Epidemiologic Trends and Distributions of Imported Infectious Diseases Among Travelers to Japan Before and During the COVID-19 Pandemic, 2016 to 2021: A Descriptive Study.

BACKGROUND: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the novel coronavirus disease 2019 (COVID-19) pandemic. This article aimed to describe those among travelers to Japan. METHODS: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020). RESULTS: A total of 3,524 imported infectious disease cases were diagnosed during the study period, including 3,439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95% confidence interval [CI], 41.5-78.7), malaria (21.7; 95% CI, 10.5-33.0), and typhoid fever (9.3; 95% CI, 1.9-16.8). CONCLUSION: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance.

Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives.

Japan has had a substantial increase in syphilis cases since 2013. However, research on the genomic features of the Treponema pallidum subspecies pallidum (TPA) strains from these cases has been limited. Here, we elucidated the genetic variations and relationships between TPA strains in Japan (detected between 2014 and 2018) and other countries by whole-genome sequencing and phylogenetic analyses, including syphilis epidemiological surveillance data and information on patient sexual orientation. Seventeen of the 20 strains in Japan were SS14- and the remaining 3 were Nichols-lineage. Sixteen of the 17 SS14-lineage strains were classified into previously reported Sub-lineage 1B. Sub-lineage 1B strains in Japan have formed distinct sub-clusters of strains from heterosexuals and strains from men who have sex with men. These strains were closely related to reported TPA strains in China, forming an East-Asian cluster. However, those strains in these countries evolved independently after diverging from their most recent common ancestor and expanded their genetic diversity during the time of syphilis outbreak in each country. The genetic difference between the TPA strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes. Taken together, our results elucidated the detailed phylogenetic features and transmission networks of syphilis.

Syphilis in heterosexual women: case characteristics and risk factors for recent syphilis infection in Tokyo, Japan, 2017-2018.

In response to an increase in heterosexual syphilis notifications in Tokyo, we conducted a questionnaire-based case-control study among women aged ≥20 years and sexually active in the past six months who sought a syphilis test in Tokyo during 2017-2018. Cases were women diagnosed as recent syphilis infection based on serological tests. Controls were serologically non-reactive or those with only a past syphilis infection. We described cases and assessed for risk factors of recent syphilis using logistic regression. A total of 524 women (60 cases, 464 controls) were enrolled. Notably, among cases, 10 (16.7%) were students, 3 (5.0%) had a history of syphilis, and 14 (23.3%) had a single sex partner in the past six months. Female sex worker (FSW) status was strongly associated with syphilis (odds ratio [OR] = 3.40; 95% confidence interval [CI] = 1.96-5.90). In multivariable analysis, recent syphilis was associated with inconsistent condom use for vaginal/anal sex among FSWs (adjusted OR [aOR] = 3.42; 95%CI = 0.92-12.70) and among non-FSWs, with younger age (aOR = 0.36; 95%CI = 0.19-0.70; increase per category from 20-24, 25-29 to ≥30 years) and ≤high school education (aOR = 5.24; 95%CI = 1.95-14.10). A notable proportion of cases were those with first time infection and those with only a single partner. Moreover, risk factors differed between FSWs and non-FSWs, and a multi-pronged approach to prevent syphilis is required.

Epidemiology, molecular strain types, and macrolide resistance of Treponema pallidum in Japan, 2017-2018.

BACKGROUND: Japan has seen a substantial increase in syphilis cases since 2013 and Tokyo and Osaka prefectures accounted for about 40% of all cases in Japan. Therefore, focusing on these 2 prefectures, we assessed syphilis cases detected during 2017-2018, combining epidemiological information with molecular typing data. METHODS: Using data from surveillance reports, we described syphilis cases by gender, age, transmission route, and stage of syphilis. Clinical specimens were collected from syphilis patients in Tokyo and Osaka prefectures. Molecular typing was performed by analyzing Treponema pallidum arp, tpr, and tp0548 genes, with partial sequencing of the 23S rRNA genes for macrolide resistance. RESULTS: Between 2017 and 2018, the number of syphilis cases increased from 3934 to 4588 among males and 1895 to 2414 among females, with similar age and gender distributions during the period. The predominant strain type was 14d/f (71%, 73/103), found more frequently in women who have sex with men (86%, 25/29) and men who have sex with women (83%, 39/47) than in men who have sex with men (MSM) (33%, 9/27). The majority of the strains from heterosexuals (97%, 76/78) were macrolide-resistant, considerably higher than those from MSM (59%, 20/34). The molecular profiles in each sexual-transmission group remained similar during the 2 years. CONCLUSIONS: The epidemiological and molecular features of syphilis remained similar throughout the period, with consistent differences in strain type and macrolide resistance distributions between MSM and heterosexual cases. These findings suggest a predominantly heterosexual epidemic where the dynamics of syphilis transmission remained unchanged during 2017-2018.

Molecular Typing and Macrolide Resistance Analyses of Treponema pallidum in Heterosexuals and Men Who Have Sex with Men in Japan, 2017.

