Tuberculosis
Mycobacterium tuberculosis complex
Profile
Tuberculosis (TB) is the most common fatal infectious disease in humans worldwide. There are different tuberculosis pathogens that are categorised as part of the Mycobacterium tuberculosis complex (MTC). The most common pathogen causing tuberculosis in humans is Mycobacterium (M.) tuberculosis. The bacterium can be inactivated by pasteurisation (brief heating to 72 °C); however, it is insensitive to dehydration or cold.
Occurrence
Tuberculosis is widespread worldwide, especially in Africa, Asia and Latin America. According to estimates by the World Health Organisation (WHO), more than a third of the world's population is infected with tuberculosis(M. tuberculosis). Every year, 1.3 million people die from the infection and around 10 million are newly infected.
In Europe, the bovine tuberculosis pathogen(M. bovis) was greatly reduced after the Second World War, as a result of which many countries received the officially recognised status "free of bovine tuberculosis". Austria's cattle herd received the status "officially recognised free of bovine tuberculosis" from the EU in 1999, and since then this tuberculosis pathogen has no longer been detected in any Austrian cattle herd. With the new Animal Health Law of the European Union, Austria has the status of "disease-free" with regard to infections with the Mycobacterium tuberculosis complex(M. bovis, M. caprae and M. tuberculosis).
Since 2008, however, M. caprae has been transmitted between red deer and cattle in individual areas of the provinces of Tyrol and Vorarlberg, and M. microti has also been detected sporadically in wild animals, cattle, cats and New World camelids. However, these detections are irrelevant for Austria's recognised free status.
Pathogen reservoir
Humans are the only relevant reservoir for M. tuberculosis. For mycobacteria that can be transmitted from animals to humans, such as M. bovis and M. caprae, cattle, wild boar, goats or wild ruminants (especially red deer) are the pathogen reservoir. The reservoir for M. microti is formed by voles and shrews, for example.
Route of infection
Whether an infection occurs depends on the frequency and intensity of contact, the amount of inhaled or orally ingested pathogens and the immune status of the person affected. Infection usually occurs through the inhalation of fine droplets in the air that are released when people suffering from open pulmonary tuberculosis cough and sneeze. Open pulmonary tuberculosis refers to diseases in which pathogens can be detected in the sputum. Transmission is also possible through the consumption of raw (unpasteurised) milk from cattle infected with tuberculosis.
Infection from animal to animal occurs preferably by the aerogenic route through inhalation of fine droplets containing the pathogen, which are coughed up by sick animals. However, it can also occur through contact or orally, e.g. via contaminated feed in feeding troughs and salt licks.
Symptomatology
Humans: In humans, the disease most commonly manifests as pulmonary tuberculosis. The affected person actively coughs up mycobacteria. The main symptoms are a persistent cough, fever, night sweats and unintentional weight loss. Other mostly unspecific symptoms include fatigue, loss of performance, swollen lymph nodes and a reduced general condition. If the infection is controlled by the immune system and the pathogens are trapped in granulomas (tubercles), for example, the mycobacteria remain in a dormant state ("latent tuberculosis"). Under certain conditions (e.g. immunosuppression or old age), reactivation can occur years later, with the disease reappearing as secondary (post-primary) tuberculosis.
Before the implementation of control programmes and the pasteurisation of milk, infection with bovine tuberculosis pathogens (e.g. M. bovis) mainly resulted in manifestations outside the lungs (e.g. lymph node, intestinal or bone tuberculosis).
Animal: Chronic pulmonary tuberculosis in cattle is mainly characterised by progressive coughing and a slowly deteriorating general condition. However, disease processes can also occur in other organs. In cattle, tuberculosis can remain latent or subclinical for years.
An infection with mycobacteria should also be considered in camelids if they are in poor condition and emaciated. Respiratory symptoms may occur.
In cats, symptoms such as emaciation, deterioration in general condition, coughing and (palpable) circumferential enlargements in all parts of the body occur. Therapy-resistant skin changes have also been observed.
Infected red deer often show no specific symptoms in the early stages of the disease. In advanced cases, red deer may be in poor condition, emaciated and weakened.
Therapy
As mycobacteria are located intracellularly in tissues with poor blood supply (e.g. granulomas), they are difficult for drugs to reach. Treatment therefore takes several months and there is an increased risk of antibiotic resistance developing. If tuberculosis is confirmed, a combination therapy with several specifically effective antibiotics, so-called antituberculotics, must therefore be carried out. The duration of treatment is usually at least six months in order to prevent a relapse and the development of resistant pathogens.
Tuberculosis is a notifiable animal disease. Official control focuses on the identification and culling of infected animals, as drug therapy is not effective for animal welfare, pharmaceutical and epidemiological reasons.
