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Autoantibodies (aAbs) to type I interferons (IFNs) have been found in less than 1% of individuals under the age of 60 in the general population, with the prevalence increasing among those over 65. Neutralizing autoantibodies (naAbs) to type I IFNs have been found in at least 15% of patients with life-threatening COVID-19 pneumonia in several cohorts of primarily European descent. We aimed to evaluate the prevalence of aAbs and naAbs to IFN-α2 or IFN-ω in Japanese patients who suffered from COVID-19 as well as in the general population.Patients who suffered from COVID-19 (n = 622, aged 0-104) and an uninfected healthy control population (n = 3,456, aged 20-91) were enrolled in this study. The severities of the COVID-19 patients were as follows: critical (n = 170), severe (n = 235), moderate (n = 112), and mild (n = 105). ELISA and ISRE reporter assays were used to detect aAbs and naAbs to IFN-α2 and IFN-ω using E. coli-produced IFNs.In an uninfected general Japanese population aged 20-91, aAbs to IFNs were detected in 0.087% of individuals. By contrast, naAbs to type I IFNs (IFN-α2 and/or IFN-ω, 100 pg/mL) were detected in 10.6% of patients with critical infections, 2.6% of patients with severe infections, and 1% of patients with mild infections. The presence of naAbs to IFNs was significantly associated with critical disease (P = 0.0012), age over 50 (P = 0.0002), and male sex (P = 0.137). A significant but not strong correlation between aAbs and naAbs to IFN-α2 existed (r = - 0.307, p value 0.0001) reinforced the importance of measuring naAbs in COVID-19 patients, including those of Japanese ancestry.In this study, we revealed that patients with pre-existing naAbs have a much higher risk of life-threatening COVID-19 pneumonia in Japanese population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load dynamics in respiratory samples have been studied, but knowledge about changes in serial serum samples of infected patients in relation to their immunological response is lacking. We investigated the dynamics of SARS-CoV-2 viral load and antibody response in sequential serum of coronavirus disease 2019 (COVID-19) patients and attempted to culture the virus in the serum. A total of 81 sequential serum samples from 10 confirmed COVID-19 patients (5 with mild and 5 with moderate symptoms) were analyzed. Samples were collected during hospitalization and after discharge (median follow-up of 35 days). SARS-CoV-2 ribonucleic acid in the serum was detected by real-time polymerase chain reaction. Total antibody and IgG to SARS-CoV-2 Spike protein were analyzed by Chemiluminescent Immunoassays, and neutralizing antibodies were detected using a Surrogate Virus Neutralization Test. Viremia was observed in all cases at admission, and viral copy gradually dropped to undetectable levels in patients with mild symptoms but fluctuated and remained persistent in moderate cases. The viral culture of samples with the highest viral load for each patient did not show any cytopathic change. The antibody response was faster and higher in moderate cases. This study provides a basic clue for infectious severity-dependent immune response, viremia, and antibody acquisition pattern.

Monoclonal gammopathy (M-proteinemia) is a premalignant plasma cell disorder. The prevalence of M-proteinemia increases with age and is affected by genetic or environmental factors. Atomic bomb (A-bomb) survivors in Hiroshima are in an age range when they are susceptible to M-proteinemia. The prevalence and incidence of M-proteinemia in Hiroshima A-bomb survivors were investigated for 30 years (1989–2018) to examine the influence of radiation exposure. The overall prevalence of M-proteinemia among 38,602 A-bomb survivors was 2.4%. M-proteinemia prevalence at age 70 years and monoclonal gammopathy of undetermined significance (MGUS) incidence were not associated with radiation exposure category. Males had a 2.30-fold higher prevalence and a 2.08-fold higher incidence than females. The risk of incidence for MGUS was 4.32-fold higher in persons aged

