Evaluation of different tuberculosis diagnostic tools for detecting patients in a primary-level clinic in rural China: a real-world retrospective study

doi:10.19982/j.issn.1000-6621.20240409

Abstract

Abstract:

Objective: To evaluate the real-world performance of solid culture, GeneXpert MTB/RIF (Xpert), and Xpert MTB/RIF Ultra (Xpert Ultra) in diagnosing tuberculosis (TB) patients at primary-level health facilities. Methods: Suspected pulmonary TB patients who presented to the Wusheng County Center for Disease Control and Prevention (Wusheng CDC) from July 2018 to January 2024 were included in this study. Initial sputum samples were collected and subjected to smear microscopy, culture, Xpert and Xpert Ultra tests. The sensitivity, specificity, positive predictive value and negative predictive value of solid culture, Xpert and Xpert Ultra were calculated using liquid culture as the reference. Additionally, sensitivity and 95% confidence interval (CI) for diagnosing smear-negative patients were assessed for each method. Results: A total of 2769 individuals participated, with 24.56% (680/2769) being female. Detection rates for smear, solid culture, liquid culture, Xpert, and Xpert Ultra were 10.36% (286/2761), 23.66% (362/1530), 29.31% (730/2491), 28.06% (275/980), and 35.33% (254/719), respectively. Sensitivities of solid culture, Xpert and Xpert Ultra were 84.55% (80.53%-88.03%), 91.19% (86.72%-94.54%) and 96.20% (92.32%-98.46%), while specificities were 99.00% (98.17%-99.52%), 92.62% (90.27%-94.54%) and 86.65% (83.05%-89.73%), respectively. Among the smear-negative culture-positive patients, the sensitivities of solid culture, Xpert and Xpert Ultra were 76.08% (69.71%-81.69%), 83.74% (76.01%-89.78%) and 94.17% (88.35%-97.62%). Among culture-negative Xpert or Xpert Ultra-positive patients, 49.51% (51/103) were taking anti-TB drugs in the previous two weeks or had a history of TB. Of the samples that Xpert Ultra classified as trace, 74.19% (23/31) were true-positives. Conclusion: Liquid culture and rapid molecular tests demonstrate high sensitivity for diagnosing TB in primary-level clinics. Xpert Ultra, in particular, is effective for rapid diagnosis of paucibacillary patients. Expanding the use of liquid culture and Xpert Ultra at primary-level clinics can significantly improve detection rates and contribute to the early diagnosis and treatment of patients.

Key words: Tuberculosis, Laboratories, Diagnosis, Sensitivity and specificity, Retrospective studies

CLC Number:

R521

Qiu Yong, Quan Zhuo, Qu Rong, Tian Fajun, Li Meng, Wang Gengsheng, Wang Ya, Guo Mingcheng, Gao Qian. Evaluation of different tuberculosis diagnostic tools for detecting patients in a primary-level clinic in rural China: a real-world retrospective study[J]. Chinese Journal of Antituberculosis, 2025, 47(2): 181-188. doi: 10.19982/j.issn.1000-6621.20240409

