Multivalent rotavirus vaccine and wild-type rotavirus strain shedding in Australian infants: a birth cohort study

Rotavirus vaccines have reduced moderate-to-severe gastroenteritis episodes in infants and young children. Nevertheless, knowledge gaps exist concerning rotavirus vaccine shedding and vaccine impact upon mild and asymptomatic wild-type infections. Our primary objective was to investigate vaccine shedding in Australian infants where the multivalent human-bovine reassortant rotavirus vaccine, RotaTeq®, was part of the routine vaccination schedule.The Observational Research in Childhood Infectious Diseases (ORChID) birth cohort study was conducted in Brisbane, Australia, from September 2010 to October 2014. Newborn infants were enrolled progressively and followed until their second birthday. Parents recorded daily symptoms and mailed weekly stool swab samples from their infants to the laboratory where reverse transcription-polymerase chain reaction (RT-PCR) testing was performed, and rotavirus-positive samples underwent genotyping to distinguish between vaccine and wild-type strains.Rotavirus was detected in 1,068/11,139 (9.6%) stool swabs from 158 infants, and 994 (93.1%) were genotyped. RotaTeq® vaccine strains accounted for 951/994 (95.7%) of typed rotavirus-positive swabs. Proportions of infants shedding RotaTeq® after the first, second and third vaccine doses were 87.0%, 57.4% and 47.3% respectively and median (interquartile range) shedding duration after vaccine doses 1-3 was 3 (1-8), 1.5 (1-3) and 1 (1-2) weeks respectively. In contrast, the incidence rate of wild-type rotavirus episodes was 10.3 (95% confidence interval 6.8-15.6) per 100 child-years of observation.RotaTeq® vaccine virus was detected in stool samples from 47-87% of infants after each vaccine dose. Genotyping is an essential tool for differentiating between rotavirus vaccine and wild-type strains and monitoring vaccine impact in children

Detection of viruses in weekly stool specimens collected during the first 2 years of life: a pilot study of five healthy Australian infants in the rotavirus vaccine era

Several viruses are associated with gastroenteritis in infants. This pilot study, nested within a larger community-based project of early childhood infections, collected daily symptom data and 511 weekly stool samples from five healthy, fully vaccinated, term infants from birth until their second birthday. Real-time PCR assays were used to detect six enteric viruses. Frequent, silent shedding of one or more of the six viruses was observed, particularly involving adenovirus where shedding could be for up to 3 months without gastrointestinal symptoms. These pilot data demonstrate that a positive PCR result for enteric viruses may not always indicate the cause of childhood gastroenteritis

Over-diagnosis of rotavirus infection in infants due to detection of vaccine virus

Accurate rotavirus diagnosis is important for clinical management and monitoring active disease and vaccine effectiveness. Between 2016-2018, rotavirus-positive results in our laboratory were from vaccine virus shedding in 71/152 (46.7%) infants with a request for rotavirus testing. Routine diagnostic testing of infants should ideally distinguish vaccine from wild-type virus

Individual polyomavirus detections for symptomatic patients, including available demographic information, PCR Ct values, viral co-detections and clinical information.

*<p>Same patient collected over 5 days.</p><p>ALL – acute lymphoblastic leukaemia, AML – acute myeloid leukaemia, BMT – bone marrow transplant, TPN – total parenteral nutrition, CP – cerebral palsy, PUO – pyrexia of unknown origin, URTI – upper respiratory tract infection, HIV – human immunodeficiency virus.</p

Individual polyomavirus detections for healthy control populations, including match fecal and respiratory specimens.

<p>ND – Not detected.</p

Neighbour-Joining phylogeneic analysis of 13 MWPyV whole genome sequences (GenBank accession numbers: MA095 NC_018102, WD976 JQ898292.1, HPyV10 JX262162.1, UC-MXPyV JX259273.1 QLD02 KC549586, QLD03 KC549587, QLD04 KC549588, QLD05 KC549589, QLD09 KC549590, QLD10 KC549591, QLD11 KC549592, QLD12 KC549593, QLD13 KC549594).

<p>Neighbour-Joining phylogeneic analysis of 13 MWPyV whole genome sequences (GenBank accession numbers: MA095 NC_018102, WD976 JQ898292.1, HPyV10 JX262162.1, UC-MXPyV JX259273.1 QLD02 KC549586, QLD03 KC549587, QLD04 KC549588, QLD05 KC549589, QLD09 KC549590, QLD10 KC549591, QLD11 KC549592, QLD12 KC549593, QLD13 KC549594).</p

Study sample population details and their associated MWPyV, HPyV 6, 7 &9 and TSPyV detections.

*<p>11 positive specimens collected, three from one patient tested three times over 5 days therefore only one positive specimen was used to calculate prevalence.</p

Detection of novel polyomaviruses, TSPyV, HPyV6, HPyV7, HPyV9 and MWPyV in feces, urine, blood, respiratory swabs and cerebrospinal fluid

Eight novel human polyomaviruses have been discovered since 2007. Prevalence rates and tissue tropism for the most recent members HPyV 6, 7, 9, TSPyV and MWPyV are largely unknown. We used real-time PCR to determine the presence of HPyV 6, 7, 9, TSPyV and MWPyV in feces (n = 263), urine (n = 189), blood (n = 161), respiratory swabs (n = 1385) and cerebrospinal fluid (n = 171) from both healthy control children and children and adults undergoing diagnostic testing. Whole genome sequencing was able to be performed on 9 MWPyV positive specimens. Novel polyomaviruses were only detected in respiratory swabs and feces, with no detections of HPyV 9 in any sample type. MWPyV was found to be the most prevalent novel polyomavirus, being detected in 18 (1.5%) respiratory specimens from symptomatic patients, 16 (9.8%) respiratory sample from healthy control children, 11 (5.9%) fecal specimens from patient suffering gastrointestinal illness, and in 13 (15.3%) of feces from healthy control children. MWPyV was found only in respiratory and fecal specimens from children, the oldest being 9 years old. HPyV 6, 7, 9 and TSPyV were also detected in respiratory specimens and fecal specimens at low prevalence