Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility.

A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be ß-lactamase-producing ampicillin resistant strains, while 20.8% were ß-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were ß-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum ß-lactamase-producing E. coli was 14.3%.

Immunogenicity and safety of porcine circovirus-free human rotavirus vaccine in healthy infants: a phase III, randomized trial.

BACKGROUND: Porcine circovirus type 1 (PCV-1) material was detected in the human rotavirus vaccine (HRV) in 2010. In this study (NCT02914184) we compared immunogenicity and safety of the PCV-free HRV vaccine (PCV-free HRV) with HRV. PCV-free HRV is an HRV with no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. METHODS: Healthy infants 6-12 weeks of age were randomized (1:1:1:1) to receive 2 doses of 1 of the 3 lots of PCV-free HRV or HRV. The study objectives were to demonstrate lot-to-lot consistency of the PCV-free HRV and non-inferiority of PCV-free HRV as compared to HRV in terms of immunogenicity, 1-2 months post-dose 2. Reactogenicity and safety were also assessed. RESULTS: Overall, 1612 infants were enrolled and 1545 completed the study. Study objectives were demonstrated since the pre-defined criteria were met. Among participants receiving PCV-free HRV and HRV, 79.27% and 81.76% seroconverted and geometric mean concentrations were 159.5 and 152.8 U/mL, respectively. The incidences of adverse events and serious adverse events were similar between the pooled PCV-free HRV and HRV groups. CONCLUSIONS: The 3 PCV-free HRV lots demonstrated consistency and PCV-free HRV was non-inferior compared to HRV in terms of immunogenicity.

Characterization of unusual DS-1-like G3P[8] rotavirus strains in children with diarrhea in Japan.

The emergence and rapid spread of novel DS-1-like intergenogroup reassortant rotaviruses having the equine-like G3 genotype (DS-1-like G3P[8] strains) have been recently reported from several countries. During rotavirus surveillance in Japan in 2015-2016, three DS-1-like G3P[8] strains were identified from children with severe diarrhea. In the present study, we sequenced and characterized the full genomes of these three strains. On full-genomic analysis, all three strains showed a unique genotype constellation including both genogroup 1 and 2 genes: G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that each of the 11 genes of the three strains was closely related to that of Japanese DS-1-like G1P[8] and/or Japanese equine-like G3P[4] human strains. Thus, the three study strains were suggested to be reassortants that acquired the G3-VP7 gene from equine G3 rotaviruses on the genetic background of DS-1-like G1P[8] strains. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G3P[8] strains.

Pediatric community-acquired pneumonia treated with a three-day course of tebipenem pivoxil.

We evaluated the efficacy and safety of a 3-day treatment regimen of tebipenem pivoxil for pediatric community-acquired pneumonia. Tebipenem pivoxil was administered to 49 patients, and its effectiveness was evaluated in 36 patients 2-4 days after initiation of treatment. Thirty-two patients were cured 7-15 days after initiation of treatment. Body temperature was significantly lower on the day following initial administration (median 38.8 to 37.0 °C, n = 33). Leukocyte counts and C-reactive protein levels were significantly reduced by Day 2-4 of treatment (median 16,100 to 7800 white blood cells/µL, and 5.6 to 1.5 mg/dL, respectively; n = 28). Six of the 49 patients had mild diarrhea. Thus, we concluded that 3-day treatment with tebipenem pivoxil was safe and efficacious for treating pediatric community-acquired pneumonia.

Alice in Wonderland syndrome associated with mycoplasma infection.

Alice in Wonderland syndrome (AIWS) is a rare condition in which patients report distorted size perception of objects and their own bodies. Although specific causes and pathology have not been elucidated, an association between AIWS and infection has been suggested. To our knowledge, mycoplasma-induced AIWS has not been examined. A girl aged 7 years 11 months presented with fever (temperature, 40°C) and cough. Although the fever disappeared after approximately 10 days, she complained that her mother's face suddenly appeared smaller to her. Subsequently, she complained that objects intermittently appeared smaller than normal. Particle agglutination test indicated elevated serum antibodies against Mycoplasma pneumoniae. The patient was therefore diagnosed the patient with AIWS secondary to mycoplasma infection. Although mycoplasma infection is known to cause various central nervous system symptoms, this is the first report involving AIWS, suggesting that mycoplasma could affect visual function in children.

[Evaluation of a Rapid Antigen Detection Kit Targeting L7/L12 Ribosomal Protein for Mycoplasma pneumoniae].

