Trends and characteristics of syphilis incidence in Japan: a nationwide claims-based analysis of working-age populations and their dependents, 2016–2023 - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice BMJ Open . 2026 Apr 15;16(4):e114337. doi: 10.1136/bmjopen-2025-114337 Search in PMC Search in PubMed View in NLM Catalog Add to search Trends and characteristics of syphilis incidence in Japan: a nationwide claims-based analysis of working-age populations and their dependents, 2016–2023 Kazuhiko Ikeuchi Kazuhiko Ikeuchi 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Kazuhiko Ikeuchi 1, ✉ , Kazuya Okushin Kazuya Okushin 2 Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 3 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Kazuya Okushin 2, 3 , Yuki Arisato Yuki Arisato 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Yuki Arisato 1 , Toshiyuki Kishida Toshiyuki Kishida 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Toshiyuki Kishida 1 , Shinya Matsumoto Shinya Matsumoto 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Shinya Matsumoto 1, 2 , Akira Kado Akira Kado 3 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 4 Division for Health Service Promotion, The University of Tokyo, Bunkyo-ku, Japan Find articles by Akira Kado 3, 4 , Hiroshi Yotsuyanagi Hiroshi Yotsuyanagi 5 Department of Infectious Diseases and Applied Immunology, IMSUT Hospital, The University of Tokyo Institute of Medical Science, Minato-ku, Tokyo, Japan Find articles by Hiroshi Yotsuyanagi 5 , Takeya Tsutsumi Takeya Tsutsumi 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan Find articles by Takeya Tsutsumi 1, 2 Author information Article notes Copyright and License information 1 Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 2 Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 3 Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan 4 Division for Health Service Promotion, The University of Tokyo, Bunkyo-ku, Japan 5 Department of Infectious Diseases and Applied Immunology, IMSUT Hospital, The University of Tokyo Institute of Medical Science, Minato-ku, Tokyo, Japan Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. None declared. ✉ Dr Kazuhiko Ikeuchi; [email protected] Received 2025 Nov 26; Accepted 2026 Mar 20; Collection date 2026. Copyright © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/ . PMC Copyright notice PMCID: PMC13084880 PMID: 41985946 Abstract Abstract Objectives To examine trends and demographic characteristics of syphilis incidence in Japan using a large nationwide claims database with family linkage, with particular focus on differences by sex, age, HIV status and family relationships. Design Retrospective cohort study. Setting JMDC claims database (JMDC Inc, Tokyo, Japan), a nationwide administrative claims database in Japan, using data from 2016 to 2023. Participants Individuals aged 16–59 years enrolled in the JMDC database, including employees of medium-to-large companies and their dependents (n=12.5 million). Outcome measures Syphilis cases were defined by International Classification of Diseases, 10th Revision (ICD-10) codes (A50–A53) with concurrent treatment with relevant antibiotics. We determined syphilis incidence rates per 100 000 person-years, stratified by sex, age, HIV status and family relationships. We also investigated within-couple concordance patterns and reinfection rates. Results Among 16.4 million individuals, 9357 syphilis infections were identified among 8881 individuals. Incidence increased markedly during the pandemic, reaching 48.2 (men) and 12.9 (women) per 100 000 person-years in 2023. Men showed consistently high incidence in their 20s–50s, whereas female incidence peaked in the 10s–20s. Among 2 294 184 married couples, dependent women (ie, housewives) showed comparably high incidence to age-matched men (10–20 per 100 000 person-years). In 1286 couples with at least one syphilis case, 12.4% of wives in their 20s were also diagnosed, compared with 2%–3% in older groups. In 20s couples, the proportion of syphilis among wives only and husbands only was similar. Subgroup analysis revealed notably high incidence among unmarried female dependent youths (2022: 66.7 per 100 000 person-years). Individuals living with HIV had substantially elevated incidence (3000–15 000 per 100 000 person-years) and reinfection rates. Conclusions Using a large claims database with family linkage, we found that while male syphilis incidence remained dominant, high rates were also observed among dependent women and youths. These findings suggest that syphilis risk may extend beyond traditionally recognised high-risk populations and emphasise the need for targeted screening and preventive strategies in broader demographic groups. Keywords: Syphilis, Epidemiology, Sexually Transmitted Disease STRENGTHS AND LIMITATIONS OF THIS STUDY. This study used a large nationwide administrative claims database (JMDC) covering approximately 10%–20% of Japan’s working population, enabling precise incidence calculations with family linkage data. The inclusion of family relationship data allowed us to