Application of a salivary immunoassay in a prospective community study of waterborne infections

Abstract

Quantifying sporadic waterborne infections in community settings can be challenging. Salivary antibody immunoassays are a promising non-invasive tool that can be used in prospective studies of common infections, especially those involving children. This study was conducted in a Massachusetts city, which uses a microbiologically contaminated river as its water source, during summer-early winter periods before and after construction of a new drinking water treatment plant. Monthly saliva samples (7480 samples from 1170 children and 816 adults) were analyzed for immunoglobulin G (IgG) responses to recombinant proteins of Cryptosporidium, one genogroup I (GI) and two GII noroviruses. Immunoconversion was defined as at least four-fold increase in specific antibody responses between two monthly samples with a post-conversion response above a flexible age-dependent cut-off. Episodes of gastroenteritis (diarrhea or vomiting or cramps) were associated with 3.2 (95% confidence limits 1.1; 9.5) adjusted odds ratio (aOR) of immunoconversion to Cryptosporidium; episodes of combined diarrhea and vomiting symptoms were associated with 3.5 (0.8; 15.0) and 4.6 (1.7; 12.6) aORs of an immunoconversion to GI and GII noroviruses, respectively. Swimming in natural water bodies or chlorinated pools was associated with 2.3 (0.4; 15.4) and 4.9 (1.6; 15.5) aORs of immunoconversion to Cryptosporidium, respectively. In a subset of study participants who did not use home water filters, consumption of at least some amount of non-boiled tap water reported in a monthly recall survey was associated with 11.1 (1.2; 100.0) and 0.6 (0.1; 2.5) aORs of immunoconversion to Cryptosporidium before and after the new water treatment plant construction, respectively. Among individuals who used home water filters, associations between non-boiled tap water consumption and Cryptosporidium immunoconversion were not significant before and after new plant construction with aORs of 0.8 (0.2; 3.3) and 0.3 (0.1; 1.6), respectively. The interaction effect of study phase and non-boiled tap water consumption on Cryptosporidium immunoconversions was statistically significant in the entire study population with aOR of 5.4 (1.1; 25.6). This was the first study that has used a salivary antibody immunoassay to demonstrate significant associations between gastrointestinal symptoms and Cryptosporidium and norovirus infections, and between water-related exposures and Cryptosporidium infections.

Application of a multiplex salivary immunoassay to detect sporadic incident norovirus infections

“…To reduce potential false-positives resulting from variability in salivary IgG and the tendency for anti-NoV IgG to increase with age, the S2 anti-NoV IgG/anti-GST MFI ratio was required to be above an age-specific minimum cutoff value, as described previously 9,13 . To determine this cutoff, we modeled log 10 transformed anti-NoV IgG/anti-GST MFI ratio as a natural cubic spline function of age and estimated the upper bound of the 90% prediction interval (Fig.…”

Enteropathogen antibody dynamics and force of infection among children in low-resource settings

“…At the same time, large-scale serological surveillance platforms create new opportunities for expanded enteropathogen surveillance alongside other infectious diseases (Metcalf et al, 2016; Arnold et al, 2018). These challenges and opportunities have generated interest in antibody-based measurement as a complement to PCR for population-based enteropathogen surveillance (Griffin et al, 2011; Exum et al, 2016; Moss et al, 2014; Arnold et al, 2017), and for endpoints in observational and randomized studies (Crump et al, 2007; Zambrano et al, 2017; Chard et al, 2018; Vargas et al, 2017; Mosites et al, 2018; Wade et al, 2018; Egorov et al, 2018).…”

Visitors to a Tropical Marine Beach Show Evidence of Immunoconversions to Multiple Waterborne Pathogens

“…Additionally, we identified a breakthrough connection between asymptomatic norovirus infections and swimming at the beach (impacted by sewage from publicly-owned treatment works) finding that infected parties did not necessarily present with gastrointestinal symptoms (15). The assay was also applied in a prospective community study of waterborne infections to characterize associations between water-related exposures, Cryptosporidium and norovirus infections and gastrointestinal symptoms (6).…”