Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings

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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.

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Stress physiology and memory for emotional information: Moderation by individual differences in pubertal hormones.

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Background:
In contrast to a large body of work concerning the effects of physiological stress reactivity on children’s socioemotional functioning, far less attention has been devoted to understanding the effects of such reactivity on cognitive, including mnemonic, functioning. How well children learn and remember information under stress has implications for a range of educational, clinical, and legal outcomes. We evaluated 8-14 year olds’ (N = 94, 50 female) memory for negative, neutral, and positive images. Youth had seen the images a week previously as a part of a laboratory stress task. At encoding and retrieval, and in between, youth provided saliva samples that were later assayed for cortisol, salivary α amylase (sAA), testosterone, and dehydroepiandrosterone (DHEA). Overall, higher cortisol reactivity to the lab task predicted enhanced memory for emotional but not neutral images. However, cortisol further interacted with pubertal hormones (testosterone and DHEA) to predict memory. Among girls with lower pubertal hormone levels, greater cortisol reactivity was associated with enhanced memory for negative information, whereas among boys with higher pubertal hormone levels, cortisol reactivity was associated with enhanced memory for positive information. sAA, was unrelated to memory. Overall, our findings reveal that individual differences in hormone levels associated with pubertal development have implications for our understanding of how stress-responsive biological systems directly and interactively influence cognitive outcomes.

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The validity, stability, and utility of measuring uric acid in saliva.

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Background: Uric acid (UA) is associated with cardiovascular and metabolic disorders, as well as a wide range of other health conditions and behaviors. A non-invasive measure of UA would be particularly useful in biobehavioral health and clinical research. We examined the validity and stability of salivary UA as a noninvasive measure of serum UA.

Methods: To interrogate the validity of salivary UA as a marker of systemic UA, we measured UA levels in blood and saliva samples collected on a single occasion from healthy adults (n=99; age 18-36 years, 54% male). We examined the serum-saliva correlation for UA and associations between salivary UA and inflammatory markers in serum and saliva, and with self-reported oral health indices. We also tested whether associations of UA with adiponectin and C-reactive protein, circulating markers of cardiovascular health, are evident in saliva. Using longitudinal data from young adults (n=182; age 18-31 years; 46% male) we examined salivary UA stability. Correlations and latent state-trait modeling examined the stability of salivary UA levels; the percent of variance in salivary UA estimates attributable to trait and state-components; and associations of the salivary UA trait component with body mass index (BMI) and sex.

Results: We found a strong positive association between salivary and serum UA. Neither the direction nor the magnitude of this association was related to total protein in saliva, blood leakage into oral fluid, proinflammatory cytokines, or biobehavioral indices of poor oral health. Results also revealed robust inverse associations between UA and adiponectin in both serum and saliva. Salivary UA levels were also highly correlated within and between assessment points 3 hours as well as 2 months apart. Advanced statistical modeling showed the majority (62-66%) of the variance in salivary UA could be attributed to a latent trait component suggesting relative stability in salivary UA levels. Furthermore, BMI and sex were associated with the stable trait-like component of salivary UA.

Conclusions: The findings demonstrate strong measurement validity and stability when UA is measured in saliva, and provide evidence supporting salivary UA as a robust indicator of systemic UA activity. These finding suggest that salivary UA could serve as a biomarker for a wide range of potential conditions and disease states.

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Development of an oral fluid immunoassay to assess past and recent hepatitis E virus (HEV) infection.

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BACKGROUND:
Hepatitis E virus (HEV) infection causes significant morbidity and mortality worldwide, particularly among pregnant women. In clinical settings blood-based testing protocols are commonly used to diagnose HEV infection, but in community settings such invasive sampling can hinder study participation and limit discovery of the ecology and natural history of HEV infection. Oral fluid is a non-invasive biospecimen that can harbor pathogen-specific antibodies and has the potential to replace blood-based testing protocols.

OBJECTIVES:
To develop an immunoassay to assess past and recent HEV infection that uses oral fluid instead of serum or plasma.

METHODS:
The assay was validated using paired oral fluid and serum samples collected from 141 patients who presented either with (n=76) or without (n=65) symptoms of acute viral hepatitis at a clinical diagnostics center in Dhaka, Bangladesh. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgG (past HEV infection) and HEV IgA (recent HEV infection) antibodies was calculated in reference to Wantai’s (Beijing Wantai) serum-based HEV enzyme-linked immunosorbent assay (ELISA) kits for IgG and IgM antibodies, respectively.

RESULTS:
The sensitivity and specificity of the oral fluid-based immunoassay for HEV-IgG antibodies were 98.7% and 98.4%, respectively. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgA were 89.5% and 98.3%, respectively.

CONCLUSIONS:
The high concordance of our non-invasive oral fluid-based immunoassays (HEV IgG and HEV IgA) with commercial high-performance serum HEV ELISA kits (IgG and IgM) means that population-based surveillance of past and recent HEV infection could be expanded to improve understanding of its ecology and natural history.

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Adiponectin: Serum-Saliva Associations and Relations with Oral and Systemic Markers of Inflammation.

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Background:

This study addresses gaps in our understanding about the validity and utility of using salivary adiponectin to index serum adiponectin levels. Matched blood and saliva samples were collected on a single occasion from healthy adults (n=99; age 18-36 years, 53% male). Serum and saliva was assayed for adiponectin and inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα), and saliva was also assayed for markers of blood contamination (transferrin), total protein (salivary flow rate) and matrix metalloproteinase-8 (MMP-8). We examined the extent to which salivary adiponectin was associated with serum adiponectin, and the influence of potential confounders on the serum-saliva correlation, including age, sex, body mass index, and markers of inflammation, oral health, salivary blood contamination, and flow rate. Findings revealed a modest serum-saliva association for adiponectin, and strong positive associations between salivary adiponectin and salivary levels of inflammatory cytokines, MMP-8, transferrin, and total protein. By contrast, salivary adiponectin was not related to serum levels of inflammatory activity. The magnitude of the serum-saliva association was strengthened when controlling for total protein in saliva, blood leakage into oral fluid, salivary inflammatory cytokines, and MMP-8. The pattern of findings extends our understanding of salivary adiponectin and its potential use as an index of circulating adiponectin levels.

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Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings

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Background: There is increasing interest in the mechanisms and biomarkers through which physical activity influence health across the lifespan. Studies that require phlebotomy are challenging for investigations involving children. Not surprisingly, there is growing interest in the use of saliva in pediatrics for exercise-related biomarker discovery. Very little is known about the relationship of key potential salivary biomarkers (SaBs) and exercise during childhood.

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Salivary Biomarkers in Response to an Acute Bout of Exercise Before and After Training Program: Poster

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Background: There is increasing interest in the mechanisms and biomarkers through which physical activity influence health across the lifespan. Studies that require phlebotomy are challenging for investigations involving children. Not surprisingly, there is growing interest in the use of saliva in pediatrics for exercise-related biomarker discovery. Very little is known about the relationship of key potential salivary biomarkers (SaBs) and exercise during childhood.

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UCI School of Social Ecology
Social Ecology I
Irvine, CA 92697-7050
www.uci.edu
www.socialecology.uci.edu

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