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
Luther A. Bartelt, James Roche, Glynis Kolling, David Bolick, Francisco Noronha, Caitlin Naylor, Paul Hoffman, Cirle Warren, Steven Singer, Richard Guerrant
(A) Growth curves measuring the percentage of initial weight following a 20% protein diet (RP) or a 2% protein diet (LP). Day 0 is the day of infection with G. lamblia H3 cysts or PBS challenge. One group of mice challenged with PBS on day 0 (D0) was challenged with G. lamblia H3 cysts on day 7 (D 7) (n = 5–7). P < 0.05, RP: PBS vs. LP: PBS; *P < 0.05, **P < 0.01, ***P < 0.001, LP: PBS vs. LP: G. lamblia D7. (B) Growth curves showing percentage of initial weight change beginning 15 days after initiation of an LP diet. Day 7 is the day of infection. *P < 0.05; **P < 0.01; ***P < 0.001. (C) Parasite burden determined by qPCR in serial stool collections on indicated dpi and (D) in representative intestinal tissues 15 dpi (infected on day 7) and 22 dpi (infected on day 0). *P = 0.006; **P < 0.001. Dashed line represents the limit of detection on both graphs.