Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis, a highly contagious infectious disease that is characterized by a granulomatous inflammation of the lungs. The disease may spread to other organs and requires a long-term antibiotic treatment.
Even in cases of active pulmonary TB, symptoms are rather unspecific. The most common symptom is cough. Furthermore, patients suffer from general discomfort, fatigue, anorexia and weight loss . Fever may be observed, but is not always present.
Cough is initially only productive after waking up in the morning but becomes more productive as the disease progresses. The sputum is usually of yellowish or greenish color. If the disease does progress to cavitary pulmonary TB, an extensive necrosis with cavitation, the inflammation may damage vessels and hemoptysis may occur .
HIV patients may not show typical pulmonary TB symptoms due to their impaired immune system. Pulmonary TB tends to spread in these patients and extrapulmonary symptoms may then be present.
Patients usually present with unspecific general or respiratory symptoms that prompt radiographic imaging of the chest.
If lung alterations are detected, the suspected diagnosis may be further corroborated by a medical history of possible exposure to M. tuberculosis, by presence of chronic cough, weight loss and lymphadenopathy.
Sputum should be examined and cultured . While a positive tuberculin skin test or an interferon-γ release assay may be conducted after possible exposure and initiate TB diagnosis, these tests may also be carried out in order to confirm a hypothetically existent diagnosis . Unclear cases may benefit from molecular biological diagnostic techniques such as PCR .
After TB diagnosis, the patient should be tested for immunosuppressive conditions such as HIV. Also, hepatic and renal functions should be checked.
Common M. tuberculosis strains are sensitive towards several antibiotics. However, long-term treatments are necessary to eliminate these slowly metabolizing and growing pathogens. Compliance with the treatment regimen is of utmost importance and patients should generally take antibiotics for more than six weeks and in any case long after they are feeling well. Otherwise, relapses are likely and resistance development is possible. Patients have to be advised repeatedly on this risk and some physicians even prefer supervised drug intake. This directly observed therapy assures compliance and is presumably accompanied by shorter-term medication schemes and fewer relapses .
Since antibiotic resistance is a common feature of mycobacteria, treatment always includes the administration of at least two antibiotic drugs with different mechanism of action. A one-antibiotic regimen may not eliminate all pathogens and immunosuppressed patients may not be able to clear the remaining bacteria, which would lead to a relapse with mycobacteria resistant to that particular antibiotic.
In order to shorten the overall medication time, TB therapy is usually initialized with three or four different antibiotics. This approach drastically reduces bacterial load and increases chances of success.
The most commonly used antibiotics are isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin . These antibiotics are able to cure the vast majority of pulmonary TB cases (approximately 95%). Other drugs are only indicated if antibiotic resistance is detected or if there are other, absolute contraindications against the antibiotics of first choice.
Antibiotics against TB are usually taken all at once, once a day. There are formulations including more than one of these antibiotics, so the number of pills to be taken every day can be reduced. Dose schedules vary.
If pharmacological treatment does not suffice to treat pulmonary TB due to severe drug resistance, parts of the lung may be surgically removed. Surgery may also become necessary if other organs are involved and are severly compromised.
Provided that the patient is not infected with an extensively drug-resistant M. tuberculosis strain or a strain with multiple resistance, compliance with the antibiotic treatment regimen makes a complete cure very likely. Recurrence rates have been reported to range from 0 to 14%. In countries with a high prevalence of TB, recurrences might be confused with reinfections .
Prognosis worsens with age, immunosuppressive conditions, resistance to antibiotics and multiple organ infection. In a recent study, a limited innate immune response, an elevated respiratory rate at TB diagnosis and a decline in general health have been identified as poor prognostic markers .
Saliva and mucus of a person affected by pulmonary TB does contain mycobacteria and is contagious. Microorganisms can be expelled while speaking, sneezing or coughing. These bacteria may be inhaled by another person, who will subsequently become infected themselves .
Once mycobacteria reach the alveoli of the as of yet unaffected person, alveolar macrophages take them up. The bacteria, however, are able to evade the host's defense mechanisms and survive within the macrophages' phagosome. If the immune system is able to withhold the infection, a granuloma may develop and the affected person may not even show any symptoms of TB. They are then merely considered infected with M. tuberculosis or as suffering from latent TB. Clinical tests for TB may produce positive results, but the patient is not able to transmit the disease. However, as soon as the person develops clinical symptoms, they are considered to suffer from TB.
In severe cases, mycobacteria may reach the lymphatic system and the bloodstream of the host and subsequently establish infections of other organs such as liver and spleen.
Any intrinsic or environmental factor weakening the immune system is considered a risk factor for TB . Those factors comprise an HIV infection, diseases that weaken the immune system and alcoholism. Also, someone in prolonged, close contact to other people suffering from TB has a high risk of contracting TB, e.g. someone working in health care, someone living in or coming from a country with a high prevalence of the disease and someone living in poor or crowded conditions.
TB is one of the major health concerns worldwide. Case numbers amount to several millions. In 2013, for instance, approximately 9 million new infections took place, mainly in Africa, South East Asia and the Western Pacific region. About 1.5 million people died from TB, a large share of whom were HIV positive.
