General anesthesia for cesarean section in a pregnant woman with systemic vascular malformation: a case report.

BACKGROUND: Vascular malformations are composed of morphologically abnormal vascular tissue, and when located in the head and neck region, they can make it difficult to secure the airway during general anesthesia. CASE PRESENTATION: A 28-year-old pregnant woman with vascular malformations in the pharynx was scheduled to undergo a cesarean section, for which spinal anesthesia was initially chosen. However, after magnetic resonance imaging results revealed the presence of multiple vascular malformations in the lumbar multifidus muscles, spinal anesthesia was considered to be of high risk. Thus, the patient was subjected to general anesthesia tracheal intubation under sedation, and the course of the surgery was without complications. CONCLUSIONS: Because the pathophysiology and clinical sequelae of vascular malformations may be involved in complications, thorough presurgical evaluation of the patient's physical condition and careful anesthesia planning should be done.

Association between oral condition and subjective psychological well-being among older adults attending a university hospital dental clinic: A cross-sectional study.

Positive psychological well-being has a favorable impact on survival rates in both healthy and unhealthy populations. Oral health is also associated with psychological well-being, is multidimensional in nature, and includes physical, psychological, emotional, and social domains that are integral to overall health and well-being. This study aimed to identify the associations between individual and environmental characteristics, oral condition and nutritional status in relation to subjective well-being among older adults using the Wilson and Cleary conceptual model. The participants were older adults (age ≥ 60 years) attending a university hospital. Subjective well-being was assessed using the World Health Organization-5 Well-Being Index, oral condition was assessed based on the number of bacteria in the tongue coating, oral wettability, tongue pressure, occlusal force, oral diadochokinesis, and masticatory ability, and subjective swallowing function was assessed using the Eating Assessment Tool, number of remaining teeth, and number of functional teeth. In addition, factors related to well-being, including social networks, life-space mobility, nutritional status, smoking history, drinking history, and medical history were assessed. In the analysis, structural equation modeling was used to investigate the association between oral condition and subjective well-being. Confirmatory factor analysis revealed oral condition as a latent variable, including tongue pressure, oral diadochokinesis /pa/, /ta/, /ka/, occlusal force, masticatory ability, subjective swallowing function, and number of functional teeth. Structural Equation Modeling revealed that oral condition was positively correlated with nutritional status, and nutritional status was positively correlated with the World Health Organization-5 Well-Being Index. These findings suggest that oral condition may influence subjective well-being via nutritional status or social environmental factors.

Effect of oral health status and oral function on malnutrition in community-dwelling older adult dental patients: A two-year prospective cohort study.

OBJECTIVES: To survey oral status in detail and clarify the factors associated with nutritional status as evaluated by the Mini Nutritional Assessment. BACKGROUND: Malnutrition is common in older adults and increases the risk of frailty, sarcopenia, and mortality. However, few longitudinal studies have been performed to investigate the causal effect of oral status on malnutrition in detail, and the information reported in those longitudinal studies has been limited to dentition status and swallowing ability. MATERIALS AND METHODS: The participants in this prospective cohort study were patients who visited the Preventive Dentistry Clinic at Okayama University Hospital from November 2017 to January 2021. The number of teeth, periodontal condition, oral function (oral diadochokinesis, masticatory ability, number of bacteria in tongue coating, occlusal force, oral moisture, tongue pressure, swallowing function), nutritional status, the number of comorbidities, and mental health status were examined. These variables were analysed using structural equation modelling (SEM). RESULTS: The final analysis included 141 participants (40 males and 101 females; mean age, 73.5 ± 6.3 years; follow-up rate: 79.7%). The results of the SEM revealed that oral status (number of teeth present and swallowing function) was positively associated with nutritional status 2 years later. In addition, age was negatively associated with oral status. CONCLUSION: In community-dwelling older adult dental patients (age ≥60 years), oral function at baseline was associated with nutritional status two years later.

Importance of Toxin Genes and Polymerase Chain Reaction-Based Open Reading Frame Type Analyses for Severe Staphylococcus aureus Infection in Children.

