tuberculosis

In by Raphikammer

What is tuberculosis?

The Tuberculosis (TB) is a notifiable infectious disease caused by tuberculosis bacteria (mycobacteria that the so-called Mycobacterium tuberculosis complex include) is caused. The bacteria are usually transmitted by the inhalation of infectious droplet cores (aerosols) from person to person. Tuberculosis affects the lungs, but can also occur in any other organ.

If the immune defense of our body successfully restricts the pathogen after the first contact, there is a latent tuberculous infection (LTBI, proof of positive tuberculin skin test about 6-8 weeks after contact). This response to an infection that does not lead to a clinically evident disease state occurs in 90-95% of cases of infection. The formation of granulomas allows infected individuals with intact immune systems to restrict the infection without causing a disease requiring treatment. The formation of granulomas, however, the bacteria are only damned, but usually not completely killed. Through various messenger substances ( cytokines) of the cells involved, it comes to a further immune activation. Since this granulomatous tissue reaction is typical for tuberculosis, it is also referred to a specific inflammation.

If, however, especially in immunodeficiency, immediately after an infection to form a tuberculous inflammatory focus, usually with an enlargement of the accompanying lymph node (primary complex), so there is a primary tuberculosis. Through the bloodstream, the pathogens can then be scattered into other organs. The term tuberculosis comes from Latin ( tuberculum = small knot).

However, even many years after an infection, active tuberculosis, which is in need of treatment, can develop (postprimary tuberculosis), when the complex regulation mechanisms of the granulomas collapse and the pathogens can proliferate without inhibition . This “reactivation” plays an important role in the industrialized countries of Europe and North America, especially in the elderly, and the risk of developing a tuberculosis requiring treatment is highest in the first two years after infection.

Tuberculosis has probably existed since time immemorial as a widespread disease and accompanies human cultural history like almost no other disease. First descriptions of the clinical manifestations of pulmonary tuberculosis go back to Hippocrates (about 460-370 BC). The industrial revolution and the resulting social changes – especially the growing population density in the cities – led to a surge in tuberculosis in the 18th and 19th centuries. In the middle of the 19th century, one in four adult men in Germany died from tuberculosis. This was also known as the “white plague” at that time In the famous, Nobel Prize winning novel “The Magic Mountain” the author Thomas Mann very vividly and forcefully describes the influence

In the industrialized countries, tuberculosis has become very frightening due to increasing prosperity, better hygienic and nutritional conditions and not least because of the medical treatment options available since the middle of the 20th century. The mortality due to the disease has decreased significantly there.

Yet tuberculosis is still one of the most common infectious diseases worldwide, along with AIDS / HIV and malaria. One third of humankind – about two billion people affected – are infected with the virus, which accounts for 5-10% of active tuberculosis, men more than twice as likely as women, according to estimates by the World Health Organization (WHO). The vast majority of diseases affect the poor countries.

Most cases worldwide in 2013 were recorded in Asia and Africa (56% and 29%, respectively), while far fewer were registered in the Middle East, Europe and the Americas (8%, 4% and 3%). , In absolute terms, the countries with the most new TB cases are:

  • India 2.0 – 2.3 million
  • China 0.9 – 1.1 million
  • South Africa 0.41 – 0.52 million
  • Indonesia 0.41 – 0.52 million and
  • Pakistan 0.37 – 0.65 million

There were an estimated 0.55 million new cases among children under the age of 15, with an estimated 80,000 deaths among HIV-negative children. The number of new TB sufferers has fallen by about 1.5% per year over the past decade. Fortunately, the mortality due to tuberculosis has fallen by 45% since 1990. Yet, in 2013, 1.5 million people (nearly 4,000 / day) died from tuberculosis, of which 360,000 were HIV positive. Mortality is 15 deaths per 100,000 inhabitants worldwide.

