Watson Oliver J, Sumner Kelsey Marie, Janko Mark, Goel Varun, Winskill Peter, Slater Hannah C, Ghani Azra, Meshnick Steven R, Parr Jonathan B
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, UK.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
BMJ Glob Health. 2019 Jul 29;4(4):e001582. doi: 10.1136/bmjgh-2019-001582. eCollection 2019.
Surveillance and diagnosis of malaria relies predominantly on rapid diagnostic tests (RDT). However, false-negative (FN) RDT results are known to occur for a variety of reasons, including operator error, poor storage conditions, gene deletions, poor performance of specific RDT brands and lots, and low-parasite density infections. We used RDT and microscopy results from 85 000 children enrolled in Demographic Health Surveys and Malaria Indicator Surveys from 2009 to 2015 across 19 countries to explore the distribution of and risk factors for FN-RDTs in sub-Saharan Africa, where malaria's impact is greatest. We sought to (1) identify spatial and demographic patterns of FN-RDT results, defined as a negative RDT but positive gold standard microscopy test, and (2) estimate the percentage of infections missed within community-based malaria surveys due to FN-RDT results. Across all studies, 19.9% (95% CI 19.0% to 20.9%) of microscopy-positive subjects were negative by RDT. The distribution of FN-RDT results was spatially heterogeneous. The variance in FN-RDT results was best explained by the prevalence of malaria, with an increase in FN-RDT results observed at lower transmission intensities, among younger subjects, and in urban areas. The observed proportion of FN-RDT results was not predicted by differences in RDT brand or lot performance alone. These findings characterise how the probability of detection by RDTs varies in different transmission settings and emphasise the need for careful interpretation of prevalence estimates based on surveys employing RDTs alone. Further studies are needed to characterise the cost-effectiveness of improved malaria diagnostics (eg, PCR or highly sensitive RDTs) in community-based surveys, especially in regions of low transmission intensity or high urbanicity.
疟疾的监测和诊断主要依赖快速诊断检测（RDT）。然而，已知RDT结果会出现假阴性（FN），原因多种多样，包括操作人员失误、储存条件不佳、基因缺失、特定RDT品牌和批次性能不佳以及低寄生虫密度感染。我们利用2009年至2015年期间在19个国家参与人口健康调查和疟疾指标调查的85000名儿童的RDT和显微镜检查结果，探讨撒哈拉以南非洲地区FN-RDT的分布及危险因素，该地区疟疾影响最为严重。我们试图：（1）确定FN-RDT结果的空间和人口统计学模式，定义为RDT结果为阴性但金标准显微镜检查结果为阳性；（2）估计在基于社区的疟疾调查中因FN-RDT结果而漏诊的感染百分比。在所有研究中，19.9%（95%置信区间19.0%至20.9%）显微镜检查阳性的受试者RDT结果为阴性。FN-RDT结果的分布在空间上是异质的。FN-RDT结果的差异最好由疟疾流行率来解释，在较低传播强度地区、较年轻受试者以及城市地区，FN-RDT结果有所增加。仅RDT品牌或批次性能的差异并不能预测观察到的FN-RDT结果比例。这些发现描述了RDT检测概率在不同传播环境中的变化情况，并强调了仅基于使用RDT的调查对流行率估计进行谨慎解读的必要性。需要进一步研究来确定改进的疟疾诊断方法（如聚合酶链反应或高灵敏度RDT）在基于社区的调查中的成本效益，特别是在低传播强度或高城市化地区。
