title: Persistent G. lamblia impairs growth  in a murine malnutrition model.
abstract: Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/ subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia– potentiated growth decrements.
authors.affiliation: Division of Infectious Diseases and Center for Global Health, University of Virginia, Charlottesville, Virginia 22903, USA. lab2za@virginia.edu
authors.forename: Luther A
authors.initials: LA
authors.lastname: Bartelt
authors.forename: James
authors.initials: J
authors.lastname: Roche
authors.forename: Glynis
authors.initials: G
authors.lastname: Kolling
authors.forename: David
authors.initials: D
authors.lastname: Bolick
authors.forename: Francisco
authors.initials: F
authors.lastname: Noronha
authors.forename: Caitlin
authors.initials: C
authors.lastname: Naylor
authors.forename: Paul
authors.initials: P
authors.lastname: Hoffman
authors.forename: Cirle
authors.initials: C
authors.lastname: Warren
authors.forename: Steven
authors.initials: S
authors.lastname: Singer
authors.forename: Richard
authors.initials: R
authors.lastname: Guerrant
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004386:Duodenum / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D004804:Eosinophils / Q000276:immunology / Q000469:parasitology; D015870:Gene Expression; D016829:Giardia lamblia / Q000276:immunology*; D005873:Giardiasis / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D006130:Growth Disorders / Q000276:immunology / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D044342:Malnutrition / Q000150:complications* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load
chemical_list: D015848:Interleukin-5; D015847:Interleukin-4