Pediatric Infectious Disease Journal最新文献

Diagnosing hemophagocytic lymphohistiocytosis (HLH) triggers in infants is challenging. In a 9-month-old boy with unresponsive fever and pancytopenia, conventional tests were negative. Metagenomic next-generation sequencing detected Leishmania donovani , confirming Leishmania donovani -associated HLH. Targeted antiparasitic therapy replaced empiric immunosuppression, leading to rapid recovery. This case demonstrates that metagenomic next-generation sequencing is crucial for rapid pathogen identification in critically ill infants with HLH of unknown cause.

Background: Multiple epidemiologic surveys of acute encephalitis/encephalopathy have been conducted in Japan; however, information on incidence rates and related infectious diseases/pathogens remains limited.

Objective: To clarify the epidemiological characteristics of acute encephalitis/encephalopathy in Fukushima Prefecture, we investigated the number of cases and the associated infectious diseases/pathogens using polymerase chain reaction (PCR) in addition to conventional diagnostic methods.

Methods: We collected data on acute encephalitis/encephalopathy cases from 16 medical institutions in Fukushima Prefecture that provided pediatric inpatient care between 2014 and 2024. At Fukushima Medical University Hospital, PCR testing was used in addition to conventional diagnostic methods to identify the related pathogens.

Results: Over the 11-year study period, 106 cases of acute encephalitis/encephalopathy associated with infectious disease were reported, with an average of 9.6 cases per year and an annual incidence rate of 15.2 per 100,000 children aged under 5 years. Associated infectious diseases/pathogens were identified in 59.4% of cases: exanthema subitum/human herpes virus-6,7 in 22.6%, influenza/influenza virus in 18.9% and other in 17.9%. Among 50 cases admitted to Fukushima Medical University Hospital, the pathogen identification rate was 76.0%: human herpes virus-6,7 in 24.0%, influenza virus in 22.0% and other pathogens in 30.0%.

Conclusion: Based on the prospective active survey of acute encephalitis/encephalopathy in Fukushima Prefecture, the annual incidence rate is estimated to be 15.2 cases per 100,000 children under the age of 5 in Japan. Since PCR testing is effective for detecting pathogens, comprehensive PCR analysis may further improve pathogen identification in acute encephalitis/encephalopathy.

Background: The prevalence of pediatric urinary tract infections (UTIs) caused by extended-spectrum β-lactamases (ESBL)-producing bacteria is increasing worldwide and is difficult to predict. As these infections require special antibiotic treatment, which is often not started empirically, they are associated with higher rates of intensive care unit admission, morbidity and prolonged hospitalization. We aimed to develop machine learning-based tools to aid pediatricians in predicting ESBL-positive UTIs and initiate appropriate empiric antibiotics.

Methods: The electronic medical records of a large Health Maintenance Organization were searched for all children one month to 18 years of age with confirmed UTIs during January 1, 2010, to August 31, 2020. Data on demographics, clinical and laboratory information were retrieved, and following univariate analysis, machine learning-based tools were used to develop models to predict a UTI caused by an ESBL-producing bacterium.

Results: A total of 35,830 pediatric UTI events comprised the study group. Age, sex, socioeconomic status, site of infection (community or hospital), prior antibiotic use, previous ESBL-positive UTI and the specific uropathogen were significantly associated with the rates of ESBL-positive infection. Using patients' data available on presentation, the 5 models developed had a very high negative predictive value of ~0.98, indicating strong rule-out performance for ESBL-positive UTIs.

Conclusions: Our study indicates that machine learning models based on data available at UTI presentation may support clinicians in estimating the likelihood of ESBL-producing bacteria UTIs. Prospective studies are required to improve the models' performance and determine their actual impact on clinical outcomes.

Background: Sisunatovir is an investigational respiratory syncytial virus (RSV) antiviral that was effective in an adult human viral challenge study.

Methods: In 2 multicenter studies, safety and pharmacokinetics of sisunatovir were evaluated in hospitalized individuals 1 month to 36 months of age (Study 1) and outpatient and hospitalized individuals 1 day to 60 months of age (Study 2) with RSV lower respiratory tract infection (RSV-LRTI). In Study 1 Part A, participants received single sisunatovir doses; in Part B, participants received placebo or multiple ascending sisunatovir doses every 12 hours for 5 days. In Study 2, participants received weight-based sisunatovir dosing or placebo every 12 hours for 5 days.

Results: In Study 1 Part A, 19 participants received sisunatovir; 31 in Part B received sisunatovir (n = 22) or placebo (n = 9). Adverse events (AEs) were reported by 11 (57.9%) and 12 (38.7%) participants in Parts A and B, respectively. In Study 2, 10 participants received sisunatovir (n = 6) or placebo (n = 4). No treatment-related serious AEs were reported; all AEs were mild or moderate. In Study 1 Part A 12 hours post-dose, mean sisunatovir concentrations were within safety margins. In Part B, at the highest dose assessed for each group, steady-state trough concentrations surpassed those effective in the adult challenge study.

Conclusions: In children with RSV-LRTI, sisunatovir was safe and well tolerated. The pediatric multiple-dose regimen achieved plasma concentrations effective at reducing viral load and symptoms in an adult challenge study; however, further studies are needed to identify doses providing comparable exposure across pediatric populations.

Clinicaltrialsgov registration number: NCT04225897 (registered December 11, 2019); NCT06102174 (registered October 6, 2023).