Another problem is the increasing resistance of the pathogens to normally successful antibiotic therapy. For example, the proportion of pathogens that are resistant to at least one of the five standard medicines is more than 14% in 2013 and is comparatively higher than in the previous year, with an upward trend. A significant increase in WHO-reported MDR-TB cases (MDR = multi-drug resistant) has been reported since 2009. An estimated 480,000, corresponding to 3.5% of all new tuberculosis cases in 2013, were multi-drug resistant TB cases. The highest proportion of multidrug-resistances in previously pretreated TB cases is more than 20%. The majority (80%) of MDR-TB cases reported to WHO in 2013 came from WHO Europe, as well as India and South Africa.

Causes & Risk Factors

The tuberculosis is caused by bacteria of the so-called Mycobacterium tuberculosis caused complex. According to current knowledge these include the species Mycobacterium (M.) tuberculosis (most common), M. bovis, M. africanum, M. microti, M. canetti and M. bovis BCG (Bacillus Calmette Guérin) – only the last mentioned bacterial species not notifiable. Diseases caused by M. bovis , which was previously transmitted to humans by the milk of diseased cattle, have become rare in Germany. Due to the improved animal and food hygiene (pasteurization of the milk) comes the bovine tuberculosis in Germany no longer available (exception: Allgäu).

Contagious, ie suffering from open pulmonary tuberculosis patients give the coughing , talking, singing or sneezing finest infectious droplet nuclei in the environment, which can be inhaled by their fellow man. The likelihood of infection depends on the intensity and duration of the contact as well as on the amount of virus released, the virulence of the bacteria and the susceptibility of the contact person. To become ill with an intact immune system only about 5% of those infected with active Tuberculosis in need of treatment. In industrialized countries, patients with reduced immune defenses (for example due to HIV infection, tumor disease, immunosuppressive therapy, renal insufficiency, diabetes mellitus, etc.) are particularly at risk of developing tuberculosisTuberculosis is even more common in the so-called developing countries, because malnutrition and malnutrition as well as poor hygienic conditions, and above all the high HIV rates (eg in sub-Saharan Africa) favor a tuberculosis infection.

Disease

The penetration of tuberculosis bacteria via the respiratory tract causes a typical reaction in the lungs. It comes first to a nonspecific inflammation in the lungs. At the same time, the bacteria can also be transported via the lymphatics into the surrounding lymph nodes or via the bloodstream to other organs where further sources of inflammation can form.

Inflammatory and immune cells activated by the immune system form a barrier around the pathogens and try to encapsulate them against the rest of the surrounding tissue ( granuloma formation ). At the center of such a rampart, in addition to some killed tuberculosis bacteria, are resting but vital pathogens which could not be successfully controlled by the phagocytes ( macrophages ). If the body succeeds in curbing the infection successfully, there is a latent tuberculous infection (LTBI), but it can also develop immediately after the infection (primary tuberculosis) or a long time later, a disease requiring treatment (Postprimärtuberkulose) (see also ” What is tuberculosis?”).

A good defense situation can lead to the so-called tuberculoma – a larger tuberculous round focus consisting of a decaying center (due to the particular consistency of this tissue is called “caseation”) with surrounding granulation tissue.

However, if no encapsulation takes place and the cheesy, dying tissue (tissue necrosis) in the center of the tuberculous inflammatory process wins connection to a bronchial branch (bronchus) , the germ-rich material can be coughed off and cavities form, so-called caverns . In this case, there is open tuberculosis . The affected patients are considered to be highly infectious as they usually cough up many bacteria.

Latent tuberculous infection & primary tuberculosis

The first contact with M. tuberculosis leads   to a positive tuberculin   skin test after an average of 6-8 weeks by  sensitizing specific T- lymphocytes . Without simultaneous radiographic evidence of organ findings, this condition is referred to as latent tuberculous infection (LTBI). However, if a small inflammatory focus with a localized lymph node reaction (primary complex) can be detected radiologically in the lungs, a primary tuberculosis is present. Rarely is the primary complex found outside the lungs (eg tonsils, gastrointestinal tract). Often there are no symptoms, but sometimes there is a slight increase in body temperature, coughing, Night sweats, loss of appetite and fatigue. In rare cases, red-bluish nodules, very painful on pressure, appear on the extensor surfaces of the lower legs. This so-called erythema nodosum arises due to an excessive defense reaction of the immune system to the infection.

