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• A test-negative case-control study examined an effectiveness of pertussis vaccine. • 4 doses of vaccine provided a high effectiveness in subjects under 6 years of age. • Vaccine effectiveness declines with time passed since the fourth dose. • 4 doses of pertussis vaccine have no preventive effect for school-aged children. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The article presents guidelines on working group for revision of guidelines for the use of Palivizumab in Japan. Topics include the precautions and indications on the drug's information leaflet, the appropriate use of this agent should be used on a patient by patient basis; and referring to guidelines issued by healthcare societies and other professional academic organizations.

In 2008, the number of pertussis cases increased substantially among Japanese adolescents, despite high coverage with acellular pertussis vaccine (DTaP). This study examined the effectiveness of DTaP vaccine in the routine immunization program in Japan. Between April 2009 and October 2012, we conducted a multicenter, case-control study, and compared the history of DTaP vaccination between 55 newly diagnosed pertussis cases and 90 age- and sex-matched controls. DTaP vaccine history was obtained by a self-administered questionnaire completed by their parents or guardians. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. DTaP vaccination of ≥1 dose revealed a significantly lower OR for pertussis (OR = 0.20, 95%CI, 0.04–0.97), and the OR of complete vaccination (4 doses) was 0.22 (0.04–1.05). Even after limiting subjects to those whose vaccination status could be confirmed by the immunization records, the negative associations were observed. The decreasing ORs of 4-dose vaccinees remained, even among subjects who had received the fourth dose ≥9.2 years earlier (OR = 0.11, 95%CI, 0.01–1.02). In conclusion, DTaP vaccination had a preventive effect for pertussis. Effectiveness was observed even 9 or more years after the final dose. [ABSTRACT FROM AUTHOR]

Abstract: Freeze dried, cell culture-derived Japanese encephalitis vaccine (Inactivated) (JEBIK®V) is approved for a three-dose primary immunization followed by a one-dose booster immunization in Japan. We conducted a multicenter, double-blinded, randomized controlled trial of the safety and immunogenicity of the vaccine in 370 healthy children who received three doses of 5, 2.5 or 1.25μg of virus protein per 0.5mL formulation subcutaneously. Children received two doses of test vaccine 7–28 days apart followed by a dose 6–12 months after the second vaccination. The three-dose regimen showed a good safety profile with no serious vaccine-related adverse events. Fever and reactions at the injection site were common adverse reactions at each dose of vaccine. The seroconversion rates were 100%, 99.2% and 95.0% after two doses in the 5, 2.5 and 1.25μg groups, respectively, and 100.0% after three doses in all groups. The geometric mean titers were high for all three formulations after the second and third doses, with a very clear dose–response relationship. These results indicate that JEBIK®V is likely to be a useful vaccine. [Copyright &y& Elsevier]

Abstract: The incidence of reported cases with pertussis has increased in young adults in Japan and the lack of additional booster immunizations containing pertussis components is suspected to be one of the causal reasons. Instead of DT immunization at 11–12 years of age, safety and immunogenicity were investigated using 0.2ml and 0.5ml of DTaP. 176 subjects in DTaP 0.5ml, 178 in DTaP 0.2ml, and 197 in DT 0.1ml groups were enrolled in clinical trial. The relative risk of local reactions in the DTaP 0.2ml group compared to the DT 0.1ml group was 1.13 (95% CI: 0.97–1.30), and that of the DTaP 0.5ml to the DT 0.1ml group was 1.34 (95% CI: 1.18–1.53). The relative risks of local pain and heat were 1.62 (95% CI: 1.33–1.98) and 1.59 (95% CI: 1.19–2.13), respectively, in the DTaP 0.5ml group compared to the DT 0.1ml group. Sero-positive rates against PT and FHA were 54% and 82% before immunization and increased to >95% for both after vaccination with no significant difference in GMT. Instead of the scheduled DT program, 0.2ml of DTaP was acceptable and demonstrated efficient immunogenicity. [ABSTRACT FROM AUTHOR]

