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Flashcards in TB Deck (11):
1

Define primary vs latent infection

Primary tuberculous infection: initial infection with Mycobacterium tuberculosis (MTB). Almost always occurs through the respiratory tract. In immunocompetent individuals, most primary infections do not develop into active disease; instead, such individuals continue to harbor the organisms, resulting in a state of latent tuberculous infection.

Latent tuberculous infection (LTBI): Individual is infected with MTB, but has no active disease.

2

Tuberculosis (TB) and primary vs latent infection

Primary tuberculous infection: initial infection with Mycobacterium tuberculosis (MTB). Almost always occurs through the respiratory tract. In immunocompetent individuals, most primary infections do not develop into active disease; instead, such individuals continue to harbor the organisms, resulting in a state of latent tuberculous infection.

Latent tuberculous infection (LTBI): Individual is infected with MTB, but has no active disease.

3

The global threat of TB

2 billion people are infected with TB.

7-8 million new cases of TB per year.

2-3 million people die from TB per year

4

Chronology of the TB pathogenesis

Stage 1: Ingestion by resident alveolar macrophages. Some MTB killed by Phagosome-lysosome fusion or Apoptotic death of macrophages, but some macrophages experience MTB multiplication followed by necrosis and release of MTB to be taken up by other macrophages

Stage 2: “Symbiotic” stage - MTB multiplies within inactivated macrophages and macrophages accumulate into formation of early primary tubercle

Stage 3: Migration of T-cells to the site of infection. T-cells begin to activate macrophages to kill or prevent spread of MTB. Granulomas form and infection is contained

Stage 4a: LTBI - cellular level. Solid caseous center remains intact.
Stage 4b: Decline in immunity --> reactivation TB. Immunosuppression leads to loss of integrity of granuloma. Caseous necrosis occurs. Rupture and spread to other parts of the lung and to other individuals

5

Characteristics of LTBI vs Active TB

LTBI:
MTB present (small numbers), Tuberculin skin test positive, Normal chest X-ray (may have a Ghon complex), Sputum smears and cultures negative, No symptoms, Not infectious, Defined as a case of LTBI

Active TB:
MTB present (large numbers), Tuberculin skin test positive, Abnormal chest X-ray with pneumonia ± cavitary lesions, Sputum smears and cultures positive, Symptomatic with cough, fever, night sweats, and weight loss, Often infectious before treatment, Defined as a case of active TB

6

The criteria for a positive TST

Depends on the risk for reactivation TB.
≥ 5 mm for those Recent close contact to an active case of TB* and those who are HIV-positive and those on Anti-TNFa therapy
≥ 10 mm Recent tuberculin skin test converter and Immigrants from high prevalent regions for TB
≥ 15 mm All others, essentially those who are considered low risk

7

Advantages of IFNg-release assays (IGRA) over TST

Fewer patient visits, More rapid turnaround time, Quantifying IFNg levels or counting number of “spots” is more objective, Sensitivity for LTBI is probably as good or better than TST, Specificity for LTBI is considered to be better than PPD

8

Vitamin D and TB

*D3 suppresses growth of MTB in macrophages
*African-Americans have lower vitamin D levels and this may account for increased susceptibility for TB
*Vit D induces expression of cathelicidin, an antimicrobial peptide that kills MTB


9

Treatment of LTBI

9 months isoniazid (INH) (QD or BIW)
A common alternative is rifampin daily for 4 months

10

T Spot Test

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11

Quantiferon Test

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