Tuberculosis (TB) is an infectious disease caused by bacteria whose scientific

name is Mycobacterium tuberculosis. It was first isolated in 1882 by a German

physician named Robert Koch who received the Nobel Prize for this discovery. TB
most commonly affects the lungs but also can involve almost any organ of the
body. Many years ago, this disease was referred to as "consumption" because
without effective treatment, these patients often would waste away. Today, of
course, tuberculosis usually can be treated successfully with antibiotics.

Mycobacterium tuberculosis:

  CMN group: Corynebacterium, Mycobacterium, Nocardia are grouped together on

the basis of distinguishing factors that include complex cell wall components, presence
and type of mycolic acids, adjuvant activity, presence of cord factor, sulfolipids, iron-
chelating compounds, polyphosphate, and serological cross-reactivity.

  Very slow growing

  Prototrophic (ability to build all required components from basic carbon and nitrogen
sources) with glucose (carbon source) and ammonium ion (NH4+)(nitrogen source) or
glycerol and asparagine

  Many specific mycobacteriophages

  Acid-fast bacilli red on blue background with Ziehl-Nielsen acid-fast stain

  Non-spore former, resistant to drying, sunlight, and chemical disinfectants,

particularly in sputum

  Obligate aerobe, but facultative intracellular pathogen with two clinical forms:

1. Pulmonary disease
2. Extra-pulmonary disseminated disease

  Many immunoreactive substances. Important antigens include: purified protein

derivative (PPD), cord factor, and old tuberculin (OT).

  Correlation of strain virulence with cord factor, but specific determinants of

pathogenicity have not been identified.

  Tuberculosis is leading cause of reportable infectious diseases; 8-10 million new

cases and 3 million deaths every year.

  Single most critical factor in tuberculosis infection is the severity of infectiousness of

the source case
   Organisms transmitted from infectious cases via droplet nuclei suspended in the air.
Aerosols produced by talkin, coughing, sneezing, breathing dry to droplet nuclei (1-10
um diameter) that are inhaled deep into the alveoli of the lungs.

  Factors that influence risk of contracting tuberculosis disease, i.e., progressing from
infection to disease include: age, sex, race, personal habits, co-existing disease, and
socioeconomic status

  Treatment with Isoniazid (INH) or rifampin and second line drugs or attempted
preventive therapy with INH and BCG prophylaxis

  Primary pulmonary infection with secondary infection of pulmonary or extra-

pulmonary sites

  Tissue destruction and fibrosis (fibrous walling off of lesions, i.e. granulomatous
reaction) caused by host response to infection.

  Initially, a the host mounts a non-specific inflammatory response: organisms are

phagocytosed by alveolar macrophages, inhibition of phagolysosome fusion,
intracellular multiplication, and spread to regional lymph nodes, then the blood stream
and seeded throughout the body. Secondary infection is either in a pulmonary site, from
ongoing multiplication of organisms seeded to apices of the lungs or in any
extrapulmonary site.

  Two to four weeks after infection, cell-mediated immunity and tuberculin

hypersensitivity develops.

  Cytokines derived from T-cells activate the macrophages and render them capable
of killing the bacteria. A small antigenic burden (limited number of infecting cells) results
in destruction of the bacilli and minimal tissue necrosis. With a large antigenic burden
(large number of bacilli), this cellular immune response results in tissue necrosis.

  The hypersensitivity response to tuberculin results in localized collections of

cytokine-activated macrophages (granulomas) prevent further spread of the organisms.
Larger, necrotic or walled-off granulomas become surrounded by fibrin (tubercle
formation) which effectively protects the organisms from macrophage killing. Bacilli
remain dormant (quiescent) in this stage for years or decades. When immunological
response wanes, bacilli can reactivate.

  Secondary or reinfection tuberculosis resulting from reactivation of quiescent foci of

bacilli; occurs in small number of infected persons despite acquired cellular immunity.
Lesions remain localized because of cell-mediated immunity Hypersensitivity promotes
fibrotic walling-off of foci (characteristic tubercle granuloma).
   Koch demonstrated Koch’s postulates with M. tuberculosis, but noone has yet been
able to satisfy his postulates with this pathogen’s sister species M. leprae. M. leprae has
never been cultured in vitro.

Mycobacterium bovis:

  Formerly important cause of bovine tuberculosis transmitted by ingestion of

contaminated milk. Is uncommon in the United States, since the advent of
pasteurization and herd surveillance.

  Now important as species from which attenuated strain (M. bovis, Bacillus of
Calmette and Guerin (BCG)) is used for preparation of tuberculosis BCG vaccine