背景:侧流快速诊断测试(RDT)能够检测血清中的麻疹特异性免疫球蛋白M(IgM)抗体,毛细血管血,和口腔液的准确性与酶免疫分析(EIA)一致。该研究的目的是:1)评估两个诊所工作人员之间的麻疹RDT读者之间的协议;2)评估麻疹RDT相对于低传播环境下的标准监测测试的敏感性和特异性;3)评估知识,态度,以及使用RDT的诊所工作人员的做法;4)评估RDT测试对马来西亚麻疹公共卫生应对措施的影响。
方法:基于临床的前瞻性评估包括2019年9月至2020年6月在马来西亚15个卫生区的34个故意选择的诊所进行的常规麻疹监测所捕获的所有疑似麻疹病例,随后进行了为期一天的区域RDT使用培训。知情同意后,从每个疑似病例中收集了四个样本,包括常规收集的标准监测[用于EIA的血清和用于定量逆转录酶聚合酶链反应(RT-qPCR)的咽拭子]以及在研究期间用RDT测试的毛细血管血液和口腔液。通过比较RDT实施前(2018年12月至2019年8月)和RDT实施期(2019年9月至2020年6月)之间麻疹公共卫生应对的速度,评估了RDT的影响。为了评估知识,态度,以及RDT使用的实践,对选定地点参与麻疹公共卫生管理的工作人员进行了调查。
结果:在436个疑似病例中,两名健康诊所工作人员对麻疹RDT设备的直接视觉读数的一致性是毛细血管血(k=0.94)的99%和口腔液(k=0.90)的97%。在总数中,45(10%)麻疹IgMEIA阳性(n=44,包括5个也通过RT-qPCR阳性)或仅RT-qPCR(n=1),38例RDT阳性(使用毛细血管血或口腔液)。以麻疹IgMEIA或RT-qPCR为参考,使用毛细血管血的RDT敏感性为43%(95%CI:30%-58%),特异性为98%(95%CI:96%-99%);使用口服液,敏感度(26%,95%CI:15%-40%)和特异性(97%,95%CI:94%-98%)较低。训练九个月后,参与麻疹公共卫生管理的工作人员的RDT知识较高(平均测验得分为80%),在接受过正规培训的人员中最高(88%),其次是在监督访问期间受过培训的人(83%)。在RDT实施期间,从病例确认到开始公众回应的天数减少了约5天。
结论:麻疹IgMRDT显示>95%的读者之间的一致性,高度保留RDT知识,和更快速的公共卫生反应。然而,尽管使用毛细血管血或口腔液的RDT特异性≥95%,RDT灵敏度<45%。需要使用高度特异性IgM测定和系统RT-qPCR进行病例确认的更高能力的研究,以确定RDT在消除麻疹设置中的作用。
BACKGROUND: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia.
METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed.
RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days.
CONCLUSIONS: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.