Cost-effectiveness analysis of 20-valent pneumococcal conjugate vaccine for routine pediatric vaccination programs in Japan.

BACKGROUND: The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. METHODS: A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. RESULTS: PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). CONCLUSIONS: As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.

Invasive pneumococcal disease caused by non-vaccine Streptococcus pneumoniae serotype 24B in an immunocompetent child.

Invasive pneumococcal disease typically occurs in immunocompromised patients, although some vaccine strains of Streptococcus pneumoniae have been reported to cause invasive pneumococcal disease in immunocompetent vaccine recipients. In this study, we presented a case of a 16-month-old immunocompetent patient with lung abscess and empyema caused by nonvaccine S. pneumoniae serotype 24B. A consolidation occupying the right upper lobe in the chest computed tomography results, as observed at presentation, changed to thick-walled cavitary lesions at the end of a month of intravenous antibiotics, and antibiotics were continued for a total of two months. To the best of our knowledge this is the first report that focuses on the risk of invasive pneumococcal disease caused by S. pneumoniae serotype 24B in an immunocompetent child.

Catheter-associated urinary tract infection and urinary tract abnormalities in young children: A retrospective study.

INTRODUCTION: Studies investigating the role of urinary tract abnormalities in the development of catheter-associated urinary tract infections (CAUTI) in young children are limited. Thus, in the present study, we aimed to determine whether there is an association between CAUTI and urinary tract abnormalities. METHODS: We performed abdominal imaging studies on all patients aged <6 years with CAUTI admitted to the pediatric intensive care units (PICU) and high care unit (HCU) at Keio university or Fukuoka Children's Hospital from April 1, 2018 to July 31, 2022. Among 40 children who developed CAUTI, 13 (33 %) had abnormal urogenital images. Further, two case-control studies were conducted before and after propensity score matching, and the groups were compared using multivariable logistic regression models to analyze the effects of various factors on CAUTI development. RESULTS: In the multivariate logistic regression models, abnormal urogenital images (OR 5.30 [95 % CI, 2.40-11.7] and OR 3.44 [95 % CI, 1.16-9.93]) and duration of catheterization >10 days (OR 2.76 [95 % CI, 1.28-5.96] and OR 3.44 [95 % CI, 1.16-9.93]) were found to be significantly associated with development of CAUTI, both before (39 cases, 459 controls) and after propensity score matching (36 cases, 72 controls). Further, CAUTI in young children in the PICU or HCU was significantly associated with imaging abnormalities of the urinary tract. CONCLUSIONS: These results suggest that not only the presence of catheters, but also urinary tract malformations may contribute to the development of CAUTI in young children.

Pneumocystis jirovecii pneumonia after CD4+ T-cell recovery subsequent to CD19-targeted chimeric antigen receptor T-cell therapy: A case report and brief review of literature.

BACKGROUND: CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim-sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T-cell count is >200/µL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/µL after CAR-T cell therapy. CASE: A 14-year-old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B-cell acute lymphoblastic leukemia (B-ALL). Twenty-one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19-targeted CAR-T cell therapy for the relapse. After CAR-T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR-T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B-cell aplasia persisted. Ten months after CAR-T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated. CONCLUSION: The patient in the present case developed PJP despite a CD4+ T-cell count of >200/µL after CAR-T cell therapy, probably because of inadequate CD4+ T-cell activation caused by B-cell depletion after CAR-T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR-T cell therapy according to each case, as well as the CD4+ T-cell count.

Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2022.

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.

Effectiveness of inactivated influenza and COVID-19 vaccines in hospitalized children in 2022/23 season in Japan - The first season of co-circulation of influenza and COVID-19.

We have analyzed the inactivated vaccine effectiveness (VE)for preventing influenza hospitalization by test-negative design in the 2022/23 season. This is the first season of co-circulation of influenza and COVID-19, and a unique period because all inpatients received COVID-19 screening. Among 536 children hospitalized with fever, none were positive for both influenza and SARS-CoV-2. The adjusted VE for preventing influenza A for all children, the 6-12-year-old group, and those with underlying diseases was 34 % (95 ％CI, -16 %-61 %, n = 474), 76 % (95 ％ CI, 21 %-92 %, n = 81), and 92 % (95 ％ CI, 30 %-99 %, n = 86), respectively. Only 1 out of 35 hospitalized cases with COVID-19, and 42 out of 429 controls, had been immunized with COVID-19 vaccine. This is the first report showing influenza VE by age group in children in this limited season. We still recommend the inactivated influenza vaccine for children based on the significant VE in subgroup analysis.

