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Diagnosis of pulmonary tuberculosis in adults
Mahnaz Mozdourian,MD
Assistant Professor of PulmonologyMUMS
General diagnostic approach
• The diagnosis of pulmonary TB should be suspected in patients with relevant clinical manifestations (cough >2 to 3 weeks' duration,lymphadenopathy, fevers, night sweats, weight loss) and relevant epidemiologic factors (history of prior TB infection or disease, known or possible TB exposure, and/or past or present residence in or travel to an area where TB is endemic)
• definitively established by isolation of M. tuberculosis from a bodily secretion (eg, culture of sputum, bronchoalveolar lavage, or pleural fluid) or tissue (pleural biopsy or lung biopsy).
• Additional diagnostic tools include sputum acid-fast bacilli (AFB) smear and nucleic acid amplification (NAA) testing; a positive NAA test (with or without AFB smear positivity) in a person at risk for TB is considered suficient for diagnosis of TB .
• Radiographic studies are important supportive diagnostic tools
• Patients meeting clinical criteria should undergo chest radiography; if imaging suggests TB of the lungs or airways, three sputum specimens (obtained via cough or induction at least eight hours apart and including at least one early-morning specimen) should be submitted for AFB smear, mycobacterial culture, and NAA testing .
• a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) should be performed.
• These are tools designed for diagnosis of TB infection; a positive result supports (but cannot be used to establish) a diagnosis of active TB disease, and a negative result does not rule out active TB disease .
• In immunocompromised individuals or in HIV-infected patients with CD4 counts <100 cells/mm3, mycobacterial cultures of blood and urine should also be performed.
Obtaining clinical specimens
• Sputum
• Sputum may be obtained spontaneously (by coughing) or it may be induced
• understand that nasopharyngeal discharge and saliva are not sputum.
• Sputum should represent secretions from the lower respiratory tract, and at least 5 to 10 mL is optimal for adequate diagnostic yield ; A series of at least three single specimens should be collected in 8- to 24-hour intervals (with at least one specimen obtained in the early morning), although the diagnosis often can be made with two specimens].
Obtaining clinical specimens
• Obtaining three specimens is useful for culture even if the first or second specimen is smear positive. Sputum should be collected in an area with appropriate environmental controls.
• For patients who have difficulty producing sputum, sputum may be induced by inhalation of aerosolized hypertonic saline generated by a nebulizer.
•the yields of induced sputum and bronchoalveolar lavage specimens are comparable, and induced sputum is safer and less costly
Bronchoscopy specimens
• Unsuccessful attempts to obtain adequate expectorated or induced sputum samples
● Negative sputum studies in the setting of a high clinical suspicion for TB
● Potential alternative diagnosis for which diagnostic bronchoscopy is required
● Urgent diagnostic information is needed
Bronchoscopy specimens
• Sputum produced after bronchoscopy (during the immediate period following bronchoscopy and the day following the procedure) should also be collected for AFB smear and mycobacterial culture to optimize diagnostic yield.
Tissue biopsy
• Tissue biopsy may establish a definitive diagnosis of TB when other testing is not diagnostic. Biopsy specimens allow for both microbiologic studies and histopathologic examination.
Tissue biopsy
• in the setting of TB typically demonstrates granulomatous inflammation. Granulomas of TB characteristically contain epithelioid macrophages, Langhans giant cells, and lymphocytes . The centers of tuberculous granulomas often have characteristic caseation ("cheese-like") necrosis; organisms may or may not be seen with acid-fast staining.
• it is not pathognomonic; culture is required to establish a laboratory diagnosis and to perform drug susceptibility testing
Other specimens
• include pleural fluid, whole blood, gastric aspiration and serum.
•In general, gastric aspiration is not used for adults; it can be useful in children who cannot produce sputum.
•There is no role for use of serologic testing in diagnosis of TB; such tests are neither accurate nor cost-effective .
• (WHO) issued a strong negative recommendation against the use of serologic testing
DIAGNOSTIC TOOLS
•CXR• the initial approach to a diagnostic evaluation of a patient with suspected TB;
• for evaluating symptomatic patients with appropriate epidemiologic risk factors for TB .
• Active pulmonary TB often cannot be distinguished from inactive disease on the basis of radiography alone, and readings of “fibrosis" or "scarring" must be interpreted in the context of the clinical and epidemiologic presentation
• Reactivation pulmonary TB classically presents with focal infiltration of the upper lobe(s) (usually of the apical and/or posterior segments) or the lower lobe(s) (usually of the apical
• Disease may be unilateral or bilateral. Cavitation may be present, and inflammation and tissue destruction may result in fibrosis with traction and/or enlargement of hilar and mediastinal lymph nodes.
• " atypical " radiographic appearance ?
• Lobar or segmental infiltration may be visualized in other lung regions, with or without hilar adenopathy, lung mass (tuberculoma), small fibronodular lesions (termed "miliary“), pleural effusions .
• among patients with advanced HIV disease
• Chest computed tomography (CT) is more sensitive than plain chest radiography for identifying early or subtle parenchymal and nodal processes.
