Epidemiology of amebiasis around the COVID-19 pandemic period in Japan

doi:10.21203/rs.3.rs-4950019/v1

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Epidemiology of amebiasis around the COVID-19 pandemic period in Japan

https://doi.org/10.21203/rs.3.rs-4950019/v1

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Amebiasis cases in Japan are reported to the government according to the Infectious Diseases Control Law. Previous studies have shown significant reductions in total case numbers after 2018 and during the COVID-19 pandemic. This study aimed to clarify the recent trends of amebiasis in Japan, including during the pandemic period, with details on places of infection and disease types, using government surveillance data from January 1, 2001, to December 31, 2022. Multiple comparisons by Dunnett’s test were performed to compare case numbers of three time periods (2015-2017, 2018-2019, and 2020-2022). Significant decreases in reported amebiasis cases were observed in 2018 (24.5%) and in 2020 (45.3%). This downward trend was observed regardless of place of infection (domestic or imported) and disease type (intestinal or extraintestinal). Male cases predominated, with most male cases in their 40s and 50s.Most cases of amebiasis have been reported in metropolitan areas. These results suggest that the decreased case numbers during the COVID-19 pandemic were due to not only the travel ban, but less socioeconomic activity. Furthermore, the epidemiology of amebiasis is similar to that of HIV infection in Japan, but the case numbers of amebiasis have not yet recovered, showing a different trend from HIV infection and syphilis.

Health sciences/Medical research/Epidemiology

Health sciences/Diseases/Infectious diseases/Parasitic infection

amebiasis

Japan

epidemiology

COVID-19

Amebiasis is an infectious disease caused by Entamoeba histolytica. This pathogen induces amoebic colitis, which is a major cause of diarrhea in developing countries. In developed countries, though it causes travelers’ diarrhea, men who have sex with men (MSM) are known to have a higher risk of amebiasis. Thus, amebiasis is a sexually transmitted disease (STD), as well as a gastrointestinal infection [1]. Amebiasis is included in notifiable disease surveillance under Japan’s Infectious Disease Control Law. For all amebiasis cases in Japan, physicians are required to report relevant information to the government. Therefore, nationwide epidemiological trends in amebiasis cases can be tracked in Japan. The National Institute of Infectious Diseases (NIID) published a partial summary report of the epidemiology of amebiasis for the decade up to 2016 online [2]. Ishikane et al. analyzed amebiasis cases in Japan up to 2013 and reported an increase in the number of domestic cases [3]. More recently, Hadano et al. identified a significant decrease in amebiasis cases in the country after 2018, when commercial distribution of antibody test reagents was stopped [4]. Hirae et al. demonstrated that the total number of amebiasis cases in Japan decreased along with other communicable diseases during the COVID-19 pandemic period [5]. However, to the best of our knowledge, there have not been any reports of the recent epidemiology of amebiasis in Japan including the COVID-19 pandemic period, by place of infection (domestic or imported) and by disease type (intestinal amebiasis or extraintestinal amebiasis). The primary objective of this study was to clarify recent epidemiological trends in amebiasis in Japan, including the COVID-19 pandemic period, with details on places of infection and disease types. In addition, summary charts of the epidemiology of amebiasis in Japan up to 2022 (by sex, age class, and prefecture), making clear the epidemiological trends in amebiasis in the country, are provided.

This was a retrospective study using data from January 1, 2001, to December 31, 2022, obtained from the National Epidemiological Surveillance of Infectious Diseases (NESID) made available by NIID. The surveillance is conducted in accordance with the Infectious Diseases Control Law. According to the government guideline [6], each amebiasis case is confirmed by one of the following methods: (i) detecting pathogen by microscopy, (ii) detecting antigen of the pathogen by ELISA, (iii) detecting genes of the pathogen by PCR, (iv) detecting antigen of the pathogen by immunochromatography, or (v) detecting antibody. Of the methods listed above, (i), (ii), and (iii) use stool, biopsy, or abscess fluid samples, (iv) uses stool samples, and (v) uses serum samples. Physicians who diagnose amebiasis are required to report a case to the government in 7 days. The reporting form includes information on the patient’s sex and age, disease type (intestinal or extraintestinal), diagnosis method, route of infection, and place of infection. For disease types, the government guideline describes intestinal amebiasis as chronic intestinal infection with symptoms of diarrhoea, bloody stool, tenesmus and so forth. It also describes extraintestinal amebiasis as abscess formation, typically in the liver, mostly caused by spread of the pathogen through the bloodstream. When reporting, physicians select the category into which each case falls. NESID data are tentatively summarized and published weekly. Yearly summaries are provided as annual reports [7], which include tables of notifiable infectious diseases by week, by place of infection, by disease type, by sex, by age group, and by prefecture.

