Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2.

The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal antibodies and antiviral drugs for COVID-19 against these variants1,2. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries3. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone4, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.

Association of gut microbiota with the pathogenesis of SARS-CoV-2 Infection in people living with HIV.

BACKGROUND: People living with HIV (PLWH) with chronic inflammation may have an increasing risk for coronavirus disease 2019 (COVID-19) severity; however, the impact of their gut microbiota on COVID-19 is not fully elucidated. Here, we analyzed the temporal changes in the gut microbiota composition of hospitalized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected PLWH (PLWH-CoV) and their correlation with COVID-19 severity. RESULT: The 16S rRNA analysis results using stool samples (along the timeline from disease onset) from 12 hospitalized PLWH-CoV, whose median CD4 + T cell count was 671 cells/µl, were compared to those of 19 healthy people and 25 PLWH. Bacterial diversity in PLWH-CoV is not significantly different from that of healthy people and SARS-CoV-2 non-infected PLWH, but a significant difference in the microbiota diversity was observed in the classification according to the disease severity. Immediately after the disease onset, remarkable changes were observed in the gut microbiota of PLWH-CoV, and the changing with a decrease in some short-chain fatty acid-producing bacteria and an increase in colitis-related pathobiont. In the second week after disease onset, relative amounts of specific bacteria distinguished between disease severity. One month after the disease onset, dysbiosis of the gut microbiota persisted, and the number of Enterobacteriaceae, mainly Escherichia-Shigella, which is potentially pathogenic, increased and were enriched in patients who developed post-acute sequelae of COVID-19 (PASC). CONCLUSION: The changes in the gut microbiota associated with SARS-CoV-2 infection observed in PLWH in this study indicated a persistent decrease in SCFA-producing bacteria and an intestinal environment with an increase in opportunistic pathogens associated with enteritis. This report demonstrates that the intestinal environment in PLWH tends to show delayed improvement even after COVID-19 recovery, and highlights the importance of the dysbiosis associated with SARS-CoV-2 infection as a potential factor in the COVID-19 severity and the PASC in PLWH.

Characterization of mutations in hepatitis B virus DNA isolated from Japanese HBsAg-positive blood donors in 2021 and 2022.

Missense mutations in certain small envelope proteins diminish the efficacy of antibodies. Consequently, tracking the incidence and types of vaccine-escape mutations (VEMs) was crucial both before and after the introduction of universal hepatitis B vaccination in Japan in 2016. In this study, we isolated hepatitis B virus (HBV) DNA from 58 of 169 hepatitis B surface antigen (HBsAg)-positive blood samples from Japanese blood donors and determined the nucleotide sequence encoding the small envelope protein. DNA from six (10%) of the samples had VEMs, but no missense mutations, such as G145R, were detected. Complete HBV genome sequences were obtained from 29 of the 58 samples; the viral genotype was A1 in one (3%), A2 in three (10%), B1 in nine (31%), B2 in five (17%), B4 in one (3%), and C2 in 10 (34%) samples. Tenofovir-resistance mutations were detected in two (7%) samples. In addition, several core promoter mutations, such as 1762A>T and 1764G>A, and a precore nonsense mutation, 1986G>A, which are risk factors for HBV-related chronic liver disease, were detected. These findings provide a baseline for future research and highlight the importance of ongoing monitoring of VEMs and drug resistance mutations in HBV DNA from HBsAg-positive blood donors without HBV antibodies.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease.

AIM: Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. METHODS: We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). RESULTS: Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). CONCLUSIONS: Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Attenuation of hepatitis A antibody after immunization with hepatitis A vaccine (Aimmugen) in people living with HIV.

AIM: Hepatitis A (HA) is a vaccine-preventable disease. In regions with good sanitation, men who have sex with men (MSM) are the key affected populations. During the 2018-2019 HA outbreak among MSM in Japan, we actively vaccinated MSM living with HIV (MSM-LWHIV) with Aimmugen. As previously reported, their antibody seroconversion rate due to vaccination was lower than that of healthy individuals. However, the durability of Aimmugen in people living with HIV has not yet been reported. We evaluated attenuation after the one-series vaccination (comprising three inoculations) and the factors associated with attenuation. METHODS: We retrospectively examined anti-HA immunoglobulin G (anti-HA-IgG) titers and other clinical data from our hospital's medical records. Patients with no history of vaccination or HA infection (i.e., negative HA-IgG titers) who received one series of Aimmugen, achieved seropositivity, and anti-HA-IgG antibodies were tested ≥2 years after three doses were included. Fisher's exact test and the Mann-Whitney U-test were performed. p < 0.05 was considered statistically significant. RESULTS: Fifty-one MSM-LWHIV were included. All were seropositive after the third dose with a median HA-IgG titer of 10.1 (interquartile range, 7.2-12.2) (sample/cut-off values [s/co]). In 45 (40-49) months, seropositivity decreased to 90% (46/51) and was attenuated to a median of 4.4 (2.3-6.5) s/co. Lower baseline B cell counts (p = 0.049), lower anti-HA-IgG levels after the second dose (p = 0.002), and lower anti-HA-IgG levels after the third dose (p = 0.003) were associated with seronegativity. CONCLUSIONS: Anti-HA-IgG titers of vaccinated MSM-LWHIV may be attenuated; thus, additional immunizations should be considered.

Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan.

In 2018, there was a hepatitis A outbreak in Japan, and hepatitis A virus (HAV) infection is considered a sexually transmitted disease. In general, patients with hepatitis A should be given attention, and this disease should be prevented more than ever. The Japan Agency for Medical Research and Development (AMED) Hepatitis A and E viruses (HAV and HEV) Study Group has worked on the project to create "Recent Advances in Hepatitis A Virus (HAV) Research and Clinical Practice Guidelines for HAV Infection in Japan". The group consists of expert hepatologists and virologists who gathered at virtual meeting on August 5, 2023. Data about the pathogenesis, infection routes, diagnosis, complications, several factors for the severities, vaccination, and current and future treatments for hepatitis A were discussed and debated for a draft version. The participants assessed the quality of cited studies. The finalized recommendations are presented in this review. The recent advances in HAV research and clinical practice for HAV infection in Japan, have been reviewed by the AMED HAV and HEV Study Group.

Recent advances in hepatitis E virus research and the Japanese clinical practice guidelines for hepatitis E virus infection.

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.

Brief communications: changes in inflammatory biomarkers and lipid profiles after switching to long-acting cabotegravir plus rilpivirine.

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.

Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study.

BACKGROUND: This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. METHODS: Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. RESULTS: A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5-64.9%; mean age: 35.3-37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. CONCLUSIONS: Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. CLINICAL TRIALS REGISTRATION: Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Incidence of sexually transmitted hepatitis C virus infection among men who have sex with men in Japan from 2009 to 2023.

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct-acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty-two cases were newly confirmed to be HCV infection in 2009-2019 and a total of 9 cases in 2020-2023, with an incidence rate of 5.04 per 1000 person-years in 2009-2019 and 5.55 per 1000 person-years in 2020-2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non-HIV-infected persons, may be much higher.

Research article antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination.

BACKGROUND: The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear. METHODS: Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b. RESULTS: The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia. CONCLUSIONS: These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.

Injection drug use and sexually transmitted infections among men who have sex with men: A retrospective cohort study at an HIV/AIDS referral hospital in Tokyo, 2013-2022.

Men who have sex with men (MSM) who use injection drugs (MSM-IDU) are at high risk of sexually transmitted infections (STIs), but the long-term incidence is unclear. We conducted a single-centre retrospective cohort study using the clinical records of non-haemophilia men with human immunodeficiency virus (HIV) who visited the Institute of Medical Science, the University of Tokyo (IMSUT) Hospital, located in Tokyo, Japan, from 2013 to 2022. We analysed 575 patients including 62 heterosexual males and 513 MSM patients, of whom 6.8% (35/513) were injection drug use (IDU). Compared to non-IDU MSM, MSM-IDU had a higher incidence of hepatitis C virus (HCV) (44.8 vs 3.5 /1,000 person-years (PY); incidence rate ratio (IRR) [95% confidence interval (95% CI)], 12.8 [5.5-29.3], p < 0.001) and syphilis (113.8 vs 53.3 /1,000 PY; IRR, 2.1 [1.4-3.1], p < 0.001). The incidence of other symptomatic STIs (amoebiasis, chlamydia, and gonorrhoea infections) was <4/1,000 PY. In multivariable Poisson regression analysis, HCV incidence was associated with MSM (IRR, 1.8 × 106 [9.9 × 105-3.4 × 106], p < 0.001), IDU (IRR, 10.1 [4.0-25.6], p < 0.001), and syphilis infection during the study period (IRR, 25.0 [1.2-518.3]/time/year, p < 0.001). Among men with HIV, the prevalence of IDU in MSM and the long-term incidence of STIs in MSM-IDU were high. IDU and sexual contact are important modes of transmission of HCV among HIV-infected MSM in Tokyo.

Triglyceride level and soft drink consumption predict nonalcoholic fatty liver disease in nonobese male adolescents.

