Tuberculosis

Mycobacterium tuberculosis

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Changed on: 14.12.2018
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Mycobacterium caprae, elektronenmikroskopische Aufnahme
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Mycobacterium caprae, elektronenmikroskopische Aufnahme, © AGES, Tiergesundheit / Image: Mycobacterium caprae, electron-microscopic image, © AGES, Animal Health

Mycobacteria, as the pathogens of tuberculosis in animals and humans, are among the most important bacterial pathogens. The actual tuberculosis pathogens are pooled in the so-called Mycobacterium tuberculosis complex (MTC), based on their close genetic relationship. Mycobacterium tuberculosis, which causes tuberculosis in humans, and M. bovis, the agent that causes bovine tuberculosis, are endemic worldwide. Other pathogens of the Mycobacterium tuberculosis complex (MTC) are: M. caprae, M. africanum, M. microti, M. canetti, M. pinnipedii, M. mungi, M. orygis, M. suricattae and Dassie bacillus.

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Mycobacterium caprae, elektronenmikroskopische Aufnahme
caption
Mycobacterium caprae, elektronenmikroskopische Aufnahme, © AGES, Tiergesundheit / Image: Mycobacterium caprae, electron-microscopic image, © AGES, Animal Health

Mycobacteria, as the pathogens of tuberculosis in animals and humans, are among the most important bacterial pathogens. The actual tuberculosis pathogens are pooled in the so-called Mycobacterium tuberculosis complex (MTC), based on their close genetic relationship. Mycobacterium tuberculosis, which causes tuberculosis in humans, and M. bovis, the agent that causes bovine tuberculosis, are endemic worldwide. Other pathogens of the Mycobacterium tuberculosis complex (MTC) are: M. caprae, M. africanum, M. microti, M. canetti, M. pinnipedii, M. mungi, M. orygis, M. suricattae and Dassie bacillus.

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Incidence

Incidence

Tuberculosis in Humans

More than a third of the world’s population is infected with tubercolosis (M. tubercolosis) according to estimates by the World Health Organisation (WHO). About 1.6 million people die as a result of the infection and every year, with 9 million becoming infected annually. This makes tuberculosis the most common infectious disease in the world. While infections in Austria have decreased, infection rates in Africa and some parts of Asia have gone up considerably, also as a result of the AIDS epidemic. The number of tuberculosis resistant to drug treatment (MDR TB; Multidrug-resistant tuberculosis) has risen dramatically in the former Soviet Union and its successor states over recent years.

Tuberculosis is an infectious disease that can be passed between humans and animals -- thus, it is a zoonotic disease as it can be basically transmitted from animals to humans and vice versa. M. bovis is under control in most European countries, thanks to governmental control measures. There is a serious risk to humans in countries where the disease is widespread in cattle. M. bovis or M. caprae infections in humans are not very common in Central Europe. However, infections caused by these two pathogens can be almost as serious as an infection with M. tuberculosis.

Tuberculosis in Animals

The Mycobacterium tuberculosis complex plays a role as the tuberculosis pathogen in various pets and zoo and feral animals. Bovine tuberculosis (M. bovis) must be notified to the authorities in Austria and internationally (see homepage of the BMG/Consumer Health). Austria has been officially free of bovine tuberculosis (decision by the EU Commission of 23rd June 2003, 2003/467/EC) since 1999.

However, free-rangeing animals, such as red deer, can play a significant role as a reservoir for M. caprae. M. caprae was also detected in a doe and a red fox in Austria. Winter feeding of free-ranging animals is a problematic issue – transmission of the pathogen and lower natural mortality rates, as well as the gathering of animals around the feeding areas, help the bacteria to spread. The transmission of the infection from red deer to cattle as a result of the use of the same pastures by cattle herds and red deer has been observed in Austria since 2008, especially in the pasture and Alpine pasture period.

Further literature

Transmission

Transmission

Transmission Human to Human/Animal to Human

The most common infection route of tuberculosis is through the air: mycobacteria are enclosed in tiny water droplets during coughing and spread through the air. However, while only a minute number of mycobacteria suffice to cause an infection, long (more than eight hours) and close contact with a patient suffering from active tuberculosis is required to get infected.
Transmission from animals to humans occurs via direct contact with infected animals.

Other forms of transmission, such as the consumption of contaminated food, are very rare and of little significance. The zoonotic transmission via unpasteurised cow dairy products used to be of significance in the past.

Scientific commentary on the risk assessment of dairy products upon suspicion of TB (in German).

