Identifying thresholds to classify moderate-to-heavy soil-transmitted helminth intensity infections for FECPAKG2, McMaster, Mini-FLOTAC and qPCR
Identifying thresholds to classify moderate-to-heavy soil-transmitted helminth intensity infections for FECPAKG2, McMaster, Mini-FLOTAC and qPCR
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DOI：
10.1371/journal.pntd.0008296
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发表时间：
2020-07-01
影响因子：
3.8
通讯作者：
Vercruysse, Jozef
中科院分区：
文献类型：
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作者：
Levecke, Bruno;Cools, Piet;Vercruysse, Jozef
中至重度感染（M&HI）的流行率是衡量肠道蠕虫大规模驱虫计划成功与否的关键指标，因为它们占蠕虫可归因发病率的大部分。目前，当使用标准诊断方法在粪便中显微镜检测到的虫卵数量超过世界卫生组织设定的阈值时，肠道蠕虫感染被归类为M&HI。多年来，各种新的有前途的诊断方法被引入肠蠕虫的诊断。尽管它们比目前的标准方法有一些重要的优势，但尚不清楚它们是否能可靠地对M&HI感染进行分类。这是因为他们的测试结果要么系统地表明卵数较低，要么以每克粪便中卵数以外的单位表示（例如，蠕虫DNA的浓度），因此需要特定方法的阈值。我们定义了特定方法的阈值，并验证它们是否增加了M&HI感染的正确分类。总体而言，我们的研究结果表明，方法特异性阈值改善了M&HI感染的分类，但在将其推荐用于评估大规模驱虫计划中M&HI感染的发生率之前，还需要进一步验证。世界卫生组织（世卫组织）根据加藤-卡茨法测量的每克粪便中卵的具体数值，定义了土壤传播蠕虫（类蚓蛔虫、毛线虫和两种钩虫，十二指肠钩虫和美洲钩虫）的中至重度感染。有多种新的显微镜和基于dna的方法，但目前尚不清楚将世卫组织目前的阈值应用于这些方法是否允许对M&HI感染进行可靠的分类。我们评估了新的显微镜（FECPAK（G2）、McMaster和Mini-FLOTAC）和基于dna （qPCR）的诊断方法对M&HI感染分类的WHO和方法特异性阈值。为此，我们在两项多国药物疗效研究中确定了对M&HI感染进行最佳分类的方法特异性阈值（由Kato-Katz和WHO阈值定义；参考方法）。随后，我们验证了与参考方法相比，应用这些方法特异性阈值是否提高了M&HI感染分类的一致性。当我们应用WHO阈值时，新的显微方法主要将M&HI误诊为低强度感染，并在较小程度上将低强度感染误诊为M&HI。对于FECPAK(G2)，应用方法特异性阈值显着提高了蛔虫（中度- b>严重），滴虫和钩虫（中度- b>中度）的一致性。对于Mini-FLOTAC，仅在钩虫（一般->中等）上观察到显著改善的一致性。对于其他STHs，协议几乎是完美的，保持不变。对于麦克马斯特来说，具体方法的阈值显示了一个公平的实质性协议，但没有显着改善协议。对于qPCR，基于每ml DNA基因组当量的方法特异性阈值与钩虫和滴虫感染的参考方法基本一致。对于阿斯卡里斯，我们达成了实质性的协议。我们定义了特定于方法的阈值，以改进M&HI感染的分类。需要进行验证研究，然后才能建议在规划环境中普遍用于评估M&HI感染。
Author summary The prevalence of moderate-to-heavy intensity (M&HI) infections is a key indicator for measuring the success of large-scale deworming programs for intestinal worms because they account for the majority of the worm attributable morbidity. Currently, intestinal worm infections are classified as M&HI when the number of worm eggs that are microscopically detected in stool using a standard diagnostic method exceeds a threshold set by the World Health Organization. Over the years, a variety of new promising diagnostic methods have been introduced for the diagnosis of intestinal worms. Although they have some important advantages over the current standard method, it is not clear whether they can reliably classify M&HI infections. This is because their test results either systematically indicate lower egg counts or are expressed in a unit other than eggs per gram of stool (e.g, concentration of worm DNA), warranting the need for method-specific thresholds. We defined method-specific thresholds and verified whether they increased the correct classification of M&HI infections. Overall, our results indicate that method-specific thresholds improved the classification of M&HI infections, but that further validation is required before they can be recommended for evaluating the occurrence M&HI infections in large-scale deworming programs.World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides,Trichuris trichiuraand the two hookworms,Ancylostoma duodenaleandNecator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAK(G2), McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAK(G2), applying the method-specific thresholds significantly improved the agreement forAscaris(moderate -> substantial),Trichurisand hookworms (fair -> moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair -> moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworms andTrichurisinfections. ForAscaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.