We evaluated the usefulness of a rapid antigen detection assay for L7/L12 ribosomal protein (Ribotest Mycoplasma; Asahi Kasei Pharma) for diagnosis of Mycoplasma pneumoniae (M. pneumoniae) infection. Nasopharyngeal swabs were obtained from patients with pneumonia and/or bronchitis; real-time PCR and the L 7/L12 antigen assays were performed with each sample. Serum was also taken from each patient, and the particle agglutination (PA) method was used to detect anti-M. pneumoniae antibody in these samples. Macrolide-resistance genes were detected and M. pneumoniae P1 protein subtyping was performed on PCR-positive samples. PCR assays were positive for 85 of 212 specimens (40.1%). Sensitivity and specificity of the L7/L12 antigen assays relative to the PCR standard were 74.1% (63/85) and 81.1% (103/127), respectively. For PCR-positive specimens with a large quantity of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be high. In PCR-positive specimens with fewer than 1.0 x 10(6) copies/mL of M. pneumoniae nucleic acid, sensitivity of the L7/L12 antigen assays seemed to be low. When the PA method was used as the standard, the relative sensitivity and specificity of the L7/L12 antigen assays were 41.7% (5/12) and 75.3% (58/77), respectively, for single serum and 60.9% (14/23) and 85.7% (18/21), respectively, for paired sera. The macrolide-resistance gene A2063G was detected in 20 of the 30 tested PCR-positive specimens (66.7%). Of these 20 A2063G-positive specimens, 13 (65.0%) were positive for the L7/L12 antigen assays. Tne numbers of M. pneumoniae P1 subtypes were as follows: types I (22), IIa(2), IIc(1), and untypable (5). The L7/L12 antigen assays gave positive results for 17 of 21 (81.0%) subtype I, 1 of 2 (50.0%) IIa, and 1 of 1(100%) IIc specimens.

How adolescent Japanese girls arrive at human papilloma virus vaccination: A semistructured interview study.

We examined the human papilloma virus (HPV) vaccination process in adolescent Japanese girls, including protective and obstructive factors to develop and practice enlightenment activities and educational interventions for promoting HPV vaccination to adolescent Japanese girls and their families. We conducted semistructured interviews with 20 adolescent Japanese girls who lived in the wider Tokyo area. To analyze the interview data, we adopted the modified grounded-theory approach. We identified three stages in the vaccination process: first encounter with cervical cancer and HPV vaccine, thoughts about vaccination, and adjustment with parents toward vaccination. The girls "knew" their knowledge and information on cervical cancer and the HPV vaccine from experts, parents, and friends, "considered and discussed" HPV vaccination in their own way or with parents, and "arranged" actual vaccination. This process was influenced by the promoting/obstructive factors in each stage. Healthcare providers should understand the experiences and feelings of adolescent girls who were confronted with HPV vaccination in the context of their vaccination process and conduct enlightenment activities to promote vaccination, keeping the promoting and obstructive factors suggested in this study in mind.

Comparison of clinical efficacy between 3-day combined clavulanate/amoxicillin preparation treatment and 10-day amoxicillin treatment in children with pharyngolaryngitis or tonsillitis.

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 ß-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 ß-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 ß-hemolytic Streptococcus.

[Usefulness of a newly developed immunochromatographic assay kit for the detection of norovirus in stool specimens].

We evaluated the usefulness of ImmunoCatch-Noro (Eiken Chemical Co., Ltd.) (IC-A), a newly developed immunochromatography kit using Au colloid, for the detection of norovirus in stool specimens collected from patients with acute gastroenteritis during the three-year period from 2008-2011. When a total of 316 specimens were tested by RT-PCR and direct sequencing of the PCR products, norovirus was detected in 198 specimens (62.7%), including nine genotypes (GI/2, GI/4, GI/8, GII/1, GII/2, GII/3, GII/4, GII/6 and GII/ 13). The most frequently isolated genotypes were GII/3 (64), GII/2 (59) and GII/4 (58), accounting for about 90% of the positive specimens. As compared to RT-PCR, the sensitivity, specificity and concordance rate of IC-A were 87.4% (173/198), 100% (118/118) and 92.1% (291/316), respectively. Twenty-five positive specimens that were positive by RT-PCR were negative by IC-A, however there were no false-positive results of IC-A. On the other hand, the commercially available immunochromatography kit (IC-B), which was tested for comparison, had a sensitivity, specificity and concordance rate of 59.6% (118/198), 96.6% (114/118) and 73.4% (232/316), respectively, containing 80 false-negative and four false-positive specimens. All of the 118 specimens positive by both IC-B and RT-PCR were also interpreted as positive by IC-A. The detection rates of the predominant genotypes (GII/2, GII/3 and GII/4) by IC-A were 88.1%, 87.5% and 89.7%, respectively. In contrast, those by IC-B were only 32.2%, 67.2% and 81.0%, respectively. These results show that IC-A had adequate sensitivity and cross-reactivity for a wide range of GI and GII genotypes, and also had high specificity. In conclusion, IC-A is a useful rapid-diagnostic kit for the detection of norovirus, however, its current application is limited for stool specimens.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Clinical practice guidelines for the diagnosis and management of otitis media with effusion (OME) in children in Japan - 2022 update.

