Definitions
Probability of Transmission
probability that an infected person will transmit the organism
Pathogenesis
inhaled Mycobacterium turberculosis bacilli reach the alveoli of lungs and are ingested by macrophages --> bacilli multiply in macrophages and spread through bloodstream
-M. tuberculosis releases substances that prevent pH drop in macrophages so lysozymes become less effective
Age group that primary infection typically occurs in vs age group that post-primary infection typically occurs in
primary infection: usually childhood in endemic countries
post primary infection: usually in adults; occurs after latent period after primary infection
Clinical diagnosis
-Clinical examination
-Tuberculin (Mantoux) testing; IGRAs (only tells you if you have been infected NOT if you have disease)
-chest x-ray
What stain is necessary for Mycobacterium tuberculosis?
Acid-fast stain
Probability of infection
probability that an exposed person will acquire infection
Lung pathology
-granulomas, cavitation, caseous "cheesy" necrosis, may lead to extensive fibrosis
-cavities usually communicate with airways and persons with these are the most infectious
Primary infection features
-bacilli multiplying in alveoli locally in a lobe of the lung --> Ghon focus (primary lesion in lung)
-Ghon focus + hilar lymphadenopathy forms the primary complex (Ranke complex) (basically ghon focus develops and becomes calcified w/ lymph node swelling)
-some people have apical scarring
-Immune response develops within 4-6 weeks
Laboratory diagnosis
-sputum smear examination for acid-fast bacteria
-culture for mycobacteria (+ sensitivity testing)
-rapid diagnosis by GeneXpert (PCR which detects presence of TB and sensitivity to Rifampicin)
Can you identify TB with smear alone?
No. most mycobacteria look alike in smears
Probability of disease
Probability that an infected person will get the disease
-90% of people with normal immune system will NOT have disease
Conditions that increase risk of progression to TB disease
***HIV
-substance abuse, recent infection, diabetes mellitus, silicosis, prolonged corticosteroid therapy, other immunosuppression (cancer, malnutrition, etc.)
Post-primary TB features
-occurs by reactivation or reinfection
-usually affects the lungs; can be elsewhere
-characteristically presents with upper lobe infiltrates, extensive lung destruction (caseation) with cavity formation & positive sputum smear
Latent tuberculosis infection diagnosis
-PPD/Tuberculin skin test/Mantoux test
-IGRAs: interferon gamma release assays (quantiferon gold or T-SPOT TB assay)
Importance of culture
-culture should be on all specimens even if smear is positive (bc test for antibiotic sensitivity)
Open case of TB (& how many they can infect)
- can infect 15 people per year
Natural outcomes of Disease
pulmonary TB patients without treatment at 5 years of disease:
-50% will die
-25% will be self-cured
-25% will remain ill with chronic, infectious TB
Clinical features (most important symptoms)
-cough > 3 weeks
-Sputum production
-Weight loss
People at high risk for exposure/infection with TB (who should be tested for LTBI)
-close contacts of person known or suspected to have TB
-foreign born people from TB endemic area
-residents and employees of high-risk settings
-healthcare workers serving high risk clients
-medically underserved, low-income populations
-high risk racial or ethnic minority populations
-children exposed to adults in high risk categories
-persons who inject illicit drugs
First line treatment drugs
-Isoniazid (H) and Rifampicin (R): strongest bactericidal; active against all strains of TB that are not resistant
-Pyrazinamide (Z):bactericidal; active intracellularly (in macrophages)
-Streptomycin (S): bactericidal; active against rapidly multiplying extracellular organisms; not commonly used bc toxic
-Ethamabutol (E): bacteriostatic drug used in combination with bactericidal drugs to prevent antibiotic resistant
--> we typically give HRZE
MDR-TB (what drugs is it resistant to)
Always resistant to Isoniazid and Rifampicin
Stages of disease (just the names)
Primary infection, latent tuberculosis infection, post-primary tuberculosis
Common sites of TB disease
**Lungs
**Pleura
-CNS, lymphatic system, genitourinary systems, bones and joints, disseminated (miliary TB)
-persons with HIV infection
-persons recently infected with M. tuberculosis
-persons who are immunosuppressed
-persons who inject illicit drugs
-persons with a history of inadequately treated TB
BCG Vaccine and DOTS definition
-DOTS: directly observed therapy, short course
-BCG vaccine (developed in 1921) is only vaccine available; recommended in pediatric populations in places with high TB rates