In recent years, syphilis notifications have increased dramatically in Japan. We carried out molecular typing and macrolide resistance analyses of Treponema pallidum subsp. pallidum samples collected from patients at four clinics and a hospital in Tokyo and Osaka prefectures in 2017. The macrolide resistant strain type 14d/f (SS14-like clade) was found in significantly more cases of syphilis among heterosexuals than in those among men who have sex with men (MSM); i.e., 79% (31/39) of the strains from heterosexuals were 14d/f compared to 37% (7/19) of those from MSM (odds ratio [OR], 6.6; 95% confidence interval [CI], 1.7 to 26.7; P = 0.002). In addition, 83% (50/60) of the strains were identified as macrolide resistant with an A2058G mutation in the 23S rRNA gene; 90% (35/39) of the strains from heterosexuals were macrolide resistant compared to 58% (11/19) of those from MSM. The odds of having the resistant mutation were considerably higher in the former (OR, 6.4; 95% CI, 1.3 to 33.5; P = 0.02). Heterosexual women and heterosexual men showed similar distributions, and the association remained the same when restricted to men. The strain type distribution and the prevalence of macrolide resistance differed substantially between syphilis strains from heterosexual cases and from MSM cases, suggesting distinct epidemiologic profiles for the two communities and providing important insight into the dynamics of syphilis in Japan.

Epidemiology of vaccine-preventable diseases in Japan: considerations for pre-travel advice for the 2019 Rugby World Cup and 2020 Summer Olympic and Paralympic Games.

INTRODUCTION: In 2019 and 2020, Japan will host two international sporting events estimated to draw a combined 22 million visitors. Mass gatherings like these ones increase the risk of spread of infectious disease outbreaks and international transmission. Pre-travel advice reduces that risk. METHODS: To assist ministries of health and related organizations in developing pre-travel advice, we summarized national surveillance data in Japan (2000-2016, to the extent available) for rubella, invasive pneumococcal disease, measles, non-A and non-E viral hepatitis, hepatitis A, invasive Haemophilus influenzae disease, tetanus, typhoid fever, invasive meningococcal disease, Japanese encephalitis, influenza, varicella, mumps and pertussis by calculating descriptive statistics of reported cases and reviewing trends. (See Annex A for details of reviewed diseases.). RESULTS: Our findings showed notable incidences of rubella (1.78 per 100 000 person-years), influenza (243.5 cases per sentinel site), and mumps (40.1 per sentinel site); seasonal increases for influenza (November-May) and Japanese encephalitis (August-November); and a geographical concentration of Japanese encephalitis in western Japan. Measles cases decreased from 11 013 in 2008 to 35 in 2015, but outbreaks (n = 165 cases) associated with importation occurred in 2016. Though invasive meningococcal disease incidence was only 0.03 per 100 000, international transmission occurred at a mass gathering in Japan in 2015. DISCUSSION: Ministries of health and related organizations should use these findings to develop targeted pre-travel advice for travellers to the 2019 Rugby World Cup and the 2020 Summer Olympic and Paralympic Games, especially for mumps, measles, rubella, influenza, and meningitis. Travellers with increased exposure risk should also be advised about hepatitis A and Japanese encephalitis.

Rapid Increase in Reports of Syphilis Associated With Men Who Have Sex With Women and Women Who Have Sex With Men, Japan, 2012 to 2016.

BACKGROUND: In Japan, syphilis reports have recently increased rapidly. However, unlike other developed countries where men who have sex with men (MSM) were associated with the rise, the increase in Japan has been attributed more to men who have sex with women (MSW) and women who have sex with men (WSM). We report on this increase based on surveillance data. METHODS: Syphilis is a notifiable disease requiring all laboratory-confirmed cases to be reported; stage and sex of the sex partner(s) suspected as the infection source are also reported. Focusing on primary and secondary (P&S) cases, we describe the temporal, demographic, and geographic distributions of reported cases in 2012 through 2016. RESULTS: A total of 7040 (64.0%) of 10,997 cases were P&S; the annual rate of increase was greatest for P&S and the proportion of P&S increased over time. Among P&S cases (1609 MSM, 2768 MSW, and 1323 WSM), MSW and WSM each surpassed MSM cases in 2016. Men were older with a wider age distribution (median, 37 years; interquartile range, 28-46 years) relative to women (median, 26 years; interquartile range, 21-34 years). Among women, 20- to 24-year-olds consistently had the highest reporting rate, reaching 9.0 per 100,000 in 2016. Congenital syphilis reports increased from 0.4 in 2012 to 1.4 per 100,000 live births in 2016. Although Tokyo prefecture had the highest reporting rate (3.98 per 100,000 person-years), the proportionate contribution from Tokyo decreased in 2016. CONCLUSIONS: Reports on P&S syphilis increased yearly among MSW and WSM. Young women seem to be at particular risk, and with increased reports of congenital syphilis, syphilis prevention and control is currently a public health priority in Japan.

Severe Thrombocytopenia and Acute Cytomegalovirus Colitis during Primary Human Immunodeficiency Virus Infection.

We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection.

[Kaposi's Sarcoma Herpesvirus-associated Inflammatory Cytokine Syndrome (KICS) Improved by Antiretroviral Therapy in an HIV-infected Patient].

We report a case of a 63-year-old HIV-positive Japanese male with a CD4 cell count of 127/µL who was admitted to our hospital because of suspected malignant lymphoma. Initial blood tests revealed anemia, thrombocytopenia, hypoalbuminemia, and hypergammaglobulinemia. Imaging tests revealed a lung nodule, bilateral pleural effusion, hepatosplenomegaly and generalized lymphadenopathy. No evidence of malignant lymphoma or multicentric Castleman's disease was noted on biopsy specimens; however, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen-1-positive cells were observed as well as an elevated interleukin (IL)-6, IL-10 and KSHV viral load. He fulfilled the novel diagnostic criteria for KSHV-associated inflammatory cytokine syndrome (KICS). After initiating antiretroviral therapy, his symptoms and radiological abnormalities drastically improved. After 1-year follow-up, his HIV was well controlled without any relapsing symptoms.