This study analyzed 26 Staphylococcus aureus strains, including 16 methicillin-resistant S. aureus (MRSA) and 10 methicillin-susceptible S. aureus (MSSA), collected from eight medical institutions in the Chiba Prefecture that requested a toxin gene analysis between 2015 and 2021. A total of 14 Panton-Valentine leukocidin (PVL) positive strains were identified, including MSSA. PVL-positive strains were classified into seven types according to polymerase chain reaction-based open reading frame typing (POT); of these types, three POT MRSA strains have not been previously reported, and one has been previously reported as PVL-negative. Some strains tested positive for both PVL and toxic shock syndrome toxin 1. One POT type was identified in both PVL-positive and PVL-negative strains. To the best of our knowledge, this is the first report on the regional spread of highly pathogenic S. aureus strains based on the POT method in children from multiple medical institutions. This method is useful for estimating the spread of toxin gene-carrying strains in the community owing to its association with toxin genes. As the number of PVL-positive strains in Japan increases, it is important to analyze the isolates of severe S. aureus infections in children by combining toxin gene analyses with the POT method.

Increase in prevalence of Streptococcus pneumoniae serogroup 24 in children upon introducing 13-valent pneumococcal conjugate vaccine in Japan.

After introducing the 13-valent pneumococcal conjugate vaccine (PCV13) for children, a change in the prevalence of different Streptococcus pneumoniae serotypes that cause invasive pneumococcal diseases (IPDs) has been observed. The prevalence of vaccine serotypes has decreased and that of non-vaccine serotypes has increased. Currently, serogroup 24 has become one of the major non-vaccine serotypes causing IPDs in children in Japan. The aim of this study was to characterize clinical and genomic features of S. pneumoniae serogroup 24 strains isolated from sterile body sites in Japanese children. Serotyping, multi-locus sequence typing and genomic analysis of capsular polysaccharides of 61 strains of serogroup 24 were performed from 2015 to 2021. Among the 61 strains, 36, 23 and two belonged to serotypes 24F, 24B and 24C, respectively. The 24F sequence type (ST) 2572 and 24B ST 2572 were the major serotypes and sequence types observed from 2015 to 2019. By contrast, 24F ST 162 and 24B ST 2754 were the two major serotypes and sequence types observed after 2020. Two strains of serotype 24C were detected for the first time in Japan. Sequence analysis of the abpA gene, which plays a role in the synthesis of capsular polysaccharides in S. pneumoniae , was performed to distinguish different strains of serogroup 24. After the introduction of PCV13 in Japan, serogroup 24 has become one of the most prevalent non-vaccine serotypes causing IPDs in children. This serogroup has not been targeted in the next-generation pneumococcal conjugate vaccines. Therefore, monitoring of S. pneumoniae serogroup 24 that causes IPDs in children is essential.

Epidemiology and bacterial characteristics of invasive group B streptococcus disease: a population-based study in Japan in 2010-2020.

This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.

Trends in Self-Rated Oral Health and Its Associations with Oral Health Status and Oral Health Behaviors in Japanese University Students: A Cross-Sectional Study from 2011 to 2019.

Self-rated oral health (SROH) is a valid, comprehensive indicator of oral health status. The purpose of this cross-sectional study was to analyze how oral health behaviors and clinical oral status were associated with SROH and how they had changed over the course of nine years in Japanese university students. Data were obtained from 17,996 students who underwent oral examinations and completed self-questionnaires from 2011 to 2019. Oral status was assessed using the decayed and filled teeth scores, bleeding on probing (BOP), probing pocket depth, the Oral Hygiene Index-Simplified (OHI-S), oral health behaviors, and related factors. SROH improved from 2011 to 2019. The logistic regression model showed that university students who were female and had a high daily frequency of tooth brushing, no BOP, no decayed teeth, no filled teeth, and a low OHI-S score and were significantly more likely to report very good, good, or fair SROH. An interaction effect was observed between survey year and regular dental check-ups (year × regular dental check-ups). The improvement trend in SROH might be associated with changes in oral health behaviors and oral health status.

Real-world safety and effectiveness of pembrolizumab in Japanese patients with radically unresectable melanoma: An all-case postmarketing surveillance in Japan.

