Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Nationwide epidemiologic and genetic surveillance of hepatitis E in Japan, 2014-2021.

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis. To clarify the epidemiology of HEV and characterize the genetic diversity of the virus in Japan, nationwide enhanced surveillance and molecular characterization studies of HEV in Japan were undertaken from 2014 to 2021. In total, 2770 hepatitis E cases were reported, of which 88% were domestic cases, while only 4.1% represented cases following infection abroad. In addition, 57% of domestic infections occurred in males aged in their 40s-70s. For domestic cases, infection via pork meat consumption continued to be the most reported route. Analysis of the 324 sequences detected between 2016 and 2021 showed that the majority of domestic HEV strains belong to Genotype 3a (G3a) and G3b. In contrast, six of eight cases of G1 HEV reflected infection abroad. Our results suggest that HEV is circulating widely in Japan, with genotypes G3a and G3b being most prevalent. Continued surveillance is necessary to monitor future trends and changes in the epidemiology of HEV in Japan.

Atypical diarrhoeagenic Escherichia coli in milk related to a large foodborne outbreak.

A foodborne outbreak related to milk cartons served in school lunches occurred in June 2021, which involved more than 1,800 cases from 25 schools. The major symptoms were abdominal pain, diarrhoea, vomiting, and fever. Although major foodborne toxins and pathogens were not detected, a specific Escherichia coli strain, serotype OUT (OgGp9):H18, was predominantly isolated from milk samples related to the outbreak and most patients tested. The strains from milk and patient stool samples were identified as the same clone by core genome multilocus sequence typing and single-nucleotide polymorphism analysis. The strain was detected in milk samples served for two days related to the foodborne outbreak at a rate of 69.6% and levels of less than ten most probable number/100 mL but not on days unrelated to the outbreak. The acid tolerance of the strain for survival in the stomach was similar to that of enterohaemorrhagic E. coli O157:H7, and the same inserts in the chu gene cluster in the acid fitness island were genetically revealed. The pathogenicity of the strain was not clear; however, it was indicated that the causative pathogen was atypical diarrhoeagenic E. coli OUT (OgGp9):H18.

Multijurisdictional Outbreak of Enterohemorrhagic Escherichia coli O157 Caused by Consumption of Ready-to-Eat Grilled Skewered Meat in Niigata, Japan.

Enterohemorrhagic Escherichia coli O157 (EHEC) causes severe complications such as hemolytic uremic syndrome. Contaminated ready-to-eat (RTE) food is one of the vehicles of multijurisdictional outbreaks of foodborne disease worldwide. Multijurisdictional (covering cities, towns, and villages) outbreaks of EHEC are usually linked to an increase in cases, and here we describe such an outbreak involving 29 cases in October 2017 in the Niigata Prefecture. After prefecture-wide active case finding, we conducted a case-control study of 29 cases with eligible data who tested positive for EHEC. To determine the association of the outbreak with risk factors, we compared these cases with 38 controls selected from family and acquaintances who were both symptom free and tested negative for EHEC. The largest number of cases was in the 20-29-year age group (7/29; 24%) and most were women (20/29; 69%). All 29 cases had an identical or similar multilocus variable number tandem-repeat analysis (MLVA) profile. Of these, 76% (22/29) had consumed some type of grilled skewered meat. Also, 69% (20/29) had consumed grilled skewered meat produced by company X. EHEC infection was strongly associated with the consumption of grilled skewered meat produced by any food processing company (odds ratio [OR] = 11.8, confidence interval [95% CI]: 3.7-37.4) and by company X (OR = 9.8, 95% CI: 3.2-30.7). At company X, the skewered meat was grilled to 95°C and then removed from the grilling area to meat trays. The meat trays were not sufficiently washed and disinfected. Testing indicated that the facility was negative for EHEC but four asymptomatic employees tested positive for EHEC. Company X was temporarily closed and voluntarily recalled the foods. We recommend that all employees sufficiently wash and disinfect meat trays to prevent contamination of RTE food, avoid cross-contamination of grilled skewered meat through the environment by regularly cleaning the facility, and appropriately practice self-health care.

Factors associated with knowledges and attitudes about measles and rubella immunization in a non-health care occupational setting in Japan.

