Nationwide epidemiology of hospitalized schistosomiasis in Japan: Coexistence of residual Schistosoma japonicum and non-japonicum infections

Abstract

Schistosomiasis remains a global public health concern, and although transmission of Schistosoma japonicum was eliminated in Japan in 1977, patients continue to be encountered as chronic sequelae of past infections and as imported infections acquired overseas. However, nationwide data on hospitalized patients are limited. We conducted a nationwide retrospective study using the Japanese Diagnosis Procedure Combination inpatient database to clarify the contemporary epidemiological and clinical characteristics of hospitalized patients with schistosomiasis between fiscal years 2014 and 2020. A total of 111 unique hospitalized patients were identified, of whom 103 (93%) had S. japonicum infection and 8 (7%) had non-japonicum schistosomiasis. Patients with S. japonicum infection were older than those with non-japonicum infection (mean age 77.4 vs. 43.8 years), and the age distribution showed a predominant peak in elderly individuals, with a smaller relative increase among middle-aged adults. Coexisting hepatobiliary conditions among S. japonicum cases, including liver cirrhosis (25%) and hepatocellular carcinoma (14%), and colorectal cancer was identified in 4% of patients. Geographic clustering was evident in historically endemic regions, particularly Yamanashi and Fukuoka Prefectures. In contrast, non-japonicum cases were sporadic and more frequently observed in younger individuals. Praziquantel was administered to 4 patients (4%), consistent with the predominance of chronic sequelae rather than active infection. In conclusion, the current inpatient burden of schistosomiasis in Japan predominantly reflects the long-term clinical legacy of past S. japonicum transmission, underscoring the importance of continued clinical awareness and surveillance despite the elimination of domestic transmission.

Graphical abstract

1. Introduction

Schistosomiasis is an important parasitic disease classified by the World Health Organization (WHO) as one of the neglected tropical diseases (NTDs) requiring sustained global control efforts (World Health Organization, 2026). Recent WHO guidelines and the NTD roadmap 2021–2030 have further emphasized the importance of sustained surveillance and long-term management strategies for schistosomiasis control and elimination, including in post-elimination settings (Lo et al., 2022; World Health Organization, 2020). The disease has been reported in 78 countries, and as of 2021, approximately 250 million people worldwide were estimated to require preventive chemotherapy (World Health Organization, 2026). Five species of schistosomes are known to infect humans, including Schistosoma japonicum, each with distinct geographic distributions and clinical manifestations (Colley et al., 2014; Gryseels et al., 2006). Despite ongoing global control efforts, schistosomiasis remains associated with substantial chronic hepatointestinal morbidity and socioeconomic burden in endemic regions (Tabilin et al., 2025). While S. haematobium primarily causes urogenital disease, other species, including S. japonicum, are characterized by intestinal and hepatosplenic involvement (Colley et al., 2014).

Human infection occurs through percutaneous penetration by cercariae released from freshwater snail intermediate hosts (Colley et al., 2014; Gryseels et al., 2006). After maturation, adult worms reside within the venous system and deposit eggs that induce granulomatous inflammation and progressive tissue damage. A proportion of eggs become trapped in organs such as the liver, leading to chronic complications including portal hypertension, hepatic fibrosis, and hepatosplenic disease (Colley et al., 2014; Gryseels et al., 2006).

In Japan, S. japonicum infection was historically endemic in limited areas, including the Kofu Basin in Yamanashi Prefecture, the Chikugo River basin (Fukuoka and Saga Prefectures), and parts of Hiroshima Prefecture (Tanaka and Tsuji, 1997). Through comprehensive public health interventions, including eradication of the intermediate host snail (Oncomelania hupensis nosophora), domestic transmission was successfully eliminated, with the last locally acquired case reported in Yamanashi in 1977 (Tanaka and Tsuji, 1997). Since then, no indigenous transmission has been documented.