analyse intra-couple transmission patterns, a methodological strength not available in most surveillance datasets. The database overrepresents employees of medium-to-large companies and their dependents and therefore may not be representative of the broader Japanese population, particularly those in smaller companies, self-employed individuals or the elderly. Laboratory data (eg, serological test results) were unavailable, so the case definition relied on ICD-10 codes combined with prescription records, which may affect diagnostic accuracy. The married-couple analysis was limited to households in which the husband was the primary insured and the wife was a dependent, excluding dual-income couples; thus, findings from this subgroup should be interpreted with caution. Introduction Syphilis, caused by Treponema pallidum , is a sexually transmitted infection known since the 16th century. 1 Despite its easy diagnosis and curability with benzathine penicillin G, 2 its control remains challenging due to the lack of a vaccine and the possibility of reinfection. 3 Symptoms of early syphilis may resolve spontaneously while the pathogen persists, making self-recognition difficult. 1 4 In addition, the clinical manifestations of syphilis are highly protean and often atypical, which may further complicate diagnosis. Untreated cases may progress to serious complications, including neurosyphilis and congenital infection. 1 The WHO estimated 8 million global infections in 2022 among individuals aged 15–49. 5 Prior to the pandemic, a resurgence of syphilis had been documented across multiple countries worldwide during the 2010s, including in Asia and Europe. 6 , 8 The COVID-19 pandemic has also had a notable impact on syphilis trends. Although syphilis case reports declined in many countries in 2020—possibly due to reduced mobility during lockdowns and/or decreased healthcare-seeking behaviour—this was followed by a sharp resurgence. 9 , 13 Since 2021, syphilis incidence has rebounded in the USA and across Europe, and the number of reported cases remains at historically high levels. While syphilis has traditionally been concentrated among men who have sex with men (MSM) in high-income countries, 1 a shifting trend has emerged. In the USA, the number of reported syphilis cases among women doubled between 2014 and 2018, 14 and the number of congenital syphilis cases increased ninefold between 2012 and 2021. 12 Similarly, in Japan, syphilis was previously concentrated among MSM, but a notable increase in heterosexual transmission has been reported, 8 particularly through commercial sex work. 15 Distinct strains of T. pallidum have been identified in MSM and heterosexual networks. 16 As in other countries, Japan experienced a transient decline in reported syphilis cases in 2020, likely influenced by the COVID-19 pandemic. However, the number of cases reached an all-time high in 2022 and remained at similarly elevated levels in 2023 and 2024. 8 Preventive efforts like doxycycline post-exposure prophylaxis (Doxy-PEP) are being studied among MSM, 17 but strategies for heterosexual populations are limited. 18 Public awareness campaigns, routine screening and consistent condom use remain the primary strategies for syphilis prevention in these populations. Understanding the transmission patterns, affected populations and incidence rates is therefore essential for tailoring effective interventions. This study aimed to examine trends and demographic characteristics of syphilis incidence in Japan using a nationwide administrative claims database with family linkage, with particular focus on differences by sex, age, HIV status and family relationships before and after the COVID-19 pandemic. Methods Study design and data source We conducted a retrospective cohort study using the JMDC claims database (JMDC, Tokyo, Japan), which includes health insurance data from employees of medium-to-large companies and their dependents. As of 2023, the database covers approximately 11 million individuals (cumulatively ~17 million), accounting for ~10%–20% of Japan’s working population. It contains information on diagnoses (ICD-10 coded), prescriptions, procedures and laboratory tests. Enrolment and withdrawal dates are recorded even for those without healthcare use, enabling accurate risk population definitions and incidence rate calculations. The database also includes family relationship data (eg, spouse, child). In Japan, dependants are legally defined as family members with annual income below ~1.3 million JPY and supported by the insured. When both spouses are independently insured, their relationship is not captured; thus, identified spousal pairs primarily represent households with a financially dependent partner (typically female in Japan). Consequently, identifiable married couples in this database predominantly represent households in which the husband is the primary insured and the wife is registered as a dependent spouse. Children listed as dependents are presumed to be financially dependent and not employed. As the database primarily covers employees of medium-to-large