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COVID-19 has become widespread in Japanese children. However, the impact of varying immunization coverage on the seroprevalence of SARS-CoV-2 in children is unknown. We examined the SARS-CoV-2 antibody in children aged 0 to 18 who were hospitalized at a university hospital from June 2020 through May 2023. The SARS-CoV-2 anti-nucleoprotein (N) antibody and anti-RBD spike (S) protein antibody was measured. A total of 586 cases were enrolled. The median age was 4 years old (interquartile range 1–9), and 362 (61.8 %) were male. The seroprevalence of anti-S antibodies gradually increased from October 2021 and reached 60 percent by early 2023. The anti-N antibody increased starting in January 2022 and reached 50 percent in May 2023. There was a discrepancy in the seroprevalence of anti-S and N antibodies in children 0 years of age or 12 years and older until the fall of 2022. This discrepancy was minimal for children 1–4 years of age and relatively small in the 5–11-year-old group. The data suggests that approximately half of the children in our cohort had been infected with SARS-CoV-2 by May 2023. The discrepancy in seropositivity between the anti-S and N antibodies corresponded to the reported vaccine uptake of each target age group, which suggested protective effects of immunization. However, this effect appeared to diminish after early 2023. Age dependent discrepancy between SARS-CoV-2 anti-N and anti-S antibody in children reflected differences in vaccine coverage. [ABSTRACT FROM AUTHOR]

Live attenuated vaccines are contraindicated for patients on immunosuppressive agents or biological agent, except for live attenuated varicella vaccine, although previous reports showed their effectiveness and safety. This study is the nationwide cross-sectional research about the current utilization of live attenuated vaccines for patients on immunosuppressive agents or biological agents in Japan. We sent questionnaires to pediatric centers and examined whether each institution offered live attenuated vaccines to patients with immunosuppressive agents or biological agents (institutional research). We also examined adverse events associated with live attenuated vaccines between 2013 and 2017 (patient research). In the institutional research, 46 out of 334 institutions (13.8%) administered live attenuated vaccines to patients receiving immunosuppressive agents. In contrast, only six out of 270 institutions (2.2%) administered live attenuated vaccines to patients receiving biological agents. However, 66.3% of physicians answered that patients receiving immunosuppressive agents should be immunized with live attenuated vaccines, and only 7.0% disagreed with them. In the patient research, data for 781 patients were collected. Vaccine-associated infections were observed in only two patients (0.3%), both of whom had varicella, although they recovered promptly. No life-threatening adverse events were noted. Conclusion: In pediatric centers, the demand for live attenuated vaccines in patients receiving immunosuppressive agents was high and most physicians think they should be immunized. Immunization with live attenuated vaccines appeared safe in patients receiving immunosuppressive agents, although further studies are needed for patients receiving biological agents What is known: • Live attenuated vaccines (LAV) are generally contraindicated for patients on immunosuppressive agents (IS) or biological agents (BA), except for live attenuated varicella vaccine, as immunocompromised patients are at greater risk for serious viral infection from the vaccine strains. • Viral infections, such as measles and varicella, cause serious complications in children receiving IS. • Several previous reports showed that LAV is relatively effective and safe for patients receiving IS. What is new: • In Japan, the demand for LAV in patients receiving IS was high, and most physicians hoped they should be immunized. • Vaccine-associated infection is rarely observed in patients with IS after LAV administration. • Immunization with LAV appeared safe in patients receiving IS. Trial registration: University Hospital Medical Information Network (UMIN). Trial registration number: UMIN000029176. Date of registration: 2017/09/19. [ABSTRACT FROM AUTHOR]

Patients receiving immunosuppressive agents are at risk of life-threatening infections. However, live vaccines are generally contraindicated in them. We conducted a prospective study regarding live attenuated vaccines for them. Patients elder than one year of age with immunosuppressive agents who showed negative or borderline antibody titers (virus-specific IgG levels < 4.0) against one or more of measles, rubella, varicella, and mumps and fulfilled the criteria (CD4 cell counts ≥ 500/mm3, stimulation index of lymphocyte blast transformation by PHA ≥ 101.6, serum IgG level ≥ 300 mg/dl, no steroid use or prednisolone < 1 mg/kg/day or < 2 mg/kg/2 days, trough levels of tacrolimus or cyclosporine were < 10 ng/ml or < 100 ng/ml and under good control of primary disease) were enrolled. Sixty-four vaccinations were administered to 32 patients. The seroconversion rates for measles, rubella, varicella, and mumps were 80.0%, 100.0%, 59.1%, and 69.2%, respectively. No life-threatening adverse events were observed, although one patient suffered from vaccine-strain varicella who showed cellular and humoral immunodeficiency (CD4 cell counts = 511/mm3, stimulation index of lymphocyte blast transformation by PHA = 91.1, serum IgG level = 208 mg/dl). This girl was immunized before we established the criteria for vaccination. Immunization with live attenuated vaccines for patients receiving immunosuppressive agents might be effective and safe if their cellular and humoral immunological parameters are within normal levels. However, determining the criteria for vaccination by immunological parameters should be established to guarantee the safety of live vaccines in the future. Clinical Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000007710. The date of registration: 2012/4/13. [ABSTRACT FROM AUTHOR]

