Use of Serologic Responses against Enteropathogens to Assess the Impact of a Point-of-Use Water Filter: A Randomized Controlled Trial in Western Province, Rwanda

Abstract

Diarrhea is a leading contributor to childhood morbidity and mortality in sub-Saharan Africa. Given the challenge of blinding most water, sanitation, and hygiene (WASH) interventions, diarrheal disease outcome measures in WASH intervention trials are subject to potential bias and misclassification. Using the platform of a cluster-randomized controlled trial of a household-based drinking water filter in western province, Rwanda, we assessed the impact of the drinking water filter on enteric seroconversion in young children as a health outcome and examined the association between serologic responses and caregiver-reported diarrhea. Among the 2,179 children enrolled in the trial, 189 children 6-12 months of age were enrolled in a nested serology study. These children had their blood drawn at baseline and 6-12 months after the intervention was distributed. Multiplex serologic assays for ,, , norovirus,, enterotoxigenic and were performed. Despite imperfect uptake, receipt of the water filter was associated with a significant decrease in seroprevalence of IgG directed against Cp17 and Cp23 (relative risk [RR]: 0.62, 95% confidence interval [CI]: 0.44-0.89). Serologic responses were positively associated with reported diarrhea in the previous 7 days for both (RR: 1.94, 95% CI: 1.04-3.63) and (RR: 2.21, 95% CI: 1.09-4.50). Serologic responses for all antigens generally increased in the follow-up round, rising sharply after 12 months of age. The water filter is associated with reduced serologic responses against, a proxy for exposure and infection; therefore, serologic responses against protozoa may be a suitable health outcome measure for WASH trials among children with diarrhea.

The Epidemiology of Cholera in Zanzibar: Implications for the Zanzibar Comprehensive Cholera Elimination Plan

“…Given the irregular interannual occurrence of cholera in Zanzibar and the heterogeneity in the geography of each outbreak, providing quantitative estimates of the impact of ZACCEP will be challenging, without careful thought. Key indicators for measuring progress could include the distribution of times between outbreaks, the proportion of the population infected by cholera (but not necessarily symptomatic, eg, [ 17 ]), and changes in RR within shehias regularly affected by cholera.…”

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Child Enteric Protozoan Infections in Rural Bangladesh: A Cluster-Randomized Controlled Trial

“…Thus, children living in environments contaminated with feces have a higher risk of acquiring intestinal protozoan infections. There is limited and mixed evidence assessing the effect of combined water, sanitation, and handwashing (WSH), or nutritional interventions on protozoan infections: 2 trials with limited statistical power reported no effect of water treatment on Cryptosporidium or Giardia [ 7 , 8 ], 1 water treatment trial reported a reduction in Cryptosporidium [ 9 ], 1 sanitation trial reported a reduction in Giardia [ 10 ], and exclusive breastfeeding and improved nutritional status potentially confer immunity against protozoan infections [ 11–13 ].…”

Enteropathogen seroepidemiology among children in low-resource settings

“…Recombinant Campylobacter p18 and p39 antigens [60][61][62] were expressed and purified as previously described [17] . E. histolytica LecA antigen [14,63,64] was kindly provided by William Petri (University of Virginia) and Joel Herbein (TechLab).…”

“…The β subunit protein from cholera toxin was purchased from Sigma Chemical. The GST negative control protein (15 μg), Cryptosporidium Cp17 (6.8 μg) and Cp23 (12.5 μg) proteins and the Campylobacter p39 protein (25 μg) were coupled to 1.25 x 10 7 beads using the indicated protein amounts [17] . The Giardia , E. histolytica , ETEC, cholera, and Campylobacter p18 proteins were coupled using 30 μg of protein per 1.25 x 10 7 beads.…”

“…At the same time, large-scale serological surveillance platforms create new opportunities for expanded enteropathogen surveillance alongside other infectious diseases [10,11] . These challenges and opportunities have generated interest in antibody-based measurement as a complement to PCR for population-based enteropathogen surveillance [12][13][14][15] , and for endpoints in observational and randomized studies [16][17][18][19][20][21][22] .…”