Figures/Tables 4

References 28

[1]	World Health Organization. Global tuberculosis report 2024. Geneva: World Health Organization, 2024.
[2]	Uplekar M, Weil D, Lonnroth K, et al. WHO’s new end TB strategy. Lancet, 2015, 385(9979): 1799-1801. doi:10.1016/S0140-6736(15)60570-0. pmid: 25814376
[3]	郑之国, 孙闪华, 丁北川, 等. 北京市各级结核病防治机构实验室配置及人力资源分析. 中国防痨杂志, 2019, 41(7): 790-794. doi:10.3969/j.issn.1000-6621.2019.07.017.
[4]	刘二勇, 王前, 周林, 等. 我国部分地区病原学检测阴性肺结核诊断质量现状分析. 中国防痨杂志, 2020, 42(9): 916-920. doi:10.3969/j.issn.1000-6621.2020.09.006.
[5]	吴雪琼. 提高结核实验室检验水平促进与临床诊断协调发展. 中国防痨杂志, 2017, 39(12): 1261-1263. doi:10.3969/j.issn.1000-6621.2017.12.001.
[6]	孔宛如, 张浩军, 吴明华, 等. 甘肃省146家医疗机构结核病实验室现状初步调查分析. 结核与肺部疾病杂志, 2023, 4(1): 54-59. doi:10.19983/j.issn.2096-8493.20220143.
[7]	王垚, 林珍丽, 陈新朝, 等. Xpert MTB/RIF Ultra在快速检测结核分枝杆菌和利福平耐药中的应用. 分子诊断与治疗杂志, 2023, 15(5): 871-875. doi:10.3969/j.issn.1674-6929.2023.05.037.
[8]	Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-World Evidence-What Is It and What Can It Tell Us?. N Engl J Med, 2016, 375(23): 2293-2297. doi:10.1056/NEJMsb1609216.
[9]	Jiang Q, Ji L, Qiu Y, et al. A randomised controlled trial of stepwise sputum collection to increase yields of confirmed tuberculosis. Int J Tuberc Lung Dis, 2019, 23(6): 685-691. doi:10.5588/ijtld.18.0524. pmid: 31315700
[10]	Tostmann A, Kik SV, Kalisvaart NA, et al. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Clin Infect Dis, 2008, 47(9): 1135-1142. doi:10.1086/591974. pmid: 18823268
[11]	Yang C, Shen X, Peng Y, et al. Transmission of Mycobacterium tuberculosis in China: a population-based molecular epidemiologic study. Clin Infect Dis, 2015, 61(2): 219-227. doi:10.1093/cid/civ255.
[12]	Sinshaw W, Kebede A, Bitew A, et al. Prevalence of tuberculosis, multidrug resistant tuberculosis and associated risk factors among smear negative presumptive pulmonary tuberculosis patients in Addis Ababa, Ethiopia. BMC Infect Dis, 2019, 19(1): 641. doi:10.1186/s12879-019-4241-7.
[13]	Kwak SH, Choi JS, Lee EH, et al. Characteristics and risk factors associated with missed diagnosis in patients with smear-negative pulmonary tuberculosis. Korean J Intern Med, 2021, 36(Suppl 1): S151-S159. doi:10.3904/kjim.2019.435.
[14]	Battaglioli T, Soto A, Agapito J, et al. Manual liquid culture on simple Middlebrook 7H 9 or MGIT for the diagnosis of smear-negative pulmonary tuberculosis. Trop Med Int Health, 2014, 19(12): 1500-1503. doi:10.1111/tmi.12384. pmid: 25244047
[15]	Zhao P, Yu Q, Zhang Y. Evaluation of a manual identification system for detection of Mycobacterium tuberculosis in a primary tuberculosis laboratory in China. J Int Med Res, 2019, 47(6): 2666-2673. doi:10.1177/0300060519844399.
[16]	Dorman SE, Schumacher SG, Alland D, et al. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis, 2018, 18(1): 76-84. doi:10.1016/S1473-3099(17)30691-6. pmid: 29198911
[17]	Opota O, Zakham F, Mazza-Stalder J, et al. Added Value of Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting. J Clin Microbiol, 2019, 57(2): e01717-18. doi:10.1128/JCM.01717-18.
[18]	Wang G, Wang S, Jiang G, et al. Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: A prospective cohort study. J Infect, 2019, 78(4): 311-316. doi:10.1016/j.jinf.2019.02.010. pmid: 30796951
[19]	Mansfield M, McLaughlin AM, Roycroft E, et al. Diagnostic Performance of Xpert MTB/RIF Ultra Compared with Predecessor Test, Xpert MTB/RIF, in a Low TB Incidence Setting: a Retrospective Service Evaluation. Microbiol Spectr, 2022, 10(3): e0234521. doi:10.1128/spectrum.02345-21.
[20]	Wang G, Huang M, Jing H, et al. The Practical Value of Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis in a High Tuberculosis Burden Setting: a Prospective Multicenter Diagnostic Accuracy Study. Microbiol Spectr, 2022, 10(4): e0094922. doi:10.1128/spectrum.00949-22.
[21]	Li M, Qiu Y, Guo M, et al. Comparison of Xpert MTB/RIF Ultra with Xpert MTB/RIF for the detection of Mycobacterium tuberculosis and rifampicin resistance in a primary-level clinic in rural China. Tuberculosis (Edinb), 2023, 142: 102397. doi:10.1016/j.tube.2023.102397.
[22]	Dowling WB, Whitelaw A, Nel P. Tracing TB: Are there predictors for active TB disease in patients with Xpert Ultra trace results? Int J Infect Dis, 2022, 114: 115-123. doi:10.1016/j.ijid.2021.10.056.
[23]	Mazzola E, Monte PD, Piersimoni C, et al. Multicenter evaluation of xpert MTB/RIF ultra tests reporting detection of “Trace” of Mycobacterium tuberculosis DNA. Int J Mycobacteriol, 2021, 10(1): 101-103. doi:10.4103/ijmy.ijmy_200_20. pmid: 33707382
[24]	Amedeo A, Beci G, Giglia M, et al. Evaluation of trace calls by Xpert MTB/RIF ultra for clinical management in low TB burden settings. PLoS One, 2022, 17(8): e0272997. doi:10.1371/journal.pone.0272997.
[25]	Kendall EA, Kitonsa PJ, Nalutaaya A, et al. The Spectrum of Tuberculosis Disease in an Urban Ugandan Community and Its Health Facilities. Clin Infect Dis, 2021, 72(12): e1035-e1043. doi:10.1093/cid/ciaa1824.
[26]	World Health Organization. Global Laboratory Initiative STP.Planning for country transition to Xpert MTB/RIF Ultra cartridges. Geneva: World Health Organization, 2017.
[27]	World Health Organization. WHO consolidated guidelines on tuberculosis: Module 3: Diagnosis-Rapid diagnostics for tuberculosis detection. Geneva: World Health Organization, 2024.
[28]	Mishra H, Reeve BWP, Palmer Z, et al. Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study. Lancet Respir Med, 2020, 8(4): 368-382. doi:10.1016/S2213-2600(19)30370-4. pmid: 32066534