Background : The nationwide epidemiology and clinical practice patterns for younger children hospitalized with urinary tract infections (UTIs) were unclear. Methods: We conducted a retrospective observational study consisting of 32,653 children aged < 36 months who were hospitalized with UTIs from 856 medical facilities during fiscal years 2011–2018 using a nationally representative inpatient database in Japan. We investigated the epidemiology of UTIs and changes in clinical practice patterns (e.g., antibiotic use) over 8 years. A machine learning algorithm of multivariate time-series clustering with dynamic time warping was used to classify the hospitals based on antibiotic use for UTIs. Results: We observed marked male predominance among children aged < 6 months, slight female predominance among children aged > 12 months, and summer seasonality among children hospitalized with UTIs. Most physicians selected intravenous second- or third-generation cephalosporins as the empiric therapy for treating UTIs, which was switched to oral antibiotics during hospitalizations for 80% of inpatients. Whereas total antibiotic use was constant over the 8 years, broad-spectrum antibiotic use decreased gradually from 5.4 in 2011 to 2.5 days of therapy per 100 patient-days in 2018. The time-series clustering distinctively classified 5 clusters of hospitals based on antibiotic use patterns and identified hospital clusters that preferred to use broad-spectrum antibiotics (e.g., antipseudomonal penicillin and carbapenem). Conclusions: Our study provided novel insight into the epidemiology and practice patterns for pediatric UTIs. Time-series clustering can be useful to identify the hospitals with aberrant practice patterns to further promote antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Background Coagulase-negative Staphylococcus (CoNS) is the predominant cause of catheter-related bloodstream infections (CRBSI). Infants in neonatal intensive care units (NICU) often suffer from CoNS CRBSI, which are often refractory to treatment. Objectives We sought to evaluate risk factors for developing persistent bacteremia due to CoNS CRBSI in infants, in order to identify those who require early aggressive management. Methods We conducted a retrospective case-control study of infants in the NICU who developed CRBSI due to CoNS. Patient demographics, condition and management of CRBSI were compared between those with persistent and non-persistent bacteremia. Furthermore, prognosis of infants in the NICU after CoNS CRBSI was evaluated. Results Seventy six episodes of CRBSI, including 17 persistent bacteremia and 59 non-persistent bacteremia, were analyzed. In univariate analyses, persistent bacteremia was significantly associated with corrected age equivalent to gestational age of 22–28 weeks at onset of CRBSI [Odds ratio (OR) = 4.33; P = 0.04], platelet count <100,000/μL (OR = 11.5; P < 0.001), use of vasopressor (OR = 5.38; P = 0.003), and delayed CVC removal (OR = 6.25; P = 0.003). In multivariate analysis, persistent bacteremia was significantly associated with platelet count <100,000/μL (OR = 7.80; P = 0.007), and delayed CVC removal (OR = 5.07; P = 0.03). Infants with persistent bacteremia tended to have a lower survival rate after CoNS CRBSI, however this was not statistically significant ( P = 0.21). Conclusions Early CVC removal should be considered for the treatment of CRBSI due to CoNS in infants with platelet counts of less than 100,000/μL. [ABSTRACT FROM AUTHOR]

Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research. [ABSTRACT FROM AUTHOR]

Genetic mapping studies may provide association between sequence variants and disease susceptibility that can, with further experimental and computational analysis, lead to discovery of causal mechanisms and effective intervention. We have previously demonstrated that polymorphisms in immunity-related GTPases (IRG) confer a significant difference in susceptibility to Chlamydia psittaci infection in BXD recombinant mice. Here we combine genetic mapping and network modeling to identify causal pathways underlying this association. We infected a large panel of BXD strains with C. psittaci and assessed host genotype, IRG protein polymorphisms, pathogen load, expression of 32 cytokines, inflammatory cell populations, and weight change. Proinflammatory cytokines correlated with each other and were controlled by a novel genetic locus on chromosome 1, but did not affect disease status, as quantified by weight change 6 days after infection In contrast, weight change correlated strongly with levels of inflammatory cell populations and pathogen load that were controlled by an IRG encoding genetic locus (Ctrq3) on chromosome 11. These data provided content to generate a predictive model of infection using a Bayesian framework incorporating genotypes, immune system parameters, and weight change as a measure of disease severity. Two predictions derived from the model were tested and confirmed in a second round of experiments. First, strains with the susceptible IRG haplotype lost weight as a function of pathogen load whereas strains with the resistant haplotype were almost completely unaffected over a very wide range of pathogen load. Second, we predicted that macrophage activation by Ctrq3 would be central in conferring pathogen tolerance. We demonstrated that macrophage depletion in strains with the resistant haplotype led to neutrophil influx and greater weight loss despite a lower pathogen burden. Our results show that genetic mapping and network modeling can be combined to identify causal pathways underlying chlamydial disease susceptibility. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is an important cause of sexually transmitted infection that can manifest as acute cervicitis, pelvic inflammatory disease, and most commonly, chronic asymptomatic infection. The basis of this wide spectrum of manifestations and the factors that lead to clearance or chronic infection are poorly understood. We reviewed specific literature pertaining to clearance of primary genital tract infections in animal models, including mice, guinea pigs, pigs, sheep, and nonhuman primates. T helper 1 cell responses involved in cell-mediated immunity are key immune parameters that define efficient clearance in the murine and guinea pig models of chlamydial infection, which are useful for studying C. trachomatis clearance. However, there may be some differences between humans and other animals in innate and adaptive immune responses to chlamydial infection. Studies have suggested that differences in the induced T cell subsets and the species- specific differences in interferon γ-mediated effector mechanisms may play a significant role in these discrepancies. To close these gaps in knowledge, translational research in humans is a critical next step. However, for questions about specific mechanisms of host-pathogen interaction that cannot be answered feasibly or ethically in humans, animal models will continue to be important. Future research should include use of humanized and nonmurine models that establish prolonged infection to improve understanding of chronic human infections. [ABSTRACT FROM AUTHOR]

Abstract: Immunizations using live-attenuated vaccines are not recommended for post-liver transplant children due to its theoretical risks. However, they will encounter vaccine-preventable viral diseases upon returning to real-life situations. We performed a total of 70 immunizations with four individual live-attenuated vaccines to 18 pediatric post-living donor liver transplant (LDLT) recipients who fulfilled a clinical criteria including humoral and cell-mediated immunity. The seroconversion rates at the first dose for measles (strain AIK-C), rubella (strain TO-336), varicella (strain Oka), and mumps (strains Hoshino) were 100% (15/15), 100% (15/15), 82% (9/11), and 82% (9/11), respectively. During observed period (−5 years 11 months), a few cases with waning immunity (antibodies were once produced but the levels fell over time) were seen except after rubella immunization. Clinical diseases after seroconversion or definite serious adverse effects due to immunization were not observed. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. [Copyright &y& Elsevier]