companies and their dependents, the study population may overrepresent individuals with stable employment, higher socioeconomic status and urban residence compared with the general Japanese population. Study population We included individuals enrolled in the JMDC database between 1 January 2016 and 31 August 2023, aged ≥16 and ≤59 years. The lower age reflects Japan’s age of sexual consent; the upper bound reflects retirement-associated disenrolment from employment-based insurance. The investigators had full access to anonymised diagnostic, prescription and family structure data for all insured individuals during the study period. Definitions and data preparation Syphilis was defined as an ICD-10 diagnosis (A50–A53) including congenital syphilis (A50), early syphilis (A51), late syphilis (A52) and other or unspecified syphilis (A53), with treatment initiated in the same calendar month. As intramuscular benzathine penicillin G became available in Japan only in 2021, treatment was defined as: (1) ≥14 days of oral amoxicillin, penicillin, minocycline or doxycycline or (2) ≥10 days of IV penicillin G or ceftriaxone. Laboratory data were unavailable; thus, reinfection was defined as new treatment ≥365 days after a prior episode. Repeated treatment for late-stage, neurosyphilis or congenital syphilis was not considered reinfection. Baseline variables included age, sex, dependent status, pregnancy and HIV status. Pregnancy was estimated by identifying newborn dependents added in the same month as their birth and assuming the biological mother was pregnant during the prior 280 days. HIV infection was defined by ICD-10 codes (B20–B24) plus antiretroviral therapy prescription. Individuals with ambiguous or missing family structure data were included in overall analyses but excluded from subgroup analyses requiring precise relationship classification. Statistical analysis We calculated incidence rates per 100 000 person-years with 95% CIs, excluding 365 days after each syphilis episode to avoid misclassifying ongoing infections as new events. CIs were estimated assuming a Poisson distribution. Age was defined per calendar year based on the start of follow-up in each year. Subgroup analyses included: all males and females; insured males and females; married couples (husband as primary insured); dependent youths; and HIV-positive males. Due to small sample sizes, HIV-positive females and households with insured wives and dependent husbands were not analysed in detail. Among married couples in which the husband was primary insured and at least one partner was diagnosed with syphilis, we calculated the proportion of spouses tested within 90 days and the overall proportion ever diagnosed with syphilis, regardless of timing, to account for latency. Analyses were performed using Stata V.18 (StataCorp). Patient and public involvement None. Results Patient selection Between 1 January 2016 and 31 August 2023, a total of approximately 16 450 374 participants (8 433 456 men and 8 016 918 women) were registered in the JMDC database. Among them, 6 439 993 men and 6 176 363 women were observed during the period in which they were aged 16–59 years. The median age at the beginning of each participant’s observation period was 34 years (IQR, 23–45). The median observation period per participant was 1247 days (IQR, 517–2192), corresponding to a total of 4.66 × 10⁷ person-years of follow-up. Incidence of syphilis by sex and age During the study period, a total of 9357 syphilis cases were identified among 8881 individuals (7798 episodes in 7354 men and 1559 episodes in 1527 women). The distribution of cases by sex and dependent status is shown in online supplemental figure S1 . Overall, the incidence of syphilis increased from 2016 (men: 18.2 per 100 000 person-years (95% CI 16.4 to 20.1); women: 2.8 (2.0 to 3.7)) to 2019 (men: 25.8 (24.2 to 27.6); women: 6.4 (5.5 to 7.4)). This was followed by a temporary decline in 2020 and a marked resurgence thereafter, reaching 48.2 (45.6 to 51.0) among men and 12.9 (11.4 to 14.5) among women in 2023 ( figure 1A ). Figure 1. Syphilis incidence by sex and age. (A) Overall syphilis incidence by sex (all ages). (B) Men, by age group. (C) Women, by age group. Shaded bands indicate 95% CIs. PY, person-years. Open in a new tab When stratified by age ( figure 1B and C ), syphilis incidence among men remained consistently high from their 20s to 50s. Although the incidence among teenage males was relatively low, it continued to increase through 2023, unlike other male age groups. Among women, incidence peaked in the teens and 20s, with adolescent females exhibiting higher rates than their male counterparts. Incidence dropped sharply among women aged 30 years and older. Notably, teenage females also continued to show an upward trend in 2023, mirroring the pattern seen in teenage males. Subgroup analysis: syphilis among married couples We analysed syphilis incidence among 2 294 184 married couples in which the male partner was the primary insured. Figure 2A and B illustrates the incidence rates among insured male spouses and their dependent