Transmission Animal to Animal / Human to Animal

Mycobacteria are present in saliva, bronchial mucus, faeces, milk, urine, vaginal mucus and sperm. While the bacteria do not multiply in the environment, they can still remain infectious for months. Given the fact that Austria is officially free of bovine tuberculosis, infections are caused by other animals. The winter feeding of free-ranging animals is a problematic issue: the transmission of the pathogen and lower natural mortality rates, as well as the gathering of animals around the feeding areas, help the pathogen to spread.

Infection between animals occurs predominantly through the air, breathing in fine droplets containing the bacterium that were shed by infected animals via coughing. However, contact or oral ingestion of the bacterium may also cause an infection -- e.g. when feeding from contaminated fodder in mangers or licking salt.

Additionally, retransmission – from infected humans to animals – can also occur. M. tuberculosis is also pathogenic for animals. However, infections in livestock caused by this pathogen are rare.

Symptoms

Symptoms

Symptoms in Humans

Following an infection with the pathogens of the Mycobacterium tuberculosis complex, the patient will often suffer from unnoticed primary tuberculosis, which will then turn into a latent tuberculosis infection.

The most common form (80 %) of active tuberculosis is pulmonary tuberculosis. Its most important symptoms are a yellow-green sputum producing cough that is prolonged over several weeks, night sweats, tiredness, fatigue and fever. The destruction of lung tissue (forming of caverns) results in the pathogen getting into the bronchia without treatment, which makes it possible for the bacterium to be discharged via the sputum – the patient will now be able to infect other people.

Symptoms in Animals

Chronic pulmonary tuberculosis is visible in cattle via progressing coughing and the slow deterioration of general health condition. Infections can also occur in other organs.

Symptoms also see:
Compendium Bovine Tuberculosis by the BVET Switzerland – Forms of Bovine Tuberculosis during Meat Examinations

Homepage of the Federal Food Safety and Veterinary Office Switzerland

Images of Symptoms

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Rotwild, eitrige Granulome in Lunge /
Red deer, purulent granuloma in the lung
Rotwild, eitrige Granulome in Lunge / Red deer, purulent granuloma in the lung
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Rotwild, vergrößerter Leberlymphknoten /
Red deer, enlargened lymphatic nodes of the liver
Rotwild, vergrößerter Leberlymphknoten /
Red deer, enlargened lymphatic nodes of the liver
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Hirsch, eitrige Granulome entlang der Aorta /
Stag, purulent granuloma along the Aorta
Hirsch, eitrige Granulome entlang der Aorta /
Stag, purulent granuloma along the Aorta
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Rotwild, rechter retropharyngealer Lymphknoten, granulomatös /
Red deer, right retropharyngeal lymph nodes show signs of granuloma
Rotwild, rechter retropharyngealer Lymphknoten, granulomatös /
Red deer, right retropharyngeal lymph nodes show signs of granuloma
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M. caprae, rasterelektronenmikroskopische Aufnahme, Kultur /
M. caprae scanning electron microscopic image, culture
M. caprae, rasterelektronenmikroskopische Aufnahme, Kultur /
M. caprae scanning electron microscopic image, culture
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granulomatöse Lymphadenitis mit Bakterien (Microphoto, ZN-Färbung /
Lymphadenitis granuloma with bacteria (micro photo, Ziehl-Neelson stain)
granulomatöse Lymphadenitis mit Bakterien (Microphoto, ZN-Färbung /
Lymphadenitis granuloma with bacteria (micro photo, Ziehl-Neelson stain)
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Rind, eitrige Granulome in Lunge / Cattle, purulent granuloma in the lung
Rind, eitrige Granulome in Lunge / Cattle, purulent granuloma in the lung
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Rind, eitrige Granulome in einem Mediastinallymphknoten / Cattle, purulent granuloma in a mediastinal lymph node
Rind, eitrige Granulome in einem Mediastinallymphknoten / Cattle, purulent granuloma in a mediastinal lymph node
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Rind, eitrige Granulome in einem Mediastinallymphknoten / Cattle, purulent granuloma in a mediastinal lymph node
Rind, eitrige Granulome in einem Mediastinallymphknoten / Cattle, purulent granuloma in a mediastinal lymph node

Control, Prevention

Control, Prevention

Treatment and Prevention in Humans

Anti-tuberculosis therapy is very long-term and must be continued for a minimum of six months, as a result of the slow growth of the pathogen. It is mandatory to administer more than three effective drugs during the first two months of treatment at least, to prevent the bacteria becoming resistant.

Should there be resistance to one or more antibiotics, older antibiotics with even with more side effects must be administered.

