Independent and combined effects of nutrition and sanitation interventions on enteric pathogen carriage and child growth in rural Cambodia: a factorial cluster-randomised controlled trial

Abstract

Background Childhood exposure to fecal pathogens contributes to growth faltering, which is linked with adverse side effects later in life. The prevalence of stunting remains high in rural Cambodia, despite rapid economic development over the last two decades. This study aimed to assess the independent and combined effects of nutrition and sanitation programming on child growth outcomes in rural Cambodia. Methods We conducted a factorial cluster-randomized controlled trial of 4,015 households with 4,124 children (1-28 months of age) across rural Cambodia. Fifty-five communes (clusters) were randomly assigned to a control arm or one of three treatments: a nutrition-only arm, a sanitation-only arm, and a combined nutrition and sanitation arm receiving both treatments. The primary outcome was length-for-age Z-score (LAZ). Secondary outcomes were weight-for-age Z-score (WAZ), weight-for-height Z-score (WHZ), stunting, wasting, underweight, and caregiver-reported diarrhea. Analysis was by intention-to-treat. The trial was pre-registered with ISRCTN Registry (ISRCTN77820875). Findings Compliance in the arms receiving the nutrition intervention was high, but compliance in the arms receiving the sanitation intervention was low. Compared with a mean LAZ of -1.04 (SD 1.2) in the control arm, children in the nutrition-only arm (LAZ +0.08, 95% CI: -0.01-0.18) and combined nutrition and sanitation arm (LAZ +0.10, 95% CI: 0.01-0.20) experienced greater linear growth; there were no measurable differences in LAZ in the sanitation-only arm. Similarly, compared with a mean WAZ of -1.05 (SD 1.1) in the control arm, children in the nutrition-only arm (WAZ +0.10, 95% CI 0.00-0.19) and combined-intervention arm (WAZ +0.11, 95% CI 0.03-0.20) were heavier for their age; there was no measurable difference in WAZ in the sanitation-only arm. There were no differences between arms in prevalence of stunting, wasting, underweight status, or one week period prevalence of diarrhea. Interpretation Improvements in child growth in nutrition and combined nutrition and sanitation arms are consistent with other recent trials but we found no evidence that this sanitation intervention improved child growth. The sanitation intervention achieved only modest changes in sanitation access and use suggesting that more effective approaches are needed to reduce open defecation in this setting.

Long-term impacts of an urban sanitation intervention on enteric pathogens in children in Maputo city, Mozambique: study protocol for a cross-sectional follow-up to the Maputo Sanitation (MapSan) trial five years post-intervention

“…Stool-based molecular detection is performed for 27 enteric pathogens commonly implicated in both symptomatic and asymptomatic childhood infections globally, including those identified at the Global Enteric Multicenter Study (GEMS) study site in Manhiça, Mozambique [12,36,56,61]. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is conducted by custom TaqMan Array Card (TAC; Thermo Fisher, Carlsbad, CA, USA) to simultaneously quantify genetic targets corresponding to 13 [62]. We also include the respiratory virus SARS-CoV-2 on the custom TAC, which is shed in the stool of many infected individuals, enabling surveillance through fecal waste streams [63,64].…”

“…Child weight and recumbent length (child age < 24 months) or standing height (24 -60 months) are assessed according to standard World Health Organization (WHO) protocols and transformed to age-adjusted z-scores using WHO reference populations to obtain height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z-scores [69,70]. Secondary outcomes include continuous HAZ, WAZ, and WHZ, as well as prevalence of binary growth outcomes stunting (HAZ < -2), underweight (WAZ < -2), and wasting (WHZ < -2) [13].…”

“…Similar to the fecal indicator paradigm for monitoring fecal pollution, the sheer number of potential pathogens that must be considered to comprehensively assess efforts to interrupt fecal-oral disease transmission demands a simple indicator of intervention impact [82]. Recent developments in molecular diagnostic platforms enabling simultaneous detection of multiple enteric pathogens in stool and environmental matrices have been rapidly adopted [10,11,13,34,36,37,49] and the inherent limitations of symptomatic diarrhea as a trial endpoint increasingly recognized [14,35]. In addition to providing objective measures of prior pathogen exposure, these efforts have already offered more granular insight into the behaviors and responses of particular organisms in different settings.…”

“…However, many diarrheal episodes are not attributable to infectious etiologies [3,7], while the etiology of attributable diarrhea varies widely by setting and only certain diarrheal pathogens are consistently implicated in reduced linear growth [2,8,9]. Far more prevalent is asymptomatic enteric pathogen shedding in stool [3,7,[10][11][12][13][14], which may be more strongly associated with poor growth than diarrheal illness [2,[15][16][17], potentially by contributing to intestinal inflammation, gut permeability, and nutrient malabsorption in a condition known as environmental enteric dysfunction (EED) [18][19][20][21]. In addition to the diverse negative impacts of stunting [22], specific adverse health outcomes associated with enteric infection and EED include delayed cognitive development [23][24][25] and reduced oral vaccine efficacy [26,27].…”

“…Combined WASH interventions with high fidelity and adherence reduced stool-based detection of Giardia, hookworm, and possibly Ascaris among 30 month-old children (but not younger children) and enteric viruses in rural Bangladesh [10,39,40], Ascaris in rural Kenya [41], and the number of co-detected parasites in rural Zimbabwe [11], but not bacterial pathogens or those most associated with stunting in any setting [2]. The sanitation-only intervention arm in rural Bangladesh reduced Trichuris prevalence in child stool [39] and may have reduced pathogenic Escherichia coli on child hands in more crowded households [42], while a sanitation intervention in rural Cambodia did not impact any pathogens measured in child stool [35]. Viewed collectively, a clear picture emerges of pervasive childhood polymicrobial exposures that were not meaningfully prevented by lowcost WASH interventions [43][44][45].…”