The Mycobacterium tuberculosis complex (MTBC) represents a group of closely related bacterial species responsible for causing tuberculosis (TB), a significant infectious disease affecting humans and animals globally. TB remains a major public health challenge, leading to millions of new cases and deaths each year. Understanding the composition of this bacterial complex, how it spreads, and the methods used for its diagnosis and treatment is important for controlling its impact.
Members of the Mycobacterium Tuberculosis Complex
The primary member and most common cause of human TB worldwide is Mycobacterium tuberculosis, responsible for the vast majority of human infections.
Mycobacterium bovis primarily causes tuberculosis in cattle and other animals. Historically, M. bovis was a significant cause of human TB, particularly where unpasteurized milk was consumed. Milk pasteurization and bovine TB eradication programs have greatly reduced human infections caused by M. bovis.
Mycobacterium africanum is another member, a substantial cause of human TB in parts of West Africa. Other members include M. microti, which infects small rodents, and M. canettii, a rarer species. M. canettii is thought to have an environmental origin, with no observed human-to-human transmission.
Transmission and Disease Progression
Tuberculosis primarily spreads through airborne transmission when an individual with active pulmonary TB coughs, sneezes, or speaks, releasing tiny droplets containing Mycobacterium tuberculosis bacteria into the air. These microscopic droplets can then be inhaled by others.
After exposure, there are two main outcomes. The immune system may contain the bacteria, preventing symptoms; this is latent TB infection (LTBI). Individuals with LTBI do not feel sick and cannot spread the bacteria, but the dormant bacteria remain. Without treatment, approximately 5% to 10% of people with LTBI will develop active TB disease, often within the first two years of infection.
Alternatively, the immune system may fail to contain the bacteria, allowing them to multiply and cause active TB disease. This can happen soon after initial infection or years later, especially if the immune system becomes weakened due to conditions like HIV infection. Active pulmonary TB commonly presents with symptoms such as a persistent cough lasting three weeks or longer, fever, night sweats, and unexplained weight loss. Coughing up blood or sputum can also be a sign.
Diagnosis of Tuberculosis
Diagnosis of Mycobacterium tuberculosis infection involves a combination of tests, depending on whether latent infection or active disease is suspected. For detecting TB infection, two primary methods are used. The tuberculin skin test (TST) involves injecting a small amount of purified protein derivative (PPD) under the skin; a reaction indicates an immune response to TB proteins, suggesting infection. Interferon-gamma release assays (IGRAs) are blood tests that measure the immune system’s response to specific TB antigens, offering higher specificity than TST and are not affected by prior BCG vaccination.
To confirm active TB disease, diagnostic tools include a chest X-ray, which can reveal lung abnormalities suggestive of pulmonary TB. Sputum smear microscopy involves examining a patient’s sputum sample under a microscope to visually identify TB bacteria. A positive smear indicates an active, infectious form of the disease.
Molecular tests, such as Nucleic Acid Amplification Tests (NAATs), provide rapid and accurate results. These tests can detect the DNA of Mycobacterium tuberculosis directly from sputum samples, often within hours. Some NAATs can also detect genetic mutations associated with rifampicin resistance, which helps guide early treatment decisions.
Treatment and Drug Resistance
Treating drug-susceptible tuberculosis involves multiple antibiotics taken in combination. The standard regimen for active TB disease usually includes four different medications, such as isoniazid, rifampicin, pyrazinamide, and ethambutol, taken daily. This multi-drug approach aims to eliminate all bacteria and prevent drug resistance. The total duration of treatment is commonly around six months.
Completing the entire prescribed course of treatment is important. Stopping medication early or taking it inconsistently can lead to treatment failure, relapse, and the emergence of drug-resistant strains of Mycobacterium tuberculosis. Drug resistance occurs when bacteria evolve mutations that make them unaffected by certain antibiotics, complicating treatment.
Multidrug-resistant TB (MDR-TB) is defined as TB caused by bacteria resistant to at least the two most effective first-line anti-TB drugs: isoniazid and rifampicin. Treating MDR-TB is more challenging, requiring longer and more complex regimens that often involve second-line anti-TB drugs. These regimens can last from 9 to 24 months and may include newer drugs like bedaquiline, pretomanid, and linezolid.
Extensively drug-resistant TB (XDR-TB) is a more severe form of resistance. XDR-TB is defined as MDR-TB with additional resistance to a fluoroquinolone and at least one of the other important second-line injectable drugs or newer agents like bedaquiline or linezolid. XDR-TB is difficult to treat, often requiring individualized regimens with fewer effective drug options and a greater risk of treatment failure and adverse reactions.