This is an update of the 2015 Guidelines developed by the Japan Otological Society and Oto-Rhino-Laryngeal Society of Japan defining otitis media with effusion (OME) in children (younger than 12 years old) and describing the disease rate, diagnosis, and method of examination. Recommended therapies that received consensus from the guideline committee were updated in consideration of current therapies used in Japan and based on available evidence. METHOD: Regarding the treatment of OME in children, we developed Clinical Questions (CQs) and retrieved documents on each theme, including the definition, disease state, method of diagnosis, and medical treatment. In the previous guidelines, no retrieval expression was used to designate a period of time for literature retrieval. Conversely, a literature search of publications from March 2014 to May 2019 has been added to the JOS 2015 Guidelines. For publication of the CQs, we developed and assigned strengths to recommendations based on the collected evidence. RESULTS: OME in children was classified into one group lacking the risk of developing chronic or intractable disease and another group at higher risk (e.g., children with Down syndrome, cleft palate), and recommendations for clinical management, including follow-up, is provided. Information regarding management of children with unilateral OME and intractable cases complicated by adhesive otitis media is also provided. CONCLUSION: In clinical management of OME in children, the Japanese Clinical Practice Guidelines recommends management not only of complications of OME itself, such as effusion in the middle ear and pathologic changes in the tympanic membrane, but also pathologic changes in surrounding organs associated with infectious or inflammatory diseases.

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033).

BACKGROUND: This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. METHODS: Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2-6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12-15 months of age. Adverse events (AEs) were collected on Days 1-14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 µg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. RESULTS: Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > -10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI -10.6). CONCLUSION: In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.

Determining Optimal Intervals for In-Person Visits During Video-Based Telemedicine Among Patients With Hypertension: Cluster Randomized Controlled Trial.

BACKGROUND: Introducing telemedicine in outpatient treatment may improve patient satisfaction and convenience. However, the optimal in-person visit interval for video-based telemedicine among patients with hypertension remains unreported in Japan. OBJECTIVE: We determined the optimal in-person visit interval for video-based telemedicine among patients with hypertension. METHODS: This was a cluster randomized controlled noninferiority trial. The target sites were 8 clinics in Japan that had a telemedicine system, and the target patients were individuals with essential hypertension. Among patients receiving video-based telemedicine, those who underwent in-person visits at 6-month intervals were included in the intervention group, and those who underwent in-person visits at 3-month intervals were included in the control group. The follow-up period of the participants was 6 months. The primary end point of the study was the change in systolic blood pressure, and the secondary end points were the rate of treatment continuation after 6 months, patient satisfaction, health economic evaluation, and safety evaluation. RESULTS: Overall, 64 patients were enrolled. Their mean age was 54.5 (SD 10.3) years, and 60.9% (39/64) of patients were male. For the primary end point, the odds ratio for the estimated difference in the change in systolic blood pressure between the 2 groups was 1.18 (90% CI -3.68 to 6.04). Notably, the criteria for noninferiority were met. Patient satisfaction was higher in the intervention group than in the control group. Furthermore, the indirect costs indicated that lost productivity was significantly lesser in the intervention group than in the control group. Moreover, the treatment continuation rate did not differ between the intervention and control groups, and there were no adverse events in either group. CONCLUSIONS: Blood pressure control status and safety did not differ between the intervention and control groups. In-person visits at 6-month intervals may cause a societal cost reduction and improve patient satisfaction during video-based telemedicine. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000040953; https://tinyurl.com/2p8devm9.

Characterization of Influenza A(H1N1)pdm09 Viruses Isolated in the 2018-2019 and 2019-2020 Influenza Seasons in Japan.

