Super-infections and relapses occur in chronic norovirus infections

Abstract

Background: Norovirus causes chronic infections in immunocompromised patients with considerable associated morbidity. It is not known whether chronic infections involve super- or re-infections or relapses.

Objectives: To retrospectively investigate whether longitudinal sampling in chronically infected patients demonstrates persistent infection with the same virus, or super- or re-infection.

Study design: Norovirus full genomes were generated from 86 longitudinal samples from 25 paediatric patients. Consensus sequences were used for phylogenetic analysis and genotyping.

Results: Super-infections occurred in 17% of chronically infected patients who were continuously PCR positive; including two with mixed norovirus infections. The median duration of infection was 107days longer in those with super-infections; however this was not statistically significant. A third of patients with interrupted norovirus shedding continued to be infected with the same virus despite up to 2 months of PCR negative stools, classified as a relapse. The majority (67%) of patients with interrupted shedding were re-infected with a different genotype.

Conclusions: Chronically infected patients who are continuously PCR positive are most likely to remain infected with the same virus; however super-infections do occur leading to mixed infection. Patients with interrupted shedding are likely to represent re-infection with a different genotype, however relapsing infections also occur. Our findings have implications for infection control as immunosuppressed patients remain susceptible to new norovirus infections despite current or recent infection and may continue to be infectious after norovirus is undetectable in stool. The relevance to children without co-morbidities remains to be determined.

Keywords: Chronic; Full genomes; Norovirus; Re-infection; Relapse; Super-infection.