Characteristics of intussusception among children in Hokkaido, Japan, during the pre- and post-rotavirus vaccine eras (2007-2016).

AIM: To analyse the epidemiology of intussusception in Hokkaido Prefecture, Japan during a 10-year period spanning the introduction of the rotavirus (RV) vaccine (2007-2016). METHODS: Using a standard questionnaire, a retrospective surveillance was conducted across 17 hospitals with paediatric beds in Hokkaido Prefecture. We compared the data between the pre-vaccine era (2007-2011) and post-vaccine era (2012-2016). RESULTS: In total, 208 and 110 intussusception cases were in the pre- and post-vaccine eras, respectively. A significant reduction of the intussusception incidence in children aged <1 year was observed from the pre- to the post-vaccine era (102.4-56.5 per 100 000 infants; incidence rate ratio, 0.55; p = 0.004). There was a relatively high-positive RV antigen detection rate (29.4%, 5/17) during the RV epidemic period in Japan (March-May) in the pre-vaccine era. None of the intussusception cases in the 31 patients with a history of RV vaccination occurred within 1 month after the administration of an RV vaccine dose. CONCLUSIONS: The incidence of intussusception in children aged <1 year decreased significantly after RV vaccine introduction in Japan. Another survey is needed to determine how the incidence of intussusception has changed further since the introduction of routine RV vaccination in 2020.

Molecular characterization of the first human G15 rotavirus strain of zoonotic origin from the bovine species.

Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.

Molecular and clinical characterization of the equine-like G3 rotavirus that caused the first outbreak in Japan, 2016.

Since 2013, equine-like G3 rotavirus (eG3) strains have been detected throughout the world, including in Japan, and the strains were found to be dominant in some countries. In 2016, the first eG3 outbreak in Japan occurred in Tomakomai, Hokkaido prefecture, and the strains became dominant in other Hokkaido areas the following year. There were no significant differences in the clinical characteristics of eG3 and non-eG3 rotavirus infections. The eG3 strains detected in Hokkaido across 2 years from 2016 to 2017 had DS-1-like constellations (i.e. G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2), and the genes were highly conserved (97.5-100 %). One strain, designated as To16-12 was selected as the representative strain for these strains, and all 11 genes of this strain (To16-12) exhibited the closest identity to one foreign eG3 strain (STM050) seen in Indonesia in 2015 and two eG3 strains (IS1090 and MI1125) in another Japanese prefecture in 2016, suggesting that this strain might be introduced into Japan from Indonesia. Sequence analyses of VP7 genes from animal and human G3 strains found worldwide did not identify any with close identity (>92 %) to eG3 strains, including equine RV Erv105. Analysis of another ten genes indicated that the eG3 strain had low similarity to G2P[4] strains, which are considered traditional DS-1-like strains, but high similarity to DS-1-like G1P[8] strains, which first appeared in Asia in 2012. These data suggest that eG3 strains were recently generated in Asia as mono-reassortant strain between DS-1-like G1P[8] strains and unspecified animal G3 strains. Our results indicate that rotavirus surveillance in the postvaccine era requires whole-genome analyses.

Rotavirus vaccination in Japan: Efficacy and safety of vaccines, changes in genotype, and surveillance efforts.

In Japan, a monovalent rotavirus vaccine (RV1) and a pentavalent rotavirus vaccine (RV5) were launched as voluntary vaccinations in November 2011 and July 2012, respectively. Rotavirus (RV) vaccine coverage in Japan increased from 30.0% in 2012 to 78.4% in 2019. The number of RV gastroenteritis hospitalizations decreased after 2014 in Japan, and is expected to decrease further following the introduction of RV vaccines into the national immunization program in October 2020. The incidence rates of intussusception (IS) among children aged <1 year were 102.8 and 94.0 per 100,000 person-years in the pre-vaccine (2007-2011) and post-vaccine (2012-September 2014) eras, respectively. IS incidence did not increase following RV vaccine introduction in Japan. The efficacy and safety of RV vaccination were both documented in Japan. To reduce the risk of IS following RV vaccination, it is important that children receive a first dose of RV vaccine at age <15 weeks, preferably at age 2 months. Some strains that have emerged since RV vaccine introduction, such as DS-1-like G1P[8], eG3, and G8P[8], have spread nationwide. These three emerging genotypes did not affect the severity of the RV infection. Continuous city-level surveillance, using analysis of all 11 RV genome segments, is necessary to elucidate the genetic characteristics of prevalent RV strains. These efforts would also clarify the influence of vaccination on genetic changes of RV strains and the emergence of new genotypes.

Tetanus in a partially immunized child.

A 13-year-old boy developed tetanus, although he had protective antitoxin antibody raised by three doses of tetanus toxoid vaccine. Four days after injury, he presented with muscle rigidity of his posterior neck, excessive diaphoresis, and risus sardonicus and was subsequently diagnosed with tetanus. Tetanus is rare in developed countries, particularly during childhood, but must be promptly diagnosed based on clinical symptoms.

Children's cognition and attitudes during long-term cancer treatment: an ethnographic study.

