Human parechovirus infections in Australian infants during the first 2-years of life: A community-based birth cohort study

Abstract

Background: Human parechoviruses (HPeVs), consisting of 19 genotypes, are mainly associated with mild, acute respiratory infections (ARI) and gastroenteritis. Infection in childhood is common with >70% seroprevalence by 5-years of age. Most studies however have been in hospitalised populations and besides seroprevalence studies, the epidemiology of HPeVs in infants and young children in the community remains uncertain. Recently, HPeV-3, has gained increasing recognition following global reports of sepsis-like illness and meningoencephalitis in infants aged <3-months. For this study, we have used a longitudinal community-based birth cohort study - Observational Research in Childhood Infectious Diseases (ORChID) - to investigate the nature of HPeV infections in unselected healthy infants. Methods: Stool (n = 11,201) and nasal (n = 11,515) swabs from 158 healthy infants were collected weekly, and daily symptoms were recorded by parents from birth until their child's 2nd birthday. Sampleswere posted to the QPID laboratory where nucleic acidwas extracted. We used an RT-PCR assay to screen extracts for HPeVs. Genotyping was conducted by a conventional PCR assay targeting the viral protein (VP) 3/1 junction. Phylogenetic analysis was performed to identify potential distinct clusters. Results: HPeVs were detected in 1,456 (13%) and 27 (0.2%) weekly nappy and nasal swabs, respectively. They were detected year round, but peaked in summer/autumn months (January-March). Overall, 79% of participants had ≥1 discrete virus detection episodes of HPeV infection (mean = 2.4 episodes/child). Of these 291 episodes, 6were associated with symptoms of fever alone (2%), 118 ARI (41%), or 20 diarrhoea (7%). None were hospitalised. Primary infection appeared at a median 31 (interquartile range 19-47) weeks of age with the earliest detection on day 1 of life. The mean (standard deviation) shedding period in stools was 5.98 (SD = 4.52) weeks (maximum duration 23-weeks in two subjects). HPeV-1was the predominant genotype with other genotypes (2-6) also observed. Mostly, one genotypewas detected at each episode; however in some cases of prolonged shedding, sequential detection of different genotypes was also observed. Respiratory viruses, primarily rhinoviruses, were co-detected in 64 (54%) symptomatic ARI episodes. Phylogenetic analysis revealed multiple clusters caused by different genotypes circulating in the community. Conclusion: HPeVs are detected early in life, 45% are associated with symptoms. Most healthy children have had at least 1 HPeV infection by their 2nd birthday. HPeVs shedding duration can last many weeks. Various genotypes (predominantly HPeV-1) cocirculate in the community, contributing to multiple episodes in individuals.L6220941272018-05-16 <br />