Background. Despite small genomic differences, Chlamydia trachomatis biovars exhibit diverse disease manifestations and different growth rates in vivo and in cell culture models. Methods. Chlamydial inclusion-forming units were enumerated over time in HeLa cells, to evaluate the length of the developmental cycle for C. trachomatis strains A, B, C, and E/Bour (ocular strains) as well as D, E/UW5/Cx, F, and L2 (genital strains). Prototype strains A, D, and L2 were selected for detailed analysis of reticulate body growth, division, and genomic replication. The impact that changing host cells and that coinfection with different strains has on growth was also assessed. Results. The genital strains completed the developmental cycle in 36–44 h, whereas the ocular strains lagged behind considerably. Differences were the result of a longer lag phase (entry plus differentiation) and generation time for the ocular strains. A prototype ocular strain grew faster in conjunctival cells than in cervical cells. Coinfection with genital (D or L2) and ocular strains expedited recovery of the ocular strain. Conclusions. Precise temporal evaluation of the chlamydial developmental cycle for selected genital and ocular C. trachomatis biovars provides a means for investigating genomic differences that define chlamydial pathotype. [ABSTRACT FROM AUTHOR]

This report presents three cases of neonatal group B streptococcal ventriculitis and assesses seven others identified by a literature review. In contrast to the well described acute manifestations of group B streptococcal meningitis, disease onset tended to be insidious with four of seven cases presenting over a period of 1 to 6 weeks and six cases presenting with nonspecific signs and symptoms without fever. Persistent protein content elevation and low glucose level in the cerebrospinal fluid was observed, indicating chronic inflammation. All patients developed obstructive hydrocephalus requiring ventriculoperitoneal shunt placement. One child died, and six of nine survivors were left with significant neurologic deficits. Physicians should be aware of this indolent but serious manifestation of group B streptococcal infection. [Copyright &y& Elsevier]

Discordant views regarding host cell death induction by Chlamydia are likely owing to the different methods used for evaluation of apoptosis. Apoptotic and non-apoptotic death owing to both caspase-dependent and -independent activation of the Bax protein occur late in the productive growth cycle. Evidence also suggests that Chlamydia inhibits apoptosis during productive growth as part of its intracellular survival strategy. This is in part owing to proteolytic degradation of the BH3-only family of pro-apoptotic proteins in the mitochondrial pathway. Chlamydia also inhibits apoptosis during persistent growth or in phagocytes, but induces apoptosis in T cells, which suggests that apoptosis has an immunomodulatory role in chlamydial infections. The contribution of apoptosis in disease pathogenesis remains a focus for future research. [Copyright &y& Elsevier]

Data on the safety and antibody response of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in children aged 5–11 years with underlying diseases are limited. Thus, our study aimed to address this gap. This prospective observational study investigated the antibody titers for SARS-CoV-2 spike protein receptor-binding domain (S-IgG) and nucleocapsid protein (N-IgG) in patients aged 5–11 years with chronic underlying diseases following two doses of BNT162b2. Additionally, a questionnaire was used to assess adverse events (AEs) arising within 7 days after each dose. Data on severe AEs arising within 28 days after each dose were extracted from the patients' electronic medical records. Among 122 patients, 24.6% (30/122) were immunocompromised. Furthermore, 79 patients experienced at least one AE following vaccination, but all recovered without sequelae, including one severe case after the first dose. The seropositivity rate after the second dose was 99.1% (116/117). Excluding 19 N-IgG-positive patients, the geometric mean antibody titer (GMT) was significantly higher in immunocompetent patients than in immunocompromised patients (1496 U/mL [95% confidence interval 1199–1862] vs. 472 U/mL [200−1119], p = 0.035). Additionally, the GMT of S-IgG was higher in N-IgG-positive patients than in N-IgG-negative patients (8203 [5847–11482] U/mL vs. 1127 [855–1486] U/mL, p < 0.001). BNT162b2 is acceptably safe and immunogenic for children aged 5–11 years with underlying diseases. Although seroconversion was satisfactory in immunocompromised patients, the titers were lower than in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a global issue, and implementation of antimicrobial stewardship programs in outpatient settings is crucial. Japan has also focused on outpatient oral antimicrobial stewardship programs and difficulties in standardizing prescriptions have led to overprescription in primary emergency medical centers. There is a lack of research investigating the antibiotic prescription status of pediatric primary emergency medical centers and the benchmark prescription rates in pediatric outpatient settings. We conducted a multi-center, cross-sectional study of seven pediatric primary emergency medical centers located in five prefectures of Japan. We retrospectively extracted data from health claims or directly obtained them from charts at each institution and evaluated trends in the antibiotic prescription rate based on the AWaRe classification between April 2016 and December 2019. Our study included 383,525 encounters, with the most common infectious disease diagnosis being acute upper respiratory tract infection in 93,449 cases (24.4 %). The antibiotic prescription rate during the study period was 7.4 %, representing a decrease of 46 %, from 10.2 % in 2016 to 5.5 % in 2019. The percentage of prescriptions in the Access group increased at all institutions; however, it exceeded 60 % in only three facilities in 2019. The percentage of third-generation cephalosporins varied among facilities, ranging from 1.7 % to 59.4 %, as of 2019. For pediatric primary emergency medical centers where antimicrobial stewardship programs are implemented, we suggest 5 % as a reasonable benchmark level for the antibiotic prescription rate. Prescribing the antibiotics in the Access groups less frequently remains a domestic challenge in Japan. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic posed substantial challenges to healthcare systems. Understanding the responses of pediatric health services is crucial for future pandemic planning and preparedness, yet such data remains limited. In this retrospective cohort study, we analyzed data from administrative databases developed by Japan Medical Data Center and DeSC Healthcare Inc. The dataset comprised records of 2,612,511 children, totaling 60,224,888 person-months, from January 2020 to May 2022. Multivariate generalized estimation equations were used to examine the incidence rates of COVID-19 and associated health resource use. Our analysis revealed that the incidence rates of COVID-19 gradually increased from Wave I (2.2 cases per 100,000 person-months) to Wave V (177.8cases per 100,000 person-months), with a notable elevation during Wave VI (2367.7 cases per 100,000 person-months). While nucleic acid amplification tests were primarily used during Waves I–V, the use of rapid antigen tests markedly increased in Wave VI. The hospitalization rates increased gradually from 0.2 in Wave I to 10.2 events per 100,000 person-months in Wave VI, and the case-hospitalization risk decreased from 14.9% in Wave II to 0.7% in Wave VI. Additionally, we observed decreasing trends in the use of antibiotics (Wave I, 31.8%; Wave VI, 9.0%), whereas antipyretic use rose from Wave I (56.1%) to Wave VI (86.6%). Our study highlighted essential changes in the nationwide pediatric healthcare system's response to the COVID-19 pandemic. These findings provide valuable insights into the future pandemic planning and preparedness. [ABSTRACT FROM AUTHOR]