Objectives: Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) has proven innovative modality for analyzing 3D morphology and is useful for understanding the pathophysiology of various cardiovascular disease. To elucidate mechanisms of aneurysmal wall enlargement after endovascular aortic repair (TEVAR or EVAR), we evaluated aortic wall samples after TEVAR and EVAR with XPCT. Methods: Human aortic samples of the descending aorta or abdominal aorta were obtained during open aortic repair for aortic aneurysm (Group-A; n=5),and for aneurysm expansion after endovascular repairs (Group-E: n=7). Normal aorta (Group-N: n=10), obtained from autopsy, were also investigated. Effective resolution of XPCT in Japan Synchrotron Radiation Research Institute / SPring-8 is 11.7 μm. Pathological analysis was performed, subsequently. Results: Age of patients was 76.8 ± 5.4 years old in Group-A, 83.4 ± 5.2 in Group-E, and 57.5 ± 9.5 in Group-N. In Group-E, time from endovascular repair to open aortic repair was 64.2 ± 7.2 months, and initial endovascular repair included TEVAR (n=2) and EVAR (n=5). Representative findings of three groups were demonstrated in figures, including XPCT findings (Fig.A), changes of wall density (B), and pathological findings (C). In Group-N, density of the tunica media was not different within tunica media and average of medial density was 1.085 ± 0.003g/cm3. In Group-A, thickness of aortic wall was lower than Group-N, but density of the tunica media was unchanged (1.079 ± 0.022g/cm3). On contrast, in Group-E, density of the tunica media was significantly lower than Group-N (1.063 ± 0.008; p < 0.005), and differences in density within tunica media were well correlated with distribution of elastic fibers and existence of medial necrosis in pathological analysis. Conclusions: X-ray phase-contrast tomography was a cutting-edge modality to understand aortic structures and degeneration of tunica media in aneurysm expansion after endovascular repair was clearly demonstrated. [ABSTRACT FROM AUTHOR]

Aims Post-extubation dysphagia (PED), an often overlooked problem, is a common and serious complication associated with mortality and major morbidity after cardiovascular surgery. Dysphagia is considered an age-related disease, and evaluating its long-term effects is a pressing issue with rapidly progressing ageing worldwide. Therefore, we examined the effect of PED on functional status and long-term cardiovascular events in patients undergoing cardiovascular surgery. Methods and results This single-centre, retrospective cohort study included 712 patients who underwent elective cardiovascular surgery and met the inclusion criteria. Patients were divided into PED and non-PED groups based on their post-operative swallowing status. The swallowing status was assessed using the Food Intake Level Scale. Functional status was evaluated as hospital-associated disability (HAD), defined as a decrease in activities of daily living after hospital discharge compared with preoperative values. The patients were subsequently followed up to detect major adverse cardiac and cerebrovascular events (MACCEs). Post-extubation dysphagia was present in 23% of the 712 patients and was independently associated with HAD (adjusted odds ratio, 2.70). Over a 3.5-year median follow-up period, MACCE occurred in 14.1% of patients. Multivariate Cox proportional hazard analysis revealed HAD to be independently associated with an increased risk of MACCE (adjusted hazard ratio, 1.85), although PED was not significantly associated with MACCE. Conclusion Post-extubation dysphagia was an independent HAD predictor, with the odds of HAD occurrence being increased by 2.7-fold due to PED. Hospital-associated disability accompanied by PED is a powerful predictor of poor prognosis. Perioperative evaluation and management of the swallowing status, and appropriate therapeutic interventions, are warranted. [ABSTRACT FROM AUTHOR]

• In Japan, Prenatal DTaP vaccination lacks required safety information. • Pertussis seroprevalence is approximately 70% among pregnant Japanese women. • Maternal antibody titers in early pregnancy reflect infant antibody titers. • Preconception DTaP vaccination is one way to obtain maternal immunity. • A national survey to evaluate the safety information of prenatal DTaP is necessary. An increasing number of countries have been introducing acellular pertussis vaccination during pregnancy for the prevention of neonatal pertussis. In response to the fact that infantile pertussis cases of 0–5 months age groups remained unchanged despite the universal vaccination program, prenatal pertussis vaccination has been a rising issue in Japan. Hence, we investigated the seroprevalence of pertussis, diphtheria, and tetanus antibodies in Japanese pregnant women and neonates, and evaluated the necessity of diphtheria-tetanus-acellular pertussis (DTaP) vaccination during the preconception or prenatal period. Maternal PT-IgG (EIA) and FHA-IgG (EIA) for the first trimester, within 1 week after delivery, and cord blood were collected, along with colostrum pertussis-IgA (ELISA), diphtheria-IgG (EIA), tetanus-IgG (EIA), and blood samples from the first trimester. The maternal seroprevalence of PT-IgG and FHA-IgG was 69 % and 75 %, respectively. All tested participants were positive for diphtheria-IgG and tetanus-IgG (100 %). First trimester PT-IgG/FHA-IgG antibody titers were significantly associated with cord blood PT-IgG/FHA-IgG titers (P < 0.001). We found that pertussis seroprevalence among pregnant Japanese women was approximately 70 %. The antibody seropositivity rate of pertussis was lower than that of diphtheria and tetanus. Fetal acquired passive immunity against pertussis is higher when the level of maternal antibody in the first trimester is sufficient. At least 30 % of study population did not reach to the threshold value to provide sufficient pertussis immunity for the neonates and themselves. The acellular pertussis vaccine (DTaP) approved in Japan lacks safety information for pregnancy, hence, a solution for prompt administration of prenatal acellular pertussis vaccination might be introducing DTaP in the preconception period. [ABSTRACT FROM AUTHOR]