This all-case postmarketing surveillance (PMS) survey (101 centers; February 15, 2017, to March 3, 2020) captured factors that impact the safety and effectiveness of newly initiated pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan. Eligible patients were enrolled both retrospectively and prospectively, and followed up at 1, 3, 6, and 12 months. Safety assessments included treatment-related adverse events (TRAEs), adverse events of special interest (AEOSIs) from the Japanese Risk Management Plan (J-AEOSIs), and J-AEOSIs related to pembrolizumab. Effectiveness assessments included objective response rate (ORR; complete response/partial response) and disease control rate (DCR) according to the RECIST criteria. Overall, 294 and 236 patients comprised the safety and effectiveness (RECIST) assessment sets, respectively. Median (range) age of the patients was 70 (22-94) years, and the majority (60.4%) received pembrolizumab as first-line therapy. The most common type of melanoma was cutaneous (41.5%), followed by mucosal (29.3%), acral (24.8%), and unknown (4.4%). Overall, 45.2% and 24.8% of patients experienced TRAEs and AEOSIs, respectively. In total, 24.8% and 9.2% of patients experienced any-grade and grade ≥3 pembrolizumab-related AEOSIs, respectively. The most common grade ≥3 pembrolizumab-related AEOSIs were endocrine disorders and liver dysfunction (2.4% each), followed by colitis/severe diarrhea (2.0%), interstitial lung disease (1%), and type 1 diabetes (0.7%). No grade 5 J-AEOSIs were observed. ORR was 16.5% at the 1-year follow-up: mucosal melanoma (20%), acral melanoma (10%), and cutaneous melanoma (17.5%). ORR was higher among patients who did not receive versus those who did receive previous systemic therapy across all three melanoma types. DCR was 52.1% at the 1-year follow-up: cutaneous melanoma (57.3%), acral melanoma (51.7%), and mucosal melanoma (43.1%). This all-case PMS survey confirmed the real-world safety and effectiveness of pembrolizumab monotherapy for the treatment of radically unresectable melanoma in Japan.

Real-world outcomes of pembrolizumab monotherapy in non-small cell lung cancer in Japan: A post-marketing surveillance.

This post-marketing surveillance (PMS) was initiated in Japan to identify factors affecting the safety and effectiveness of pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) expression. This PMS was conducted from December 2016 to June 2019 at 717 centers across Japan. Patients with unresectable advanced/recurrent NSCLC who received pembrolizumab monotherapy as first-line (1L) treatment for PD-L1-expressing tumors (Tumor Proportion Score [TPS] ≥ 50%) or second-line or later (2L+) treatment for tumors with PD-L1 TPS ≥ 1% were enrolled and followed up for 1 year. Of 2805 registered patients, 2740 and 2400 comprised the safety and effectiveness analysis sets, respectively. The median age (range) was 69 (27-92) years; 55.7% and 29.2% of patients experienced treatment-related adverse events and adverse events of special interest (AEOSIs), respectively. More common AEOSIs included interstitial lung disease, endocrine disorders, liver dysfunction, colitis/severe diarrhea, infusion reactions, and severe skin disorders. The frequency of experiencing ≥2 AEOSIs was low (1L, 6.5%; 2L+, 2.8%). Most AEOSIs occurred within 150 days after initiation of pembrolizumab monotherapy. At 1-year follow-up, the objective response rate was 39.2% (1L, 51.5%; 2L+, 30.0%). In conclusion, the 1-year safety and effectiveness of pembrolizumab monotherapy in patients with unresectable advanced/recurrent NSCLC as 1L treatment for tumors with PD-L1 TPS ≥ 50% and 2L+ treatment for tumors with PD-L1 TPS ≥ 1% were similar to those reported in phase 2/3 trials.

Clinical and Bacteriological Analysis of Pediatric Pneumococcal Meningitis after 13-Valent Pneumococcal Conjugate Vaccine Introduction in Japan.

