Viral loads of parainfluenza virus type 3 and severity of respiratory diseases in children.

BACKGROUND: Parainfluenza virus type 3 (PIV-3) is one of the common pathogens for respiratory infections in children. Whether viral load of PIV-3 is associated with severity of respiratory diseases in children is not yet known. Our aim was to determine significance of PIV-3 viral load among infected children. METHODS: We conducted a single-center, retrospective study at Tokyo Metropolitan. Children's Medical Center, Japan, from June to August 2021. Hospitalized children were screened with a posterior nasal swab for multiplex PCR, and viral load was subsequently measured from remained samples by real-time PCR. Demographic data were collected from digital charts. PIV-3 positive patients were categorized into mild group with no oxygen demand, moderate group with low-flow oxygen demand and severe group with high-flow nasal cannula oxygen or non-invasive positive pressure ventilation or mechanical ventilation. Viral loads were compared among mild, moderate and severe groups. RESULTS: 151 patients were positive for PIV-3. We found no statistically significant association among PIV-3 viral load and severity of respiratory diseases (p = 0.35), and no statistically significant association between severity of illness and co-detection of other viruses. In each severity group, relatively high viral load per posterior nasal swab was observed at the time of testing. CONCLUSION: Among PIV-3 patients, we could not find statistically significant between viral load and their severity, therefore we could not conclude that viral load is a good surrogate marker for clinical severity of PIV-3.

Post coronavirus disease 2019 condition in children at a children's hospital in Japan.

BACKGROUND: Acute coronavirus disease 2019 (COVID-19) is associated with chronic symptoms. These have been termed the "post COVID-19 condition." The data on this condition in children are still limited. We therefore aimed to elucidate the characteristics of this post COVID-19 condition. METHODS: Children referred to a long COVID-19 clinic were included at Tokyo Metropolitan Children's Medical Center between October 2021 and July 2022. Children with another diagnosis and those who failed to meet criteria for post COVID-19 condition were excluded. Demographic and clinical data were collected retrospectively. RESULTS: Of 33 referrals, nine were excluded, and 24 fulfilled the criteria for post COVID-19 condition. The median age and percentage of girls were 12.5 (IQR: 11-13) years and 29.2%, respectively. All the patients had mild, acute COVID-19. Dysgeusia and brain fog was observed more frequently during the Delta and Omicron variant periods, respectively. School absenteeism >4 weeks was observed in 41.6% of the patients. Common symptoms included malaise, headache, dysgeusia, and dysosmia. The median duration of post COVID-19 condition was 4.5 (IQR: 2.8-5.2) months. Pain management and counseling using the pacing approach were the most commonly offered treatments. Symptom resolution and improvement was observed in 29.2% and 54.2% of the patients, respectively. CONCLUSIONS: One third of the patients referred for long COVID did not fit the definition of the post COVID-19 condition. After a median follow up of 4.5 months, the majority of the cases resolved or improved.

Epidemiology of group B streptococcal disease in infants younger than 1 year in Japan: a nationwide surveillance study 2016-2020.

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

Relationship between intrapartum antibiotic prophylaxis and group B streptococcal colonization dynamics in Japanese mother-neonate pairs.

INTRODUCTION: In Japan, universal screening for group B streptococcal (GBS) colonization in pregnant women and intrapartum antibiotic prophylaxis (IAP) are recommended to prevent neonatal GBS infection. However, the dynamics of GBS colonization in Japanese mother/neonate pairs have not been adequately studied. METHODS: A prospective cohort study was conducted from July 2018 to March 2019. Rectovaginal samples were collected from pregnant women (33-37 gestation weeks) once. In neonates, nasopharyngeal and rectal samples were collected at three time points: after birth, 1 week after birth, and 1 month after birth. All samples were analyzed for GBS using real-time PCR testing and culture methods. Capsular typing was performed for all GBS isolates and GBS-positive samples using real-time PCR testing. RESULTS: The overall maternal and neonatal GBS-positivity rates were 22.7% (57/251) and 8.8% (22/251), respectively. IAP for GBS-positive mothers (96.5%) was highly administered. Eleven (19.3%) neonates born to GBS-positive mothers were GBS-positive, which was significantly higher than the 11 (5.7%) neonates born to GBS-negative mothers. The rate of GBS-positivity in neonates increased with an increased number of GBS colonies in mothers. More neonates were GBS-positive 1 month after birth than 1 week after birth, and there was a higher rate of GBS-positive rectal swabs than nasopharyngeal swabs. Capsular types of GBS that were isolated from each mother and neonate pair were the same, namely, Ib, III, V, and VI. CONCLUSIONS: These findings indicate that the efficacy of IAP in preventing GBS transmission to neonates might be limited to within a few weeks after birth.

