Progresses Toward Polio Eradication in Asian Countries: Its History and Japan's Contributions.

Japan experienced a large outbreak of wild poliovirus in the 1960s. The government made an exceptional decision to import oral polio vaccines (OPVs) from the Soviet Union and Canada while bypassing the usual approval process for medical products. Mass vaccination and subsequent, routine immunization successfully contained the wild poliovirus; the last case in Japan was reported in 1980. Domestic OPV had been used to sustain Japan's polio-free state. In 2012, the world's first inactivated polio vaccine developed from the Sabin vaccine replaced OPVs. Domestic vaccines combined with Sabin-derived inactivated polio vaccine are currently used in Japan. When the World Health Assembly announced the Global Polio Eradication Initiative in 1988, the Japanese government made a commitment to support endemic countries. The Japan International Cooperation Agency supported the establishment of microbiological laboratories, surveillance, distribution of polio vaccines and capacity building. Vaccine-derived poliovirus emerged as a new, international risk in the early 2000s. Vaccine-derived poliovirus was also detected in several Asian countries and required an outbreak response with additional vaccinations and strengthened surveillance. Genetically stable, novel, oral polio vaccine type 2 became available for use in outbreak responses and was used in Indonesia. Japan maintains its commitment to work toward the eradication of the poliovirus.

Joint Fluid Cell Count in Acute Bacterial Arthritis Patients Proven Positive Culture in Children.

BACKGROUND: Acute bacterial arthritis (ABA) is a serious, pediatric infection that can result in motor comorbidities. Normally, a joint fluid white blood cell (WBC) count of 50,000 or more cells/mm 3 is used to make a presumptive diagnosis of ABA. This study evaluated the utility of the joint fluid WBC count for diagnosing pediatric ABA confirmed by a positive culture result. METHODS: Patients with ABA between March 2010 and March 2023 at Tokyo Metropolitan Children's Medical Center were included. ABA was confirmed by positive joint fluid culture results for a pathogenic organism. Patients with negative results and those without a joint fluid WBC count were excluded. Electronic medical records were retrospectively reviewed for demographic data, timing of arthrocentesis, culture results and the joint fluid WBC count. RESULTS: Ninety-five patients with ABA were identified; of these, 22 were included. The median age was 5 years [interquartile range (IQR): 2-10 years]. Males comprised 55% of the population. The median joint fluid WBC count was 19,575 (IQR: 6806-47,388) cells/mm 3 , and 23% of the patients had 50,000 cells/mm 3 or more. The median time from symptom onset to arthrocentesis was 3 days (IQR: 2-5 days). The isolated organisms were methicillin-susceptible Staphylococcus aureus (50%), methicillin-resistant S. aureus (9%), Streptococcus pyogenes (27%), Streptococcus pneumoniae (5%), Klebsiella pneumoniae (5%) and Salmonella spp. (5%). CONCLUSIONS: Most of the patients with ABA confirmed by positive results of a joint fluid culture had a joint fluid WBC count of less than 50,000 cells/mm 3 .

Viral loads of parainfluenza virus type 3 and severity of respiratory diseases in children.

BACKGROUND: Parainfluenza virus type 3 (PIV-3) is one of the common pathogens for respiratory infections in children. Whether viral load of PIV-3 is associated with severity of respiratory diseases in children is not yet known. Our aim was to determine significance of PIV-3 viral load among infected children. METHODS: We conducted a single-center, retrospective study at Tokyo Metropolitan. Children's Medical Center, Japan, from June to August 2021. Hospitalized children were screened with a posterior nasal swab for multiplex PCR, and viral load was subsequently measured from remained samples by real-time PCR. Demographic data were collected from digital charts. PIV-3 positive patients were categorized into mild group with no oxygen demand, moderate group with low-flow oxygen demand and severe group with high-flow nasal cannula oxygen or non-invasive positive pressure ventilation or mechanical ventilation. Viral loads were compared among mild, moderate and severe groups. RESULTS: 151 patients were positive for PIV-3. We found no statistically significant association among PIV-3 viral load and severity of respiratory diseases (p = 0.35), and no statistically significant association between severity of illness and co-detection of other viruses. In each severity group, relatively high viral load per posterior nasal swab was observed at the time of testing. CONCLUSION: Among PIV-3 patients, we could not find statistically significant between viral load and their severity, therefore we could not conclude that viral load is a good surrogate marker for clinical severity of PIV-3.

Lessons From the Wrong Isolation Policy Violating Human Rights for Leprosy in Japan.

