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Abstract Background Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire AVPR2 locus and approximately half of the Rho GTPase-activating protein 4 (ARHGAP4) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity. ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking AVPR2 and all of ARHGAP4 showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells. Methods PCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique. Results We evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire AVPR2 locus and approximately half of the ARHGAP4. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking ARHGAP4 revealed that expression of RhoGAP family genes was not influenced greatly by the lack of ARHGAP4. Conclusion These results suggest that loss of ARHGAP4 expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of ARHGAP4 does not result in clinical immunodeficiency.

Background Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. Methods A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. Results Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005–15 than that during 1995–2004 (4.3 × 10–3 vs 1.1 × 10–3 per 100000, respectively; P =.04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. Conclusions Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children and is characterised as necrotising vasculitis predominantly affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD) is a common systemic vasculitis, typically observed in children, which affects the medium-sized vessels, including the coronary arteries. An 11-year-old girl who developed AAV while receiving PTU therapy for Graves' disease is described. She was admitted to hospital following a 2-day history of fever, cervical adenopathy, cheilitis and papular rash, 3 weeks after an increase in the PTU dose. Despite discontinuation of PTU and the administration of intravenous antibiotic therapy, her clinical condition deteriorated and over the next 2 days she developed severe diarrhoea, conjunctival injection and swelling and redness of the right index finger. Additional findings included liver dysfunction, hydrops of the gallbladder, coagulopathy and urine abnormalities, suggesting glomerulonephritis. She met the diagnostic criteria for KD and received intravenous immunoglobulin (IVIG) combined with prednisolone, with rapid resolution of clinical and laboratory parameters. Peeling of the right index fingertip became evident on Day 12 of admission. Serial ultrasound cardiography demonstrated no evidence of cardiac involvement. A high titre of myeloperoxidase ANCA was detected in the patient's serum on admission, and the titre decreased during the convalescent stage. This case demonstrates that children with PTU-associated AAV may present with clinical features mimicking KD, and that IVIG along with corticosteroid therapy may be effective in treating patients with drug-induced severe systemic AAV. [ABSTRACT FROM AUTHOR]

Intense pain may be an important marker of severe staphylococcal scalded skin syndrome. Our case presented with relentless pain requiring opioids even before the skin desquamation was noted, in addition to more than 30% of the affected skin, despite normal vital signs. In cases of suspected staphylococcal scalded skin syndrome with severe pain, prompt vancomycin administration should be considered. [Extracted from the article]

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Objective　Following the case of a 10-month-old with Japanese encephalitis in Chiba in 2015, the Chiba Pediatric Association and Chiba Medical Association recommended that children receive the Japanese encephalitis vaccine at six months of age. In this study, we investigated early vaccinations and standard vaccinations of children in a patient outbreak area. Additionally, we examined changes in the timing of vaccination initiation and the acquisition and maintenance of protective immunity before and after the early vaccination recommendation.Methods　With the cooperation of the medical institution designated for Type II Infectious Diseases, which treated affected children in 2015, the history and timing of vaccinations for children who visited the hospital between October 2018 and March 2020 were investigated, and serum samples were collected. The data obtained in this study and the Ministry of Health, Labour and Welfare's Community Health Service Report were used to investigate the timing of vaccinations. Neutralizing antibody titers in serum were quantified with the focus measurement method and examined with respect to the number of vaccinations, doses, and number of days since vaccination.Results　A total of 154 samples were obtained, with 89 from the vaccinated group and 65 from the unvaccinated group. There was no difference in the percentage of children based on the age of first vaccination between Japan, Chiba Prefecture, and the study subjects until FY2015, but from FY2016 onward, the percentage of children vaccinated early was higher among the study subjects, as well as for children from Chiba Prefecture and Japan, in that order. The antibody possession rate by vaccination frequency was 9.2% for the unimmunized, 87.5% for those vaccinated once, 95.1% for those vaccinated twice, and 100% for those vaccinated three times. In the group vaccinated twice, antibody titers of children who received half the vaccine dose were significantly lower than those of children who received the normal dose.Conclusion　In the districts targeted in this study, significantly more children under three years of age were vaccinated before the early vaccination recommendation, suggesting the effectiveness of that recommendation. In addition, the high rate of antibody positivity among unvaccinated children suggests that it is important to promote early vaccination in areas at high risk for Japanese encephalitis. In this study, there was no evidence of attenuation of antibody titers over time after early immunization, but the possibility remains that the children who completed early immunization received a booster due to pathogen exposure and maintained antibody titers, given that Japanese encephalitis was endemic in the target area.

Background: Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children., Methods: A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles., Results: Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005-15 than that during 1995-2004 (4.3 × 10-3 vs 1.1 × 10-3 per 100000, respectively; P = .04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis., Conclusions: Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)