Currently, schistosomiasis in Japan presents in two distinct contexts: chronic sequelae among individuals previously infected in historically affected regions, and imported infections associated with overseas exposure (Kirinoki et al., 2015). However, contemporary epidemiological data in Japan have largely been derived from case reports or small case series. Comprehensive nationwide data focusing on hospitalized patients, comorbidities, temporal trends, and geographic distribution remain limited. In particular, the current epidemiological characteristics of S. japonicum infection across historically affected and other regions have not been fully characterized at the national level.

The Diagnosis Procedure Combination (DPC) database is a nationwide administrative inpatient database that captures a large proportion of acute-care hospitalizations in Japan and has been extensively utilized for nationwide epidemiological and health services research (Hayashida et al., 2021). Previous validation studies have demonstrated the reliability of diagnostic, procedural, and laboratory data recorded in the DPC system (Yamana et al., 2017; Yasunaga, 2024). Recently, nationwide epidemiological analyses using the Japanese DPC database have also been reported for several parasitic diseases, including paragonimiasis (Ikushima et al., 2024), echinococcosis (Nakamura et al., 2026), and diphyllobothriasis (Sakakibara et al., 2026), highlighting the utility of administrative inpatient databases for evaluating rare parasitic diseases in Japan. Therefore, we conducted a nationwide retrospective study using the DPC inpatient database to clarify the epidemiological features, clinical characteristics, temporal trends, and geographic distribution of hospitalized patients with schistosomiasis in Japan.

2. Materials and methods

2.1. Study design and data source

This nationwide retrospective observational study was conducted using the Japanese DPC inpatient database. We collected these data through the DPC Research Institute and used them in this analysis. The DPC system is a case-mix–based reimbursement system implemented by the Ministry of Health, Labour and Welfare of Japan and widely adopted by acute-care hospitals nationwide. The database includes comprehensive inpatient information such as patient demographics, primary and secondary diagnoses coded according to the International Classification of Diseases, 10th Revision (ICD-10), procedures and interventions, prescribed medications, length of hospital stay, and discharge status (Matsuda, 2016). Because participation in the DPC system is widespread among tertiary referral centers and community hospitals, the database provides extensive nationwide inpatient data. All data were anonymized before being provided for research purposes. The study period encompassed fiscal years 2014 to 2020.

2.2. Patient identification

Hospitalized patients with schistosomiasis were identified using ICD-10 codes B65.0–B65.2 and B65.8–B65.9. These codes correspond to infections caused by S. japonicum, S. mansoni, S. haematobium, S. intercalatum, and other or unspecified schistosomiasis. Cases coded as B65.3 (cercarial dermatitis) were excluded, as this condition does not represent systemic schistosomiasis. To avoid double counting, repeated hospitalizations of the same individual during the study period were excluded, and only the first hospitalization was included in the analysis. Microbiological, serological, stool, or pathological confirmation data were not available in the DPC database. We examined whether schistosomiasis was recorded as a primary diagnosis or as a secondary diagnosis in the DPC database.

Patients were subsequently categorized into two groups according to ICD-10 subcodes:

• 1.S. japonicum infection.
• 2.Non-japonicum schistosomiasis (including S. mansoni, S. haematobium, S. intercalatum, and unspecified species).

2.3. Variables and clinical characteristics

The following patient characteristics were extracted:

• •Age at admission
• •Sex
• •Length of hospital stay
• •Geographic distribution based on the prefecture of the patient's address.

To evaluate coexisting clinical conditions recorded among hospitalized patients with schistosomiasis, diagnoses recorded in the DPC database were reviewed to identify the following conditions:

• •Liver cirrhosis
• •Hepatic encephalopathy
• •Biliary tract disorders
• •Hepatocellular carcinoma
• •Esophageal varices
• •Ascites
• •Colorectal cancer
• •Cystitis
• •Esophageal cancer

These conditions were identified based on diagnostic entries recorded for each hospitalization.