INTRODUCTION: Elimination of measles and rubella has been achieved in several countries and some regions. After verified measles elimination, some countries have reported outbreaks among adults in occupational settings such as health care institution and school setting. Studies have reported that knowledge and attitude for measles and/or rubella are significantly associated with immunization uptake in adults, but few studies have been conducted in settings other than health care facilities and schools. METHODS: We conducted a cross-sectional study among 134 office employees during a routine health checkup in June 17-20, 2014, to examine the association between willingness to receive immunization and knowledge and attitudes. RESULTS: Approximately 75% had a protective level of antibody for measles (PA≥1:256) and rubella (HI ≥ 32 IU/mL). After adjustment for sex, age and immune status, the attitudes that immunization prevents measles (adjusted odds ratio [aOR] = 7.8, 95% confidence interval [95%CI]: 2.5-24.7) and prevents infection and transmission to others (aOR = 4.0, 95%CI: 1.4-11.4). Knowing that males are the vulnerable group for rubella infection (aOR = 5.8, 95%CI: 2.4-13.9), attitude that immunization prevents rubella infection (aOR = 7.9, 95%CI: 2.4-26.5), and prevents infection and transmit to others (aOR = 6.7, 95%CI: 2.2-20.1) were significantly associated with willingness to receive immunization after adjustment for sex, age, and immune status. CONCLUSIONS: Studies have shown that physicians and other health care workers are important source of information for promotion of immunization. Thus, we recommend that physicians educate and promote immunization for measles and/or rubella to adults working in offices during routine health checks.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020.

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

A shigellosis outbreak associated with a sports festival at a kindergarten in Kitakyushu City, Japan.

INTRODUCTION: Shigellosis cases have decreased gradually in Japan in recent years, but indigenous shigellosis outbreaks sometimes occur in childcare facilities. From national surveillance data, we identified a shigellosis outbreak involving a kindergarten. METHODS: After detecting Shigella sonnei in Kitakyushu City, we conducted active case finding and epidemiological investigation in Kindergarten Z, including stool specimen collection and interviews. The stool specimens were cultured, and isolated strains were subjected to pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem-repeat analysis (MLVA). RESULTS: Between September 1 and December 31, 2014, we identified 19 cases: 14 confirmed, 2 suspected, and 3 asymptomatic. Of the 19 cases, 16 were epidemiologically associated with Kindergarten Z (10 pupils, 5 family members, and 1 teacher). On October 19, a pupil with gastrointestinal illness participated in the kindergarten's sports festival, in which the pupils were split into "red" and "white" teams; the pupil in question belonged to the red team. Attack rates of the red and white teams were 8% (7/82) and 0% (0/108), respectively (relative risk, 10.5; 95% confidence interval, 1.3-82.1). PFGE patterns were identical or similar for the isolates in all 17 cases; 7 isolates were identical, and the others had one locus difference on MLVA. CONCLUSIONS: We concluded that contact during the sports festival could have been responsible for spread of the shigellosis outbreak at the kindergarten, although the infection source was not determined. It is vital to inform guardians immediately after detection of shigellosis cases that symptomatic pupils should not participate in activities such as sports festivals.

Characteristics and Outcomes of Influenza-Associated Encephalopathy Cases Among Children and Adults in Japan, 2010-2015.

Background: Influenza-associated encephalopathy (IAE) can result in severe neurologic disease with high mortality. Most IAE cases are reported among children worldwide. Understanding of IAE among adults is limited. Methods: Data were collected on IAE cases reported through the National Epidemiological Surveillance of Infectious Diseases database in Japan from 2010 through 2015. IAE cases were stratified by age category and analyzed using descriptive statistics to assess differences in characteristics and outcomes. Results: Among 385 IAE cases, median age at diagnosis was 7 years (range, 0-90), and 283 (74%) were aged <18 years. Mean seasonal incidence of IAE cases among children and adults (aged ≥18 years) was 2.83 and 0.19 cases per 1000000 population, respectively. IAE incidence did not vary by predominant influenza A virus subtype. IAE frequency was highest in school-aged (5-12 years) children (38%), followed by children aged 2-4 years (21%) and adults aged 18-49 years (11%). The proportion of cases with seizures was more common in children. There were more cases with cerebrospinal fluid pleocytosis among adults than in children (P < .01), especially among those aged 18-49 (17%) and 50-64 (19%) years. Case fatality proportion was highest in those aged 40-64 (17%) and ≥65 (20%) years. Conclusions: We found differences in the clinical features of IAE between adults and children in Japan. Although IAE incidence was higher in children, mortality was higher in adults. Efforts are needed to prevent and improve survival of patients with IAE, especially in adults.

