Whole-genome analysis of human group A rotaviruses in 1980s Japan and evolutionary assessment of global Wa-like strains across half a century.

Historically, the Wa-like strains of human group A rotavirus (RVA) have been major causes of gastroenteritis. However, since the 2010s, the circulation of non-Wa-like strains has been increasingly reported, indicating a shift in the molecular epidemiology of RVA. Although understanding RVA evolution requires the analysis of both current and historical strains, comprehensive pre-1980's sequencing data are scarce globally. We determined the whole-genome sequences of representative strains from six RVA gastroenteritis outbreaks observed at an infant home in Sapporo, Japan, between 1981 and 1989. These outbreaks were mainly caused by G1 or G3 Wa-like strains, resembling strains from the United States in the 1970s-1980s and from Malawi in the 1990s. Phylogenetic analysis of these infant home strains, together with Wa-like strains collected worldwide from the 1970s to 2020, revealed a notable trend: pre-2010 strains diverged into multiple lineages in many genomic segments, whereas post-2010 strains tended to converge into a single lineage. However, Bayesian skyline plot indicated near-constant effective population sizes from the 1970s to 2020, and selection pressure analysis identified positive selection only at amino acid 75 of NSP2. These results suggest that evidence supporting the influence of rotavirus vaccines, introduced globally since 2006, on Wa-like RVA molecular evolution is lacking at present, and phylogenetic analysis may simply reflect natural fluctuations in RVA molecular evolution. Evaluating the long-term impact of RV vaccines on the molecular evolution of RVA requires sustained surveillance.

Human transmission and outbreaks of feline-like G6 rotavirus revealed with whole-genome analysis of G6P[9] feline rotavirus.

Group A rotaviruses (RVAs) are generally highly species-specific; however, some strains infect across species. Feline RVAs sporadically infect humans, causing gastroenteritis. In 2012 and 2013, rectal swab samples were collected from 61 asymptomatic shelter cats at a public health center in Mie Prefecture, Japan, to investigate the presence of RVA and any association with human infections. The analysis identified G6P[9] strains in three cats and G3P[9] strains in two cats, although no feline RVA sequence data were available for the former. A whole-genome analysis of these G6P[9] strains identified the genotype constellation G6-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3. The nucleotide identity among these G6P[9] strains exceeded 99.5% across all 11 gene segments, indicating the circulation of this G6P[9] strain among cats. Notably, strain RVA/Human-wt/JPN/KF17/2010/G6P[9], previously detected in a 3-year-old child with gastroenteritis, shares high nucleotide identity (>98%) with Mie20120017f, the representative G6P[9] strain in this study, across all 11 gene segments, confirming feline RVA infection and symptomatic presentation in this child. The VP7 gene of strain Mie20120017f also shares high nucleotide identity with other sporadically reported G6 RVA strains in humans. This suggests that feline-origin G6 strains as the probable source of these sporadic G6 RVA strains causing gastroenteritis in humans globally. Moreover, a feline-like human G6P[8] strain circulating in Brazil in 2022 was identified, emphasizing the importance of ongoing surveillance to monitor potential global human outbreaks of RVA.

A significant outbreak of respiratory human adenovirus infections among children aged 3-6 years in Hokkaido, Japan, in 2023.

Human adenovirus (HAdV) infections present diverse clinical manifestations upon infecting individuals, with respiratory infections predominating in children. We surveyed pediatric hospitalizations due to respiratory HAdV infections across 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to March 2024, recording 473 admissions. While hospitalizations remained below five cases per week from July 2019 to September 2023, a notable surge occurred in late October 2023, with weekly admissions peaking at 15-20 cases from November to December. There were dramatic shifts in the age distribution of hospitalized patients: during 2019-2021, 1-year-old infants and children aged 3-6 years represented 51.4%-54.8% and 4.1%-13.3%, respectively; however, in 2023-2024, while 1-year-old infants represented 19.0%-20.1%, the proportion of children aged 3-6 years increased to 46.2%-50.0%. Understanding the emergence of significant outbreaks of respiratory HAdV infections and the substantial changes in the age distribution of hospitalized cases necessitates further investigation into the circulating types of HAdV in Hokkaido Prefecture and changes in children's neutralizing antibody titers against HAdV.

