IASR 43(4), 2022【THE TOPIC OF THIS MONTH】 Respiratory syncytial virus infection, 2018-2021, Japan
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The topic of This Month Vol.43 No.4(No. 506)
Respiratory syncytial virus infection, 2018-2021, Japan
(IASR Vol. 43 p79-81:April 2022)
Respiratory syncytial virus (RSV) belongs to the family Pneumoviridae, genus orthopneumovirus. The virus was formerly named RSV as a virus belonging to the family Paramxyoviridae, subfamily Pneumovirinae, genus pneumovirus, but currently, its off icial nomenclature is human orthopneumovirus, and RSV is its common name. RSV is broadly divided into two subgroups (subgroups A and B) depending on the character of the attachment glycoprotein (G protein) and further divided into several genotypes based on the G protein sequence (see pp. 82 and 84 of this issue). RSV is present globally and almost everyone experiences infection during childhood. RSV induces various clinical manifestations from mild flu-like illness to lower respiratory tract infection; in particular, infants under 6 months of age tend to have severe disease (see p. 85 of this issue). In addition, RSV easily re-infects adults, and severe infections in the elderly have become a public health concern in developed countries in recent years (see p. 87 of this issue). In Japan, symptomatic RSV infection is classified as a Category V Infectious Disease under the Infectious Diseases Control Law, monitored via pediatric sentinel sites; the designated notification sites (approximately 3,000 sentinel pediatric medical facilities) must report to the Public Health Center every week. Laboratory diagnosis is mandatory for notification (https://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-15.html).
Epidemiologic situation of RSV infections
The number of reported RSV infection cases per sentinel site started to increase from week 27 (July) in both 2018 and 2019, peaked at week 37 (September) (2018, 2.46 reports/sentinel; 2019, 3.45 reports/sentinel), and decreased toward the end of the year. In 2020, although the number of reported cases per sentinel site was similar to previous years through around week 15 (April), it shifted to a lower level from May to August. The number of reported cases increased in September, but there was no remarkable epidemic throughout the year. In 2021, the increasing trend from the previous year continued, and the number peaked at week 28 in July (5.99/per sentinel site). The respective number of reported cases per sentinel site and the total number of reported cases for each year were as follows: 2018, 38.29 and 120,743; 2019, 44.39 and 140,093; 2020, 5.74 and 18,097; 2021, 71.96 and 226,823 (Fig. 1).
Since 2014, RSV infections have tended to start in Okinawa Prefecture in the summer and then spread throughout Japan (IASR 35: 137-139, 2014). Although the epidemic peaked at the end of the calendar year through 2015, it began earlier from 2016 and peaked in September in 2017. In both 2018 and 2019, an epidemic was observed in Okinawa Prefecture in the summer, followed by a nationwide epidemic with a peak in September. In 2020, the number of reports began to increase in Okinawa and Kagoshima Prefectures from September, and from 2021, the trend continued to increase, mostly in the Kyushu and Kinki regions, through around March 2021. The epidemic subsequently spread nationwide, peaking in July. After a temporary decline, the epidemic increased from September in Kagoshima Prefecture and from October in Okinawa Prefecture to the end of the year (Fig. 2).
Regarding the age distribution of patients with RSV infection from 2018 to 2021, reports of patients aged 2 years or younger accounted for about 85% (2018, 88.6%; 2019, 86.8%; 2020, 85.0%) during the 3 years from 2018 to 2020, with the most frequent report by age group being one-year-olds, followed by zero- and then two-year-olds. In 2021, the number of reports for children aged 2 years or younger decreased to about 74%, and the order by age was one-year-olds (30.3%), two-year-olds (24.4%), and zero-year-olds (18.9%). In addition, the proportion of those aged 3–9 years in 2021 was 26.1%, higher than that of the three years from 2018 to 2020 (2018, 11.1%; 2019, 12.9%; 2020, 14.3%). The proportion of male patients was slightly higher throughout the observation period (54.2% in 2018, 53.4% in 2019, 53.1% in 2020, and 52.5% in 2021) (Fig. 3).
Detection of RSV and other respiratory viruses
As at February 28, 2022, respiratory viruses detected from samples collected between 2018 and 2021 at Public Health Institutes and reported to the Infectious Agents Surveillance System (IASS), National Epidemiological Surveillance of Infectious Diseases (NESID), included influenza virus, rhinovirus, RSV, parainfluenza virus, human metapneumovirus, human bocavirus, human coronaviruses, and SARS-CoV-2 (Table) (see p. 88 of this issue). In 2018 and 2019, detections of influenza virus were the most frequent (2018, 9,140; 2019, 10,229), accounting for nearly 70% of the total reported detections, while in 2020 and 2021, SARS-CoV-2 was the most frequently detected owing to the COVID-19 pandemic. On the other hand, in 2020 and 2021, detections of influenza virus decreased substantially from 2,730 (12.8%) in 2020 to 6 (0.03%) in 2021, probably because there was no circulation of influenza. Although the distribution of detected viruses varied depending on the year, the number of RSV (rank based on number of detections) was 1,030 (3rd) in 2018, 1,029 (3rd) in 2019, 132 (6th) in 2020, and 841 (2nd) in 2021. Because the reporting process may take time in IASS, the presented number of cases detected in 2021 may be lower than the actual number (Table and Fig. 4). Temporal detections of RSV correlated with the epidemic situation of RSV infection occurrence, and the number of detections increased from June to December in 2018 and 2019, and from March to September in 2021 (Fig. 1). Among the 3,032 cases of RSV detection, the most commonly used method was gene detection (2,906 cases, 95.8%) and the most frequently used specimen was pharyngeal swab (2,969 cases, 97.9%). Among the patients with RSV detection, 2,623 (86.5%) showed symptoms associated with upper or lower respiratory tract infection, and 263 (8.7%) had also developed pneumonia. In addition, 22 cases (0.7%) were detected from patients with encephalitis/encephalopathy, indicative of severe infection.
Vaccine development and global surveillance for RSV
In 2015, the World Health Organization (WHO) started discussions on the RSV global surveillance system, which utilizes the pre-existing Global Influenza Surveillance and Response System (GISRS) platform (see pp. 90 and 92 of this issue). The background context was that the maternal vaccine developed by Novavax Inc. was to be approved around 2018, and there was an urgent need to establish an RSV surveillance system. The first phase of pilot surveillance started in 2016 and the second in 2019; however, Novavax’s vaccine has not yet been approved, and pilot surveillance has not progressed due to the COVID-19 pandemic. On the other hand, many new formulations have been approved as COVID-19 vaccines, which has helped accelerate the development of RSV vaccines (see p. 94 of this issue).
Issues for the future
Because RSV often causes severe infection in infants and the elderly, it is important to monitor its epidemics. However, since RSV surveillance in Japan is based only on reports from pediatric sentinel sites, it is diff icult to understand the epidemiology of RSV infections in patients other than children. In addition, because there are no surveillance data that apply syndromes/symptoms as the denominator, it is diff icult to calculate the disease burden. It is necessary to understand the disease burden in all age groups and evaluate preventive measures. In addition, it is also essential to discuss how to participate in RSV global surveillance, promoted by WHO with the purpose of RSV vaccine and drug development.
