Pathogenic Mechanisms of Cryptosporidium and Giardia

Intestinal protozoa are important etiological agents of diarrhea, particularly in children, yet the public health risk they pose is often neglected. Results from the Global Enteric Multicenter Study (GEMS) showed that Cryptosporidium is among the leading causes of moderate to severe diarrhea in children under 2 years. Likewise, Giardia infects approximately 200 million individuals worldwide, and causes acute diarrhea in children under 5 years. Despite this recognized role as pathogens, the question is why and how these parasites cause disease in some individuals but not in others. This review focuses on known pathogenic mechanisms of Cryptosporidium and Giardia, and infection progress towards disease. Infection by Cryptosporidium or Giardia can result in symptoms in some individuals but can lead to an asymptomatic state in others. Common effects on host epithelial cells include disruption of the mucus layer, attachment to (Giardia and Cryptosporidium) and/or invasion of epithelial cells (Cryptosporidium), release of effector molecules into the host cell cytoplasm and secretion of toxins. However, pathogenic mechanisms are not identical. For instance, Giardia is the only unicellular eukaryote that escapes the host immune reaction in the gut by antigenic variation. While both protozoa cause disruption of tight junctions, only C. parvum has the ability to induce gastrointestinal cancer linked to cytoskeleton alterations, at least in an animal model. To fully understand their pathogenicity, it is essential to consider the complex ecologic interactions of these protozoa with gut microbiota, as well as nutritional and host-related factors.