Epidemiology and bacterial characteristics of invasive group B streptococcus disease: a population-based study in Japan in 2010-2020.

This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.

Remitting and exacerbating white matter lesions in leukoencephalopathy with thalamus and brainstem involvement and high lactate.

BACKGROUND: Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a hereditary disorder caused by biallelic variants in the EARS2 gene. Patients exhibit developmental delay, hypotonia, and hyperreflexia. Brain magnetic resonance imaging (MRI) reveals T2-hyperintensities in the deep white matter, thalamus, and brainstem, which generally stabilize over time. Herein, we report a case of LTBL, showing remitting and exacerbating white matter lesions. CASE DESCRIPTION: A non-consanguineous Japanese boy exhibited unsteady head control with prominent hypotonia, with no family history of neurological diseases. Brain MRI at one year of age revealed extensive T2-hyperintensities on the cerebral white matter, cerebellum, thalamus, basal ganglia, pons, and medulla oblongata. Magnetic resonance spectroscopy of the lesions showed lactate and myoinositol peaks. Whole-exome sequencing yielded novel compound heterozygous EARS2 variants of c.164G>T, p.Arg55Leu and c.484C>T, p.Arg162Trp. Interestingly, the lesions were reduced at three years of age, and new lesions emerged at eight years of age. At 10 years of age, the lesions were changed in the corpus callosum, deep cerebral white matter, and cerebellum, without physical exacerbation. The lesions improved one year later. CONCLUSION: We present the first case with remitting and exacerbating brain lesions in LTBL. EARS2 could relate to selective and specific brain regions and age dependency. Although the exact role of EARS2 remains unknown, the remitting and exacerbating imaging changes may be a clue in elucidating a novel EARS2 function in LTBL.

Two pediatric cases of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction of gastric lavage.

Detecting Pneumocystis jirovecii by bronchoalveolar lavage or lung biopsy is the gold standard for diagnosis of P. jirovecii pneumonia (PJP); however, these techniques are not always applicable in children because of their high invasiveness. We report two pediatric cases of PJP diagnosed by polymerase chain reaction (PCR) of gastric lavage that were successfully treated. To date, there are no reported cases of using PCR of gastric lavage to diagnose PJP. On the day of PJP onset, both the infants required respiratory support and infiltrative shadows were observed in both lung fields on chest radiography. Furthermore, their (1 â†’ 3)-ß-D glucan levels were elevated. P. jirovecii was detected by PCR of gastric lavage and trimethoprim-sulfamethoxazole was administered for 3 weeks, following which their condition improved. They were long-term steroid users, but without any prophylaxis. PCR of gastric lavage in cases of suspected PJP may help in confirming the diagnosis in children who have mild to moderate airway symptoms, or have difficulty with invasive examination like bronchoscopy.

Clinical and Bacteriologic Analysis of Nontypeable Haemophilus influenzae Strains Isolated from Children with Invasive Diseases in Japan from 2008 to 2015.

Haemophilus influenzae type b (Hib) conjugate vaccines have led to dramatic reductions in Hib disease among young children worldwide. Nontypeable H. influenzae (NTHi) is now the major cause of invasive H. influenzae infections. We investigated the clinical characteristics of invasive NTHi diseases among children in Japan, to clarify the pathogenicity of isolated NTHi strains. The mortality rate was 10.7%, with deaths occurring mainly among children with underlying comorbidities. Biotypes II and III were the most common, and most strains (64.3%) had multiple amino acid substitutions at the Asp-350, Ser-357, Ser-385, and/or Met-377 sites of penicillin-binding protein 3. Two strains were ß-lactamase positive and ampicillin-clavulanate resistant. Biofilm indices varied widely, and IS1016 was detected in 10.7% of the strains tested. Moreover, there was wide variation in the characteristics of invasive NTHi strains. NTHi strains, showing great genetic diversity, are responsible for most invasive H. influenzae infections in children in the postvaccine era. Continuous monitoring of NTHi strains responsible for invasive diseases in children is important to detect changes in the epidemiology of invasive H. influenzae infections in the postvaccine era.

Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan.

Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g. penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae. The evolution of bacterial resistance since TFLX approval is not known. To clarify the influence of quinolones administered to children since their approval, we examined the resistance mechanism of TFLX-resistant S. pneumoniae isolated from paediatric patients as well as patient clinical characteristics. TFLX-resistant strains (MIC ≥ 2 mg/L) were detected among clinical isolates of S. pneumoniae derived from children (≤15 years old) between 2010 and 2014. These strains were characterised based on quinolone resistance-determining regions (QRDRs), i.e. gyrA, gyrB, parC, and parE. In addition, the antimicrobial susceptibility, serotype, and multilocus sequence type of strains were determined, pulsed-field gel electrophoresis was performed, and patient clinical characteristics based on medical records were assessed for cases with underling TFLX-resistant strains. Among 1168 S. pneumoniae isolates, two TFLX-resistant strains were detected from respiratory specimens obtained from paediatric patients with frequent exposure to TFLX. Both strains had mutations in the QRDRs of gyrA and parC. One case exhibited gradual changes in the QRDR during the clinical course. This is the first study of quinolone-resistant S. pneumoniae isolated from children, including clinical data, in Japan. These data may help prevent increases in infections of quinolone-resistant S. pneumoniae in children; specifically, the results emphasise the importance of administering fluoroquinolones only in appropriate cases.

[Comparison of the clinical effectiveness of three neuraminidase inhibitors for Japanese pediatric patients with influenza in the 2013/2014 season].

We investigated the clinical symptoms of 206 pediatric patients with influenza virus infection and compared them among oseltamivir-treated, zanamivir-treated, and laninamivir-treated groups in 2013/2014 influenza season. The drug compliance of each neuraminidase inhibitor was good in all three groups. Although the duration of fever after administration of the first dose of each neuraminidase inhibitor were significantly prolonged in the patient with influenza B infection than in the patient with influenza A infection, no statistically significant difference in the clinical efficacy and the side effect among three groups were found. The number of biphasic fever episodes in patients treated with neuraminidase inhibitor was rare (two episodes of oseltamivir-treated group and one episode of zanamivir-treated group). In conclusion, under the good drug compliance, the efficacy of all three neuraminidase inhibitor was the same for the treatment of influenza virus infection in children.

The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture, Japan before and after the introduction of conjugate vaccines.

The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26, p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.