[Neutralizing antibody titer after recommended early vaccination against Japanese encephalitis].

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.

Differences in Clinical Findings Based on the Duration of Symptoms and Age of Children With Ileocolic Intussusception: A Single-Institution Survey in Rural Japan.

OBJECTIVES: The objective of this study was to determine whether the rates of abdominal pain or irritability, vomiting, and hematochezia differ depending on the duration of symptoms and age of the children with ileocolic intussusception. METHODS: We retrospectively investigated the charts of ileocolic intussusception children between January 2008 and December 2017 at a rural general hospital in Japan. Children were separated into 2 groups: the early visiting group, including children examined within 6 hours after onset, and the late visiting group, including children examined more than 6 hours after onset. We further separated them into 2 groups based on age: the infant group (age, <18 months) and the child group (age, ≥18 months). We compared clinical features, such as abdominal pain or irritability, vomiting, and hematochezia, between each group. RESULTS: Among 105 children with ileocolic intussusception, 51 were in the early visiting group and 49 were in the infant group. Hematochezia less frequently occurred in the early visiting group than in the late visiting group (29% vs 50%, P = 0.046). Furthermore, abdominal pain or irritability occurred less frequently in the infant group than in the child group (79.6% vs 98.2%, P = 0.003). Conversely, vomiting and hematochezia were more frequent in the infant group than in the child group (83.7% vs 51.8%, P < 0.001; 55.1% vs 26.8%, P = 0.005). CONCLUSIONS: Clinical features of pediatric ileocolic intussusception may depend on symptom duration and age.

Reconstitution of Oseltamivir Capsules for Pediatric Use on a Long-Term Cruise: A Treatment Option.

Influenza is a concerning disease in terms of risk management for cruise passengers during a voyage. Currently, cruise passengers include children in addition to elderly people. Oral oseltamivir can be used to treat pediatric influenza. In addition, early antiviral treatment may reduce the spread of influenza on board. However, the capsule form of oseltamivir is not of the recommended dosage for children. In this report, we describe 2 siblings who acquired influenza during travel on a world cruise ship and were treated with decapsulated oseltamivir. The siblings' mother was instructed to decapsulate a 75 mg oseltamivir capsule, suspend the powder in 15 mL of water (5 mg·mL-1), stir well, and administer the required amount of medicine orally to each patient using a syringe. Both patients recovered successfully with no complications. The presented case suggests that suspending decapsulated oseltamivir in water and measuring the required amount with a syringe for orally administration to children with influenza can be a safe treatment strategy in resource-limited settings.

A Nationwide Survey of Pediatric-onset Japanese Encephalitis in Japan.

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.

Febrile status epilepticus due to respiratory syncytial virus infection.

BACKGROUND: Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. METHODS: We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. RESULTS: A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. CONCLUSIONS: RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae.

Macadamia Nut-Induced Anaphylactic Shock Requiring Repeated Intramuscular Adrenaline Administration in a Three-Year-Old Girl.

Cases of macadamia nut-induced anaphylactic shock have been rarely reported. We report the case of a three-year-old girl with anaphylactic shock who presented with generalized erythema two hours after ingesting macadamia nuts. She required two doses of intramuscular adrenaline for the treatment of anaphylactic shock. The diagnosis of macadamia nut allergy was confirmed by a prick-by-prick skin test using roasted and raw macadamia nut paste extracts and elevated serum macadamia nut-specific immunoglobulin E (IgE) levels. Appropriately using a prick-by-prick test may contribute to accurately diagnosing macadamia nut allergy, thus preventing the unnecessary avoidance of other nuts. Considering the potential for severe shock induced by macadamia nut allergy, vigilant monitoring of blood pressure changes is imperative in children presenting with immediate-type allergic reactions, such as vomiting and skin symptoms, following macadamia nut ingestion.

Atypical Cat Scratch Disease With Splenic Lesion Mimicking Kawasaki Disease in a Healthy 5-Year-old Girl.