wives, respectively. Figure 2. Syphilis incidence in population subgroups. (A) Married men (primary insured), by age group. (B) Married women (dependent), by age group. (C) Dependent male youths. (D) Dependent female youths. Shaded bands indicate 95% CIs. PY, person-years. Open in a new tab Among husbands, incidence remained relatively consistent across those in their 20s to 50s. The rates showed a steady upward trend over time, rising from approximately 10 per 100 000 person-years in 2016 to between 20 and 30 per 100 000 person-years in 2023. Despite this increase, incidence in this group tended to be lower than that observed in the overall male population. Among dependent female spouses (ie, housewives), incidence was low in those aged 30 years and older. In contrast, women in their 20s exhibited incidence rates similar to their husbands. For example, in 2023, the incidence among dependent wives in their 20s was 24.7 per 100 000 person-years (95% CI 9.9 to 50.9). A total of 1286 couples (2572 individuals) had at least one partner diagnosed with syphilis. Among these, only 164 couples (12.8%) had the other partner undergo syphilis testing within 90 days of the index case’s diagnosis. Testing rates were higher among younger wives and decreased with age: 0% (0/1) in their 10s, 28.9% (28/97) in their 20s, 19.1% (72/376) in their 30s, 8.1% (38/469) in their 40s and 7.6% (26/343) in their 50s. Overall, 77.8% (1001/1286) of couples had infection in the husband only, 17.4% (224/1286) in the wife only, and 4.7% (61/1286) in both partners ( table 1 ). When stratified by the wife’s age group, the proportion of co-infection decreased with wife’s age: 12.4% (12/97) in 20s, 7.7% (29/376) in 30s, 2.6% (12/469) in 40s and 2.3% (8/343) in 50s. Among couples with wives in their 20s, the proportions with infection only in the husband and only in the wife were comparable at 41.2% (40/97) and 46.4% (45/97), respectively. In contrast, with increasing age, infection was more frequently observed in the husband only; in couples with wives in their 50s, 87.8% (301/343) had infection in the husband only, while only 9.9% (34/343) had infection in the wife only. Table 1. Syphilis infection among married couples. Wife’s age group Total couples Syphilis in husband only Syphilis in wife only Both 10s * 1 1 (100.0%) 0 (0.0%) 0 (0.0%) 20s 97 40 (41.2%) 45 (46.4%) 12 (12.4%) 30s 376 263 (69.9%) 84 (22.3%) 29 (7.7%) 40s 469 396 (84.4%) 61 (13.0%) 12 (2.6%) 50s 343 301 (87.8%) 34 (9.9%) 8 (2.3%) Total 1286 1001 (77.8%) 224 (17.4%) 61 (4.7%) Open in a new tab * Includes individuals aged 16 years and older only. Among 2 294 184 married couples, a total of 272 918 couples experienced 345 653 childbirths during the study period. Among these pregnancies, 45 pregnant women were diagnosed with syphilis, and treatment was provided in 47 instances (13.5 cases per 100 000 pregnancies (95% CI 9.9 to 17.9)). During the same period, the husband was diagnosed with syphilis during his wife’s pregnancy in 38 instances (11.0 cases per 100 000 pregnancies (95% CI 7.9 to 15.3)). In total, there were eight couples in which both the pregnant woman and her husband were diagnosed with syphilis. Among the 345 653 live-born children, eight received treatment for syphilis after birth. In two of these cases, the mother had received treatment during pregnancy, while in the remaining six, the mother had not received treatment for syphilis during pregnancy. Subgroup analysis: dependent youths We conducted a subgroup analysis focusing on dependent youths ( figure 2C and D ). Overall, trends among dependent youths were similar to those observed in individuals of comparable age and sex. However, the syphilis incidence was notably high among females in their 20s. In 2022, the incidence rate in this group peaked at 66.7 per 100 000 person-years (95% CI 53.0 to 82.8), one of the highest rates among all subgroups. Although the incidence among females in their 20s declined in 2023 to 42.0 (28.8 to 59.4), the incidence among teenage females continued to rise, increasing from 17.2 (12.2 to 23.5) in 2022 to 33.3 (24.2 to 44.7) per 100 000 person-years in 2023. Subgroup analysis: men living with HIV Among men living with HIV, the incidence of syphilis was extremely high ( figure 3 ). The incidence was approximately 5000 per 100 000 person-years in 2016 and gradually increased to around 10 000 per 100 000 person-years in subsequent years. The incidence was highest among individuals in their 20s to 40s and slightly lower in those in their 50s. While a slight plateau was observed in the 30s to 50s age groups during 2022–2023, the incidence among individuals in their 20s continued to rise in 2023, similar to the trend observed in the non-HIV population. Figure 3. Syphilis incidence among men living with HIV Shaded bands indicate 95% CIs. PY, person-years. Open in a new tab Reinfection rate Among the 7354 men who were diagnosed with syphilis, 5.2% (380/7354) experienced reinfection. The reinfection incidence rate was 4137 per 100 000 person-years (95% CI 3761 to 4540), indicating a very high risk. Among men living