Pulmonary tuberculosis (TB) persists as a great public health problem in Korea. Increases in the overall age of the population and the rise of drug-resistant TB have reinforced the need for rapid diagnostic improvements and new modalities to detect TB and drug-resistant TB, as well as to improve TB control. Standard guidelines and recent advances for diagnosing pulmonary TB are summarized in this article. An early and accurate diagnosis of pulmonary TB should be established using chest X-ray, sputum microscopy, culture in both liquid and solid media, and nucleic acid amplification. Chest computed tomography, histopathological examination of biopsy samples, and new molecular diagnostic tests can be used for earlier and improved diagnoses, especially in patients with smear-negative pulmonary TB or clinically-diagnosed TB and drug-resistant TB.
Tuberculosis (TB) is a global health concern for both developing and developed countries and has recently become more complex due to persistence in aging populations and the rise of drug-resistant strains, even in Korea
In this article, recent advances that allow better and earlier diagnosis of active pulmonary TB are summarized and diagnostic algorithms in clinical practice are recommended, focusing on the intermediate burden setting in Korea, based on updated literature reviews and standard guidelines
Anyone with a cough that lasts for two weeks or more or with unexplained chronic fever and/or weight loss should be evaluated for TB
Although chest X-ray is the primary diagnostic tool for evaluating pulmonary TB, chest computed tomography (CT) is generally required to detect fine lesions that can be overlooked on chest X-ray, to define equivocal lesions, or to evaluate complications
For pulmonary TB, sputum is the most critical sample for laboratory testing. Direct sputum smear microscopy is the most widely used method for diagnosing pulmonary TB and is available in most primary health-care laboratories at the health-center level
Conventional light microscopy of Ziehl-Neelsen-stained smears prepared directly from sputum specimens is the most widely available test for diagnosing TB in resource-limited settings. Ziehl-Neelsen microscopy is highly specific, but its sensitivity is variable (20%-80%). Conventional fluorescence microscopy is more sensitive (10%) than the Ziehl-Neelsen and takes less time, but it is limited by the high cost of mercury vapor light sources, the need for regular maintenance, and the dark room requirement
Laboratory diagnosis of TB relies on direct microscopic examination of sputum specimens. However, the technique, although specific, has low and variable sensitivity and cannot identify drug-resistant strains. Clinicians have been advised to obtain culture confirmation of TB whenever possible. This not only confirms the diagnosis, but also obtains material for crucial drug susceptibility testing (DST)
Nucleic acid amplification (NAA) tests are a reliable way to increase the specificity of diagnosis, but the sensitivity is too poor to rule out disease, especially in smear-negative (paucibacillary) disease where clinical diagnosis is equivocal and where the clinical need is greatest
The United States' Centers for Disease Control and Prevention (CDC) recommends that NAA testing should be performed on at least one respiratory specimen using a Food and Drug Administration (FDA)-approved test
Conventional methods for mycobacteriological culture, identification of an
LPA technology is performed in the following steps, including extracting DNA from mycobacterial isolates or directly from clinical specimens, polymerase chain reaction (PCR) amplification of the resistance-determining region of the gene, hybridization of labeled PCR products with oligonucleotide probes immobilized on a strip, and colorimetric development that allows for lines to be seen where the probes are located. According to systematic reviews and meta-analyses to evaluate assay performance, results that compared conventional DST methods showed that LPA are highly sensitive (≥97%) and specific (≥99%) for detecting rifampicin resistance, alone or in combination with isoniazid (sensitivity ≥90%; specificity ≥99%), in
The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA; hereafter referred to as Xpert MTB/RIF) is a novel, rapid, automated, and cartridge-based NAA test that can detect TB along with rifampicin resistance directly from sputum within 2 hours of collection
In a recent study of the performance of Xpert MTB/RIF, among the 561 culture-positive patients (561/1730), a single, direct Xpert MTB/RIF test identified 98.2% (551 out of 561) of the sputum smear-positive TB cases and 72.5% (124 out of 171) of those with sputum smear-negative TB. The test was specific in 604 of 609 patients (99.2%) not affected by TB. A second Xpert MTB/RIF test among patients with sputum smear-negative, culture-positive TB increased detection sensitivity by 12.6% and a third by 5.1%, to reach 90.2%. When compared to phenotypic DST, the Xpert MTB/RIF assay correctly identified 97.6% (200 out of 205) of patients harboring rifampicin-resistant strains and 98.1% (504 out of 514) of those with rifampicin-susceptible strains
People suspected of having TB should be referred for medical evaluation. A posterior-anterior chest X-ray should be taken, and a chest X-ray that appears suggestive of TB should be followed by further diagnostic investigation. Multiple sputum samples (at least two, possibly three samples) that allow at least, first one front-loaded sputum specimen should, if possible, be sent for TB microscopy and cultured for suspected respiratory TB before starting treatment
NAA tests can rapidly confirm TB diagnosis and distinguish
Current TB diagnostics are still suboptimal in performance, especially for smear-negative TB. Because TB can present with many different symptoms, the first obstacle in diagnosing smear-negative TB is discerning the varied clinical presentations, to determine which conditions are highly suspicious and should be included in the differential diagnosis. A diagnostic approach to an AFB smear-negative patient with possible TB includes, where available, a detailed medical history and clinical examination as well as radiological, microbiological, molecular, and histological investigations
NAA testing is recommended to perform the initial diagnosis of patients that are suspected to have TB, even in smear-negative patients. If the NAA result is positive and the AFB smear result is negative, the clinician must consider the case as TB positive and begin anti-TB treatment while awaiting culture results
Diagnosing TB worldwide still consists of methods that are intended to isolate the pathogen, which is a major limitation when the mycobacterial load is low or the site of infection is not easily accessible. For these reasons, diagnosis of smear-negative TB is often delayed, and such a diagnosis is often made based on the clinical response to empiric anti-TB treatment without microbiological confirmation
Clinicians who manage patients with suspected TB should ensure that their diagnostic practices align with the guidelines for TB, and use sputum smear microscopy and culture to investigate adult patients with suspected active TB
No potential conflict of interest relevant to this article was reported.