Leprosy, caused by Mycobacterium leprae , is one of the so-called "neglected tropical diseases" and is found today mainly in Africa, Asia and South America. Although oral antibiotics capable of curing leprosy are now available, the disease is still misunderstood and feared by the public because of the unsightly deformities that it may cause. In Japan, leprosy has been present since the 8th century and was regarded as a hereditary disease; people avoided marrying into a family with a member affected by leprosy. At the beginning of the 20th century, the Japanese government instituted a policy of lifetime quarantine of individuals with leprosy to eradicate the disease, thereby purposely disseminating negative and inaccurate perceptions of the disease as deadly and highly contagious and fostering a long-lasting prejudice among the general public towards those affected. Even after effective treatments became available, the government continued quarantining patients until 1996. The government has since then apologized to the patients for violating their constitutionally guaranteed human rights. Children with leprosy and children born to parents with leprosy were also victims of the policy and prejudice created. We describe herein the history of leprosy-related policies in Japan to emphasize the importance of balancing public health policy with human rights.

Post coronavirus disease 2019 condition in children at a children's hospital in Japan.

BACKGROUND: Acute coronavirus disease 2019 (COVID-19) is associated with chronic symptoms. These have been termed the "post COVID-19 condition." The data on this condition in children are still limited. We therefore aimed to elucidate the characteristics of this post COVID-19 condition. METHODS: Children referred to a long COVID-19 clinic were included at Tokyo Metropolitan Children's Medical Center between October 2021 and July 2022. Children with another diagnosis and those who failed to meet criteria for post COVID-19 condition were excluded. Demographic and clinical data were collected retrospectively. RESULTS: Of 33 referrals, nine were excluded, and 24 fulfilled the criteria for post COVID-19 condition. The median age and percentage of girls were 12.5 (IQR: 11-13) years and 29.2%, respectively. All the patients had mild, acute COVID-19. Dysgeusia and brain fog was observed more frequently during the Delta and Omicron variant periods, respectively. School absenteeism >4 weeks was observed in 41.6% of the patients. Common symptoms included malaise, headache, dysgeusia, and dysosmia. The median duration of post COVID-19 condition was 4.5 (IQR: 2.8-5.2) months. Pain management and counseling using the pacing approach were the most commonly offered treatments. Symptom resolution and improvement was observed in 29.2% and 54.2% of the patients, respectively. CONCLUSIONS: One third of the patients referred for long COVID did not fit the definition of the post COVID-19 condition. After a median follow up of 4.5 months, the majority of the cases resolved or improved.

Natto intake is a risk factor of Bacillus subtilis bacteremia among children undergoing chemotherapy for childhood cancer: A case-control study.

BACKGROUND: Natto, a popular, daily food in Japan, is made from soybeans fermented by Bacillus subtilis. The aim of this retrospective case-control study (matched 1: 4) is to determine whether natto intake is a risk factor of B. subtilis bacteremia in this population. METHODS: The retrospective, matched case-control study was conducted at Tokyo Metropolitan Children's Medical Center between April 2012 and June 2020 and included pediatric patients younger than 15 years who received chemotherapy for cancer. Patients who received hematopoietic stem cell transplantation were excluded. Patients with B. subtilis bacteremia were compared with controls matched for age and underlying diseases. Dietary information within seven days from the date of blood culture collection was extracted from medical records. Multivariate logistic regression was performed to define the risk factors of B. subtilis bacteremia. RESULTS: In total, 23 patients with B. subtilis bacteremia were identified and matched to 92 controls. The percentage of patients and controls who ingested natto within seven days from the date of blood culture collection was 78% and 50%, respectively. On univariate analysis, the odds ratio of natto intake for B. subtilis bacteremia was 3.6 (95% confidence interval [CI]: 1.2-10.5). Multivariable logistic regression tests after controlling for neutropenia revealed that B. subtilis bacteremia was associated significantly with natto intake at odds ratio 3.3 (95% CI: 1.1-9.6). CONCLUSION: Natto intake was associated with B. subtilis bacteremia during chemotherapy for childhood cancer.

Clinical characteristics and treatment of IMP-type carbapenemase-producing Enterobacteriaceae bacteremia: Case series and literature review.

BACKGROUND: Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. METHODS: Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. RESULTS: Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. CONCLUSIONS: We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.

Clinical evaluation of a new rapid immunochromatographic test for detection of Bordetella pertussis antigen.

A more rapid and less complicated test to diagnose pertussis is required in clinical settings. We need to detect Bordetella pertussis, which mainly causes pertussis, as early as possible, because pertussis is more likely to become severe in infants, and people around them can easily become a source of infection due to its strong infectivity. Nevertheless, methods that can detect B. pertussis rapidly and efficiently are lacking. Therefore, we developed a new immunochromatographic antigen kit (ICkit) for the early diagnosis of pertussis. The ICkit detects B. pertussis antigens in a nasopharyngeal swab without equipment and provides the result in about 15 min with a simple procedure. Additionally, a prospective study to evaluate the ICkit was conducted in 11 medical institutions, involving 195 cases with suspected pertussis. Compared with the real-time polymerase chain reaction (rPCR), the sensitivity and specificity of the ICkit were 86.4% (19/22) and 97.1% (168/173), respectively. The ICkit detected the antigen in both children and adults. Furthermore, the ICkit detected the antigen until the 25th day from the onset of cough, when rPCR detected the antigen. Thus, the ICkit demonstrated a high correlation with rPCR and would help diagnose pertussis more rapidly and efficiently.