Administration of praziquantel during hospitalization was identified from medication records in the DPC database.

2.4. Outcomes

The primary objective was to describe the contemporary epidemiological and clinical characteristics of hospitalized patients with schistosomiasis in Japan. Secondary analyses compared demographic features, coexisting clinical conditions, and treatment patterns between patients with S. japonicum infection and those with non-japonicum schistosomiasis.

2.5. Statistical analysis

Continuous variables are presented as mean (standard deviation). Categorical variables are expressed as numbers and percentages. All statistical analyses were performed using SPSS software (version 27; IBM Corp., Armonk, NY, USA).

2.6. Ethical approval

This study was conducted in accordance with the Declaration of Helsinki. Because the DPC database consists of anonymized administrative data, the requirement for informed consent was waived. This study was approved by the Institutional Review Board of the authors' institution (approval number: R4–045).

3. Results

3.1. Patient characteristics

During the study period (FY2014–FY2020), 111 unique hospitalized patients with schistosomiasis were identified after exclusion of duplicate admissions. Among them, 103 patients (93%) were diagnosed with S. japonicum infection and 8 patients (7%) with non-japonicum schistosomiasis. Schistosomiasis was recorded as the primary diagnosis in 16 patients (14%), whereas the majority of cases (86%) were recorded as secondary diagnoses. The baseline characteristics of these patients are summarized in Table 1. The overall mean age was 75.0 years (standard deviation (SD) 18.6). Patients with S. japonicum infection were older than those with non-japonicum infection (77.4 (SD 16.0) vs. 43.8 (SD 22.1) years). The majority of S. japonicum cases occurred in elderly individuals, particularly those aged 70 years or older, whereas non-japonicum cases were more frequently observed in younger and middle-aged adults. Male patients accounted for 63 cases (57%) overall. The mean length of hospital stay was 21.2 (SD 22.9) days and was similar between the two groups. In-hospital mortality occurred in 7 patients (6%) overall. All in-hospital deaths occurred among patients with S. japonicum infection. Praziquantel was administered to 4 patients (4%). Praziquantel administration was numerically more frequent in non-japonicum cases than in S. japonicum cases (25% vs. 2%). However, the number of non-japonicum cases was very small, and these findings should be interpreted cautiously.

Table 1.

Characteristics of hospitalized patients with schistosomiasis (n = 111).

Characteristics	S. japonicum	Non-japonicum	Total
	(n = 103)	(n = 8)	(n = 111)
Clinical outcomes
Length of hospital stay, days, mean (SD)	21.6 (23.3)	16.1 (17.1)	21.2 (22.9)
In-hospital mortality, n (%)	7 (7%)	0 (0%)	7 (6%)
Demographic characteristics
Age, years, mean (SD)	77.4 (16.0)	43.8 (22.1)	75.0 (18.6)
Male sex, n (%)	57 (55%)	6 (75%)	63 (57%)
Comorbidities
Liver cirrhosis	26 (25%)	0 (0%)	26 (23%)
Hepatocellular carcinoma	14 (14%)	0 (0%)	14 (13%)
Biliary tract disorders	7 (7%)	0 (0%)	7 (6%)
Hepatic encephalopathy	7 (7%)	0 (0%)	7 (6%)
Esophageal varices	6 (6%)	0 (0%)	6 (5%)
Ascites	6 (6%)	0 (0%)	6 (5%)
Colorectal cancer	4 (4%)	0 (0%)	4 (4%)
Cystitis	2 (2%)	0 (0%)	2 (2%)
Esophageal cancer	1 (1%)	0 (0%)	1 (1%)
Treatments
Praziquantel administration	2 (2%)	2 (25%)	4 (4%)

Data are presented as mean (standard deviation) or number (%).

