石和田 稔彦

We present herein the case report of bacterial meningitis caused by nontypeable Haemophilus influenzae (NTHi) in a 1-year-7-month-old girl with no medically significant history. NTHi from cerebrospinal fluid (CSF) was the beta-lactamase non-producing ampicillin resistant strain (BLNAR). Some beta-lactams were administrated, but fever was prolonged. Finally, rifampicin seemed to be effective. In NTHi, compared with H. influenzae type b (Hib), the prevalence of BLNAR is high. Hence, complicated cases may increase in the near future if the use of the Hib vaccine becomes widespread, and meningitis caused by NTHi increases. It may be necessary to consider combination therapy or use of non-beta-lactams that have a different antimicrobial mechanism from beta-lactams. PCR analysis revealed the possibility that the CSF isolate lacked the P5 protein gene. Though deficiency of P5 fimbriae is known to reduce the affinity of NTHi for the human respiratory epithelium, determining whether P5 deficient NTHi induced meningitis will require further study.

Streptococcus gallolyticus subsp. pasteurianus was formerly classified as S. bovis biotype II/2, which is recognized as a rare cause of neonatal sepsis and meningitis. Since the taxonomy classification change, there have not been many reports of meningitis due to S. gallolyticus subsp. pasteurianus. Moreover, the pathogenesis of late onset S. gallolyticus subsp. pasteurianus meningitis in infants is unclear. Here we report a case of meningitis in a 5-week-old infant with preceding diarrhea. S. bovis biotype II/2 was isolated from the blood, cerebrospinal fluid and stool, and then was identified as S. gallolyticus subsp. pasteurianus on 16S rRNA gene sequencing. Isolates from all three sample types had identical profiles on pulsed-field gel electrophoresis. The intestinal tract was thought to be the source of the infection.

Antibody responses to the infecting serotype in children who are vaccinated with pneumococcal conjugate vaccine (PCV) after having invasive pneumococcal diseases (IPD) have not been fully investigated. Of 56 children diagnosed with IPD between October 2009 and April 2013 in whom the infecting serotype was confirmed, 17 who were vaccinated with PCV7 following IPD were tested to determine the geometric mean concentration of serotype-specific immunoglobulin G (IgG) and the geometric mean titers of opsonization indices (OIs) using paired sera obtained at the onset of IPD and after PCV doses following the resolution of IPD. The geometric mean concentrations of serotype-specific IgG for all PCV7 serotypes other than serotype 6B were significantly increased after the last PCV7 dose compared with those at the time of IPD onset (P<0.01), as were the geometric mean titers of OIs for all PCV7 serotypes. In 14 children with IPD caused by PCV7 serotypes for whom both IgG and OI results were available, the OIs for the infecting serotype at the time of IPD onset were <8, although the IgG levels varied between from <0.2 to >5.0μg/ml. After the last PCV7 dose, the OIs for the infecting serotype remained <8 for six (43%) of 14 children. In these six children, hyporesponsiveness to PCV7 was specific for the infecting serotype. Hyporesponsiveness was found for serotypes 6B (n=5) and 23F (n=1). No difference was found between the responders (n=8) and the hyporesponders (n=6) with regard to any clinical characteristics. Our data suggest that hyporesponsiveness to the infecting serotype may occur in children vaccinated with PCV7 following IPD.

To evaluate the biofilm formation of non-typeable Haemophilus influenzae (NTHi) and H. influenzae type b (Hib) clinical isolates, we conducted the following study. Serotyping and polymerase chain reaction were performed to identify β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS), β-lactamase-negative ABPC-resistant (BLNAR), TEM-1 type β-lactamase-producing ABPC-resistant (BLPAR)-NTHi, and Hib. Biofilm formation was investigated by microtiter biofilm assay, as well as visually observation with a scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) in a continuous-flow chamber. As a result, totally 99 strains were investigated, and were classified into 4 groups which were 26 gBLNAS, 22 gBLNAR, 28 gBLPAR-NTHi and 23 Hib strains. The mean OD600 in the microtiter biofilm assay of gBLNAS, gBLNAR, gBLPAR-NTHi, and Hib strains were 0.57, 0.50, 0.34, and 0.08, respectively. NTHi strains were similar in terms of biofilm formations, which were observed by SEM and CLSM. Five Hib strains with the alternated type b cap loci showed significantly increased biofilm production than the other Hib strains. In conclusion, gBLNAS, gBLNAR, and gBLPAR-NTHi strains were more capable to produce biofilms compared to Hib strains. Our data suggested that resistant status may not be a key factor but capsule seemed to play an important role in H. influenzae biofilm formation.

