Tuberculosis: essential facts

The most common causative agent of tuberculosis (TB) in humans, Mycobacterium tuberculosis, is a member of the M. tuberculosis complex (MTBC) which includes six other closely related species: M. bovis, M. africanum, M. microti, M. pinnipedii, M. caprae and M. canettii. Two billion people are infected with Mycobacterium tuberculosis (latent TB) worldwide. Around 5-10% of these individuals will develop active TB disease. If an individual has both latent TB and human immunodeficiency virus (HIV) infection, his or her risk of developing active TB is 50-fold higher compared with those who are HIV negative. A total of 9.27 million new cases (1.37 million of them in HIV positive people) were reported in 2007. Two million deaths worldwide and 4.1 million infectious cases were estimated in 2007[1]. According to recent estimates, 9.4 million new active disease cases corresponding to an estimated incidence of 139 per 100,000 population occurred throughout the world in 2008 [2]. Only 5.7 million of 9.4 million cases of TB (new cases and relapse cases) were notified to national tuberculosis programs of various countries while the rest were based on assessments of effectiveness of surveillance systems. The highest number of TB cases occurred in Asia (55%) followed by Africa (30%). The highest incidence rate (351 per 100,000 populations) was recorded for the African region, mainly due to high prevalence of HIV infection. An estimated 1.4 million (15%) of incident TB patients were coinfected with HIV in 2008. Globally, the total prevalent TB cases in 2008 were 11.1 million corresponding to 164 cases per 100 000 population that resulted in 1.8 million deaths (including 0.5 million TB patients coinfected with HIV). Nearly 440 000 cases of multidrug-resistant TB (MDR-TB, defined as infection with M. tuberculosis strains resistant at least to the two most important first-line drugs, rifampicin and isoniazid) occurred in 2008. By 2009, extensively drug-resistant TB (XDR-TB; defined as MDR-TB strains additionally resistant to a fluoroquinolone and a second-line anti-TB injectable agent such as kanamycin, amikacin, or capreomycin) has been found in 58 countries. While MDR-TB is difficult and expensive to treat, XDR-TB is virtually an untreatable disease in most of the developing countries. Infection with M. tuberculosis begins with the phagocytosis of tubercle bacilli by antigen-presenting cells in human lung alveoli. This sets in motion a complex infection process by the pathogen and a potentially protective immune response by the host. M. tuberculosis has devoted a large part of its genome towards functions that allow it to successfully establish progressive or latent infection in majority of infected individuals. The failure of immune-mediated clearance is due to multiple strategies adopted by M. tuberculosis that blunt the microbicidal mechanisms of infected immune cells and formation of distinct granulomatous lesions that differ in their ability to suppress or support the persistence of viable M. tuberculosis (LTBI) [2]. TB is a major cause of morbidity and mortality in India and accounts for 1/5th of the world population. According to World Health Organization (WHO), each year an estimated 9.4 million new cases of TB are detected leading to nearly 2 million deaths, and almost one third of world population is infected by Mycobacterium tuberculosis. About 40% of all Indians are infected. MDR TB levels are less than 3% in new cases and 12% among retreatment cases as per the recent studies. In India drug resistant pattern vary widely across different parts of the country.

In the United States, tuberculosis is uncommon among young adults of European descent, who have only rarely been exposed to M. tuberculosis infection during recent decades. In contrast, the prevalence of M. tuberculosis infection is relatively high among elderly Caucasians, who remain at increased risk of developing active tuberculosis. Tuberculosis in the United States is also a disease of young adult members of the HIV-infected, immigrant, and disadvantaged/marginalized populations. Similarly, in Europe (see fig. 1-3), tuberculosis has reemerged as an important public health problem, mainly as a result of cases among immigrants from high-prevalence countries. Relatively recent data on trends indicate that in 2005 tuberculosis incidence was stable or falling in most regions; the result is a small decline globally from figures in previous years. This global reduction is due largely to an apparent peaking in sub-Saharan Africa, where incidence had risen steeply since the 1980s as a result of the HIV epidemic and the paucity of health services. In Eastern Europe, incidence increased during the 1990s because of deterioration in socioeconomic conditions and the health care infrastructure; however, after peaking in 2001, incidence has recently stabilized [3].

National TB control programmes play a vital role in curing TB patients and preventing deaths; the diagnosis and treatment of active TB have significantly reduced disease transmission and incidence in some countries. However, treatment programmes have not had a major, detectable effect on incidence on a large scale. The possible reasons are that: (i) patients are not diagnosed and treated soon enough to significantly reduce transmission; (ii) case detection, cure and TB incidence trends cannot be measured accurately; (iii) there has been insufficient time to see the effects of reduced transmission; and (iv) any effects on transmission are offset by a growing risk of developing TB following infection [4].


 

Figure 4. General principles for designing an empirical regimen
to treat MDR-TB [5].

 

Figure 5. Molecular mechanisms of drug resistance in Mycobacterium tuberculosis. Extracted from source [8].
Figure 6. Basic antituberculosis therapy. Redesigned from source [9].

Web resources:

http://www.who.int/gtb
http://www.stoptb.org/
http://www.stoptb.org/GDF/default.asp
http://www.childsurvival.com/vrc
http://www.kncvtbc.nl
http://www.moz.gov.ua
http://www.ifp.kiev.ua
http://health.unian.net/rus
http://www.fdu.org.ua
http://www.euro.who.int/prisons


References:

  1. Jarvis M. Tuberculosis: infection control in hospital and at home // Nursing Standard (Royal College Of Nursing (Great Britain): 1987). – 2010. – 25, № 2. – P. 41-47.
  2. Ahmad S. New approaches in the diagnosis and treatment of latent tuberculosis infection // Respiratory Research. – 2010. – 11, №. – P. 169-185.
  3. Fauci A., Braunwald E., Kasper D., Stephen L.: Harrison’s textbook of internal medicine. Edited by 15th. New York: McGraw-Hill, 2009, p. 2567.
  4. Dye C., Lönnroth K., Jaramillo E., Williams B.G., Raviglione M. Trends in tuberculosis incidence and their determinants in 134 countries // Bulletin Of The World Health Organization. – 2009. – 87, № 9. – P. 683-691.
  5. Chiang C.Y., Centis R., Migliori G.B. Drug-resistant tuberculosis: past, present, future // Respirology. – 2010. – 15, № 3. – P. 413-432.
  6. Zager E.M., McNerney R. Multidrug-resistant tuberculosis // BMC Infectious Diseases. – 2008. – 8, № 1. – P. 1-5.
  7. Devaux I.K. Clusters of Multidrug-Resistant Mycobacterium tuberculosis Cases, Europe // Emerging Infectious Diseases. – 2009. – 15, № 7. – P. 1052.
  8. Yew W.W., Leung C.C. Management of multidrug-resistant tuberculosis: Update 2007 // Respirology. – 2008. – 13, № 1. – P. 21-46.
  9. Ferguson L.A., Rhoads J. Multidrug-resistant and extensively drug-resistant tuberculosis: The new face of an old disease // J Am Acad Nurse Pract. – 2009. – 21, № 11. – P. 603-609.