PDF(Pubmed)
Abstract：
BACKGROUND: Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician\'s expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan.
METHODS: This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.
RESULTS: Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.
CONCLUSIONS: When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device\'s specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.
METHODS: This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.
RESULTS: Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.
CONCLUSIONS: When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device\'s specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.
摘要：
背景：疟疾寄生虫的显微镜检测是劳动密集型的，耗时,和专业知识的要求。此外，幻灯片解释高度依赖于染色技术和技术人员的专业知识。因此,人们对下一代越来越感兴趣，全集成或半集成显微镜，可以改善载玻片制备和检查。本研究旨在评估miLab™(NoulInc.，大韩民国),一种完全集成的自动化显微镜设备，用于在苏丹的现场护理中检测有症状的患者的疟疾寄生虫。
方法：这是一个前瞻性的，在喀土穆农村初级卫生保健机构进行的病例对照诊断准确性研究，2020年苏丹根据常规现场显微镜测试的结果，在医疗机构就诊且年龄在5岁或以上的100名疟疾阳性和90名疟疾阴性患者被连续纳入。所有同意的患者均接受miLab™测试，结果为阴性或可疑。对于主要分析，可疑结果被视为阳性(自动模式).对于二次分析，操作员检查了可疑结果，并将其分类为阴性或阳性（校正模式）。巢式聚合酶链反应（PCR）用作参考标准，和专家光学显微镜作为比较器。
结果：在190名患者中，112例通过PCR确认了疟疾诊断，78例排除。在自动化模式下，miLab™的灵敏度为91.1%(95%置信区间[CI]84.2-95.6%)，特异性为66.7%(95%Cl55.1-67.7%)。特异性提高到96.2%（95%Cl89.6-99.2%），在校正模式下进行操作员干预。在自动模式下，miLab与专家显微镜的一致性很大(kappa0.65[95%CI0.54-0.76])，但在校正模式下几乎完美(卡帕0.97[95%CI0.95-0.99])。在专家显微镜和miLab™之间的一致性的Bland-Altman分析中发现了0.359的平均差异用于定量寄生虫计数。
结论：当用于临床时，miLab™显示高灵敏度但低特异性。在当前版本中，需要专家干预以提高设备的特异性。在校正模式下的miLab™类似于专家显微镜进行。临床应用前,需要更多的改进，以确保完全的工作流程自动化和消除人为干预。试验注册ClinicalTrials.gov：NCT04558515。
方法：这是一个前瞻性的，在喀土穆农村初级卫生保健机构进行的病例对照诊断准确性研究，2020年苏丹根据常规现场显微镜测试的结果，在医疗机构就诊且年龄在5岁或以上的100名疟疾阳性和90名疟疾阴性患者被连续纳入。所有同意的患者均接受miLab™测试，结果为阴性或可疑。对于主要分析，可疑结果被视为阳性(自动模式).对于二次分析，操作员检查了可疑结果，并将其分类为阴性或阳性（校正模式）。巢式聚合酶链反应（PCR）用作参考标准，和专家光学显微镜作为比较器。
结果：在190名患者中，112例通过PCR确认了疟疾诊断，78例排除。在自动化模式下，miLab™的灵敏度为91.1%(95%置信区间[CI]84.2-95.6%)，特异性为66.7%(95%Cl55.1-67.7%)。特异性提高到96.2%（95%Cl89.6-99.2%），在校正模式下进行操作员干预。在自动模式下，miLab与专家显微镜的一致性很大(kappa0.65[95%CI0.54-0.76])，但在校正模式下几乎完美(卡帕0.97[95%CI0.95-0.99])。在专家显微镜和miLab™之间的一致性的Bland-Altman分析中发现了0.359的平均差异用于定量寄生虫计数。
结论：当用于临床时，miLab™显示高灵敏度但低特异性。在当前版本中，需要专家干预以提高设备的特异性。在校正模式下的miLab™类似于专家显微镜进行。临床应用前,需要更多的改进，以确保完全的工作流程自动化和消除人为干预。试验注册ClinicalTrials.gov：NCT04558515。