The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. To investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the PCV7 and Hib vaccines in healthy children attending a day care centre in Japan during 2011-2012. Despite a virtual disappearance of PCV7 serotypes over time, the overall pneumococcal carriage rate remained unchanged. Although others have reported an increase in PCV13 serotypes following PCV7 vaccination, only non-PCV13 serotypes were observed to have increased in this study. The majority of H. influenzae isolates were non-typeable and Hib was not found. Our data identified an unexpected pattern of pneumococcal serotype replacement following PCV7. Continuous monitoring of pneumococcal carriage is important for decisions regarding the future of national vaccination policy in Japan.

Helicobacter cinaedi, a gram-negative spiral bacillus that inhabits the intestinal tracts of rodents and primates, is associated with gastroenteritis in humans. H. cinaedi infection has been commonly reported in immunocompromised individuals such as human immunodeficiency virus-infected patients, but rarely in immunocompetent individuals. Prior contact with animals has attracted attention as a possible source of H. cinaedi infection. We report a case of meningitis in an immunocompetent 34-year-old woman who had daily contact with a kitten for a month. She developed acute headaches, fevers, and chills. Neurological examination revealed neck stiffness and her cerebrospinal fluid (CSF) exhibited polymorphonuclear pleocytosis and a decreased concentration of glucose. Blood and CSF cultures were negative; however, the pathogen responsible for her condition was identified as H. cinaedi by polymerase chain reaction in CSF. This is the first adult case of meningitis caused by H. cinaedi. Thus, this bacillus should be considered a possible causative agent of bacterial meningitis in healthy adults.

Human herpesvirus 6 (HHV-6) is the only virus known to integrate into human chromosomes and be transmitted from parents to offspring. Less than 1% of the population carries integrated HHV-6 in their genomes. Here, we report the case of a 9-year-old Japanese girl with an extraordinarily high copy number of HHV-6B in her genome. The integrated virus genome was detected by real-time polymerase chain reaction (PCR) in cerebrospinal fluid and serum during the treatment of meningoencephalitis and pneumonia caused by Mycoplasma pneumoniae infection. Furthermore, the HHV-6B genome was detected in hair follicle, plasma, and whole blood in the patient and her mother, but not in the patient's father. Fluorescence in situ hybridization revealed that the viral genome was integrated into chromosome 22. Therefore, these results emphasize the importance of screening for chromosomally integrated HHV-6 prior to starting unnecessary antiviral therapies, particularly for patients harboring HHV-6 with a high copy number.

Group B Streptococcus (GBS) is one of the leading causes of neonatal bacterial infections. Population-based surveillance of GBS-related invasive diseases among newborns and infants from 10 prefectures in Japan was performed between 2007 and 2012. The characteristics of cases and isolated GBS are described in this study. The incidence rate of GBS-related invasive diseases was 0.13 per 1,000 live births. Analysis of GBS samples obtained from 60 invasive cases showed that the most frequent serotypes were III (48.3%), Ia (30.0%), and Ib (10.0%). All isolates were susceptible to penicillin G, ampicillin, cefotaxime, imipenem, and panipenem. However, 14, 2, and 7 isolates were resistant to erythromycin, clindamycin, and both erythromycin and clindamycin, respectively. Multilocus sequence typing revealed that GBS sequence type (ST) 23, ST17, and ST335 caused higher incidences of meningitis. These data show that serotypes III, Ia, and Ib together caused more than 80% of invasive infections in Japanese infants, and that GBS strains are still susceptible to β-lactam antibiotics.