Streptococcus pneumoniae is one of the leading causes of meningitis in children. In Japan, since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), the number of pneumococcal meningitis due to non-PCV13 serotypes in children has increased. To clarify the clinical outcomes, serotype distributions, and antimicrobial susceptibility of isolated S. pneumoniae strains from pediatric pneumococcal meningitis, we clinically and bacteriologically analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the PCV13 introduction era in Japan. The median age at diagnosis was 1 year (range: 3 months-13 years). Ten (29.4%) patients had underlying diseases. Twenty-nine (85.3%) patients had received at least one dose of any pneumococcal vaccine. Of the 34 patients with pneumococcal meningitis, 6 had sequelae, and 4 died. Nine (26.5%) strains were resistant to penicillin; five (15%) strains to meropenem, with an MIC of 0.5 µg/mL. All strains were susceptible to vancomycin and linezolid. Daptomycin's MIC50 was 0.064 µg/mL and MIC90 was 0.094 µg/mL. Among the tested strains, only four were PCV13 serotypes. Penicillin-resistant S. pneumoniae was isolated from 30.0% of the patients with sequelae and death. Particularly, the proportion of serotype 10A in the sequelae and deceased cases was significantly higher than that in the complete recovery cases. We should carefully monitor the serotype and drug susceptibility of S. pneumoniae strains isolated from patients with meningitis after the PCV13 era and reconsider the treatment strategy to prepare against further drug-resistant pneumococcal strains. IMPORTANCE We analyzed 34 cases of pediatric pneumococcal meningitis that were reported after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction era in Japan. Our study revealed that pneumococcal meningitis in children was mainly caused by non-PCV13 serotypes; all cases with sequelae and death were caused by non-PCV13 serotypes. Moreover, all serotypes of penicillin resistant Streptococcus pneumoniae strains (26.5%; 9/34) were non-PCV13 serotypes. We also analyzed antimicrobial susceptibilities of glycopeptides, linezolid (LZD), and daptomycin (DAP) of isolated S. pneumoniae strains. All tested strains were susceptible to vancomycin, teicoplanin, LZD, and DAP. Especially. DAP demonstrated the best outcome among the tested antibiotics, with MIC90 of 0.094 µg/mL. Pneumococcal meningitis in children continues to persist and is difficult to control with the current conjugate vaccines. Therefore, it is important to monitor the serotype and antimicrobial susceptibility of S. pneumoniae strains isolated from patients with meningitis and accordingly reconsider the treatment strategy.

Epidemiological characteristics in serotype 24 paediatric invasive pneumococcal disease according to an 11-year population-based study in Japan.

After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.

Immunogenicity and safety of routine 13-valent pneumococcal conjugate vaccination outside recommended age range in patients with hematological malignancies and solid tumors.

Hematological malignancy and solid tumor are major risks for invasive pneumococcal disease. Thirteen-valent pneumococcal conjugate vaccine (PCV13) is recommended for immunocompromised patients aged 6 years and older and adults who had not received the vaccine previously. However, vaccination for these individuals is not publicly subsidized in Japan. We measured pneumococcal serotype-specific IgGs (Pn-IgGs) and opsonophagocytic activities (Pn-OPAs) against PCV13 serotypes (1, 3, 5, 6A, 7F, and 19A) in patients with hematological malignancies and solid tumors who were outside the recommended age range for routine vaccination at baseline and at 1 and 6 months after the first dose of PCV13. Pneumococcal serotype-specific memory B cells (Pn-MBCs) against serotype 3 were measured from a portion of the study samples. Thirty-seven patients (30 in the young patient group and 7 in the adult patient group) completed the study. Pn-IgGs were significantly elevated at 1 month post-vaccination and persisted in protection level for 6 months after the first vaccination against all six serotypes measured except serotype 3. Pn-OPAs were significantly elevated and persisted as well against all six serotypes. Pn-MBCs were measured in 10 patients, and 90% of them had at least one detectable Pn-MBC, and 70% of them showed an increased frequency of Pn-MBCs against serotype 3. No serious adverse events were observed up to 1 month after vaccination. PCV13 is thus safe and immunogenic, including against serotype 3, in patients with hematological malignancies and solid tumors outside the recommended age range for routine vaccination.

Oral Factors as Predictors of Frailty in Community-Dwelling Older People: A Prospective Cohort Study.

The purpose of this prospective cohort study was to identify predictors for frailty among possible oral factors in community-dwelling older people. Ninety-seven participants (≥60 years old) without frailty at baseline were included and assigned to either the robust or the frailty group after 2-year follow-up. The frailty was defined using the Japan Cardiovascular Health Study index. The numbers of present and functional teeth and periodontal disease severity were recorded. Bacterial counts on the dorsum of the tongue, oral moisture, tongue pressure, occlusal force, masticatory ability, and the oral diadochokinesis (ODK) rate were measured. Swallowing function, along with psychosocial status, relationships with communities and people, nutritional status, medical history, and comorbidities were evaluated using a questionnaire. The newly identified frailty group at follow-up showed significantly lower values in the number of teeth present, ODK/ta/sound and ODK/ka/sound rates, and clinical attachment level at baseline compared to the robust group. A logistic regression model showed a significantly negative association between the ODK/ta/sound rate at baseline and the incidence of frailty. Articulatory oral motor skill was found to be a predictor of frailty after two years.

Recombinant thrombomodulin attenuates hyper-inflammation and glycocalyx damage in a murine model of Streptococcus pneumoniae-induced sepsis.

