Understanding Risk Factors to Cryptosporidium parvum: Studies in Gnotobiotic PigsEPA Grant Number: R826138
Title: Understanding Risk Factors to Cryptosporidium parvum: Studies in Gnotobiotic Pigs
Investigators: Ward, Lucy A.
Institution: The Ohio State University
EPA Project Officer: Hiscock, Michael
Project Period: February 20, 1998 through February 19, 2001 (Extended to December 19, 2002)
Project Amount: $332,084
RFA: Drinking Water (1997) RFA Text | Recipients Lists
Research Category: Drinking Water , Water
Water sampling has demonstrated that Cryptosporidium is ubiquitous in the environment and will always likely be present as a waterborne pathogen. Although researchers frequently recover small numbers of oocysts from treated drinking water, it is not known if the number of oocysts present in drinking water constitutes a sufficient dose to cause illness or if the infective dose is significantly lower in immunosuppressed persons or if isolates of C. parvum vary in infectivity and virulence. Consequently, the true risk associated with consumption of drinking waters contaminated with small numbers of C. parvum oocysts is unknown. The limitations imposed on investigators using human subjects necessitates the use of an animal model that is similar to humans in terms of risk susceptibility and host response to Cryptosporidium. To this end, we will utilize a gnotobiotic pig model of cryptosporidiosis to assess risk as a function of specific host factors identified to increase (or decrease) susceptibility to disease following C.parvum exposure. Our goal is to increase our knowledge and understanding of risks associated with cryptosporidiosis. To achieve this, we will utilize a gnotobiotic pig model and pursue three objectives: 1) Assess and compare the pathogenesis (infectivity and virulence) of C.parvum in neonatal versus older gnotobiotic pigs; 2) Evaluate the susceptibility and clinical responses of immunosuppressed gnotobiotic pigs to C.parvum; and 3) Characterize the humoral (B cell), cellular (T cell), and cytokine immune responses in gnotobiotic pigs with cryptosporidiosis.
Detailed pathogenesis and basic immunity studies in gnotobiotic pigs of different ages and immune status will be done following inoculation with a human C.parvum isolate. This model will also be used to isolate, propagate and study other potential human C.parvum isolates obtained from local public waters and sewage effluents. Key questions to be addressed from these studies include: "What is the infective dose of C. parvum?"; "What is the progression of disease and lesion development following C.parvum exposure?"; "Is age a determinant of risk to cryptosporidiosis?"; "Are immunosuppressed animals more susceptible to cryptosporidiosis than their immunologically healthy counterparts?"; and "Which immune factors are most relevant to risk assessment in cryptosporidiosis?".
This proposal, taken to completion, will increase our knowledge and understanding of risks associated with Cryptosporidium exposure through delineating specific host factors involved in risk to cryptosporidial disease. In addition, our studies will assess the potential of this animal model as an alternative tool for diagnostic screening of water samples for determination of permissible limits of this organism in our public waters, and for amplification of C.parvum isolates from specimens that are of limited quantity or contain few oocysts to ensure that adequate amounts of resource' organisms are available for scientists to study. Findings from the proposed study will provide the foundation upon which to build more comprehensive studies for evaluating immunity factors in risk assessment and study the impact of this organism on our environment.