Tuberculosis: Causes, Epidemiology, and Treatment

Causative Agent

Tuberculosis is an infectious disease of animals and humans. The most common causative agent of the disease is a bacterium — a mycobacterium — known as Mycobacterium tuberculosis. This bacterium was first discovered by Robert Koch in 1882. The physiology of this bacterium is aerobic, and it therefore requires very high oxygen levels. It is primarily a pathogen of the mammalian respiratory system and infects the lungs. The most common methods used to diagnose tuberculosis are acid-fast staining, the tuberculin skin test, and chest radiography.

M. tuberculosis requires oxygen in order to grow. Due to the presence of mycolic acid, M. tuberculosis has an unusual waxy coating on its surface that makes the cells impervious to Gram staining. It cannot retain any bacteriological stain as a result of the high lipid content in its cell wall; therefore, acid-fast staining (also known as Ziehl-Neelsen staining) is used instead. Despite this, M. tuberculosis is still considered to be a Gram-positive bacterium. While mycobacteria do not fit the Gram-positive category from a strictly empirical standpoint, they can be classified as acid-fast Gram-positive bacteria because they lack an outer membrane.

M. tuberculosis divides once every 15–20 hours, which is relatively slow compared to other bacteria that divide in minutes. It is a small bacillus, and as a result it is able to withstand weak disinfectants and can survive for weeks in a dry state. The mycolic acid found in its cell wall contributes to this resistance and is a key virulence factor. When the bacteria are in the lungs, they are taken up by alveolar macrophages, but those macrophages are unable to digest and eliminate the bacterium. The cell wall of the bacteria prevents fusion between the phagosome and the lysosome, which contains various antimycobacterial factors. M. tuberculosis blocks the bridging molecule, but this blockage does not prevent the fusion of vesicles filled with nutrients, allowing the bacteria to multiply unchecked within the macrophage. M. tuberculosis also carries the UreC gene, which prevents phagosome acidification, and it produces isotuberculosinol, which prevents phagosome maturation. The bacterium is also able to evade macrophage killing by neutralizing reactive nitrogen intermediaries.

History of Tuberculosis

Tuberculosis has been known to humanity since ancient times. The disease was historically referred to by many names, including consumption — due to the severe weight loss and the way the infection seemed to consume the patient — phthisis pulmonaris, and the white plague, owing to the extreme pallor observed in infected individuals. The organism that causes tuberculosis has existed for over 15,000–20,000 years. Evidence of it has been found in relics from ancient India, Egypt, and China. Spinal tuberculosis, known as Pott's disease, has been detected by archaeologists in Egyptian mummies. Evidence of tuberculosis of the lymph nodes of the neck — referred to as scrofula — is found dating from the Middle Ages. This was called the "king's evil," and there was a belief that the kings of England and France could cure scrofula simply by touching infected individuals. Tuberculosis reached its peak in the 18th century in Europe, with a prevalence as high as 900 deaths per 100,000 people. Poor ventilation, crowded housing, malnutrition, primitive sanitation, and other risk factors drove this rise — the period during which the term "white plague" emerged.

There have been many inaccurate misconceptions about the cause and transmission of tuberculosis throughout history. People frequently believed that TB was transmitted by direct contact with an infected person's skin or through the sharing of eating utensils. A significant social stigma has also been associated with TB, which has had a marked impact on the willingness of individuals to be tested and to seek treatment. In more recent times, however, public education campaigns have equipped people with accurate information about TB. As a result, misconceptions have diminished, and more people are coming forward to be tested and to receive appropriate treatment. The knowledge and attitudes toward tuberculosis have changed substantially over time (Mandal, 2014).

Epidemiology

Roughly one third of the world's population has been infected by M. tuberculosis. New infections occur at a rate of approximately one per second. However, not all M. tuberculosis infections cause active tuberculosis disease, and many infections remain asymptomatic. An estimated 13.7 million chronic cases were recorded in 2007; in 2008, 8.8 million new cases were reported and 1.45 million deaths were recorded, most occurring in developing countries. Tuberculosis is the second most common infectious cause of death, behind HIV. TB distribution is not uniform across the world: approximately 80% of the population in African and Asian countries test positive for TB, while only 5–10% of the population in the United States tests positive. In 2012, Swaziland had the highest estimated incidence rate, with 1,200 cases per 100,000 people.

India had the largest total incidence, with an estimated 2 million cases. In developed countries, tuberculosis is less common and tends to be an urban disease. TB incidence also varies with age: in Africa, it primarily affects young adults and adolescents, while in countries with low TB incidence it is more commonly a disease of older people. Tuberculosis is seasonal, with peak incidence generally in spring and summer. When a person with tuberculosis coughs, sneezes, or spits, they release infectious aerosol droplets, each of which is capable of transmitting the disease because the infectious dose of TB is very small. Those with prolonged and frequent close contact with TB patients are at the highest risk of becoming infected, with an estimated infection rate of 22% (Mathema, Kurepina, Bifani, & Kreiswirth, 2006).