Evidence regarding the performance of digital dentures (DDs) fabricated using 3D printing is insufficient. This study aimed to evaluate patient satisfaction with conventional dentures (CDs) and DDs fabricated using 3D printing.This randomized controlled trial was conducted between November 2017 and May 2020. In the CD-DD group, CDs were fabricated before DDs, while the protocol was reversed in the DD-CD group. The primary outcome was patient satisfaction, quantified using a 100-mm visual analog scale, which assessed chewing efficiency, pain, stability, retention, comfort, esthetics, ease of cleaning, phonetics, and general satisfaction. Secondary outcomes were quality of life (QOL), number of visits, time required for definitive denture fabrication, number of adjustment appointments, and time required for denture stabilization after denture delivery.Patient satisfaction with CDs was superior in terms of phonetics, ease of cleaning, stability, comfort, and general satisfaction. Secondary outcomes such as social disability and the number of clinic visits were significantly lower in patients with DDs. However, the two groups showed no significant differences in the other outcomes. Although patient satisfaction with DDs was inferior to that with CDs, 20% of patients preferred and used DDs (12 patients preferred CDs, and three patients opted for DDs).Although patient satisfaction or QOL with DDs may be somewhat inferior to that with CDs, 20% of patients preferred and used DDs daily. Thus, DDs fabricated using 3D printing may have comparable practicality and efficacy to CDs.

Introduction The BNT162b2 and mRNA-1273 COVID-19 vaccines are the main vaccines that have been used for mass vaccination in Japan. Information on adverse reactions to COVID-19 vaccines in the Japanese population is limited. Methods We conducted an online survey on self-reported adverse reactions in individuals who had received two doses of the BNT162b2 or mRNA-1273 vaccine. The incidence of adverse events after each dose of vaccine was investigated. Propensity score matching was used to compare the incidence of adverse reactions after the second dose of the BNT162b2 and mRNA-1273 vaccines. Results After the first and second doses of the BNT162b2 vaccine, and the first and second doses of the mRNA-1273 vaccine, 890, 853, 6401, and 3965 individuals, respectively, provided complete responses. Systemic reactions, including fever, fatigue, headache, muscle/joint pain, and nausea were significantly more common in females, individuals aged

Background Hepatitis B virus (HBV) infection is one of the major public health problems globally as well as in Cambodia. Continuous information on HBV infection burden is required to implement effective disease control strategies. This study aimed to determine the prevalence and genotype distribution of HBV infection in Cambodia through a systematic review with meta-analysis. Methods Four databases (PubMed, Web of Science, Scopus, and Google Scholar) were used to search published studies reporting either HBV prevalence or genotype distribution in Cambodia until August 21, 2020. Reviews, modeling studies, and studies conducted among Cambodian permanently living abroad were excluded. The Freeman–Tukey double arcsine transformation was implemented to achieve approximate normality. The DerSimonian and Laird method was used to compute pooled estimates based on the transformed values and their variance. Possible publication bias was assessed by the Egger test and the funnel plot. Results A total of 22 studies were included, covering 22,323 people. Ten studies reported HBV prevalence in the general population. The HBV infection prevalence was 4.73% (95%CI: 2.75–7.17%) in the general population and 19.87% (95%CI: 10.95–30.63%) in high-risk/co-infected groups. By sub-group analysis, the prevalence was 6.81% (95% CI: 4.43–9.66) in adults older than 15 years old, 2.37% (95% CI:0.04–7.05) in children 6–15 years old, and 2.47% (95% CI: 0.96–4.59) in children less than five years old. The prevalence of HBV infection decreased over time. Predominant HBV genotypes were genotypes C and B with 82.96% and 16.79%, respectively. Conclusions The decrease in HBV infection prevalence in Cambodia demonstrates the effects of national hepatitis B immunization, improved clinical hygiene, and the use of disposable devices. However, the estimated HBV prevalence among the general population indicates an intermediate endemicity level of HBV infection. Therefore, population screening and linkage to care, high vaccination coverage, health promotion, and HBV surveillance are essential to meet the WHO 2030 goal.