The melting temperature (T m) mapping method (TM) identifies bacterial species by intrinsic patterns of T m values in the 16S ribosomal RNA gene (16S rDNA) extracted directly from whole blood. We examined potential clinical application of TM in children with bloodstream infection (BSI). This was a prospective observational study at a children's hospital in Japan from 2018 to 2021. In patients with diagnosed or suspected BSI, we investigated the match rates of pathogenic bacteria identified by TM and blood culture (BC), the inspection time to identification of TM, and the amount of bacterial DNA in blood samples. The median age of 81 patients (93 samples) was 3.6 years. Of 23 samples identified by TM, 11 samples matched the bacterial species with BC (positive-match rate, 48 %). Of 64 TM-negative samples, 62 samples were negative for BC (negative-match rate, 97 %). Six samples, including one containing two pathogenic bacterial species, were not suitable for TM identification. In total, the matched samples were 73 of 93 samples (match rate, 78 %). There were seven samples identified by TM in BC-negative samples from blood collected after antibiotic therapy. Interestingly, the bacteria were matched with BC before antibiotic administration. These TM samples contained as many 16S rDNA copies as the BC-positive samples. The median inspection time to identification using TM was 4.7 h. In children with BSI, TM had high negative-match rates with BC, the potential to identify the pathogenic bacteria even in patients on antibiotic therapy, and more rapid identification compared to BC. UMIN000041359 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000047220. [ABSTRACT FROM AUTHOR]

The coronavirus disease-2019 (COVID-19) pandemic presented an unprecedented challenge to societies, necessitating adaptations in infection prevention measures. While there is ample data on infection prevention practices in workplace and healthcare settings, comprehensive data specific to childcare facilities has been lacking. We conducted a nationwide web-based survey capturing responses from various childcare facilities (N = 549). This aimed to understand the adaptation in infection prevention measures between fiscal years 2022 and 2023, the status of events and activities, and the factors influencing decision-making related to infection prevention. From 2022 to 2023, most childcare facilities reduced infection prevention practices like mandatory mask-wearing (46.9 %–7.5 %) and eating without conversing (56.5 %–7.4 %), whereas they continued high levels of hand sanitization and checking child's health condition before attendance. The frequency of events and activities (e.g., athletic meets, field trips) increased, with many being held without restrictions. Surprisingly, 62.8 % of facilities used items not recommended for infection prevention. The influence of local government guidelines (risk ratio, 0.69; 95%CI, 0.53–0.90) and the input from junior teachers (risk ratio, 0.85; 95%CI, 0.72–0.99) were associated with reduced risk of using inappropriate items. Furthermore, childcare facilities emphasized the need to collaborate with public health and medical professionals for more accurate and efficient decision-making during pandemics. The survey provides insights into the evolving practices of Japanese childcare facilities during the COVID-19 pandemic. It underscores the importance of refining information sources, enhancing decision-making processes, and fostering collaboration with the medical community for future pandemics and natural disasters. [ABSTRACT FROM AUTHOR]

Maintaining good asthma control minimizes the risk of exacerbations and lung function decline and is a primary goal of asthma management. The Japanese Pediatric Asthma Guidelines (JPGL) employs different classification criteria for control status from other guidelines, stressing a higher level of control. Based on JPGL, we previously developed a caregiver-completed questionnaire for assessing and achieving best asthma control in preschoolers. In this study, we aimed to develop a questionnaire for school-age children and adolescents. A working questionnaire comprising 14 items for patients and 34 items for caregivers was administered to 362 asthma patients aged 6–15 years and their caregivers. Separately, physicians filled out a questionnaire to determine JPGL-defined control. Logistic regression analysis was performed to construct a model to predict control levels using data from a randomly selected set of completed questionnaires from two-thirds of the subjects. Validation was performed using the remaining questionnaires. A set of 7 questions, encompassing self-assessed control status at the time of the visit and in the past month, and nocturnal/early morning asthma symptoms for patients and frequency of asthma symptoms, dyspnea, rescue beta-agonist use, and asthma hospitalization for caregivers, were selected and the 7-item model showed a good statistical fit with AIC of 110.5. The model has been named the Best Asthma Control Test for School Children and Adolescents (Best ACT-S). Best ACT-S scores differed significantly in the hypothetical direction among the groups of different JPGL-defined control levels, step-up/down treatment decisions, and presence/non-presence of exacerbations in the previous year. The Best ACT-S is a valid questionnaire for children/adolescents aiming for best asthma control. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the recent epidemiology of Pneumocystis pneumonia (PCP) in Japan using a nationwide database. We extracted data of inpatients with PCP from the Diagnostic Procedure Combination database, a national inpatient database in Japan, from January 2010 to December 2016. During the study period, 4293 PCP patients were identified, including 4073 adults and 220 children. In adults, the most common comorbidity was hematologic malignancy (31%), followed by diabetes mellitus (30%), rheumatic/collagen diseases (26%), and solid organ tumors (18%). In children, there were few patients with rheumatic diseases (5%) or diabetes mellitus (2%), but immunodeficiency (without human immunodeficiency virus) was more common (28%). Few biological products were used for adult and pediatric patients; CD20 inhibitors, TNF-α inhibitors, interleukin receptor inhibitors, and CTLA-4 inhibitor were used for 8.6% and 2.4%, 1.3% and 0%, 1.2% and 4.7%, and 0.2% and 0% of adult and pediatric patients, respectively. Based on data stratified by bed count, the annual numbers of PCP patients in Japan were estimated as 2221 adults and 123 pediatric patients. The mortality was higher in adults (27%) than in pediatric patients (21%) (P = 0.041). The underlying disease and mortality were apparently different between adult and pediatric PCP patients. [ABSTRACT FROM AUTHOR]

