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tuberculosis

Etiology: 1) inhalation of aerosolized droplets containing MTB 2) direct inoculation of abraded skin 3) risk factors for primary progression or reactivation of quiescent disease a) immunosupression - HIV1 infection - immunosuppressive agent - TNF-alpha inhibitors b) malnutrition, alcoholism c) chronic renal failure d) diabetes mellitus e) ileojejunal bypass f) head & neck cancer g) pulmonary fibrosis, silicosis h) injection drug use i) incarceration, homelessness, living in shelter j) stress k) cigarette smoking may be risk factor [17] Epidemiology: 1) 2 billion people worldwide believed to have latent TB 2) each year worldwide, ~9 million people develop active tuberculosis [4] 3) lifetime risk of a person infected with tuberculosis for developing active disease is 5-10% 4) coinfection of HIV & tuberculosis a) when coinfected with MTB & HIV, risk of active TB is increased to 8-40%/year b) average CD4 count of AIDS patients developing tuberculosis is 150-200/mm3 c) 6-8% of patients with MTB are coinfected with HIV [19,30] d) > 1/3 of patients with HIV1 infection worldwide are coinfected with MTB 4) 20% of deaths in patients with HIV1 infection are due to tuberculosis [4] 5) outbreaks of multi-drug resistant tuberculosis have occurred in urban populations at risk for TB & HIV 6) 5.1 cases/100,000 people in 2003 [9] 7) 60-65% of new TB cases in foreign born individuals [4,9]; 30% of these cases diagnosed within 2 years of entry into the US; 45% lived in U.S. for >= 10 years [39] 8) prevalence of tuberculosis is 11-15 times higher in foreign- born US residents than US-born residents [4,30,39] 9) Asians have highest incidence of tuberculosis (0.018%); whites have lowest incidence 0.0006% [30,39] 10) California, Florida, New York, & Texas account for 50% of tuberculosis in U.S. [30] Pathology: - progression to active tuberculosis can occur after initial infection or by reactivation of latent tuberculosis - pulmonary disease (most frequent clinical presentation) - accounts for 70% of active disease [4] - lymphatic/reticuloendothelial disease - genitourinary disease - osteomyelitis (lower spine 'Pott's disease') - meningitis, peritonitis, pericarditis, adrenalitis - miliary TB - immunocompromised patients are more likely to have extrapulmonary tuberculosis - Mycobacterial isocitrate lyase protects MTB against interferon-mediated macrophage elimination - a human-like protein kinase G renders mycobacteria resistant to bactericidal activity of macrophages, probably by inhibiting fusion of phagosomes with lysosomes [10] - iron-binding acute phase protein detected with variable frequency in serum of patients with tuberculosis (non-specific) - granulomas contain macrophages that possess CYP27B1, the 5-hydroxyvitamin D-1 alpha hydroxylase that forms calcitriol from calcifediol, resulting in hypercalcemia Genetics: - polymorphisms in vitamin D3 receptor may determine Mycobacterium tuberculosis susceptibility - polymorphisms in SLC11A1 determine Mycobacterium tuberculosis susceptibility - polymorphisms in CCL2 determine Mycobacterium tuberculosis susceptibility Clinical manifestations: 1) productive chronic cough over weeks or months a) patients typically present with chronic cough b) absence of cough in immunocompetent patient sufficient to rule out pulmonary tuberculosis [29] c) purulent sputum [4], may be blood-tinged 2) hemoptysis 3) pleuritic chest pain 4) dyspnea with extensive disease or pleural effusion 5) fever with night sweats 6) malaise, fatigue 7) anorexia 8) weight loss 9) if CNS involvement, basilar meningitis & cranial nerve palsy 10) immunocompromised patients may not present with typical signs/symptoms - AIDS patients more likely to present with extrapulmonary tuberculosis [4] 11) may be asymptomatic, especially a) initial phase b) HIV patients [4] c) most patients asymptomatic, develop latent tuberculosis [4] d) latent tuberculosis is asymptomatic 12) case report of non-pulmonary abdominal tuberculosis presenting as urinary tract infection [40] Laboratory: 1) sputum: a) a sputum volume of at least 3 mL (optimally, 5-10 mL) is required [36] b) acid fast smears provide presumptive ID, but Nocardia & other Mycobacterium spp also appear acid fast on smear c) 3 specimens for microscopy & culture prior to treatment [4,36] d) initial diagnostic test of choice for active tuberculosis [50,51] - exception appears to be lymphocyte predominant pleural effusion [46] 2) sputum culture of 3 specimens a) obtain when actve disease suspected, even when acid fast smears are negative or when Mycobacterium tuberculosis nucleic acid is positive [4] b) both liquid & solid mycobacterial cultures should be performed for every specimen [36] c) recovered isolates should be identified according to standard criteria [36] d) culture