Imported Infectious Diseases, Tropical Diseases and Local Endemic Infectious Diseases in Japan.

We aimed to describe the historical perspectives and the current epidemiology of tropical, imported and local endemic infectious diseases in Japan in this review. Public health legislation for infectious diseases and immigration statistics were overviewed to provide the background of the infectious disease situation in Japan. Many tropical diseases were successfully controlled and eliminated in the latter half of the 20th century and the majority of those diseases are imported today. The trend of the main 15 imported infectious diseases before the advent of COVID-19 was summarized as well as local endemic infectious diseases in Japan. Transmission risks of traditional cuisines, lifestyles and nature exposures in Japan are introduced to guide clinicians for travel advice to prevent those local infectious diseases.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants.

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

Predictor of Early Administration of Antibiotics and a Volume Resuscitation for Young Infants with Septic Shock.

(1) Background: It is critical to administer antibiotics and fluid bolus within 1 h of recognizing sepsis in pediatric patients. This study aimed to identify the predictor of the successful completion of a 1-h sepsis bundle for infants with suspected sepsis. (2) Methods: This is an observational study using a prospective registry including febrile young infants (aged < 90 days) who visited a pediatric emergency department with a core body temperature of 38.0 °C or higher and 36.0 °C or lower. Univariate and logistic regression analyses were conducted to determine the predictor (s) of successful sepsis bundle completion. (3) Results: Of the 323 registered patients, 118 patients with suspected sepsis were analyzed, and 38 patients (32.2%) received a bundle-compliant treatment. Among potential variables, such as age, sex, and vital sign parameters, the logistic regression analysis showed that heart rate (odds ratio: OR 1.02; 95% confidence interval: 1.00-1.04) is a significant predictor of the completion of a 1-h sepsis bundle. (4) Conclusions: We found that tachycardia facilitated the sepsis recognition and promoted the successful completion of a 1-h sepsis bundle for young infants with suspected septic shock and a possible indicator for improving the quality of the team-based sepsis management.

Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility.

A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be ß-lactamase-producing ampicillin resistant strains, while 20.8% were ß-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were ß-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum ß-lactamase-producing E. coli was 14.3%.

School-based approach for parasitic disease control in Japan and Africa.

Japan has achieved significant improvements in the control and prevention of parasitic infections through a school-based approach since the 1930s. The use of chemical fertilizers in agriculture, safe water and food, and improved sanitation and hygiene also contributed to the near eradication of endemic parasites. However, parasite infections continued to affect children mostly in resource-limited countries. The African continent has one of the highest burdens of such infections. The application of school-based approaches has several advantages where the structure of health-care systems is not optimal. In Africa, soil-transmitted helminths and schistosomiasis are frequently targets for school-based public health intervention. Mass drug administration by teachers at school can reach targeted children effectively and safely. The limitations of this approach include missing unattended children and absentee of teachers. Initially, mass drug administration at school for parasitic infections was thought to improve health and even socioeconomic status of children in the community. However, more recently the socioeconomic impact has been questioned although the reduction of parasitic diseases is still apparent. Moreover, other basic public health measurements such as increased toilet use, assuring safe water access and avoiding the use of human excrement as an agricultural fertilizer, are equally important for control and prevention of parasitic diseases. Further global efforts should be continued to achieve equal health for every child in a sustainable way.

National trends in appropriate antibiotics use among pediatric inpatients with uncomplicated lower respiratory tract infections in Japan.

BACKGROUND: Japan was ranked as the worst country of 36 high-income countries in terms of oral antibiotic consumptions for children. Knowing the patterns and variations of antibiotic use for pediatric inpatients with uncomplicated respiratory infections is an important step to promote judicious antibiotic use. METHODS: Discharge records were extracted for children aged between 3 months and 15 years with acute lower respiratory tract infections for the fiscal years 2010-2014 using a national inpatient database in Japan. We investigated the trends in antibiotic use using mixed effect regression models and ascertained variations and clustering of the practice patterns across different hospitals using unsupervised machine learning methodology. RESULTS: A total of 280,298 children were included in the study. Total and broad-spectrum antibiotic use, except for fluoroquinolone, showed decreasing trends from 2010 to 2014. Additionally, the proportions of patients who received no antibiotics or only penicillin increased from 17.1% to 9.9% in 2010 to 24.5% and 13.7% in 2014, respectively. Cluster analysis showed that only one-quarter of hospitals used no antibiotics for 28.8% of children and only penicillin for 53.7% of children. In the remaining clusters of hospitals, the piperacillin, 3rd generation cephalosporins, and penicillin beta-lactamase inhibitors were used for 68.5%, 68.5%, and 69.6% of the patients who received antibiotics. CONCLUSIONS: Slightly increasing trends in narrow-spectrum antibiotics were observed. However, the treatment strategy in only one-quarter of hospitals was consistent with the current recommendations. Hospital level interventions to promote and monitor antibiotic use could be helpful to improve antibiotic use for pediatric inpatients.