Differentials
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
Community-acquired pneumonia
SIGNS / SYMPTOMS
Signs of lobar or atypical pneumonia including crackles and dyspnea. Generally, shorter duration of symptoms compared with TB. If there is doubt, consider treating for bacterial pneumonia first (without using fluoroquinolones or other antibiotics with significant antituberculous activity) and assess for response.
INVESTIGATIONS
Sputum examination with presence of bacteria other than normal flora.
Lung cancer
SIGNS / SYMPTOMS
TB and lung cancer may coexist; malignancy may erode granulomas. Despite acid-fast bacilli in sputum, if features suggest cancer (e.g., irregular cavities) or lung abnormalities progress in patients on antituberculous treatment, further evaluation for cancer should be pursued.[53]
INVESTIGATIONS
Sputum cytology; CT of the chest; tissue biopsy.
Nontuberculous mycobacteria
SIGNS / SYMPTOMS
Nontuberculous mycobacteria, present in soil and water, such as Mycobacterium avium complex and Mycobacterium kansasii may present as non-cavitary or cavitary lung disease. Patient risk factors for TB may point to most likely diagnosis.
INVESTIGATIONS
If sputum acid-fast bacilli culture is positive, DNA probe may be used for species identification. Similarly a nucleic acid amplification test that is negative for TB on a smear-positive sputum (95% sensitivity) makes Mycobacterium tuberculosis less likely after polymerase chain reaction inhibitors have been excluded. Nontuberculous mycobacteria is more common in patients with underlying lung disease.
Fungal infection
SIGNS / SYMPTOMS
Potential fungi include histoplasmosis, coccidioidomycosis, and blastomycosis. Travel history may help narrow the differential diagnosis.
INVESTIGATIONS
Sputum culture and serum antibody titers positive for fungal infection and negative for Mycobacterium tuberculosis.
Sarcoidosis
SIGNS / SYMPTOMS
Other features of sarcoidosis, such as intrathoracic lymphadenopathy and arthralgias, may be present.
INVESTIGATIONS
Sputum culture will be negative in sarcoidosis.
Nocardiosis
SIGNS / SYMPTOMS
Clinical differentiation is difficult. In immunocompetent patients, cavities are more frequently related to tuberculosis. In immunocompromised patients, particularly patients with AIDS, cavities are less frequently associated with tuberculosis and very common in nocardiosis.[56]
INVESTIGATIONS
Mycobacterium can be differentiated from Nocardia in clinical samples, because mycobacteria do not stain well with Gram stain and modified acid-fast stain. They are also microscopically different from Nocardia.[57]
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