PURPOSE: The anticoagulant agent recombinant thrombomodulin (rTM) activates protein C to prevent excessive coagulation and also possibly regulates hyper-inflammation via neutralization of high-mobility-group B1 (HMG-B1). The glycocalyx layer in endothelial cells also plays a pivotal role in preventing septic shock-associated hyperpermeability. The present study examined the effect of rTM in a murine model of Streptococcus pneumoniae-induced sepsis. METHODS: Male C57BL/6N mice were injected intratracheally via midline cervical incision with 2 × 107 CFU of S. pneumoniae (capsular subtype 19A). Control mice were sham-treated identically but injected with saline. rTM (10 mg/kg) was injected intraperitoneally 3 h after septic insult. Blood concentrations of soluble inflammatory mediators (interleukin [IL]-1ß, IL-6, IL-10, and tumor necrosis factor [TNF]-α) were determined using a microarray immunoassay. Serum concentrations of HMG-B1 and syndecan-1, as a parameter of glycocalyx damage, were determined by enzyme-linked immunosorbent assay. The glycocalyx was also evaluated with electron microscopy. The lungs were removed, and digested to cells, which were then stained with a mixture of fluorophore-conjugated antibodies. Anti-mouse primary antibodies included PE-Cy7-conjugated anti-CD31, AlexaFluor 700-conjugated anti-CD45, PerCP-Cy5.5-conjugated anti-CD326, APC-conjugated anti-TNF-α, PE-conjugated anti-IL-6, and PE-conjugated anti-IL-10. A total of 1 × 106 cells per sample were analyzed, and 2 × 105 events were recorded by flow cytometry, and parameters were compared with/without rTM treatment. RESULTS: The blood concentration of TNF-α was significantly reduced 24 h after intratracheal injection in S. pneumoniae-challenged mice treated with rTM (P = 0.016). Levels of IL-10 in the lung endothelium of rTM-treated S. pneumoniae-challenged mice increased significantly 12 h after intratracheal injection (P = 0.03). Intriguingly, serum HMGB-1 and syndecan-1 levels decreased significantly (P = 0.010 and 0.015, respectively) in rTM-treated mice 24 h after intratracheal injection of S. pneumoniae. Electron microscopy indicated that rTM treatment preserved the morphology of the glycocalyx layer in septic mice. CONCLUSIONS: These data suggest that rTM modulates local inflammation in the lung endothelium, thus diminishing systemic inflammation, i.e., hypercytokinemia. Furthermore, rTM treatment reduced serum syndecan-1 levels, thus preventing glycocalyx damage. The use of rTM to treat sepsis caused by bacterial pneumonia could therefore help prevent both excessive inflammation and glycocalyx injury in the lung endothelium.

Oral function, nutritional status and physical status in Japanese independent older adults.

OBJECTIVES: To clarify the associations among oral status, nutritional status and physical status in Japanese independent older adults. BACKGROUND: It is important to focus on factors affecting physical status associated with life dysfunction, long-term care and mortality. However, there are very few reports of the associations among oral status, nutritional status and physical status. MATERIALS AND METHODS: Patients who visited the Preventive Dentistry Clinic at Okayama University Hospital from November 2017 to January 2019 participated in this cross-sectional study. Number of teeth, periodontal condition and oral function were recorded. Bacteria counts in tongue dorsum, oral wettability, tongue pressure, tongue and lip movement function [oral diadochokinesis (ODK)], masticatory ability, bite force and swallowing function were measured. Nutritional status was assessed by the Mini Nutritional Assessment. Physical frailty status and Elderly Status Assessment Set were also evaluated. These variables were analysed by structural equation modelling (SEM). RESULTS: Data from 203 patients were analysed (63 males and 140 females). Patients ranged in age from 60 to 93 years. The final model of the path diagram was completed by SEM. ODK was positively associated with nutritional status, and nutritional status was negatively associated with frailty. Age was associated with ODK, nutritional status and frailty. CONCLUSION: Based on the associations among age, ODK, nutritional status and frailty, maintaining tongue movement function may contribute to good nutritional status and physical status in Japanese independent older adults.

Invasive Haemophilus influenzae type b infection in a patient with transient hypogammaglobulinemia of infancy.

