Seroepidemiology of norovirus-associated travelers' diarrhea

Abstract

Background: Noroviruses (NoVs) are the most common cause of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and were recently identified as a leading cause of travelers' diarrhea (TD) in US and European travelers to Mexico, Guatemala, and India.

Methods: Serum and diarrheic stool samples were collected from 75 US student travelers to Cuernavaca, Mexico, who developed TD. NoV RNA was detected in acute diarrheic stool samples using reverse transcription-polymerase chain reaction (RT-PCR). Serology assays were performed using GI.1 Norwalk virus (NV) and GII.4 Houston virus (HOV) virus-like particles (VLPs) to measure serum levels of immunoglobulin A (IgA) and IgG by dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA); serum IgM was measured by capture enzyme-linked immunosorbent assay (ELISA), and the 50% antibody-blocking titer (BT50 ) was determined by a carbohydrate-blocking assay.

Results: NoV infection was identified in 12 (16%; 9 GI-NoV and 3 GII-NoV) of 75 travelers by either RT-PCR or fourfold or more rise in antibody titer. Significantly more individuals had detectable preexisting IgA antibodies against HOV (62/75, 83%) than against NV (49/75, 65%) (p = 0.025) VLPs. A significant difference was observed between NV- and HOV-specific preexisting IgA antibody levels (p = 0.0037), IgG (p = 0.003), and BT50 (p = <0.0001). None of the NoV-infected TD travelers had BT50 > 200, a level that has been described previously as a possible correlate of protection.

Conclusions: We found that GI-NoVs are commonly associated with TD cases identified in US adults traveling to Mexico, and seroprevalence rates and geometric mean antibody levels to a GI-NoV were lower than to a GII-NoV strain.

Figure 1

Comparison between pre-existing serum antibody levels against Norwalk virus (NV) virus like particle (VLP) and Houston virus (HOV) VLP. A. Anti-NV and –HOV IgA levels, p=0.0037; Wilcoxon signed rank test, cutoff: 1.4μg/mL. B. Anti-NV and –HOV IgG levels p=0.003; Wilcoxon signed rank test, cutoff: 1.6μg/mL. C; BT₅₀ values of NV- and HOV-blocking antibodies, p=<0.0001; Wilcoxon signed rank test). Bars represent geometric means and dotted lines the cutoff value.