Resurgence of human metapneumovirus infection and influenza after three seasons of inactivity in the post-COVID-19 era in Hokkaido, Japan, 2022-2023.

Following the coronavirus disease 2019 (COVID-19) outbreak in February 2020, incidences of various infectious diseases decreased notably in Hokkaido Prefecture, Japan. However, Japan began gradually easing COVID-19 infection control measures in 2022. Here, we conducted a survey of children hospitalized with human metapneumovirus (hMPV), influenza A and B, and respiratory syncytial virus infections in 18 hospitals across Hokkaido Prefecture, Japan, spanning from July 2019 to June 2023. From March 2020 to June 2022 (28 months), only 13 patients were hospitalized with hMPV, and two patients had influenza A. However, in October to November 2022, there was a re-emergence of hMPV infections, with a maximum of 27 hospitalizations per week. From July 2022 to June 2023 (12 months), the number of hMPV-related hospitalizations dramatically increased to 317 patients, with the majority aged 3-6 years (38.2%, [121/317]). Influenza A also showed an increase from December 2022, with a peak of 13 hospitalizations per week in March 2023, considerably fewer than the pre-COVID-19 outbreak in December 2019, when rates reached 45 hospitalizations per week. These findings suggest the possibility of observing more resurgences in infectious diseases in Japan after 2023 if infection control measures continue to be relaxed. Caution is needed in managing potential outbreaks.

Sequence analysis of a feline- and porcine-origin G3P[9] rotavirus A strain in a child with acute gastroenteritis in Japan.

We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.

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.

Surveillance in hospitalized children with infectious diseases in Japan: Pre- and post-coronavirus disease 2019.

INTRODUCTION: The epidemic of coronavirus disease 2019 (COVID-19) rapidly spread worldwide, and the various infection control measures have a significant influence on the spread of many infectious diseases. However, there have been no multicenter studies on how the number of hospitalized children with various infectious diseases changed before and after the outbreak of COVID-19 in Japan. METHODS: We conducted a multicenter, prospective survey for hospitalized pediatric patients in 18 hospitals in Hokkaido Prefecture, Japan, from July 2019 to February 2021. We defined July 2019 to February 2020 as pre-COVID-19, and July 2020 to February 2021 as post-COVID-19. We surveyed various infectious diseases by sex and age. RESULTS: In total, 5300 patients were hospitalized during the study period. The number of patients decreased from 4266 in the pre-COVID-19 period to 701 (16.4%) post-COVID-19. Patients with influenza and RSV decreased from 308 to 795 pre-COVID-19 to zero and three (0.4%) post-COVID-19. However, patients with adenovirus (respiratory infection) only decreased to 60.9% (46-28) of pre-COVID levels. Patients with rotavirus, norovirus, and adenovirus gastroenteritis decreased markedly post-COVID-19 to 2.6% (38-1), 27.8% (97-27) and 13.5% (37-5). The number of patients with UTIs was similar across the two periods (109 and 90). KD patients decreased to 31.7% (161-51) post-COVID-19. CONCLUSIONS: We suggest that current infection control measures for COVID-19 such as wearing masks, washing hands, and disinfecting hands with alcohol are effective against various infectious diseases. However, these effects vary by disease.

Verification of pharmacogenomics-based algorithms to predict warfarin maintenance dose using registered data of Japanese patients.