We describe a patient with invasive Haemophilus influenzae type b (Hib) infection despite being completely immunized by a conjugate Hib vaccine. Although Hib vaccination has contributed to significant reduction in invasive Hib infection, there are some case reports of invasive Hib infections despite immunization. Immunoglobulin (Ig) deficiency is the main cause of primary vaccine failure, and IgG2 subclass deficiency is known to be the leading cause. A previously healthy 13-month-old boy visited the outpatient clinic with a 5-day history of fever (40.0 °C), cough, and vomiting, and was diagnosed with bacterial meningitis, purulent pericarditis, and arthritis. Hib was recovered from blood, cerebrospinal fluid, and pericardial fluid. Immunological examination revealed subnormal IgG and IgA titers at 13 and 17 months of age. Serum IgG2 titer was recovered at 17 months of age despite being low at 13 months. Comprehensive gene analysis for primary immunodeficiency syndromes (primary antibody deficiency, common variable immunodeficiency, and toll-like receptor abnormalities) were negative. The antibody titer against Hib [anti-polyribosylribitol phosphate (PRP) antibody] was lower than the long-term protective titer (1.0 µg/ml) at 13 months of age, but was reactively increased to 2.38 µg/mL two months after booster immunization. Transient hypogammaglobulinemia of infancy (THI) is described as an accentuation and prolongation of the physiologic Ig nadir that is normally observed during infancy and defined as low IgG and IgA levels in the first three years of life. We speculate that he developed an invasive Hib infection as a result of primary Hib vaccine failure caused by THI.

Pneumococcal serotype-specific IgG and opsonophagocytic activity in young Japanese patients with asplenia.

Patients with asplenia are at high risks of severe infections caused by encapsulated bacteria, particularly Streptococcus pneumoniae. Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) are recommended for invasive pneumococcal disease prevention; however, little is known about the immunity to pneumococci in young patients with asplenia. We measured pneumococcal serotype-specific IgG (Pn-IgG) levels and pneumococcal opsonophagocytic activity (Pn-OPA) against some PCV13-contained serotypes (1, 3, 5, 6A, 7 F, 19A) in 23 young patients with asplenia using surplus serum samples. In this study, 5 and 13 patients had received PCV13 during routine immunizations and PPSV23, respectively; however, >5 years had passed since the last dose in most cases. The geometric mean concentrations (GMCs) of Pn-IgG in all study patients were not under the cutoff level against six serotypes, but they were lower than the those of age-matched healthy controls, as we have previously published. The patients who had received only PPSV23 had significantly lower GMCs against four serotypes (serotypes 1, 6A, 7 F, and 19A) than that of the patients who had received at least one PCV13 vaccination. The patients who had received only PPSV23 also had significantly lower geometric mean titers (GMTs) of Pn-OPA against all three serotypes we measured (serotypes 3, 5, and 19A) than that of the patients who had received at least one PCV13 vaccination. Our findings are useful data that can indicate insufficient immunity in young patients with asplenia against some PCV13 pneumococci serotypes and suggest the need for appropriate vaccinations in the post-PCV13 era.

Emergence of Haemophilus influenzae with low susceptibility to quinolones isolated from pediatric patients in Japan.

INTRODUCTION: In 2010, oral fluoroquinolone tosufloxacin (TFX) granules were released as the first oral respiratory quinolone for children in Japan. METHODS: To investigate the recent trend of H. influenzae strains with low susceptibility to quinolones in children, we analyzed the gene sequences of quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE of 23 clinical isolates from 15 patients aged <15 years with an MIC of ≥0.5 µg/mL for TFX from 2010 to 2018. RESULTS: Amino acid substitutions were observed in both GyrA and ParC in 13 strains (81%, 13/16), except two strains with a TFX MIC of 0.5 µg/mL with amino acid substitution in only GyrA and one strain with a TFX MIC of 1 µg/mL with no amino acid substitution. Four ST422 strains were observed in 2018, the detection age range was wide (0-7 years), and the residential city was varied. A total of 3/15 patients had a clear history of TFX treatment. CONCLUSIONS: Even for the strain with an MIC of 0.5 µg/mL for TFX, it is highly possible that it harbors a mutation in gyrA, which is the first step toward quinolone resistance, and it may also harbor mutations in both gyrA and parC. Furthermore, several specific sequence type quinolone-resistant H. influenzae strains, particularly ST422, may be widespread among children in Japan. It is necessary to investigate changes in resistance both at the MIC and gene levels. The continuous monitoring of strains and the use of antimicrobial drugs in treatment should be carefully observed.