Natural history and impact of Giardia lamblia on child growth attainment and associated pathway-specific biomarkers in a Nicaraguan birth cohort

Background: Giardia lamblia (Giardia) is one of the most common intestinal parasitic infections globally, with an estimated 280 million symptomatic infections annually. In children from low- and middle-income countries (LMICs), Giardia is highly prevalent and has been associated with loss of intestinal barrier function, nutrient-metabolic dysregulation, and linear growth impairment, but specific mechanisms linking Giardia to these outcomes remain poorly understood. Methods and results: We used data and samples from a subset of 76 children in a longitudinal birth cohort in Nicaragua to evaluate the natural history and geospatial distribution of Giardia infections, child growth outcomes (weight-for-age [WAZ] and length-for-age [LAZ] z scores), and relationships with established biomarkers of inflammation, intestinal damage, and growth-signaling. During the first 36 months of life, we tested 2,305 stools (1,903 surveillance stools and 402 diarrheal stools) for Giardia by qPCR. The incidence of Giardia-positive stools was 59.6 per 100 child-years. Any detection of Giardia was associated with a reduction in LAZ at 36 months of life (β:-0.16, P = 0.042). This effect increased when considering persistent or recurrent Giardia detections (β:-0.26, P=