A Test for More Accurate Diagnosis of Pulmonary Tuberculosis Lin Sun, PhD,a,b Xue Qi, MS,a,b Fang Liu, MS,b,c Xirong Wu, PhD,b,d Qingqin Yin, PhD,b,d Yan Guo, MS,b,d Baoping Xu, PhD,b,d Anxia Jiao, PhD,b,c Yajie Guo, MD,a,b Weiwei Jiao, PhD,a,b Chen Shen, PhD,a,b Jing Xiao, PhD,a,b Adong Shen, MSa,b OBJECTIVES: Xpert Mycobacterium tuberculosis and rifampicin (MTB/RIF) Ultra assay has abstract increasingly been used in adult tuberculosis diagnosis, but data relating to its diagnostic accuracy in children are lacking. Because a qualified sputum specimen is difficult to obtain in children, this study evaluated the diagnostic value of Ultra in childhood tuberculosis using bronchoalveolar lavage fluid. METHODS: The accuracy of Ultra was calculated by using bacteriologic results and clinical evidence as reference standards. Concordance between Ultra and Xpert MTB/RIF assays was assessed by using к coefficients. RESULTS: In total, 93 children with pulmonary tuberculosis and 128 children with respiratory tract infections were enrolled. The sensitivity of Ultra, in all pulmonary tuberculosis cases and in bacteriologically confirmed tuberculosis cases, was 70% and 91%, respectively. Ultra could detect Mycobacterium tuberculosis in 58% of cases with negative culture or acid-fast–staining results. The specificity of Ultra was 98%. There was no significant difference in sensitivity between samples with a volume #1 and .1 mL (66% vs 73%; P = .50; odds ratio [OR] = 0.71). Among 164 children for which Ultra and Xpert were simultaneously performed, the sensitivity was 80% and 67%, respectively, indicating good agreement (к = 0.84). An additional 6 children were identified as Ultra-positive but Xpert-negative. The positive rate decreased from 93% to 63% after 1 month (P = .01; OR = 0.12) and to 71% after 2 months (P = .03; OR = 0.18) of antituberculosis treatment. CONCLUSIONS: Ultra using bronchoalveolar lavage fluid has good sensitivity compared with bacteriologic tests and adds clinical value by assisting the rapid and accurate diagnosis of pulmonary tuberculosis in children. aBejing Key Laboratory of Pediatric Respiratory Infectious Diseases, Beijing Pediatric Research Institute, Beijing, WHAT’S KNOWN ON THIS SUBJECT: Early diagnosis of China; bNational Clinical Research Center for Respiratory Disease, National Key Discipline of Pediatrics, Key childhood tuberculosis can reduce child mortality, but Laboratory of Major Diseases in Children, and National Center for Children’s Health, Ministry of Education of the it is often hindered by a lack of bacteriologic evidence. ’ ’ Peoples Republic of China, Beijing Childrens Hospital, Capital Medical University, Beijing, China; and We evaluated the diagnostic value of Xpert MTB/RIF cInterventional Pulmonary Department and dDepartment of Respiratory Medicine, Beijing Children’s Hospital, Beijing, China Ultra in childhood tuberculosis using bronchoalveolar lavage fluid (BALF). Dr Sun and Mr Shen conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript; Mr Qi and Dr Guo collected data and performed the tests; Ms WHAT THIS STUDY ADDS: Xpert MTB/RIF Ultra using Liu, Ms Guo, and Drs Wu, Yin, Xu, and Jiao enrolled the subjects and collected the samples; Drs Jiao, BALF offers higher sensitivity than bacteriologic tests. Shen, and Xiao analyzed the data; and all authors approved the final manuscript as submitted and In children with tuberculosis, Xpert MTB/RIF Ultra agree to be accountable for all aspects of the work. using BALF provides early and accurate etiologic DOI: https://doi.org/10.1542/peds.2019-0262 results. A comparison between Xpert MTB/RIF and Xpert MTB/RIF Ultra was performed in this study. Accepted for publication Aug 13, 2019 To cite: Sun L, Qi X, Liu F, et al. A Test for More Accurate Diagnosis of Pulmonary Tuberculosis. Pediatrics. 2019; 144(5):e20190262 Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 144, number 5, November 2019:e20190262 ARTICLE Children carry nearly 10% of the a conditional test for children appears to be a good alternative global tuberculosis disease burden suspected of having tuberculosis.4,5 sample for children who have and account for 15% of the total Nowadays, the Xpert MTB/RIF Ultra difficulty producing sputum. The deaths.1 The World Health assay has been developed as a next- sensitivity of MTB culture from BALF Organization (WHO) estimated that generation assay to overcome these is significantly higher than that from there were 99 000 new pediatric limitations. To improve sensitivity for sputum samples (39.2% vs 35.3%) in tuberculosis cases in China in 2017, the detection of MTB, another 2 adult patients with tuberculosis.12 but only 10% of them were notified multicopy amplification targets Positive