World Tuberculosis Day | Li Liang: Work together to prevent and treat tuberculosis

Li Liang

March 24 this year is the 28th World Tuberculosis Day. This journal specially invited Professor Li Liang, former chairman of the Tuberculosis Branch of the Chinese Medical Association and vice president of Beijing Chest Hospital affiliated to Capital Medical University, to share the current status of tuberculosis prevention and control.

Could you please briefly introduce World Tuberculosis Day?

Li Liang: Tuberculosis is a very old disease, and its pathogen, Mycobacterium tuberculosis, has existed for almost as long as human history. However, for a long time, humans did not have a correct understanding of tuberculosis, did not understand its pathogens and pathogenesis, and naturally did not achieve good results in treatment. This situation did not change until March 1882, when Robert Koch, a German physician and Nobel Prize winner in Physiology or Medicine, discovered Mycobacterium tuberculosis for the first time in the world. To commemorate Koch's important discovery, in 1995 WHO designated March 24 of each year as "World Tuberculosis Day."

What is the current incidence of tuberculosis both internationally and domestically?

Li Liang: Tuberculosis is still the most important infectious disease in the world. There are about 10 million new cases every year in the world. The number of people suffering from the disease is huge and has not changed much over the years, which shows that the disease is still prevalent and the number of people suffering from the disease is increasing. There are about 800,000 new cases of tuberculosis in China every year, ranking third in the world. Beijing is a region with a low incidence of tuberculosis, but the number of new cases of tuberculosis in Beijing's registered population is still about 6,000 to 7,000 each year. This shows that tuberculosis is still a very serious infectious disease that needs to be actively addressed.

What are the characteristics of tuberculosis and what are the difficulties in its prevention and control?

Li Liang: In addition to hair, teeth, nails and other parts, almost all human organs and tissues can be infected with tuberculosis bacteria, but the most common site of infection is the lungs, that is, pulmonary tuberculosis, accounting for about 85% of tuberculosis infection. Since the lungs are connected to the outside world through the respiratory tract, patients with pulmonary tuberculosis can easily discharge tuberculosis bacteria into the air through coughing, sneezing, etc., so pulmonary tuberculosis is the most contagious, and extrapulmonary tuberculosis such as bone tuberculosis, intestinal tuberculosis, and skin tuberculosis are very low in contagiousness. Since pulmonary tuberculosis can be transmitted through the respiratory tract, it increases the difficulty of tuberculosis prevention and control. Whether the human body develops disease after inhaling tuberculosis bacteria depends mainly on the virulence of tuberculosis bacteria and the body's resistance. If the virulence of tuberculosis bacteria is very strong, and the body's resistance happens to be low, the tuberculosis bacteria will easily multiply in the human body, and the infected person will be very likely to develop the disease and become an active tuberculosis patient. On the contrary, if the human body's resistance is particularly strong and the virulence of tuberculosis bacteria is relatively weak, then the human body can directly kill the tuberculosis bacteria and will not develop the disease. When the body's resistance and the virulence of tuberculosis bacteria are similar, tuberculosis bacteria can show their "cunning" side and enter a dormant state. Once the body's immunity decreases, the dormant tuberculosis bacteria will become active again, multiply in the human body, and cause tuberculosis. The dormant state of tuberculosis bacteria can exist for months, years, or even decades, giving tuberculosis an unclear incubation period, which poses a great challenge to the prevention and control of tuberculosis and makes it impossible for us to prevent its onset according to the prevention and control measures for acute infectious diseases.

The most common method for diagnosing pulmonary tuberculosis is to use sputum smears to look for tuberculosis bacilli. If tuberculosis bacilli are found, the diagnosis can be confirmed. However, if the amount of bacteria in sputum is low, it is difficult to detect, resulting in a positive rate of only about 30%. Although the sensitivity of sputum smears to look for tuberculosis bacilli is not high, it is still the core method for diagnosing pulmonary tuberculosis because its technical requirements are not high, especially in grassroots areas. The second method for diagnosing pulmonary tuberculosis is sputum culture, which can confirm the diagnosis if tuberculosis bacilli are cultured. The sensitivity of sputum culture can be increased by about 10% to 40% compared with sputum smears, but it takes 2 to 3 weeks. The above two traditional diagnostic methods have limited sensitivity, and it is obviously not enough to rely on them for diagnosis. In recent years, some new tuberculosis diagnostic methods have emerged, the most common of which is molecular biology method, which shortens the detection time to a few hours and is more sensitive, accurate and convenient. However, due to its high price and lack of medical insurance coverage, it is currently only used in large hospitals in large cities and has a low penetration rate at the grassroots level. Another important diagnostic method for tuberculosis is imaging, such as CT examination. Imaging diagnosis requires the experience of doctors and can only be used as an auxiliary method, not for diagnosis. At present, some new and promising methods for TB diagnosis have been developed, such as blood tests for TB antigens or antibodies, but the most specific antigens and antibodies for TB are still lacking. In short, the limitations in diagnosis also seriously affect the prevention and control of TB.

