Emergence of ciprofloxacin- and penicillin-resistant Neisseria meningitidis isolates in Japan between 2003 and 2020 and its genetic features.

Although we previously reported that some meningococcal isolates in Japan were resistant to penicillin (PCG) and ciprofloxacin (CIP), the antibiotic susceptibilities of Neisseria meningitidis isolates obtained in Japan remained unclear. In the present study, 290 N. meningitidis isolates in Japan between 2003 and 2020 were examined for the sensitivities to eight antibiotics (azithromycin, ceftriaxone, ciprofloxacin, chloramphenicol, meropenem, minocycline, penicillin, and rifampicin). All isolates were susceptible to chloramphenicol, ceftriaxone, meropenem, minocycline, and rifampicin while two were resistant to azithromycin. Penicillin- and ciprofloxacin-resistant and -intermediate isolates (PCGR, CIPR, PCGI and CIPI, respectively) were also identified. Based on our previous findings from whole genome sequence analysis, approximately 40% of PCGI were associated with ST-11026 and cc2057 meningococci, both of which were unique to Japan. Moreover, the majority of ST-11026 meningococci were CIPR or CIPI. Sensitivities to PCG and CIP were closely associated with genetic features, which indicated that, at least for Japanese meningococcal isolates, PCGR/I or CIPI/R would be less likely to be horizontally conferred from other neisserial genomes by transferring of the genes responsible (penA and gyrA genes, respectively), but rather that ancestral N. meningitidis strains conferring PCGR/I or CIPI/R phenotypes clonally disseminated in Japan.

Genomic characterization of Japanese meningococcal strains isolated over a 17-year period between 2003 and 2020 in Japan.

While invasive meningococcal disease (IMD) is a major public concern worldwide, IMD is categorized as a rare infectious disease in Japan and, thus, its causative agents and epidemiology have not yet been characterized in detail. In the present study, we used molecular methods to epidemiologically characterize 291 meningococcal strains isolated in Japan over a 17-year period between 2003 and 2020 by whole genome sequencing (WGS). Serogroup Y meningococci (MenY) were the most abundant, followed by B (MenB) and then C and W among meningococci from IMD patients, while non-groupable as well as MenY and MenB were the most abundant among isolates from healthy carriers. Sequence type (ST) defined by multilocus sequence typing (MLST) showed that ST-1655 and ST-23 belonging to clonal complex (cc) 23 were dominant among Japanese IMD isolates, while ST-11026 (cc32) unique to Japan as well as ST-23 were dominant among Japanese non-IMD isolates. Phylogenetic analyses of ST by MLST revealed that Japanese isolates were classified with 12 ccs, including recently reported cc2057. Phylogenic analyses by WGS showed that isolates of ST-11026 and of ST-1655 were genetically close, whereas ST-23 isolates appeared to be diverse. Moreover, comparisons with other cc11 isolates isolated worldwide indicated that some Japanese cc11 isolates were genetically close to those isolated in Europe and China. An in silico analysis suggested that 14.3 and 44.2% of Japanese MenB were cross-reactive with 4CMenB and rLP2086 MenB vaccines, respectively. The results in the present study revealed that some epidemiological features were unique to Japan.

Vasovagal reactions after COVID-19 vaccination in Japan.

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10-19 years and 20-29 years, respectively. In individuals aged 10-29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.

Severe encephalopathy associated with SARS-CoV-2 Omicron BA.1 variant infection in a neonate.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), including the Omicron variant, is less severe in children than in adults. To date, there has been no detailed description of COVID-19-associated severe encephalopathy due to the Omicron variant during the neonatal and early infantile periods. CASE PRESENTATION: During the outbreak of the Omicron variant, a 29-day-old male presented with a pale and ill appearance. The patient was intubated for mechanical ventilation owing to recurrent apnea, which subsequently turned out to be a breath-holding that may have been caused by seizure. In addition, nonconvulsive status epilepticus was observed. Total duration of repetitive seizure activities was approximately 30 min per hour when seizures were most severe. Brain magnetic resonance imaging (MRI) on day 14 revealed extensive hyperintensity in the T2 sequence, hypointensity in the fluid-attenuated inversion recovery (FLAIR) sequence in the deep and subcortical white matter, and diffusion restriction in the corpus callosum. The Omicron BA.1 variant of the severe acute respiratory syndrome coronavirus 2 was detected in his respiratory sample. Follow-up MRI on day 45 revealed multiple cystic cavitations. CONCLUSION: Although COVID-19 is not severe in most children, life-threatening conditions such as COVID-19-associated severe encephalopathy can occur during the neonatal and early infantile periods.

Genetic characterization of clonal complex sequence type 2057 (cc2057) serogroup B Neisseria meningitidis strains unique to Japan and identification of a capsular-switched serogroup Y isolate cc2057.

Introduction. Only approximately 40 cases of invasive meningococcal diseases are reported annually in Japan, and the dominant strains are serogroup Y meningococci (MenY) followed by serogroup B meningococci (MenB). Within the last 10 years, Neisseria meningitidis strains belonging to clonal complex (cc)2057 have become dominant among Japanese MenB and have not been identified in countries other than Japan.Hypothesis/Gap Statement. The uniqueness of cc2057 N. meningitidis strains was considered to be epidemiologically of importance, and some genetic features could be hidden in the genome of cc2057 meningococci.Method. We investigated 22 cc2057 MenB and one cc2057 MenY using whole genome sequencing (WGS) and also predicted the potential coverage of 4CMenB and bivalent rLP2086 vaccines in silico.Results. cc2057 N. meningitidis strains were phylogenetically assigned to two clades. Three hypothetical genes homologous to those in Neisseria lactamica and sequences related to a new CRISPR Cas9 system were found only in the genome of cc2057 strains. Moreover, one cc2057 MenY strain was presumed to be capsular-switched at the capsule synthesis (cps) locus. The potential coverage of 4CMenB and rLP2086 for cc2057 MenB strains was estimated to be very low.Conclusion. To the best of our knowledge, this is the first study to provide genetic insights from epidemiologically unique N. meningitidis cc2057 strains isolated only in Japan, an island country.