The influenza A(H1N1)pdm09 virus that emerged in 2009 causes seasonal epidemic worldwide. The virus acquired several amino acid substitutions that were responsible for antigenic drift until the 2018-2019 influenza season. Viruses possessing mutations in the NA and PA proteins that cause reduced susceptibility to NA inhibitors and baloxavir marboxil, respectively, have been detected after antiviral treatment, albeit infrequently. Here, we analyzed HA, NA, and PA sequences derived from A(H1N1)pdm09 viruses that were isolated during the 2018-2019 and 2019-2020 influenza seasons in Japan. We found that A(H1N1)pdm09 viruses possessing the D187A and Q189E substitutions in HA emerged and dominated during the 2019-2020 season; these substitutions in the antigenic site Sb, a high potency neutralizing antibody-eliciting site for humans, changed the antigenicity of A(H1N1)pdm09 viruses. Furthermore, we found that isolates possessing the N156K substitution, which was predicted to affect the antigenicity of A(H1N1)pdm09 virus at the laboratory level, were detected at a frequency of 1.0% in the 2018-2019 season but 10.1% in the 2019-2020 season. These findings indicate that two kinds of antigenically drifted viruses-N156K and D187A/Q189E viruses-co-circulated during the 2019-2020 influenza season in Japan.

Full genome-based characterization of an Asian G3P[6] human rotavirus strain found in a diarrheic child in Japan: Evidence for porcine-to-human zoonotic transmission.

Human rotavirus strains having the unconventional G3P[6] genotype have been sporadically detected in diarrheic patients in different parts of the world. However, the full genomes of only three human G3P[6] strains from Asian countries (China, Indonesia, and Vietnam) have been sequenced and characterized, and thus the exact origin and evolution of G3P[6] strains in Asia remain to be elucidated. Here, we sequenced and characterized the full genome of a G3P[6] strain (RVA/Human-wt/JPN/SO1199/2020/G3P[6]) found in a stool sample from a 3-month-old infant admitted with acute gastroenteritis in Japan. On full genomic analysis, strain SO1199 was revealed to have a unique Wa-like genogroup configuration: G3-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1. VP6 genotype I5 and NSP1 genotype A8 are commonly found in porcine rotavirus strains. Furthermore, phylogenetic analysis demonstrated that all 11 genes of strain SO1199 were closely related to those of porcine and/or porcine-like human rotaviruses and thus appeared to be of porcine origin. Thus, strain SO1199 was shown to possess a porcine-like genomic backbone and thus is likely to be the result of interspecies transmission of a porcine rotavirus strain. Of note is that all 11 genes of strain SO1199 were phylogenetically located in clusters, distinct from those of the previously identified porcine-like human G3P[6] strains from around the world including Asia, suggesting the occurrence of independent porcine-to-human zoonotic transmission events. To our knowledge, this is the first report on full genome-based characterization of a human G3P[6] strain that has emerged in Japan. Our findings revealed the diversity of unconventional human G3P[6] strains in Asia, and provide important insights into the origin and evolution of G3P[6] strains.

Pharmacotherapy focusing on for the management of otitis media with effusion in children: Systematic review and meta-analysis.

OBJECTIVE: To examine the evidence for treating children with otitis media with effusion with pharmacotherapy. DATA SOURCES: For the systematic review, data were retrieved from PubMed, Cochrane database, and the Japan Medical Abstracts Society Database (1st January 1995 through 31th May 2019). STUDY SELECTION: Articles addressing pharmacotherapy for the management of otitis media with effusion in children were selected in English. DATA EXTRACTION: The database was searched using the keywords "Otitis Media with effusion or secretory otitis media" and the following medical agents: carbocysteine, antihistamines, leukotriene receptor antagonist, and steroid nasal spray. DATA SYNTHESIS: After a critical review of 18 studies, studies addressing steroid nasal spray were eligible for quantitative synthesis. Intranasal steroids for OME showed no benefit with OR 1.155 (95% CI 0.834-1.598) within one month. Conversely, intranasal steroids have effects for OME with OR 1.858 (95% CI 1.240-2.786) for more than one month. CONCLUSIONS: We found evidence of benefit from treatment of OME in children with intranasal steroids and S-carboxymethylcysteine at longer-term follow-up.

Rapid Spread in Japan of Unusual G9P[8] Human Rotavirus Strains Possessing NSP4 Genes of E2 Genotype.

