Tuberculosis
Week 7 (Set 2)
Terms
undefined, object
copy deck
- M. Tuberculosis Complex
- • Mycobacterium tuberculosis -This is the primary one in the development of tuberculosis • Mycobacterium africanum • Mycobacterium bovis • Mycobacterium bovis BCG • Mycobacterium microti • Mycobacterium canettii • Mycobacterium pinnipedii • Mycobacterium mungi
- General Features of TB
- • The primary infection is generally pulmonary, but dissemination to any organ can occur • Epidemiologically may be the most important infection on Earth
- Important Definitions
- • Exposure- close contact with someone with active infectious tuberculosis disease • Infection- proliferation of Mycobacterium tuberculosis at the site of contact before progression to symptomatic disease. primary TB • Disease- active tuberculosis developing either immediately after primary infection or later on by reactivation of latent infection
- Epidemiology
- • Mycobacterium tuberculosis infects 1/3 of the world's population • 10% of those infected develop disease • Estimated 6 million new cases of active tuberculosis/year • Worldwide, the leading cause of death due to any single infectious agent
- Risk Factors in Canada
- -Country of origin with high rates -Aboriginal Background -Homelessness -Substance Abuse -Time Spent in correctional facility -Contact with known TB patient -Older age -Travel (Asia and Pacific is the most prevalent place you get it) -Health Care occupation
- Infectious Process
- • Acid-fast bacillus • Slow-growing • Resistant to drying • Resistant to most antibiotics • Resistant to host killing • Intracellular survival
- Transmission of TB
- • "Droplet spread" from a person with pulmonary tuberculosis disease • Aerosol particles generated by coughing, sneezing, talking • 6000 infectious droplet nuclei= - One sneeze - Two coughs - Talking continuously for 5 minutes • Droplets may remain suspended for hours
- Probability of Transmission
- Depends on a number of factors related to the host and bug: • Infectiousness of person with TB • Environment in which exposure occurred • Duration of exposure • Virulence of the organism
- Pathogenesis of TB-Primary Infection
- • Inhalation of droplet nuclei- deposition of M. tuberculosis in terminal airways, usually subpleural, in mid-lung zones • Replication of organism in alveoli and within alveolar and tissue macrophages ("Ghon focus") • Transport of infected macrophages to regional lymph nodes • Development of delayed-type hypersensitivity (Mantoux reaction)
- RIsk of Developing Disease
- It is not that likely.. • After exposure, 5% immunocompetent patients develop primary disease, 37% AIDS patients develop primary disease • Latent tuberculosis infection, 5-10% lifetime risk of developing disease immunocompetent versus 10% per year in HIV patients In healthy individuals you get 95% of people ending up with a latent infection -of these only 5% get a postprimary TB reactivation 90% don't get any disease at all!!
- Locations of TB Manifestation
- • Pulmonary • Extra-pulmonary • Respiratory • Non-respiratory
- Primary Tuberculosis
- You get balls within the lung tissue -You can also get Tuberculous Caseating Granuloma filled with Langhan's Giant Cells!!
- Tuberculous Granuloma
- You have a Langharns Giant cell Surrounded by: 1) Lymphocytes and fibroblasts 2) Epitheliod Histocytes 3) Caseous Necrosis
- Clinical Features of Primary TB
- In order of decreasing liklehood -Cough -Weight Loss -Fatigue -Tactile Fever -Night Sweats -Chills -Anorexia -Chest Pain
- Cavitary TB Diagnosis
- • Sputum (expectorated or induced) - Acid fast bacilli (AFB) smear - Acid fast bacilli culture Why culture? • Non-cavitary pulmonary tuberculosis can be smear negative and only culture positive • Many non-tuberculous mycobacterium can cause lung disease (NTM) • Want to know the drug susceptibility profile -The growth period can take up to 7 weeks -The more bugs you have the faster it will grow and the worse the infection actually is
- Tuberculous Pleurisy
- This is when the TB causes a pleuritits/ effusion and it fills with fluid!! Symptoms: -Dyspnea -Chest Pain -Fevers -Weight Loss Diagnosis: • Pleural fluid for AFB smear (10%) • Pleural fluid for culture (25%) • Pleural fluid assessment - lymphocytosis • Sputum for smear and culture • Pleural biopsy - Granulomatous inflammation/AFB seen/AFB grown > 90%
- Miliary/Disseminated TB
- Miliary Symptoms: - Fever - anorexia, weight loss - Fatigue - organ-specific symptoms Pathology: • Progressive disseminated hematogenous TB • Elderly patients, immunocompromised • Systemic illness Diagnosis: • Sputum • Blood, urine, stool • Biopsy - Liver - Bone marrow - Lung (All for AFB, culture, and histopathology)
- Non-Pulmonary TB
- This is a much less common manifestation of the disease although it does happen -It appears in areas like the Lymph nodes and around the body: Lymph Nodes Testing: • FNA for - AFB smear, culture, and histopathology • Excisional biopsy for - AFB smear, culture, and histopathology Other Areas include: -Miliary -Meninges -Abdominal -Bones and Joints -Geitourinary -Other These have the Similar diagnostic Criteria as the other form of TB +++ • Stupor, indolent, CN palsies • CSF analysis - low glucose, high protein, lymphocyte predominant • CSF - AFB and culture • Poor yield on assessment, High morbidity and mortality with tuberculous meningitis, tend towards empiric treatment