Background Detailed characteristics of Hepatitis C virus (HCV) infection in Burkina Faso are scarce. The main aim of this study was to assess HCV seroprevalence in various settings and populations at risk in Burkina Faso between 1990 and 2020. Secondary objectives included the prevalence of HCV Ribonucleic acid (RNA) and the distribution of HCV genotypes. Methods A systematic database search, supplemented by a manual search, was conducted in PubMed, Web of Science, Scopus, and African Index Medicus. Studies reporting HCV seroprevalence data in low and high-risk populations in Burkina Faso were included, and a random-effects meta-analysis was applied. Risk of bias was assessed using the Joanna Briggs institute checklist. Results Low-risk populations were examined in 31 studies involving a total of 168,151 subjects, of whom 8330 were positive for HCV antibodies. Six studies included a total of 1484 high-risk persons, and 96 had antibodies to HCV. The pooled seroprevalence in low-risk populations was 3.72% (95% CI: 3.20–4.28) and 4.75% (95% CI: 1.79–8.94) in high-risk groups. A non-significant decreasing trend was observed over the study period. Seven studies tested HCV RNA in a total of 4759 individuals at low risk for HCV infection, and 81 were positive. The meta-analysis of HCV RNA yielded a pooled prevalence of 1.65% (95% CI: 0.74–2.89%) in low-risk populations, which is assumed to be indicative of HCV prevalence in the general population of Burkina Faso and suggests that about 301,174 people are active HCV carriers in the country. Genotypes 2 and 1 were the most frequent, with 60.3% and 25.0%, respectively. Conclusions HCV seroprevalence is intermediate in Burkina Faso and indicates the need to implement effective control strategies. There is a paucity of data at the national level and for rural and high-risk populations. General population screening and linkage to care are recommended, with special attention to rural and high-risk populations.

Aim As our society ages, the number of people living with dementia also steadily increases. Some work has focused on masticatory behaviour as a form of daily health care that could help prevent cognitive impairment and dementia. However, it is not yet clear how masticatory behaviour influences various cognitive functions. Therefore, the purpose of this study was to examine the effect of masticatory behaviour on the decline of generalized attention, an important cognitive function. Methods Participants were 35 healthy, dentulous individuals without stomatognathic abnormalities (24 men, 11 women; mean age: 56.8 ± 4.8 years). All participants completed three interventions: mastication, foot-stepping, and none (control). Pre- and post-intervention measures of generalized attention were measured by using neuropsychological tests to examine general attention; the results were then compared. Simultaneously, during the generalized attention task, the functional activity of the prefrontal cortex was observed on functional near-infrared spectroscopy. Results Response time of generalized attention improved in both the masticatory and foot-stepping interventions. There was a transient increase in oxyhaemoglobin activity in the right and left prefrontal cortices in the masticatory intervention. Conclusions Masticatory behaviour may be involved in a partial improvement of generalized attention and may induce prefrontal cortex activity in middle-aged and older adults.

Objective The fecal occult blood (FOB) test is commonly used for colorectal cancer screening; however, it is uncertain if further diagnostic interventions, such as a colonoscopy, should be performed based on its results. Method To better understand patient behavior following the FOB test, 6,414 patients (3,807 men and 2,607 women) who underwent colonoscopy between August 2015 and March 2016 at any of the 26 medical institutions throughout Hiroshima Prefecture were invited to participate in the study. All patients provided their written consent, after which they completed a questionnaire, and their colonoscopy results were obtained. These datasets were analyzed in a blinded manner, and the unique codes linking the records were revealed at the end of the analysis. Results Of the total study population, 4,749 patients (74.0%) had previously undergone FOB testing. After classification of common behavioral responses that the patients displayed following their FOB test, the group who had undergone the test several times, who had not had positive test results in the past, and whose latest FOB test results were positive had a significantly higher diagnosis rate of both early- and advanced-stage cancer than the other groups. Furthermore, patients in whom several previous FOB test results had been negative whose previous colonoscopy was positive were associated with a higher diagnosis rate of early-stage cancer than other groups. Conclusion These results suggested that colonoscopy should be performed immediately for patients with positive FOB test results due to their association with colorectal cancer and the possible detection of cancer at an early stage.

