Summary. The symptoms of pulmonary TB include cough, chest pain, and hemoptysis; the specific symptoms of extrapulmonary TB depend on the site of disease. Systemic symptoms consistent with TB also include fever, chills, night sweats, easy fatigability, loss of appetite, and weight loss. TB should be considered in persons who have these symptoms. Persons suspected of having TB should be referred for a complete medical evaluation, which should include a medical history, a physical examination, a Mantoux tuberculin skin test, a chest radiograph, and any appropriate bacteriologic or histologic examinations. A positive bacteriologic culture for M. tuberculosis confirms the diagnosis of TB. However, if TB disease is not ruled out, treatment should be initiated; clinicians should not wait for bacteriologic culture results before starting therapy.
A complete medical evaluation for TB should include a medical history, a physical examination, a Mantoux tuberculin skin test, a chest radiograph, and any appropriate bacteriologic or histologic examinations.
The symptoms of pulmonary TB include a productive, prolonged cough (duration of more than 3 weeks), chest pain, and hemoptysis. Systemic symptoms of TB include fever, chills, night sweats, easy fatigability, loss of appetite, and weight loss. TB should be considered in persons who have these symptoms.
Approximately 15% of TB cases are extrapulmonary. The symptoms of extrapulmonary TB depend on the site affected. TB of the spine may cause pain in the back; TB of the kidney may cause blood in the urine. Extrapulmonary TB should be considered in the differential diagnosis of ill persons who have systemic symptoms and who are at high risk for TB.
It is important to ask persons suspected of having TB about their history of exposure to TB and history of TB disease or infection. Clinicians may also contact the local health department for information about whether a patient has received TB treatment. If a regimen was inadequate or if the patient did not adhere to therapy, TB may recur and may be drug resistant.
It is also important to consider demographic factors (country of origin, age, ethnic or racial group, occupation) that may increase the patient's risk for exposure to TB.
In addition, clinicians should determine whether the patient has medical conditions, especially HIV infection, that increase the risk for TB disease (see Transmission and Pathogenesis). Patients who have risk factors for HIV infection but who do not know their current HIV status should be referred for HIV counseling and testing.
A physical examination is an essential part of the evaluation of any patient. It cannot be used to confirm or rule out TB, but it can provide valuable information about the patient's overall condition and other factors that may affect how TB is treated.
The tuberculin skin test is useful for:
The preferred method of tuberculin testing is the Mantoux tuberculin skin test. The administration of the Mantoux test and interpretation of its results are discussed in Screening for TB Disease and Infection.
Some persons may have a false-negative reaction to the tuberculin skin test if they are tested too soon after being exposed to TB. In general, it takes 2 to 10 weeks after infection for a person to develop an immune response to tuberculin. Persons who have recently been around someone who has TB and who have a negative reaction to the tuberculin skin test should be retested 10 weeks after the last time they were exposed to infectious TB.
Children younger than 6 months of age may have a false-negative reaction to the tuberculin skin test because their immune systems are not yet fully developed.
As noted in Screening for TB Disease and Infection, a negative reaction to the tuberculin test does not exclude the diagnosis of TB, especially for patients with severe illness or HIV infection.
A posterior-anterior view of the chest is the standard radiograph needed for the detection and description of chest abnormalities. In some instances, other views (e.g., lateral, lordotic) or additional studies (e.g., CT scans) may be necessary.
In pulmonary TB, chest radiograph abnormalities often occur in the apical and posterior segments of the upper lobe or in the superior segments of the lower lobe. However, lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation, especially in HIV-infected and other immunosuppressed persons.
In HIV-infected persons with pulmonary TB, the chest radiograph may have an unusual appearance. For example, TB may cause infiltrates without cavities in any lung zone, or it may cause mediastinal or hilar lymphadenopathy. In HIV-infected persons, almost any abnormality on a chest radiograph may indicate TB. In fact, the radiograph of an HIV-infected person with TB disease may even appear entirely normal.
Abnormalities on chest radiographs may be suggestive of, but are never diagnostic of, TB. However, chest radiographs may be used to rule out the possibility of pulmonary TB in a person who has a positive reaction to the tuberculin skin test and no symptoms of disease.
An isolated granuloma on a chest radiograph is not considered a fibrotic lesion compatible with previous TB. Clinicians may wish to consult with a radiologist or clinician expert in the interpretation of such radiographs to become more familiar with this categorization.
Persons suspected of having pulmonary or laryngeal TB should have at least three sputum specimens examined by smear and culture. A health care worker should coach and directly supervise the patient at least the first time sputum is collected. It is best to obtain a series of three early morning specimens collected on different days.
Patients should be properly instructed how to produce a good specimen. They should be informed that sputum is the material brought up from the lungs and that mucus from the nose and throat and saliva are not good specimens. They should be instructed to follow these steps for producing a sputum specimen.
Coaching patients individually on how to expectorate can facilitate sputum collection. Unsupervised patients are seldom successful in providing an adequate specimen, especially the first time. The amount of coaching required on later visits will depend on individual patient needs.
