Utilization and Performance of a Laboratory Developed Nucleic Acid Amplification Test for the Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in a Low Prevalence Area: A 14 Year Study

Abstract

BackgroundTuberculosis (TB) is a significant global health problem. Nucleic acid amplification tests (NAATs) are valuable in reducing delays to initiation of therapy and infection control protocols. A retrospective study was performed to assess the utilization and performance of a laboratory developed Mycobacterium tuberculosis complex (MTBC) PCR assay (TBPCR) for diagnosis of pulmonary (PTB) and extrapulmonary (EPTB) tuberculosis.MethodsStudy site was a 4 hospital system in suburban Chicago. All culture confirmed TB specimens with complete laboratory data from January 2002 to December 2016 were included. Patient records were accessed using an electronic data warehouse, following approval from Institutional Review Board. Standard microbiology procedures were followed for smear and culture of MTBC. A lab-developed real time PCR targeting a 123 bp region of the IS6110 insertion sequence of MTBC was performed on smear positive specimens or if ordered by physician. Clinical and laboratory data was compared with TBPCR results for all culture confirmed cases.ResultsThere were 151 culture positive patients and 2186 TBPCR performed. Median age of patients at diagnosis was 49 years (IQR 33–66), 74 (49%) were female and 14 were on immunosupressive therapy. The mean number of samples tested per patient was 2. Of culture positive specimens, 59% were from a respiratory source and 3 were MDR; ordering of TBPCR was higher in specimens from PTB source (58.4%) as compared with EPTB source (37%). Combined sensitivity of the TBPCR on all specimen types was 86.6% (95% CI 76.3–93.1); 90.3% for PTB specimens alone (95% CI 78.2–96.4). Specificity was 100% (95% CI 99.5–100), PPV 100% (95% CI 90.5–100%) and NPV 99.5% (95% CI 98.8–99.8%), and were similar for all specimen types. Sensitivity of TBPCR was 97% in smear positive and 79% in smear negative PTB specimens. The median time to culture positivity was 7 days longer in specimens that were TBPCR negative compared with those that were positive (P = 0.14, NS), however, TBPCR shortened time to diagnosis by 13 days.ConclusionWe found TBPCR to be underutilized in both PTB and EPTB although it was found to be a rapid and reliable method for early diagnosis. Education regarding utility of NAATs could be useful in low burden areas where paucibacillary disease is more common, especially in EPTB.Disclosures All authors: No reported disclosures.