Seki Fumio, Miyoshi Masahiro, Ikeda Tatsuya, Nishijima Haruna, Saikusa Miwako, Itamochi Masae, Minagawa Hiroko, Kurata Takako, Ootomo Rei, Kajiwara Jumboku, Kato Takashi, Komase Katsuhiro, Tanaka-Taya Keiko, Sunagawa Tomimasa, Oishi Kazunori, Okabe Nobuhiko, Kimura Hirokazu, Suga Shigeru, Kozawa Kunihisa, Otsuki Noriyuki, Mori Yoshio, Shirabe Komei, Takeda Makoto
Department of Virology 3, National Institute of Infectious Diseases, Tokyo, Japan.
Hokkaido Institute of Public Health, Sapporo, Japan.
Front Microbiol. 2019 Jul 4;10:1470. doi: 10.3389/fmicb.2019.01470. eCollection 2019.
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.
支持中断地方性麻疹病毒（MV）传播的基因分型证据是实现消除麻疹所需核实的基本标准之一。自2014年以来，日本在全国各都道府县的公共卫生机构对大多数麻疹病例进行了MV基因型分析。凭借这些强大的分子流行病学数据，日本于2015年3月被证实已消除麻疹。然而，即使在消除麻疹之后的时期，日本仍反复检测到散发病例和小规模麻疹疫情。本研究调查了2008年至2017年期间日本全国范围内MV的分子流行病学情况。基于N基因450个核苷酸序列区域（N450），2008年至2017年期间的891株病毒属于7种基因型（D5、D4、D9、H1、G3、B3和D8）以及124种不同的MV序列变异株。2015年至2017年消除麻疹之后时期的311株MV病毒分别被归类为D9、H1、B3和D8基因型中的1种、7种、8种和32种不同的N450序列变异株。对各个N450序列变异株检测时期的分析表明，大多数MV毒株仅在短时间内被检测到。然而，世界卫生组织（WHO）指定的毒株MVs/Osaka.JPN/29.15/ [D8]和MVi/Hulu Langat.MYS/26.11/ [D8]在2015年至2017年的两三年间在许多病例中被检测到。这些WHO指定的毒株已在全球传播，在许多国家引发疫情。流行病学调查显示这些WHO指定的毒株多次传入日本。要在同一毒株多次传入的情况下证明消除状态（地方性传播的中断）具有挑战性。尽管如此，对单个MV毒株的详细序列分析以及对这些毒株的时间顺序分析提供了充分证据，表明日本在2017年仍保持其麻疹消除状态。
