What does TBC mean in medical terms

tuberculosis

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Tuberculosis has been on the rise again for several years. It usually occurs in the lungs, but can also manifest itself in other organs and affect the nervous system. The number of cases has risen again in Germany in recent years. At the same time, the number of multidrug-resistant tuberculosis diseases that respond to fewer and fewer drugs is increasing worldwide.

Tb, Tbc, Koch's disease, (pulmonary) consumption

definition

Tuberculosis (TB) is an infectious disease that is widespread around the world. It is triggered by mycobacteria. The main pathogen is Mycobacterium tuberculosis. An infection can also be triggered by Mycobacterium bovis or Mycobacterium africanum.

A distinction is made between pulmonary tuberculosis and extrapulmonary tuberculosis or organ tuberculosis and between open TB and closed TB. In pulmonary tuberculosis, a distinction is also made between primary and post-primary tuberculosis. In the case of primary tuberculosis, the disease breaks out immediately after infection. In the case of post-primary TB, however, the disease often only breaks out at a much later point in time. The organs affected by extrapulmonary tuberculosis are usually the liver, spleen, kidneys, bones or the central nervous system.

Tuberculosis infections in which the affected patients actively excrete pathogens and the tuberculosis focus (s) are connected to the respiratory tract are considered to be open TB. This occurs primarily in pulmonary tuberculosis diseases. If, on the other hand, the focus of infection is encapsulated and the patient is not infectious, one speaks of closed tuberculosis.

Miliary tuberculosis or disseminated TB is a special form of tuberculosis.It is characterized by numerous millet-sized infiltrates in the lungs or other organs.

Epidemiology

It is estimated that one in three people worldwide is infected with tuberculosis. In most people, however, the onset of the disease takes a long time or does not break out at all. Only around five to ten percent of infected adolescents and adults actually develop tuberculosis that requires treatment.

The TB is triggered by mycobacteria. The main pathogen responsible for tuberculosis in Germany is Mycobacterium tuberculosis with a good 82%. Among the organs, a manifestation of Tbc in the lungs is leading with a good 70%. Most of them have what is known as an open form of pulmonary tuberculosis with a good 80%.

In 2013, 4,318 people were newly diagnosed with the infectious disease. Since then the numbers have increased slightly. In recent years, a good 5,400 cases of tuberculosis have been reported in Germany every year. The incidence of tuberculosis in 2017 was 6.7 patients per 100,000 population. Many sick people are foreign nationals (68.1%). It is believed that some of the diseases could be related to migration.

One third of those affected are adult men and one third are women. Children under 15 are only represented with 4.3%. The mortality in Germany is a good one percent with an incidence of 0.15 male deaths per 100,000 population and 0.10 female deaths per 100,000 population among adults. If miliary tuberculosis occurs, the mortality increases to 90%.

Epidemiologists are concerned about the increasing number of resistant tuberculosis pathogens. In Europe, around 1,300 TB cases are reported each year that were triggered either by multi-resistant pathogens that do not respond to isoniazid or rifampicin, or extensively resistant pathogens that are also resistant to any fluoroquinolones or second-line TB drugs such as amikacin, Capreomycin or kanamycin. Infections with these resistant TB pathogens are particularly difficult to treat. According to the European Center for Disease Prevention and Control, treatment is only successful in a third of these cases. According to the WHO, TB has therefore been a health emergency for years.

TB is highly contagious as long as there is an open tuberculosis disease. According to projections, a single contagious patient with open TB in Germany infects between two and ten other people.

causes

The TB is triggered by mycobacteria. The pathogens include Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium africanum. The main pathogen in Germany is M. tuberculosis. The bacterium has a lipid-rich cell wall and is therefore particularly difficult for the immune system to eliminate. The bacterium is also insensitive to dehydration and cold. Humans are the only reservoir for the bacteria M. tuberculosis and M. africanum. M. bovis is found in humans and cattle, sometimes also in wild animals.

People become infected through saliva, droplet infection (infectious aerosols), urine or stool. Not every patient who is a carrier of M. tuberculosis also excretes the TB pathogen, because many infected people have what is known as closed TB, in which they carry the bacterium but excrete few or no bacteria. Every patient with open tuberculosis, on the other hand, is contagious and excretes bacteria. Tuberculosis is considered to be open if the bacteria have access to the respiratory tract and can thus leave the host body. Most critical are usually patients with open lung tuberculosis, as they can excrete bacteria as infectious aerosols. Tbc manifestations in other organs are considered to be relatively low in infection, as they are rarely or not at all excreted. Only with medical interventions or injuries does the risk of becoming contagious increase.