Isolation of multidrug-resistant Haemophilus influenzae harbouring multiple exogenous genes from a patient diagnosed with acute sinusitis.

In paediatric patients, ß-lactams and macrolides are widely used to treat acute otitis media and sinusitis, which are often caused by either Streptococcus pneumoniae or Haemophilus influenzae. However, resistant isolates have emerged and are becoming more prevalent. H. influenzae generally acquires antimicrobial resistance by mutation or by expression of ß-lactamase. In this study, we isolated H. influenzae from a paediatric patient diagnosed with acute sinusitis. This strain harboured multiple exogenous resistance genes: blaTEM-1, mef(A) and tet(M). DNA sequencing suggested that both mef(A) and tet(M) had been transferred from S. pneumoniae or another Streptococcus. This typical outpatient had not been exposed to excessive levels of antibiotics and had no underlying diseases, strongly suggesting that this type of resistant isolate could become more prevalent.

Group B Streptococcal Disease in Infants in Japan.

This review describes the epidemiology of group B Streptococcus (GBS) infection in infants in Japan and discusses unresolved issues and future perspectives. Guidelines for the prevention of vertical transmission in Japan were implemented in 2008. The incidence of early-onset disease in Japan has remained stable at approximately 0.10/1000 livebirths or less, which is lower than in Europe and North America. The incidence of late-onset disease is also low, but has increased over the last decade, with an estimated 0.29/1000 livebirths in 2020. National surveillance studies in 2011-2015 and 2016-2020 reported case fatality rates of 4.5% and 6.5% for early-onset disease and 4.4% and 3.0% for late-onset disease, respectively. Sequelae of neurodevelopmental impairments were considerably associated with infants who developed meningitis. Predominant neonatal invasive strains have remained in the following order of serotypes: III, Ia, Ib and V, for the past 30 years. Conversely, the predominant serotypes of maternal colonization strains markedly changed from serotypes VI and VIII around 2000 to serotypes Ia, Ib, III and V over the last decade. Recurrence rates among infants < 1-year-old were estimated to be 2.8%-3.7%, and preterm birth and antenatal maternal GBS colonization were risk factors for recurrence. Several unresolved issues remain. First, the exact disease burden remains unclear because Japan does not have a nationwide system to register all infants affected by invasive GBS disease, and even population-based surveys are limited to up to 10 of the 47 prefectures. Others include low adherence to prevention guidelines of vertical transmission and the development of strategies based on Japanese epidemiological evidence rather than the Center for Disease Control and Prevention guidelines. The effectiveness of introducing maternal vaccines in Japan, where the disease incidence is low, needs to be carefully verified.

Joint Fluid Cell Count in Acute Bacterial Arthritis Patients Proven Positive Culture in Children.

BACKGROUND: Acute bacterial arthritis (ABA) is a serious, pediatric infection that can result in motor comorbidities. Normally, a joint fluid white blood cell (WBC) count of 50,000 or more cells/mm 3 is used to make a presumptive diagnosis of ABA. This study evaluated the utility of the joint fluid WBC count for diagnosing pediatric ABA confirmed by a positive culture result. METHODS: Patients with ABA between March 2010 and March 2023 at Tokyo Metropolitan Children's Medical Center were included. ABA was confirmed by positive joint fluid culture results for a pathogenic organism. Patients with negative results and those without a joint fluid WBC count were excluded. Electronic medical records were retrospectively reviewed for demographic data, timing of arthrocentesis, culture results and the joint fluid WBC count. RESULTS: Ninety-five patients with ABA were identified; of these, 22 were included. The median age was 5 years [interquartile range (IQR): 2-10 years]. Males comprised 55% of the population. The median joint fluid WBC count was 19,575 (IQR: 6806-47,388) cells/mm 3 , and 23% of the patients had 50,000 cells/mm 3 or more. The median time from symptom onset to arthrocentesis was 3 days (IQR: 2-5 days). The isolated organisms were methicillin-susceptible Staphylococcus aureus (50%), methicillin-resistant S. aureus (9%), Streptococcus pyogenes (27%), Streptococcus pneumoniae (5%), Klebsiella pneumoniae (5%) and Salmonella spp. (5%). CONCLUSIONS: Most of the patients with ABA confirmed by positive results of a joint fluid culture had a joint fluid WBC count of less than 50,000 cells/mm 3 .

