石和田 稔彦

The members of the Japanese Society for Pediatric Infectious Diseases and the Japanese Society of Pediatric Pulmonology have developed Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating appropriate diagnosis, treatment and prevention of respiratory infections in children. The first edition was published in 2004 and the fifth edition was published in 2022. The Guideline 2022 consists of 2 parts, clinical questions and commentary, and includes general respiratory infections and specific infections in children with underlying diseases and severe infections. This executive summary outlines the clinical questions in the Guidelines 2022, with reference to the Japanese Medical Information Distribution Service Manual. All recommendations are supported by a systematic search for relevant evidence and are followed by the strength of the recommendation and the quality of the evidence statements.

症例は3歳女児で、発熱と活気不良を主訴とした。胆道閉鎖症に対し生後6ヵ月で生体肝移植後シクロスポリンを内服中であった。尿培養で肺炎球菌が分離され、分離された肺炎球菌はワクチン含有血清型の3型で培地上はムコイド形成を認めた。本症例は肝移植後に13価肺炎球菌結合型ワクチンを2回、その後23価肺炎球菌莢膜多糖体ワクチンを1回接種していたが、血清型3型に対する特異抗体価とオプソニン活性は、急性期では比較的低値で回復期に有意に上昇し、同菌による尿路感染症(UTI)と診断した。アンピシリンの経静脈的投与により入院3日目に解熱し、アモキシシリン内服変更し計14日間の治療を完遂した。起炎菌が血清型3型肺炎球菌であり、免疫抑制剤内服中であったため、ワクチン接種後にも関わらず同菌によるUTIを発症したと考えられた。

定期外来通院中の血液腫瘍患者20名(小児11名,成人9名)を対象として,自己喀出による唾液検体を用いて肺炎球菌特異遺伝子に対するreal-time PCRを複数の手法で行い,上咽頭の肺炎球菌保菌状況を検討した。インターカレーション法によるreal-time PCR(lytA遺伝子:A法,SP2020遺伝子:B法),マイクロ流路型遺伝子定量装置GeneSoCを用いたreal-time PCR(C法)それぞれの検出率は,順に60.0%,30.0%,70.0%と,従来の鼻咽頭培養での検出率より高い傾向だった。A法における検出率は,成人検体では22.2%である一方,小児検体では90.9%と高く,B法,C法も同様の傾向だった。鼻咽頭培養で発育を確認できなかった患者においても唾液検体でのPCR陽性となる場合もみられた。一方,唾液培養は他の口腔内常在菌の発育により,肺炎球菌の同定が困難だった。唾液検体によるPCR法を用いた肺炎球菌保菌検査は低侵襲かつ比較的高感度に上咽頭の肺炎球菌保菌を検出できる可能性がある。(著者抄録)

2020年2月～2022年4月に専用データベースに報告された小児コロナウイルス感染症2019患者のうち、0～15歳の5411例(男児2889例、女児2522例)の急性期における臨床的特徴を解析した。オミクロン株流行により感染経路は家庭内感染から学校・幼稚園・保育所へ変化した。オミクロン株流行期に初発症状でけいれん発作を起こした割合は1～4歳で13.4%、5～11歳で7.4%、オミクロン株流行期に初発症状で悪心・嘔吐を認めた割合は1～4歳で12.2%、5～11歳で22.6%、12～15歳で14.6%であり、いずれもデルタ株流行前またはデルタ株流行期と比較して大幅に増加した。最終的に全体の約2%にけいれんを伴う合併症が報告された。肺炎の合併率は変異株の違いによる変化をほとんど認めなかった。発症後28日を超えた症例報告書が提出された1697例(男児899例、女児798例、年齢中央値6.3歳)のうち、55例(3.2%)に発症後28日を超えても何らかの症状が残存した。

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.

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan. METHODS: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021. RESULTS: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups aged 1-4 and 5-11 years, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%). CONCLUSIONS: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients.

COVID-19流行後,細菌性呼吸器疾患の多くは明らかに減少した.要因として,政府のCOVID-19政策や人々の行動変容が考えられる.SARS-CoV-2は時に細菌と共感染,重複感染を起こし重症化するが,COVID-19患者に対しても,抗菌薬の適正使用を心がける必要がある.(著者抄録)

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.