BACKGROUND: Atypical cat scratch disease (CSD) and Kawasaki disease (KD) are differential diagnoses of pediatric febrile illnesses. Diagnosing atypical CSD can be challenging because of its wide range of symptoms. However, its similarity to KD has rarely been addressed. METHODS: We present the case of a 5-year-old girl with atypical CSD and splenic lesions who fulfilled the diagnostic criteria for KD. We also conducted a literature review of previous cases in which CSD was suspected alongside KD and detailed the diagnosis and treatment processes. RESULTS: A previously healthy 5-year-old girl with prolonged fever and symptoms resembling those of KD was admitted to our hospital. There was no evidence of an abnormal coronary artery, and her condition did not improve after the initial treatment for KD and bacterial infection. A history of contact with cats and multiple granulomatous lesions in the spleen on abdominal ultrasonography led to a clinical diagnosis of atypical CSD. Trimethoprim-sulfamethoxazole treatment resulted in symptom resolution. Elevated serum Bartonella henselae IgG and IgM antibodies confirmed the diagnosis of CSD. In this case, we avoided second-line treatment for KD with an alternative CSD diagnosis. Additionally, we identified 4 documented cases of CSD presenting with KD-like features in the literature. Intravenous immunoglobulin was ineffective in all cases, including the present case. CONCLUSIONS: In cases of atypical CSD where KD is suspected, actively seeking organ-specific symptoms may facilitate an early clinical diagnosis of CSD. Adopting this approach could yield multiple advantages, including reduced invasiveness for the patient and decreased healthcare-related expenditures.

A Case of Aseptic Meningitis Without Rash Possibly Associated With Varicella Vaccine.

Varicella-zoster virus (VZV) may cause aseptic meningitis in the pediatric age group. We describe a pediatric case of aseptic meningitis with a substantial increase of the paired serum antibody to VZV in which the child did not have skin rash during the course of illness. The patient was a 13-year-old boy without any history of exposure to VZV who was admitted with headache, vomiting, and low-grade fever. He had received one dose of varicella vaccine derived from the Oka/Biken strain (vOka) at the age of one year. Cerebrospinal fluid (CSF) analysis on admission revealed an elevated white blood cell count at 609/mm3 with 99.6% mononuclear cells. As his symptoms resolved after lumbar puncture alone, he was discharged on the seventh day of hospitalization without receiving any specific medication. Serum VZV-IgG titer was found to be substantially elevated after two weeks. VZV infection and reactivations associated with vaccination, as well as past infections, should be included in the differential diagnoses of pediatric aseptic meningitis, even in the absence of skin rash in the entire course. Polymerase chain reaction (PCR) testing for VZV DNA in CSF should be performed in all cases, if available.

Food Protein-Induced Enterocolitis Syndrome Causing Hypovolemic Shock in Infants With Down Syndrome.

This study aimed to investigate the clinical characteristics of severe food protein-induced enterocolitis syndrome (FPIES) in patients with Down syndrome. We report the cases of three infants with Down syndrome who were diagnosed with FPIES. All patients presented with hypovolemic shock, metabolic acidosis, and acute kidney injury after introducing a milk-based formula. They required aggressive fluid resuscitation and alternative nutrition. All three patients survived without any complications after the treatment. FPIES may cause hypovolemic shock in infants with Down syndrome and these patients need prompt fluid resuscitation.

[Group B streptococcal bacteremia in a 10-year-old girl undergoing corticosteroid therapy].

Group B streptococcus (GBS), a major cause of neonate and pediatric sepsis and meningitis, rarely causes invasive infection beyond infancy. We report the case of a 10-year-old girl developing GBS bacteremia during corticosteroid therapy for chronic idiopathic thrombocytopenic purpura. Brought to the emergency room due to sudden high fever and abdominal pain, she was in compensated shock. White blood cell count was 19,600/mm3 and C-reactive protein 0.18 mg/dL. She was diagnosed with sepsis and admitted for evaluation. Cefotaxime (100 mg/kg/day) administration and fluid replacement were begun immediately after blood culture. Her condition improved over the next 6 hours and she was afebrile by the next day. GBS isolated from blood had a serotype of Ib. Based on routine susceptibility testing, this strain was susceptible to penicillin, cephem, carbapenem, erythromycin, clindamycin, and vancomycin, but resistant to quinolone, including levofloxacin (MIC > or = 8.0 microg/mL) and gatifloxacin (MIC > or = 4.0 microg/mL). She was discharged on hospital day 8. This is, to our knowledge, the first report of pediatric meningitis-free GBS bacteremia in Japan. Physicians should therefore be aware of the possibility of invasive GBS infection such as bacteremia in this age group, especially during immunosuppressive therapy, because epidemiological studies in the US have showed significant mortality in those aged 1 to 14 years old with invasive GBS.

