Mycobacterium tuberculosis is a thin, slightly curved bacillus. A member of the Mycobacterium tuberculosis complex, it is an obligate aerobic bacterium that is the etiologic agent of the majority of tuberculosis cases.
The worldwide incidence of tuberculosis was 8.7 million in 2011 (13% of these were coinfected with HIV). The mortality in 2011 was 1.4 million, of which 430,000 cases were HIV-positive.
Despite these persistently high figures, The WHO Millennium Development Goal target to halt and reverse the TB epidemic by 2015 has already been achieved.
The worldwide incidence has been falling for several years now, at a rate of 2.2% between 2010 and 2011. The mortality rate has decreased 41% since 1990 and the world is on track to achieve the global target of a 50% reduction by 2015, however, the African and European regions are not on track to achieve that goal.
The wall of the bacterium contains high levels of lipids, and as such does not retain standard bacteriological stains such as Gram stain. Despite this characteristic, M. tuberculosis is classified as a Gram-positive bacterium due to the lack of an outer cell membrane. The division rate of M. tuberculosis is very slow at up to 20 hours. The lipid-rich wall accounts for its capacity to survive in a dry condition for many weeks, and for its virulence.
Ziehl-Neelsen or acid-fast stains are used. M. tuberculosis appears as small round bacilli stained red by the acid-fast stain. Caseating granulomas containing Langhans giant cells (not to be confused with Langerhans cells) is a hallmark.
M. tuberculosis is transmitted airborne, i.e. by droplet infection. M. tuberculosis is a facultative intracellular parasite. When inhaled, the organism is taken up by alveolar macrophages. Several mechanisms stop macrophages from killing the bacteria, and hence they can multiply unhindered within macrophages.
From the lungs, spread to other organs is haematogenous. Pulmonary tuberculosis is contagious, non-pulmonary tuberculosis is not.
At-risk groups for infection are:
- immunocompromised including HIV infection, diabetes, long-term immunosuppressants
- close contact with others with active TB
- malnourishment, alcoholism and intravenous drug use
- patient from endemic countries
- workers and residents in long-term residential facilities including jails, nursing homes, care homes.
The Mantoux tuberculin skin test involves the subdermal injection of tuberculin, a complex of purified M. tuberculosis proteins, into the skin of the forearm. The size of the developing skin reaction is measured in millimeters. A positive reaction indicates that a person has been infected with TB bacteria in the past. It cannot determine whether active infection is present.
Similarly, interferon-gamma release assays (IGRAs) such as QuantiFERON®-TB Gold are surrogate markers of M. tuberculosis infection and indicating an immune response to M. tuberculosis, but cannot distinguish between latent infection and active tuberculosis. These tests are not affected by prior Bacillus Calmette–Guérin (BCG) vaccination. Since 2010 the IGRAs are the preferred testing method as recommended by the CDC.
To determine whether the active disease is present, a chest radiograph and sputum for culture and acid-fast stain are needed to determine whether the person has active disease.
Treatment and prognosis
Treatment consists of combination antibiotic therapy for at least six months. The agents isoniazid, rifampin, ethambutol, and pyrazinamide are considered first-line antituberculosis agents.
Multidrug-resistant TB (MDR-TB) is defined as disease caused by M. tuberculosis resistant to at least isoniazid and rifampin. Treatment is a challenge and involves second-line therapies for up to two years.
Extensively drug-resistant TB (XDR-TB) progresses very rapidly and can be fatal within weeks. XDR-TB is defined as TB that has developed resistance to at least rifampin and isoniazid, plus any agent of the fluoroquinolone family, plus at least one of the aminoglycosides or polypeptides.
Isolation of cases, improve ventilation and vaccination with BCG in endemic countries (this vaccine has good efficiency in children only).
History and etymology
- 2400 BCE: evidence of spinal tuberculosis in an Egyptian mummy
- 460 BCE: Hippocrates termed the condition phthisis (Greek for consumption), a term used throughout the centuries
- 1720: Benjamin Marten writes "A theory of Consumption" and hypothesizes that tuberculosis may be caused by "small living creatures that are transmitted through the air to other patients"
- 1854: dissertation by Hermann Brehmer entitled “Tuberculosis is a Curable Disease”
- 1882: discovery of M. tuberculosis by Robert Koch wins the 1905 Nobel Prize
- 1921: Bacillus Calmette–Guérin (BCG) vaccine first used in human trials
- 1944: discovery of streptomycin by Selwan Waxman
- 1998: genome of M. tuberculosis sequenced