In the present study, the annual reports through 2022 were further summarized and analyzed. Annual trends in amebiasis cases reported in Japan were summarized by place of infection (domestic or imported, from 2001 to 2022) and by disease type (i.e., intestinal and/or extraintestinal amebiasis, from 2008 to 2022). To observe recent trends, case numbers from 2018 to 2022 were summarized in tables, and percentage changes compared to the average of 2015 to 2017 were calculated. For statistical analyses, multiple comparisons by Dunnett’s test of three consecutive time periods, 2015–2017, 2018–2019, and 2020–2022, were performed for the numbers of reported cases by place of infection and by disease type. For all analyses, p values were two-sided, and p < 0.05 was considered significant. Statistical analyses were conducted with EZR [8], which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). In addition, summary charts of amebiasis cases reported in Japan by sex, by age class, and by prefecture (from 2001 to 2022) were created using the NESID data.

The annual trends in amebiasis cases reported in Japan from 2001 to 2022 by place of infection are shown in Fig. 1a. After 2014, the total number of reported cases reached a plateau. The average number of total cases in 2015–2017 was 1116.3 cases/year. In 2018, the total case numbers decreased to 843 cases/year (-24.5%, compared with the average number of cases in 2015–2017; Table 1). In 2020, they further decreased to 611 cases/year (-45.3% compared with the same average), and this trend continued through 2022. Numbers of total, domestic, and imported cases decreased significantly over the three periods (2015–2017, 2018–2019, and 2020–2022; Fig. 1b).

Table 1

Recent trends in reported cases of amebiasis in Japan by place of infection
	Average (2015–2017)	2018	2019	2020	2021	2022
Domestic cases	936.7	555	567	417	353	343
% change		-40.7	-39.5	-55.5	-62.3	-63.4
Imported cases	136.7	109	92	48	47	30
% change		-20.3	-32.7	-64.9	-65.6	-78.1
Unknown cases	43	179	194	146	137	160
% change		316.3	351.2	239.5	218.6	272.1
Total cases	1116.3	843	853	611	537	533
% change		-24.5	-23.6	-45.3	-51.9	-52.3
Values are shown as percentages (compared with the average of 2015–2017, rounded to the second decimal place).

Figure 2a shows the annual trends in amebiasis cases reported in Japan by disease type (intestinal amebiasis, extraintestinal amebiasis, and intestinal/extraintestinal amebiasis) from 2008 to 2022. The average number of extraintestinal cases in 2015–2017 was 121.7 cases/year. In 2018, the number of extraintestinal amebiasis cases decreased to 47 cases/year (-61.4%, compared with the average number above; Table 2). Numbers of intestinal amebiasis cases and extraintestinal amebiasis cases in Japan showed significant decreases over the three periods (2015–2017, 2018–2019, and 2020–2022; Fig. 2b).

Table 2

Recent trends in reported cases of amebiasis in Japan by disease type
	Average (2015–2017)	2018	2019	2020	2021	2022
Intestinal amebiasis	956	776	791	553	485	492
%change		-18.8	-17.3	-42.2	-49.3	-48.5
Extraintestinal amebiasis	121.7	47	42	28	23	25
%change		-61.4	-65.5	-77	-81.1	-79.5
Intestinal and extraintestinal amebiasis	38.7	20	20	30	29	16
%change		-48.3	-48.3	-22.5	-25.1	-58.7
Values are shown as percentages (compared with the average of 2015–2017, rounded to the second decimal place).

The yearly numbers of reported cases of amebiasis in Japan by sex from 2001 to 2022 are shown in Fig. 3a (domestic cases) and Fig. 3b (imported cases). As previously reported [3], male cases predominated in both domestic and imported cases, and recent years have not seen a change in this trend.

The numbers of reported amebiasis cases in Japan by sex and age class, from 2001 to 2022, for domestic and imported cases are shown in Fig. 4a and b, respectively. Male cases predominated in age classes of the 30s to 70s, with the most frequent age classes of male cases being the 40s and 50s.

Figure 5a shows the number of amebiasis cases by prefecture (2001–2022). As previously reported [3], most amebiasis cases in Japan have been reported in metropolitan areas such as Tokyo, Osaka, Kanagawa, and Aichi prefectures. Figure 5b shows the number of cases per 100,000 population (population data were obtained from estimates by the government [9]). As shown in this figure, there is still a higher incidence in populated areas such as Tokyo and Osaka.

The number of reported amebiasis cases in Japan decreased significantly in 2018 and 2020 (Figs. 1 and 2, Tables 1 and 2), and these significant decreases were seen regardless of place of infection (domestic or imported) and disease type (intestinal or extraintestinal amebiasis). Hadano et al. showed significant decreases in the numbers of total, intestinal, and extraintestinal weekly reported cases of amebiasis in 2018 and 2019 compared with the preceding years (2014–2017) [4]. Of note, the present study showed that the same period saw significant reductions of the numbers of both domestic and imported cases. In this period, the antibody test reagent stopped being distributed commercially [4, 10], which might have reduced the number of reported amebiasis cases, regardless of the place of infection. Hirae et al. demonstrated a significant decrease in the total number of amebiasis cases in Japan in the intra-pandemic period (2020–2021) compared with the pre-pandemic period (2015–2019) [5]. The present results show that the COVID-19 pandemic might have reduced the number of amebiasis cases regardless of place of infection (domestic or imported) and disease type (intestinal or extraintestinal amebiasis). One can infer that the reduction of amebiasis cases in the intra-pandemic period was brought about not only by the travel ban to and/or from other countries [5], but also by the reduction of socioeconomic activity within the country during that period.