provides basis for drug susceptibility testing [4] e) sputum acid-fast staining & culture most likely to confirm diagnosis of active pulmomary tuberculosis [4] 3) blood culture: positive in 26-42% of AIDS patients 4) Mycobacterium tuberculosis nucleic acid - PCR (sputum, CSF) for Mycobacterium tuberculosis DNA when diagonosis suspected but not confirmed [4,32] - Mycobacterium tuberculosis rRNA - molecular testing of sputum samples facilitates sooner discontinuation of respiratory isolation & provides clinical & economic benefits [41] - excludes nontuberculous Mycobacteria [4] - a negative test does not exclude tuberculosis [4] 5) QuantiFERON-TB test (IFN-gamma release) or tuberculin skin testing - latent tuberculosis - tuberculin skin testing or QuantiFERON-TB test for all patients with suspected active TB - does not confirm active tuberculosis, culture needed [4] - QuantiFERON-TB test is preferred to tuberculin skin testing unless <5 years [4] - may be negative in patients with anergy, miliary or disseminated TB [4] 6) HIV testing - test if disease status unknown - CD4 count if positive; with CNS involvement, CD4 count generally > 300/uL [4] 7) see ARUP consult [20] 8) serum calcium, serum phosphorus 9) genotyping for epidemiological reasons [36] 10) RNA expression signatures obtained from peripheral blood may provide data that helps distinguish tuberculosis from other diseases [26] 11) Mycobacterium tuberculosis rifampin resistance & optionally Mycobacterium tuberculosis isoniazid resistance in patients at risk for drug-resistant tuberculosis [36] - other resistance testing includes - Mycobacterium tuberculosis aminoglycoside resistance - Mycobacterium tuberculosis ethambutol resistance - Mycobacterium tuberculosis ethionamide resistance - Mycobacterium tuberculosis fluoroquinolone resistance - Mycobacterium tuberculosis pyrazinamide resistance 12) adenosine deaminase in body fluid for extrapulmonary TB [36] - pleural fluid adenosine deaminase (tuberculous pleural effusion) 13) elevated interferon-gamma in pleural fluid virtually diagnostic of tuberculous pleuritis in patients with lymphocytic exudates [45] 14) acid-fast stain. mycobacterial culture & histopathology for extrapulmonary tuberculosis [4] 15) baseline laboratory values: a) serum alanine aminotransferase (serum ALT) b) serum aspartate aminotransferase (serum AST) c) serum bilirubin d) complete blood count (CBC) e) serum creatinine 16) complete blood count (CBC): - pancytopenia suggests bone marrow involvement 16) investigational: - nanoparticles coated with antibodies that recognize peptides specific for Mycobacterium tuberculosis may be useful for diagnosis of extrapulmonary tuberculosis for blood samples [37] Special laboratory: - bronchoscopy with bronchoalveolar lavage for patients with suspected active TB, but negative sputum acid fast smears [4] - including patient on TNF-alpha inhibitors [49] - thoracentesis & pleural biospy for tuberculous pleural effusion [4,46] - sputum acid-fast bacilli smears have low diagnostic yield for pleural disease [45] Radiology: - chest X-ray a) upper lobe cavitary lesions without air-fluid levels may be associated with latent TB, reactivation TB or primary progressive TB [4] b) infiltrates in apical-posterior segments of upper lobe & superior segment of lower lobe in reactivation TB c) primary progressive TB - infiltrates, pleural effusion, hilar lymphadenopathy d) interstitial disease, bilateral infiltrates & pleural effusions may be seen in patients with severe immunosuppression - radiologic findings may absent with severe immunosuppression [4] e) HIV infection strongest predictor of non upper-lobe lesion [12] f) millet seed appearance (uniform reticulonodular infiltrate) in milliary TB [4] g) multiple small pulmonary nodules h) pleural thickening - chest CT may identify abnormalities not seen on chest X-ray Complications: - tuberculous sepsis -> systemic inflammatory response syndrome ->septic shock (immunosuppressed patients) [4] Differential diagnosis: - other Mycobacterium Management: 1) pulmonary TB: (treatment after laboratory verification of infection) a) INH 300 mg PO QD + (50 mg pyridoxine PO QD) b) rifampin (RIF) 600 mg PO QD c) pyrazinamide (PZA) 1.5-2.0 g PO QD d) ethambutol (EMB) 15 mg/kg PO QD or streptomycin 15 mg/kg IM QD e) treatment for 6-9 months f) 4 drug regimen for 2 months followed by INH + rifampin for 4-7 months [4] g) if isolate is found to be susceptible to INH & rifampin, ethambutol or streptomycin may be dropped & 3 drugs: - INH, rifampin, & pyrazinamide continued for 8 weeks followed by 4-7 months of INH & rifampin - 7 months recommended for patients with cavitary disease at diagnosis, patients who did not receive pyrazinamide as part of initial therapy, positive cultures after initial 2 months of therapy [4] h) rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary TB - rifapentine, isoniazid, pyrazinamide, moxifloxacin for 4 months [48] i) respiratory isolation 1] all hospitalized patients with pulmonary TB in a negative pressure room 2] remove from respiratory isolation when patient is on adequate anti-tuberculous drug therapy for 2 weeks & a] has had a significant clinical response, & b] has had 3 consecutive negative sputum smears collected >= 8 hours apart [4] 3] hospitalization for respiratory isolation is not required 2) extrapulmonary TB: a) treat same as pulmonary TB for 6-9 months b) tuberculous pericarditis: - include prednisone for 11 weeks - 60 mg/day for 4 weeks, 30 mg/day for 4 weeks, 14 mg/day for 2 weeks & 5 mg.day for 1 week [4,22] 3) INH-resistant TB: 1) rifampin 600 mg PO QD 2) pyrazinamide 1.5-2.0 g PO QD 3) ethambutol 15 mg/kg PO QD or 4) streptomycin 15 mg/kg IM QD 5) duration of therapy 6 months 4) multidrug resistant TB: a) empiric therapy should consist of 5-6 drugs - isoniazid (INH), rifampin, pyrazinamide, ethambutol, streptomycin, fluoroquinolone b) treatment should consist of at least 3 drugs to which the organism is sensitive c) addition of linezolid may be of benefit [21] - adverse effects common d) addition of bedaquiline (Sirturo) may be of benefit [24] e) consider surgery for which the bulk of the disease is resectable f) continue 5-6 drug intensive phase for 5-7 months after culture negative g) follow with 4 drugs for at least 15-21 months months (continuation phase) h) associated with increased mortality [4] 5) patients who must be treated parenterally a) INH 300 mg IV QD + (50 mg pyridoxine PO QD) b) rifampin 600 mg IV QD c) amikacin 500 mg IV every 12 hours 6) other 1st line agents a) rifapentine b) rifabutin 7) other 2nd line agents a) cycloserine b) ethionamide c) kanamycin plus amikacin d) fluoroquinolones - ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, gatifloxacin - treatment of fluoroquinolone-sensitive tuberculosis for 4 months is inadequate [27] e) para-aminosalicylate 6) new drug(s) on the horizon - R207910, a diarylquinolone [11] - 10-fold more effective than INH or rifampin 7) monitoring therapy at least monthly [4] a) directly observed therapy 1] recommended when medication administration is <7 days/week 2] recommended because medical noncompliance can result in: a] transmission of tuberculosis b] treatment failure c] drug resistance [4] b) pulmonary TB: 1] weekly sputum smears & cultures for the 1st 6 weeks of therapy 2] smears & cultures obtained thereafter until cultures are negative 3] continued positive smears or cultures after 3 months suggest drug-resistance or non-compliance with medications c) routine laboratory testing recommended for patients with baseline laboratory abnormalities or increased risk of adverse effects - liver function should be monitored often, perhaps as often as every 2 weeks [8] d) patients taking ethambutol should be tested for visual acuity & red-green color perception 8) treatment does not affect HIV antiretroviral therapy [15] 9) never add a single drug to a failing regimen [4] 10) discontinuation of therapy for >= 2 weeks - restart orginal antituberculous regimen from the beginning [22] 11) see screening for tuberculosis 12) see chemoprophylaxis for latent tuberculosis 13) prevention - Bacillus Calmette-Guerin (BCG) - live virus vaccine - most effective in preventing disseminated infection & tuberculous meningitis in children [3] - MTB vaccines in clinical trials [33] 14) The Health Dept. should be notified in all cases of TB. 15) infection control - N95 respirator is used by medical personel in contact with tuberculosis patients [13] - airborne precautions (surgical face mask) for visitors [31] - determination patient is no longer contagious requires - appropriate antimicrobial therapy for >= 2 weeks - 3 negative sputum smears collected >= 8 hours apart - clinical improvement [4]

Interactions

disease interactions

Related

chemoprophylaxis for tuberculosis contacts of persons with tuberculosis Mycobacterium tuberculosis (MTB) Mycobacterium tuberculosis DNA purified protein derivative (PPD, Tubersol) QuantiFERON-TB test; interferon gamma release assay (IGRA) screening for tuberculosis tuberculin-skin testing (TST)

Specific

cutaneous tuberculosis; includes tuberculous chancre, tuberculosis verrucosa cutis drug-resistant tuberculosis extensively drug-resistant tuberculosis (XDR-TB) HIV1/tuberculosis coinfection latent tuberculosis; inactive tuberculosis scrofula silicotuberculosis tuberculoma tuberculous arthritis tuberculous enteritis tuberculous meningitis tuberculous peritonitis tuberculous pleural effusion tuberculous pleurisy

General

mycobacterial infection granulomatous disease

Database Correlations

OMIM 607948

References

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