IASR 43(5), 2022【THE TOPIC OF THIS MONTH】Enterohemorrhagic Escherichia coli (EHEC) infection in Japan, as at March 2022
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The topic of This Month Vol.43 No.5(No. 507)
Enterohemorrhagic Escherichia coli (EHEC) infection in Japan, as at March 2022
(IASR Vol. 43 p103-106:May 2022)
Enterohemorrhagic Escherichia coli (EHEC) infection is caused by E. coli that produces Verotoxin/Shiga toxin (VT/Stx) and/or possesses VT-encoding genes. The main signs and symptoms of EHEC infection include abdominal pain, watery diarrhea, and bloody stools. Vomiting and/or fever (≥38°C) are occasionally observed. VT-producing EHEC can cause hemolytic uremic syndrome (HUS), which involves thrombocytopenia, hemolytic anemia, and acute kidney injury. Complications, such as encephalopathy, may also occur, with potentially fatal outcomes.
In Japan, EHEC infections are classified as a Category III notifiable infectious disease under the Infectious Diseases Control Law. Physicians who diagnose an EHEC infection must immediately notify the local public health center (PHC) (https://www.mhlw.go. jp/bunya/kenkou/kekkaku-kansenshou11/01-03-03.html). The information collected by the PHC is then reported to the National Epidemiological Surveillance of Infectious Diseases (NESID) system. When an EHEC infection is classified as food poisoning by a physician or the director of the PHC, the local government investigates the incident and submits a report to the Ministry of Health, Labour and Welfare (MHLW) in compliance with the Food Sanitation Law. Prefectural and municipal public health institutes (PHIs) perform isolation/identification of EHEC, serotyping of the isolate, and typing of the VT (VT or VT gene), and report the laboratory results to the Infectious Agents Surveillance System under the NESID (Table on p.105). The Department of Bacteriology I of the National Institute of Infectious Diseases (NIID) conducts confirmatory tests upon request and conducts molecular epidemiologic analysis of EHEC using multiple-locus variable-number tandem-repeat analysis (MLVA), pulsed-field gel electrophoresis (PFGE), and whole genome sequencing analysis [molecular epidemiological assessment based on single nucleotide polymorphism (SNP) analysis] (see pp.107, 108, and 109 of this issue). The results of the analyses are returned to the PHI and, when necessary, to local governments through the National Epidemiological Surveillance of Foodborne Disease (NESFD) system.
Cases notified under the NESID system: Based on NESID, in 2021, a total of 3,236 cases of EHEC infection were reported, including 2,022 symptomatic cases and 1,214 asymptomatic cases (asymptomatic cases are detected during active epidemiologic investigations or routine stool specimen screening of food handlers) (Table 1). The total number of cases reported in 2021 was 84.1% (80.3% in 2020) of the average number of cases reported between 2011 and 2019. Consistent with previous years, the number of cases peaked in summer (Fig. 1), but there were more reported cases in 2021 than in 2017-2020 during weeks 49-52. Reports from the 10 prefectures with the most notifications, Tokyo, Kanagawa, Hokkaido, Osaka, Fukuoka, Aichi, Saitama, Chiba, Ibaraki, and Hiroshima, accounted for 56% of all notified cases (including asymptomatic cases). The annual number of notified cases per 100,000 population was highest in Iwate Prefecture (6.4), followed by Nagasaki (6.3) and Shiga (5.4) prefectures (Fig. 2). The notification rate per 100,000 population among 0-4-year-olds was highest in Nara (43.2), Nagasaki (40.8), and Kagoshima (30.6) Prefectures (Fig. 2). The proportion of symptomatic cases among notified cases was high among the <20-year-old and ≥70-year-old age groups in both males and females (Fig. 3).