Highlights • This study proved of Cambodia achieving WHO 2017 target of, Background: Hepatitis B virus (HBV) infection is highly endemic in most low income countries including Cambodia. This nationwide serosurvey was conducted to assess the impact of hepatitis B vaccination and to determine whether Cambodia met the WHO regional 2017 target of hepatitis B surface antigen (HBsAg) seroprevalence less than 1% in five-year-old children. Methods: A cross-sectional multi-stage cluster survey was conducted among children born during 2010–2012 and their mothers in Cambodia. HBsAg prevalence was estimated by rapid point-of-care testing, and demographic data, including vaccination history, was collected. Vaccine coverage in children and the prevalence of HBsAg among children and mothers was calculated taking into account the complex survey design. Factors associated with children’s failure to receive timely (within 24 h) vaccination were analysed by multivariate logistic analysis. Findings: A total of 2,520 children 5–7 years old and 2,028 mothers were recruited. In total, 78.4% of children received hepatitis B vaccination birth-dose (HepB-BD); of these, 58.7% were administered ≤ 24 h. Birth at home or “other” location were independent risk factors for children’s failure to receive timely HepB-BD. Overall HBsAg seroprevalence was 4.39% (95%CI: 3.53%–5.45%) among mothers and 0.56% (95%CI: 0.32%–0.98%) among children. The prevalence among children without hepatitis B vaccination was 4.62% (95%CI: 1.31%–14.97%). Among children with a HBsAg-positive mother, prevalence was 10.11% (95%CI: 5.41%–18.11%). Interpretation: Having achieved the 2017 target of less than 1% HBsAg prevalence among 5 years old children, Cambodia can now focus on eliminating mother-to-child transmission of HBV. Moreover, the high HBsAg prevalence among mothers suggests that routine screening with proper linkage to care and treatment is needed. Strengthening measures to improve vaccination coverage further and eliminate mother-to-child transmission by coordinated programming with other services offering additional HBV interventions will help move towards the global goal of hepatitis B elimination by 2030. Funding: As per sources of funding.

Background Health care workers (HCWs) are at high risk of contracting blood-borne infections including hepatitis B virus (HBV) infection. In Japan, all HCWs are required to receive HB vaccination before beginning work. This study aimed to investigate the dynamics of the HB surface antibody (anti-HBs) titer after a three-dose HB vaccination in HCWs and to determine effective scheduling of HB vaccination for non-responders. Methods Subjects included 832 medical and dental students who had received a three-dose HB vaccination (Bimmugen® 0.5 ml/vial). Anti-HBs was measured three times (before the third dose and 1 and 5 months after the third dose) using the CLIA method. The cut-off value of anti-HBs acquisition was 10 mIU/mL. After booster doses (three maximum) were administered to non-responders, the anti-HBs titers were measured again. Results Out of 832 students, 491 were analyzed, of which 58.9% (289) were male. Anti-HBs-positive rates before the third dose and 1 and 5 months later were 47.9%, 95.9%, and 89.0%, respectively. The relationship between the antibody titer at one month (x) and 5 months (y) was estimated by log10y = log10x − 0.134 (P Conclusion Anti-HBs titer decreases by an average of 20% within 4 months between the 1st and 5th month after the third dose. Therefore, anti-HBs titer should be measured periodically after completing the three-dose vaccination. Additionally, results suggested that booster doses are effective if administered with the same schedule as primary vaccination.

This study determined the prevalence of total hepatitis A antibody (anti-HAV) among 5–7 years old children and their mothers in the whole Cambodia, using a nationwide study, and examined the differences between the two cohorts. A total of 4535 dried blood spot-driven (DBS) samples (2021 mothers and their 2514 children of 5–7 years old) and the concomitant 922 whole blood samples (subset of the whole participants) were collected using a multistage random sampling strategy throughout Cambodia in 2017. Total anti-HAV was detected using the chemiluminescence enzyme immunoassay method. Compared to gold standard whole blood samples, the sensitivity and specificity of DBS mediated anti-HAV detection were 94.8% and 98%, respectively. Total anti-HAV prevalence among mothers was 91.2% (95%CI: 90.0–92.5%), and that of their children was 31.5% (95%CI: 29.7–33.3%). In our study, the low prevalence of total anti-HAV among children indicates the country’s improvement of safe water and food supply, hygiene and sanitation. If the hygiene and sanitation are consistently improved in Cambodia, the prevalence might be no longer increased when the children become adults.