While the incidence of Haemophilus influenzae type b (Hib) meningitis is expected to decrease with the widespread use of the Hib vaccine, the resistance of Hib has actually increased. Therefore, selection of the initial antibiotics used for treatment must be performed with resistant bacteria, including beta-lactamase negative ampicillin resistant H. influenzae (BLNAR), in mind. Tazobactam/piperacillin (TAZ/PIPC) has a satisfactory minimum inhibitory concentration (MIC) against BLNAR and is a beta-lactamase inhibitor. Although there is no insurance coverage for its use in patients with meningitis, the penetration of TAZ/PIPC into cerebrospinal fluid (CSF) in animal experiments promises a satisfactory result, and we have been using a combination of ceftriaxone (CTRX) and TAZ/PIPC as an initial treatment and a resistant bacteria countermeasure in patients with Hib meningitis at our hospital since 2008. We examined the concentration of TAZ/PIPC in CSF to further investigate the possibility of using TAZ/PIPC as an antibiotic treatment against bacterial meningitis. In cases treated with a 1: 8 drug formulation of TAZ/PIPC against Hib meningitis at our hospital, we used the remaining portion of a CSF sample collected after the initiation of TAZ/PIPC administration and then measured the concentrations of TAZ and PIPC in the CSF. Six specimens from 5 patients between the ages of 6 and 59 months were examined. The dosage of TAZ/PIPC was 95.7-113.6 mg/kg/dose x 3 times/day, and the CSF concentrations at 0-105 minutes after the completion of the administration were 0.319-1.32 microg/mL for TAZ and 2.54-7.74 microg/mL for PIPC. With the approved dosage, the peak concentration level during the acute period indicated a sufficient CSF concentration level for the antibacterial and beta-lactamase inhibition effects against Hib. As an antibiotic treatment for H. influenzae meningitis, the combined usage of TAZ/PIPC is likely to be effective as a resistant bacteria countermeasure, in addition to third-generation cephem drugs and meropenem.

CASE REPORT: Bacterial meningitis is a rare complication of adenotonsillectomy. We present a case of meningitis due to nontypeable Haemophilus influenzae and Streptococcus pneumoniae after adenotonsillectomy. Pulsed-field gel electrophoresis patterns indicated that the oral cavity was the source of H. influenzae and S. pneumoniae isolated from the cerebrospinal fluid. BLOOD CULTURE STUDY: As bacteremia is thought to be one of the etiologies of meningitis, we prospectively investigated the rate of bacteremia as a complication of adenotonsillectomy. Of the 46 patients included in the study, mean age of five years old, 11 (24%) had positive blood cultures during the operation. H. influenzae was the commonest organism grown (seven cultures), three of seven produced beta-lactamase, followed by S. pneumoniae (one culture), H. parainfluenzae (one culture), Peptostreptococcus micros (one culture), and Veillonella spp. (one culture). The bacteria were composed of tonsil or adenoid surface cultures in eight of 11 patients (73%). CONCLUSIONS: We present a rare case of meningitis complicating a adenotonsillectomy procedure, in a three years old boy. Meningitis is a rare complication of adenotonsillectomy, but bacteremia which may lead to meningitis occurs frequently, as the results.

BACKGROUND: Estimates of the disease burden from childhood pneumonia are available for most developed countries, but they are based mainly on models. Measured country-specific pneumonia burden data are limited to a few nations and differ in case definitions and case ascertainment methods. This review describes pneumonia disease burden in developed countries. METHODS: We reviewed studies describing childhood pneumonia incidence in North America, Europe, Australia, New Zealand and Japan. Available estimates suggest that each year in developed countries there are up to 2.6 million cases of pneumonia, including 1.5 million hospitalized cases and around 3000 pneumonia deaths (compared with approximately 640 annual deaths from meningitis) in children <5 years of age. RESULTS: Data to inform policy decisions would be improved by information on burden and etiology of severe pneumonia, population-based incidence of ambulatory visits and hospitalizations and prevalence of complications and sequelae.