For patients unable to cough up sputum, aerosol induction can be used to stimulate the production of sputum. Patients should be instructed to take several normal breaths of aerosol mist, inhale deeply, cough hard, and then expectorate into the specimen container. They should be given time--15 minutes is usually sufficient--to produce sputum, which is usually brought up by a deep cough. Because induced sputum is very watery and resembles saliva, it should be labeled "induced" to ensure that the laboratory staff do not discard it.
Bronchoscopy can be done if the patient cannot cough up sputum and there is reasonable suspicion of TB. Bronchial washings, brushings, and biopsy specimens may be obtained, depending on the diagnostic possibilities and findings. Sputum collected after bronchoscopy may also be useful for a diagnosis.
Gastric aspiration can also be used to obtain swallowed sputum specimens, but it is uncomfortable and invasive. It is, however, the best way to obtain specimens from infants and some young children who cannot produce sputum even with aerosol inhalation.
During specimen collection, patients produce an aerosol that may be hazardous to health care workers or other patients in close proximity. For this reason, precautionary measures for infection control must be followed during sputum induction, bronchoscopy, and other common diagnostic procedures (see Infection Control).
Because TB can occur in almost any anatomical site, a variety of clinical specimens other than sputum (e.g., urine, cerebrospinal fluid, pleural fluid, pus, or biopsy specimens) may be submitted for examination when nonpulmonary mycobacterial disease is suspected. Tissue specimens for the culture of M. tuberculosis should be placed in a saline solution, not in formalin, and should be delivered to the laboratory promptly.
Detection of acid-fast bacilli (AFB) in stained smears examined microscopically may provide the first bacteriologic clue of TB. Fluorescent staining with Auramine O is the preferred staining method because it is faster and more sensitive than the traditional methods in which Ziehl-Neelsen or Kinyoun stains are used. Smear examination is an easy and quick procedure; results should be available within 24 hours of specimen collection. However, smear examination permits only the presumptive diagnosis of TB because the AFB on a smear may be mycobacteria other than M. tuberculosis. Furthermore, many TB patients have negative AFB smears.
A positive culture for M. tuberculosis confirms a diagnosis of TB; however, TB may also be diagnosed on the basis of clinical signs and symptoms in the absence of a positive culture. Culture examinations should be done on all specimens, regardless of AFB smear results. When a liquid medium is inoculated for growth (using the BACTEC radiometric system) and rapid methods are used for species identification, culture results should be available within 10 to 14 days of specimen collection. If a solid medium and conventional biochemical tests are used, the isolation of the organism can take 6 to 12 weeks.
Nucleic acid probes specific for the genus Mycobacterium, the M. tuberculosis complex, M. avium, and M. intracellulare provide a rapid method of species identification. Once the mycobacteria have been grown in culture, nucleic acid probes can identify the species in 2 to 8 hours. High-performance liquid chromatography (HPLC), which detects differences in the spectrum of mycolic acids in the cell wall, is equally rapid. A test inhibition by NAP can identify M. tuberculosis in 3 to 5 days.
Polymerase chain reaction (PCR) techniques are being developed that could be performed directly on sputum or other clinical specimens to diagnose TB disease more quickly. However, until the evaluation of this method is completed, PCR should be considered an experimental technique; it is not available for the routine diagnosis of TB. In the future, this technique may become widely available to clinicians.
Follow-up bacteriologic examinations are important for assessing the patient's infectiousness and response to therapy. At a minimum, specimens should be obtained at monthly intervals until culture conversion to negative.
Laboratories should report positive smears and positive cultures within 24 hours by telephone or fax to the primary health care provider. Follow-up results may be reported by mail. It is the responsibility of the primary health care provider to report promptly all suspected or confirmed cases of TB to the health department so that a contact investigation can be initiated as quickly as possible (see Community TB Control).
For all patients, the initial M. tuberculosis isolate should be tested for drug susceptibility. It is crucial to identify drug resistance as early as possible in order to ensure appropriate treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately or who have positive culture results after 2 months of therapy. Susceptibility results from laboratories should be promptly forwarded to the health department.
The radiometric BACTEC method, which uses liquid media cultures, is faster than conventional methods for determining susceptibility to first-line TB medications. When BACTEC is used, results can be obtained within 5 days of inoculation; conventional methods, which use solid media for growth, can take as long as 21 days after inoculation.
Patients at an increased risk for drug resistance include:
Restriction fragment length polymorphism (RFLP), a method of DNA fingerprinting, can be used to identify specific strains of M. tuberculosis and thus to track TB transmission during outbreaks. The restriction enzymes used in this technique cut DNA at certain sites to produce fragments. These fragments are separated by size to produce a pattern, or "fingerprint," that is specific for each strain. Related isolates show the same pattern.
Further details about the collection and processing of specimens, smear examination and culture, and drug susceptibility testing can be found in the article "Diagnostic Standards and Classification of Tuberculosis" (American Thoracic Society and Centers for Disease Control, Am Rev Respir Dis 1990;142:725-735).