High positivity rates and titers of norovirus (NV)-specific immunoglobulin A (NV-IgA) in breast milk correlated with reduced diarrheal symptoms in infants with NV, suggesting that maternal NV-IgA might have a protective effect, according to findings from a study published in EClinicalMedicine.
Humoral and fecal IgA responses have been associated with protection against NV, which causes acute gastroenteritis in infants. However, whether breast milk IgA has preventive activity against NV infection and resulting diarrhea is unknown. Therefore, the investigators sought to evaluate the role of breast milk IgA in NV infection and diarrhea in infants.
The study included 95 breast milk samples from mothers enrolled in a Peruvian birth cohort study between 2016 and 2017. Mothers who did not breastfeed were excluded from the study. Those whose infants were NV-positive or -negative but were co-infected with other diarrheal pathogens such as sapovirus or enterotoxigenic Escherichia coli were also excluded.
The samples were tested for total IgA and NV-IgA by enzyme-linked immunosorbent assay using GII-4 variants and non–GII-4 genotype virus-like particles (VLPs). Samples were grouped based on NV infection and infant diarrheal status: NV-positive with diarrhea (n=18); NV-positive without diarrhea (n=37); and NV-negative without diarrhea (n=40). Diarrheal status was assessed during or within 7 days of the start or end of a diarrheal episode. These groups were compared in terms of percent positivity and titer of NV-IgA.
Infants who were NV-negative and did not have diarrhea had a higher percentage of days of exclusive breastfeeding compared with the NV-positive infants with diarrhea (100.0 vs 97.4 days, respectively; P =.06) with borderline significance. Exclusive breastfeeding was defined as no other food or drink beyond breast milk, including water. The difference in days of exclusive breastfeeding was statistically significant in the group of NV-negative infants without diarrhea vs the group of NV-positive infants without diarrhea (100.0 vs 85.5 days; P =.02).
All 95 samples contained IgA that reacted to GII-4 Sydney 2012, GII-4 Farmington Hills 2002, GII-6, GII-17, GI-1, and GI-9 VLPs. A high NV-IgA positivity rate was observed against GII and ranged between 89% and 100%. In a cross-reactivity analysis, NV-IgA against different GII-4 intra-variants had a high P value (P <.001); against intragenogroup, it was moderate to moderately high (P <.001). The value was low against intergenogroup (P <.01).
A “significantly higher” NV-IgA percent positivity was observed in the group of infants who were NV-positive without diarrhea compared with the group of infants who were also NV-positive but did experience diarrhea (89% vs 61%, respectively; P =.03). A higher median titer of NV-IgA against GI-1 VLPs was also seen in the former group compared with the latter group (1:100 vs 50; P =.01).
The researchers noted that IgA antibodies, which are transferred to the infants through breast milk, were likely the protective factors against diarrhea in the infants. Regarding mechanism, IgA is thought to temporarily coat the gastrointestinal microbiota or block the binding site of NV to human cells, thereby reducing diarrheal symptoms in infants.
A limitation of this study included the small sample sizes in each mother-infant subgroup, especially the NV-negative, diarrhea-positive subgroup. Additionally, this study included the “relatively small” number of mothers in the NV-positive, diarrhea-positive infant subgroup, according to the study authors. A lack of information on mothers’ past or current NV infections and a limited number of mother-submitted stool samples comprised additional limiting factors.
The study findings reinforce “the need to continue breastfeeding practice up to 1 year to promote the health of both mothers and infants,” concluded the investigators.
Labayo HKM, Pajuelo MJ, Tohma K, et al. Norovirus-specific immunoglobulin A in breast milk for protection against norovirus-associated diarrhea among infants. Published online October 5, 2020. EClinicalMedicine. doi: 10.1016/j.eclinm.2020.100561