Could you please tell us about the development of tuberculosis treatment?

Li Liang: There are drug therapy, surgical treatment, immunotherapy, nutritional therapy, etc. for the treatment of tuberculosis. The core treatment of tuberculosis is drug therapy, also known as chemotherapy. In 1944, the first tuberculosis treatment drug, streptomycin, was developed. This was a revolutionary achievement. Before that, there were almost no drugs for tuberculosis. The treatment mainly involved recuperation in a good environment, sunbathing, and nutritional supplements. Of course, these methods also improved many patients by enhancing their resistance, but only with the emergence of streptomycin did tuberculosis treatment really enter the active stage. Since then, especially in the 20 years from 1944 to 1963, it has entered the golden age of tuberculosis drug development. Most of the tuberculosis drugs we use now, such as isoniazid, rifampicin, ethambutol, and pyrazinamide, were discovered during this period. This combination of four drugs has the best efficacy. For common tuberculosis, the cure rate can reach more than 90%, and the current course of treatment has gradually shortened from the initial 24 months to 6 months. However, since 1963, drug treatment for tuberculosis has faced huge challenges. First, no new drugs have been developed in 50 years, and second, traditional anti-tuberculosis drugs have developed resistance. People need to continue to develop new drugs, shorten the course of treatment, and reduce drug resistance. After a long period of fruitless years, some new anti-tuberculosis drugs have finally appeared since 2010, such as bedaquiline and delamanid. The emergence of new drugs has given us new weapons to fight tuberculosis.

What measures should be taken in the future to promote the prevention and treatment of tuberculosis?

Li Liang: The WTO has proposed to end the tuberculosis epidemic by 2035, but it is still difficult to achieve this goal. To effectively control or even eliminate an infectious disease, at least three conditions must be met: First, there must be good diagnostic tools that can achieve rapid diagnosis and high sensitivity. However, the traditional detection methods for tuberculosis take a long time and have low sensitivity, and the promotion of new and better detection methods at the grassroots level is still insufficient. Second, the treatment drugs are effective and have a short course of treatment. Although some new drugs have appeared, there is still a long way to go to achieve a good treatment goal. Third, a good vaccine must be developed. At present, the only vaccine for tuberculosis is BCG, which has been around for more than 100 years, but the effect of preventing tuberculosis is not satisfactory. It is helpful for preventing childhood tuberculosis, especially severe tuberculosis, but has limited effect on adults. The Chinese government attaches great importance to the prevention and control of tuberculosis. It formulates a tuberculosis prevention and control plan about every five years; it has established a tuberculosis prevention and control network at all levels from the national to the county level, as well as a relatively extensive tuberculosis hospital system. At present, there are about 300 tuberculosis specialized hospitals at the prefecture and city level and above in the country; a large amount of funds have been invested in tuberculosis prevention and control. However, due to the characteristics of tuberculosis transmission and the limitations of diagnosis, treatment and prevention technology, tuberculosis prevention and control needs to be further strengthened. For example, more active tuberculosis screening should be carried out among key tuberculosis populations, such as the elderly, diabetics, AIDS patients, and immunosuppressed people; better isolation of infection sources should be done; and better tuberculosis knowledge should be popularized to the public. In short, the whole society should work together to do a better job in tuberculosis prevention and control.

What tuberculosis prevention and control work has the Tuberculosis Branch of the Chinese Medical Association carried out?

Li Liang: The Tuberculosis Branch of the Chinese Medical Association was established in 1937. It is one of the earliest specialized branches of the Chinese Medical Association. At present, the Tuberculosis Branch is committed to promoting the prevention and treatment of tuberculosis in my country through various channels, mainly including: (1) formulating guidelines and standards. This is the branch's key work. In recent years, the branch has formulated nearly 10 guidelines and standards to promote the standardized development of tuberculosis prevention and treatment. (2) Academic exchanges. The branch holds the Chinese Medical Association Tuberculosis Academic Annual Conference every year, and the scale of the conference is getting bigger and bigger, from 200 to 3000 people in 2004 to 2,000 to 3,000 people at present. (3) Talent training, especially the training of young tuberculosis medical talents. (4) Supporting tuberculosis prevention and treatment work in grassroots areas in central and western China. (5) International cooperation. The branch has very good cooperation channels with tuberculosis prevention and treatment institutions in many countries and has held many training courses for the "Belt and Road" region and Africa. In addition, the branch has collected a large amount of historical information related to tuberculosis, carried out tuberculosis knowledge publicity and information tours, and planned to establish a tuberculosis history museum to allow more medical workers, especially young people, to understand the tuberculosis profession and be willing to work in this field.