Table_5_Nationwide Molecular Epidemiology of Measles Virus in Japan Between 2008 and 2017.XLSX

Genotyping evidence that supports the interruption of endemic measles virus (MV) transmission is one of the essential criteria to be verified in achieving measles elimination. In Japan since 2014, MV genotype analyses have been performed for most of the measles cases in prefectural public health institutes nationwide. With this strong molecular epidemiological data, Japan was verified to have eliminated measles in March, 2015. However, even in the postelimination era, sporadic cases and small outbreaks of measles have been detected repeatedly in Japan. This study investigated the nationwide molecular epidemiology of MV between 2008 and 2017. The 891 strains in the total period between 2008 and 2017 belonged to seven genotypes (D5, D4, D9, H1, G3, B3, and D8) and 124 different MV sequence variants, based on the 450-nucleotide sequence region of the N gene (N450). The 311 MV strains in the postelimination era between 2015 and 2017 were classified into 1, 7, 8, and 32 different N450 sequence variants in D9, H1, B3, and D8 genotypes, respectively. Analysis of the detection period of the individual N450 sequence variants showed that the majority of MV strains were detected only for a short period. However, MV strains, MVs/Osaka.JPN/29.15/ [D8] and MVi/Hulu Langat.MYS/26.11/ [D8], which are named strains designated by World Health Organization (WHO), have been detected in many cases over 2 or 3 years between 2015 and 2017. The WHO-named strains have circulated worldwide, causing outbreaks in many countries. Epidemiological investigation revealed repeated importation of these WHO-named strains into Japan. To demonstrate the elimination status (interruption of endemic transmission) in situations with repeated importation of the same strains is challenging. Nevertheless, the detailed sequence analysis of individual MV strains and chronological analysis of these strains provided sufficient evidence to show that Japan has still maintained its measles elimination status in 2017.可证实地方性麻疹病毒（measles virus, MV）传播中断的基因分型证据，是麻疹消除目标达成过程中需验证的关键标准之一。自2014年起，日本全国各都道府县公共卫生研究所已针对绝大多数麻疹病例开展MV基因型分析工作。依托这一坚实的分子流行病学数据，日本于2015年3月通过麻疹消除认证。然而，即便在消除后时代，日本仍反复出现散发病例与小规模麻疹暴发疫情。本研究针对2008至2017年间日本全国范围内的MV分子流行病学特征展开调查。基于N基因450核苷酸序列区域（N450）的分析结果显示，2008至2017年整体时段的891株MV毒株可归类为7种基因型（D5、D4、D9、H1、G3、B3及D8）与124种不同的MV序列变异株。2015至2017年消除后时代的311株MV毒株，分别可归类为D9、H1、B3及D8基因型下的1、7、8及32种不同的N450序列变异株。对单株N450序列变异株的检出时段分析结果表明，绝大多数MV毒株仅在短时间内被检出。然而，由世界卫生组织（World Health Organization, WHO）命名的MV毒株MVs/Osaka.JPN/29.15/[D8]与MVi/Hulu Langat.MYS/26.11/[D8]，在2015至2017年间多次被检出，且其传播循环时长可达2至3年。这些经WHO命名的毒株已在全球范围内传播，并在多个国家引发暴发疫情。流行病学调查显示，上述经WHO命名的毒株曾多次被输入日本境内。在同一毒株反复输入的情境下，证实麻疹消除状态（即地方性传播中断）极具挑战性。尽管如此，针对单株MV毒株的精细序列分析及毒株时序演变分析，已提供充分证据证实日本在2017年仍维持麻疹消除状态。