3.2. Comorbidities

Liver cirrhosis was present in 26 patients (23%), followed by hepatocellular carcinoma in 14 (13%). Other coexisting diagnoses included biliary tract disorders in 7 patients (6%), hepatic encephalopathy in 7 (6%), esophageal varices in 6 (5%), and ascites in 6 (5%). In contrast, no cases of liver cirrhosis or hepatocellular carcinoma were observed among patients with non-japonicum schistosomiasis. These comorbidities were not mutually exclusive, and multiple conditions could be present in a single patient.

3.3. Annual trends and age distribution

The annual number of hospitalized cases and age distribution by species are shown in Fig. 1A and B. The number of S. japonicum cases varied during the study period, with relatively higher counts in fiscal years 2015 and 2016, fewer cases in 2019, and a slight increase in 2020. In contrast, non-japonicum cases were sporadic throughout the study period, ranging from 0 to 2 cases per year without a consistent increasing trend. Marked differences were also observed in age distribution. S. japonicum cases occurred predominantly in elderly individuals, with the highest frequency in the 80–89-year age group. In contrast, non-japonicum cases were mainly observed in younger and middle-aged adults, particularly those in their 20s to 50s.

Fig. 1.

Annual trends and age distribution of hospitalized patients with schistosomiasis in Japan (2014–2020).

(A) Annual number of hospitalized patients with schistosomiasis by species from fiscal years 2014 to 2020. The majority of cases were attributable to Schistosoma japonicum, with a peak observed in 2015–2016, followed by a gradual decline. Non-japonicum cases were sporadic throughout the study period.

(B) Age distribution of hospitalized patients with schistosomiasis by species. S. japonicum cases were predominantly observed in elderly individuals, particularly those aged 70 years or older, likely reflecting chronic sequelae of past domestic transmission before elimination in Japan, with a smaller peak in middle-aged adults. In contrast, non-japonicum cases were mainly distributed among younger and middle-aged adults, possibly reflecting imported infections associated with overseas exposure. Age groups are shown in years. Because only eight patients with non-japonicum schistosomiasis were identified during the study period, comparisons between the two groups should be interpreted cautiously.

3.4. Geographic distribution

The overall geographic distribution of hospitalized schistosomiasis cases is presented in Fig. 2. Among 111 patients with schistosomiasis infection, the largest number of cases was observed in Yamanashi Prefecture (n = 41), followed by Fukuoka (n = 22), Saga (n = 6), and Hiroshima (n = 4). Additional cases were identified in several prefectures, including Kumamoto (n = 3). Cases were also recorded in multiple other prefectures, including Tokyo (n = 9), Kanagawa (n = 5), and Saitama (n = 3). The overall distribution largely reflected historically affected areas. In contrast, the eight non-japonicum cases were distributed sporadically across multiple prefectures: Tokyo (n = 2), and one case each in Saitama, Aichi, Kyoto, Shiga, Ishikawa, and Hiroshima.

Fig. 2.

Geographic distribution of hospitalized patients with schistosomiasis in Japan (2014–2020).

Choropleth map showing the geographic distribution of all hospitalized patients with schistosomiasis in Japan based on the Diagnosis Procedure Combination (DPC) inpatient database. Color intensity represents the total number of cases recorded in each prefecture during the study period (fiscal years 2014–2020), with darker shading indicating a higher number of patients. The distribution largely reflects cases of Schistosoma japonicum, which accounted for the majority of hospitalized patients and were concentrated in historically affected areas of Japan where domestic transmission had occurred before elimination in 1977. Prefectures shown in gray indicate that no hospitalized cases were recorded during the study period.

4. Discussion

In this nationwide retrospective study using a large-scale inpatient database, we evaluated the contemporary epidemiological and clinical characteristics of hospitalized patients with schistosomiasis in Japan. Most cases were attributable to S. japonicum and were predominantly observed in elderly individuals from historically affected areas. The fact that schistosomiasis was recorded as a secondary diagnosis in the majority of cases suggests that many patients were hospitalized for coexisting chronic conditions rather than for active infection.