PURPOSE: Large inter-individual differences in warfarin maintenance dose are mostly due to the effect of genetic polymorphisms in multiple genes, including vitamin K epoxide reductase complex 1 (VKORC1), cytochromes P450 2C9 (CYP2C9), and cytochrome P450 4F2 (CYP4F2). Thus, several algorithms for predicting the warfarin dose based on pharmacogenomics data with clinical characteristics have been proposed. Although these algorithms consider these genetic polymorphisms, the formulas have different coefficient values that are critical in this context. In this study, we assessed the mutual validity among these algorithms by specifically considering racial differences. METHODS: Clinical data including actual warfarin dose (AWD) of 125 Japanese patients from our previous study (Eur J Clin Pharmacol 65(11):1097-1103, 2009) were used as registered data that provided patient characteristics, including age, sex, height, weight, and concomitant medications, as well as the genotypes of CYP2C9 and VKORC1. Genotyping for CYP4F2*3 was performed by the PCR method. Five algorithms that included these factors were selected from peer-reviewed articles. The selection covered four populations, Japanese, Chinese, Caucasian, and African-American, and the International Warfarin Pharmacogenetics Consortium (IWPC). RESULTS: For each algorithm, we calculated individual warfarin doses for 125 subjects and statistically evaluated its performance. The algorithm from the IWPC had the statistically highest correlation with the AWD. Importantly, the calculated warfarin dose (CWD) using the algorithm from African-Americans was less correlated with the AWD as compared to those using the other algorithms. The integration of CYP4F2 data into the algorithm did not improve the prediction accuracy. CONCLUSION: The racial difference is a critical factor for warfarin dose predictions based on pharmacogenomics.

Rib stress fracture in a female athlete caused by bouncing the barbell in bench press exercise: A case report.

Rib stress fractures can occur in sports involving repetitive trunk muscle contractions. Few documented cases show rib fractures from repetitive upper-limb training. This report presents a case of a rib stress fracture from micro blunt trauma during bench press exercises. The patient was a 24-year-old elite female sprinter with a history of left navicular stress fracture and secondary amenorrhea treatment a year prior. She modified her bench press technique to involve bouncing the barbell on her rib cage. Within weeks, she experienced anterior chest pain, exacerbated by sneezing. Computed tomography revealed a fifth rib fracture with callus formation. After refraining from bench presses for 4 weeks, her chest pain subsided, allowing her to resume upper-limb training. When athletes performing bench press exercises experience chest pain, rib fractures should be considered, even without acute trauma. Additionally, research on the safety of the bouncing bench pressing technique is required.

Changing Patterns of Infectious Diseases Among Hospitalized Children in Hokkaido, Japan, in the Post-COVID-19 Era, July 2019 to June 2022.

BACKGROUND: Many reports have reported a reduction in respiratory infectious diseases and infectious gastroenteritis immediately after the coronavirus disease 2019 (COVID-19) pandemic, but data continuing into 2022 are very limited. We sought to understand the current situation of various infectious diseases among children in Japan as of July 2022 to improve public health in the post-COVID-19 era. METHODS: We collected data on children hospitalized with infectious diseases in 18 hospitals in Japan from July 2019 to June 2022. RESULTS: In total, 3417 patients were hospitalized during the study period. Respiratory syncytial virus decreased drastically after COVID-19 spread in early 2020, and few patients were hospitalized for it from April 2020 to March 2021. However, an unexpected out-of-season re-emergence of respiratory syncytial virus was observed in August 2021 (50 patients per week), particularly prominent among older children 3-6 years old. A large epidemic of delayed norovirus gastroenteritis was observed in April 2021, suggesting that the nonpharmaceutical interventions for COVID-19 are less effective against norovirus. However, influenza, human metapneumovirus, Mycoplasma pneumoniae , and rotavirus gastroenteritis were rarely seen for more than 2 years. CONCLUSIONS: The incidence patterns of various infectious diseases in Japan have changed markedly since the beginning of the COVID-19 pandemic to the present. The epidemic pattern in the post-COVID-19 era is unpredictable and will require continued careful surveillance.

Expanding the PURA syndrome phenotype with manifestations in a Japanese female patient.

We report on a 15-year-old Japanese female patient with hypotonia and global developmental delay from the neonatal period who was revealed to carry a known pathogenic PURA variant (NM_005859.5:c.697_699del, p.Phe233del) by whole-exome sequencing. She had previously unreported clinical features, including a rectovestibular fistula, extremely short stature, and underweight, expanding the known phenotype of PURA syndrome.

