Mycobacterium Tuberculosis

Mycobacterium tuberculosis (Multidrug-Resistant [MDR] TB) – Mycobacterium tuberculosis (Multidrug-Resistant [MDR] TB)

Mycobacteria are gram-positive, nonmotile, pleomorphic rods, related to the Actinomyces species.(1) Most mycobacteria are found in water or soil. However, a few are intracellular pathogens of animals and humans. Mycobacterium tuberculosis (Mtb) and M. bovis, M. africanum, and M. microti all cause the disease tuberculosis (TB) and are members of the TB species complex. Each member of the TB complex is pathogenic, but Mtb is pathogenic for humans whereas M. bovis is usually pathogenic for animals. TB complex organisms are obligate aerobes, growing in tissues with high oxygen content (e.g., lungs). The bacteria are facultative intracellular pathogens, usually infecting mononuclear phagocytes. TB complex organisms are known as “acid-fast bacilli,” because of their lipid-rich cell walls. Once stained with basic dyes combined with phenol, the cells resist decolorization with acidified organic solvents and are therefore called acid-fast. Figure 2-8 provides details on the clinical, biological weapon, and public health features of TB.

Clinical Features

Use as Biological Weapon

Public Health Issues

Nonspecific symptoms include fever, night sweats, loss of weight and appetite, fatigue, and persistent cough

Diagnosis by positive tuberculin skin test, an immune reaction to a small quantity of tuberculosis antigens, often confirmed by chest X-ray and microscopic examination of sputum for presence of acid-fast bacilli

In lung, organism is taken up by alveolar macrophages and carried to lymph nodes, where it spreads to multiple organs

Cell-mediated immunity and delayed type hypersensitivity develop 2–8 weeks following infection, leading to containment in immunocompetent individuals

Inflammatory immune responses to infection eventually result in significant lung damage

Prophylactic vaccination using live, attenuated strain of M. bovis (bacillus Calmétte-Guerin [BCG] vaccine) used as prevention in many countries

Currently treated by intensive 2-month combination therapy, using cocktails of three to four drugs (usually isoniazid, rifampicin, pyrazinamide, and streptomycin or ethambutol)

TB is a highly infectious bacterial disease transmitted through the air by coughing and sneezing

Although little evidence exists to suggest that Mtb has been developed into a biological weapon, its high infectivity rate, easy transmission, and MDR mutant strains suggest that deliberate release could have significant effects in urban populations

Re-emerged as a leading cause of death worldwide

~1.9 billion humans infected with Mtb; ~8 million new cases reported annually(2)

Annual 1997 mortality rate 1.87 million

Host genes (polymorphisms of HLA-DQ, HLA-DR, NRAMP-1, IFN-gR, IL-12R, vitamin D receptor and MBP) influence severity of Mtb(3)

Polymorphisms in N-acetyl-transferase gene influence efficacy and toxicity of isoniazid (anti-TB medication)

MDR Mtb strains simultaneously resist rifampicin and isoniazid and threaten control and prevention efforts

Molecular and genetic studies attribute Mtb drug resistance to accumulating mutations in/over-expression of drug target genes (e.g., RNA polymerase and catalase-peroxidase)(4)

CDC reported 7.4% of U.S. TB cases resistant to isoniazid; 1% of cases resistant to isoniazid and rifampin

The WHO estimates ~50 million persons worldwide infected with MDR TB, which indicates it is re-emerging as a major public health threat

References

1. Mandell GL, Douglas RG, Bennett JE, Dolin R, eds Principles and Practice of Infectious Diseases. (ed 4th). New York, Edinburgh, London, Madrid, Melbourne, Milan, Tokyo: Churchill Livingstone; 1995.
2. Dye C, Williams BG, Espinal MA, Raviglione MC. Erasing the world’s slow stain: strategies to beat multidrug-resistant tuberculosis. Science. 2002;295:2042–2046.
3. McNicholl JM, Downer MV, Udhayakumar V, Alper CA, Swerdlow DL. Host-pathogen interactions in emerging and re-emerging infectious diseases: a genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera. Annu Rev Public Health. 2000;21:15–46.
4. Rattan A, Kalia A, Ahmad N. Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives. Emerg Infect Dis. 1998;4:195–209.