The age distribution of hospitalized patients with S. japonicum infection (Fig. 1B) demonstrated a predominantly elderly distribution, with a small relative increase among individuals in their 40s. The younger peak may partly reflect imported infections associated with overseas exposure, whereas the older peak appears to represent chronic or long-standing sequelae of past domestic transmission. However, definitive classification was not possible because travel history and nationality were unavailable in the database. Consistent with this interpretation, patients with S. japonicum infection were older than those with non-japonicum infection (mean age 77.4 vs. 43.8 years), indicating that most hospitalized cases were elderly individuals with historical exposure. Although travel history and nationality were not available in the present database, a previous report analyzing case reports from 2010 to 2014 indicated that most imported S. japonicum cases in Japan occurred among individuals of Philippine nationality, many of whom were young adults aged 21–50 years (Kirinoki et al., 2015). Moreover, S. japonicum remains endemic in parts of Southeast and East Asia, particularly the Philippines, and recent reports have described persistent or newly identified endemic foci in the Philippines (World Health Organization, 2026; Tabilin et al., 2025). Taken together, the relative increase in younger patients observed in this study may partly reflect imported infections from endemic countries, including the Philippines.

The predominance of elderly patients with S. japonicum infection in the present study was accompanied by a high frequency of coexisting hepatobiliary complications. Liver cirrhosis was observed in 25% of patients and hepatocellular carcinoma (HCC) in 14%, findings consistent with the well-recognized chronic pathological consequences of schistosomal infection (Colley et al., 2014). The pathogenesis of chronic S. japonicum infection involves egg deposition within the portal venous system, leading to granulomatous inflammation, periportal fibrosis, and progressive portal hypertension (Colley et al., 2014). Over time, these processes may culminate in cirrhosis and hepatic dysfunction. The International Agency for Research on Cancer (IARC) has classified infection with schistosomes, including S. japonicum, as possibly carcinogenic to humans (Group 2B), reflecting evidence linking chronic schistosomal inflammation to hepatocellular and colorectal carcinogenesis (Infection with schistosomes (Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum), 1994). In our cohort, colorectal cancer was identified in 4% of patients with S. japonicum infection. Previous studies have suggested that persistent egg-induced inflammation may promote epithelial hyperplasia and adenomatous change, potentially contributing to colorectal carcinogenesis (Hamid, 2019). Nevertheless, because of the nature of this administrative database study, the observed associations should be interpreted cautiously, and causal relationships between schistosomiasis and these coexisting diagnoses cannot be established.

Because the vast majority of hospitalized cases were attributable to S. japonicum, the overall geographic distribution (Fig. 2) largely reflected that of S. japonicum infection. The geographic distribution showed a marked concentration in historically affected areas. Yamanashi Prefecture accounted for the largest proportion of cases (40%), followed by Fukuoka (19%). Additional cases were observed in Saga, Kumamoto, and Hiroshima Prefectures, which correspond to areas previously reported to have schistosomiasis occurrence, including the Kofu Basin and Fuji River basin in Yamanashi, the Chikugo River basin in Fukuoka and Saga, and the Katayama district in Hiroshima (Ross et al., 2002; Motomura et al., 2016). This distribution is consistent with earlier Japanese case-based analyses, in which Yamanashi accounted for approximately 40% of reported cases (Kirinoki et al., 2015). In this context, the absence of domestic transmission since the eradication of the intermediate host, Oncomelania hupensis nosophora, further supports the interpretation that current cases are likely to reflect historical infection rather than ongoing transmission.