Monoclonal gammopathy (M-proteinemia) is a premalignant plasma cell disorder. The prevalence of M-proteinemia increases with age and is affected by genetic or environmental factors. Atomic bomb (A-bomb) survivors in Hiroshima are in an age range when they are susceptible to M-proteinemia. The prevalence and incidence of M-proteinemia in Hiroshima A-bomb survivors were investigated for 30 years (1989-2018) to examine the influence of radiation exposure. The overall prevalence of M-proteinemia among 38,602 A-bomb survivors was 2.4%. M-proteinemia prevalence at age 70 years and monoclonal gammopathy of undetermined significance (MGUS) incidence were not associated with radiation exposure category. Males had a 2.30-fold higher prevalence and a 2.08-fold higher incidence than females. The risk of incidence for MGUS was 4.32-fold higher in persons aged 10 years at the time of the A-bombing and 2.56-fold higher in those aged 10-19 years compared with those aged over 30 years. IgG type M-proteinemia was common and the IgM type developed 5-8 years later than other immunoglobulin types. Exposure to radiation was not clearly associated with the prevalence of M-proteinemia or incidence of MGUS in Hiroshima A-bomb survivors. However, males and those aged 20 years at A-bombing had higher susceptibility to MGUS.

This study aimed to investigate the prevalence trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and their genotype distribution among hemodialysis patients, determining their long-term prognosis and the risk factors to the mortality. This cohort study used both the medical data and the blood samples of hemodialysis patients at nine dialysis centers in Hiroshima from 1999 to 2017. Hepatitis B surface antigen (HBsAg) and anti-HCV were screened and then amplification was done to positive sera by polymerase chain reaction for genotyping. Data were employed for multiple regressions to determine the associated risk factors. A total of 3968 patients were subdivided into three groups: who started hemodialysis before 1990, during 1991 to 2001, and after 2002. The periodic prevalence of HBsAg decreased from 2.8% to 1.3% and that of anti-HCV from 33.3% to 9.5% in the three groups. By multiple regressions, the adjusted hazard ratio of diabetes mellitus (DM) ranges from 1.59 to 2.12 and that of HCV RNA positivity ranges from 1.18 to 1.48 (P < .05). Heart failure is the primary cause of death in all groups. Genotype C2 is predominant for HBV and genotype 1b is predominant for HCV. The decreasing trend of both HBV and HCV was found in the cohort. DM and HCV RNA were the significant risk factors leading to poor prognosis among hemodialysis patients. The similar genotype distribution of both HBV and HCV was found as general population. This alarmed to provide early diagnosis, prompt, and adequate treatment to HCV infection among hemodialysis patients.

The high genetic variability of hepatitis C virus (HCV) is the main obstacle to developing a vaccine. E2 has attracted attention for vaccine development because targeting this protein could potentially overcome issues related to the genetic diversity of HCV. In this study, we analyzed HCV genes in the general population of Cambodia and investigated the E2 locus as a candidate for vaccine development. HCV sero-epidemiological surveys were conducted between the period 2010 and 2014, with an HCV RNA&ndash, positive rate of 1.3% (11/868). Follow-up blood samples were collected from four anti-HCV&ndash, and HCV RNA&ndash, positive patients (genotype 1b: 2 cases, 6e: 1 case, 6r: 1 case) after 4.12 years. Analysis of HCV full-length nucleotide sequences in paired specimens revealed that the mutation rates of HCV genotypes 1b and 6e/6r were 1.61&ndash, 2.03 &times, 10&minus, 3 and 2.52&ndash, 2.74 &times, 3 substitutions/site/year, respectively. Non-synonymous substitutions were detected in HVR1, the front layer of the CD81 binding site, and the &beta, sandwich, but not in the N-terminal region or adjacent to the CD81 binding site. Therefore, we conclude that the CD81 binding site is a promising locus for HCV vaccine development.

