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Giardia: Both a Harmless Commensal and a Devastating Pathogen Giardia: both a harmless commensal and a devastating pathogen Herbert L. DuPont J Clin Invest. 2013;123(6):2352-2354. https://doi.org/10.1172/JCI69932. Commentary The highly prevalent protozoan Giardia lamblia is an enteropathogen that can be asymptomatic in some individuals, while leading to persistent diarrhea and substantial morbidity in others. In this issue of the JCI, Bartelt et al. describe a mouse model of the disease and investigate the contribution of coincident malnutrition with the development of symptomatic infection. This work in part explains how Giardia infection can lead to growth retardation, and may offer insights that guide future therapeutic strategies. Find the latest version: https://jci.me/69932/pdf commentaries 2003;95(12):868–878. Invest. 2012;122(5):1589–1595. 20. Renwick N, et al. Multicolor microRNA FISH 3. Schröder FH, et al. Screening and prostate-cancer 13. Glinskii AB, et al. 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J Clin Biol. 2012;13(8):R75. types of cancer. J Clin Invest. 2005;115(6):1503–1521. Giardia: both a harmless commensal and a devastating pathogen Herbert L. DuPont University of Texas School of Public Health and Medical School, St. Luke’s Episcopal Hospital, Baylor College of Medicine, and the Kelsey Research Foundation, Houston, Texas, USA. The highly prevalent protozoan Giardia lamblia is an enteropathogen that The two faces of Giardia infection can be asymptomatic in some individuals, while leading to persistent diar- In rural areas of the developing world, rhea and substantial morbidity in others. In this issue of the JCI, Bartelt Giardia is ubiquitous and infects nearly et al. describe a mouse model of the disease and investigate the contribution all children, although most remain free of coincident malnutrition with the development of symptomatic infection. of symptoms (3). In these endemic areas, This work in part explains how Giardia infection can lead to growth retarda- infants experience an acute clinical disease tion, and may offer insights that guide future therapeutic strategies. only when first exposed to the protozoan, but quickly recover from infection without Giardia lamblia (synonymous with G. intes- many over the years to conclude that the adverse long-term effects (4). Self-limiting tinalis and G. duodenalis), referred to herein organism is not a pathogen. Giardia can be diarrhea from a Giardia infection is com- as Giardia, was first detected in 1681 by identified in stools of 2% to 5% of presum- mon in young children newly attending Antonie van Leeuwenhoek when looking ably healthy people living in industrialized day care centers (5, 6) and in international at his own stools and was later described in countries like the United States and in 20% travelers (7) to endemic areas when first 1859 by Lambl (1). Finding the organism as to 30% of people in developing regions (2). exposed to the protozoa. After initial expo- frequently in patients without symptoms It is found in water sources and infects sure in otherwise healthy people, symptom- as in those with diarrheal illness has led many animal species. The organism can be atic infection occurs rarely. Risk factors for classified into at least 8 different genotypes first symptomatic infection in young chil- Conflict of interest: In the past 12 months, the called assemblages in humans and animals, dren were shown in one study carried out in author’s university, University of Texas-Houston, has with assemblages A and B being the most rural Egypt to include young age, poverty, received research grants from Dr. Falk Pharma and INC important in human infection. Each year low education level, in-home storage of (Santarus Corporation). The author has received com- in the United States, we identify approxi- drinking water, and unhygienic treatment pensation for serving as an expert witness for several lawsuits related to foodborne illness. mately 20,000 people with Giardia infec- of girls related to gender discrimination Citation for this article: J Clin Invest. 2013; tion, but the actual prevalence is estimated (8). A proportion of infected people, mainly 123(6):2352–2354. doi:10.1172/JCI69932. to be much higher. underweight children with preexistent mal- 2352 The Journal of Clinical Investigation http://www.jci.org Volume 123 Number 6 June 2013 commentaries the pathophysiology of asymptomatic and symptomatic giardiasis. Modeling Giardia infection In this issue of the JCI, Bartelt et al. (22) describe a novel animal model of giardiasis in which malnourished, weaned mice devel- oped epithelial apoptosis and crypt hyper- plasia associated with a Th2-mediated inflammatory response, persistent shed- ding of the infecting strain, and growth retardation secondary to Giardia infection. In this model, Giardia infection was asso- ciated with vitamin A and zinc deficiency and further impairment in nutrition. Vita- min A and zinc may be particularly relevant because reduced levels of each have been shown to contribute to the persistence of diarrhea. When vitamin A and zinc are administered with oral rehydration to chil- dren with diarrhea, the occurrence of per- sistent diarrhea is reduced (23). Figure 1 In the study by Bartelt et al. in this issue Pathogenesis of Giardia infection. of the JCI (22), infection by an assemblage B strain of Giardia led to decreased growth and mucosal histopathological changes nutrition, suffer from persistent infection an immature adaptive immune system in similar to those seen in chronic human with chronic diarrhea and dramatic health infants (17), particularly in those with pre- giardiasis (24). The model allows a char- impairments (9), including worsening of existent nutritional deficits. acterization of mucosal histopathological nutrition (10), growth retardation, and Long-term follow-up studies in chil- response to Giardia infection mimicking cognitive impairment (11). In severe cases dren and adults with Giardia infection are that seen in humans, characterized by of giardiasis, during infection Giardia tro- needed to understand the relationship apoptosis of epithelium with intraepithelial phozoites attach to the epithelium of the between infection and growth and learn- eosinophils, decreased height of villi, altera- proximal small bowel aided by their ventral ing defects, persistent abdominal symp- tion of crypt depth and cellularity, and a adhesive discs, evade host defenses possibly toms (18), postinfectious functional bowel Th2-based immune response.
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