Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions.
Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions.
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DOI：
10.1371/journal.pone.0268685
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
对结核病流行地区健康受试者进行的干扰素-γ释放测定（IGRA）的前瞻性研究尚未检验连续测定的长期变异性。该问题与基于预防感染的结核病 (TB) 疫苗试验的解释相关。在坦桑尼亚的结核病疫苗试验期间，对健康青少年进行了手动 T-SPOT.TB 检测，在 3 年内每隔 5 次进行一次。检测结果被定义为阴性、阳性、临界或无效。随后，通过自动读数器对微量滴定板进行分析，以获得用于本分析的斑点形成细胞（SFC）的定量计数。对来自 928 名青少年的 3387 个 T-SPOT.TB 样本进行了分析；手动和自动检测结果的一致性为 97%。根据定量结果，143 名（15%）参与者在基线时普遍呈 IGRA 阳性，没有资格进行进一步研究。在剩下的 IGRA 阴性参与者中，IGRA 的年转化率为 2·9%。在进行重复测定的 43 个 IGRA 转换器中，12 个 (28%) 是持续转换器，16 个 (37%) 是瞬时转换器，15 个 (35%) 包含一个定义为不规则转换器的新类别（≥2 个不同的后续结果）。 ESAT-6 和 CFP-10 反应的普遍性高于事件阳性：CFP-10 为 53 vs 36 (p < 0·007)； ESAT-6 为 44 与 34 (p = 0·12)。 IGRA 转换、恢复和持久性的定义主要取决于测试频率。结核病流行国家青少年类别的多次转变可能代表多重感染、亚临床感染的不同宿主反应或检测变异。在基于预防感染的结核病疫苗试验的设计和解释中应考虑这些发现。家庭接触研究可以确定即使是短暂的 IGRA 转变是否也可能代表接触了结核分枝杆菌疾病的活跃病例。
Prospective studies of interferon-gamma release assays (IGRA) on healthy subjects in tuberculosis-endemic regions have not examined the long-term variability of serial assays. This issue is relevant to the interpretation of tuberculosis (TB) vaccine trials based on prevention of infection. T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (≥2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.
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影响因子：
3.7
作者：
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DOI：
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发表时间：
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影响因子：
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