New approaches in the diagnosis and treatment of tuberculosis

Tuberculosis is one of the most important problems in modern health care. About 1/3 of the world's population is infected with Mycobacterium tuberculosis. According to the WHO, in 2000, 8.3 million new cases of infection were detected and 1.8 million deaths from tuberculosis were recorded, which places this infection in second position after HIV infection among the leading causes of death from infectious diseases worldwide. Over 95% of infections and 98% of deaths occur in developing countries. For the period from 1997 to 2000. in USA, the incidence of this infection has increased by 9% per year.

All of the above determines the importance of timely and adequate diagnostic and therapeutic measures.

Despite the low sensitivity and specificity, tuberculin skin tests remain the standard for the diagnosis of latent tuberculosis infection (LTI). In recent years, new tests have been developed, notably in vitro diagnostics (see. A new test for laboratory diagnosis of tuberculosis), which have significantly higher sensitivity and specificity ( 89% and 98%, respectively).

The gold standard for diagnosing tuberculosis is the detection of M. tuberculosis in bacterioscopic or cultural studies. The main limitations of the bacterrioscopic method are its low sensitivity (50 to 70%) and its inability to determine the spectrum of sensitivity of the microorganism to antibiotics. The traditional culture technique on solid medium has a higher sensitivity, but it requires a long period of time (several weeks to 2 months). New enriched liquid culture techniques (BACTEC 460 method) and the Mycobacterial growth indicator tube (MGIT) system results in less time. Nucleic acid amplification techniques are currently considered to be the most promising. According to a certain number of studies, their sensitivity and specificity reach respectively 93% and 84%. The main drawback is the inability to perform antibiotic susceptibility testing. A urine and blood plasma study for the detection of mycobacterial antigens is not currently recommended for general use, as the reliability of the results of the methods has not been confirmed during the studies.

Treating ITL is an effective way to prevent infection and has the greatest effect in people with HIV and those in close contact with TB patients. A mandatory requirement before its implementation is the exclusion of an active tuberculosis process. The standard regimen for LTI therapy is the administration of isoniazid at a dose of 5 mg / kg / day up to 300 mg / day or during DOTS (Directly Observed Therapy Short Course, “therapy with short courses under supervision ») 2 times a week at 15 mg / kg / day up to 900 mg / day for 6-9 months. Poor compliance necessitated the development of shorter combined regimens, in frequency, a 2-month treatment with rifampicin and pyrazinamide. However, the identification of pronounced hepatotoxicity in this regimen has led to its limited use in cases where the probability of undergoing complete treatment with isoniazid is low. Another therapeutic alternative is the use of isoniazid in combination with rifampicin for 3 months.

The effectiveness of highly active antiretroviral therapy (HAART) in preventing tuberculosis in people infected with HIV has also been demonstrated.

Therapy is carried out in combined modes for long periods. In the treatment of non-resistant infections, isoniazod, rifampicin, pyrazinamide, ethambutol and streptomycin are used as first-line drugs. In recent years, a number of new drugs have been developed to treat this infection. Thus, the activity of new fluoroquinolones, in particular gatifloxacin and moxifloxacin, and linezolid against M. tuberculosis has been shown.

Tuberculosis is the main opportunistic infection in people with HIV, which greatly increases the risk of HIV progression and death in these patients. The introduction of HAART into clinical practice has reduced the risk of progression to HIV infection and mortality, however, TB treatment with antiretroviral drugs is associated with a high risk of drug interactions and the development of reactions toxic and paradoxical. The timing of treatment is questionable. In general, in patients co-infected with HIV and tuberculosis with severe immunosuppression, HAART should be started as soon as possible to prevent the progression of HIV infection. Patients already receiving HAART at the time of TB diagnosis are advised to additionally prescribe specific TB treatment. Patients who are not receiving HAART, with a CD4 count greater than 100 / μl and a stable immune status, are treated with anti-tuberculosis treatment and at the end of its initial phase (after 2 months), HAART is started. Patients not receiving HAART with a CD4 count below 100 / μl should start anti-tuberculosis treatment followed by HAART after 2 weeks.

Many antiretroviral drugs can interact with anti-tuberculosis drugs, especially rifampicin. It is considered safe to combine efavirenz (at an increased dose of 800 mg / day) and ritonavir / saquinavir with rifampicin. In the absence of efavirenz, rifabutin (150-300 mg / day) may be prescribed. Although in some countries HIV treatment of HIV-infected patients is done with a combination of isoniazid and ethambutol for 6 months to avoid drug interactions, this regimen has been shown to be less effective than rifampicin.

With the start of anti-TB treatment, patients may experience an increase in symptoms of the infection, the so-called paradoxical reaction. Most often, it develops in people infected with HIV (in 7 to 36% of cases), in particular with the simultaneous initiation of HAART and anti-tuberculosis treatment. The diagnosis should be made after a thorough examination and the exclusion of other possible causes of the deterioration of the patient's condition. A mild to moderate paradoxical reaction is treated symptomatically and, as a rule, goes away on its own. In severe cases, short doses of prednisone are recommended at the initial dose of 1 mg / kg / day.

TNF-α plays an important role in the pathogenesis of many chronic inflammatory diseases, which leads to the use of its inhibitors (monoclonal antibodies infliximab and adalimumab and soluble receptor of the TNF dimer, etanercept) in the treatment of these conditions. During treatment with TNF inhibitors, an increase in the incidence and severity of opportunistic infections, most often tuberculosis, was also noted, in approximately half of the patients, the infectious process was extrapulmonary. According to the United States Food and Drug Administration (FDA), tuberculosis develops in 54 of 100,000 patients treated with infliximab and 28 in 100,000 patients treated with etanercept. Activation of a latent infection was also noted. In the context of the above, it is recommended that tuberculosis screening be recommended before the appointment of TNF inhibitors, and prophylactic anti-tuberculosis therapy should be administered to people with latent infection.

Tuberculosis infection is considered to be multidrug-resistant with confirmed in vitro resistance to at least isoniazid and rifampicin. Multidrug-resistant tuberculosis is currently a global problem. The only diagnostic method is to test the sensitivity of M. tuberculosis to antibacterial drugs.

Therapy is carried out using alternative drugs, including fluoroquinolones.