Treatment of MDR TB becomes especially problematic if the pathogen is resistant to at least the two most important drugs: Isoniazid and Rifampicin. In such cases, surgery must be used during which the affected part of the lung is removed. Therapy for a newer, special form called extensively drug-resistant TB (XDR TB) is even more difficult and takes several years.

Preventative inoculation with the vaccine strain BCG has not resulted in satisfactory infection prevention, despite having been used for many years. The best prevention is the identification of an outbreak. This means that the patients’ environment is examined for potential TB infections following diagnosis and treatment is started if required. It is important to compare the pathogen’s genetic fingerprint when trying to identify unclear infection routes. However, these laborious techniques make it possible to identify the index case even years after transmission.

Human TB Monitoring: Tuberculosis in the Epidemiologic Warning System (in German).

Control and Surveillance Measures in Animals

Control focuses on the identification of infected animals during the examination of slaughtered animals and the dissection of animals that have died. M. bovis has not been detected in livestock in Austria since the country was declared TB-free. The EU cross-border project “Tuberculosis (TB) in Alpine Wildlife” was completed in 2013. Austria, Germany, Italy, Switzerland and Liechtenstein teamed up in this project to develop a cross-border health and control strategy protecting livestock and, eventually, humans from imported tuberculosis from the red deer population into livestock. Cattle in certain risk areas have been examined on an annual basis as M. caprae-positive infections have been detected in wild red deer in certain regions in Tyrol and Vorarlberg.

All examinations carried out on cattle and red deer from selected risk areas in Austria (“indicator mountain pastures”) to date were/are adapted to the epidemiologic situation and the results of any previous examination periods and continued in the following years. Cattle that has been grazing on Alpine pastures in Austrian regions with a dense red deer population is examined in line with statistically safe, risk-based sample plans, to identify any potential transmission of TB from red deer to bovines.

Legal regulations and current situation in red deer and cattle

Tuberculosis in red deer in the Alpine region Folder (pdf)

Fink et al. (2015): Red Deer as maintenance host for bovine tuberculosis, alpine region

Diagnostics

Diagnostics

Diagnostic examinations must be conducted in a security-level 3 laboratory (BSL 3), given the danger potential of the Mycobacterium tuberculosis complex. Samples must be grown for up to eight weeks as a result of the pathogen’s slow growth. However, the use of molecular biological methods, such as polymerase chain reaction (PCR), can reduce the time needed for a diagnosis.

Diagnostics in Humans

The objective of all tuberculosis diagnostics is to find evidence of pathogen cultures. This is the only way of identifying a resistance pattern and an outbreak.

Latent tuberculosis infections can be diagnosed using the Mendel-Mantoux tuberculin skin test, which has been in use for several decades, or new blood tests -- the so-called interferon gamma release assays. Unlike the tuberculin skin test, the blood tests are not affected by the BCG vaccination.

Additionally, the AGES National Reference Centre for Tuberculosis has been using Next-Generation DNA Sequencing since 2015. Next-generation sequencing not only analyses small parts of bacterial DNA, but its entire genetic material within a short time period. This enables the rapid identification of antibiotic resistances, in addition to more efficient outbreak identification – a step that had only been previously possible through the isolation of pathogens in a long, drawn-out process. The AGES Reference Centre has been analysing all pathogen isolates on a routine basis using next-generation sequencing since 2016.

Diagnostics in Animals

The objective of any tuberculosis diagnostics in veterinary medicine is also to isolate the pathogen. This is the sole method that makes it possible to identify species, genotypes and outbreaks. Diagnostics in live animals are carried out using a skin test that has been used for the past century. There is also an interferon gamma release assay for bovines and bovine-like animals and an antibody blood test for bovines. A positive in-vivo test results in the diagnostic culling and pathologic-anatomical and histological examination of the animal cadaver, followed by providing evidence of the pathogen (bacteriological and molecularbiological diagnostics). A direct molecular method (PCR) will reduce the time needed for tuberculosis diagnosis.

Examination methods used in Mödling

  • Pathologic-anatomical examination 
  • Histopathological examination 
  • Ziehl-Neelson stain 
  • Isolation 
  • Molecularbiological examinations 
  • Tests to find evidence of cell-mediated immunity

Examination Laboratory Veterinary

Institute for Veterinary Examinations, Mödling (=National Reference Laboratory)
Contact:

Robert Koch-Gasse 17
A-2340 Mödling
Tel.Nr.: +43 50 555-38112
e-mail: vetmed.moedlingno@Spam@agesno.Spam.at

Contact

Dr. Erwin Hofer, erwin.hoferno@Spam@agesno.Spam.at
Dr. Maria Fink, maria.finkno@Spam@agesno.Spam.at


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