In Japan, the incidence of severe pediatric tuberculosis (TB) has decreased dramatically in recent years. However, children in Japan can still have considerable opportunities to contract TB infection from adult TB patients living nearby, and infants infected with TB may develop severe disseminated disease. A 3-month-old girl was admitted to our hospital with dyspnea and poor feeding. After admission, miliary TB and multiple brain tuberculomas were diagnosed. Anti-tuberculous therapy was initiated with streptomycin (SM), isoniazid (INH), rifampicin and pyrazinamide. Symptoms persisted after starting the initial treatment and mycobacterial cultures of gastric fluid remained positive. Drug sensitivity testing revealed the TB strain isolated on admission as completely resistant to INH and SM. Treatments with INH and SM were therefore stopped, and treatment with ethambutol and ethionamide was started in addition to rifampicin and pyrazinamide. After this change to the treatment regimen, symptoms and laboratory data gradually improved. The patient was treated with these four drugs for 18 months, and then pyrazinamide was stopped. After another 2 months, ethambutol was stopped. Treatment of tuberculosis was completed in 24 months. No adverse effects of these anti-TB drugs were observed. The patient achieved a full recovery without any sequelae. On the other hand, the infectious source for this patient remained unidentified, despite the extensive contact investigations. The incidence of drug-resistant TB is increasing in many areas of the world. Continuous monitoring for pediatric patients with drug-resistant TB is therefore needed.

The efficacy of 3-day treatment with a combined clavulanate/amoxicillin preparation (Clavamox combination dry syrup for pediatric cases) and 10-day treatment with amoxicillin against pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus was compared. Among the patients included in the efficacy evaluation (54 from the clavulanate/amoxicillin group and 43 from the amoxicillin group), the clinical response rate on completion of treatment was 98.1 % in the clavulanate/amoxicillin group and 92.9 % in the amoxicillin group, thus supporting the equivalent efficacy of these two therapies. The Group A β-hemolytic Streptococcus eradication rate at approximately 1-2 weeks after completion/discontinuation of treatment was 65.4 % in the clavulanate/amoxicillin group and 85.4 % in the amoxicillin group. Even in cases from which the pathogen continued to be isolated, relapse/recurrence of clinical symptoms was seldom seen. Urinalysis, conducted to assess the presence or absence of acute glomerulonephritis, revealed no abnormality in any patient. These results suggest that 3-day treatment with this clavulanate/amoxicillin preparation is expected to provide a valid means of treating pediatric pharyngolaryngitis and tonsillitis caused by Group A β-hemolytic Streptococcus.

Serotype-specific protective immunity in pediatric patients with invasive pneumococcal disease (IPD) has not been fully investigated. To determine the protective immunity to the infecting serotype, the serotype-specific immunoglobulin G (IgG) levels and opsonization indices (OIs) were examined in 24 Japanese pediatric patients whose serum was collected within one month of an IPD episode between May 2008 and June 2011. The median age (range) of IPD patients was 17 (10-108) months and 63% were boys. In all 17 patients tested, the levels of serotype-specific IgG to the infecting serotype were higher than 0.2 μg/ml, but the OIs to the infecting serotype were <8. The avidities of 19F- or 6B-specific IgG in patients with levels higher than 5.0 μg/ml, but with undetectable OIs, were confirmed to be lower than those in patients with high OIs. Our data demonstrated that although the levels of serotype-specific IgG to the infecting serotype were higher than 0.2 μg/ml in sera of pediatric patients with IPD, the OIs were low one month after the IPD episode. Low opsonic activities in these patients may, in part, be explained by the low avidity of serotype-specific IgG.

