Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
PLoS One. 2022 Jun 24;17(6):e0268685. doi: 10.1371/journal.pone.0268685. eCollection 2022.
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.
在结核病流行地区，对健康受试者进行干扰素-γ释放检测（IGRA）的前瞻性研究尚未检查连续检测的长期变异性。这个问题与基于预防感染的结核病（TB）疫苗试验的解释有关。
在坦桑尼亚的一项结核病疫苗试验中，对健康青少年在 3 年内的 5 个时间间隔内手动进行 T-SPOT.TB 检测。检测结果定义为阴性、阳性、边界或无效。随后，通过自动读取器分析微量滴定板以获得本分析的斑点形成细胞（SFC）的定量计数。
从 928 名青少年中分析了 3387 个 T-SPOT.TB 样本；手动和自动检测结果的一致性为 97%。根据定量结果，143 名（15%）参与者在基线时是普遍的 IGRA 阳性，不符合进一步研究的条件。在其余的 IGRA 阴性参与者中，IGRA 转换的年发生率为 2.9%。在 43 名重复检测的 IGRA 转换者中，12 名（28%）是持续转换者，16 名（37%）是短暂转换者，15 名（35%）是新的类别，定义为不规则转换者（≥2 个不同的后续结果）。在流行的阳性者中，CFP-10 和 ESAT-6 的反应高于新发病例阳性者：CFP-10 为 53 对 36（p < 0.007）；ESAT-6 为 44 对 34（p = 0.12）。
IGRA 转换、逆转和持续的定义在很大程度上取决于检测的频率。在结核病流行国家的青少年中，类别之间的多次转变可能代表多次感染、亚临床感染中的宿主反应不同或检测变异性。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 转换是否可能代表接触到活动性结核分枝杆菌疾病的病例。