Seasonal influenza vaccine (A/New York/39/2012) effectiveness against influenza A virus of health care workers in a long term care facility attached with the hospital, Japan, 2014/15: A cohort study.

The 2014/15 influenza season started earlier than usual, and intense activity was reflection of circulation of antigenically-drifted and vaccine-mismatched dominant A(H3N2) viruses. Although inpatients and health-care workers (HCWs) had a high influenza vaccination coverage rate well prior to the beginning of influenza season, numerous outbreaks of influenza A(H3N2) infection with fatal cases were reported in long-term care facilities (LTCFs) in Japan during 2014/15 influenza season. In January 2015, we were given opportunity to conduct outbreak investigation of influenza A at facility A (LTCF attached with hospital) in Western part of Japan. We evaluated overall and occupation-stratified influenza vaccine effectiveness (VE) among HCWs at facility A using a retrospective cohort design. Overall VE, occupation-stratified VE and adjusted VE (AVE) with 95% confidence intervals (CIs) were estimated using the following formula: (1-relative risks (RR) or 1-adjusted RR) × 100%. Overall vaccine coverage rate among HCWs was 85%. Overall VE for HCWs was 28% (95% CI: -70 to 67) and overall AVE was 3% (95% CI: -34 to 30). Although there was no severe cases, our results indicated that even with high vaccination coverage rate with appropriate vaccination timing, the VE was low for HCWs, which echoes with previously reported VE from other northern hemisphere countries. However, rehabilitation group who had high awareness against influenza as a group and carried out intensive precautions from early influenza season had no cases. We conclude that multiple preventive measures in addition to high vaccination rate is necessary for preventing influenza of HCWs working at LCTFs.

Enterohemorrhagic Escherichia coli outbreaks related to childcare facilities in Japan, 2010-2013.

BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) is an important cause of gastroenteritis in Japan. Although non-O157 EHEC infections have been increasingly reported worldwide, their impact on children has not been well described. METHODS: We collected national surveillance data of EHEC infections reported between 2010 and 2013 in Japan and characterized outbreaks that occurred in childcare facilities. Per Japanese outbreak investigation protocol, faecal samples from contacts of EHEC cases were collected regardless of symptomatic status. Cases and outbreaks were described by demographics, dates of diagnosis and onset, clinical manifestations, laboratory data, and relation to specific outbreaks in childcare facilities. RESULTS: During 2010-2013, a total of 68 EHEC outbreaks comprised of 1035 cases were related to childcare facilities. Among the 66 outbreaks caused by a single serogroup, 29 were serogroup O26 and 22 were O157; 35 outbreaks were caused by stx1-producing strains. Since 2010, the number of reported outbreaks steadily increased, with a rise in cases and outbreaks caused by stx1-producing O26. Of 7069 EHEC cases reported nationally in 2010-2011, the majority were caused by O157 (n = 4938), relative to O26 (n = 1353) and O111 (n = 195). However, relative to 69 cases of O157 (2%) associated with childcare facility EHEC outbreaks, there were 131 (10%) such cases of O26, and this trend intensified in 2012-2013 (O157, 3%; O26, 24%; O111, 48%). Among family members of childcare facility cases, the proportion of cases that were symptomatic declined with age; 10/16 cases (63%) aged 6 years or younger, 16/53 cases (30%) 6-19 years old, 23/120 cases (19%) 20-49 years old and 2/28 cases (7%) 50 years or older were symptomatic. Thirty one of the 68 outbreaks (46%) were classified as foodborne-related. CONCLUSIONS: Childcare facility EHEC outbreaks due to non-O157 serogroups, particularly O26 and O111, increased during 2010-2013. These facilities should pay extra attention to health conditions in children. As older family members of childcare facility cases appear to be less symptomatic, they should be vigilant about hand-washing to prevent further transmission.

Estimating influenza vaccine effectiveness among older adults using an integrated administrative database and the implications of potential bias: A population-based cohort study in Japan.