To evaluate pathogens in pediatric inpatients with community-acquired pneumonia (CAP), an Acute Respiratory Diseases Study Group organized by ten Japanese medical institutions devised a rapid, reliable process based on real-time PCR results in nasopharyngeal swab samples plus admission blood test results. From April 2008 to April 2009, we enrolled 903 children with CAP based on chest radiographs and clinical findings who were hospitalized within 5 days of onset. Comprehensive real-time PCR was used to detect 6 bacteria and 11 respiratory viruses. The swab specimens also were used for bacterial cultures. After initial determination of presence or absence of viral and mycoplasmal infections, significant bacterial contributions were defined by bacterial identification, clinical efficacy of antimicrobial agent, and reference to blood test results. Children were stratified by age: below 1 year, 1 year, 2-5 years, or at least 6 years old. Among patients studied, 34.4 % were diagnosed with viral infection; 21.8 %, bacterial infection; 17.5 %, viral/bacterial co-infection; 5.9 %, mycoplasmal infection; 0.3 %, mycoplasmal/bacterial co-infection; and 1.7 %, viral/mycoplasmal co-infection. The remaining 18.4 % had unknown pathogens. Purely viral infection was suggested mainly in infants younger than 1 year; mycoplasmal infection typically occurred in children at least 6 years old. Our results suggest usefulness of real-time PCR for nasopharyngeal samples together with blood tests in estimating etiologic agents in clinical settings.

The influenza A/H1N1 2009 epidemic has spread to many countries since 2009, including Japan. We report an immune-competent child involving rhabdomyolysis and compartment syndrome associated with influenza A/H1N1 2009. The patient was demonstrated rhabdomyolysis with myoglobinuria, hyperkalemia, cardiac dysfunction and compartment syndrome that arose during convalescence from influenza A/H1N1 2009 infection. Although RT-PCR of muscle tissue yielded negative results for influenza A/H1N1 2009 RNA and no viral positive-antigen cells were detected in the muscle lesions, the clinical picture suggested rhabdomyolysis associated with influenza A/H1N1. Rhabdomyolysis should be considered in the evaluation of muscle symptoms such as myalgia associated with novel influenza A/H1N1 2009 virus infection, particularly in critically ill patients.

Mycoplasma pneumoniae, a common pathogen causing community-acquired pneumonia, is also known to cause meningoencephalitis in pediatric patients. We report herein a pediatric patient with meningoencephalitis and macrolide-resistant M. pneumoniae infection. We emphasize that macrolide-resistant M. pneumoniae must be taken into consideration in patients with encephalitis, along with consideration for using minocycline even in pediatric patients.

使用において特に注意を要する抗菌薬(以下、特定抗菌薬)の院内における適正使用の推進を目的として、感染制御チーム(以下、ICT)と連携して定点状況調査(以下、スナップ・ショット)を用いた使用状況の把握と病棟担当薬剤師による問題症例に対する介入を試みた。本取り組み開始前後1年間における特定抗菌薬の平均使用件数および14日以上の長期投与件数を比較したところ、いずれも開始後有意な減少が認められた。また、問題症例に対するICTの提言内容は、薬剤の選択と用法・用量の変更を要するものが半数以上を占め、これらの提言に対する遵守率は96%であった。以上、スナップ・ショットを用いた問題症例の抽出と、それに続く病棟担当薬剤師とICTの連携による指導等の取り組みにより、院内における特定抗菌薬の適正使用が推進されたと考えられた。(著者抄録)

During the 10 years preceding the introduction of the Haemophilus influenzae type b (Hib) vaccine, restriction fragment length polymorphism (RFLP) analysis using pulsed-field gel electrophoresis was performed on 66 strains (22 sets) of Hib isolated simultaneously from cerebrospinal fluid, blood, and nasopharyngeal samples of 22 patients with meningitis. Strains from the 3 types of samples showed identical RFLP patterns in 18 of the 22 patients, confirming the pathway of Hib infection starting from the nasopharynx and leading to meningitis through bacteremia. In the remaining 4 patients, the RFLP patterns from the 3 sample types were also nearly identical. However, a single band in the RFLP patterns of strains from 1 of the 3 sample types showed a shift of about 20 kb. One copy of the cap-b gene had a molecular weight of 18 kb, and the discrepancy in the band's molecular weight indicated an amplification or loss of a single copy of the cap. These findings suggest that Hib caused meningitis by changing the number of copies of the cap to evade the host's immunological response.

