Giardia and growth impairment in children in high-prevalence settings: consequence or co-incidence?

Abstract

Purpose of reviewGiardia is a common intestinal parasite worldwide, and infection can be associated with clear, and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is most often not associated with or is perhaps even protective against acute diarrhea. Nonetheless, recent longitudinal studies in high-prevalence settings increasingly identify an association with long-term outcomes that has been difficult to discern. Recent findingsRecent studies have made progress in disentangling this apparent paradox. First, prospective, well characterized cohort studies have repeatedly identified associations between Giardia infection, gut function, and child growth. Second, experimental animal and in-vitro models have further characterized the biological plausibility that Giardia could impair intestinal function and subsequently child development through different pathways, depending upon biological and environmental factors. Finally, new work has shed light on the potential for Giardia conspiring with specific other gut microbes, which may explain discrepant findings in the literature, help guide future higher resolution analyses of this pathogen, and inform new opportunities for intervention. SummaryRecent prospective studies have confirmed a high, if not universal, prevalence of persistent Giardia infections in low-and-middle income countries associated with child-growth shortfalls and altered gut permeability. However, the predominance of subclinical infections limits understanding of the true clinical impact of endemic pediatric giardiasis, and global disease burdens remain uncalculated. Integrating the role of Giardia in multipathogen enteropathies and how nutritional, microbial, metabolic, and pathogenstrain variables influence Giardia infection outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.

GiardiaIncreases Macrophage Production of the Anti-Inflammatory Cytokine Interleukin-10 in Response to Lipopolysaccharide via Macrophage Galactose Binding Lectin (MGL1)

“…Giardia has been previously shown to downregulate certain signatures of inflammation both in patients and in vitro , which may play a role in the frequency of subclinical infections. High parasite burdens in children have been linked to reduced markers of environmental enteric dysfunction, namely reduced alpha-1-antitrypsin, myeloperoxidase, and neopterin in fecal samples (Dougherty and Bartelt 2022; Giallourou et al 2023; Rogawski et al 2018). In vitro data shows that cathepsin B cysteine proteases released by the parasite directly degrade CXCL8, a chemokine released by enterocytes during inflammation to promote neutrophil recruitment (Cotton, Bhargava, et al 2014; Zhu et al 2021).…”

Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target in Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum

“…In severe cases, patients develop complications that lead to gastrointestinal disorders such as irritable bowel syndrome, malabsorption syndrome, and malnutrition [ 11 , 12 , 13 ]. The population with the highest incidence and severity of symptoms is children under five years old, who may experience delays in both physical and intellectual development [ 14 ]. The first-line of treatment for giardiasis is the metronidazole (MTZ) drug.…”

Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection

“…duodenalis ) is an intestinal protozoan parasite causing the diarrhoeal disease giardiasis in a variety of animal species [ 1 , 2 ]. ~180 million symptomatic human infections are estimated to occur worldwide every year [ 3 ], with the number of asymptomatic infections predicted to be even higher [ 4 ]. Giardia intestinalis , hereafter referred to as G .…”

“…Most infections are self-limiting but recurring G . intestinalis infections can result in malnutrition and stunting in children [ 4 , 8 , 13 ]. Common giardiasis symptoms are watery diarrhoea, bloating, epigastric pain, vomiting and nausea [ 2 ].…”