In 95% of cases, infection occurs through inhalation of droplets containing the pathogen. In principle, TB pathogens can also be transmitted via unpasteurized cow's milk from sick animals. In Germany and Central Europe, however, according to the current state of knowledge, the animal populations are largely free of tuberculosis and strict guidelines apply.

Pathogenesis

It takes an average of six to eight weeks from the time of infection to the onset of the disease. The pathogenesis of TB is divided into primary tuberculosis and post-primary TB, the latter as a reactivation disease.

Primary tuberculosis

After inhalation, the bacteria are phagocytosed by two types of immune defense cells in the lung alveoli: alveolar macrophages and dendritic cells. Since the pathogen successfully prevents phagosomes and lysosomes in the immune cells from fusing with one another and the immune defense cells cannot kill the bacteria due to their thick lipid layer, the bacteria continue to multiply in the cells. After a while, the infected host cell dies. The Tbc bacteria are released and phagocytosed by the next alveolar macrophage cell. The cycle begins again. The cell disintegration of the immune cells creates a local focus of inflammation, the primary effect, within ten to fourteen days after infection with the TB pathogens. If the bacteria now migrate via the lymphatic system to regional lymph nodes, the primary complex is created, consisting of the primary effect and infected regional lymph nodes.

At the same time a granuloma develops, further macrophages are activated and a tuberculin allergy develops. The immunologically determined phase of primary tuberculosis with T-cell activity begins six to fourteen weeks after infection. As a result, the primary complex becomes scarred and calcified. In 90% of all infections, tuberculosis stagnates at this point. In the clinical sense, there is no longer a disease, as the pathogens can no longer multiply or spread. For years to decades, the immune system can manage to keep the tuberculosis focus in check and prevent the disease from breaking out.

In individual cases, however, the primary tuberculosis progresses. Then, among other things, a progressive primary TB develops in the lungs, in which the focus of the infection necroses before the formation of a primary complex and forms a caseating necrosis. In rare cases, especially in immunocompromised patients, this progressive primary TB develops into primary miliary tuberculosis, which is colloquially referred to as "galloping consumption" and which is fatal without treatment. A sub-form of sepsis, Landouzy sepsis, has also been observed. If meninges are affected, primary tuberculous meningitis occurs. Dispersion via the lymph is also possible if bacteria pass through lymph nodes during the state of the primary effect and spread in the body. In this case one speaks of a primary scattering focus.

Post-primary tuberculosis

In about 5% of those infected with tuberculosis, the delicate balance between bacteria and immune defense is out of order within the first two years, in another 5% later in life. The tuberculosis reactivates and the actual disease breaks out with symptoms. T cells activate macrophages via IFN-gamma and other cytokines, which in turn release TNF-alpha and other cytokines. Casing necrosis forms in the granuloma center. A cavern is created, the center of which in some cases consists of liquefied necrosis. In the liquid center of the cavern, the TB pathogens find optimal conditions to continue to multiply. The antigen load in the tuberculosis focus increases, as a result of which the immune response is strengthened and the focus continues to grow. At this point at the latest, clinical symptoms of TB appear.

If the caseating necrosis is located near a bronchus, pathogens can spread through it. In addition, open tuberculosis develops, which is highly contagious. It can also spread to other organs as soon as the tuberculosis focus is connected to blood vessels.

The reactivation is often triggered by a weakening of the immune system. This can happen through malnutrition, stress, heavy physical strain, measles, cortisone or radiation treatment, diabetes mellitus, drug or alcohol abuse, silicosis, old age, puberty or an acquired immune deficiency.

Symptoms

Many patients suffer from tuberculosis without any typical distinctive signs. In pulmonary tuberculosis, one of the key symptoms at the beginning of the disease is cough with or without sputum, also bloody in nature. Difficulty breathing and chest pain can also occur. Other possible symptoms of TBC are often fever, weight loss, loss of appetite, tiredness, general weakness or symptoms of a flu-like infection, decreased general well-being and night sweats.