The 7-valent pneumococcal conjugate vaccine (PCV7) is reported to decrease the incidence of community-acquired pneumonia (CAP) in children. To determine the annual incidence of CAP before the introduction of PCV7, we counted the number of children hospitalized with CAP between 2008 and 2009 in Chiba City, Japan. We investigated serotype and multilocus sequence typing (MLST) for Streptococcus pneumoniae isolates in CAP cases. The annual incidence of hospitalized CAP in children aged &lt;5 years was 17.6 episodes/1000 child-years. In 626 episodes, S. pneumoniae was dominant in 14.7% and 0.8% of sputum and blood samples, respectively. The most common serotypes were 6B, 23F and 19F. The coverage rates of PCV7 were 66.7% and 80% in sputum samples and blood samples, respectively. MLST analysis revealed 37 sequence types. Furthermore, 54.1% of the sputum isolates and 40% of the blood isolate were related to international multidrug-resistant clones.

生後11ヵ月時と1歳2ヵ月時に血清型6Bの肺炎球菌性髄膜炎を反復した女児。分離菌のmultilocus sequence typing解析より、同一株による再発と判明した。初発、再発後に7価肺炎球菌結合型ワクチンを接種したが、6Bに対する抗体価が上昇しなかった。一部の血清型の肺炎球菌上咽頭常在例や、侵襲性肺炎球菌感染症罹患後には、ワクチン接種後の抗体価上昇が不良な場合があるとされており、注意を要する。このような例を防ぐためにも、早急なPCV7の定期接種化が望まれる。(著者抄録)

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. METHODS: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti-polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme-linked immunosorbent assay method. Antibody positivity was defined as levels >1 µg/mL. RESULTS: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 µg/mL. This compares with the 92.4% reported in full-term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. CONCLUSIONS: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full-term infants. It may therefore be preferable to modify the proposed immunization schedule.

Streptococcus pneumoniae is a major cause of systemic infection and respiratory tract infection. All age groups may be affected, but the highest rates of pneumococcal disease occur among young children and elderly individuals. Now, two pneumococcal vaccines are available in Japan. The 23-valent pneumococcal polysaccharide vaccine(PPV23) is the vaccine to prevent invasive pneumococcal disease and pneumonia among adults. The 7-valent pneumococcal conjugate vaccine (PCV7) is the vaccine to prevent invasive pneumococcal disease and respiratory tract infection among young children. Unfortunately, so far, both of the vaccines have used as a voluntary vaccine in Japan. The widely use of PPV23 and PCV7 is expected for the prevention of pneumococcal disease in Japanese people.

Haemophilus influenzae type b conjugate vaccine was recently introduced to Japan for voluntary immunizations. H. influenzae type b remains a leading cause of pediatric invasive diseases in Japan. The purposes of this study were to verify the suitability of the H. influenzae type b conjugate vaccine for immunizing children with a history of invasive H. influenzae type b disease and to determine whether H. influenzae type b conjugate vaccine is immunogenic in these children. The subjects comprised 64 children with a history of invasive H. influenzae type b disease. Serum samples from 64 patients with H. influenzae type b systemic infection in the acute and convalescent phases were analyzed. Serum anti-polyribosylribitol phosphate antibody responses of patients < 2 years old were poorer than those observed in patients ≥ 2 years old. Nineteen of the 64 patients received a single dose of H. influenzae serotype b conjugate vaccine, and then follow-up serum was taken and analyzed. Eighteen of 19 patients had ≥ 1 μg/mL of anti-polyribosylribitol phosphate antibody titer after the first dose of H. influenzae type b conjugate vaccine. H. influenzae type b conjugate vaccine is immunogenic in children with invasive H. influenzae type b disease. Children < 4 years old, and particularly < 2 years old, with invasive H. influenzae type b disease should receive subsequent immunization with a H. influenzae type b conjugate vaccine.