BACKGROUND: Japan lacks an established framework for routine seasonal influenza vaccine effectiveness (SIVE) assessment at the national and municipal levels. This study aimed to estimate SIVE among older adults using an innovative population-based administrative database linking medical fee claims data with vaccination records, while also exploring its potential bias. METHODS: In this retrospective population-based cohort study, we assessed SIVE against medically attended influenza during the 2017/18 season among older adults aged ≥65 years in a Japanese city. A Cox proportional hazards model was used to estimate hazard rate ratios, treating vaccination status as time-dependent. To explore potential biases, multivariate logistic regression analysis was used to investigate the association between vaccination status and acute respiratory infection (ARI) diagnosis and trauma/injury during the non-influenza season. RESULTS: This study included 82 % (n = 110,892) of the city's older adult population, with 39.7 % vaccination coverage. The estimated SIVE was 2.9 % (95 % confidence interval: -6.2-11.2), showing no statistical significance. Similarly, subgroup analyses by age and comorbidities revealed no significant protective effect of SIVE. In the non-season analysis, adjusted odds ratios of vaccination were significantly higher for ARI [1.3 (1.3-1.4)] and trauma/injury [1.2 (1.1-1.2)]. However, no significance was observed for hospitalizations with these diagnoses, which include severe conditions less associated with healthcare-seeking behaviors [0.9 (0.8-1.1) and 0.8 (0.6-1.0), respectively]. CONCLUSIONS: No significant SIVE was observed during the 2017/18 season. Our real-world observational study, based on medical fee claims data, indicates a potential underestimation of SIVE owing to bias related to healthcare-seeking behaviors.

[Training programs for staff at local Infectious Disease Surveillance Centers: the needs and usefulness].

OBJECTIVES: The objective of this study was to assess the need for and usefulness of training programs for Local Infectious Disease Surveillance Center (LIDSC) staff. METHODS: A structured questionnaire survey was conducted to assess the needs and usefulness of training programs. The subjects of the survey were participants of a workshop held after an annual conference for the LIDSC staff. Data on demographic information, the necessity of training programs for LIDSC staff, the themes and contents of the training program, self-assessment of knowledge on epidemiology and statistics were covered by the questionnaire. RESULTS: A total of 55 local government officials responded to the questionnaire (response rate: 100%). Among these, 95% of participants believed that the training program for the LIDSC staff was necessary. Basic statistical analysis (85%), descriptive epidemiology (65%), outline of epidemiology (60%), interpretation of surveillance data (65%), background and objectives of national infectious disease surveillance in Japan (60%), methods of field epidemiology (60%), and methods of analysis data (51%) were selected by over half of the respondents as suitable themes for training programs. A total of 34 LIDSC staff answered the self-assessment question on knowledge of epidemiology. A majority of respondents selected "a little" or "none" for all questions about knowledge. Only a few respondents had received education in epidemiology. CONCLUSION: The results of this study indicate that LIDSC staff have basic demands for fundamental and specialized education to improve their work. Considering the current situation regarding the capacity of LIDSC staff, these training programs should be started immediately.

Identification of Kudoa septempunctata as the causative agent of novel food poisoning outbreaks in Japan by consumption of Paralichthys olivaceus in raw fish.

BACKGROUND: Outbreaks of an unidentified food-borne illness associated with the consumption of raw fish have increased in Japan since 2003. Those affected with this illness develop diarrhea and emesis within 2-20 hours after a meal including raw fish. No known causative agents such as bacteria, viruses, bacterial toxins, or toxic chemicals have been detected in the foods that were ingested. Fortunately, this illness is self-limiting with good prognosis in all cases. METHODS: We conducted an epidemiological analysis of outbreaks that occurred during 2008 and 2010 and analysed a fish sample from one outbreak by metagenomic DNA sequencing, real-time polymerase chain reaction, and direct microscopic observations. The pathogenicity of a putative risk factor identified by these techniques was assessed using the suckling-mouse test and a house musk shrew emetic assay. RESULTS: The epidemiological analysis of outbreaks in 24 municipalities involving >1300 subjects implicated an olive flounder (Paralichthys olivaceus) as the causative food source. The presence of Kudoa septempunctata, a recently-described myxosporean species in P. olivaceus, was prevalent in the causative foods. K. septempunctata induced watery stools and an elevated fluid accumulation ratio in suckling mice, as well as vomiting in house musk shrews. CONCLUSIONS: These results identify K. septempunctata as the etiological agent of this novel food-borne illness outbreak associated with consumption of raw P. olivaceus. This is the first report, to our knowledge, demonstrating the human pathogenicity of Kudoa spores.