Although hepatitis B (HBV) and C (HCV) virus infections are still global health issues, measuring sero-markers by standard venipuncture is challenging in areas limited with the adequate human resources and basic infrastructure. This study aimed to inform the usefulness of dried blood spot (DBS) sampling technique for epidemiological study of HBV and HCV in the resources limited areas. We compared specimen recovery rate expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV between serum specimens and DBS samples (HemaSpot vs Whatman903). Sensitivity ratio was calculated as the ratio of the measured value from DBS to the measured value from serum. Then both the qualitative and quantitative comparisons of HBsAg detection by DBS were done using Cambodian samples. HBsAg, HBcAb and anti-HCV sensitivity ratios for the highest sample dilution (8-fold) were 31.2:1, 38.9:1 and 32.0:1 for Whatman903 card and 17.6:1, 23.5:1 and 26.3:1 for HemaSpot respectively. Detection efficacy of HemaSpot (80%) was not inferior to Whatman903 (60%) after 1 month storage, and no significant difference in any hepatitis virus sero-markers was observed in HemaSpot-spotted patient samples stored for 2 weeks at −25 °C and 29 °C. All reference HemaSpot -spotted 400 HBsAg sero-negative samples showed negative. Sensitivity and specificity of HBsAg in HemaSpot were 92.3% and 100%. The recovery expressed as analytical sensitivity ratio of HBsAg, HBcAb and anti-HCV of HemaSpot specimen were not inferior to Whatman903. Therefore, DBS with its usefulness proved as an acceptable tool for large epidemiological study of HBV and HCV in resources limited remote area.

Aims This study aimed to detect Hepatitis B virus (HBV) genome sequences and their variants as of nationwide scale using dried blood spot (DBS) samples and to provide up-to-date reference data for infection control and surveillance in Cambodia. Method Among 2,518 children age 5-7 years and their 2,023 mothers participated in 2017 Cambodia nationwide sero-survey on hepatitis B surface antigen (HBsAg) prevalence using multistage random sampling strategy, 95 mothers and 13 children positive to HBsAg were included in this study. HBV DNA was extracted from DBS, then performed polymerase chain reaction. HBV genotypes and potential variants were examined by partial and full length genomic analysis. Results HBV DNA positive rate was 3.46% (70/2023) in mothers and 0.48% (12/2518) in their children. Genotype C (80.49%) was abundantly found throughout the whole Cambodia whilst genotype B (19.51%) was exclusively found in regions bordering Vietnam. HBs mutants were found in 24.29% of mothers and 16.67% of children with HBV DNA positive sera. Full-length genome analysis revealed the homology of 99.62-100% in each mother-child pair. Genotype B was clarified to recombinant genotype B4/C2 and B2/C2. Double (48.39%) and combination mutation (32.26%) were observed in core promoter region of HBV C1 strains. Conclusion This study showed the capable of DBS for large-scale molecular epidemiological study of HBV in resource limited countries. Full-genome sequences yield the better understanding of sub-genotypes, their variants and the degree of homology between strains isolated from mother-child pairs calls for effective strategies on prevention, control and surveillance of mother-to-child HBV transmission in Cambodia.

Background and Aim Although mortality rates of colorectal cancer (CRC) have been increasing in Japan, its screening rates remain stagnant at 19.2% among Japanese population aged > 40 years in 2014. To evaluate the importance of CRC screening by fecal occult blood test (FOBT), this study estimated the incidence of FOBT-positivity and CRC by sex–age stratification and clarified the risk factors for CRC. Methods Between 2007 and 2014, 56 324 residents (21 517 men and 34 807 women) were enrolled in this study. The sex–age-stratified incidence rates of FOBT-positivity and CRC were estimated by records from health checkups and colonoscopy. Regarding CRC incidence rate in particular, positive predictive value was adopted to adjust bias of FOBT-positivity that did not undergo colonoscopy by person-year method. To investigate the risks of CRC onset, a nested case–control study with 1:10 person-matching on sex and age was performed. Results Incidence rates of FOBT-positivity and CRC are 4183/100 000 person-year (100 Kpy) and 141.3/100 Kpy, respectively. In both cases, men has higher incidence rate than women (1.3 times for FOBT; 4977 vs 3718/100 Kpy and 2.3 times for CRC; 217.0 vs 96.4/100 Kpy). Conclusions The records from health checkups were useful to estimate incidence rates of CRC with this procedure. The age-stratified incidence rate indicated the importance of CRC screening by FOBT, especially for men and those aged > 50 years. Additionally, it is strongly recommended to do further investigation if positive for initial FOBT screening especially for those who are > 70 years.

