Abstract：
BACKGROUND: Passive diagnosis of human African trypanosomiasis (HAT) at the health facility level is a major component of HAT control in Guinea. We examined which clinical signs and symptoms are associated with HAT, and assessed the performance of selected clinical presentations, of rapid diagnostic tests (RDT), and of reference laboratory tests on dried blood spots (DBS) for diagnosing HAT in Guinea.
METHODS: The study took place in 14 health facilities in Guinea, where 2345 clinical suspects were tested with RDTs (HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT). Seropositives underwent parasitological examination (reference test) to confirm HAT and their DBS were tested in indirect enzyme-linked immunoassay (ELISA)/Trypanosoma brucei gambiense, trypanolysis, Loopamp Trypanosoma brucei Detection kit (LAMP) and m18S quantitative PCR (qPCR). Multivariable regression analysis assessed association of clinical presentation with HAT. Sensitivity, specificity, positive and negative predictive values of key clinical presentations, of the RDTs and of the DBS tests for HAT diagnosis were determined.
RESULTS: The HAT prevalence, as confirmed parasitologically, was 2.0% (48/2345, 95% CI: 1.5-2.7%). Odds ratios (OR) for HAT were increased for participants with swollen lymph nodes (OR = 96.7, 95% CI: 20.7-452.0), important weight loss (OR = 20.4, 95% CI: 7.05-58.9), severe itching (OR = 45.9, 95% CI: 7.3-288.7) or motor disorders (OR = 4.5, 95% CI: 0.89-22.5). Presence of at least one of these clinical presentations was 75.6% (95% CI: 73.8-77.4%) specific and 97.9% (95% CI: 88.9-99.9%) sensitive for HAT. HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT were respectively 97.5% (95% CI: 96.8-98.1%), 99.4% (95% CI: 99.0-99.7%) and 97.9% (95% CI: 97.2-98.4%) specific, and 100% (95% CI: 92.5-100.0%), 59.6% (95% CI: 44.3-73.3%) and 93.8% (95% CI: 82.8-98.7%) sensitive for HAT. The RDT\'s positive and negative predictive values ranged from 45.2-66.7% and 99.2-100% respectively. All DBS tests had specificities ≥ 92.9%. While LAMP and m18S qPCR sensitivities were below 50%, trypanolysis and ELISA/T.b. gambiense had sensitivities of 85.3% (95% CI: 68.9-95.0%) and 67.6% (95% CI: 49.5-82.6%).
CONCLUSIONS: Presence of swollen lymph nodes, important weight loss, severe itching or motor disorders are simple but accurate clinical criteria for HAT referral in HAT endemic areas in Guinea. Diagnostic performances of HAT Sero-K-Set and SD Bioline HAT are sufficient for referring positives to microscopy. Trypanolysis on DBS may discriminate HAT patients from false RDT positives. Trial registration The trial was registered under NCT03356665 in clinicaltrials.gov (November 29, 2017, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03356665 ).
METHODS: The study took place in 14 health facilities in Guinea, where 2345 clinical suspects were tested with RDTs (HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT). Seropositives underwent parasitological examination (reference test) to confirm HAT and their DBS were tested in indirect enzyme-linked immunoassay (ELISA)/Trypanosoma brucei gambiense, trypanolysis, Loopamp Trypanosoma brucei Detection kit (LAMP) and m18S quantitative PCR (qPCR). Multivariable regression analysis assessed association of clinical presentation with HAT. Sensitivity, specificity, positive and negative predictive values of key clinical presentations, of the RDTs and of the DBS tests for HAT diagnosis were determined.
RESULTS: The HAT prevalence, as confirmed parasitologically, was 2.0% (48/2345, 95% CI: 1.5-2.7%). Odds ratios (OR) for HAT were increased for participants with swollen lymph nodes (OR = 96.7, 95% CI: 20.7-452.0), important weight loss (OR = 20.4, 95% CI: 7.05-58.9), severe itching (OR = 45.9, 95% CI: 7.3-288.7) or motor disorders (OR = 4.5, 95% CI: 0.89-22.5). Presence of at least one of these clinical presentations was 75.6% (95% CI: 73.8-77.4%) specific and 97.9% (95% CI: 88.9-99.9%) sensitive for HAT. HAT Sero-K-Set, rHAT Sero-Strip, and SD Bioline HAT were respectively 97.5% (95% CI: 96.8-98.1%), 99.4% (95% CI: 99.0-99.7%) and 97.9% (95% CI: 97.2-98.4%) specific, and 100% (95% CI: 92.5-100.0%), 59.6% (95% CI: 44.3-73.3%) and 93.8% (95% CI: 82.8-98.7%) sensitive for HAT. The RDT\'s positive and negative predictive values ranged from 45.2-66.7% and 99.2-100% respectively. All DBS tests had specificities ≥ 92.9%. While LAMP and m18S qPCR sensitivities were below 50%, trypanolysis and ELISA/T.b. gambiense had sensitivities of 85.3% (95% CI: 68.9-95.0%) and 67.6% (95% CI: 49.5-82.6%).
CONCLUSIONS: Presence of swollen lymph nodes, important weight loss, severe itching or motor disorders are simple but accurate clinical criteria for HAT referral in HAT endemic areas in Guinea. Diagnostic performances of HAT Sero-K-Set and SD Bioline HAT are sufficient for referring positives to microscopy. Trypanolysis on DBS may discriminate HAT patients from false RDT positives. Trial registration The trial was registered under NCT03356665 in clinicaltrials.gov (November 29, 2017, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03356665 ).