The emergence of unusual G9P[8]-E2 human rotaviruses in the Tokyo metropolitan area, Japan, in 2018 has been reported. During rotavirus strain surveillance in different regions of Japan (Mie, Okayama, and Chiba prefectures), G9P[8]-E2 strains were detected in children with diarrhea from all three prefectures. Here, we characterized the whole genome of seven representative G9P[8]-E2 strains. In the full-genome-based analysis, the seven study strains exhibited a unique genotype configuration with the NSP4 gene of genogroup 2 in a genogroup 1 genomic backbone: G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1. This genotype constellation was shared by the Tokyo G9P[8]-E2 strains. Phylogenetic analysis showed that all 11 genes, except NSP4, of the seven study strains appeared to have originated from co-circulating Wa-like G9P[8]-E1 strains. In contrast, NSP4 appeared to have originated from the co-circulating DS-1-like G2P[4]-E2 strains. Thus, G9P[8]-E2 strains appear to be derived through reassortment between G9P[8]-E1 and G2P[4]-E2 strains in Japan. Notably, the seven study G9P[8]-E2 strains and Tokyo G9P[8]-E2 strains were revealed to have 11-segment genomes almost indistinguishable from one another in their sequences (99.3-100%), indicating all these G9P[8]-E2 strains had a common origin. To our knowledge, this is the first description of the rapid spread of G9P[8]-E2 strains across a country.

Perceptions and Attitudes Toward Telemedicine by Clinicians and Patients in Japan During the COVID-19 Pandemic.

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. In Japan, the spread of COVID-19 was recognized and a state of emergency declared in April 2020. In response, public health interventions, such as discouraging people from leaving their homes unnecessarily, were enacted across the country. Under these circumstances, telemedicine has received a great deal of social attention, and it has become necessary to identify the perceptions of and attitudes toward telemedicine by clinicians and patients and to clarify the problems and advantages. Materials and Methods: Ten clinicians and 10 family members (if the patient was pediatric or elderly, a caregiver was included) were invited to participate in individual private interviews in 2020. All interviews were conducted from October to December 2020 using a semistructured interview guide. All transcripts were coded using thematic content analysis. Results: Four categories from clinicians and five from patients were identified as perceptions of and attitudes toward telemedicine. Both evaluated the usefulness and convenience of telemedicine in the same manner, but there was a large gap in the content under the safety and problem categories. Discussion: It is necessary to disseminate information about the communication techniques unique to telemedicine to doctors and to improve the "operation and introduction" and "communication environment and device settings" when starting or using telemedicine for all patients. Conclusions: The perceptions and attitudes identified in this study will be useful for establishing and developing a telemedicine system in Japan.

Effects of maoto (ma-huang-tang) on host lipid mediator and transcriptome signature in influenza virus infection.

Maoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. In this study, we evaluated the effects of maoto as an herbal multi-compound medicine on host responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus [A/PR/8/34 (H1N1)], maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host's inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza.

Investigation of pneumonia-causing pathogenic organisms in children and the usefulness of tebipenem pivoxil for their treatment.

We investigated the usefulness of the novel oral carbapenem antibiotic tebipenem pivoxil (TBPM-PI) for treating bacterial pneumonia in children. Sputum and nasopharyngeal swabs were collected simultaneously, and causative organisms were identified by conventional bacterial culture together with exhaustive bacterial and viral identification by real-time polymerase chain reaction (PCR). The subjects were eight patients diagnosed with mild or moderate pneumonia at Sotobo Children's Clinic Outpatient Department between October 2006 and June 2007. TBPM-PI was administered at the recommended clinical dose of 4 mg/kg b.i.d. to five patients and at a high dose of 6 mg/kg b.i.d. to three patients. Sputum was collected from all patients, and 11 strains were detected from washed sputum culture. Causative organisms were mainly Streptococcus pneumoniae (3 strains) and Haemophilus influenzae (6 strains), and nasopharyngeal swabs showed the same organisms as coughed-up sputum. Real-time PCR for individual viruses and Mycoplasma pneumoniae identified four cases of only bacterial infection, one case of M. pneumoniae coinfection, two cases of viral coinfection, and one case of both viral and M. pneumoniae coinfection. The clinical results indicated efficacy in all patients, and causative organisms were 100% eliminated. In the four patients with only bacterial infection, the average fever of 38.9 degrees C at the start of treatment normalized the following day, showing excellent efficacy. No clinically problematic adverse events occurred, and compliance was good. We consider that these cases provide valuable insights into the identity of pathogenic organisms of pneumonia in children and the possible role of TBPM-PI in outpatient treatment.