If the tuberculosis infection spreads to other organs, further organ-specific symptoms can occur:

  • Pleura: pleuritic pain, accompanying inflammation and pleural effusion
  • Lymph nodes: mainly cervical, axillary, inguinal and hilar lymph nodes affected; noticeable swelling of the lymph nodes
  • Urogenital tract: recurrent cystitis
  • Skeletal system: neck and back pain; 30% of those affected also suffer from poor gait and neurological symptoms
  • Central nervous system: prolonged meningitis with headache, nausea, impaired consciousness, vomiting, stiff neck and neurological deficits.
  • Intestinal tract: chronic abdominal pain, nausea, weight loss, diarrhea
  • Miliary tuberculosis: acute respiratory distress syndrome, shock symptoms, headache (meningitis), abdominal pain (peritonitis), pleuritic pain (pleurisy)

Diagnosis

Tuberculosis can be diagnosed using various molecular biological, microscopic and cultural methods, the tuberculin skin test or the interferon gamma release assay.

Material extraction

If pulmonary TBC is suspected, spontaneous morning sputum (sputum) must be obtained on three different days, if possible before the start of therapy. In addition, 5% saline solution can be used as an inhalation. If morning sputum cannot be obtained with this either, there is still the option of bronchoalvelolar lavage to obtain sputum, bronchial secretion or tracheal secretion.

If the tuberculosis has manifested outside the lungs, stool or urine samples, gastric juice, pleural exudate, other body fluids, liquor, or puncture or biopsy samples are usually sufficient.

Sample transport

The material should be cooled as quickly as possible (2-8 ° C) and transported to the laboratory in a cool place. The purpose of the cooling is to prevent other fast-growing bacteria from overgrowing the mycobacteria and thus falsifying the test.

microscopy

Highly infectious patients can be identified at an early stage using inexpensive and fast microscopy. For this purpose, the material is colored according to Ziehl-Neelsen or Kinyoun staining. Alternatively, fluorescence microscopic methods such as auramine, auramine-rhodamine or acridine orange can also be used. However, the method cannot differentiate between different mycobacterial strains and thus lead to false positive test results in non-tuberculous mycobacteria. Microscopy is not suitable as the sole diagnosis of TB.

Culture

According to the guidelines, the cultural examination is the "gold standard" for the detection of pathogens. If mycobacteria grow in a culture, rapid immunochromatographic tests must be carried out to ensure that the mycobacteria are causing tuberculosis. A further study of the culture is necessary, also to filter out vaccine strains. However, the test result should always be viewed in the context of the clinic.

Tuberculin skin test

The tuberculin skin test according to the Mendel-Mantoux method is a supplementary diagnosis. For this purpose, a small amount of purified tuberculin is injected under the patient's skin about six to fourteen weeks after the onset of infection. If swelling and reddening develop at the puncture site within the next three days, the test is positive.

Since the test can be positive even after a vaccination against tuberculosis or after being sensitized, it is not considered to be meaningful enough to diagnose or rule out tuberculosis. The tuberculin skin test can also turn out negative in infected people. In this case one speaks of anergy.

Interferon gamma release test

During the infection, more T cells are activated and developed. An increased IFN-gamma production specific for M. tuberculosis bacteria can be detected in the blood of the patient by means of an antigen test in the laboratory. In contrast to the tuberculin skin test, this test is very specific and only detects true tuberculin infections, but not vaccinations.

X-ray diagnostics

X-ray imaging enables a quick and inexpensive way to identify part of the pulmonary tuberculosis foci. It is an important part of diagnostics.

Molecular biological methods

If there is justified suspicion of tuberculosis, a PCR (nucleic acid amplification test, or NAT for short) can also be carried out. The test has a high sensitivity and specificity, but is not conclusive on its own in patients with negative microscopic material. It is not suitable as a therapy control or screening method.

Antibiotic resistance and susceptibility testing

In the context of the increasing numbers of resistance worldwide, antibiotic resistance testing is becoming increasingly important as part of diagnostics. Therefore, both the guidelines and the Robert Koch Institute recommend that a susceptibility test be carried out on every TB patient from the first isolate. This is intended to filter out drug resistance at an early stage. If tuberculosis pathogens can still be detected after more than eight weeks of therapy, the susceptibility test should be repeated with new samples and the therapy adjusted if necessary.

therapy

Tuberculosis is usually treated with standard therapy according to guidelines. For this it is necessary that no drug resistance is known and that all drugs of standard therapy can be used over the entire therapy period.