Background: Few studies have characterized the clinical manifestations of delayed antibiotic hypersensitivity (AH) diagnosed using objective methods. The lymphocyte transformation test (LTT) is a reproducible method to diagnose type IV hypersensitivity. The purpose of the study was to evaluate the characteristics of delayed AH diagnosed on LTT in children. Methods: We performed a retrospective analysis of patients who were evaluated for AH using LTT at National Center for Child Health and Development, Tokyo, from 2002 to 2014. We extracted patient demographics, type and duration of antibiotics, and clinical characteristics from the medical records. Clinical manifestations were compared between LTT‐positive and LTT‐negative cases. Results: Seventy‐five cases for which 101 drugs were tested were included in this study. LTT was positive against 34 drugs in 26 cases. Median age was 5 years (IQR, 1–9 years), and 49% of patients had underlying disease. LTT was performed at a median of 18 days (IQR, 4–59 days) after the suspected episode. The median number of days from the initiation of therapy to the onset of symptoms was 4. Rash was the most common manifestation (89%). Fever (>38°C) was observed in 20 cases (27%). Onset of fever preceded the rash in nine cases (45%), appeared simultaneously in five (25%), appeared afterwards in four (20%), and was unknown in two (10%). Fever was an independent factor associated with AH when comparing LTT‐positive and LTT‐negative cases (OR, 3.61; 95%CI: 1.03–12.64). Conclusions: Fever was a common presenting symptom of delayed AH in children aged ≤18 years. [ABSTRACT FROM AUTHOR]

There are few reports on the association between antipyretic use and antibody titers in adolescents and young adults following SARS-CoV-2 vaccination. Multivariable linear regression analyses were performed to examine the association between antipyretic use and antibody titers. The use of antipyretics was not associated with antibody titers (β coefficient [95% CI] = −0.107 [–0.438 to 0.224]). [ABSTRACT FROM AUTHOR]

A response by Isao Miyairi and colleagues to a letter to the editor about their article "Different Growth Rates of Chlamydia Trachomatis Biovars Reflect Pathotype" published in a previous issue is presented.

Provides information on a medical case presented involving an immunocompetent child infected with cryptococcal meningitis and was cured without any sequelae or relapse with six months of antifungal treatment. Symptoms experienced by the Japanese boy upon admission to a local hospital; Methods used which detected Cryptococcus neoformans; Findings of the cerebrospinal fluid culture conducted on the child.

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333). [ABSTRACT FROM AUTHOR]

• We evaluated trends of pediatric varicella and herpes zoster incidence for 18 years. • Varicella was largely reduced after the vaccine introduction and COVID-19 pandemic. • The vaccine and COVID-19 pandemic had a small impact on herpes zoster incidence. • Risk of herpes zoster was low in children born after the routine vaccine. To determine the epidemiological trends in pediatric varicella and herpes zoster incidence and changes in healthcare resource use from 2005 to 2022 using a nationally representative database in Japan. We conducted a retrospective observational study consisting of 3.5 million children with 177 million person-months during 2005–2022 using Japan Medical Data Center (JMDC) claims database in Japan. We investigated trends in incidence rates of varicella and herpes zoster and changes in healthcare resource use (e.g., antiviral use, office visits, and healthcare costs) over 18 years. Interrupted time-series analyses were used to investigate the impact of the routine varicella vaccination program in 2014 and infection prevention measures against COVID-19 on incidence rates of varicella and herpes zoster and related healthcare utilization. After the introduction of the routine immunization program in 2014, we observed level changes in incidence rates (45.6 % reduction [95 %CI, 32.9–56.0] of varicella cases, antiviral use (40.9 % reduction [95 %CI, 25.1–53.3]), and relevant healthcare costs (48.7 % reduction [95 %CI, 38.2–57.3]). Furthermore, infection prevention measures against COVID-19 were associated with additional level changes in varicella rates (57.2 % reduction [95 %CI, 44.5–67.1]), antiviral use (65.7 % reduction [59.7–70.8]), and healthcare costs (49.1 % [95 %CI, 32.7–61.6]). In contrast, the changes in incidence and healthcare costs for herpes zoster were relatively small, which showed 9.4 % elevated level change with a decreasing trend and 8.7 % reduced level change with a decreasing trend after the vaccine program and the COVID-19 pandemic. The cumulative incidence of herpes zoster in children born after 2014 was lower than that before 2014. Varicella incidence and healthcare resource use were largely affected by the routine immunization program and infection prevention measures against COVID-19, while these impacts on herpes zoster were relatively small. Our study indicates that immunization and infection prevention measures largely changed pediatric infectious disease practices. [ABSTRACT FROM AUTHOR]

Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome (STEC-HUS). Understanding its prognostic factors is essential for immediate interventions. We examined early-phase unfavorable prognostic factors among patients with STEC-HUS using a nationwide database. This is a retrospective cohort study to analyze practice patterns and identify prognostic factors among patients with STEC-HUS. We used the Diagnosis Procedure Combination Database, which includes approximately half of the acute-care hospitalized patients in Japan. We enrolled patients who were hospitalized for STEC-HUS from July 2010 to March 2020. The composite unfavorable outcome included in-hospital death, mechanical ventilation, dialysis, and rehabilitation at discharge. Unfavorable prognostic factors were assessed using a multivariable logistic regression model. We included 615 patients with STEC-HUS (median age, 7 years). Of them, 30 (4.9%) patients had acute encephalopathy and 24 (3.9%) died within 3 months of admission. Unfavorable composite outcome was observed in 124 (20.2%) patients. Significant unfavorable prognostic factors were age of 18 years or older, methylprednisolone pulse therapy, antiepileptic drug administration, and respiratory support within 2 days of admission. Patients requiring early steroid pulse therapy, antiepileptic drugs, and respiratory support were considered to be in poor general condition; such patients should receive aggressive intervention to avoid worse outcomes. [ABSTRACT FROM AUTHOR]

