Latent TB Flashcards
Compare latent TB and active TB infections
Latent tuberculous infection (LTBI): individual is infected with MTB, but has no active disease.
Tuberculosis (TB) - individual has active disease due to MTB. Most active disease are due to reactivation of LTBI.Latent tuberculous infection (LTBI): individual is infected with MTB, but has no active disease.
Tuberculosis (TB) - individual has active disease due to MTB. Most active disease are due to reactivation of LTBI.
TB pathogenesis
Stage 1: Ingestion by resident alveolar macrophages. Stage 2: “Symbiotic” stage - MTB multiplies within macrophages and macrophages accumulate forming an early primary tubercle. Stage 3: Migration of T-cells to the site of infection. T cells activate macrophages to prevent spread of MTB and a granuloma forms which contains infection. Stage 4a: LTBI - cellular level. Solid caseous center remains intact and any bugs that escape are ingested by macrophages. Stage 4b: Decline in immunity –> reactivation TB via loss of integrity of granulomaStage 1: Ingestion by resident alveolar macrophages. Stage 2: “Symbiotic” stage - MTB multiplies within macrophages and macrophages accumulate forming an early primary tubercle. Stage 3: Migration of T-cells to the site of infection. T cells activate macrophages to prevent spread of MTB and a granuloma forms which contains infection. Stage 4a: LTBI - cellular level. Solid caseous center remains intact and any bugs that escape are ingested by macrophages. Stage 4b: Decline in immunity –> reactivation TB via loss of integrity of granuloma
TB and HIV
- In AIDS patients, CD4+ lymphopenia results in granuloma breakdown, resulting in the inability to control the primary infection or in reactivation of latent infection
CXR of latent TB vs active TB
latent: Ranke complexes (calcified lung nodule plus calcified regional hilar and/or mediastinal lymph nodes) and Ghon complexes (calcified lung nodule at site of initial infection) form, but rest of lung is clear. Active: diffuse infiltrates, pneumonia and cavitary lesions
Compare latent TB vs active TB: MTB amount, TB skin test, chest X ray, sputum smears, symptoms, infectivity
Latent: MTB present in small numbers, TB skin test positive, normal CXR w/ Ghon complex, sputum is negative, no symptoms, not infectious. Active: MTB present in large numbers, TB skin test positive, abnormal CXR, sputum positive, symptomatic (cough, fever, night sweats), infectious
classic Test for TB
Tuberculin skin test (PPD)- inject PPD (culture filtrate of MTB) intradermally and measure diameter of induration (NOT erythema) after 48-72 hrs
Positive values for PPD test
> 5mm induration if close contact with TB, HIV +, old TB, organ transplant, anti-TNFalpha therapy. >10mm if immigrant from high prevalence region for TB, high risk groups. >15mm if low risk
Disadvantages of PPD test
False positivity occurs with those who received BCG vaccine and if infected with environmental mycobacteria. False negativity occurs in those who are T cell depleted (ie. AIDS, transplants, chemo, aging), subjective measuring of induration
New tests for TB
IFN-gamma release assays- Quantiferon incubates MTB antigens with patients whole blood O/N and meausre IFN gamma by ELISA. T-SPOT.TB adds patients blood to plate coated with IFN gamma. This is more sensitive than quantiferon
Advantages of IFN gamma release assays over PPD
Fewer visits, rapid turnaround, sensitivity is better in immunocompromised patients, and specificity is better
Which medical conditions have a high risk of reactivation of TB
advanced HIV, old untreated TB, chronic renal failure, infliximab therapy, diabetes (poorly controlled), silicosis, underweight, gastrectomy
What specifically makes HIV + individuals more susceptible to TB
Depletion of CD4+ T cells leads to lowered IL-2, IFNgamma, macrophage activation and granuloma integrity. These all lead to reactivation of TB
Vitamin D and TB
•1,25-(OH)2 D3 suppresses growth of MTB in macrophages by inducing expression of cathelicidin (antimicrobial peptide). African americans have lower Vitamin D which may account for increased susceptibility for TB
Treatment of latent TB infection
9 months isoniazid (INH) (QD or BIW). A common alternative is rifampin daily for 4 months. INH-associated hepatitis is a concern in older EtOH usage, active liver disease, other hepatotoxic drugs. New treatment is 3HP (INH 900 mg + rifapentene 900 mg ONCE WEEKLY x 3 months ) which has better outcomes, but higher rates of adverse events
