Rotavirus May Be Overdiagnosed Due to Vaccine Virus Shedding

By Reuters Staff

January 02, 2020

NEW YORK (Reuters Health) - Nearly half of infants with rotavirus in their stool test positive due to vaccine virus shedding, new findings show.

"Routine diagnostic testing of infants should ideally distinguish vaccine from wild-type virus," Dr. David M. Whiley of The University of Queensland in Brisbane, Australia, and colleagues conclude in their report in Clinical Infectious Diseases.

Both available rotavirus vaccines are live-attenuated, the authors note, so the virus replicates in the gut and is shed in stool after immunization. They previously identified rotavirus vaccine shedding for up to 14 weeks after the third dose of RotaTeq RV5 (Merck & Co.) in their birth cohort study of 158 healthy infants, and found shedding occurred in up to 87% of infants after each vaccine dose.

"These studies highlighted the importance of examining the influence vaccine strain shedding may have on clinical diagnosis and rotavirus surveillance data," Dr. Whiley and his team write. "Our interest in the potential for rotavirus positive results caused by vaccine shedding was also prompted by local pediatric infectious disease clinicians expressing clinical concerns over the specificity of stool rotavirus results in infants following the transition from antigen-based to PCR assay testing by our local diagnostic laboratory in 2014."

The authors analyzed 465 rotavirus-positive stool samples submitted to a central laboratory in Queensland from November 2016 to March 2018.

Bank 1 included 65 samples collected before July 2017, when the state switched from RV5 to Rotarix RV1 (GSK Biologicals), and Bank 2 included 400 samples collected after the switch. About one-quarter of the samples in Bank 1 and one-third of those from Bank 2 were from infants younger than a year old.

Seven (10.8%) samples from Bank 1, all from infants under 1 year, were positive for RV5, accounting for 43.8% of positive samples from infants.

Sixty-four (16%) samples from Bank 2 were positive for RV1, and all were from infants aged 6 to 28 weeks, aside from one from a 3-year-old and another from a man in his 50s. Two infants tested positive for RV 5. In Bank 2, RV1 accounted for 45.6% of samples from infants under age 1, while RV5 accounted for 1.5%.

"These data highlight the potential for sensitive NAAT methods to over-diagnose rotavirus infection in infants due to shedding of either RV1 or RV5 vaccine virus," the authors write. "Positive results caused by vaccine shedding in young infants may adversely affect clinical management by delaying serious alternative diagnoses and their treatment, such as urinary tract infections or intra-abdominal sepsis and prolonging unnecessary infection control precautions."

UK researchers also recently reported high rates of vaccine-derived strains in stool samples testing positive for rotavirus in the Archives of Disease in Childhood. Dr. Shamez Ladhani of Public Health England in London and colleagues found 8% of 2,637 rotavirus-positive samples collected between July 2013 and September 2016 were from vaccine-derived strains. None of the Rotarix-derived strains were found in children who had not been immunized, while 82% of positive samples from 2-month-old babies and 68% of those from 3-month-old infants were vaccine-derived.

Thirteen of the samples containing vaccine-derived strains had been collected more than seven weeks after a child's last rotavirus vaccination, and 10 of these samples were from six children later diagnosed with severe combined immunodeficiency (SCID).

Children with vaccine-derived rotavirus strains were less likely to have fever, vomiting, dehydration or severe gastroenteritis compared to children infected with wild-type strains.

The authors conclude: "SCID remains the major contraindication to rotavirus vaccination; those with prolonged gastrointestinal symptoms and Rotarix vaccine-derived G1P(8) strains identified in stools should be investigated for underlying immunodeficiency, including SCID."

SOURCE: Clinical Infectious Diseases, online December 18, 2019, and Archives of Disease in Childhood, online December 23, 2019.