Mycobacterium tuberculosis

 

 

Epidemiology

Worldwide, 1/3 of the world's population is infected with TB, and over 16 million existing cases of disease and 8 million new cases occur each year. It is an important complication in patients with AIDS.

Countries with the highest TB prevalence are found in Southeast Asia, sub-Saharan Africa, and Eastern Europe, although resurgence is occurring in many developed countries.

 

Risk factors for TB exposure include:

Risk factors for active TB include:

 

 

Classification and Characteristics

M. tuberculosis is a slightly curved or straight bacilli. It is aerobic, non-motile, and slow-growing (doubling time 18h).

The bacterium is known as acid-fast due to high concentration of mycolic acids (lipid) in cell wall that withstands decolorization

Most strains grow on relatively simple media; some are fastidiuous and some cannot be cultured.

 

 

 

Virulence Factors

M. tuberculosis lives in intracellular vesicles within macrophages, inhibiting lysosomal merging.

 

 

 

Transmission and Infection

TB is spread by airborne droplets (nuclei) 1-5 μm in size. Probability of transmission includes infectousness of person, environment and duration of exposure, and virulence of organism. A 50% infective dose is <10 bacilli (check this).

 

Once settled in the terminal airways, bacteria are phagocytosed by unactivated alveolar macrophages. Phagosomal acidifacation and lysosomal fusion are prevented, and the bacteria multiply freely. Infected macrophages eventually are destroyed, with further cycles of phagocytosis, bacterial proliferation, and lysis occurring.

 

Higher oxygen tension in the upper lobes facilitates bacterial growth.

 

Circulating macrophages and lymphocytes are attracted to the area of infection, forming multinucleated giant cells formed from fused macrophages (Langerhans cells) and resulting in granulomas.

 

Infected macrophages can travel to local lymph nodes, as well as into the blood stream and to other tissues such as bone marrow, spleen, kidneys, and the CNS.

 

 

 

Immune Response

Presentation of bacteria bits on MHC IImolecules activates a CD4+ Th1 response, resulting in IFN-gamma production and angry macrophage transformation. This attenuates bacterial activity.

 

 

Clinical Manifesations

Primary infection is asymptomatic, though symptoms can be seen in children and HIV+ adults.

 

Secondary TB is reactivation of bacteria. Clinical manifestations are primarily due to host response to infection, and the enhanced immune response causes significant damage. They develop slowly and are nonspecific, including

As CD4+ cells die, latent TB infections can emerge from macrophages, become reinfectious, and spread acround the body.

 

Pulmonary TB often appears as chronic productive cough, with or without hemoptysis. Sputum may be scant, purulent, or bloody. Sputum and hemoptysis suggests tissue destruction, as accompanies cavitary disease. One or both upper lobes are usually involved in patients with active disease, resulting in pneumonitis, absecess formation, or cavitation. Chest X-ray can show consolidation, cavitation, and lymphadenopathy.

 

Miliary TB represents widely spread bacteria, with seeding across the lungs, abdomen, bone marrow and CNS. It derives its name from the seed-like (millet) appearance of multiple 2-4 mm lesions, as can be seen on X-ray.

 

Extrapulmonary TB can have many manifestations, including lymphadenitis, pericarditis, pleuritis, hepatitis, peritonitis, meningitis, osteomyelitis (Pott's disease of the vertebra), adrenal infection (Addison's disease), pyelonephritis, and ovary infection.

 

 

 

 

Diagnosis

 

Chest X ray and physical examination can result in findings of consolidation or cavitation in the apices of the lungs. Ultimately, however, tuburcle bacilli must be identified.

 

Acid-fast smears or auramine-o fluorescent staining of sputum should be performed. Liquid media culture can provide results within two weeks, while conventional cultures can take up to 10 weeks. Culture remains the gold standard, as it allows drug resistance testing.

PCR amplification can detect as few as 10 bacteria, as compared to 10,000 required for smear diagnosis.

 

The PPD (Mantoux) test uses delayed type hypersensitivity to diagnose the presence of CD4+ Th1 memory cells, suggesting prior or current infection.

False negative tests occur in 20-25% of people.

BCG vaccinations can result in a high level of false positives.

 

Histology

Pathologic features include:

 

 

Treatment

Isolation practices are required for patients with TB.

Anti-mycobacterial agents are used in combination.

Prophylaxis is used in people who have latent TB or are exposed to the pathogen.

BCG vaccine

 

Active surveillance, therapeutic intervention, and careful case monitoring.

 

 

Public Health Involvement

Tuberculosis is a reportable disease.

Direct observed therapy.

Contact tracing is useful. Prophylaxis using isoniazid should be done for people in close contact.

If skin test is positive in close contacts, treat with isoniazid for 6 months-one year.

If someone off the street has positive skin test, the size of the induration comes into play for determining

 

Resources and References

 

Cain KP et al. 2008. Tuberculosis Among Foreign-Born Persons in the United States. JAMA. 300(4):405-412.