Aim We aimed to estimate hepatitis B surface antigen (HBsAg) positivity among birth year-stratified pregnant women in Hiroshima, Japan, and compare prevalence rates between women born before and after implementation of a national immunoprophylactic vaccination program for babies born to hepatitis B virus (HBV) carrier mothers in Japan. Methods Pregnant women who gave birth at all delivery hospitals/clinics in Hiroshima prefecture between 1 April 2010 and 31 March 2011 were eligible. Lists collected from each institution included survey items such as age (pregnant woman's birth year) and HBsAg and hepatitis C virus (HCV) antibody (anti-HCV) test results, which were posted anonymously and non-consolidated from medical records. We calculated the HBsAg and anti-HCV prevalence in our cohort according to the mothers' birth year. Results In 41 of 58 hospitals/clinics, 15 233 and 15 035 pregnant women underwent HBsAg and anti-HCV testing, corresponding to 59.6% and 58.9% of 25 546 births in the 2010 fiscal year, respectively. The overall HBsAg positive rate was 0.51% (95% confidence interval [CI], 0.40–0.63%), and an extremely low prevalence (0.10%; 95% CI, 0.00–0.25%) was observed among pregnant women born after 1986. However, the prevalence in this study was slightly higher than the nationwide value (0.31%) and the Chugoku region-specific value (0.46%) among first-time blood donors at Japanese Red Cross blood centers between 2001 and 2006. No significant difference in anti-HCV positivity was observed. Conclusion Only two pregnant women born after the preventive program implementation were HBsAg-positive. Perinatal HBV transmission is estimated to be almost completely inhibited in the next generation.

Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P

Since the early 21st century, almost all developed countries have had a very low hepatitis A virus antibody (anti-HAV) sero-prevalence profile, as sanitation conditions and health care facilities have been optimized to a universal standard. There has not been a report on anti-HAV prevalence among a large scale population in Japan since 2003. Therefore, this study aimed to investigate the current HAV status among the general population in Hiroshima. From each age and sex specific group, a total of 1,200 samples were randomly selected from 7,682 stocked serum samples from residents’ and employees’ annual health check-ups during 2013–2015. Total anti-HAV was detected using Chemiluminescent Enzyme Immunoassay. The overall anti-HAV sero-prevalence was 16.8%. In both males and females, anti-HAV prevalence among individuals between 20–59 years of age was as low as 0.0–2.0%, whilst that among 70 s was as high as 70.0–71.0%. A large number of residents aged under 60 are now susceptible to HAV infection. The cohort reduction trend of anti-HAV in Japan exposes the high possibility of mass outbreak in the future. HAV vaccine especially to younger generation and high risk population may prevent outbreak in Japan.

Background In this study, we performed molecular characterization of SARS-CoV-2 strains in Hiroshima and its mutation pattern between the first and second waves of the outbreak. Method A total of 55 nasal swab samples from the first wave in Hiroshima and 13 from the second wave were examined quantitatively by RT-qPCR and qualitatively by nested PCR using specific primers. Four samples from each wave underwent next-generation sequencing and phylogenetic tree analysis including controls and all sequences retrieved in Japan from GISAID and GenBank. Subsequently, mutations were examined. Results Viral load ranged 7.85 × 101−1.42 × 108 copies/ml. Of 68 samples, one was Asian type-O, 65 were European type-GR, and 2 were undetectable. Phylogenetic tree analysis indicated that Japan was infected with various Asian strains (L, S, V, O) from January through April. By second week of March, European strains (G, GH, GR) had appeared, and GR strains became predominant after mid-March. The first case in Hiroshima was classified as Asian strain O, and the rest were GR strains. Then, second wave of GR strains appeared independently with 11–15 base mutations. Comparing the first- and second-wave GR strains, mutation rate was 1.17–1.36 × 10−3 base substitutions per site per year; in addition, amino acid changes occurred at S1361P and P3371S in ORF1a, A314V in ORF1b, and P151L in N. All seven GR strains were D614G variants with R202K and G203R mutations in N. A single-nucleotide insertion in ORF8 that causes a defect in ORF8 protein was found in one isolate (S66) from the second wave. Conclusion Our findings reveal the evolutionary hierarchy of SARS-CoV-2 in Japan. The predominant D614G variants and a new form of ORF8 deletion in Hiroshima provide the clue for role of viral factor in local outbreaks of SARS-CoV-2.