In the further course, primary tuberculosis can lead to various complications. If the inflammatory foci (primary cavern) melt into the blood and lymph vessels, the bacteria can spread to other regions and form further foci, which can later be the starting point for a reactivation. If the cavern is connected to the bronchial system, the pathogens enter the environment with coughing and there is open tuberculosis, which is highly contagious. If lung foci form near blood vessels, they may injure them when melted. Then it comes to bloody cough.

Lymph nodes, which lie in the area of ​​the entry points for the main bronchi (in the so-called middle skin or mediastinum), may swell as a result of the infection so that possibly a bronchus is pressed. Less ventilation or a collapse of the lung areas supplied by this bronchus is the consequence.

Frequently ill patients also pleurisy initially sometimes begins as a “dry” pleurisy and severe pain when breathing and with the stethoscope perceptible Pleural during respiration associated. When or is the pleurisy damp from the start (exudative pleurisy) forms, If there is an outflow between the pleura and the lungs, then the pain subsides, causing shortness of breath – at first only under stress, at an advanced stage even at rest.

The tuberculous pneumonia itself may be associated with high fever as a further complication, since not infrequently even more bacterial species spread to the previously damaged lung. By scattering via the bloodstream into various other organs tuberculosis bacteria can cause a so-called miliary tuberculosis, which fortunately is rare. There are millet-sized tuberculous foci in various organs, such as the liver, spleen, kidney, adrenals, bones, meninges and in the choroid of the eyes. In the lungs, the small foci in the X-ray image represent a “snowstorm”.

Post-primary tuberculosis

This is usually the reactivation of hitherto stationary pathogens (granulomas) with still living tuberculosis bacteria, which originate from the primary infection and encapsulated in the body for a long time “slumbered.” Rarely it is a renewed infection from the outside (“exogenous reinfection “). Most of the time, post-primary tuberculosis affects the lungs, but it can also affect other (extrapulmonary) organs. Classic places are peripheral lymph nodes, the pleura, kidneys and urinary tract, bones and joints, more rarely other organs (digestive tract, skin, meninges, central nervous system). The extrapulmonary infestation can occur in isolation, but here too a spread of the pathogens or miliary tuberculosis is possible.

If it comes in the lungs by melting the inflammatory herd to the formation of cavities (caverns) with connection to a draining bronchus, so pathogen-containing material can enter the environment – there is an open, infectious tuberculosis. In rare cases, a cavern wall carcinoma may later develop from the cavern walls. If blood vessels are injured during the melting process, coughing up to massive pulmonary bleeding can occur. Extensive lung involvement and scarred changes after healing can lead to shortness of breath (respiratory insufficiency) and to a right heart strain (cor pulmonale).

However, if tuberculosis is recognized in good time and treated well, it generally heals without consequences. A good defense situation can lead to the tuberculoma. As a rule, the affected patient has no complaints, but tuberculomas are difficult for the doctor to diagnose.

effects

A special feature of tuberculosis is the slow growth of the pathogens. The tuberculosis bacteria divide only about once a day, while, for example, intestinal bacteria divide every 10 minutes. As a result, the disease usually progresses slowly and develops slowly over many weeks. To safely kill all bacteria, therefore, the drug treatment must be sufficiently long and with a combination of different drugs.

The impact depends very much on which regions and institutions are affected. Without treatment, tuberculosis is thought to heal without consequences in one-third of cases, to persist chronically in one third of patients, and one-third to die after months to years. Especially at a time when no highly effective drugs were available, cavities often remained as a result of extensive pulmonary tuberculosis. Cicatricial changes in the lungs can also cause sloughing in the bronchi (bronchiectasis). In these cavities viruses, bacteria or fungi can settle and trigger new infections. As a result of connective tissue transformation and shrinking processes and distortions, pulmonary emphysema can then developed or a chronic obstructive bronchitis arise and by the right heart strain a cor pulmonale .

In particularly severe cases, it can also lead to the complete destruction of lung tissue, for example a whole lung lobe. Before this becomes the starting point for recurrent or chronic infections, surgical removal of the affected lung part may be useful.