Background Several reports have suggested that routine use of anaerobic blood culture bottles together with aerobic bottles may improve blood culture positivity. However, the information is still limited regarding the utility of anaerobic blood culture bottles in the pediatric intensive care unit (PICU), where bacteremia due to anaerobic bacteria is relatively rare. Methods A retrospective observational study was conducted at a PICU in a tertiary children's hospital in Japan from May 2016 to January 2020. Patients aged ≤15 years old with bacteremia, for which both aerobic and anaerobic blood cultures were submitted, were included in the study. We investigated whether the positive blood culture cases were from aerobic or anaerobic bottles. We also compared the amount of blood inoculated into culture bottles to determine the effect of blood volume on the rate of detection. Results During the study period, a total of 276 positive blood cultures from 67 patients were included in this study. Among the paired blood culture bottles, 22.1% were positive only for the anaerobic bottles. Escherichia coli and Enterobacter cloacae were the most common pathogens that were detected in anaerobic bottles only. Obligate anaerobic bacteria were detected in 2 (0.7%) bottles. There was no significant difference in the amount of blood inoculated into aerobic and anaerobic culture bottles. Conclusions The use of anaerobic blood culture bottles in the PICU may increase the detection rate of facultative anaerobic bacteria. [ABSTRACT FROM AUTHOR]

Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease. This prospective observational study enrolled patients age 12–25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose. Study participants were 429 patients (241 [56.2%] age 12–15 years; 188 [43.8%] age 16–25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12–15 years and in 2 (1.1%) patients age 16–25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12–15 years versus 16–25 years (1603.3 [1321.8–1944.7] U/mL vs. 949.4 [744.2–1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5–2314.7] U/mL vs. 467.9 [324.4–674.8] U/mL). Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease. [ABSTRACT FROM AUTHOR]

Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24–3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08–4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13–0.84]). Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods. [ABSTRACT FROM AUTHOR]

An abstract of the article "Chlamydia psittaci Genetic Variants Differ in Virulence by Modulation of Host Immunity," by Isao Miyairi and colleagues is presented.

Background: For addressing antibiotic overuse, Japan designed a health care policy in which eligible medical facilities could claim a financial reward when antibiotics were not prescribed for early-stage respiratory and gastrointestinal infections. The policy was introduced in a pilot manner in paediatric clinics in April 2018.Methods: We conducted a quasi-experimental, propensity score-matched, difference-in-differences (DID) design to determine whether the nationwide financial incentives for appropriate non-prescribing of antibiotics as antimicrobial stewardship [800 JPY (≈7.3 US D) per case] were associated with changes in prescription patterns, including antibiotics, and health care use in routine paediatric health care settings at a national level. Data consisted of 9 253 261 cases of infectious diseases in 553 138 patients treated at 10 180 eligible or ineligible facilities.Results: A total of 2959 eligible facilities claimed 316 770 cases for financial incentives and earned 253 million JPY (≈2.29 million USD). Compared with ineligible facilities, the introduction of financial incentives in the eligible facilities was associated with an excess reduction in antibiotic prescriptions [DID estimate, -228.6 days of therapy (DOTs) per 1000 cases (95% CI, -272.4 to -184.9), which corresponded to a relative reduction of 17.8% (95% CI, 14.8 to 20.7)]. The introduction was also associated with excess reductions in drugs for respiratory symptoms [DID estimates, -256.9 DOTs per 1000 cases (95% CI, -379.3 to -134.5)] and antihistamines [DID estimate, -198.5 DOTs per 1000 cases (95% CI, -282.1 to -114.9)]. There was no excess in out-of-hour visits [DID estimate, -4.43 events per 1000 cases (95% CI, -12.8 to 3.97)] or hospitalizations [DID estimate, -0.08 events per 1000 cases (95% CI, -0.48 to 0.31)].Conclusions: Our findings suggest that financial incentives to medical facilities for not prescribing antibiotics were associated with reductions in prescriptions for antibiotics without adverse health care consequences. Japan's new health policy provided us with policy options for immediately reducing inappropriate antibiotic prescriptions by relatively small financial incentives. [ABSTRACT FROM AUTHOR]

Background Empiric antimicrobial coverage in compromised hosts commonly includes pseudomonal coverage but often lacks coverage against Stenotrophomonas maltophilia. Identification of risk factors specific for S. maltophilia infection may lead to prompt initiation of appropriate antibiotics and improved outcome. Methods We conducted a retrospective analysis of pediatric patients with bacteremia due to S. maltophilia or Pseudomonas aeruginosa from April 2002 to July 2014 at a tertiary children's hospital. Patient demographics, underlying disease, clinical course, and treatment were compared between S. maltophilia and P. aeruginosa cases. Results Nineteen children with S. maltophilia bacteremia and 49 children with P. aeruginosa bacteremia were identified. On multivariate logistic regression analysis, use of carbapenems within 7 days prior to onset (OR, 5.00; 95%CI: 1.25-20.07; P = 0.02) and previous intensive care unit stay (OR, 3.75; 95%CI: 1.13-12.47; P = 0.03) were significantly associated with S. maltophilia bacteremia compared with P. aeruginosa bacteremia. The majority of the S. maltophilia bacteremia patients had central line-associated bloodstream infection (79%), compared with the P. aeruginosa bacteremia patients (37%, P = 0.002). There were nine children (47%) who had polymicrobial infection in the S. maltophilia bacteremia group, in contrast to four (8%) in the P. aeruginosa bacteremia group (OR, 10.13; 95%CI: 2.59-39.56; P = 0.001). Consultation with an infectious diseases physician was associated with a lower rate of persistent S. maltophilia bacteremia ( P = 0.04). Conclusions Stenotrophomonas maltophilia should be considered in breakthrough bacteremia in pediatric patients who receive carbapenems within 7 days prior to onset. [ABSTRACT FROM AUTHOR]

Background Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. Methods A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score–matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. Results During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P  = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21–23.069] and 3.871 [1.201–12.477], respectively). Conclusions Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women. [ABSTRACT FROM AUTHOR]

A more rapid and less complicated test to diagnose pertussis is required in clinical settings. We need to detect Bordetella pertussis, which mainly causes pertussis, as early as possible, because pertussis is more likely to become severe in infants, and people around them can easily become a source of infection due to its strong infectivity. Nevertheless, methods that can detect B. pertussis rapidly and efficiently are lacking. Therefore, we developed a new immunochromatographic antigen kit (ICkit) for the early diagnosis of pertussis. The ICkit detects B. pertussis antigens in a nasopharyngeal swab without equipment and provides the result in about 15 min with a simple procedure. Additionally, a prospective study to evaluate the ICkit was conducted in 11 medical institutions, involving 195 cases with suspected pertussis. Compared with the real-time polymerase chain reaction (rPCR), the sensitivity and specificity of the ICkit were 86.4% (19/22) and 97.1% (168/173), respectively. The ICkit detected the antigen in both children and adults. Furthermore, the ICkit detected the antigen until the 25th day from the onset of cough, when rPCR detected the antigen. Thus, the ICkit demonstrated a high correlation with rPCR and would help diagnose pertussis more rapidly and efficiently. [ABSTRACT FROM AUTHOR]

