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.

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan.

OBJECTIVE: The Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6-12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program. METHODS: Subjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis. RESULTS: Of 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0-8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01). CONCLUSION: Effectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.

Determinants of self-paid rotavirus vaccination status in Kanazawa, Japan, including socioeconomic factors, parents' perception, and children's characteristics.

BACKGROUND: Japan's National Immunization Program does not cover rotavirus vaccine and no government subsidies are available. This study aimed to measure the uptake of and determinants that influenced self-paid rotavirus vaccination, including socioeconomic status and relative poverty. METHODS: We conducted a cross-sectional study at health check-ups for all children aged 18 months in Kanazawa, Japan, between December 2017 and July 2018. Community nurses collected information on self-paid vaccination history, parents' perceptions of and recommendations for rotavirus vaccine, and socioeconomic status in interviews using a unified questionnaire. We used multivariable logistic regression to assess vaccine uptake and possible determinants. RESULTS: In total, 1282 participants were enrolled. The estimated rotavirus vaccine coverage was 72.9%. Perceptions that rotavirus gastroenteritis was serious and that the rotavirus vaccine was effective, pediatricians' recommendations, information from the city office, magazine and Internet articles, and higher parental education level were associated with higher rotavirus vaccine uptake. Lower household income was associated with decreased rotavirus vaccine uptake. Vaccine expense, fear of adverse reactions to the vaccine, number of household members and siblings, and children's characteristics were not correlated with rotavirus vaccination. Poverty was associated with decreased rotavirus vaccine uptake, even after adjustment for other determinants (adjusted odds ratio 0.49, 95% confidence interval: 0.26-0.90). CONCLUSION: Parents' perceptions, socioeconomic status, relative poverty, and pediatricians' recommendations are determinants of vaccination. This study suggests that appropriate information about rotavirus vaccine, subsidies for those of lower socioeconomic status, and national recommendations are necessary to achieve higher coverage.

Case-Control Study of Rotavirus Vaccine Effectiveness Compared to Test-Negative Controls or Hospital Controls.

BACKGROUND: Selection of test-negative controls takes less time and costs less than traditional control selection for evaluating vaccine effectiveness (VE). Here, rotavirus VE was evaluated using hospital controls and compared with test-negative controls to determine whether using the latter can substitute for the former. METHODS: We recorded gastroenteritis in children from 2 months to 2 years of age at six medical facilities in Saga City between January 4th and May 31st, 2014. Stools from all identified acute gastroenteritis patients were tested for rotavirus using immunochromatography. Rotavirus gastroenteritis (RVGE) cases had test-positive stool, whereas test-negative controls had gastroenteritis but no rotavirus infection; hospital controls were outpatients visiting the same facility for indications other than gastroenteritis. Vaccination status was verified by inspecting maternal and child health records, and demographic data were obtained from a questionnaire completed by the patients' guardians or from the medical records. Unconditional logistic regression analysis was used to adjust for possible confounding factors. RESULTS: Sixty-four RVGE cases, 260 test-negative controls, and 589 hospital controls were enrolled. The characteristics of the two control groups, including RV vaccination history, were similar. The RVGE cases were more likely to have used daycare services than children from either of the two control groups. The VE against RVGE estimated using hospital controls was 86.6% (95% confidence interval [CI], 55.9-96.0%), very similar to the VE using test-negative controls (84.9% [95% CI, 49.6-95.5%]). CONCLUSIONS: The estimated VE using test-negative controls and hospital controls is similar. Therefore, test-negative controls are considered appropriate for establishing VE.

Effectiveness of monovalent and pentavalent rotavirus vaccines in Japanese children.