Impact of Introducing a Multiplex Polymerase Chain Reaction Blood Culture Panel on Anti-Methicillin-Resistant Staphylococcus aureus (MRSA) and Carbapenem Antimicrobial Agents in a Children's Hospital.

BACKGROUND: With the advent of multiplex polymerase chain reaction (PCR) using samples from a positive blood culture, the time required to identify a pathogen has significantly shortened to a few hours. It can help us select appropriate antimicrobial agents more quickly. The present study aimed to assess the impact of using a multiplex PCR blood culture panel on the appropriate administration of antimicrobial agents. METHODS: Patients aged <16 years with culture-confirmed bacteremia at Tokyo Metropolitan Children's Medical Center were enrolled. A pre-intervention period (period I: December 2016 to December 2018) and a post-intervention period with multiplex PCR use for the confirmation of positive blood cultures (period II: December 2019 to December 2021) were compared for their effect on the use of antimicrobial agents for gram-positive cocci (GPC) and gram-negative rod (GNR) bacteremia. Data on patient background, blood culture results, and antimicrobial use were retrospectively collected from electronic medical records. RESULTS: Periods I and II had 174 and 154 patients, respectively. The median age at periods I and II was 14 (IQR 2-82) months and 12 (IQR 1-78) months, respectively. GPC bacteremia during periods I and II occurred in 140 and 115 patients, respectively. GNR during periods I and II occurred in 34 and 39 patients, respectively. Neither the vancomycin-resistance genes A/B nor the carbapenem-resistance gene were detected. The use of antimicrobial agents against anti-methicillin-resistant Staphylococcus aureus (MRSA) for GPC bacteremia decreased from 103/140 cases (73%) in period I to 56/115 cases (49%) in period II (p=0.047). The use of carbapenems for GNR bacteremia did not change significantly, at 23/34 (68%) in period I and 34/39 (87%) in period II (p=0.47). CONCLUSION: Introducing multiplex PCR for pediatric bacteremia decreased the use of anti-MRSA antimicrobial agents but not of carbapenems.

Change in the Acceptance of Telemedicine Use Among Older Patients with Knee Osteoarthritis During the Coronavirus Disease 2019 Pandemic.

Background: Hospital-related coronavirus disease 2019 (COVID-19) infection is of utmost concern among patients and health care workers. Expanding the use of telemedicine may be required in daily outpatient practice; however, the acceptance of telemedicine use is still low, especially among older patients. In an orthopedic practice, no studies have investigated potential factors that can contribute to changes in the acceptance of using telemedicine. Focusing on older outpatients with knee osteoarthritis (KOA), we hypothesized that a drastic surge in the number of patients with COVID-19 could trigger changes in attitudes regarding the acceptance of telemedicine use. Methods: A baseline survey was conducted after the first wave of the COVID-19 pandemic in Japan to obtain information on the willingness to use telemedicine among patients aged ≥70 years who regularly consulted an orthopedic surgeon for KOA. A follow-up survey was subsequently conducted during the third wave of the pandemic period to assess changes in the acceptance of telemedicine use in response to the rapidly increasing number of patients with COVID-19. We compared the difference in acceptance of telemedicine use and knee pain status between the baseline and follow-up surveys. Results: In the baseline survey, 11 of 43 patients (25.6%) responded that they would be willing to use telemedicine. In the follow-up survey, patients' acceptance of telemedicine did not change, with the exact same number and percentage of patients who were willing to use telemedicine as in the baseline survey, despite that ∼20% of patients reported improvement in their knee pain status. Discussion: Our findings indicate that older outpatients with KOA did not change their willingness to accept use of telemedicine, even with a drastically increased risk of hospital-related transmission of a potentially fatal infectious disease when visiting a hospital. The acceptance of telemedicine use among older patients might not be less sensitive to external environmental factors but instead might be more sensitive to patients' personal factors, such as anxiety for information technology and resistance to changes in their lifestyle.