As a rule, the tuberculosis of other organs today also heals without major consequences. However, it is particularly critical when the tuberculosis bacteria affect the meninges ( meningitis tuberculosa ). This used to be more common in the past – especially in children – but luckily it is very rare in this country today. After meningitis, so-called defect healing with neurological and psychiatric disorders can be left behind.

Precautions

Information for relatives

If a patient is suspected to have tuberculosis or has been diagnosed with infectious tuberculosis requiring treatment, it is important to protect his next of kin from infection. To find out what precautions should be taken and what should be considered regarding any transfer that may have already occurred, please contact your pulmonary specialist directly.

Special infection risks

Tuberculosis is typically transmitted through tiny droplets (aerosols) that are not visible to the naked eye and contain tuberculosis bacteria. In contact with infectious tuberculous patients, therefore, the patient and contact person should wear a nose mask. If the droplets stick to the wall or floor of a room after coughing , the risk of infection is over, as they usually will not be thrown back into the air. In dust tuberculosis bacilli can theoretically survive for a longer time, but also here the risk of infection is extremely low.

The bovine tuberculosis transmitted via infected milk (pathogen Mycobacterium bovis ) is virtually non- existent in Germany. Nevertheless, tuberculosis due to M. bovis may still occur as a reactivation of an earlier infection. In many poor countries, eg in parts of Africa or South America, however, it is still due to ingestion of infectious dairy products to tuberculosis infections. Special caution is therefore required there.

Usually, the contagion of fellow humans takes place at a time when it is not known (yet) that the transmitter is suffering from infectious tuberculosis. The prerequisites for infection usually include a certain amount of excitement, the sufficient duration and intensity of contact and a corresponding susceptibility of the contact person. Therefore, not every contact necessarily has to be a contagion.

Particularly infectious are patients in which tuberculosis bacteria can already be detected microscopically in the phlegm (expectoration). This is almost always the case with cavernous pulmonary tuberculosis, as the pathogens can be coughed off into the environment after being connected to a draining bronchial branch (bronchus) and then inhaled by persons in the immediate vicinity.

Particularly vulnerable to infection are contact persons who have an immunodeficiency, for example, by the HIV virus (AIDS) or as a result of chemotherapy against an existing tumor disease. Underweight and malnourished people also have an increased risk of infection since under- and malnutrition also weaken the immune system. For this reason, in the treatment of these tuberculosis patients attention is paid to a high calorie (high calorie) diet.

Obligation to register & environmental investigation

Any tuberculosis requiring treatment must be reported as soon as possible to the responsible health authority in accordance with the Infection Protection Act. This then determines the closer contact persons (such as family members, friends, acquaintances, work colleagues, etc.) and determines in which period and in which cases an infection could have taken place (so-called environmental investigation). The environmental examination is carried out with the help of a tuberculin skin test and / or a lung x-ray . First, the tuberculin skin test created, with a positive result then an X-ray is followed. As a rule, the tuberculin skin test can only be expected to have a positive reaction 6-8 weeks after infection. Even in the case of the development of tuberculosis in need of treatment, abnormalities only appear on the radiograph after some time. If there are no indications of an active disease at the time of the examination, follow-up examinations will be carried out at certain intervals.

Chemoprophylactic treatment

In the case of a fresh contact infection can be prevented in infants and people with weakened immune systems (especially HIV patients) by chemoprophylactic treatment with isoniazid (see also ” Therapy “). If an infection has already occurred (positive tuberculin skin test), the exclusion of an active disease should consider the need for chemoprevention. This is usually done with isoniazid over nine months. Thus, the progression of infection into an active disease can be prevented with high probability.

behavioral measures

The most effective measures to prevent infection are fast and reliable diagnostics, efficient treatment, and the immediate isolation of potentially infectious patients. This also requires a responsible health behavior of all of us. For example, a cough that lasts longer than three weeks should be medically clarified. Many diagnoses of tuberculosis are delayed by the fact that the patients – often despite pronounced complaints! – Do not seek medical treatment until very late, although in the meantime they may endanger their environment. It is of course crucial that the treating physicians then (differential diagnosis) also think of tuberculosis.

