Abstract
BackgroundHIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. We therefore assessed the diagnostic performance of a novel assay that directly quantitates serum levels of the Mycobacterium tuberculosis (Mtb) virulence factor 10-kDa culture filtrate protein (CFP-10) to overcome limitations associated with detecting Mtb bacilli in sputum or tissue biopsies.MethodsThis study analyzed HIV-positive adults enrolled in a large, population-based TB screening and surveillance project, the Houston Tuberculosis Initiative, between October 1995 and September 2004, and assigned case designations using standardized criteria. Serum samples were trypsin-digested and immunoprecipitated for an Mtb-specific peptide of CFP-10 that was quantified by liquid chromatography-mass spectrometry for rapid and sensitive TB diagnosis.ResultsAmong the 1053 enrolled patients, 110 met all inclusion criteria; they included 60 tuberculosis cases (12 culture-negative TB), including 9 relapse TB cases, and 50 non-TB controls, including 15 cases with history of TB. Serum CFP-10 levels diagnosed 89.6% (77.3–96.5) and 66.7% (34.9–90.1) of culture-positive and culture-negative TB cases, respectively, and exhibited 88% (75.7–95.5) diagnostic specificity in all non-TB controls. Serum antigen detection and culture, respectively, identified 85% (73.4–92.9) and 80.0% (67.3–88.8) of all 60 TB cases.ConclusionsQuantitation of the Mtb virulence factor CFP-10 in serum samples of HIV-infected subjects diagnosed active TB cases with high sensitivity and specificity and detected cases missed by the gold standard of Mtb culture. These results suggest that serum CFP-10 quantitation holds great promise for the rapid diagnosis of suspected TB cases in patients who are HIV-infected.
Highlights
HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates
Delayed or missed TB diagnosis is an important cause of excess mortality in HIVaffected patients, for cases with smearnegative pulmonary and extrapulmonary TB (PTB and Extrapulmonary tuberculosis (EPTB)) [4], which are found with increased incidence in this group, and autopsy studies reveal that there is a high proportion of undiagnosed TB in this population [5, 6]
Survey of the Houston Tuberculosis Initiative (HTI) records identified 1053 eligible HIVpositive HTI subjects, but 701 lacked blood samples and 242 were lost to follow-up, yielding a study population of 110 subjects (Fig. 1). This group contained 60 TB cases confirmed by mycobacterial culture or clinical findings (54.5%), including 9 relapse TB cases; 50 nonTB controls, including 15 cases with history of previously TB, who remained TB-negative at analysis; and 35 patients without evidence of TB disease and no TB history (31.8%)
Summary
HIV-associated immune defects inhibit tuberculosis (TB) diagnosis, promote development of extrapulmonary TB and paucibacillary pulmonary TB cases with atypical radiographic features, and increase TB relapse rates. Delayed or missed TB diagnosis is an important cause of excess mortality in HIVaffected patients, for cases with smearnegative pulmonary and extrapulmonary TB (PTB and EPTB) [4], which are found with increased incidence in this group, and autopsy studies reveal that there is a high proportion of undiagnosed TB in this population [5, 6]. In regions of high TB incidence, HIV-infected individuals exhibit reinfection rates of 30–50% Further complicating this situation, frontline TB diagnostics, including acid-fast bacilli (AFB) smear, mycobacterial culture, and Xpert Mycobacterium tuberculosis (MTB)/resistance to rifampin (RIF) assays all exhibit reduced sensitivity with paucibacillary TB samples (Mtb culture-negative or smear-negative), which are frequently associated with HIV-positive TB cases [9, 10]. There is an urgent unmet need for rapid, quantitative, non-sputum-based biomarker tests that can accurately diagnose new and relapse TB cases in clinically challenging patient populations, including HIVinfected subjects [11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