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]

Introduction: We have been developing a closed-circuit cardiopulmonary bypass (CPB) system ("Dihead CPB") for application during coronary artery bypass grafting (CABG) and valve surgery. To strive for minimal hemolysis during Dihead CPB, we compared the hemolysis caused by three different suction systems and performed a clinical study with the newly applied suction system. Materials & Methods: We evaluated the hemolysis caused by roller-pump suction, the SmartSuction® Harmony® and wall suction systems with respect to suction speed and compared the systems by means of in vitro studies. A clinical study was also performed on 15 volunteers to assess hemolysis and the adequacy of the newly applied suction system with Dihead CPB. Results: Pressure inside the suction cannula was −22.5 ± 0.1 mmHg at a maximum flow of 1.5 L/min for roller-pump suction and −43.4 ± 0.1 mmHg at −150 mmHg of the set vacuum pressure of wall suction. With the SmartSuction, the pressure inside the cannula varied from −76.3 ± 1.0 to −130.3 ± 1.5 mmHg, depending on suctioning conditions. Suction speed (to suction 50 ml of blood) was fastest with the SmartSuction (69.7 ± 3.58 s) whereas, with roller suction, it was 117.3 ± 8.47 s and with wall suction 96.9 ± 7.10 s. The SmartSuction had the highest hemolysis rate (2.00 ± 0.33%) vs. 0.61 ± 0.10% for roller suction and 0.41 ± 0.11% for wall suction (p<0.001). The clinical study with wall suction showed no significant increase in plasma free hemoglobin during or after CPB compared with before surgery. Conclusions: Wall suction had less hemolysis than roller suction or the SmartSuction in the in vitro study and the clinical study with wall suction showed efficient suction speed and acceptable hemolysis, suggesting that Dihead CPB with wall suction is feasible for CABG. [ABSTRACT FROM AUTHOR]

Background In September 2015, Japan experienced an unusual increase in acute asthma hospitalizations of children that coincided with an enterovirus D68 (EV-D68) epidemic. The objective of this study is to investigate whether EV-D68 had a causal relationship with the spike in asthma hospitalizations. Methods A nation-wide retrospective survey of asthma hospitalizations of children was performed for the period from January 2010 through October 2015. The Japanese Society of Pediatric Allergy and Clinical Immunology asked its affiliated hospitals to report monthly numbers of hospitalizations, ICU admissions and mechanical ventilations due to acute asthma exacerbation. The data were retrieved from medical databases using predefined search criteria: diagnosis of asthma or asthmatic bronchitis, admission, and age <20 years. Monthly numbers of EV-D68 detection were also obtained from the Infectious Disease Surveillance Center of Japan. A Granger causality test was used to analyze the association of EV-D68 detections for asthma exacerbation. Results A total of 157 hospitals reported 87,189 asthma hospitalizations, including 477 ICU admissions and 1193 mechanical ventilations, during the survey period of 5 years and 10 months. The numbers of these events increased drastically in September 2015. The Granger causality test verified the association between EV-D68 and asthma hospitalizations/mechanical ventilations. The most-affected age group was 3–6 years old. Conclusions The spike in pediatric asthma hospitalizations in Japan in September 2015 was found to be associated with the EV-D68 epidemic. Respiratory pathogens can cause “epidemics” of asthma exacerbation. Coordinated surveillance of infectious diseases and asthma may be beneficial for prevention and better control of both illnesses. [ABSTRACT FROM AUTHOR]

Pediatric Rheumatology Association of Japan has developed evidence-based guideline of vaccination in pediatric rheumatic diseases (PRDs) as a part of Guideline of Vaccination for Pediatric Immunocompromised Hosts. Available articles on vaccination in both adult rheumatic diseases and PRDs were analyzed. Non-live vaccines are generally safe and effective in patients with PRDs on corticosteroid, immunosuppressant, and/or biologics, although efficacy may be attenuated under high dose of the drugs. On the other hand, efficacy and safety of live-attenuated vaccine for the patients on such medication have not been established. Thus, live-attenuated vaccines should be withheld and, if indicated, may be considered as a clinical trial under the approval by Institutional Review Board. All patients with PRDs anticipating treatment with immunosuppressants or biologics should be screened for infection of hepatitis B and C and tuberculosis before the commencement of medication. Varicella vaccine should be considered in sensitive patients ideally 3 weeks or longer before the commencement of immunosuppressants, corticosteroids, or biologics. Bacille Calmette-Guérin should be withheld at least for 6 months after birth, if their mothers have received anti-tumor necrosis factor-α antibodies during the second or third trimester of pregnancy. [ABSTRACT FROM AUTHOR]