But TB is by far no health problem restricted to developing countries. With regards to the United States, presumably almost 10 million people are infected with M. tuberculosis and nearly 10,000 new cases or 3 cases per 100,000 people have been reported in 2013 . Of note, the case rate was significantly higher among people born abroad, particularly among those who immigrated from Asia .
Due to the immunosuppression associated with HIV infections, infections with M. tuberculosis display a particularly severe course in countries with a high HIV prevalence. Most infections with M. tuberculosis manifest as pulmonary TB.
TB is an infectious disease spread by droplet infection and M. tuberculosis has to be inhaled for bacteria to reach its host's alveoli . Here, the pathogens are engulfed by alveolar macrophages and taken up into phagosomes. However, the phagosome of an infected cell does not fuse with a lysosome and therefore does not progress to the elimination of the bacteria. M. tuberculosis inhibits phagosome-lysosome-fusion and does also evade further host defense mechanisms. It does survive inside the phagosome, multiplies and eventually kills its host cell. Mycobacteria are then released and prompt a reaction of the immune system that may continue to eliminate the pathogen, to restrain the infection (patient develops latent TB) or completely fail to do so (patient develops pulmonary TB).
If the infection can be restrained but not eliminated, macrophages and T-helper cells form a caseating granuloma with a necrotic center. Mycobacteria can be found inside this granuloma which is delimited on the outside by a lymphocytic wall. The affected person does not transmit the disease, but rather suffers from latent TB. In this condition, radiographic images of the lungs do not show any alterations but the tuberculin skin test shows positive results .
Latent TB may be re-activated and progress to active pulmonary TB. The probability for this to occur is particularly high during the first two years after infection and increases after receiving immunosuppressive treatment with corticosteroids or similar drugs as well as after acquiring immunosuppressive diseases such as HIV.
The BCG vaccine is an attenuated live vaccine extensively used to prevent TB. Vaccination with the BCG strain does not prevent pulmonary TB, but does significantly reduce TB meningitis and dissemination in children . TB vaccinations are no longer routinely administered, but may be indicated in specific cases of high risk due to unavoidable exposure, particularly to resistant strains.
Physicians should be aware of the local regulations regarding suspected or confirmed cases of TB.
The disease is spread by droplet transmission. Mycobacteria reach the alveoli, are taken up by alveolar macrophages and frequently survive inside their host cells. The immune system may be able to limit the infection and to prevent any further spreading, in which case the affected person does not develop any symptoms and does not expel contagious material either. Mycobacteria are then preserved in granulomas. On the other hand, if the infection cannot be withheld or becomes re-activated, a primary pulmonary TB develops: the patient usually presents unspecific respiratory and general symptoms, whereby cough is the leading one. Here, saliva and sputum contain mycobacteria and are highly contagious. Most cases of primary pulmonary TB result from re-activated latent forms of the disease . Reactivation may occur years after infection.
Although TB may spread to other organs, the vast majority of cases is limited to the lungs. A generalized immunosuppression may strongly increase the risk for re-activation and dissemination.
Besides the clinical examination, a chest X-ray, sputum culture, tuberculin skin test and interferon-γ release assay are valuable diagnostic measures .
If left untreated, about 50% of all patients suffering from pulmonary TB die. On the contrary, compliance with a long-term treatment regimen including several antibiotics is associated with a good prognosis.
Pulmonary TB is a bacterial infectious disease caused by M. tuberculosis. A person suffering from pulmonary TB harbors inflammatory spots in his or her lung and may expel bacteria when sneezing or coughing or even when speaking. If another person inhales these contagious droplets, they may contract TB.
Depending on the current state of the immune system and other factors, the body's immune defence may be able to eliminate or withhold the infection. If the infection is merely withheld, bacteria stay alive but inactive inside the patient's lung. In this condition, the person cannot transmit the disease. However, it is possible that the infection will be reactivated and in this case, the patient will expel contagious material. They may then infect other people.
Pulmonary TB is typically not accompanied by characteristic symptoms. Affected people may suffer from overall discomfort, loss of appetite, loss of body weight and cough. Fever may be present, but not necessarily. Some more severe cases are associated with difficulties to breathe, coughing up blood and chest pain.
A clinical examination will be carried out and may reveal swollen and tender lymph nodes as well as unusual breath sounds.
Because pulmonary TB symptoms are not easily distinguished from those caused by other diseases, further diagnostic measures have to be undertaken in order to confirm the condition.
Those diagnostic measures may include imaging of the chest by X-rays or other techniques, a bronchoscopy (looking inside the bronchial tubes), a tuberculin skin test and an examination of the patient's sputum, among others.
Pulmonary TB is a potentially curable disease. Therapy success depends largely upon the patient's compliance with long-term antibiotic therapy. Several antibiotics have to be administered at the same time because the pathogenic M. tuberculosis frequently shows resistance towards some antibiotics. Antibiotics have to be taken until long after symptoms have disappeared. Pulmonary TB is generally treated with isoniazid, rifampin, pyrazinamide, ethambutol and streptomycin. Provided that the treatment regimen is followed precisely, about 95% of all pulmonary TB cases are cured.
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