Human
In 2024, 387 human cases of tuberculosis were reported to the Epidemiological Reporting System (EMS) (as at 22 March 2025), which corresponds to 4.2 cases per 100,000 population. Of these, 300 cases could be clearly assigned to the Mycobacterium tuberculosis complex, of which M. bovis was identified in two cases.
Animal
In Austria, bovine tuberculosis is a notifiable animal disease. Austria has been recognised as free of bovine tuberculosis since 1999. From May 2000, the nationwide testing of ruminants using tuberculin tests was discontinued; the disease is monitored in the course of ante-mortem and post-mortem inspections.
Since 2008, there has been a transmission of M. caprae infection between red deer and cattle in individual areas of the provinces of Tyrol and Vorarlberg during the grazing and alpine pasture period due to the use of the same grazing areas by cattle and red deer. To determine the situation in the cattle population, special testing and monitoring areas (in accordance with the Bovine Tuberculosis Ordinance) are therefore officially designated in these regions every year. In these areas, cattle are tested for tuberculosis before and after the grazing period using a tuberculin test (simultaneous test). These tests are adapted to the epidemiological situation identified and, if necessary, appropriate area adjustments are made.
In 2023, the bovine tuberculosis pathogen M. caprae (Lechtal genotype) was detected in the NRL for bovine tuberculosis in two cattle from two farms in Vorarlberg (districts of Bludenz and Dornbirn) following abnormalities in the post-mortem inspection at the abattoir. M. microti was isolated from an alpaca from Styria.
Specialist information for human medicine
People who have close contact with patients with open (i.e. infectious) tuberculosis over a longer period of time are particularly at risk. In recent years, there has been a worrying increase in multi-resistant strains of tuberculosis pathogens (i.e. insensitivity to at least the two most important anti-tuberculosis drugs, isoniazid and rifampicin).
After a droplet infection, small centres of inflammation usually form in the lungs within the following three to six weeks, which encapsulate into nodules (tubercles) (=primary infection).
Active tuberculosis, usually a reactivation of latent pathogens, begins with unspecific general symptoms such as night sweats, subfebrile temperatures or fever, fatigue, weight loss, loss of appetite and a general feeling of illness. In pulmonary tuberculosis, tissue loss can lead to the formation of caverns in the lungs. The disease is characterised by massive, often bloody sputum. These patients are highly contagious. In rare cases, extrapulmonary infections occur, such as tuberculous meningitis (inflammation of the meninges). Miliary tuberculosis occurs when there is a disseminated infection of several organs, usually also involving the lungs.
The aim of every tuberculosis diagnosis is the cultural detection of the pathogen. Only this allows further determination of resistance and is a prerequisite for molecular typing as part of outbreak clarification.
Due to the risk potential of the Mycobacterium tuberculosis complex, a specialised laboratory with safety level 3 (BSL-3) is required. The samples are incubated for up to eight weeks due to the slow growth of the pathogens. Molecular biological methods such as nucleic acid amplification techniques (NAT) enable faster pathogen detection and provide early indications of resistance mutations of the pathogen.
Tuberculin test:
The tuberculin skin test using the Mendel-Mantoux method can be used to detect an infection without disease. This tests the immunological reaction to injected pathogen components. The test is positive as early as six weeks after an infection. However, this is increasingly being replaced by the so-called interferon-ɣ release assay (IGRA), a blood test.
Interferon-ɣ release assay (IGRA):
The IGRA test is a diagnostic tool for detecting an infection with tubercle bacilli that has taken place. The IGRA test is the diagnostic tool of choice, especially for diagnosing latent tuberculosis. The test becomes positive 2 to 6 weeks after the infection. It should be noted that the test cannot distinguish between active and latent tuberculosis. Basically, the IGRA test is used to detect infections with tubercle bacilli in people who have had contact with a case of tuberculosis (environmental examinations), who come from a high-endemic area (geographical region with an increased incidence of the disease) or before a planned immunosuppressive therapy to rule out latent tuberculosis, which can reactivate under therapy.
The diagnosis of active tuberculosis is usually made by means of pathogen detection using microscopy, molecular biological methods and cultivation (culture) as well as clinical and radiological assessment. The IGRA test is not suitable for proving the success of treatment; it can remain positive even after successful therapy.
