Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (583 page)

Typical signs and symptoms of tuberculosis depend on the age and state of immunocompetence of the patient.

   More aggressive disease is common in young children (<5 years), with risk for extrapulmonary infection. CXR demonstrates prominent hilar and mediastinal lymphadenopathy; middle and lower lung field pneumonitis may be minimal.

   In the elderly, tuberculosis is also more aggressive and may represent new infection, with mid-field pneumonitis and hilar adenopathy, or due to reactivation of latent infection, with typical apical cavitary disease.

   In adolescents and adults, primary infection may not be clinically obvious. Apical abnormality may be seen coincidentally during latent infection or at the time of reactivation of disease.

   Patients whose primary infection is controlled by their immunologic response enter a latent, asymptomatic phase of infection. Organisms, however, continue to multiply slowly in infected tissues, leading to ongoing risk of reactivation disease.

   Common symptoms of active disease include nonspecific constitutional symptoms, like fever, anorexia, weight loss, and night sweats, and specific symptoms related to the respiratory tract or other infected organ systems, like cough with sputum production, hemoptysis, or pleuritic chest pain.

Factors associated with increased risk of acquisition and transmission of tuberculosis include living in, or emigration from, a region with a high prevalence of tuberculosis, poverty and homelessness, crowded living conditions, AIDS, and intravenous drug abuse. Patients usually become noninfectious within 2 weeks after initiation of effective therapy. Negative AFB smears for three specimens, taken at least 8 hours apart, are recommended to take patients out of respiratory isolation.

   Laboratory Findings

Screening tests for tuberculosis: Screening for tuberculosis is recommended for patients at high risk of tuberculosis on the basis of clinical signs and symptoms or epidemiologic factors.

Tuberculin skin test (TST)
: TST is performed by intradermal injection of a standardized solution of a purified protein precipitate from Mtb. Induration (not erythema) at the injection site is assessed after 48–72 hours. A 5-mm cutoff is used for immunocompromised persons and other individuals with recent exposure to patients with active tuberculosis. A 10-mm cutoff is used for individuals in other risk groups. BCG vaccination is an unlikely cause of false-positive TST, unless the vaccination was administered in the prior several years. False-positive TST may also be seen in patients with infections caused by mycobacterial species other than
Mycobacterium tuberculosis
(NTM). False-negative TST reactions may occur in HIV-infected patients with advanced immunosuppression; retesting may be performed after immune recovery associated with effective antiretroviral therapy.

Interferon-γ release assays (IGRA)
: These assays measure the quantity of interferon-γ released from patient’s peripheral blood lymphocytes incubated with purified Mtb antigens. These assays have comparable sensitivity and specificity compared to TST assays. An advantage of IGRAs is that patients do not have to return for test interpretation; BCG vaccination does not cause false-positive IGRA reaction. The utility of IGRAs has not been established for young children (<5 years) or immunocompromised patients.

Specimens for AFB smear and culture
:

   
Sputum samples
: Sputum is most commonly submitted to the laboratory for analysis. First-morning specimens are recommended as most likely to yield positive results. Submission of two or three specimens, submitted at least 8 hours apart and including at least one first-morning specimen, has been recommended for evaluation of patients. Sputum specimens of at least 5-mL volume should be submitted for AFB studies; detection is decreased in lower volume specimens. Pooled sputum is not acceptable because of the high rate of culture contamination. Sputum induced by inhalation of hypertonic saline or specimens collected by bronchoalveolar lavage (BAL) are recommended for patients who are unable to provide a good quality expectorated sputum sample and for those with a continued high suspicion for tuberculosis even after negative AFB studies of expectorated sputum. First-morning gastric lavage specimens may be submitted on infants or other patients from whom sputum collection is not feasible.

   
Specimens from other potentially infected sources
, like blood, pleural fluid, urine, or CSF, should be submitted in addition to respiratory specimens.

   
Respiratory specimens, and specimens from other sources
typically contaminated with endogenous flora, are decontaminated and concentrated (centrifugation at 3,000×
g
for 15 minutes) for smear preparation and culture inoculation.

Culture
: Isolation of
Mtb
by culture is the gold standard for diagnosis; cultures should be submitted for every patient.

   Three types of media are commonly used for AFB culture: egg-based solid (e.g., Lowenstein-Jensen), agar-based solid (e.g., Middlebrook 7H11), and liquid media (e.g., Middlebrook 7H12). Cultures are incubated in 5–10% CO
₂
for up to 8 weeks.