Antimicrobial resistance (AMR) is a major problem in public health. Japan is addressing this problem with various measures based on the National Action Plan on AMR, published in 2016. In Japan, the fight against AMR is hindered by issues with the health care system, including the lack of a general practitioner registration system, an abundance of private clinics and health care for infants and toddlers being essentially free of charge. As measures against AMR in inpatient care, thorough infection prevention and the Japanese government's incentivization of collaboration in infection prevention among hospitals and regions have helped to improve infection prevention. As measures against AMR in outpatient care, the creation of official Japanese government guidelines on antimicrobial stewardship has facilitated the implementation of antimicrobial stewardship in clinics. Another unique measure taken in Japan is incentivizing the nonprescription of antimicrobials for respiratory tract infections and diarrhea. Although Asia is a hot spot for AMR bacteria, the fight against AMR is affected by various factors, including insufficient precautions against nosocomial infections and the absence of surveillance systems. To combat these problems, Japan must take a strong leadership role. AMR is a problem not only at the level of individual countries but on a global scale and should, therefore, be addressed through joint action among nations.

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.

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.

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]-1β, 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.

BACKGROUND: Pediatric parapneumonic effusion/ pleural empyema (PPE/PE) is a severe infectious condition, and its management should be guided by local epidemiology and the patient's medical history. This survey aimed to determine the clinical and bacteriologic features of PPE/PE in Japan. METHODS: A nationwide retrospective questionnaire survey was conducted, targeting 159 pediatric specialist training medical facilities for inpatients ≤18 years of age who were admitted for PPE/PE between January 2007 and December 2016. RESULTS: Valid responses were obtained from 122 facilities, and 96 patients were identified from 38 facilities. The median age (interquartile range) was 2.7 (0.8-7.8) years. Overall, 60 (63 %) patients were men and 49 (51%) had comorbidities. The causative bacteria were identified in 59% of patients by culture except in one case identified using PCR. Streptococcus pyogenes (16%), Staphylococcus aureus (14%) and Streptococcus pneumoniae (13%) were the major pathogens. Carbapenems were administered to 34% of patients without comorbidities. Chest tube drainage was performed in 71%, intrapleural fibrinolytic therapy in 9.4%, surgery in 25% and mechanical ventilation in 29% of the patients. Five patients (5.2%) had complications and one (1.1%) had sequelae, but all patients (100%) survived. CONCLUSIONS: This is first report of a nationwide survey pertaining to pediatric PPE/PE in Japan. We found that the etiology showed a different trend from that reported in other countries. It is worrisome that molecular methods were rarely used for pathogenic diagnosis and carbapenems were overused. Thus, it is imperative to establish clinical guidelines for PPE/PE in Japan.

Cryptococcus neoformans, basidiomycetous pathogenic yeast, is basically an environmental fungus and, therefore, challenged by ever changing environments. In this study, we focused on how C. neoformans responds to stress caused by cadmium that is one of high-risk pollutants. By tracking phenotypes of the resistance or sensitivity to cadmium, we undertook forward and reverse genetic studies to identify genes involved in cadmium metabolism in C. neoformans. We found that the main route of Cd2+ influx is through Mn2+ ion transporter, Smf1, which is an ortholog of Nramp (natural resistance-associated macrophage protein 1) of mouse. We found that serotype A strains are generally more resistant to cadmium than serotype D strains and that cadmium resistance of H99, a representative of serotype A strains, was found to be due to a partial defect in SMF1. We found that calcium channel has a subsidiary role for cadmium uptake. We also showed that Pca1 (P-type-ATPase) functions as an extrusion pump for cadmium. We examined the effects of some metals on cadmium toxicity and suggested (i) that Ca2+ and Zn2+ could exert their protective function against Cd2+ via restoring cadmium-inhibited cellular processes and (ii) that Mg2+ and Mn2+ could have antagonistic roles in an unknown Smf1-independent Cd2+ uptake system. We proposed a model for Cd2+-response of C. neoformans, which will serve as a platform for understanding how this organism copes with the toxic metal.

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.

肺炎球菌結合型ワクチンが保育園児の上咽頭保菌に与える影響、水平伝播の状況について調査する目的で、2017〜2019年度、足立区(3ヶ所)と国分寺市(1ヶ所)の保育園の年3回の保菌調査で、分離された肺炎球菌の血清型・薬剤感受性について調査を行った。2017年度、2018年度、2019年度の肺炎球菌分離株数は55株、69株、60株(うち1検体から2つの血清型株分離)であった。年度ごとの肺炎球菌分離率は、64〜67%と大きな違いは認めなかった。13価肺炎球菌結合型ワクチン(PCV13)含有血清型は、2017年度2株、2019年度1株で、いずれも血清型3であった。PCV13非含有血清型である15Aは2017年度、2018年度に多く、また、無莢膜株が2018年度に多く分離された。2019年度は10Aと34、35Bが増加していた。保育園の中では、年度により同じ血清型が多数分離される傾向があり、水平伝播が示唆された。PCG MIC≧2μg/mLの株は、15株あり、血清型15A(5株)、35B(3株)、10A(4株)、無莢膜株(3株)であった。同一の児から年複数回分離された血清型は7種類あり、そのうち34、10A、23Bは年間を通じて検出されていた。1〜3回目の採取時における肺炎球菌の有無と同胞の有無との関連について解析したところ、1、2回目は有意な関連が認められた。肺炎球菌の上咽頭への無症候性定着が侵襲性感染症の発症契機となること、今後、新しく開発された肺炎球菌結合型ワクチンの効果を予測する上においても、保菌調査による継続的な監視が必要である。(著者抄録)