Praziquantel remains the standard treatment for schistosomiasis and has demonstrated high efficacy against active infection (Colley et al., 2014). In the present study, however, praziquantel was administered during hospitalization in only 2% of patients with S. japonicum infection. The low rate of praziquantel administration may partly reflect the predominance of chronic sequelae rather than active infection. However, interpretation of treatment frequency requires caution because praziquantel use outside standard insurance claims may not be fully captured in the DPC database. These findings are consistent with the advanced age distribution and high frequency of coexisting hepatobiliary conditions observed in our cohort, further supporting the interpretation that contemporary inpatient cases of S. japonicum in Japan primarily reflect long-standing disease rather than ongoing transmission.

Several limitations should be acknowledged. First, this study relied on an administrative inpatient database and ICD-10 codes, which may be subject to misclassification because microbiological, serological, stool, and pathological confirmation data were unavailable. In addition, the number of non-japonicum cases was very small, limiting the reliability of subgroup comparisons. Detailed clinical information, including travel history and nationality, was not available; therefore, imported and domestically acquired infections could not be definitively distinguished. Second, the DPC database includes only hospitalized patients, and causal relationships between S. japonicum infection and associated complications cannot be established. In addition, because the DPC database captures only medications administered during hospitalization, prior or outpatient treatment with praziquantel could not be evaluated. Furthermore, praziquantel is not formally approved for schistosomiasis under the Japanese national health insurance system. In clinical practice, treatment for active schistosomiasis may therefore be administered through non-standard pathways that are not fully reflected in administrative inpatient databases. Consequently, the present findings should be interpreted primarily as reflecting the characteristics of hospitalized patients and their coexisting chronic conditions rather than the overall treatment patterns of schistosomiasis in Japan. Despite these limitations, this nationwide analysis provides valuable insight into the contemporary inpatient burden and long-term clinical consequences of schistosomiasis in Japan. Importantly, the persistence of hospitalized S. japonicum cases decades after transmission interruption highlights the long-term pathological footprint of helminth infections even in post-elimination settings, underscoring the importance of continued surveillance and clinical awareness after elimination (Lo et al., 2022).

5. Conclusion

In conclusion, this nationwide inpatient analysis demonstrated that most hospitalized cases of schistosomiasis in Japan were attributable to S. japonicum and were predominantly observed in elderly individuals from historically affected areas. The age distribution, characterized by a predominant elderly peak with a smaller relative increase among middle-aged adults, suggests a mixture of chronic sequelae of past domestic transmission and a smaller proportion of potentially imported infections. The high frequency of coexisting hepatobiliary and colorectal conditions underscores the long-term clinical impact of S. japonicum infection, despite the elimination of domestic transmission in 1977. These findings emphasize the enduring clinical impact of S. japonicum infection long after the interruption of domestic transmission.

Generative AI and AI-assisted technologies statement

During the preparation of this manuscript, the authors used ChatGPT (OpenAI, San Francisco, CA, USA) to assist with English language editing and refinement of the manuscript text. The authors reviewed and edited the output as necessary and take full responsibility for the content of the publication.

CRediT authorship contribution statement

Tatsuya Shingu: Writing – original draft, Visualization, Data curation. Naoaki Ohkubo: Writing – review & editing, Data curation. Kei Yamasaki: Writing – review & editing, Writing – original draft, Visualization, Supervision, Methodology, Formal analysis, Data curation. Ryo Torii: Writing – original draft, Visualization, Data curation. Ryosuke Hata: Writing – review & editing. Masahiro Tahara: Writing – review & editing. Kei Nakamura: Writing – review & editing. Chinatsu Nishida: Writing – review & editing. Makoto Okawara: Writing – review & editing, Data curation. Yoshihisa Fujino: Writing – review & editing, Data curation. Shinya Matsuda: Writing – review & editing. Kiyohide Fushimi: Writing – review & editing. Hiroshi Mukae: Writing – review & editing. Kazuhiro Yatera: Writing – review & editing.

Ethics approval

This study was approved by the Institutional Review Board of the University of Occupational and Environmental Health, Japan (approval number: R4–045). The requirement for informed consent was waived due to the retrospective design and the use of anonymized administrative data.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.