We aimed to define the burden and clinical features of invasive group B streptococcus (GBS) disease in infants younger than 1 year in Japan, to explore transmission route of late-onset disease (LOD), and to identify risk factors associated with recurrent GBS disease. We conducted a retrospective, questionnaire-based nationwide surveillance study between 2016 and 2020. A total of 875 GBS cases were identified, including 186 early-onset disease, 628 LOD, and 61 ultra-late-onset disease. Case fatality rate in each age category was 6.5%, 3.0%, and 3.3%, respectively. Patients with meningitis had neurodevelopmental sequelae in 21.5% (64/297). Annual incidence in infants younger than 1 year and in LOD significantly increased from 0.28 to 0.45/1000 livebirths (p = 0.021) and from 0.19 to 0.29/1000 livebirths (p = 0.046), respectively. Maternal colonization status at the LOD diagnosis was available for 148 mothers, of whom 21/58 (36.2%) had positive rectovaginal swabs and 42/117 (36.2%) had GBS in breastmilk culture. These two sites are potentially infectious routes in LOD. The four leading disease-causing serotypes III, Ia, Ib, and V represented 95% of the available serotypes. Thirty-one recurrent cases were identified, accounting for 3.7% of total patients. A multivariate regression analysis showed that prematurity (p = 0.029) and antepartum maternal GBS colonization (p = 0.032) were significantly associated with risk for the recurrence. Our findings indicated that GBS disease burden still remains with considerable mortality and morbidity in Japan, and provided important information for developing better strategies for the prevention of GBS disease, including maternal vaccination. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 15 year old male who developed multisystem inflammatory syndrome in children (MIS-C) following vaccination with the BNT162b2 mRNA SARS-CoV-2 vaccine. It is reported that the patient exhibited symptoms such as fever, chest pain, abdominal pain, and conjunctival hyperemia 50 days after the second vaccine dose. It is further reported that the patient's symptoms improved with supportive care, and imaging revealed myocardial abnormalities.

Background: The role of antibiotics in the treatment of Shiga toxin-producing Escherichia coli (STEC) infection is controversial. Objectives: To evaluate the association between treatment (antibiotics, antidiarrheal agents, and probiotics) for STEC infection and hemolytic uremic syndrome (HUS) development. Patients and methods: We performed a population-based matched case-control study using the data from the National Epidemiological Surveillance of Infectious Diseases (NESID) between January 1, 2017 and December 31, 2018. We identified all patients with STEC infection and HUS as cases and matched patients with STEC infection without HUS as controls, with a case-control a ratio of 1:5. Further medical information was obtained by a standardized questionnaire. Multivariable conditional logistic regression model was used. Results: 7760 patients with STEC infection were registered in the NESID. 182 patients with HUS and 910 matched controls without HUS were selected. 90 patients with HUS (68 children and 22 adults) and 371 patients without HUS (266 children and 105 adults) were included in the main analysis. The matched ORs of any antibiotics and fosfomycin for HUS in children were 0.56 (95% CI 0.32–0.98), 0.58 (0.34–1.01). The matched ORs for HUS were 2.07 (1.07–4.03), 0.86 (0.46−1.61) in all ages treated with antidiarrheal agent and probiotics. Conclusions: Antibiotics, especially fosfomycin, may prevent the development of HUS in children, while use of antidiarrheal agents should be avoided. [ABSTRACT FROM AUTHOR]

The article presents a report that describes five patients with blastomycosis who presented from an endemic area with respiratory symptoms that suggest bacterial pneumonia. Despite several courses of antibiotics, there was a lack of clinical improvement, resulting in the need for bronchoscopy and bronchoalveolar lavage (BAL) microbiologic testing that was diagnostic except for one case. It showed the need for an immediate early diagnostic check up to prevent complications.

Background: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post‐LT period. Methods: We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias. Results: Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p =.038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post‐transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p =.041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8+ T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT. Conclusions: We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post‐LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT. [ABSTRACT FROM AUTHOR]

In 2016, the Japanese government set the National Action Plan on antimicrobial resistance to reduce antibiotic prescriptions. However, the trends and variations of antibiotic prescription patterns in a routine healthcare setting during the fiscal year 2013–2018 across different clinics at a national level are unclear. This retrospective cohort study included all clinics with >100 pediatric outpatients with infectious diseases per month during the fiscal year 2013–2018 using a national database in Japan. We investigated the trends in antibiotic prescription rates and their patterns and variations across different clinics over the six years following the 2019 World Health Organization Access, Watch, Reserve antibiotic groups, and Amoxicillin Index. A total of 2278 clinics with 94,414,170 infectious disease-related visits were eligible for the study. Most clinics showed higher Watch percentages (median 85.4%; IQR, 68.5–95.1) than Access percentages (median, 13.8%; IQR, 4.2–30.7) and Amoxicillin Index (median, 13.3%; IQR, 3.9–30.4). The introduction of the Action Plan changed annual absolute reductions in the antibiotic prescription rates from −16.0 DOTs/1000 visitors (95%CI, −16.4–15.6) to −239.3 per 1000 visitors (95%CI, −240.0–238.6). However, these impacts were heterogeneous across clinics. From 2013 to 2018, 41.4% reduced the antibiotic prescription rates by >33.3% (median, −1035.5 DOTs/1000 visitors; IQR, −1519.4–680.2), 18.7% did not change the rates (median, −40.3 DOTs/1000 visitors; IQR, −168.4–68.6), and 7.3% increased the rates by >10% (499.5 DOTs per 1000 visitors; IQR, 232.6–837.5). We observed the National Action Plan's impacts and extensive prescription variations across different pediatric clinics. However, one-fourth of clinics did not improve antibiotic prescription patterns even after introducing the Action Plan. [ABSTRACT FROM AUTHOR]