• The resolution provided by CT usually is not required for diagnosis or management of pulmonary TB
• it may be reserved for circumstances in which moreprecise resolution of features observed in a chest radiograph is required or where an alternative diagnosis is suspected.
Microbiologic testing
• include sputum acid-fast bacilli (AFB) smear, mycobacterial culture, and molecular tests
• Laboratory tools for drug susceptibility testing (DST) include culture-based testing (which provides phenotypic information) and molecular testing (which provides genotypic information)
•
Microbiologic testing
• Conventional (phenotypic) culture-based drug susceptibility testing is the gold standard for diagnosis of drug-resistant TB; Culture may take at least amonth to perform. The time to positive culture depends on the burden of organisms, which may be lower in HIV-infected patients.
Molecular tests for drug-resistant TB have faster turnaround time than culture-based DST (results available within hours to days) and are useful forguiding initial decisions regarding therapy until definitive culture-based DST is available
Sputum AFB smear
• The detection of acid-fast bacilli (AFB) on microscopic examination of stained sputum smears is the most rapid and inexpensive
• Smears may be prepared directly from clinical specimens or from concentrated preparations; concentrated material is preferred. Sputum should be of good quality and at least 3 mL in volume
• Sputum AFB smears are less sensitive than nucleic acid amplification (NAA) or culture; approximately 10,000 bacilli per mL are needed for detection of bacteria in AFB smear using light microscopy .
• The sensitivity and positive predictive value are approximately 45 to 80 percent and 50 to 80 percent .
• Sensitivity increases with concentration of the specimen and increased specimen number and can be as high as 90 percent.
• In HIV-infected patients, the sensitivity of sputum smear is diminished because pulmonary cavities occur less frequently and the organism burden is lower in the setting of HIV infection.
• In areas with high HIV seroprevalence, sputum sensitivity is 20 to 30 percent .
• sputum specificity can be high (>90 percent) for both HIV-uninfected and HIV-infected patients .
Mycobacterial culture
• Conventional culture techniquesAll clinical specimens suspected of containing mycobacteria should be cultured.
• Conventional culture is the most sensitive tool for detection of TB and can detect as few as 10 bacteria/mL; the sensitivity and specificity of sputum culture are about 80 and 98 percent .
• Culture is required for drug susceptibility testing and for species identification.
•Rapid culture techniquesRapid culture techniques employ use of liquid rather than solid media; tools include the Mycobacteria Growth Indicator Tube (MGIT) and Microscopic Observation Drug Susceptibility (MODS) assay.
Molecular testing
• Molecular methods are available for detection of M. tuberculosis complex DNA and common mutations that are associated with drug resistance.
• There are two major types of molecular assays: probe-based (non-sequencing) tests and sequence-based assays.
• All molecular tests for drug resistance must be confirmed by culture (agar proportion method using solid media is the reference standard).
•
NAA testing
• NAA testing should be used for rapid diagnosis (24 to 48 hours) of organisms belonging to the M. tuberculosis complex in patients with suspected TB .
• Two test platforms : the Amplified Mycobacterium tuberculosis Direct (MTD) test and the Xpert MTB/RIF test.
• NAA is more sensitive than smear but less sensitive than culture; as few as 1 to 10 organisms/mL may give a positive result.
• NAA testing has excellent positive predictive value in the setting of AFB smear-positive specimens for distinguishing tuberculous from nontuberculous mycobacteria (>95 percent), and it can rapidly establish the presence of TB in 50 to 80 percent of AFB smear-negative specimens (which would eventually be culture positive).
• culture is required for confirmation of identification and for drug susceptibility testing
• Resistance to rifampin can be detected by Xpert MTB/RIF or MTBDRplus, resistance to isoniazid can be detected by MTBDRplus, and resistance to fluoroquinolones and injectable agents can be detected by MTBDRsl.
• Individuals at risk for multidrug-resistant TB with positive NAA test using an assay platform that does not test for drug resistance (eg, Amplified MTD) should have additional molecular testing for rifampin resistance .
• The Amplified MTD test is FDA approved for smear-positive or smear-negative respiratory specimens from patients with suspected pulmonary TB and fewer than seven days of treatment; it detects TB but does not detect drug resistance.
• The Xpert MTB/RIF assay is approved for only induced or xpectoratedsputum from untreated patients or patients on fewer than 3 days' therapy; it detects TB and rifampin resistance .
Urine antigen test in HIV infection
• Urine-based detection of mycobacterial cell wall glycolipid lipoarabinomannan (urine LAM) assay is a point-of-care assay for diagnosis of TB .For regions of the world with high incidence of HIV and TB, WHO, which favors use of urine LAM testing in addition to routine diagnostic tests for HIV-infected patients with signs and symptoms of pulmonary and/or extrapulmonary TB and CD4 ≤100 cells/microL,
• and for HIV-infected patients who are seriously ill (defined as respiratory rate >30/minute, temperature 39°C, heart rate >120/minute, and unable to walk unaided), regardless of CD4 count