The most important hygiene measures include sufficient room ventilation, patient behavior (cough hygiene, mouth protection) as well as personal protective measures by the supervising medical staff. Effective tuberculosis control also requires the proper training and education of all stakeholders, as well as the cooperation of public health services, laboratories, clinical and established areas. Reliable reporting allows a response to new epidemiological developments (increase in resistance, vulnerable populations). In addition, active case-finding measures such as the environmental survey mentioned above, the follow-up of persons with latent tuberculosis infection or previous tuberculosis and the study of risk groups,

So far no vaccine protection

An active vaccination with M. bovis BCG (BCG vaccination; Bacillus Calmette Guérin), a live attenuated vaccine, does not provide reliable protection. It only helps prevent severe tuberculosis in children (meningitis, miliary tuberculosis) and is therefore still prevalent in countries with a high incidence of tuberculosis. In Germany, it is generally no longer recommended since 1998 by the Standing Vaccination Commission at the RKI (STIKO) due to the decline in the number of cases and the resulting unfavorable benefit-risk ratio. Another problem is that positive tuberculin skin test results are difficult to interpret in BCG-vaccinated children. Initial clinical trials with newer, more potent vaccines are promising, but routine use is expected in a few years.

investigations

The most common site of tuberculosis is the lungspulmonary tuberculosis , in Germany 80% of patients). The crucial method of diagnosis here is an X-ray of the lungs . In unclear cases, a computed tomogram (CT) can provide additional information. There are also two other diagnostic options:

Bacteriological examination

Since there are also other diseases that may be very similar to a tuberculosis focus in the X-ray, it is important to try to detect the causative bacteria. This can be done either by the bacteriological examination of the sputum ( expectoration ) of the patient, or – if sputum can not be obtained spontaneously – by means of the examination of the material obtained by a lung reflection (bronchoscopy) . For this, the affected bronchial branch (bronchus), which leads to the suspicious hearth in the lungs, endoscopically probed with the bronchoscope and flushed targeted. Sputum or bronchoscopically extracted rinsing liquid are examined microscopically with special staining methods. It is also always trying to breed pathogens on special nutrient media (creating a bacterial culture). Molecular biological methods are also used in part. For a positive detection in the microscopic examination, however, must be contained in the examined material corresponding minimum amounts of tuberculosis bacteria. Patients in whom this microscopic direct detection is possible directly in the sputum are particularly contagious. Can the tuberculosis bacterium be detected by cultivating a culture of sputum cells, is to be expected from a much lower contagiousness, because then much fewer pathogens are included in the sputum. However, depending on the procedure, the growth of the culture takes 2 to 8 weeks.

tuberculin skin test

The fact that the body has dealt immunologically with the tuberculosis bacterium can be demonstrated approximately 6-8 weeks after infection by the tuberculin skin test. It is usually applied to the inside of the forearm by injecting a very specific amount of tuberculin directly into the skin with a thin cannula. This creates a small whitish  papule , which disappears after a short time. If the patient has formed defense cells (T lymphocytes ) against tuberculosis bacteria (see also ” What is tuberculosis? “), A palpable nodule develops after 2 to 7 days at the skin site concerned. If this exceeds a certain diameter, the test is positive.

From which diameter a test is considered positive or when the result entails further diagnostic and / or therapeutic consequences depends on the individual circumstances of the person tested (risk factors, reason of tuberculin testing, etc.) and the respective assessment by the Doctor. Due to a so-called cross-reaction with the BCG vaccine strain, BCG vaccinees (whose vaccination is no more than 10-15 years old) can have a positive reaction even though no infection has taken place. There are other reasons for false positives but also false negative ones. These must be taken into account when evaluating the tuberculin skin test result. Because of these uncertainties, the tuberculin skin test is likely to be more precise procedures will be replaced. Until then, however, it is still of great importance for the diagnosis of latent tuberculous infection. In the diagnosis of tuberculosis in need of treatment, however, it plays only a minor role, since there the above-mentioned methods (X-ray , bacteriology) are more meaningful and reliable.