BACKGROUND: Cancer treatment for children is typically long-term and difficult, and the experience is unique for each child. When designing child-centred care, individuals' values and preferences are considered equally important as the clinical evidence; therefore, understanding children's thoughts and attitudes while they receive long-term treatment could offer valuable insights for better clinical practice. METHODS: We conducted long-term consecutive participatory observations and interviews with seven children, who were hospitalised and receiving cancer treatment for the first time. The daily observational data on those children's discourses, behaviours and interactions with health professionals were systematically collected and thematically examined. The analysis was expanded to explore significant narratives for each child to capture their narrative sequence over time. RESULTS: The initial analysis identified 685 narrative indexes for all observation data, which were categorised into 21 sub-codes. Those sub-codes were assembled into five main themes by thematic analysis: making promises with health professionals, learning about the treatment procedures through participation, taking care of oneself, increasing the range of activities one can perform and living an ordinary life. CONCLUSION: We observed a forward-looking attitude toward understanding cancer, accepting treatment and looking forward to the future among children undergoing in-hospital cancer treatment. In addition, the children developed cognitively, affectively and relationally throughout cancer treatment processes. These findings have implications for better clinical practice in child-centred care, including children's participation in shared decision-making in paediatric oncology.

Molecular evolutionary analysis of novel NSP4 mono-reassortant G1P[8]-E2 rotavirus strains that caused a discontinuous epidemic in Japan in 2015 and 2018.

In the 2010s, several unusual rotavirus strains emerged, causing epidemics worldwide. This study reports a comprehensive molecular epidemiological study of rotaviruses in Japan based on full-genome analysis. From 2014 to 2019, a total of 489 rotavirus-positive stool specimens were identified, and the associated viral genomes were analyzed by next-generation sequencing. The genotype constellations of those strains were classified into nine patterns (G1P[8] (Wa), G1P[8]-E2, G1P[8] (DS-1), G2P[4] (DS-1), G3P[8] (Wa), G3P[8] (DS-1), G8P[8] (DS-1), G9P[8] (Wa), and G9P[8]-E2). The major prevalent genotype differed by year, comprising G8P[8] (DS-1) (37% of that year's isolates) in 2014, G1P[8] (DS-1) (65%) in 2015, G9P[8] (Wa) (72%) in 2016, G3P[8] (DS-1) (66%) in 2017, G1P[8]-E2 (53%) in 2018, and G9P[8] (Wa) (26%) in 2019. The G1P[8]-E2 strains (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1) isolated from a total of 42 specimens in discontinuous years (2015 and 2018), which were the newly-emerged NSP4 mono-reassortant strains. Based on the results of the Bayesian evolutionary analyses, G1P[8]-E2 and G9P[8]-E2 were hypothesized to have been generated from distinct independent inter-genogroup reassortment events. The G1 strains detected in this study were classified into multiple clusters, depending on the year of detection. A comparison of the predicted amino acid sequences of the VP7 epitopes revealed that the G1 strains detected in different years encoded VP7 epitopes harboring distinct mutations. These mutations may be responsible for immune escape and annual changes in the prevalent strains.

Impact of muscle loss in children with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation.

The widespread recognition of the concept of sarcopenia, or muscle loss, has impacted the prognosis of patients undergoing high-intensity treatments. We focused on the effect of muscle loss on the prognosis of pediatric patients with hematologic diseases. A total of 65 patients with hematologic malignancies who underwent allogeneic HCT once were investigated. The change in cross-sectional psoas muscle area (PMA) measured on computed tomography (CT) images was expressed as the muscle loss index (MLI), which was calculated by dividing the pre-HCT PMA by the baseline PMA. In this study, patients with MLI values less than 0.85 were classified into the muscle loss group. Muscle loss was observed in 27 patients (41.5%). Patients who experienced muscle loss were older than those who did not. Muscle loss was an independent predictor of higher non-relapse mortality (NRM) (p = 0.012) and inferior overall survival (OS) (p = 0.045) at 5 years. Multivariate analysis showed that muscle loss was an independent risk factor for higher NRM (p = 0.046), and inferior EFS (p = 0.048). Muscle loss observed pre-HCT may be a predictor of increased NRM, poor OS and EFS in pediatric patients with hematologic malignancies undergoing allogeneic HCT.

Genotypes and transmission routes of noroviruses causing sporadic acute gastroenteritis among adults and children, Japan, 2015-2019.

Noroviruses (NoVs) are major causes of acute viral gastroenteritis at all ages worldwide. The molecular epidemiology of sporadic cases remains poorly understood, especially in adults. Additionally, no studies have analyzed the transmission route in sporadic acute gastroenteritis. In this study, we investigated cases of very mild sporadic NoV acute gastroenteritis in adults (medical staff) who do not visit the outpatient clinic and child outpatients. We also evaluated genotype differences between adults and children and possible transmission routes in adults during 5 years. The number of NoV positives were 58 in adults and 124 in children. In adults, the NoV positivity rate in this study was higher (64.4%) than that in previous reports of outpatients (10%) and inpatients (5%) in the United State. This finding suggested that the NoV positivity rate might be high in adults with very mild acute gastroenteritis. In adults, human-to-human transmission rates from children and food-borne transmission (raw oysters) were 21.6% (11/51) and 19.6% (10/51), respectively. Among adults, GII.2, GII.4, and GII.17 were the predominant genotypes, with rates of 32.7%, 30.9%, and 21.8%, respectively. Among children, GII.4 and GII.2 were the predominant genotypes, with rates of 45.5% and 40.6%, respectively. GII.17 was only detected in 0.8% (1/123) of children. Trends in NoV genotypes are expected to differ depending on the patient's age. Investigating sporadic cases including the patient's background (age and transmission route) may be helpful to monitor the trend of NoV strains, forecast prevalent NoV GII genotypes, and develop NoV vaccines.