Letters To The Editor
In high-prevalence countries, the diagnosis may be different.
Catherine Anne Curley, MD
Division Director, Hospital Medicine, Department of Medicine, MetroHealth Medical Center, Cleveland, OH; Medical Director, Cuyahoga County TB Program; Associate Professor of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH
Address: Catherine Anne Curley, MD, Department of Medicine, MetroHealth Medical Center, 2500 Metrohealth Drive, Cleveland, OH 44109; e-mail: Ccurley@metrohealth.org
EVALUATION OF SUSPECTED TUBERCULOSIS
In general, a patient with suspected tuberculosis can be evaluated as an outpatient. However, there are a number of reasons to consider hospital admission for the initial workup and for starting treatment:
Patients with suspected active pulmonary tuberculosis should be placed in airborne infection isolation (also called respiratory or negative-pressure isolation). The purpose of this isolation method is to prevent transmission to other patients and to health care workers. Isolation and other environmental and personal controls such as ultraviolet light and N-95 masks are highly effective in preventing transmission.9
However, there are disadvantages to placing patients in isolation. Only 1 out of every 10 to 25 patients isolated actually has tuberculosis,10 and patients typically remain in isolation for 4 to 7 days. Therefore, unnecessary isolation can delay diagnostic testing for other illnesses and may waste already-limited health care resources. In addition, isolation carries the potential for decreased contact with providers.
One of the problems with airborne infection isolation is determining when it is safe to discontinue it, especially when the diagnosis of tuberculosis appears less likely.
Traditionally, we have used the requirement of three negative sputum smears for acid-fast bacilli on 3 separate days, as well as low clinical suspicion for tuberculosis. The use of three sputum smears for acid-fast bacilli is based on studies11,12 in populations that have a high prevalence of tuberculosis. These studies found that after three sputum smears were obtained, additional sputum smears were unlikely to improve the sensitivity of the test. The studies focused on maximizing the sensitivity of the test and detecting all potential cases.11,12 However, in US hospitals today, the focus is on rapidly excluding the diagnosis of tuberculosis to minimize hospital length of stay and to allow evaluation for alternative diagnoses.
A problem with isolation is when to discontinue it
Several studies have called into question the need for three negative sputum smears to discontinue isolation.13–16 Mathew et al13 found a negative predictive value of 97.8% with a single negative sputum smear for the diagnosis of culture-positive tuberculosis. Each additional sputum increased the negative predictive value by only 0.2%. The authors suggested that one or two negative sputum smears are sufficient to discontinue isolation in a region that has a low incidence of tuberculosis. These studies were all performed at single institutions in the United States and Canada, and their findings are relevant to regions that have a low incidence of tuberculosis.
The CDC continues to recommend that airborne infection isolation be discontinued only when either another diagnosis is made that explains the clinical syndrome or the patient has three negative acid-fast bacilli sputum smear results or two negative acid-fast bacilli smears and one negative nucleic amplification test (discussed below). These should be done at least 8 hours apart and should include at least one early-morning specimen.9
In a minority of cases, empiric treatment for tuberculosis is indicated despite negative sputum smears, based on clinical and radiographic manifestations. Patients receiving empiric treatment for pulmonary tuberculosis should remain in airborne infection isolation during the initiation of treatment (if a hospital stay is required) until cleared by a specialist in infectious disease or tuberculosis.
Additional tests for tuberculosis that are performed on clinical specimens have been available for the past 10 years.
Nucleic acid amplification can detect tuberculosis directly in sputum, bronchoscopy specimens, or other clinical specimens. It is available at reference laboratories, large hospitals, and many state laboratories, often with 24-hour turnaround. Both commercial and in-house tests are performed. The CDC considers nucleic acid amplification to be very helpful and underutilized. An important limitation of the test is that it performs best in smear-positive specimens, with a sensitivity of 96.8%, whereas its sensitivity in smear-negative samples is only 73%.17 For this reason, nucleic acid amplification is still not widely used in US hospitals.
The CDC recommends nucleic acid amplification testing in all patients in whom the diagnosis of tuberculosis is being considered but is not yet confirmed.18Table 1 outlines the use of nucleic acid amplification in several clinical situations. Use and interpretation of this test in suspected tuberculosis often requires consultation with clinicians who are experienced in the diagnosis of this disease.
Patients who have never tested positive for tuberculosis on a skin test should be tested by tuberculin skin testing or with an interferon-gamma-release assay during an evaluation for suspected pulmonary tuberculosis. The interferon-gamma-release assays available in the United States are the QuantiFERON-TB Gold In-Tube test and the T-Spot TB test. Most larger hospitals have one of the two available.
Of note: up to 25% of patients with active tuberculosis can have a negative skin test or interferon-gamma-release assay at the time of initial diagnosis, the number being higher in those who are immunosuppressed.
An interferon-gamma-release assay, which is performed on the patient’s serum, is preferred in those who have previously received the BCG vaccine, as there is no cross-reactivity between the vaccine and the antigens in the assay. In patients with active tuberculosis, the interferon-gamma-release assay does not perform any better than the skin test, so the choice of test should be determined by availability. Table 2 compares the characteristics of tuberculin skin testing and the interferon- gamma-release assay.19
In evaluating for active tuberculosis, a positive skin test or interferon-gamma-release assay can be helpful in increasing the likelihood of tuberculosis, but a negative result does not exclude active tuberculosis.
Additional imaging is often performed in patients with suspected pulmonary tuberculosis, or before the diagnosis of tuberculosis is considered. Computed tomography provides more detailed images of pulmonary infiltrates and may reveal more extensive disease than plain radiography, but the images are not diagnostic. Ultimately, sputum and sometimes tissue are required. Far too often, a sputum smear for acid-fast bacilli is the last test to be performed, after both computed tomography and bronchoscopy have been done. In addition, in order to undergo computed tomography, the patient must be removed from airborne infection isolation.
The decision to perform computed tomography must be individualized to the patient and to the clinical situation. It is certainly not a necessary test for the diagnosis of pulmonary tuberculosis.
Tuberculosis is a reportable illness in the United States. Although each state varies in its specific requirements, if tuberculosis treatment is being initiated or tuberculosis is strongly suspected, a report should be made to the local public health authority for tuberculosis within 24 hours.
This report allows for outreach services to be offered to the patient, often including directly observed therapy in which doses of antituberculosis treatment are provided and observed to ensure completion of treatment. In addition, public health authorities bear the responsibility for contact investigation to determine if transmission of tuberculosis has occurred in the community.
In high-prevalence countries, the diagnosis may be different.
Purified protein derivative testing and the interferon-gamma-release assay are more useful in low-prevalence countries like the United States.