ABSTRACT
Mycobacterium tuberculosis (Mtb) is an acid-fast bacillus that grows in macrophages. The route of transmission is aerial, by inhalation of infected droplet nuclei. Active disease occurs in only 5% of individuals following primary infection. About 25% of the world’s population (2 billion) is infected with Mtb. The main foci of infection are in India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa. Both innate and adaptive immunity play a role in host defense, but Mtb has many immune escape mechanisms that include inhibition of maturation and acidification of phagolysosome, inhibition of oxygen stress and function of both reactive oxygen and nitrogen intermediates, inhibition of apoptosis and autophagy. CD4+ Th-1 cells produce cytokines to help elimination of the M. tuberculosis bacteria from the macrophages. Inability to clear the microorganisms results in cytokine production leading to granuloma formation. Tuberculosis (TB) commonly presents with fever, weight loss, chronic cough, and there may be hemoptysis. Many sites other than the respiratory tract can be affected. TB can cause seizures (CNS), meningitis (CNS), fractures (bones – Pott’s disease) or Addison’s disease (adrenal gland). Diagnosis of active tuberculosis is initially a clinical decision based on an X-ray (for pulmonary TB) and treatment is started on that basis. Culture of sputum samples is still considered the “gold standard” for TB diagnosis. Ziehl-Neelsen stain is not absolutely specific for Mtb and stains M. ulcerans, M. leprae and nontuberculous mycobacteria (NTM), also. Newer rapid nucleic acid-amplification techniques using the polymerase chain reaction (PCR) are now used to detect Mtb which is also more rapid than culture and useful for detecting multidrug-resistant TB (MDR-TB). Serologic tests detect the LAM antigen and blood diagnostic tests, e.g. IGRA are now available in some laboratories. Tuberculin skin tests are used to test for latent TB. The standard anti-TB regimen is a combination of rifampicin plus isoniazid plus pyrazinamide for 2 months, followed by rifampicin and isoniazid for a further 4 months for a total treatment time of 6 months. A fully oral regimen for patients for second-line treatment of MDR-TB has been recommended by the WHO and second-line drugs include levofloxacin, moxifloxacin, bedaquiline, delamanid, linezolid, and pretomanid. Effectiveness of BCG vaccination is highly variable between geographic areas. The vaccine contains bacillus Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis. It is thought to be 70–80% effective against the most severe forms of TB such as TB meningitis but less effective against pulmonary TB. It is given only to “at-risk” groups including healthcare workers, children in high-risk communities and countries, military personnel and laboratory staff dealing with TB. A number of new TB vaccines are being developed that include various platforms including whole-cell vaccines, adjuvanted proteins, and recombinant subunit vector vaccines.
