Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings

• Published in: The Journal of infectious diseases Vol. 219; no. 8; pp. 1234 - 1242
• Main Authors: Pisanic, Nora, Ballard, Sarah-Blythe, Colquechagua, Fabiola D, François, Ruthly, Exum, Natalie, Yori, Pablo Peñataro, Schwab, Kellogg J, Granger, Douglas A, Detrick, Barbara, Olortegui, Maribel Paredes, Mayta, Holger, Sánchez, Gerardo J, Gilman, Robert H, Heaney, Christopher D, Vinjé, Jan, Kosek, Margaret N
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08.04.2019
• Subjects: Antibodies, Viral - immunology; Caliciviridae Infections - diagnosis; Caliciviridae Infections - epidemiology; Caliciviridae Infections - virology; Case-Control Studies; Child, Preschool; Cross-reactivity; Daycare; Feces - virology; Gastroenteritis; Genotype & phenotype; Genotypes; Humans; Immunoglobulin G; Immunoglobulin G - immunology; Infections; Major and Brief Reports; Medical diagnosis; Norovirus; Norovirus - genetics; Norovirus - immunology; Peru - epidemiology; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; ROC Curve; Saliva; Saliva - immunology; Saliva - virology; Sensitivity and Specificity; Peru; saliva; multiplex immunoassay; MAL-ED; noninvasive diagnostics; norovirus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiy638

Abstract Background Norovirus is a leading cause of acute gastroenteritis worldwide. Routine norovirus diagnosis requires stool collection. The goal of this study was to develop and validate a noninvasive method to diagnose norovirus to complement stool diagnostics and to facilitate studies on transmission. Methods A multiplex immunoassay to measure salivary immunoglobulin G (IgG) responses to 5 common norovirus genotypes (GI.1, GII.2, GII.4, GII.6, and GII.17) was developed. The assay was validated using acute and convalescent saliva samples collected from Peruvian children <5 years of age with polymerase chain reaction (PCR)–diagnosed norovirus infections (n = 175) and controls (n = 32). The assay sensitivity and specificity were calculated to determine infection status based on fold rise of salivary norovirus genotype-specific IgG using norovirus genotype from stool as reference. Results The salivary assay detected recent norovirus infections and correctly assigned the infecting genotype. Sensitivity was 71% and specificity was 96% across the evaluated genotypes compared to PCR-diagnosed norovirus infection. Conclusions This saliva-based assay will be a useful tool to monitor norovirus transmission in high-risk settings such as daycare centers or hospitals. Cross-reactivity is limited between the tested genotypes, which represent the most commonly circulating genotypes. This study describes the performance of a multiplex immunoassay to measure salivary immunoglobulin G responses to multiple norovirus genotypes. The assay diagnosed recent norovirus infections at the genotype level with 71% sensitivity and 96% specificity compared to stool-based polymerase chain reaction diagnosis.