Distinct association between chronic Epstein-Barr virus infection and T cell compartments from pediatric heart, kidney, and liver transplant recipients.

Chronic Epstein-Barr virus (EBV) infection after pediatric organ transplantation (Tx) accounts for significant morbidity and mortality. The risk of complications, such as posttransplant lymphoproliferative disorders, in high viral load (HVL) carriers is the highest in heart Tx recipients. However, the immunologic signatures of such a risk have been insufficiently defined. Here, we assessed the phenotypic, functional, and transcriptomic profiles of peripheral blood CD8+/CD4+ T cells, including EBV-specific T cells, in 77 pediatric heart, kidney, and liver Tx recipients and established the relationship between memory differentiation and progression toward exhaustion. Unlike kidney and liver HVL carriers, heart HVL carriers displayed distinct CD8+ T cells with (1) up-regulation of interleukin-21R, (2) decreased naive phenotype and altered memory differentiation, (3) accumulation of terminally exhausted (TEX PD-1+T-bet-Eomes+) and decrease of functional precursors of exhausted (TPEX PD-1intT-bet+) effector subsets, and (4) transcriptomic signatures supporting the phenotypic changes. In addition, CD4+ T cells from heart HVL carriers displayed similar changes in naive and memory subsets, elevated Th1 follicular helper cells, and plasma interleukin-21, suggesting an alternative inflammatory mechanism that governs T cell responses in heart Tx recipients. These results may explain the different incidences of EBV complications and may help improve the risk stratification and clinical management of different types of Tx recipients.

Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Neonates and Listeria monocytogenes in Young Children with Bacterial Meningitis in Japan.

Nationwide surveillance of pediatric bacterial meningitis in Japan from 2019 to 2021 revealed two uncommon situations not covered by the recommended empiric treatment that were not rare in Japan, namely, extended-spectrum ß-lactamase-producing-producing Escherichia coli in neonates and Listeria monocytogenes in children older than 1 month.

Trends in effectiveness of inactivated influenza vaccine in children by age groups in seven seasons immediately before the COVID-19 era.

BACKGROUND: We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups. METHODS: The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons. RESULTS: A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported. CONCLUSIONS: This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.

High success rate of nocturnal enuresis treatment during the stay-home period for COVID-19.

OBJECTIVES: To clarify whether enuresis treatment was more effective during the stay-home period for the coronavirus disease 2019 pandemic, when restrictions on activities enabled patients to concentrate on treatment. METHODS: We performed a retrospective, nonrandomized cohort study for monosymptomatic enuresis during the coronavirus disease 2019 pandemic (March-June 2020) and a 2-year comparator period (March-June 2018 and March-June 2019). Primary outcome was treatment response, defined as a change in the number of wet nights per week within 6 months following enrollment. The time-dependent occurrence of treatment response was evaluated with the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression model was used to identify risk factors for treatment response. The range of appropriate sample sizes for this primary outcome was 39-48. RESULTS: Of our 41 enrolled patients, 28 (68%) were male and mean age was 8.8 years. The complete response rate was 73% during the coronavirus disease 2019 pandemic period and 27% during the comparator period. Log-rank tests showed a higher cumulative incidence of complete response in the pandemic period (P = 0.020). Cox regression analysis identified treatment during the coronavirus disease 2019 pandemic (hazard ratio 2.533; 95% confidence interval 1.069-6.006) and dinner before 19:00 (hazard ratio 4.184; 95% confidence interval 1.56-11.252) as significantly associated with treatment response. CONCLUSIONS: The rate of enuresis treatment response was uncommonly high during the stay-home period for the coronavirus disease 2019 pandemic. Restrictions on daily life may provide opportunities to concentrate on treatments for chronic illnesses, leading to more success.

Digestive Decolonization of Colorectal Carriage of Vancomycin-resistant Enterococcus faecium in a Japanese Adult.

Patients with vancomycin-resistant Enterococcus (VRE) colonization should be managed in an isolation room with contact precautions. We herein report a patient whose colorectal carriage of VRE was successfully decolonized using concomitant bowel irrigation with polyethylene glycol, probiotics, and oral antimicrobials, linezolid and orally-administered daptomycin, for release from isolation and contact precautions. We therefore would like to suggest a potential strategy for managing patients with VRE colonization.