Emergence of Salmonella enterica subsp. enterica serovar Chester in a rural area of Japan.

In Japan, only one outbreak of Salmonella enterica subsp. enterica serovar Chester (S. Chester) has been confirmed in 1999. We performed a single-center retrospective case review of S. Chester infections that occurred in a rural area of Japan in 2016 (n=8). Case 5 and 6 occurred in twin infants who had contact with a pet dog. The dog's stool culture was positive for S. Chester. Pulsed-field gel electrophoresis and cluster analysis of S. Chester strains revealed that all the isolates appeared to be derived from the same genetic clone. Emergence of Salmonella infection can be overlooked if cases are not reported to health authorities; therefore, core hospitals should play a role to alert the occurrence of public health issue.

Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis mimicking Kawasaki disease.

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.

Longitudinal magnetic resonance imaging changes in Japanese encephalitis.

BACKGROUND: Japanese encephalitis is a flavivirus that can cause pandemic encephalitis, and is prevalent in Southeast Asia and Australia. Brain images of patients with Japanese encephalitis are characterized by thalamic lesions, distinct from those seen in viral encephalopathies caused by the herpes simplex virus and West Nile virus. AIM: Herein, we describe for the first time a time-dependent magnetic resonance imaging pattern in Japanese encephalitis in a 10-month-old Japanese boy. CASE: The patient was a previously healthy 10-month-old Japanese boy, who exhibited acute-onset flaccid tetraplegia and loss of tendon reflexes. RESULTS: Brain MRI showed characteristic thalamic changes on diffusion weighted images from spotty to uniform and from the left to the right side, associated with low apparent diffusion coefficient maps. These images suggest that the Japanese encephalitis virus may first affect the unilateral thalamus, possibly expanding to the other side, with characteristic patterns changing from spotty to uniform in a manner consistent with the presentation of cytotoxic edema. CONCLUSION: This report first showed longitudinal magnetic resonance changes in Japanese encephalitis, which may help in accurate diagnosis and in discrimination from other etiologies.

Anterior cingulate cortex involvement in non-paraneoplastic limbic encephalitis.

BACKGROUND: Non-paraneoplastic limbic encephalitis is characterized by attention deficit, loss of emotion control, and impaired memory. Viral infection can cause acute encephalitis in children, occasionally exhibiting clinical features of limbic dysfunction. However, how viral infection affects the limbic system remains to be elucidated. CASE DESCRIPTION: A 5-year-old Japanese boy was admitted to our hospital because of high fever and status epilepticus. After seizures were controlled by diazepam, he exhibited attention deficit, loss of emotion control, and impaired memory, suggesting acute limbic encephalitis. Since titers of antibodies against Coxsackie virus A10 were significantly elevated in the serum, we diagnosed him with non-paraneoplastic limbic encephalitis associated with the viral infection. Brain magnetic resonance imaging demonstrated involvement of anterior cingulate cortex as well as white matter of the frontal lobe in the acute period. After steroid pulse therapy, these brain lesions subsequently disappeared in a time-dependent manner, beginning with the frontal lobe white matter and extending to the anterior cingulate cortex, and his psychological symptoms also disappeared. CONCLUSION: To the best of our knowledge, this is the first report to show the involvement of the region from the anterior cingulate cortex to the frontal lobe white matter. Clinical features such as seizures, attention deficit, loss of emotion control, and impaired memory suggest that this viral limbic encephalitis possibly extended from the frontal white matter to the anterior cingulate cortex via inter-neuronal connections in a time-dependent manner.

Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes.

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.