AIM: Differential metabolic risk factors of nonalcoholic fatty liver disease (NAFLD) in nonobese male adolescents were analyzed examining relationships between NAFLD and clinical parameters of metabolic syndrome, including exercise and soft drink consumption, in male adolescents. METHODS: In total, 134 male university students (nonobese, n = 78; obese, n = 56) who underwent the first-year health checkup were divided into the NAFLD and non-NAFLD groups based on abdominal ultrasonography (AUS) findings. Relationships between NAFLD and metabolic parameters, including body mass index (BMI) and AUS score, were examined in nonobese students. RESULTS: Metabolic factors associated with hypertension, abdominal fat, liver damage, dyslipidemia, and impaired glucose tolerance were significantly less common in nonobese students than in obese students. The aforementioned factors and soft drink consumption were significantly more common in the NAFLD group than in the non-NAFLD group. The univariate and multivariate analyses of nonobese students showed that the triglyceride level (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.10, p = 0.001) was higher and soft drink consumption (OR, 36.8; 95% CI, 3.69-368, p < 0.001) was more common in the NAFLD group than the non-NAFLD group. CONCLUSIONS: Triglyceride level and soft drink consumption could aid in the detection of NAFLD in nonobese male adolescents. Our findings could provide useful information related to NAFLD and metabolic syndrome in nonobese adolescents.

Impact of sustained viral response for hepatitis C virus on the outcomes of liver transplantation in hemophilic patients with human immunodeficiency virus/hepatitis C virus co-infection: A nationwide survey in Japan.

AIM: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection from blood products for hemophilia has been a social problem in Japan, and liver transplantation (LT) for these patients has been a challenging procedure. However, with the advent of the direct-acting antiviral agent for HCV and change in the policy for prioritization of deceased donor LT, the results of LT for patients co-infected with HCV/HIV may have improved. METHODS: This study was conducted to provide updated results of our nationwide survey of LT for patients co-infected with HCV/HIV, from January 1997 to December 2019. We collected data on 17 patients with HIV/HCV co-infection who underwent either deceased donor LT (n = 5) or living donor LT (n = 12). RESULTS: All the patients were men with hemophilia, and the median age was 41 (range, 23-61) years. The median CD4 count before LT was 258 (range, 63-751). Most patients had poor liver function before surgery with Child-Pugh grade C and a Model for End-stage Liver Disease score of 20 (range, 11-48). The right lobe was used for most grafts for living donor liver transplantation (n = 10). Overall survival was significantly better with a sustained viral response (SVR) than without an SVR, and a univariate analysis indicated that SVR after direct-acting antiviral or interferon/ribavirin showed the highest hazard ratio for patient survival after LT. A multivariate analysis was not possible because of the limited number of cases. CONCLUSION: SVR for HCV showed the highest impact on the outcome of LT for patients with hemophilia co-infected with HIV/HCV. SVR for HCV should be achieved before or after LT for patients with hemophilia co-infected with HIV/HCV for a better outcome.

Background factors in people living with HIV in Japan who switch to cabotegravir plus rilpivirine: A pilot study.

Long-acting therapy of cabotegravir and rilpivirine is expected to free people from the negative emotions of living with HIV associated with taking drugs, but problems such as increased number of hospital visits, lack of anti-HBV activity, and limited convenience in people with concomitant drugs have been noted. In this single-center, prospective, cross-sectional study, we investigated background factors of people living with HIV in Japan who chose cabotegravir plus rilpivirine. Forty-seven percent (36 of 76) of individuals chose this regimen, but many people living with HIV who visited the hospital once every 3 months or needed concomitant medications due to complications chose this regimen and there were no significant differences in background factors that could affect convenience between the groups of those who switched and those who did not.

Mpox associated with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus among people with HIV.

We report three cases of mpox (disease caused by the monkeypox virus) that developed in people with HIV co-infected with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus (PVL-MRSA), diagnosed in mid-February 2023. All three cases had preserved HIV immune status, and their mpox was mild and resolved without antiviral medications, but the trigger for their visit was the presence and history of skin and soft tissue infections. Our cases suggest that mpox is already prevalent among sexually active MSM in Tokyo, Japan. PVL-MRSA has been extremely rare in the general population of Japan, but several literatures reported widespread prevalence of PVL-MRSA among sexually active MSM-HIV. Mpox will become prevalent in the future in a population of sexually active MSM at high risk for PVL-MRSA infection, requiring an understanding of the interaction and pathogenesis of the two diseases.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.

Immunological Correlates of Prevention of the Onset of Seasonal H3N2 Influenza.

On influenza virus infection or vaccination, immune responses occur, including the production of antibodies with various functions that contribute to protection from seasonal influenza virus infection. In the current study, we attempted to identify the antibody functions that play a central role in preventing the onset of seasonal influenza by comparing the levels of several antibody titers for different antibody functions between 5 subclinically infected individuals and 16 patients infected with seasonal H3N2 virus. For antibody titers before influenza virus exposure, we found that the nAb titers and enzyme-linked immunosorbent assay titers against hemagglutinin and neuraminidase (NA) proteins in the subclinically infected individuals were significantly higher than those in the patients, whereas the NA inhibition titers and antibody-dependent cellular cytotoxicity activities did not significantly differ between subclinically infected individuals and infected patients. These results suggest that nAb and enzyme-linked immunosorbent assay titers against hemagglutinin and NA serve as correlates of symptomatic influenza infection.