基本情况	例数	率(%)	基本情况	例数	率(%)
性别^a			Xpert检测(980例)
女性	680	24.56	阳性	275	28.06
男性	2089	75.44	高	60	21.82
涂片(2761例)			中	77	28.00
阳性	286	10.36	低	68	24.73
++++	34	11.89	极低	70	25.45
+++	77	26.92	Xpert Ultra检测(719例)
++	81	28.32	阳性	254	35.33
+	65	22.73	高	62	24.41
细菌数/300视野	29	10.14	中	50	19.69
液体培养(2491例)			低	74	29.13
阳性	730	29.31	极低	32	12.60
固体培养(1530例)			Trace	36	14.17
阳性	362	23.66

方法	敏感度	敏感度:涂阳培阳	敏感度:涂阴培阳	特异度	阳性预测值	阴性预测值
固体培养 (1380例)	84.55 (80.53~88.03; 323/382)	94.80 (90.35~97.59; 164/173)	76.08 (69.71~81.69; 159/209)	99.00 (98.17~99.52; 988/998)	97.00 (94.55~98.55; 323/333)	94.36 (92.79~95.68; 988/1047)
Xpert (850例)	91.19 (86.72~94.54; 207/227)	100.00 (96.52~100.00; 104/104)	83.74 (76.01~89.78; 103/123)	92.62 (90.27~94.54; 577/623)	81.82 (76.50~86.37; 207/253)	96.65 (94.87~97.94; 577/597
Xpert Ultra (611例)	96.20 (92.32~98.46; 177/184)	100.0 (94.40~100.00; 64/64)	94.17 (88.35~97.62; 113/120)	86.65 (83.05~89.73; 370/427)	75.64 (69.62~81.00; 177/234)	98.14 (96.21~99.25; 370/377)