The Tuberculosis

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Diagram showing infectious cycle of tuberculosis. First a droplet nuclei containing tubercle bacilli are inhaled, enter the lungs and travel to the alveoli. Next, the tubercle bacilli multiply in the alveoli. Next, the immune cells form a barrier shell around the tubercle bacilli, called a granuloma. Finally, the granuloma shell breaks down and the tubercle bacilli escape and rapidly multiply forming more tubercles.
In the infectious cycle of tuberculosis, the immune response of most infected individuals (approximately 90%) results in the formation of tubercles in which the infection is walled off. The remainder will suffer progressive primary tuberculosis. The sequestered bacteria may be reactivated to form secondary tuberculosis in immunocompromised patients at a later time. (credit: modification of work by Centers for Disease Control and Prevention)

OpenStax Microbiology

Tuberculosis (TB) is one of the deadliest infectious diseases in human history. Although tuberculosis infection rates in the United States are extremely low, the CDC estimates that about one-third of the world’s population is infected with Mycobacterium tuberculosis, the causal organism of TB, with 9.6 million new TB cases and 1.5 million deaths worldwide in 2014.

M. tuberculosis is an acid-fast, high G + C, gram-positive, nonspore-forming rod. Its cell wall is rich in waxy mycolic acids, which make the cells impervious to polar molecules. It also causes these organisms to grow slowly. M. tuberculosis causes a chronic granulomatous disease that can infect any area of the body, although it is typically associated with the lungs. M. tuberculosis is spread by inhalation of respiratory droplets or aerosols from an infected person. The infectious dose of M. tuberculosis is only 10 cells.10

After inhalation, the bacteria enter the alveoli. The cells are phagocytized by macrophages but can survive and multiply within these phagocytes because of the protection by the waxy mycolic acid in their cell walls. If not eliminated by macrophages, the infection can progress, causing an inflammatory response and an accumulation of neutrophils and macrophages in the area. Several weeks or months may pass before an immunological response is mounted by T cells and B cells. Eventually, the lesions in the alveoli become walled off, forming small round lesions called tubercles. Bacteria continue to be released into the center of the tubercles and the chronic immune response results in tissue damage and induction of apoptosis (programmed host-cell death) in a process called liquefaction. This creates a caseous center, or air pocket, where the aerobic M. tuberculosis can grow and multiply. Tubercles may eventually rupture and bacterial cells can invade pulmonary capillaries; from there, bacteria can spread through the bloodstream to other organs, a condition known as miliary tuberculosis. The rupture of tubercles also facilitates transmission of the bacteria to other individuals via droplet aerosols that exit the body in coughs. Because these droplets can be very small and stay aloft for a long time, special precautions are necessary when caring for patients with TB, such as the use of face masks and negative-pressure ventilation and filtering systems.

Eventually, most lesions heal to form calcified Ghon complexes. These structures are visible on chest radiographs and are a useful diagnostic feature. But even after the disease has apparently ended, viable bacteria remain sequestered in these locations. Release of these organisms at a later time can produce reactivation tuberculosis (or secondary TB). This is mainly observed in people with alcoholism, the elderly, or in otherwise immunocompromised individuals.

Because TB is a chronic disease, chemotherapeutic treatments often continue for months or years. Multidrug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of M. tuberculosis are a growing clinical concern. These strains can arise due to misuse or mismanagement of antibiotic therapies. Therefore, it is imperative that proper multidrug protocols are used to treat these infections. Common antibiotics included in these mixtures are isoniazid, rifampin, ethambutol, and pyrazinamide.

A TB vaccine is available that is based on the so-called bacillus Calmette-Guérin (BCG) strain of M. bovis commonly found in cattle. In the United States, the BCG vaccine is only given to health-care workers and members of the military who are at risk of exposure to active cases of TB. It is used more broadly worldwide. Many individuals born in other countries have been vaccinated with BCG strain. BCG is used in many countries with a high prevalence of TB, to prevent childhood tuberculous meningitis and miliary disease.

The Mantoux tuberculin skin test is regularly used in the United States to screen for potential TB exposure. However, prior vaccinations with the BCG vaccine can cause false-positive results. Chest radiographs to detect Ghon complex formation are required, therefore, to confirm exposure.

a) a needle injects a small bubble into a person’s skin. B) a ruler is used to measure a red area on a person’s skin.
(a) The Mantoux skin test for tuberculosis involves injecting the subject with tuberculin protein derivative. The injection should initially produce a raised wheal. (b) The test should be read in 48–72 hours. A positive result is indicated by redness, swelling, or hardness; the size of the responding region is measured to determine the final result. (credit a, b: modification of work by Centers for Disease Control and Prevention)

Source:

Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology

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