Influenza vaccine effectiveness against influenza A in children based on the results of various rapid influenza tests in the 2018/19 season.

During influenza epidemics, Japanese clinicians routinely conduct rapid influenza diagnostic tests (RIDTs) in patients with influenza-like illness, and patients with positive test results are treated with anti-influenza drugs within 48 h after the onset of illness. We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children (6 months-15 years old, N = 4243), using a test-negative case-control design based on the results of RIDTs in the 2018/19 season. The VE against influenza A(H1N1)pdm and A(H3N2) was analyzed separately using an RIDT kit specifically for detecting A(H1N1)pdm09. The adjusted VE against combined influenza A (H1N1pdm and H3N2) and against A(H1N1)pdm09 was 39% (95% confidence interval [CI], 30%-46%) and 74% (95% CI, 39%-89%), respectively. By contrast, the VE against non-A(H1N1)pdm09 influenza A (presumed to be H3N2) was very low at 7%. The adjusted VE for preventing hospitalization was 56% (95% CI, 16%-77%) against influenza A. The VE against A(H1N1)pdm09 was consistently high in our studies. By contrast, the VE against A(H3N2) was low not only in adults but also in children in the 2018/19 season.

Willingness of Patients With Knee Osteoarthritis to Use Telemedicine Amid Sars-CoV-2 Outbreak.

BACKGROUND: There is no report yet on the application of telemedicine in orthopedic practice in Japan. With a focus on patients with KOA, we investigated the willingness of patients to use telemedicine by assessing factors such as the patient's age, smartphone possession, hospital visiting time, and severity of KOA. METHODS: Data of patients who regularly consulted orthopedic surgeons at our institutions from April 2020 to June 2020 were retrospectively analyzed using an electronic medical database. The patients were diagnosed with KOA according to clinical and radiological findings, according to the Kellgren-Lawrence (KL) classification. included were patients with KOA with KL classification above grade 2. All patients were asked: 1) whether they were willing to use telemedicine (Yes or No), 2) the reason why they answered Yes, 3) the reason why they answered No, 4) if they possessed a smartphone, 5) their numeric rating scale for pain at their last outpatient visit after the Sars-CoV-2 epidemic emerged, and 6) the time required for visiting hospital from their house. Patients were stratified into 2 groups depending on whether they answered Yes (Group Y) or No (group N). Comparisons between the groups concerning smartphone possession, NRS pain, hospital visiting times, and distribution of KL grade were made. RESULTS: Only 36.7% of the patients with KOA said they were willing to use telemedicine. The average age of group Y was significantly younger than that of group N (67.9 ± 9.1 vs 73.1 ± 8.0, P = 0.0026) and the cutoff age was 70.0 years. In addition, the rate of smartphone possession was significantly higher in group Y than in group N (82.5% vs 34.5%, P < 0.001). Hospital visit times and the severity of KOA did not differ between the groups. CONCLUSION: Age is a barrier to the adoption of telemedicine.

First outbreak of Haemophilus influenzae clone ST422 with low susceptibility to quinolones in paediatric patients in Japan.