Bacterial coinfection occurs in pediatric bronchopulmonary infections caused by respiratory syncytial virus (RSV), but the incidence is uncertain. Our subjects are 188 pediatric inpatients having RSV bronchopulmonary infection in two hospitals in Chiba Prefecture between 2005 and 2007. On admission, antigen detection kits using nasopharyngeal aspirate were performed to detect RSV infection and washed sputum bacterial culture was performed to detect bacterial infection. Of the 188 pediatric inpatients with RSV bronchopulmonary infection, 95 (50.5%) patients were aged less than 1 year, 57 (30.3%) were aged 1-2 years, and 36 (19.1%) were aged 2 years or more. Thirty-six (19.1%) patients were associated with bronchial asthma attacks. Pathogenic bacteria were predominantly isolated from 43.6% of the patients. The three most frequently isolated bacteria were Haemophilus influenzae (43.9%), Streptococcus pneumoniae (36.6%), and Moraxella catarrhalis (29.3%). We found that 38.9% of H. influenzae strains were β-lactamase-nonproducing ampicillin-resistant strains. All S. pneumoniae strains were penicillin G (PcG) sensitive. However, 21.9% of S. pneumoniae strains showed PcG minimum inhibitory concentration values of 2 μg/ml. RSV bronchopulmonary infections in hospitalized children are often associated with antimicrobial-resistant bacterial infection in their lower airways. These results indicate that we should be aware of bacterial coinfections in the management of pediatric inpatients with RSV bronchopulmonary infection.

Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors.

OBJECTIVES: The purpose of the study is to evaluate the incidence, spectrum of clinical manifestations and outcome of invasive pneumococcal disease (IPD) in children in Chiba prefecture, Japan. METHODS: To determine the precise incidence of IPD in Chiba prefecture, we implemented a retrospective survey of the period from 2003 to 2005. A written questionnaire was sent to 45 hospitals that have pediatric wards, and information was obtained from all hospitals. The questionnaire included the clinical diagnosis, patient's age, underlying disease, prognosis and antimicrobial susceptibility of the isolated strains. RESULTS: During the 3 study years, 130 patients were diagnosed with IPD. The mean annual incidence rates of IPD among children <2 and <5 years were 19.5-23.8 and 12.6-13.8 per 100,000, respectively. Among 130 patients with systemic infection, 66 patients had bacteremia, 39 had pneumonia and 16 had meningitis. Five patients had neurological sequelae and 2 patients died. Seventy-four out of 115 isolates (64.3%) exhibited resistance to penicillin G. CONCLUSIONS: The annual incidence of pediatric IPD has remained constant during the study period. Two-third of isolated strains were at least partially resistant to penicillin G. Establishment of appropriate antibiotic therapy against IPD due to penicillin-resistant strains and the introduction of pneumococcal conjugate vaccines are emergent issues in Japan.

Population-based studies on community-acquired pneumonia (CAP) are rare in Japan. Among 984 Chiba City children admitted with CAP to 19 local hospitals in 2005, 854 were younger than 5 years old. The annual CAP incidence among children < 5 years old was 19.7 per 1,000. Five, 4 of whom were under 5 years old, had pneumococcus isolated from blood. The incidence of CAP with pneumococcal bacteremia was 9.21 per 100,000 among those < 5 years old.

We encountered a 14-year-old Bangladeshi boy who developed acute hepatitis E in Japan. He showed improvement without the development of fulminant hepatitis. His hepatitis E virus (HEV) genotype was I, which causes epidemics mainly in South Asia. He developed this disease more than 6 months after coming to Japan. Considering the latent period, it was suspected that he had been infected with HEV in Japan, although the HEV virus is presumed not to be indigenous to Japan.