Long-term sensor-augmented pump therapy for neonatal diabetes mellitus: a case series.

Neonatal diabetes mellitus (NDM) is a rare metabolic disorder that is mainly present in the first 6 months of life and necessitates insulin treatment. Sensor-augmented pump (SAP) therapy has been widely used in children with type 1 diabetes mellitus, but its use in patients with NDM is limited. We report three patients with NDM who received SAP therapy using the MiniMed™ 640G system starting in the neonatal period. Two patients were treated for 3 months, and one patient continued treatment up to an age of 22 mo. The MiniMed 640G system can automatically suspend insulin delivery (SmartGuard™ Technology) to avoid hypoglycemia when the sensor glucose level is predicted to approach the predefined threshold. We suggest that SmartGuard Technology is particularly useful for infants in whom hypoglycemia cannot be identified. The MiniMed 640G system automatically records the trends of sensor glucose levels and the total daily dose of insulin, which can make the management more accurate and reduce the family's effort. SAP therapy for patients with NDM automatically prevents severe hypoglycemia and is useful for long-term management; however, attention should be paid to its application.

A rare pathogen Raoultella planticola caused urinary tract infection in child with congenital anomalies of kidney and urinary tract: case report.

Raoultella planticola was previously considered an environmental organism in soil, water, and plants. However, several cases of human infection have recently been reported in association with R. planticola, some of which have been life-threatening. Most cases were in adults with reduced immunity, with few cases in children. To our knowledge, there have only been two reported cases of urinary tract infection (UTI) caused by R. planticola in children, including one case of cystitis. Here, we present the first case of UTI caused by R. planticola with congenital anomalies of kidney and urinary tract (CAKUT) in a 4-month-old male infant. The patient presented to the emergency department with fever and was diagnosed with UTI. We started third-generation cephalosporins empirically for gram-negative bacteria in the urine, presuming infection with Escherichia coli. On day 1, the patient's fever resolved immediately. On day 2, urine culture was positive for a rare pathogen, R. planticola, and we narrowed antibiotics to first-generation cephalosporins. The patient's fever did not return and he was discharged on day 7. The patient was seen in the clinic 1 week after discharge, with complete resolution of symptoms. Magnetic resonance urography and dynamic renal scintigraphy performed 2 months after discharge revealed severe bilateral hydronephroureter and obstruction of urine flow in the right kidney. As of 6 months after UTI onset, we have continued low-dose cephalexin (10 mg/kg) to prevent the recurrence of UTI and there has been no recurrence. As in this case, children with UTI caused by R. planticola may be associated with CAKUT; therefore, we should actively screen to detect CAKUT. Patients with CAKUT are at high risk of UTI recurrence, so long-term use of unnecessary broad-spectrum antibiotics should be avoided to prevent antimicrobial resistance. However, R. planticola infection is sometimes life-threatening. Hence, it is also important to use sufficiently strong antibiotics for an appropriate period. Although the optimal management of R. planticola infection in children has not been clearly established, we suggest that we can treat UTI caused by R. planticola mainly using first-generation cephalosporins.

Facial onset sensory and motor neuropathy in a pain clinic outpatient: a case report.

BACKGROUND: Facial onset sensory and motor neuropathy is a very rare sensorimotor disorder characterized by facial onset and gradual progression, with approximately 100 cases reported worldwide in 2020. We report on our experience with a facial onset sensory and motor neuropathy case in our outpatient pain clinic. CASE PRESENTATION: A 71-year-old Japanese man with a previous diagnosis of trigeminal nerve palsy complained of facial paresthesia, cervical pain, and arm numbness. Cervical facet arthropathy was diagnosed initially, but neither pharmacotherapy nor nerve blocking alleviated his symptoms. We suspected bulbar palsy based on the presence of tongue fasciculation, which prompted referral to a neurologist. Based on a series of neurological examinations, facial onset sensory and motor neuropathy was ultimately diagnosed. CONCLUSIONS: Pain clinicians must be mindful of rare diseases such as facial onset sensory and motor neuropathy; if they are unable to make a diagnosis, they should consult with other competent specialists.