Differentials

Coronavirus disease 2019 (COVID-19)

SIGNS / SYMPTOMS
INVESTIGATIONS
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
INVESTIGATIONS
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
INVESTIGATIONS
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
INVESTIGATIONS
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
INVESTIGATIONS
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
INVESTIGATIONS
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
INVESTIGATIONS
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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