Release date: 2007-08-23
New progress in tuberculosis research at the American Thoracic Society Annual Meeting 2007 (ATS 2007), the report on tuberculosis research not only highlights new developments in tuberculosis research, but also reflects future research directions, with particular emphasis on strategies for tuberculosis control should be controlled Tuberculosis is the fundamental purpose, and it is proposed to carry out multi-level and multi-field collaborative research from the laboratory to the hospital bed.
China is a high-incidence area for tuberculosis and drug-resistant tubercle bacilli infection. It has many TB patients and abundant resources of Mycobacterium tuberculosis (MTB) strains. It should make full use of our advantages to carry out tuberculosis research and provide an important step for world tuberculosis research. First-hand information. Tuberculosis trends and control targets Currently, the global tuberculosis incidence continues to increase at an annual rate of 1%. The prevalence of tuberculosis is regional, with Africa being the region with the highest prevalence. In 2004, 80% of the 9 million new cases of tuberculosis in the world were distributed in 22 countries, and 1/2 of the new cases were distributed in six Asian countries including China. Patients with MDR-TB infection are distributed in 109 countries, with 450,000 new cases.
China is one of the countries with high incidence of tuberculosis, and the number of tuberculosis patients ranks second in the world, second only to India. In China, about 45% of adults (550 million cases) have been infected with MTB, and about 5 million tuberculosis patients, 28% of whom are infected with drug-resistant bacteria. There are about 1.45 million new tuberculosis patients each year, including 650,000 highly contagious patients, and about 130,000 people die of tuberculosis each year. According to the World Health Organization (WHO) survey, a quarter of the world's new annual MDR-TB infections are distributed in China. Although tuberculosis is a curable disease, there are still 2 million people worldwide who die of tuberculosis every year, especially for people with human immunodeficiency virus (HIV) infection. Tuberculosis is the leading cause of death.
In view of the grim situation of controlling tuberculosis, in 2006 the WHO proposed the “2006-2015 Global Stop TB Programâ€, which includes curbing the increasing trend of prevalence, developing new anti-tuberculosis drugs and vaccines, treating 50 million tubercle bacilli infected patients and 80 Patients with M. tuberculosis infection. Tuberculosis diagnosis and outcomes Many studies have shown that host individual genetic factors affect the outcome of MTB exposed, and 10% of MTB infected patients develop active tuberculosis. The single nucleotide polymorphism (SNP) of the interleukin (IL)-10 gene promoter, the promoter region of the gene encoding interferon (IFN) γ, the INF gene SNP, and the natural defense-associated macrophage protein (NRAMP1) gene Morphology, Toll-like receptor polymorphism, SLC11A1 gene polymorphism and some cytokines (such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, transforming growth factor- The polymorphisms of α, etc. coding genes are associated with the development of active tuberculosis in patients with MTB infection, which is also a hot spot for tuberculosis susceptibility research. Diagnosing MTB infection is a key link in controlling tuberculosis. Compared with the diagnostic methods of active tuberculosis, there is no satisfactory diagnostic tool for MTB recessive infection. The tuberculin skin test (TST) is currently a common method for diagnosing latent infection of MTB, but its specificity is poor. The IFN-γ assay can also be used to diagnose MTB infection. The principle is that MTB antigen-sensitized T cells produce IFN-γ when they are exposed to MTB antigen again. MTB-specific antigens that are not cross-linked with mycobacteria such as BCG are usually selected. To diagnose patients with latent infection of MTB. Research on the specificity and sensitivity of this method is another hot spot in the field of tuberculosis research, but its clinical use value is controversial.
New drug research for tuberculosis treatment Increasing the bactericidal activity of anti-tuberculosis drugs, simplifying the treatment plan, and shortening the course of treatment are one of the main research directions of tuberculosis treatment. Currently, 6 types and 8 kinds of new anti-tuberculosis drugs have entered or passed the phase I clinical trial. Moxifloxacin (mox in vitro bactericidal activity, minimum inhibitory concentration (MIC90) value of 0.125 μg / ml. MXF has long half-life, strong early bactericidal activity, long-term patient tolerance and can be combined with other anti-tuberculosis drugs, etc. Features, and thus the first line of anti-tuberculosis drugs that shorten the course of treatment.
Nuermberger et al reported that the bactericidal activity of MXF in the mouse tuberculosis model was comparable to that of isoniazid (INH). The bactericidal activity of MXF combined with RFP and pyrazinamide (PZA) was stronger than the standard combination of INH, RFP and PZA, and treatment 4 A stable cure is achieved after a month (ie no tuberculosis recurrence), and a combination of INH, RFP, and PZA requires a six-month course of treatment to achieve recurrence-free efficacy. Rosenthal's latest study, reported at ATS 2007, showed that MXF combined with long-acting rifapentine and PZA for 3 months resulted in a stable response, ie, the rate of tuberculosis recurrence was almost zero. The results suggest that MXF may replace INH and shorten the course of treatment to three months or less. The results also showed that the early bactericidal activity of MXF (400 mg once daily) was similar to that of INH during the first 2 days of treatment, while on days 3 to 7, the bactericidal activity of MXF was stronger than that of INH. The replacement of EMB with MXF, combined with INH, RFP and PZA treatment in February, at the 4th week, the patient's sputum conversion rate was greater than the combination of INH, RFP, EMB and PZA, and the patient was well tolerated. Based on the above laboratory and clinical findings, two phase II clinical studies evaluating the efficacy of MXF in combination with RFP and PZA are ongoing. Fluoroquinolone and drug-resistant tuberculosis fluoroquinolones are a broad-spectrum antibiotic widely used in various infectious diseases. While evaluating the efficacy of MXF against MTB, the problem to be solved is to avoid MTB resistance and delay the diagnosis of tuberculosis due to the use of fluoroquinolones.
Basic research has found that MTB resistance to fluoroquinolone can occur spontaneously or due to improper use of drugs. The gene gyrA mutation results in a laboratory rate of spontaneous resistance of 2 x 10-6 to 1 x 10-8. MTB has cross-resistance to fluoroquinolones, and there is no cross-resistance between fluoroquinolone and other anti-tuberculosis drugs. The fluoroquinolone monotherapy for tuberculosis for 2 weeks can quickly select resistant MTB strains. The incidence of MTB resistance to MXF has significant regional differences. Dexter et al. reported that the resistance rate of MTB to fluoroquinolone was higher than that predicted during 2000-2004 (see Table 1). Devasia et al reported that 136 patients with tuberculosis who had been treated with fluoroquinolone for a short course of treatment prior to tuberculosis showed that patients were diagnosed with tuberculosis after receiving fluoroquinolone for an average of 80 days (27-250 days). Thirty-nine patients (4%) were diagnosed before dying. These research data suggest that doctors in the first line of clinical practice should pay attention to the differential diagnosis of tuberculosis in the treatment of various infectious diseases, and use fluoroquinolone antibiotics with caution. ——Midi Medical Network
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