The pneumococcal conjugate vaccines successfully decreased the incidence of invasive pneumococcal diseases and pneumococcal antibiotic resistance. However, they also led to serotype replacements. According to a report by the National Institute of Infectious Diseases (NIID) in 2017, 96% of pneumococcal isolates obtained from children with IPD aged < 5 years were non-PCV13 serotypes. Here, we report the case of a Japanese immunocompetent and vaccinated child who developed refractory meningitis caused by Streptococcus pneumoniae nonvaccine serotype 10A. PCR revealed genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) with triple mutations (pbp1a + 2b + 2x). Multilocus sequence typing identified the strain as a sequence type (ST) 11189. The ST11189 strain has not been reported in Japan, but it has recently been reported as a cause of invasive infections in Korea. The clinical course was complicated by the development of brain and subdural abscesses that necessitated prolonged antibiotic treatment and multiple burr hole drainages. Unfortunately, the neurological sequelae persisted. Continued molecular surveillance is needed for monitoring emerging virulent clinical strains.

症例は1歳5ヵ月男児で川崎病と診断され,入院日よりγグロブリン製剤投与を開始した。翌日に解熱し川崎病の症状は改善したが,入院時に実施した咽頭培養から,Neisseria meningitidis分離が報告された。ご両親に無症状でもN.meningitidisは検出されることがあることを説明するも不安が強く,除菌のための抗菌薬治療を行い,咽頭培養再検査,セカンドオピニオンのための他医療機関への受診も行った。後日,N.meningitidisと報告された菌株について16SrRNAおよびrecA遺伝子(recA protein)の塩基配列の相同性を検討した結果,N.polysacchareaと同定した。質量分析法を用いたことによるN.meningitidisの誤同定であった。(著者抄録)

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.

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.

Japan has not been able to eliminate rubella; as a result, the large rubella epidemic has occurred. Considering the complicated history of the vaccine policy in Japan, some susceptible populations became infected with rubella, resulting in an outbreak. We conducted a large serosurveillance against rubella in Chiba city after initiating free rubella-specific antibody testing and an immunization campaign during 2018-2019. The total number of rubella specific antibody tests that was conducted in the nationwide campaign and Chiba city original campaign was 8277 and 6104, respectively. The proportion of participants with an antibody titer of ≤1:16 using the hemagglutination inhibition (HI) test was higher in those in their 20-30s. On the contrary, the proportion of participants with an antibody titer of <1:8 using the HI test was higher in men in their 40-50s. This discrepancy possibly reflects the complicated history of the vaccine policy. The number of participants in the nationwide immunization campaign in this city was 1517, whereas that in the Chiba city campaign was 3607. The Chiba city campaign was effective against women in their 20-30s (child-bearing generation); however, the nationwide campaign was not sufficiently effective against men in their 40-50s because many workers were did not visit medical facilities to receive the measles-rubella vaccine.

診断に骨シンチグラフィが有用であったMethicillin-sensitive Staphylococcus aureus;MSSAによる腸腰筋膿瘍の一例を経験した。症例は14歳女児,発熱と体動困難で前医を受診し,感染巣不明のMSSA菌血症として抗菌薬を2週間投与され退院となった。しかし,1週間後に発熱と体動困難が再燃し,当院へ入院した。精神発達遅滞のため,症状の把握が困難であったが,筋骨格系感染症を疑い骨シンチグラフィを施行したところ,右骨盤内に集積を認めた。その後MRIを施行し,右腸腰筋膿瘍および右腸骨,仙骨骨髄炎と診断した。洗浄ドレナージを施行し,同時に採取した膿汁よりMSSAを分離,6週間の抗菌薬投与により後遺症なく治癒した。腸腰筋膿瘍は,感染巣の特定に難渋することがある。治療方針や抗菌薬投与期間の決定のため,画像検査等積極的な感染巣の検索が必要である。(著者抄録)