Norovirus Pseudo‐outbreak in a Neonatal Intensive Care Unit

Abstract

Noroviruses are best known for explosive outbreaks of enteritis with vomiting, affecting both children and adults. Such outbreaks frequently occur in closed settings. However, asymptomatic infections are common (1–3). On the tertiary care neonatal intensive care unit (NICU) in our hospital we recently thought to observe an outbreak of norovirus infections. A father of a hospitalised preterm baby suffered from an acute diarrheal illness and tested positive for norovirus in the stool. The families of the patients in our NICU are often in close contact. We were alerted when a baby, sharing a room with the baby of the norovirus-infected father, developed acute watery diarrhea. Two of 4 possibly incubated babies in the room tested positive for norovirus antigen in the stool by an enzyme-linked immunosorbent assay (ELISA; Oxoid, Wesel, Germany). Intensive infection control measures were taken. When another baby, not exposed to potentially infected individuals, developed diarrheal illness, all of the preterm and newborn babies hospitalised in the NICU were tested for norovirus antigen in the stool. A total of 25 of 37 babies were found to be positive for norovirus antigen in the stool. Because the vast majority of these babies were asymptomatic, we were concerned about the specificity of the ELISA results. Therefore, a total of 13 antigen-positive stool samples were sent to the German norovirus reference laboratory at the Robert-Koch-Institut in Berlin for confirmatory polymerase chain reaction (PCR) testing. All of the stool samples turned out to be negative both by nested-PCR and real-time PCR for norovirus genogroups 1 and 2. We assume that all of the norovirus-positive stool samples were actually false positives in the ELISA. According to the manufacturer's product leaflet, the ELISA used is reported to have a sensitivity of 73% and a specificity of 100% compared to real-time PCR, determined with a panel of 118 samples. However, it is not known whether any samples from newborns were included in this panel. The reason for the high rate of false positive tests in the preterm and newborn babies in the ELISA is unknown to us. Similar phenomena were reported for early rotavirus assays. It may be speculated that factors of the immature gastrointestinal immune system interact with ingredients of the test assay or resemble the virus antigen structure.