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Abstract：
BACKGROUND: Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future \"screen and treat\" strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests.
METHODS: During active screening, venous blood samples from 1095 individuals from Côte d\'Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar.
RESULTS: One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1-99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5-88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7-84.2%); DCN HAT RDT 78.2% (95% CI: 75.7-80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9-80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7-100% (n = 399) and 93.0-100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity.
CONCLUSIONS: Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based \"screen and treat\" strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT.
BACKGROUND: The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.
METHODS: During active screening, venous blood samples from 1095 individuals from Côte d\'Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar.
RESULTS: One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1-99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5-88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7-84.2%); DCN HAT RDT 78.2% (95% CI: 75.7-80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9-80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7-100% (n = 399) and 93.0-100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity.
CONCLUSIONS: Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based \"screen and treat\" strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT.
BACKGROUND: The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022.
摘要：
背景：血清学筛查试验在诊断冈比亚人非洲锥虫病（gHAT）中起着至关重要的作用。目前,他们预选个人进行微观确认，但在未来的“筛选和治疗”策略中，他们将确定需要治疗的个体。报告的特异性的可变性，新的快速诊断试验(RDT)的发展以及疟疾感染可能降低RDT特异性的假设,促使我们评估5gHAT筛查试验的特异性.
方法：在主动筛查期间，来自科特迪瓦和几内亚的1095名个体的静脉血样本进行了连续商业测试(CATT，HATSero-K-SeT,雅培BiolineHAT2.0)和原型(DCNHATRDT,HATSero-K-SeT2.0）gHAT筛查测试和疟疾RDT。gHAT筛查试验≥1阳性的个体接受了显微镜检查和进一步的免疫学检查（用T.b.gambienseLiTat1.3、1.5和1.6进行胰蛋白酶分解；间接ELISA/T.b.gambiense；用T.b.gambienseLiTat1.3和1.5VSG进行T.b.7SL佐恩，和TgsGP；锥虫虫S2-RT-qPCR18S2，177T，GPI-PLC和TgsGP多重；RT-qPCRDT8、DT9和TgsGP多重）。显微镜锥虫检测证实gHAT，而其他人则被认为是无gHAT。通过卡方评估组间分数的差异，并通过McNemar对同一个体进行2次测试之间的特异性差异。
结果：诊断为一例gHAT病例。总体测试特异性(n=1094)为:CATT98.9%(95%CI:98.1-99.4%);HATSero-K-SeT86.7%(95%CI:84.5-88.5%);BiolineHAT2.082.1%(95%CI:79.7-84.2%);在疟疾阳性中，gHAT筛查测试似乎不太具体，但仅在几内亚，雅培BiolineHAT2.0（P=0.03）和HATSero-K-Set2.0（P=0.0006）的差异显着。gHAT血清阳性的免疫学和分子实验室检测的特异性为98.7-100％（n=399）和93.0-100％（n=302），分别。在44个参考实验室测试阳性中，只有确诊的gHAT患者和1个筛查试验血清阳性的结合免疫学和分子参考实验室检测阳性。
结论：虽然不能排除疟疾的轻微影响，gHATRDT特异性远低于WHO目标产品概况规定的95%最低特异性，这是一种简单的诊断工具，用于识别符合治疗条件的个体。除非特异性得到改善，基于RDT的“筛查和治疗”策略将导致大规模的过度治疗。鉴于其结果不一致,参考实验室测试的诊断性能的额外比较评估是为了更好地识别，在筛查测试阳性中，那些对gHAT越来越怀疑的人。
背景：该试验于2022年7月15日在clinicaltrials.gov中根据NCT05466630进行回顾性注册。
方法：在主动筛查期间，来自科特迪瓦和几内亚的1095名个体的静脉血样本进行了连续商业测试(CATT，HATSero-K-SeT,雅培BiolineHAT2.0)和原型(DCNHATRDT,HATSero-K-SeT2.0）gHAT筛查测试和疟疾RDT。gHAT筛查试验≥1阳性的个体接受了显微镜检查和进一步的免疫学检查（用T.b.gambienseLiTat1.3、1.5和1.6进行胰蛋白酶分解；间接ELISA/T.b.gambiense；用T.b.gambienseLiTat1.3和1.5VSG进行T.b.7SL佐恩，和TgsGP；锥虫虫S2-RT-qPCR18S2，177T，GPI-PLC和TgsGP多重；RT-qPCRDT8、DT9和TgsGP多重）。显微镜锥虫检测证实gHAT，而其他人则被认为是无gHAT。通过卡方评估组间分数的差异，并通过McNemar对同一个体进行2次测试之间的特异性差异。
结果：诊断为一例gHAT病例。总体测试特异性(n=1094)为:CATT98.9%(95%CI:98.1-99.4%);HATSero-K-SeT86.7%(95%CI:84.5-88.5%);BiolineHAT2.082.1%(95%CI:79.7-84.2%);在疟疾阳性中，gHAT筛查测试似乎不太具体，但仅在几内亚，雅培BiolineHAT2.0（P=0.03）和HATSero-K-Set2.0（P=0.0006）的差异显着。gHAT血清阳性的免疫学和分子实验室检测的特异性为98.7-100％（n=399）和93.0-100％（n=302），分别。在44个参考实验室测试阳性中，只有确诊的gHAT患者和1个筛查试验血清阳性的结合免疫学和分子参考实验室检测阳性。
结论：虽然不能排除疟疾的轻微影响，gHATRDT特异性远低于WHO目标产品概况规定的95%最低特异性，这是一种简单的诊断工具，用于识别符合治疗条件的个体。除非特异性得到改善，基于RDT的“筛查和治疗”策略将导致大规模的过度治疗。鉴于其结果不一致,参考实验室测试的诊断性能的额外比较评估是为了更好地识别，在筛查测试阳性中，那些对gHAT越来越怀疑的人。
背景：该试验于2022年7月15日在clinicaltrials.gov中根据NCT05466630进行回顾性注册。