with HIV (n=692), the reinfection rate reached 19 004 (16 314 to 22 010) per 100 000 person-years, whereas among HIV-negative men (n=6662), the rate was 2715 (2399 to 3062). Among the 1527 women diagnosed with syphilis, 2.0% (31/1527) experienced reinfection. The reinfection rate in women was 2174 (1487 to 3069) per 100 000 person-years. Discussion This study examined syphilis incidence using a nationwide administrative claims database with family linkage. In this relatively high-income population, syphilis incidence was significantly higher among men, but in their 20s, incidence was nearly equal between sexes. Notably, younger wives showed a high incidence, with many cases where only the wife was infected. Although our study population comprised employees of medium-to-large companies and their dependents, overall trends closely paralleled national surveillance data 8 : a gradual rise in the 2010s, slight decline in 2020, and sharp increase thereafter. Notably, the male-to-female incidence ratio was higher in our data (4–5:1) compared with the national average of 2:1. In 2023, estimated national incidence per 100 000 person-years among those aged 15–59 was 25.8 (8736/33 875 000) for men and 15.9 (5187/32 803 000) for women. 8 19 In contrast, incidence among men in our cohort was nearly double the national estimate, while rates in women were slightly lower. This may reflect a higher prevalence of commercial sex service use among higher-income men, a group previously linked to such behaviour. 20 Our findings suggest that men employed in large companies may represent a high-risk group for syphilis infection in Japan. Interestingly, even among dependents of employed men (ie, housewives), the incidence of syphilis was similar to that of their male spouses. Given that married women are generally regarded as a low-risk group for syphilis, 21 this represents a notably high incidence. These findings suggest that syphilis is no longer limited to transmission between commercial sex workers and their clients, but is now more widely circulating in the general population. In our study, the incidence among pregnant women was 13.5 per 100 000 pregnancies. Because this estimate was derived from births and did not capture pregnancies ending in miscarriage or abortion, the true burden is likely higher, underscoring the critical importance of strengthening syphilis prevention and screening in maternal health. Some infections among wives may have been acquired before marriage and diagnosed later, but the high rate among young wives remains notable. As wives age, husband-only infections become more common, suggesting that men may acquire syphilis outside the marriage, possibly via commercial sex workers or other partners. Although reported transmission rates among heterosexual partners vary widely (9%–64%), 22 23 the 12% co-infection rate observed in couples with wives in their 20s, compared with only 2%–3% in older age groups, suggests that sexual activity between spouses declines with age. Notably, only ~12% of spouses received syphilis testing within 90 days of their partner’s diagnosis, likely underestimating transmission rates. This low partner testing rate may contribute to continued community spread, highlighting the need to strengthen partner notification and testing. We also observed particularly high incidence rates among female dependent youths, referring to unmarried individuals such as university students or those who are not financially independent. This may reflect phenomena such as ‘ papa-katsu’ , a form of compensated dating in which young women engage in relationships with older men in exchange for financial or material support. The COVID-19 pandemic had a significant impact on the labour market, with women reportedly being more affected than men. 24 25 Although incidence among women in their 20s declined in 2023, mirroring Tokyo trends, 8 this may reflect post-pandemic behavioural normalisation. Further research should explore transactional relationships among non-professional women. Among individuals living with HIV, the syphilis incidence was extremely high, approximately 100 to 200 times higher than in the general population. These rates are consistent with previous reports from Japan and support the validity of our case definition. 26 In contrast to the rising syphilis incidence among heterosexual populations, previous studies have reported that incidence among people with HIV remained relatively stable prior to the COVID-19 pandemic. 