Background: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population. Methods: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates. Results: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls. Conclusions: Children with allergies mount and maintain a comparable immune response to the measles vaccine. [ABSTRACT FROM AUTHOR]

Recent guidelines suggest that LAVs may be given to LT recipients meeting certain criteria. However, information is still limited. We sought to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to LT recipients following our clinically based immunization protocol for LT recipients. We conducted a case‐series analysis on safety of LAVs for measles, rubella, varicella, and mumps given to LT recipients at our institution from July 2010 to July 2019. Patients who underwent LT at age <20 years who visited our immunization clinic were included. LT recipients were vaccinated if 2 years had lapsed from LT, had no signs of rejection within 6 months, and were on minimal immunosuppressants. Patient demographics, underlying diseases, type and number of vaccines administered, date of vaccination, and adverse events occurring within 4 weeks after vaccination were extracted from their medical records. During the study period, LAVs were administered 422 times to 209 patients who met criteria and included 225 doses of MR combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver diseases (n = 125), followed by metabolic diseases (n = 33) and acute liver failure (n = 19). Nine non‐critical adverse events (2.1%) possibly associated with LAVs were reported, but there were no serious adverse events, including hospitalizations or deaths. In conclusion, LAVs administered to LT recipients were safe without any serious adverse events following our relatively simple institutional protocol. [ABSTRACT FROM AUTHOR]

The characteristics of pneumococcal isolates and their associations with outcomes in pediatric meningitis are unclear. This study aimed to clarify serotypes and resistance genotypes of Streptococcus pneumoniae from children with meningitis and evaluate the patient prognoses and backgrounds. Large-scale surveillance was conducted from 2002 to 2016 through periods I–V. Serotypes and penicillin (PEN) resistance genotypes were analyzed for pneumococcal isolates (n = 459) and cerebrospinal fluid (CSF) samples (n = 25). Furthermore, underlying diseases (n = 251), prognoses (n = 202), and laboratory data were evaluated. The number of meningitis cases decreased drastically after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) to −53.6% and after switching to PCV13 to −70.2%. In particular, this reduction was apparent at ≤3 years of age. The proportion of the PCV7 serotype decreased sharply from 70.1% before introduction to 2.6% during period V; however, the non-vaccine type increased from 17.5% to 87.2%. The PEN resistance rate (gPRSP) was decreased from approximately 49% to 12.2% during period V. Among cases revealed prognosis, sequelae and mortality rates were 16.3% and 5.4%, respectively. The rate of the patients with underlying diseases was 26.3% and relatively high in ≥6 years. Laboratory data associated with a poor prognosis were low white blood cell count (<12.7 × 103/μL), low platelet count (<28.1 × 104/μL), low CSF-glucose (<36 mg/dL), and high CSF-protein (≥142 mg/dL). Changes in serotype prevalence warrant continuous monitoring to observe future trends of pneumococcal meningitis, and further developments in multivalent conjugate vaccines are required. [ABSTRACT FROM AUTHOR]

6 Non-chlamydial non-gonococcal urethritis [Executive summary] • Male urethritis in which neither N. gonorrhoeae nor C. trachomatis is detected is called non-chlamydial non-gonococcal urethritis (I, B). Non-gonococcal urethritis in which chlamydia is detected is called chlamydial urethritis, and urethritis in which neither gonococcus nor chlamydia is detected is called non-chlamydial non-gonococcal urethritis (I, B). Urethritis and cervicitis are frequently caused by Neisseria gonorrhoeae and Chlamydia trachomatis, and gonococcal urethritis and cervicitis and chlamydial urethritis and cervicitis have been used as terms to indicate these conditions. 4 Non-gonococcal urethritis • Urethritis in which gonococci are not detected is called non-gonococcal urethritis (I, A). Urethritis is classified into gonococcal and non-gonococcal urethritis depending on detection or no detection of gonococcus. [Extracted from the article]

The article presents a case study of a four-year-old boy who was diagnosed with Epstein-Barr virus (EBV) infection after being admitted for high fever and ulcerative lesions surrounded by swelling and tenderness on the right forearm after bitten by mosquitoes. It notes his parents mentioned recurring and unusual reaction after mosquito bites in one summer.

In 2019, the Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases reported nationwide, cross-sectional questionnaire survey data investigating the clinical status of clinic doctors' attitudes to antimicrobial stewardship. This study aimed to identify factors determining clinic doctors' attitudes concerning antimicrobial prescription for patients with a common cold or bronchitis. In February 2018, 1500 randomly selected community-based medical clinics in Japan were sent a questionnaire. Primary and secondary endpoints were clinic doctors' attitudes concerning antimicrobial prescription, and antimicrobial medication types prescribed for patients with a common cold or bronchitis, respectively. We used multivariable linear regression analysis to identify factors associated with primary and secondary outcomes. We analyzed 269 of 274 responses (response rate, 18.3%). Linear regression analysis was used to identify determinants of proactive attitudes to antimicrobial prescription, including whether clinic doctors encountering patients with upper respiratory symptoms and no underlying illnesses, and diagnosed with a common cold would prescribe antimicrobial medication (β = 0.283, t = 4.279, p = 0.000); whether clinic doctors frequently experienced requests from patients (or their families) with a common cold to prescribe antimicrobial medication (β = 0.389, t = 6.133, p = 0.000), and; clinic doctors' awareness of antimicrobial stewardship in the past year (β = −0.157, t = −2.456, p = 0.015). Determinants of proactive attitudes to prescribing broader-spectrum antimicrobials for patients with a common cold included clinic doctors' attitudes concerning antimicrobial prescription (β = 0.165, t = 2.622, p = 0.009), whether the respondent was a pediatrician (β = −0.288, t = −4.583, p = 0.000), and clinic doctors' attitudes to antimicrobial prescription (β = 0.262, t = 4.075, p = 0.000) for patients with bronchitis. This study identified factors among clinic doctors that determined their attitudes to antimicrobial prescription concerning patients with a common cold or bronchitis. Identification and targeting of clinic doctors who unnecessarily prescribe antimicrobial medication is urgently required to promote antimicrobial stewardship in an outpatient setting. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). A total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. The prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). Our findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents. [ABSTRACT FROM AUTHOR]