Introduction. Recently, a Haemophilus influenzae clone with low susceptibility to quinolones emerged in paediatric patients in Japan. Isolates of this clone survived for a long time when exposed to the therapeutic concentration of quinolones, despite being classified as 'susceptible' under the criteria of the Clinical and Laboratory Standards Institute. In the present study, we report the first outbreak of this clone in paediatric patients in 2018.Aim. Our aim was to characterise the first outbreak of an H. influenzae clone with low susceptibility to quinolones.Methodology. All H. influenzae isolates (n=62), collected at a Japanese teaching hospital in 2018, were characterized by both antimicrobial susceptibility tests and multilocus sequence typing. In addition, the similarity in genetic backgrounds was analysed by PFGE.Results. Among all the isolates (n=62), quinolone low-susceptible isolates accounted for 19.4 % (n=12). Seven out of 12 isolates were identified as sequence type 422 (ST422) and showed more than 90 % similarity to each other by PFGE analysis. All ST422 isolates exhibited identical amino acid substitutions in both quinolone resistance-determining regions in GyrA and ParC. In addition, all these isolates were from paediatric patients who had been referred by different primary care clinics and had no relationship to each other.Conclusion. In this study, we describe an outbreak of a quinolone low-susceptible ST422 clone in paediatric patients in Japan. Because ST422 isolates have already been reported in at least five other countries, it has the potential to spread worldwide.

Emergence of Haemophilus influenzae with low susceptibility to quinolones and persistence in tosufloxacin treatment.

BACKGROUND: The use of non-ß-lactam agents has increased in Japan due to the prevalence of ß-lactam-resistant pathogens. This study aimed to clarify the recent trend of antimicrobial susceptibility and molecular epidemiological features in Haemophilus influenzae. METHODS: Fifty-seven Haemophilus influenzae isolated from a Japanese teaching hospital in 2017 were characterised, and the data were compared with those of a previous study. The MICs were determined using the broth dilution method. Genetic backgrounds were compared by multilocus sequence typing. The bactericidal activity of tosufloxacin at, or near, the therapeutic Cmax was determined in vitro, with susceptible isolates and quinolone low-susceptible isolates by time-kill assay. RESULTS: The results of the susceptibility tests showed that >90% of isolates were susceptible to cephalosporins and carbapenems, whereas ampicillin-susceptible and clarithromycin-susceptible isolates decreased. Regarding quinolones, low-susceptible isolates were noted in 2017, although all isolates were judged as susceptible. All low-susceptible isolates had an amino acid substitution in GyrA, and two isolates had an additional substitution in ParC. These isolates had different genetic backgrounds. Furthermore, the time-kill kinetic assay using the Cmax of tosufloxacin indicated that the low-susceptible isolates could persist for at least 8hours. CONCLUSIONS: This study revealed that Haemophilus influenzae has demonstrated multidrug low-susceptibility in recent years. The low-susceptible isolates had genetic diversity, meaning that resistance occurred independently.

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013-18.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses. METHODS: VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed. RESULTS: In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505-0.621], 0.550 [95% CI, 0.516-0.586]), 0.549 [95% CI, 0.517-0.583], and 1.014 [95% CI, 0.907-1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1-12 years, especially among those aged 1-5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A. CONCLUSIONS: Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.

Inactivated influenza vaccine effectiveness and an analysis of repeated vaccination for children during the 2016/17 season.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age during the 2016/17 season. In addition, we estimated the impact of repeated vaccination in children on VE. METHODS: Our study for VEs in preventing influenza and admission due to influenza were conducted according to a test-negative case-control design (TNCC) based on influenza rapid diagnostic test results. We also analyzed the VE by vaccine status in the current and previous seasons for the impact of repeated vaccination. RESULTS: During the 2016/17 season, the quadrivalent IIV was used in Japan. The adjusted VE in preventing influenza illness was 38% (95% CI, 29-46) against influenza A and 39% (95% CI, 18-54) against influenza B. Infants showed no significant VE. The VE in preventing hospitalization was not demonstrated. For the analysis of repeated vaccination, the vaccine was effective only when immunization occurred in the current season. The children who were immunized in two consecutive seasons were more likely to develop influenza compared to those immunized in the current season only (odds ratio, 1.58 [95% CI, 1.05-2.38], adjusted odds ratio, 1.53 [95% CI, 0.99-2.35]). However, the odds ratio of repeated vaccination was not significant when the analysis excluded those who developed influenza in the previous season. CONCLUSIONS: VE in children in the 2016/17 season was similar to values previously reported. Repeated vaccination interfered with the VE against any influenza infection in the 2016/17 season. The results of our study suggest that decreased VE by repeat vaccination phenomenon was associated with immunity by influenza infection in the previous season. However, the influenza vaccine should be recommended every season for children.