Recent epidemiological trends in amebiasis cases in Japan during and after the COVID-19 pandemic period might have behaved differently from other STDs such as syphilis and HIV. Reported cases of amebiasis in Japan decreased after 2018 and 2020, and the number has not rebounded up to 2022 (Fig. 1a, Table 1). The annual report has not been published yet as of July 16, 2024, but according to the year-end issue of the weekly report [7] of 2023, the tentative accumulated number of reported amebiasis cases in that year was 485 (the number for 2022 was 533, according to the annual report). Reduced numbers of cases in 2020 were also reported for HIV [11] and syphilis [12]. Komori et al. [12] showed a rapid resurgence of the number of syphilis cases reported in Japan in 2021. The rebound trend has also been reported for HIV [13] in 2023. The reason why epidemiological trends differ between amebiasis and these diseases is unclear, but amebiasis as a fecal-oral transmitted disease might have been the key.

Japan is among a few countries where nationwide epidemiological data for amebiasis are available, as well as Taiwan, and trends are similar between the two nations. In Japan, the mode age class of male amebiasis cases was in the 40s and 50s (Fig. 4), which is older than that of female cases, with most cases reported in metropolitan areas (Fig. 5). In Taiwan, the age class mode of male domestic cases was in the 30s, older than that of female cases [14]. In addition, about 40% of male domestic cases were reported in the capital city, Taipei. For comparison, in Western Sydney, Australia, 88% of confirmed cases of amebiasis were male cases, with a median age of 49 years [15]. Although nationwide epidemiological information is scarce for developed countries other than Japan and Taiwan, we can infer that the same trends in amebiasis cases (male-to-female difference and urban occurrence) might apply to other developed nations.

Inside Japan, there exists epidemiological similarity between amebiasis and HIV infection. Ruzicka et al. analyzed a hospital claims database in Japan, showing that 90% of people living with HIV on antiretrovirals are male, and the most frequent age class is in the 40s [16]. This feature coincides with the epidemiology of amebiasis shown in the present study (Figs. 3 and 4), which has been partially mentioned in the previous literature [3, 17]. To the best of our knowledge, no reports have shown that amebiasis is spread among MSM using nationwide epidemiological data, but, given the similarity with HIV epidemiology, one can infer that one aspect of the spread of amebiasis is as an STD among MSM.

There are several limitations in this study. First, even though the government has not taken any measures to prevent amebiasis from spreading in recent years, significant reductions of case numbers in 2018 and 2020 might have been due to a natural decrease caused by improvement of general hygiene. Second, the NESID reporting system is well established and considered to be reliable, but there may be a discrepancy between the reported numbers and the actual numbers of cases. Of concern, amebiasis cases without subjective symptoms are not diagnosed and not reported. Furthermore, though amebiasis as an STD among MSM was discussed, based on the similarity of its epidemiology with that of HIV, the most frequent reported route of infection [3] is “unknown”; thus, the actual status of amebiasis as an STD remains unclear. Future studies are needed to clarify actual routes of infection of amebiasis, and if possible, describe routes of infection by sex and by age class.

In conclusion, the number of amebiasis cases reported in Japan decreased significantly in 2018 and 2020 regardless of the place of infection (domestic or imported) and disease type (intestinal or extraintestinal amebiasis). The 2020 decrease coincided with the COVID-19 pandemic, which might have reduced the amebiasis case numbers through not only the travel ban to/from overseas, but less socioeconomic activity during the period. A rebound of case numbers in Japan, which has been seen for syphilis and HIV infection after the COVID-19 pandemic, has not yet been observed for amebiasis. In terms of the male-to-female ratio and the common age classes of reported cases, there is similarity between amebiasis and HIV infection. Why the epidemiological trends in amebiasis behave differently from those of HIV infection and syphilis after the pandemic remains unknown.

Ethical approval

This study was not subject to ethics application. Permission to use the NESID data is on the NIID’s website [18]. Information of reported cases is already anonymized in the weekly and annual reports of NESID and widely used for academic research.

Data availability

The datasets generated and/or analyzed during the current study are available. https://www.niid.go.jp/niid/ja/idwr.html

Author contributions

KI conceived of and designed this study, interpreted the data, drafted the manuscript, and revised the manuscript for important intellectual content. HM conceived and designed this study, interpreted the data, and revised the manuscript for important intellectual content. YH, AM, and TN conceived this study and revised the manuscript for important intellectual content. All authors contributed to the acquisition of data, and reviewed, discussed, and approved the final manuscript.

Funding: None

Competing interests: None

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No competing interests reported.

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Epidemiology of amebiasis around the COVID-19 pandemic period in Japan

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