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Figure 1. The clinical spectrum of Giardia infection Global efforts to improve child health in resource-limited settings situate Giardia infections amidst the broader context of childhood malnutrition, a multitude of diverse and frequent enteric pathogen exposures Dolutegravir cell line [34], and new understandings of the role of environmental enteropathy (a form of chronic gastrointestinal dysfunction and inflammation possibly inclusive of the previously termed clinical condition ��tropical sprue��) [11,35] and microbiota [36] on childhood development and growth. The most recent analyses, equipped with more rigorous surveillance methods and more sensitive molecular diagnostics [37�C39], have not only reiterated the wide range of variability in pediatric Giardia infection outcomes seen in prior studies [3] but unveiled a much greater burden of exposure than estimates based on microscopic techniques [39,40]. These and other studies have raised provocative considerations, including the potential for Giardia to be protective against acute diarrhea [41�C43]. In light of the incompletely understood pathology attributable to Giardia infection, recent advances in parasite and gastrointestinal biology hope to clarify how and when Giardia causes disease. These advances address fundamental questions regarding how Giardia interacts within the complex ecology of microbial, nutritional, and host factors within the small intestine, the determinants of host susceptibility, and whether and how host inflammation contributes to pathogenesis (Figure 2). Figure selleck 2. Proposed determinants and mechanisms of Giardia infection outcomes Endemic pediatric giardiasis equipoise In 1971, after charting weights of children in Guatemala, Leonardo J. Mata reported an association between arrested growth and frequent episodes of diarrhea [44]. A follow-up analysis of these children associated increased duration and frequency of Giardia episodes with a greater detrimental growth impact [45]. Since then, several studies have attempted to demonstrate how early Giardia infections promote diarrhea and developmental shortfalls. CDK9 A 2012 meta-analysis found that, although Giardia infection was associated with persistent diarrhea (>14 days; odds ratio [OR] 3.2, 95% confidence interval [CI] 1.50-6.76; P