Standard therapy

According to the guidelines and recommendations of the World Health Organization as well as national guidelines, active tuberculosis is treated as standard with a quadruple therapy consisting of isoniazid, rifampicin, pyrazinamide and ethambutol. The duration of therapy in the initial phase is two months, and it is taken on an empty stomach. Thereafter, therapy with isoniazid and rifampicin should be continued in the stabilization phase for a further four months. If the findings are particularly pronounced, the total duration of therapy can be increased to nine months.

Two to four weeks after the start of treatment and then every four weeks if the findings are normal, check-ups with laboratory values ​​(blood count, liver function values ​​and kidney function values) and weight control should be carried out. An ophthalmological check-up is also recommended in the initial phase and then every four weeks. A microbiological follow-up should also be carried out in accordance with the recommendations of the guidelines. Eight weeks after the start of therapy and after the end of therapy, an X-ray should also be taken as a follow-up check for thoracic tuberculosis. Separate rules apply to children.

Therapy for resistance

If resistant pathogens are found in the antibiogram during the diagnosis, the therapy must be adapted to the respective resistances. The respective therapy depends on the resistance found.Since unwanted side effects can occur more frequently with replacement therapies, the treatment should only be carried out at specialized centers and at least under the advice of an experienced doctor.

Chemoprevention and chemoprophylaxis

Not all tuberculosis is contagious. If a person is infected but otherwise both clinically healthy and non-contagious, chemopreventive therapy is sufficient. The same applies to people who have been exposed to tuberculosis pathogens but do not (yet) show an immune reaction. In this case, chemoprophylaxis is recommended to prevent a possible infection or to treat an existing one promptly. The decision as to whether a therapy should be carried out should be based on guidelines and age. Separate rules and guidelines apply to children.

Preventive chemotherapy can be carried out with various combinations or as monotherapy with the active ingredients isoniazid, rifampicin and rifapentin (currently not approved in Germany). The duration of therapy depends on the respective active ingredients.

Only the active ingredient isoniazid is used for chemoprophylaxis. A second check for tuberculosis pathogens is carried out no earlier than eight weeks after contact with the infection. If this second test is negative and the person concerned remains symptom-free, the therapy is ended.

Multi-resistant infections

The German Center for Infection Research (DZIF) at the Clinical Tuberculosis Center of the Medical Clinic of the Borstel Research Center and the German Central Committee for Combating Tuberculosis at the Heckeshorn Lung Clinic in Berlin offer a telephone advice service for multi-resistant tuberculosis infections.

forecast

With adequate drug therapy, uncomplicated tuberculosis can be treated and cured well if the treatment is continued to the end. Relapses are rare. Exceptions are simultaneous infections with HIV and tuberculosis: HIV co-infection increases TB-associated morbidity and mortality.

More complex tuberculosis infections such as miliary tuberculosis are associated with poorer prognoses. Acute miliary tuberculosis, which manifests as shock or acute respiratory distress syndrome, has a mortality rate of 90%.

prophylaxis

Since open tuberculosis is highly contagious, a rapid diagnosis and detection of a TB infection is important in order to contain the spread. Infected patients with open tuberculosis should be isolated and receive efficient therapy as soon as possible. Even non-infectious patients require rapid therapy, which is continued until the bacteria are eradicated.

In order to filter out non-symptomatic infected people, contact persons should be examined in the vicinity of infectious TB patients. The Robert Koch Institute recommends treating infected but not yet ill contact persons preventively with chemotherapy for pulmonary tuberculosis or at least considering treatment in order to prevent the infection from progressing.

In addition, security measures must be taken to protect hospital staff. These include aerosol-sealed breathing masks for staff and rooms with negative pressure and a lock in which infectious patients can be accommodated. According to the recommendation of the Robert Koch Institute, the sick person should also wear mouth and nose protection as soon as he leaves the isolation room or other people are present.

vaccination

Until 1998, young children were vaccinated intracutaneously against tuberculosis with virulence-weakened, living strains of M. bovis (BCG vaccination). Based on the recommendations of the WHO that general BCG vaccination should not be given in populations with an infection risk of less than 0.1%, vaccinations against tuberculosis have not been routinely carried out in Germany since 1998.

Reporting requirement

The TBC is notifiable. Cases of tuberculosis must be reported by name to the health department. A refusal of treatment by the patient or a discontinuation of treatment must also be reported to the health department within 24 hours.