Association between seasonal influenza vaccination in 2008-2009 and pandemic influenza A (H1N1) 2009 infection among school students from Kobe, Japan, April-June 2009.

We assessed the effect of seasonal trivalent inactivated influenza vaccination (TIV) on pandemic influenza 2009 (pH1N1)-related illness from April to June 2009 among 2849 students (aged 12-18 years). TIV was associated with an increase in the frequency of pH1N1-related illness among subjects (adjusted odds ratio, 1.47; 95% confidence interval, 1.14-1.89). TIV during the 2008-2009 season increased the risk of pH1N1-related illness from April to June 2009.

Inter-rater reliability of self-reported response on foreskin status in questionnaire among Japanese adult men.

OBJECTIVES: To determine whether foreskin status is a measurable marker for evaluating the effect of the foreskin on sexually transmitted infections. METHODS: Inter-rater comparison of the responses on foreskin status and circumcision in a self-report questionnaire with the findings of a physical examination by an experienced well-trained urologist was performed for patients who visited a healthcare facility in Kanagawa, Japan. Foreskin status was defined using a five-point graphical scale based on the degree to which the foreskin covers the foreskin and the glans penis in a non-erectile condition: type 1, a fully exposed glans penis; types 2-4, the glans penis partly covered by the foreskin and type 5, phimosis. Linear weighted κ and per cent agreement were used to evaluate the reliability of responses. RESULTS: Among 188 participants who were evaluated about their foreskin status, linear weighted κ and per cent agreement were 0.74% and 68.4%, respectively. Linear weighted κ improved from 0.74 to 0.80 when the number of categories was changed to three. All the self-reported responses on circumcision were in agreement with the findings of the physical examination. Seventeen participants (9.0%) had been circumcised, and among them, three (17.6%) had approximately one-half of their glans penis covered by the foreskin. In 90 among the 171 uncircumcised participants (52.6%), the foreskin did not cover the glans penis. CONCLUSIONS: The self-reported response on foreskin status in this questionnaire has sufficient reliability to replace physical examination, and this questionnaire can facilitate further studies about the effect of foreskin on sexually transmitted infections.

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR). Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection. Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

Knowledge, Attitudes, and Practices Associated with Pertussis Vaccination during Pregnancy: Japan, 2016-2017.

Neonatal pertussis can potentially cause severe complications and even death. Mothers have been most frequently identified as the source of neonatal pertussis. Approximately a dozen countries have implemented pertussis vaccination programs for pregnant women to protect neonates; however, in Japan, this has not been implemented. The aim of this questionnaire-based study was to ascertain the willingness of women to be vaccinated during pregnancy and the factors associated with willingness. The subjects were 977 pregnant women who visited either of the two selected hospitals for maternity health checks. Most of the women were in their first pregnancy (96%), and approximately half of them considered a physician to be the most reliable source of information about vaccination (481/977, 49%). "Willingness to receive pertussis vaccination" was significantly associated with the factors "no fear of receiving vaccination" (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 2.21-4.34), "necessary to prevent pertussis" (OR = 8.70, 95% CI: 6.17-12.28), "effective in pregnancy" (OR = 5.46, 95% CI: 3.94-7.56), and "no concern about the side effects after vaccination" (OR = 3.03, 95% CI: 1.66-5.55). Pregnant women are likely to consider vaccination if they have a good understanding of the disease and its outcomes. Physicians are well positioned to improve knowledge and attitudes toward pertussis vaccination during pregnancy.

Enhanced event-based surveillance for imported diseases during the Tokyo 2020 Olympic and Paralympic Games.

