
• In disease-free Member States or zones, notification to EU ADIS of primary outbreaks of MTBC is mandatory within 24 hours
• Member States must also notify the European Commission, through ADIS, of any secondary outbreaks on their territory at the latest on the first working day of the week (for cases concerning the previous week).
• Commission Delegated  Regulation (EU) 2020/689  lays down specific rules for the eradication (in non-disease-free zones) and surveillance (in disease-free zones) of MTBC in domestic bovine animals.
• In addition, Regulation (EU) 2020/689 reports the requirements for the granting, maintenance, suspension and withdrawal of the disease-free status at the level of establishments and the granting and maintenance of the disease-free status at the level of Member States or zones.
• Annex II of  Regulation (EU) 2021/620  lays down rules for the application of Regulation (EU) 2016/429 of the European Parliament and the Council and lists Member States or zones thereof with disease-free status from infection with M. bovis, M. caprae and M. tuberculosis, in animals. Annex II also reports the updated Member States or zones thereof with approved eradication programmes in place for these pathogens.

Surveillance of antimicrobial resistance

• There is no antimicrobial resistance surveillance for M. bovis and M. caprae in the EU.

An important component of food safety is safeguarding the health of animals: food safety begins at the farm with the prevention of animal diseases. To protect consumers from this threat, the EU has adopted an integrated approach to food safety from farm to fork, involving all key players: the EU Member States, the European Commission, the European Parliament, EFSA, the ECDC and European Union Reference Laboratories.

Data on the occurrence of M. bovis and M. caprae in animals and food, and in humans are collected by EFSA and ECDC, respectively, and analysed in the annual  EU One Health Zoonoses report  prepared by EFSA and the ECDC.

EFSA has a crucial role in the following:

• Collecting and analysing EU-wide data on the prevalence of M. bovis and M. caprae in food and animals
• Supplying independent scientific advice and assistance on the food safety and animal health aspects of M. bovis and M. caprae through EFSA's Panel on Biological Hazards and EFSA's Panel on Animal Health and Welfare
• Supporting European and national risk managers in monitoring and evaluating the prevalence of M. bovis and M. caprae in animals and suggesting control measures when needed
•  Preparedness and response (EFSA)  in the event of food or feed safety incidents or crisis
• Developing and assessing tools and measures for the prevention and control of animal diseases
• Reporting on surveillance activities carried out within the EU

EFSA is assisted by its network of zoonoses monitoring data, a pan-European network of national representatives and international organisations that support EFSA by gathering and sharing information on zoonoses in their respective countries.

The European Union Reference Laboratories (EURLs)

The European Union Reference Laboratories (EURLs) are appointed by the European Commission and aim to ensure high-quality methods of analysis, as well as uniform testing and diagnosis within the areas of animal health and food microbiology in the EU. EURLs also aim to coordinate the activities of national reference laboratories and provide necessary support to EFSA in monitoring zoonoses (guidance for reporting, advice, etc.).

The EURL for Bovine tuberculosis is hosted by the  Visavet Health Surveillance Centre of the University Complutense of Madrid  (Spain).