Upfront Xpert MTB/RIF testing on various specimen types for presumptive infant TB cases for early and appropriate treatment initiation

BackgroundDiagnosis of tuberculosis (TB) in infants is challenging due to non-specific clinical presentations of the disease in this age-group and low sensitivity of widely available TB diagnostic tools, which in turn delays prompt access to TB treatment. Upfront access to Xpert/MTB RIF (Xpert) testing, a highly sensitive and specific rapid diagnostic tool, could potentially address some of these challenges. Under the current project, we assessed the utility and feasibility of applying upfront Xpert for diagnosis of tuberculosis in infants, including for testing of non-sputum specimens.MethodsA high throughput lab was established in each of the four project cities, and linked to various health care providers across the city, through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all infant (ResultsA total of 7,994 presumptive infant TB cases were enrolled in the project from April 2014 to October 2016, detecting 465 (5.8%, CI: 5.3–6.4) TB cases. The majority (93.9%; CI: 93.4–94.4) of patient specimens were non-sputum and TB positivity was higher amongst non-sputum specimens. Further, a high proportion (5.6% CI 3.8–8.1) of infant TB cases were found to be rifampicin resistant. Covering large cities with a single lab per city over more than two years, the project demonstrated the feasibility of same-day diagnosis with upfront Xpert testing. This in turn led to prompt treatment initiation, with a two-day median turnaround time to treatment initiation. Case mortality observed in the project cohort of diagnosed TB cases was 11.0% (CI 8.4–14.1), the majority of which was pre- or early treatment mortality, in spite of prompt access to treatment for most diagnosed cases.ConclusionThe current project demonstrated the feasibility of applying rapid and upfront Xpert testing for presumptive infant TB cases. Rapid TB diagnosis in turn facilitates prompt and appropriate treatment initiation. Further, levels of rifampicin resistance observed in infants TB cases highlight the additional benefit of upfront resistance testing. However, high rates of early case mortality, in spite of prompt diagnosis and treatment initiation, highlight the need for further research in infant patient pathways for overall improvement in TB care for infant populations.【背景】婴幼儿肺结核的诊断颇具挑战，原因在于该人群的疾病临床表现缺乏特异性，且当前广泛使用的结核诊断工具灵敏度较低，进而导致患儿无法及时获得抗结核治疗。Xpert/MTB RIF（Xpert）是一种灵敏度与特异性俱佳的快速诊断工具，提前开展该检测有望部分解决上述难题。本项目评估了提前开展Xpert检测用于婴幼儿肺结核诊断的实用性与可行性，包括非痰标本检测的应用。 【方法】本项目在4个试点城市各建立1个高通量实验室，通过快速标本运输与电子报告联动机制，将实验室与全市各医疗卫生机构对接。所有婴幼儿均可免费接受Xpert检测。 【结果】2014年4月至2016年10月，本项目共纳入7994例疑似婴幼儿肺结核病例，检出465例肺结核患者，检出率为5.8%（95%置信区间：5.3~6.4）。其中93.9%（95%置信区间：93.4~94.4）的患者标本为非痰标本，且非痰标本的结核阳性率更高。此外，5.6%（95%置信区间：3.8~8.1）的婴幼儿肺结核病例被检出利福平耐药。本项目在每个试点城市设置1个实验室、持续运行两年多，证实了提前开展Xpert检测可实现当日诊断的可行性。这一结果推动了治疗的及时启动，从检测到启动治疗的中位周转时间仅为2天。本项目确诊的肺结核病例中，病例死亡率为11.0%（95%置信区间：8.4~14.1），其中多数为治疗前或治疗早期死亡，尽管大多数确诊病例可及时获得治疗。 【结论】本项目证实了对疑似婴幼儿肺结核病例开展快速提前Xpert检测的可行性。快速结核诊断可推动及时且恰当的治疗启动。此外，在婴幼儿肺结核病例中检出的利福平耐药水平，凸显了提前开展耐药检测的额外价值。然而，尽管能够及时完成诊断并启动治疗，婴幼儿肺结核病例仍存在较高的早期死亡率，这凸显了需要进一步研究婴幼儿患者诊疗路径，以全面提升婴幼儿人群的结核诊疗水平。