In the IGRA test, the test person's blood is incubated in a blood collection tube coated with Mycobacterium tuberculosis-specific antigen (ESAT6 and CFP10). If the test person's immune system has been sensitised to tubercle bacilli (i.e. they have already had contact with tuberculosis pathogens), the responsible T lymphocytes are stimulated to produce interferon-gamma, which is measured. The Quantiferon TB Gold Plus test requires 4 ml of blood. You do not need to be fasting to take the blood sample. Special blood collection tubes are used and filled with 1 ml each. Alternatively, lithium heparin tubes can be used for blood collection and the blood can then (within 16 hours) be transferred to the Quantiferon Plus tubes. After blood collection, the tubes must be inverted 10 times. Transport to the laboratory must take place within 16 hours of blood collection at room temperature (22 °C ± 5 °C). The samples are then incubated at 37 °C for 16 to 24 hours and can then be stored at 4 - 27 °C for a maximum of 3 days. After incubation, the tubes are centrifuged and can be further processed or stored at 4 °C for a maximum of 4 weeks.
A positive test result indicates that contact with the Mycobacterium tuberculosis complex has taken place. However, a positive IGRA result does not allow any statement to be made about the degree of activity of the disease or even the need for treatment. Therefore, a positive IGRA test result always requires further diagnostic clarification. A negative result indicates that a TB infection has occurred and thus the presence of latent tuberculosis.
Imaging procedures:
X-ray diagnostics can be used to recognise characteristic images of a lung infection, but some other lung diseases cannot be ruled out with certainty in the differential diagnosis. Therefore, the diagnosis of tuberculosis is usually confirmed by a combination of several examination procedures.
Bacteriological diagnostics:
The detection of mycobacterial nucleic acid provides an initial diagnosis within hours. The time-consuming cultural detection of MTC bacteria confirms the diagnosis of tuberculosis. The advantage of cultural detection lies in the possibility of testing the mycobacteria for their sensitivity to specific antimicrobial drugs (resistance testing) and molecular biological typing of the isolates obtained.
Molecular biological diagnostics:
In accordance with the latest standards, the samples are analysed using whole genome sequencing (WGS). This allows matching strains to be identified and chains of infection to be clarified epidemiologically. In addition, WGS enables further resistance genes to be recognised and facilitates the assignment of species within the Mycobacterium tuberculosis complex.
Veterinary medicine
The causative agents of tuberculosis in humans and animals are closely related mycobacterial species, which are summarised as the Mycobacterium tuberculosis complex. This complex comprises the described species Mycobacterium (M.) tuberculosis, M. africanum, M. canettii, M. bovis, M. caprae, M. pinnipedii (seals), M. mungi (mongoose), M. orygis (antelope), M. suricattae (meerkat), Dassie Bacillus (rock hyrax) and M. microti (mice, secondary hosts e.g. cats, red deer, wild boar, camelids, cattle).
Chronic pulmonary tuberculosis in cattle mainly manifests itself in a progressive cough and slowly worsening general condition. However, disease processes can also occur in other organs. In cattle, tuberculosis can remain latent or subclinical for years.
In red deer, tuberculosis is a chronic disease. Clinical symptoms, if present, are often non-specific. The route of infection is usually oral or aerogenic. If the disease generalises to the head, thorax or abdomen, pathogens can be excreted in large quantities and - with the potential for transmission to other animal species - contaminate the environment. Winter feeding of wild animals is problematic: transmission is encouraged by pathogen transmission and lower natural mortality as well as accumulations of animals in the feeding area.
Diagnostics in animals
The early detection of infected cattle is an important point in the fight against bovine tuberculosis and depends on in vivo tests such as the skin and g-interferon test. In Tyrol and Vorarlberg, cattle in certain risk areas for infections with M. caprae (special testing and monitoring areas) must be tested annually using a tuberculin test (simultaneous test). In addition, a blood test (g-interferon test) can also be carried out. If the test is non-negative, the cattle are slaughtered for diagnostic purposes. A direct examination of tissue samples using MTC PCR enables a rapid diagnosis.
Camelids can also be tested for MTC disease using a tuberculin test. A subsequent antibody test increases the detection rate of infected animals.
Tissue samples from red deer killed during hunting are also analysed for the presence of the bovine tuberculosis pathogen M. caprae and other mycobacteria of the Mycobacterium tuberculosis complex using MTC PCR and bacterial culture. The selection of the animals to be sampled is based on a sampling plan.
The identification of the MTC species and genotyping of the culturally isolated bacterial strains is carried out using various molecular biological methods (RD4 PCR, DNA strip technology, MIRU VNTR analysis). Due to the classification as a risk group 3 pathogen, the cultivation of tuberculosis pathogens may only be carried out in the safety level L3 laboratory, the Centre for Biological Safety at the National Reference Laboratory for Bovine Tuberculosis in Mödling.
Contact
Leitung
Priv.-Doz. Mag. Dr. Alexander Indra
- humanmed.wien@ages.at
- +43 50 555 37111
-
1090 Wien
Währingerstraße 25a
Institut für veterinärmedizinische Untersuchungen Mödling
- vetmed.moedling@ages.at
- +43 50 555 38112
-
2340 Mödling
Robert Koch-Gasse 17
Last updated: 01.08.2025
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