The first case report of pediatric acute appendicitis caused by "Candidatus Actinobaculum timonae".

A 14-year-old boy presented to the hospital with pain in the right lower abdomen. His condition was diagnosed as acute appendicitis. An emergency operation was performed, and histopathological examination revealed an actinomycete-related organism in the excised appendicitis specimen. On 16S rRNA gene sequence analysis, "Candidatus Actinobaculum timonae" was identified, which is the first known case in a pediatric patient.

Risk factors in pediatric hospitalization for influenza A and B during the seven seasons immediately before the COVID-19 era in Japan.

INTRODUCTION: The risk factors in pediatric influenza immediately before the COVID-19 era are not well understood. This study aims to evaluate the risk factors for hospitalization in pediatric influenza A and B for the recent seasons. METHODS: Children with a fever of ≥38 °C and laboratory-confirmed influenza at 20 hospitals in outpatient settings in Japan in the 2013/14 to 2019/20 seasons were retrospectively reviewed. Possible risk factors, including gender, age, comorbidities, nursery school or kindergarten attendance, earlier diagnosis, no immunization, lower regional temperature, earlier season, and period of onset, were evaluated using binary logistic regression methods. RESULTS: A total of 13,040 (type A, 8861; B, 4179) children were evaluated. Significant risk factors (p < 0.05) in multivariate analyses were young age, lower regional temperature, earlier season, respiratory illness (adjusted odds ratio [aOR]:2.76, 95% confidence interval [CI]:1.84-4.13), abnormal behavior and/or unusual speech (aOR:2.78, 95% CI:1.61-4.80), and seizures at onset (aOR:16.8, 95% CI:12.1-23.3) for influenza A; and young age, lower regional temperature, respiratory illness (aOR:1.99, 95% CI:1.00-3.95), history of febrile seizures (aOR:1.73, 95% CI:1.01-2.99), and seizures at onset (aOR:9.74, 95% CI:5.44-17.4) for influenza B. CONCLUSIONS: In addition to previously known factors, including young age, seizures, and respiratory illness, abnormal behavior and/or unusual speech and lower regional temperature are new factors. Negative immunization status was not a risk factor for hospitalization. A better understanding of risk factors may help improve the determination of indications for hospitalization during the future co-circulation of influenza and COVID-19.

Lack of persisting antibody in a post-transplant patient after vaccine-strain varicella.

BACKGROUND: LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post-transplant, children without severe immunosuppression can generate anti-varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. CLINICAL PROGRESS: A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine-type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. CONCLUSIONS: This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine-type strain, repeated vaccinations may be necessary for post-transplant patients who develop varicella.

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.

Comparison of 0.5% chlorhexidine gluconate alcohol with 10% povidone-iodine for skin disinfection in children to prevent blood culture contamination.

INTRODUCTION: Various disinfectants, such as povidone iodine (PVI)1, alcohol preparations, and chlorhexidine gluconate ethanol (CHG-ALC), are used for disinfection prior to blood sampling for culture. METHODS: This retrospective cohort study compared the usefulness and effectiveness of CHG-ALC and PVI in pediatric venipuncture. We applied 0.5% w/v CHG-ALC or 10% PVI as an antiseptic for phlebotomies on pediatric outpatients and inpatients with suspected bacterial infection between November 2017 and April 2019. We conducted logistic regression analysis to define the differences associated with the choice of disinfectant, collection site, and the staff member collecting the blood sample (explanatory variables) and the presence of contamination (objective variable). Based on these results, we performed propensity score matching. RESULTS: The total number of specimens was 1460. The propensity score matching indicated that CHG-ALC reduced the incidence of blood culture contamination more effectively than PVI (0.4%, 2/479 cultures versus 2.5%, 12/479 cultures; relative risk, 0.163 [95% confidence interval, 0.036 to 0.733]; P = 0.012). There were no differences in the contamination rates between cultures of blood drawn from a vascular catheter and those of blood obtained percutaneously. Higher contamination rates were found when junior residents performed the venipuncture. CONCLUSIONS: Compared with PVI, CHG-ALC dries rapidly with no pigmentation and has a long-lasting antiseptic effect. Overall, CHG-ALC skin preparations were more efficacious than the PVI preparations for blood sampling in children.