Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters.

Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. While attention has been on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (p<0.05, in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (p<0.05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.

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.

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.

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.

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.

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.

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.

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.

Recent trends in pediatric bacterial meningitis in Japan, 2016-2018 - S. agalactiae has been the most common pathogen.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan. The overall incidence of bacterial meningitis decreased thereafter. Streptococcus agalactiae has become the main organism. OBJECTIVES: The purpose of the present study was to investigate the incidence rate per 1000 admissions of bacterial meningitis and the change in causative organisms in subsequent years. METHODS: A cross-sectional, multicenter, non-interventional retrospective study regarding pediatric bacterial meningitis was conducted in Japan in 2019. We analyzed the epidemiological and clinical data for 2016-2018, and compared the information obtained in our previous nationwide survey database. We also investigated the risk factors for disease outcome. RESULTS: In the 2016-2018 surveys, 197 patients from 153 hospitals from all prefectures were evaluated. S. agalactiae (0-3 months, 39%), Streptococcus pneumoniae (2-112 months, 20%), and E. coli (0-136 months, 13%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.00 to 1.68 in 2000-2010 to 0.38 in 2013-2015, bu remained stable thereafter (0.35-0.40 in 2016-2018). Only one case with Neisseria meningitidis was reported. Nine cases with death were reported, including four cases with S. agalactiae. Risk factors for death and sequelae were consciousness disturbance, duration of convulsion, low CSF glucose levels, and disuse of dexamethasone (p < 0.05). CONCLUSIONS: The incidence in pediatric bacterial meningitis remained low, and S. agalactiae remains the most common cause of bacterial meningitis in Japan since 2012. S. pneumoniae is the most common cause after 3 months of age.

Effectiveness of inactivated quadrivalent influenza vaccine in the 2015/2016 season as assessed in both a test-negative case-control study design and a traditional case-control study design.

Both traditional case-control studies (TCCSs) and test-negative case-control studies (TNCCSs) are commonly used to assess influenza vaccine effectiveness (VE). To compensate for the fact that observational studies are susceptible to bias, we combined both methods to assess VE in one geographical area during the 2015/2016 season, when influenza A (H1N1)pdm was dominant. Our TNCCS covered 331 children aged 6 months to 15 years who visited our hospital with fever, including 182 with influenza, and our TCCS covered 812 pediatric outpatients aged 6 months to 15 years, including 214 with influenza. Influenza infection and vaccination history were reviewed, and VE was calculated as (1 - odds ratio) × 100. In the TNCCS, VE against influenza A was 68% (95% CI 47-81) overall, and 70% (48-83) for those given two doses; against influenza B, VE was 37% (- 12-64) overall and 49% (2-74) for two doses. In the TCCS, VE against influenza A was 44% (15-63) overall and 44% (13-64) for two doses, and VE against influenza B was 24% (- 19-52) overall and 41% (3-64) for two doses. CONCLUSION: Both studies confirmed significant VE against influenza A, significant two-dose VE against influenza B, and better two-dose VE than one-dose VE. What is Known: • Influenza vaccine effectiveness (VE) varies from year to year. • Observational studies are conventionally used for VE assessment. However, they are inherently susceptible to bias and confounding. What is New: • This is the first report of influenza VE assessment using more than one observational study and performed in a specific area during the same season. • VE estimates obtained in our traditional case-control study were lower than those in our test-negative case-control study, but both studies found significant VE against influenza.

Purulent lymphadenitis caused by Staphylococcus argenteus, representing the first Japanese case of Staphylococcus argenteus (multilocus sequence type 2250) infection in a 12-year-old boy.

Staphylococcus argenteus is a novel species separated from a strain of coagulase-positive, non-pigmented S. aureus. Although S. argenteus has been reported to occur globally, multilocus sequence type (ST) 2250 is mainly found in Northeastern Thailand. Because conventional biochemical testing misidentifies this pathogen as S. aureus, multilocus sequence typing (MLST) or nucA sequencing is recommended to distinguish between S. argenteus and S. auereus. The patient was a previously healthy 12-year-old boy who was admitted because of right inguinal lymphadenitis and cellulitis. Although intravenous cefazolin was administered, his lymphadenitis worsened and formed an abscess on day 6 of hospitalization. Incision and drainage were performed on day 7 of hospitalization. Cefazolin was changed to oral cefaclor, and the patient was successfully treated over a period of 5 weeks. No recurrence was observed throughout 12-months of follow-up. He had a history of right axillary lymph node abscess 2 months before this admission, which was successfully treated with incision, drainage, and antibiotic therapy. He has lived in Japan since birth and never traveled abroad. He had no opportunity to interact with foreigners. His immune function, especially neutrophil function, was tested and we did not find any dysfunction. First, methicillin-sensitive S. aureus was misidentified from the abscess culture. Subsequently, the causative agent was re-identified as S. argenteus ST2250 based on MLST. To our knowledge, this is the first case of S. argenteus ST2250 infection in Japan. This pathogen should be taken into consideration in the diagnosis if the patient has atypical non-pigmented S. aureus.

Pediatric bacterial meningitis in Japan, 2013-2015 - 3-5 years after the wide use of Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines.