In 2021, the National Institute of Infectious Diseases, Japan, undertook enhanced event-based surveillance (EBS) for infectious diseases occurring overseas that have potential for importation (excluding coronavirus disease 2019 [COVID-19]) for the Tokyo 2020 Olympic and Paralympic Summer Games (the Games). The pre-existing EBS system was enhanced using the World Health Organization Epidemic Intelligence from Open Sources system and the BlueDot Epidemic Intelligence platform. The enhanced EBS before and during the Games did not detect any major public health event that would warrant action for the Games. However, information from multiple sources helped us identify events, characterize risk and improve confidence in risk assessment. The collaboration also reduced the surveillance workload of the host country, while ensuring the quality of surveillance, even during the COVID-19 pandemic.

Genetic polymorphisms of 17 ß-hydroxysteroid dehydrogenase 3 and the risk of hypospadias.

INTRODUCTION: Hypospadias is a common congenital anomaly caused by incomplete fusion of urethral folds. Development of the urethra and external genital system in the male fetus is an androgen-dependent process. In this regard, enzymes 17 ß-hydroxysteroid dehydrogenase type 3 (17 ß HSD3, encoded by HSD17B3) and steroid 5 α-reductase type 2 (encoded by SRD5A2) play crucial roles. AIM: To investigate the possible associations between common polymorphisms in HSD17B3 as well as well-known V89L polymorphism in SRD5A2 and risk of hypospadias. METHODS: A case-control study was performed between 1999 and 2005. There were 89 Japanese boys with hypospadias and 291 newborn controls. We genotyped HSD17B3-1999T>C, +10A>G, +20A>G, +139G>A (V31I), +913G>A (G289S), and SRD5A2+336G>C (V89L) polymorphisms by allelic discrimination assay. We measured mRNA expression of the wildtype G289 allele and the mutant S289 allele of the HSD17B3 gene in the transfected human fetal kidney HEK293 cells. MAIN OUTCOME MEASURES: Assessment of hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood samples: allele and genotype distribution of single nucleotide polymorphisms in these two genes in cases and controls. RESULTS: In our study, the risk of hypospadias was significantly higher in subjects carrying homozygous HSD17B3+913A (289S) alleles (odds ratio [OR]: 3.06; 95% confidence interval [CI]: 1.38-6.76). The risk of severe hypospadias was much higher in these subjects (OR: 3.93; 95% CI: 1.34-11.49). The mRNA expression levels of HSD17B3 G289 were higher than those of HSD17B3 S289 mutant (P < 0.001). In addition, the risk of severe hypospadias increased in boys carrying the SRD5A2+336C (89L) allele (OR: 3.19; 95% CI: 1.09-9.36). CONCLUSIONS: These results suggest that the HSD17B3 G289S polymorphism may be a potential risk modifier for hypospadias. Our findings provide evidence that a certain genotype related to androgen production may potentiate risk of hypospadias.

Rubella outbreak among workers in three small- and medium-size business establishments associated with imported genotype 1E rubella virus-Shizuoka, Japan, 2015.

On 12 February 2015, a local health department (LHD) in Shizuoka prefecture identified two reported rubella cases in its jurisdiction as employees of the same company. As other employees at the company resided both inside and outside of the health department's jurisdiction, it began collaborating with two additional LHDs and the National Institute of Infectious Diseases to investigate and respond to the outbreak, which subsequently identified cases in two additional companies. We obtained epidemiological, clinical, and outbreak response information from the national epidemiological surveillance of infectious disease system's database, the local health departments, and the associated companies. One specimen for genetic sequencing was collected from each of the three companies. The outbreak included a total of twenty-five cases, with seventeen confirmed and eight probable cases from three companies. Among them, 24 (96%) were male, 22 (88%) were employees of one company (Company X), and none had rubella vaccination history. The median age was 45 years (interquartile range: 40-51). Epidemiological information did not reveal the source of infection nor transmission route. All rubella viruses sequenced from the three specimens were classified into genotype 1E. The nucleotide sequences in the 739 bp-window region were completely identical in two specimens, with only one nucleotide difference in the third specimen. According to phylogenetic analysis, these strains were closely related to the Southeast and East Asian lineage. This rubella outbreak at three companies, ranging in size from small- to medium-size, in Japan occurred among unvaccinated employees aged at least 30 years, most of whom were male. Virologic analyses suggest all cases were infected with the same viral strain imported from Southeast Asia. Similar to these companies, most employees at small- and medium-size businesses in Japan are males with no vaccination history for rubella, which poses a serious risk for associated cases of congenital rubella syndrome (CRS).