- Tuberculosis-Pericarditis
- • Pericardial fluid for AFB smear (< 10%) • Pericardial fluid for culture (25%) • Pericardial fluid assessment - lymphocytosis • Pericardial biopsy - Granulomatous inflammation/AFB seen/AFB grown (50%)
- Pediatric TB
- • Those under five years of age often progress rapidly from primary infection to disease (disseminated disease including meningitis) - These patients are treated differently!!! • Pediatric pulmonary disease presents differently than adult pulmonary disease
- Management of TB
- • Management of Patient - Isolation - Antibiotic treatment - HIV testing - Follow Up • Management of Contacts - identification of those infected - identification of those with disease - treatment
- 1st Line Chemotherapy for TB
- • Empiric Treatment - TB has the potential for intrinsic resistance - Treat with multiple (3-4) drugs simultaneously -Guided by susceptibilty - DOT (Directly Observed Therapy) • When Susceptibility results available: - tailor treatment to resistance pattern Drugs that are used include: "First Line" Isoniazid: -This acts by inhibiting Mycolic Acid - interacts with anti-seizure meds - 1-3% risk of hepatitis - peripheral neuropathy • vitamin B6 if renal failure, DM, malnourished, HIV Rifampin: - A rifamycin - Inhibits DNA dependent RNA polymerase - interacts with many medications • CYP3A4 inducer (potent) - BCP - Coumadin - ARV/Abx/AFx - 1-3% risk of hepatitis - thrombocytopenia Pyrazinamide: - Blocks FAS and may also impact translation - hepatitis, progressive hepatic failure Ethambutol: - Blocks arabinoysl transferase - renally excreted, don't use in renal failure - optic nerve damage Streptomycin: - Aminoglycoside - renal dysfunction - ototoxicity - vestibular toxicity - cumulative dosing You need to keep people on all these drugs as a concoction othewise you run the risk of developing resistance
- Resistant Strains
- Use this concoction in resistant strains giving you grief: MDR-> INH + Rifampin don't work XDR-> INH + Rifampin + Fluoroquinolone and injectables Burden of MDR -accounts for 3.8% of cases (440000 per year)
- Length of Treatment (Normal)
- • Fully susceptible organism - 6 months of treatment if can use PZA - 9 months of treatment if can't use PZA - Outcome is very good if take medication • (> 90% cure rates) - DOT
- Treatment of MDR
- • (Very) Difficult to cure • Long length of treatment (highly toxic) • Long time of infectiousness • ...Worse yet with XDR
- Management of Latent TB
- • Consider those at highest risk -AIDS -HIV -Transplantation -Silicosis • Identify infection -Mantoux Test (look for the swelling on the arm) -Greater than 1cm is when you get into the range of it being positive -Interferon Gamma Release Assay (blood test for the production of interferon by T-Lymphocytes after exposure to M. Tuberculosis antigen • Ensure individual does not have active tuberculosis disease - Rule out active disease - Symptom inquiry - CXR - Further testing if required • Offer preventive therapy - Isoniazid (INH) 300 mg po od x 9 months - INH & Rifampin x 4 months - Rifampin and Pyrazinamide x 2 months, significant liver toxicity and not currently recommended • Follow for response
- When do you get a Positive Chest X-ray
- When you have a CD4 count greater than 200!! -Your liklihood of getting Extrapulmonary TB increases with AIDS
- Diagnosis TB with HIV
- • Slight decrease in sputum smear positivity in pulmonary TB in HIV • (30-60% vs 50-70%) • increase in extra-pulmonary disease • difficulties in diagnosis in low-income countries that rely on smear and have no culture facilities
- Treatment Regimes with HIV
- • 6 month regime has been shown to be adequate in HIV (7 prospective studies) - recurrence rates < 5% • Concern has been raised about the intermittent regimes • non rifamycin containing regimes, increased mortality rates Intermittent Regimes are an option: • Once weekly rifapentine/INH in continuation phase in HIV - 17% versus 10% recurrence of disease • Intermittent regime of pTB with INH/Rif increased recurrence rate (CD4 < 100ug/ul) Tolerability: • Some studies have shown increased side effects while others have not • increased risk of peripheral neuropathy (pyridoxine) • ? Increased risk of liver toxicity (varied between studies as well) • not use thiacetazone (Stevens-Johnson syndrome)
- Anti-retroviral Therapy + Incidence of TB
- • Use of anti-retroviral therapy in HIV patients in high incidence areas decreases tuberculosis incidence • 1085 HIV non ART compared to 270 HIV patients on ART • analyzed by CD4 count
- ART and Latent TB
- • 129 patients, 7 new tuberculin skin test positivity (5%) • immune re-institution versus new exposure • suggest that HIV patients with previously negative tuberculin skin tests should be retested after immune reconstitution and Rx for latent tuberculosis infection if positive Treatment: • Multiple issues • interaction of rifampin and PI, NNRTI • side-effects • when to initiate therapy • paradoxical reactions • IRIS (immune-reconstitution inflammatory syndrome) • MDR and XDR TB