BACKGROUND: Haemophilus influenzae type b (Hib) vaccine and pneumococcal conjugated vaccine (PCV) have been widely used since 2010 in Japan when both vaccines were supported by the regional governments, and they were covered as routine recommended vaccines in 2013. The incidence of bacterial meningitis due to these organisms decreased in 2011 and 2012, but meningitis due to Streptococcus agalactiae and Escherichia coli remained unchanged. OBJECTIVES: We planned to confirm whether the incidence also decreased in subsequent years. METHODS: We analyzed the epidemiological and clinical data for 2013-2015, and compared the information obtained in the previous nationwide survey database and our previous reports. We also investigated the risk factors for disease outcome. RESULTS: In the 2013-2015 surveys, 407 patients from 366 hospitals from all prefectures were evaluated. S. agalactiae (33%), Streptococcus pneumoniae (25%), and E. coli (10%) were the main organisms. The total number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.19 in 2009-2010 to 0.37 in 2013-2015 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis significantly decreased from 0.66 in 2009-2010 to 0.01 in 2013-2015, and from 0.30 to 0.09, respectively (p < 0.001). Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2015. The fatality rates for H. influenzae, S. pneumoniae, S. agalactiae, and E. coli in 2013-2015 were 0.0, 4.1, 3.1, and 2.6%, respectively. Risk factors for death and sequelae were consciousness disturbance, convulsion, low CSF glucose, and Staphylococcus sp. as a causative organism (p < 0.01). CONCLUSIONS: Hib vaccine and PCV have decreased the rate of bacterial meningitis. S. agalactiae has subsequently become the most common cause of bacterial meningitis in Japan.

Utility of fractional excretion of urea in the differential diagnosis of acute kidney injury in children.

INTRODUCTION: The fractional excretion of sodium (FENa) has been used as an index for the differential diagnosis of acute tubular necrosis (ATN) and prerenal acute kidney injury (AKI). The reliability of this index, however, decreases with the use of the diuretic agent furosemide. The fractional excretion of urea nitrogen (FEUN) has been shown to be useful in such settings in adults. The objective of this study was to examine whether FEUN is also useful in these settings in children. METHODS: We assessed 102 episodes of AKI in 74 children, classifying these into three groups based on history, physical examination, urine examination and subsequent clinical course: (1) prerenal AKI without furosemide (N = 37), (2) prerenal AKI with furosemide (N = 32) and (3) ATN (N = 33). RESULTS: Of the 37 prerenal AKI episodes without furosemide, 35 showed low FENa of <1 %, with an overall average of 0.35 ± 0.11 %, whereas prerenal AKI with furosemide (1.63 ± 0.37 %) and ATN (8.76 ± 2.11 %) were associated with a higher FENa. FEUN in the clinical setting of prerenal AKI was lower than that in ATN (27.9 ± 2.1 vs. 51.6 ± 3.8 %, respectively) and, in contrast to FENa, not significantly different between the categories of prerenal AKI with and without furosemide (29.2 ± 3.1 vs. 25.1 ± 2.9, respectively). The sensitivity of FEUN <35 % was 75 % in prerenal AKI with furosemide, whereas that of FENa was 53 %. CONCLUSIONS: FEUN is useful in detecting prerenal AKI in children administered furosemide.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan.

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case-control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

Catheter-related blood stream infection caused by Dermacoccus barathri, representing the first case of Dermacoccus infection in humans.

A 7-year-old boy undergoing home parenteral nutrition with totally implantable central venous access device for chronic intestinal pseudo-obstruction experienced repeated episodes of fever with a temperature above 39.0 °C despite the antibiotic treatment. The fever was considered to be catheter-related blood stream infections, as no other etiology could be justified. Repeated blood culture tests revealed negative after 1-week incubation, whereas some samples of blood collected from the central venous catheter yielded positive and gram-positive rods were detected. These bacteria were detected repeatedly, then the central venous access device was removed with consideration for the possibility of this bacteria being a pathogen. Thereafter, the fever did not recur and the blood culture tests were negative. The causative agent was identified as Dermacoccus barathri based on the 16S rRNA gene sequence and phylogenetic analysis of 6118-bp concatenated sequences of 4 housekeeping genes. Genus Dermacoccus are one form of Actinomycetes isolated from human skin and water, but human infection with Dermacoccus spp. has not been previously reported and the pathogenicity of the bacteria remains unclear. To our knowledge, this is the first reported case of Dermacoccus infection in humans.

High rate of inducible clindamycin resistance in Staphylococcus aureus isolates--a multicenter study in Tokyo, Japan.

The resistance of Staphylococcus aureus (S. aureus) to antibiotics is an increasing problem. Clindamycin has been used as empiric therapy for the rising incidence of community-acquired methicillin-resistant S. aureus (MRSA). As such, the local rate of inducible resistance against clindamycin is an important consideration. This multicenter study was conducted to identify the incidence of inducible clindamycin resistance of S. aureus isolates in Tokyo, the most populous city in Japan. A total of 2408 adult and pediatric samples were collected from a university hospital and two pediatric hospitals between January 2011 and December 2011. Among the 2341 samples analyzed, the incidence of inducible clindamycin resistance in erythromycin-resistant and clindamycin-susceptible/intermediate isolates was found to be 91% (n = 585), a figure much higher compared to most reports from other countries. In conclusion, we found a very high rate of inducible clindamycin resistance in macrolide-resistant S. aureus isolates in our geographic area.

Recent trends in pediatric bacterial meningitis in Japan--a country where Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines have just been introduced.

To investigate the trends in incidence and the characteristics of bacterial meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7-valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010, respectively, which was 5-20 years after their introduction in western countries. The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was performed in 2011 and 2012. We analyzed the epidemiological and clinical data, and compared the information obtained in the previous nationwide survey database. We also investigated the risk factors for disease outcome. In the 2011-2012 surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae, Streptococcus agalactiae and Escherichia coli were the main organisms. The number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.31 in 2009 to 0.43 in 2012 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30 to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2012. The median patient age was 10-12 months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001-2012 among the four organisms. Risk factors for death and sequelae were convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children.