摘要：
背景：在医疗机构一级被动诊断人类非洲锥虫病（HAT）是几内亚HAT控制的主要组成部分。我们检查了哪些临床体征和症状与HAT相关，并评估选定临床表现的表现，快速诊断测试(RDT)，以及用于诊断几内亚HAT的干血点（DBS）的参考实验室测试。
方法：这项研究在几内亚的14个医疗机构进行，2345名临床嫌疑人接受了RDT测试(HATSero-K-Set，rHATSero-Strip,和SDBioline帽子）。血清阳性接受了寄生虫学检查（参考测试），以确认HAT及其DBS已在间接酶联免疫测定（ELISA）/布氏锥虫中进行了测试。胰蛋白酶,loopamp布氏锥虫检测试剂盒(LAMP)和m18S定量PCR(qPCR)。多变量回归分析评估了临床表现与HAT的关联。灵敏度,特异性，关键临床表现的阳性和阴性预测值，确定了用于HAT诊断的RDT和DBS测试。
结果：HAT患病率，正如寄生虫学证实的那样，为2.0%（48/2345，95%CI：1.5-2.7%）。对于淋巴结肿大的参与者，HAT的赔率（OR）增加（OR=96.7，95％CI：20.7-452.0），重要的体重减轻（OR=20.4，95％CI：7.05-58.9），严重瘙痒（OR=45.9，95％CI：7.3-288.7）或运动障碍（OR=4.5，95％CI：0.89-22.5）。这些临床表现中的至少一种的存在是75.6%(95%CI:73.8-77.4%)特异性和97.9%(95%CI:88.9-99.9%)对HAT敏感。HATSero-K-Set,rHATSero-Strip,和SDBiolineHAT分别为97.5％（95％CI：96.8-98.1％），99.4%（95%CI：99.0-99.7%）和97.9%（95%CI：97.2-98.4%）和100%（95%CI：92.5-100.0%），59.6％（95％CI：44.3-73.3％）和93.8％（95％CI：82.8-98.7％）对HAT敏感。RDT的阳性和阴性预测值分别为45.2-66.7%和99.2-100%。所有DBS测试的特异性≥92.9%。虽然LAMP和m18SqPCR敏感性低于50%，胰蛋白酶和ELISA/T.b.冈比亚的敏感性分别为85.3％（95％CI：68.9-95.0％）和67.6％（95％CI：49.5-82.6％）。
结论：淋巴结肿大，重要的减肥，严重瘙痒或运动障碍是几内亚HAT流行地区HAT转诊的简单但准确的临床标准.HATSero-K-Set和SDBiolineHAT的诊断性能足以将阳性标记为显微镜。DBS上的锥虫溶解可能会将HAT患者与假RDT阳性区分开。试验注册该试验在clinicaltrials.gov（2017年11月29日，回顾性注册https://clinicaltrials.gov/ct2/show/NCT03356665）中根据NCT03356665注册。
方法：这项研究在几内亚的14个医疗机构进行，2345名临床嫌疑人接受了RDT测试(HATSero-K-Set，rHATSero-Strip,和SDBioline帽子）。血清阳性接受了寄生虫学检查（参考测试），以确认HAT及其DBS已在间接酶联免疫测定（ELISA）/布氏锥虫中进行了测试。胰蛋白酶,loopamp布氏锥虫检测试剂盒(LAMP)和m18S定量PCR(qPCR)。多变量回归分析评估了临床表现与HAT的关联。灵敏度,特异性，关键临床表现的阳性和阴性预测值，确定了用于HAT诊断的RDT和DBS测试。
结果：HAT患病率，正如寄生虫学证实的那样，为2.0%（48/2345，95%CI：1.5-2.7%）。对于淋巴结肿大的参与者，HAT的赔率（OR）增加（OR=96.7，95％CI：20.7-452.0），重要的体重减轻（OR=20.4，95％CI：7.05-58.9），严重瘙痒（OR=45.9，95％CI：7.3-288.7）或运动障碍（OR=4.5，95％CI：0.89-22.5）。这些临床表现中的至少一种的存在是75.6%(95%CI:73.8-77.4%)特异性和97.9%(95%CI:88.9-99.9%)对HAT敏感。HATSero-K-Set,rHATSero-Strip,和SDBiolineHAT分别为97.5％（95％CI：96.8-98.1％），99.4%（95%CI：99.0-99.7%）和97.9%（95%CI：97.2-98.4%）和100%（95%CI：92.5-100.0%），59.6％（95％CI：44.3-73.3％）和93.8％（95％CI：82.8-98.7％）对HAT敏感。RDT的阳性和阴性预测值分别为45.2-66.7%和99.2-100%。所有DBS测试的特异性≥92.9%。虽然LAMP和m18SqPCR敏感性低于50%，胰蛋白酶和ELISA/T.b.冈比亚的敏感性分别为85.3％（95％CI：68.9-95.0％）和67.6％（95％CI：49.5-82.6％）。
结论：淋巴结肿大，重要的减肥，严重瘙痒或运动障碍是几内亚HAT流行地区HAT转诊的简单但准确的临床标准.HATSero-K-Set和SDBiolineHAT的诊断性能足以将阳性标记为显微镜。DBS上的锥虫溶解可能会将HAT患者与假RDT阳性区分开。试验注册该试验在clinicaltrials.gov（2017年11月29日，回顾性注册https://clinicaltrials.gov/ct2/show/NCT03356665）中根据NCT03356665注册。