27 Our data revealed age-specific increases, with modest rises in the 30s and sharp increases in the 20s after 2020. This may reflect a shift in transmission dynamics among younger MSM and warrants close monitoring. We also found that reinfection rates were remarkably high. These findings highlight that sexually active individuals are at risk of repeated infections. Currently, preventive interventions such as Doxy-PEP are limited to MSM 17 ; however, identifying other high-risk populations may allow for expanded prevention strategies. Given that syphilis is a disease with no immunity conferred by prior infection, patient education on the risk of reinfection is essential. A major strength of this study is the use of claims data based on both diagnostic codes and prescriptions. In Japan, syphilis is a notifiable disease under the Infectious Disease Control Law (Category V), but there are no penalties for non-reporting, and underreporting is likely. Additionally, access to family relationship data was a key advantage of this study. While the involvement of commercial sex workers has long been a concern in syphilis transmission, our findings raise the possibility that syphilis is also spreading among women not engaged in sex work. This study has several limitations. First, the absence of laboratory results may affect diagnostic accuracy, though the use of specific treatment regimens and consistency with prior HIV cohort data support our case definition. Retreatment for slow serological response could have led to overestimation of reinfection, but we applied a 1 year buffer and excluded late/neurosyphilis cases to minimise misclassification. In addition, staging information was not reliably available in the claims data. ICD-10 codes for early and late syphilis may not accurately reflect the clinical stage, and a substantial proportion of cases may be classified as unspecified syphilis. Because staging information is therefore unreliable in administrative claims data, stage-specific transmission analyses were not performed. Second, incidence reflects diagnosis timing rather than infection onset, complicating interpretation. Some infections—such as those in housewives—may have occurred earlier, but this limitation is common across studies. Third, the JMDC database primarily includes employees of medium-to-large companies and their dependents and therefore may not fully represent the general Japanese population. In particular, the cohort may overrepresent individuals with stable employment, higher socioeconomic status and urban residence while underrepresenting self-employed individuals, part-time workers and rural populations. However, the sex distribution in the JMDC cohort (approximately 51% men) was broadly comparable to that of the national working-age population reported in national statistics. 19 In addition, overall temporal trends in syphilis incidence closely paralleled those observed in national surveillance data. Because incidence rates were calculated within age and sex strata, differences in demographic composition between the JMDC cohort and the national population are unlikely to substantially affect within-stratum incidence estimates. Fourth, the married-couple analysis was restricted to households in which the husband was the primary insured and the wife was registered as a dependent spouse, systematically excluding dual-income couples. Therefore, couple-level findings should not be generalised to all married households in Japan. In addition, sexual orientation data were not available in the database; some male primary insured individuals may be MSM, which could contribute to the observed within-couple discordance. However, evidence from a large nationwide survey in Japan suggests that the proportion of gay and bisexual men with female partners is relatively small (6.3% identified as gay or bisexual, and about one-fifth reported having a female partner), 28 and thus the potential impact on the overall estimates is likely limited. Conclusions Using nationwide claims data with family linkage, this large-scale study revealed distinct patterns of syphilis transmission in Japan. Notably, we found a rising burden among dependent youths and unexpectedly high incidence among housewives, traditionally seen as low-risk. These findings suggest that syphilis risk may extend beyond traditionally recognised high-risk populations and highlight the need for enhanced prevention strategies, including improved partner notification and screening in both clinical and public health settings. Supplementary material online supplemental file 1 bmjopen-16-4-s001.tif (27.9MB, tif) DOI: 10.1136/bmjopen-2025-114337 Footnotes Funding: This work was supported by the Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO) (Grant Number JPMJPR23R1) Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2025-114337 ). Provenance and peer review: Not commissioned; externally peer reviewed. Patient consent for publication: Not applicable. Data availability free text: The data used in this study were obtained from JMDC and are not publicly available because of contractual and privacy restrictions. Relevant analytic data are available from the corresponding author on reasonable request at [email protected]. Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. Ethics approval: This study was approved by the Research Ethics Committee of the University of Tokyo (approval number: 2024216NIe). The requirement for informed consent was waived because the study used fully anonymised secondary data that were not individually identifiable. Data confidentiality was maintained in accordance with the Declaration of Helsinki. 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