Human Parechovirus Infections in Healthy Australian Children During the First 2-Years of Life: A Community-Based Longitudinal Birth Cohort Study

Abstract

Background: Hospital-based studies identify human parechovirus (HPeV), primarily HPeV3, as important causes of severe infections in young children. However, few community-based studies have been published and the true HPeV infection burden is unknown. We therefore investigated HPeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study. Methods: Australian children (n=158) enrolled in the Observational Research in Childhood Infectious Diseases (ORChID) study were followed from birth until their second birthday. Weekly stool and nasal swabs, and daily symptom diaries, were collected. Swabs were tested for HPeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus co-detections were investigated. Findings: HPeV was detected in 1423/11127 (12·8%) and 17/8100 (0·2%) stool and nasal swabs, respectively. Major genotypes amongst the 306 infection episodes identified were HPeV1 (47·9%), HPeV6 (20·1%), and HPeV3 (18·3%). The incidence rate was 144 episodes/100 child-years (95% CI 128-160). First infections appeared at a median age of 8·0-months (interquartile range 6·0-11·7). Annual seasonal peaks changing from HPeV1 to HPeV3 were observed. Infection was positively associated with age ≥6-months, summer season, non-exclusive breastfeeding at age <3-months, and formal childcare attendance before age 12-months. Sole HPeV infections were either asymptomatic (38·4%) or mild (32·7%), while co-detection with other viruses was common (64·4%). Interpretation: Unlike in hospital-based studies, diverse, dynamically changing HPeV genotypes circulate in the community causing mild or subclinical infections in children. Funding: Australia National Health and Medical Research Council (GNT615700) and Children's Hospital Foundation Queensland (5006). Declaration of Interest: All authors declare no competing interests. Ethical Approval: The Children’s Health Queensland, Royal Brisbane and Women’s Hospital, and The University of Queensland Human Research Ethics Committees approved the study.