Countermeasures against hepatitis B and C virus (HBV, HCV) infection at work sites in Japan have not yet been implemented. This study aimed to determine the status of viral hepatitis infection among employees in Japan.We undertook a workplace-based cross-sectional study from 2011 to 2016 in Hiroshima, Japan. Hepatitis B virus and HCV markers were identified during a routine checkup of employees in 15 enterprises. The screening results were sent to employees directly and not to employers. A thorough examination of the participants who screened positive was encouraged by forwarding to them a referral letter by our research group to specialized medical institutions.Of the 3015 employees, 2420 (80.3%) underwent hepatitis virus screening. Of these, 13.8% had been screened for hepatitis virus before this survey. The prevalence of hepatitis B surface antigen was 0.95% (n = 23; 95% confidence interval, 0.6-1.3%). The prevalence of hepatitis B core antibody was as high as 31.5% at age 60-69 years, and 41.5% at age 70 years and over. The HCV carrier rate was 0.45% (n = 11; 0.2-0.7%) and 54.5% of them had genotype 2. Thirty-four carriers were detected, and 44.1% of them were detected for the first time; 53.3% of the newly detected carriers visited medical institutions with the referral, and underwent a periodic follow-up or treatment.Promoting hepatitis virus screening for employees may help detect carriers who are unaware of their infection and require treatment. Submitting the results to employees with a referral letter to medical institutions at the time of positive diagnosis may be effective.

Although mortality rates of colorectal cancer (CRC) have been increasing in Japan, its screening rates remain stagnant at 19.2% among Japanese population aged 40 years in 2014. To evaluate the importance of CRC screening by fecal occult blood test (FOBT), this study estimated the incidence of FOBT-positivity and CRC by sex-age stratification and clarified the risk factors for CRC.Between 2007 and 2014, 56 324 residents (21 517 men and 34 807 women) were enrolled in this study. The sex-age-stratified incidence rates of FOBT-positivity and CRC were estimated by records from health checkups and colonoscopy. Regarding CRC incidence rate in particular, positive predictive value was adopted to adjust bias of FOBT-positivity that did not undergo colonoscopy by person-year method. To investigate the risks of CRC onset, a nested case-control study with 1:10 person-matching on sex and age was performed.Incidence rates of FOBT-positivity and CRC are 4183/100 000 person-year (100 Kpy) and 141.3/100 Kpy, respectively. In both cases, men has higher incidence rate than women (1.3 times for FOBT; 4977 vs 3718/100 Kpy and 2.3 times for CRC; 217.0 vs 96.4/100 Kpy).The records from health checkups were useful to estimate incidence rates of CRC with this procedure. The age-stratified incidence rate indicated the importance of CRC screening by FOBT, especially for men and those aged 50 years. Additionally, it is strongly recommended to do further investigation if positive for initial FOBT screening especially for those who are 70 years.

This study aimed to survey the prevalence and incidence of hepatitis B (HBV) and hepatitis C virus (HCV) infection among elementary school students in Siem Reap province, Cambodia and to evaluate the effects of a national infant HBV vaccination program introduced in 2001.Students in 3rd grade during the 2011, 2012, and 2013 academic years were enrolled in this study; at the time of the second examination, in the 2014-2015 academic year, the students were in 5th or 6th grade. The incidence and prevalence rates of HBV and HCV infection were estimated and full HBV sequences were analyzed.Among 248 students (107 male and 141 female) born between 1999 and 2005, five students were HBV surface antigen (HBs-Ag) positive (2.02%), and all of them were infected with genotype C. Among them, subgenotype C1 was found in four students and, unexpectedly, complete genetic sequence identity of subgenotype C1 was found in two students from different families. The anti-HBV core (HBc) and anti-HBs prevalence rates were 10.89% and 16.13%, respectively. Twenty-five students were positive for anti-HBs and negative for both HBsAg and anti-HBc (10.08%; estimated serological vaccination rate); this rate increased significantly with the birth year (P = 0.0229). Prevalence of anti-HCV was 2.82%, and HCV RNA was not detected. The estimated incidence of HBV and HCV infection were both 0/1000 person-years (PY) (95% confidence interval, 0-20.61/1000 PY and 0-14.50/1000 PY, respectively).Hepatitis B virus full-genome sequencing and serological analysis revealed the possibility of horizontal transmission of HBV among Cambodian schoolchildren. However, the anti-HBc positivity rate decreased along with increasing age and estimated serological vaccination rates.