rates obtained from smears and reported.1 Precise data on the (IS6110 and IS1081) and a larger DNA and MTB culture by using gastric percentage of pediatric tuberculosis reaction chamber are used in Ultra. aspirates or BALF are similar and are cases confirmed microbiologically are Furthermore, melting higher than those obtained by using not reported by many countries.1 The temperature–based analysis replaces sputum samples from children with large number of missing cases real-time polymerase chain reaction suspected complicated intrathoracic suggests poorer access to diagnosis to improve the accuracy of rifampicin tuberculosis.13 and treatment in childhood resistance detection.6 BALF shows a superior diagnostic tuberculosis than in adult Although Ultra has gradually been yield in patients with smear-negative tuberculosis. Timely and accurate introduced for diagnosing or sputum-scarce pulmonary diagnosis will be crucial to achieve tuberculosis in adults,7,8 data are still tuberculosis. However, there are little the global aim of minimizing lacking regarding its diagnostic data about its diagnostic value in childhood tuberculosis. accuracy in children. A multicenter pulmonary tuberculosis in children. However, management of childhood comparative study in children For this study, we enrolled children tuberculosis is hampered by demonstrated the higher sensitivity of with indications for fiber-optic difficulties in attaining an etiologic Ultra over Xpert using sputum bronchoscopy and had the following diagnosis because of the challenge of samples but slightly reduced aims: (1) evaluate the diagnostic obtaining samples and low bacterial specificity compared with Xpert in value of Ultra in childhood loads. In general, the diagnosis of detecting pulmonary tuberculosis.9 tuberculosis by using BALF, (2) pediatric tuberculosis in the clinic Most current research uses sputum compare the accuracy of Ultra with mainly depends on contact history, specimens or gastric aspirates to that of Xpert, and (3) confirm the clinical symptoms, and chest diagnose pulmonary tuberculosis in value of Ultra in monitoring radiography results.2 On the basis of children.10,11 However, qualified treatment effectiveness. The results their higher sensitivity, molecular sputum specimens are difficult to presented provide data for informed tests have increasingly been used to obtain in children, especially those of management of childhood confirm the presence of younger age. tuberculosis. Mycobacterium tuberculosis in Bronchoalveolar lavage is an effective patients with active tuberculosis3 as tool to control severe infection. Fiber- METHODS a promising alternative to traditional optic bronchoscopy is also an diagnostic methods. important intervention in children Study Population and Samples The Xpert Mycobacterium tuberculosis who present with dyspnea, This retrospective study was and rifampicin (MTB/RIF) assay is an obstructive pneumonia, pulmonary performed at the Beijing Children’s automated molecular test based on atelectasis, or localized emphysema. Hospital affiliated with Capital seminested real-time polymerase It is sometimes difficult to confirm Medical University. Children were chain reaction and molecular beacon whether pulmonary atelectasis is due defined as those ,15 years old technology targeting the rifampicin- to extrinsic compression on according to the WHO definition5 and resistance–determining region of the a bronchus from regional were enrolled in the study if (1) they rpoB gene.4 Rifampicin resistance is lymphadenopathy or from caseous had suspected symptoms of viewed as an indicator of multidrug- necrosis in an airway by using tuberculosis; (2) they had the resistant tuberculosis because most standard pulmonary imaging. In indications to undergo fiber-optic patients with rifampicin resistance children who present with these signs bronchoscopy, including those who also have isoniazid resistance. The or symptoms in addition to presented with dyspnea, obstructive WHO officially endorsed this assay as pulmonary tuberculosis, fiber-optic pneumonia, or localized emphysema, a primary diagnostic test for children bronchoscopy can be used to confirm and those needing further suspected of having multidrug- the reasons for pulmonary atelectasis microbiologic confirmation because resistant tuberculosis or HIV- and improve ventilation.7 As such, of atypical imaging changes, no associated tuberculosis and as bronchoalveolar lavage fluid (BALF) contact history with an index patient Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 SUN et al with confirmed tuberculosis, or described earlier.15 A 1:1 RESULTS negative microbiologic results by volume of sample reagent was using sputum or gastric aspirates;