Fifty-nine cases had HUS complication (2.9% of symptomatic cases), and EHEC was isolated from 38. The O-serogroup was O157 in 29 cases, and the toxin type was VT2 (VT2 alone or VT1 & VT2) in 23 cases, with six isolates of unknown VT type (see p.111 of this issue). Among the symptomatic cases, the proportion of cases with HUS was highest in 5-9-year-olds (5.8%), followed by 0-4-year-olds (4.5%) (see p.111 of this issue). In 30-40% of HUS cases, EHEC was not isolated; detection of toxins in the stool or detection of agglutinating antibodies against the major O serogroup of EHEC in the blood by serodiagnosis confirms the diagnosis of HUS due to EHEC infection (see p.111 of this issue).
EHEC detection reported by PHIs: In 2021, PHIs detected 1,430 isolates of EHEC (Table on p.105). This figure is lower than the number of notified cases of EHEC infection (Table 1) because this number represents the number of detected strains submitted by medical facilities and commercial laboratories upon request by the PHCs. The most frequently detected O-serogroup was O157 (47.1%), followed by O26 (18.2%) and O111 (9.3%) (Table on p.105). In terms of toxin types, in 2021, VT1 & VT2-positive was the most common for O157 as in previous years, accounting for 60.4% of O157, and VT2-positive accounted for 38.1%. For O26 and O103, VT1-positive was the most common as in previous years, accounting for 96.9% and 93.7%, respectively; for O111 VT1-positive accounted for 70.7%. The main clinical signs/symptoms among the 674 cases in which O157 was isolated were diarrhea (63.8%), abdominal pain (58.8%), bloody stool (43.6%), and fever (21.2%).
Outbreaks: As in previous years, EHEC outbreaks in nursery schools and other locations occurred in 2021 and were presumed to be due to person-to-person transmission (Table 2). In June 2021, an outbreak of O172 VT2 infection was reported (see p.107 of this issue). Additionally, nine outbreaks of food poisoning events due to EHEC, with a total of 42 patients (including EHEC isolation-negative cases), were reported under the Food Sanitation Law (32 outbreaks involving 456 cases in 2018; 20 outbreaks involving 165 cases in 2019; five outbreaks involving 30 cases in 2020) (Table on p.106, see pp.112 and 114 of this issue). Analysis by the Department of Bacteriology I of the NIID revealed that strains exhibiting the same MLVA type or SNP among sporadic cases of unknown epidemiologic association were isolated from a wide geographic area (see pp.108 and 109 of this issue).
Prevention and measures to be implemented: In response to food poisoning events caused by raw beef, the MHLW revised the standards for beef sold for raw consumption (MHLW notice No. 321, October 2011). Furthermore, upon the detection of EHEC O157 from the inner section of cattle liver, the MHLW banned the sale of beef liver for raw consumption (notice No. 404 in July 2012). In 2012, in response to O157-based food poisoning outbreaks attributed to contaminated pickles, the MHLW revised the hygiene code for processing pickles (food safety inspection notice 1012, No. 1, October 2012).
As EHEC can cause infections at bacterial counts as low as ~100, it can easily spread via person-to-person transmission or person-to-food ingredients/products. EHEC-associated food poisoning events attributed to restaurants occurred in 2021 as in previous years (Table on p.106). To prevent EHEC infections, it is essential to observe the basic principles of proper food hygiene (prevention of bacterial contamination, growth, and survival) and continue to remind people not to eat raw or undercooked meat (https://www.gov-online.go.jp/useful/article/201005/4.html, https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/shokuhin/syokuchu/index.html).
Furthermore, EHEC outbreaks continue to occur in large numbers in nursery schools. To prevent such outbreaks, appropriate hygienic practices, such as routine hand washing and hygiene management when using portable swimming pools, should be implemented (“Infection Control Guidelines for Nurseries” revised in 2018) (https://www.mhlw.go.jp/file/06-Seisakujouhou-11900000-Koyoukintoujidoukateikyoku/0000201596.pdf). When a case of EHEC infection is detected within a household or care facility, the PHC should ensure that appropriate measures are strictly implemented to prevent further transmission.