Vaccine-Related Viral Shedding Leads to High Rate of Rotavirus Overdiagnosis

Over a 2-year period, roughly half of positive cases of rotavirus in infants were the result of vaccine-related viral shedding.

At a diagnostic laboratory between 2016 and 2018, 46.7% of positive cases of rotavirus in infants were the result of vaccine-related viral shedding, according to a study published in Clinical Infectious Diseases. Investigators emphasized the importance of distinguishing vaccine virus from the wild type in the routine diagnostic testing of infants.

The advent and implementation of the rotavirus vaccine has had a significant positive effect on the need for medical attention as a result of this infection. However, because the vaccine contains a live-attenuated version of the virus, which replicates in the gut and thus shed in stool, it can exert a confounding effect on the diagnosis of rotavirus infection in people who have received the vaccine.

Accurate diagnosis is crucial for the clinical management and monitoring of active rotavirus and vaccine effectiveness. This Brisbane, Queensland cohort study collected weekly stool samples to assess the issue of rotavirus vaccine virus shedding in infants as part of the statewide immunization program. Using specific assays for rotavirus strains 1 and 5 (RV1 and RV5, respectively), a total of 465 rotavirus-polymerase chain reaction (PCR)-positive samples were retested, of which 65 (n=16, 24.6% infants aged <1 year) were collected during the time period Queensland used the RV5 vaccine (bank 1) and 400 (n=136, 34.0% infants aged <1 year) from the time period during which the RV1 vaccine was used (bank 2).

Of the bank 1 samples that tested positive for rotavirus, 10.8% tested positive for RV5; all were from infants aged <1 year. Of the bank 1 samples that were from infants aged <1 year (n=16), 43.8% of detections were RV5 positive. Of the bank 2 samples, 64 (16.0%) tested positive for RV1, and all but 2 were from infants. Additionally, 2 samples from infants in the bank 2 pool were positive for RV5.

No significant differences were seen in vaccine virus detection among infants between samples from bank 1 and bank 2 (relative risk, 0.93; 95% CI, 0.52-1.67).  In many cases, the symptoms prompting rotavirus testing were most likely due to other pathogens present along with the vaccine virus. Such codetections were found in 12 of 65 (18.5%) bank 1 samples and 80 of 400 (20.0%) bank 2 samples. The most commonly identified codetected pathogens were norovirus, adenovirus and non-typhoidal Salmonella; investigators noted that in cases of codetection, these pathogens were more likely the cause of diarrheal symptoms.

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The investigators concluded, “these data emphasize the need for rotavirus diagnostic and screening methods to distinguish vaccine from wild-type virus when testing recently vaccinated infants using [nucleic acid amplification test] platforms…in settings where available tests cannot distinguish vaccine and wild-type virus, then a suitable comment should accompany the test result indicating that detection of rotavirus RNA in infants is not necessarily an indication of infection, but may be due to vaccine shedding.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Whiley DM, Ye S, Tozer S, et al. Over-diagnosis of rotavirus infection in infants due to detection of vaccine virus [published online December 18, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz1196