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a 'well-controlled level' for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Palivizumab effectively prevents severe respiratory syncytial virus (RSV) disease in preterm infants. Our objective was to test whether palivizumab prophylaxis given to preterm infants during the first RSV season reduces the incidence of subsequent recurrent wheezing up to 3 years of life. METHODS: We conducted an observational prospective multicenter (52 registered hospitals in Japan) case-control study in preterm infants with a gestational age between 33 and 35 weeks followed for 3 years. During the 2007-2008 RSV season, the decision to administer palivizumab was made based on standard medical practice. In April 2008, 52 hospitals were recruited. Study participants were pro- spectively followed to the age of 3 years. Parents of study subjects reported the infants' physician's assessment of recurrent wheezing, used a report card and a novel mobile phone-based reporting system by using the Internet. The primary end point was the incidence of physician-diagnosed recurrent wheezing. RESULTS: Of 444 preterm infants enrolled, 349 received palivizumab during the first 6 months of life and 95 infants did not. Physician- diagnosed recurrent wheezing was observed in 6.4% and 18.9% of infants in the treated and untreated groups, respectively (P < .001). This difference remained significant after adjustment for known risk factors of recurrent wheezing (P < .001). CONCLUSIONS: Palivizumab prophylaxis administered to preterm infants 33 to 35 weeks' gestational age is associated with a significantly lower incidence of recurrent wheezing during the first 3 years of life. [ABSTRACT FROM AUTHOR]

Background: Young infants with influenza virus infection are frequently hospitalized, and are at risk of serious complications including death. With the emergence of pandemic influenza A/H1N1 2009, oseltamivir was approved for use in Europe and the USA, including use in infants aged < 3 months. However, few data are available regarding the safety of oseltamivir treatment for influenza in infants aged < 3 months. Methods: The clinical data from Japanese infants aged < 3 months with laboratory-confirmed influenza virus infections, who were treated with oseltamivir between October 2009 and April 2011, were collected and analyzed. Results: Forty-four infants were included in the study. The median age was 1 month (range 4 days to 2 months) and median body weight was 4.5 kg (range 2.6-7.6 kg). Thirty-eight infants (86%) had no underlying diseases. The most common presenting symptom was fever (42 infants, 95%). There were no cases of influenza-associated encephalopathy or myocarditis. The median time between the onset of influenza symptoms and initiation of oseltamivir treatment was 0 days (range 0-7 days), with treatment initiated within 1 day in 40 infants (91%). The oseltamivir dose was 1.5-2 mg/kg twice daily in 98% of infants. No serious adverse events were identified during treatment. All infants recovered completely. Conclusions: Treatment of influenza with oseltamivir 1.5-2 mg/kg twice daily may be safe in infants aged < 3 months. [ABSTRACT FROM AUTHOR]

Members of the Japanese Society of Pediatric Pulmonology and the Japanese Society for Pediatric Infectious Diseases developed the Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating the appropriate diagnosis and treatment of childhood respiratory infections. To date, a first edition (2004) and a revised edition (2007) have been issued. Many problems complicate the diagnosis of the pathogens responsible for bronchopulmonary infections in children. The Guidelines were the first pediatric guidelines in the world to recommend treatment with antimicrobials suited to causative pathogens as identified from cultures of sputum and other clinical specimens collected from infection sites and satisfying assessment criteria. The major causative microorganisms for pneumonia in infants and children were revealed to be Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. This manuscript describes the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2007, with a focus on pneumonia. [ABSTRACT FROM AUTHOR]

The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005. [ABSTRACT FROM AUTHOR]

Members of the Japanese Society of Pediatric Pulmonology and the Japanese Society for Pediatric Infectious Diseases developed the Guidelines for the Management of Respiratory Infectious Diseases in Children with the objective of facilitating the appropriate diagnosis and treatment of childhood respiratory infections. To date, a first edition (2004) and a revised edition (2007) have been issued. Many problems complicate the diagnosis of the pathogens responsible for bronchopulmonary infections in children. The Guidelines were the first pediatric guidelines in the world to recommend treatment with antimicrobials suited to causative pathogens as identified from cultures of sputum and other clinical specimens collected from infection sites and satisfying assessment criteria. The major causative microorganisms for pneumonia in infants and children were revealed to be Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. This manuscript describes the Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan 2007, with a focus on pneumonia. [ABSTRACT FROM AUTHOR]