Forecast & History

Tuberculosis was once one of the most terrible epidemics (“white plague”). Many people were literally carried away by them (” consumption Tuberculosis has declined drastically, especially through hygiene measures and improved nutrition, and a further significant decline has been achieved with tuberculosis-active drugs, although in industrialized nations such as Germany, the effects of globalization and the concomitant migratory movements are immigration noticeably from countries with high incidence of tuberculosis. Thus, tuberculosis is much higher than for the population born in Germany, for example, among ethnic and immigrants from the former Soviet Union or other regions of the world with high TB rates. the increase resistant Tuberculosis strains – and here too the states of the former Soviet Union are particularly affected – are reflected in the epidemiological development in Germany.

Uncomplicated tuberculosis can be cured with sufficiently long and appropriate medical treatment, the risk of relapse is then extremely low. The healing prospects are all the better the earlier the diagnosis is made and the therapy is started. Severe concomitant diseases, which often occur in older patients in particular, pose a special challenge for the attending physician. Therefore, care should be provided by physicians with sufficient experience in tuberculosis therapy , especially if drug intolerance and / or resistance necessitates deviations from the standardized treatment (see also ” TherapyIf the standard medicines are not used, the treatment will be extended, sometimes for up to two years, and patients with pathogens that have complicated resistance patterns – in the worst case ineffective against each of the five standard medicines – are very high difficult to treat and their therapy has significantly worse prospects of success.

therapy

Without drug treatment, about one-third of tuberculosis diseases would heal, one-third of patients would develop chronic tuberculosis and the last third die from it.

The gradual introduction of effective anti-tuberculosis drugs since the 1950s has made tuberculosis a treatable infectious disease. Because tuberculosis bacteria under treatment with only one drug relatively fast  resistance develop a multiple treatment with 3 or 4 anti tuberculosis is performed. The therapeutic standard is the combination of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB). Alternatively, instead of EMB streptomycin (SM) may also be given, which however is not available as a tablet but must be administered in the muscle (intramuscularly) or in the vein. It is usually treated for 2 months with 4 antituberculosis (INH, RMP, PZA, EMB) and then with a 2-combination (INH, RMP) for another 4 months. The total duration of treatment is normally 6 months. This allows uncomplicated tuberculosis to be completely cured.

The most important side effects of antituberculous treatment include impaired liver function and even jaundice (INH, RMP, PZA). Also blood picture changes occur occasionally. For this reason, the liver values ​​and the blood count are regularly monitored under therapy.

Isoniazid (INH) sometimes causes nerve inflammation, which can be prevented by the simultaneous administration of vitamin B6. Ethambutol (EMB) can impair eyesight (color vision), which is why ophthalmological checks are required at regular intervals. Streptomycin (SM) can affect the hearing, especially at higher doses, which is why auditory hearing aids are included.

It can be problematic if patients do not take the antituberculosis drugs regularly, discontinue therapy early or omit one of the prescribed medications. This often happens because patients feel significantly better after only a few weeks of treatment, and they are not aware of the absolute necessity of a complete therapy of adequate length. If there are doubts about the regular intake of the correct dose of medication or if the patient is for some reason unable to do so, a directly supervised therapy (DOT) is performed, ie the medication is taken under supervision.

In addition to the risk of relapse, inappropriate therapy may lead to the development of resistance to one or more antituberculosis drugs. The most dreaded form is the multi-resistance. Multidrug-resistant tuberculosis is said to be resistant to the two main antibiotic drugs of choice (rifampicin and isoniazid and possibly others). Other people who have been infected by the affected then infected with resistant pathogens. If drug intolerances and / or resistances exist, so-called reserve medications are used – eg other aminoglycosides, fluoroquinolones, prothionamide (PTH), para-aminosalicylic acid (PAS), cycloserine, rifabutin, linezolid. However, these are usually less effective than the standard medicines mentioned, often poorly tolerated, and usually much more expensive. In most cases, the duration of therapy must be significantly extended.