BACKGROUND: Rotavirus (RV) vaccination has been available in Japan since November 2011, but is not yet part of Japan's national immunisation programs. There are insufficient data on vaccine effectiveness (VE) among Japanese children. METHODS: Between the months of January and May in 2014 and 2015, we conducted active surveillance of gastroenteritis among children at 14 medical facilities. Rectal swabs from all patients with diarrhoea or vomiting were tested for RV by immunochromatography, and positive specimens were genotyped. Demographic data and immunisation records were obtained from a questionnaire completed by their parents/guardians or medical records. A test-negative case-control design was used to examine vaccine effectiveness (VE) using unconditional logistic regression analysis adjusted for possible confounding factors. RESULTS: Among the 1519 eligible subjects (children with acute gastroenteritis symptoms aged ≥2 months to <3 y visiting medical facilities) recruited, 487 cases and 925 controls were enrolled. Cases had more severe symptoms than controls, requiring more intensive treatment, including intravenous rehydration or hospitalisation. VE against all rotavirus gastroenteritis (RVGE) was 80.0% (95% confidence interval [CI], 72.8-85.5%), and VEs against RV1 and RV5 were similar, at 80.6% (95%CI, 70.7-87.1%) for RV1 and 80.4% (95% CI, 69.1-87.6%) for RV5. Although VEs of both vaccines decreased with age, VEs against all RVGE were >70% up to 2 years after vaccination. VEs increased with severity of RVGE, and VE against severe RVGE, requiring intravenous rehydration or hospitalisation, was 97.3% (95% CI, 88.8-99.3%). VEs of RV1 and RV5 against G1P[8] and G2P[4] were comparable, at RV1, 89.8% (95% CI, 78.2-95.5%) and 78.3% (95% CI, 23.6-93.8%); and RV5, 85.8% (95% CI, 72.8-92.6%) and 88.1% (95% CI, 10.1-98.4%), respectively. CONCLUSIONS: Rotavirus vaccines were effective in preventing mild to severe RVGE, irrespective of vaccine type, time since vaccination, or RV genotype.

De novo GABRA1 mutations in Ohtahara and West syndromes.

OBJECTIVE: GABRA1 mutations have been identified in patients with familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy, and idiopathic familial generalized epilepsy. In addition, de novo GABRA1 mutations were recently reported in a patient with infantile spasms and four patients with Dravet syndrome. Those reports suggest that GABRA1 mutations are associated with infantile epilepsy including early onset epileptic encephalopathies. In this study, we searched for GABRA1 mutations in patients with infantile epilepsy to investigate the phenotypic spectrum of GABRA1 mutations. METHODS: In total, 526 and 145 patients with infantile epilepsy were analyzed by whole-exome sequencing and GABRA1-targeted resequencing, respectively. RESULTS: We identified five de novo missense GABRA1 mutations in six unrelated patients. A p.R112Q mutation in the long extracellular N-terminus was identified in a patient with infantile epilepsy; p.P260L, p.M263T, and p.M263I in transmembrane spanning domain 1 (TM1) were identified in three unrelated patients with West syndrome and a patient with Ohtahara syndrome, respectively; and p.V287L in TM2 was identified in a patient with unclassified early onset epileptic encephalopathy. Four of these mutations have not been observed previously. SIGNIFICANCE: Our study suggests that de novo GABRA1 mutations can cause early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome.

Estimating rotavirus vaccine effectiveness in Japan using a screening method.

Rotavirus gastroenteritis is a highly contagious, acute viral disease that imposes a significant health burden worldwide. In Japan, rotavirus vaccines have been commercially available since 2011 for voluntary vaccination, but vaccine coverage and effectiveness have not been evaluated. In the absence of a vaccination registry in Japan, vaccination coverage in the general population was estimated according to the number of vaccines supplied by the manufacturer, the number of children who received financial support for vaccination, and the size of the target population. Patients with rotavirus gastroenteritis were identified by reviewing the medical records of all children who consulted 6 major hospitals in Saga Prefecture with gastroenteritis symptoms. Vaccination status among these patients was investigated by reviewing their medical records or interviewing their guardians by telephone. Vaccine effectiveness was determined using a screening method. Vaccination coverage increased with time, and it was 2-times higher in municipalities where the vaccination fee was supported. In the 2012/13 season, vaccination coverage in Saga Prefecture was 14.9% whereas the proportion of patients vaccinated was 5.1% among those with clinically diagnosed rotavirus gastroenteritis and 1.9% among those hospitalized for rotavirus gastroenteritis. Thus, vaccine effectiveness was estimated as 69.5% and 88.8%, respectively. This is the first study to evaluate rotavirus vaccination coverage and effectiveness in Japan since vaccination began.