Cryptosporidium parvum is one of the leading parasitic causes of diarrhea in the United States and abroad. Recent data suggest that children less than one year of age (but not older children) who acquire C. parvum infection suffer subsequent enhanced morbidity due to increased episodes of diarrhea and stunted growth. This post-cryptosporidial increase in acute diarrheal illness is not due to either recurrent or relapsing C. parvum infection. Based on these data, we have hypothesized that age-dependent differences in systemic and/or intestinal immune responses to C. parvum infection accounts, at least in part, for the observed differences between younger and older children in the clinical course after C. parvum infection. To date, no prospective studies have examined either the systemic or intestinal immunologic responses of young immunocompetent children to C. parvum infection nor attempted to correlate the clinical course of the child with these immunologic responses. Thus, the primary goal of this proposal is to initiate pilot studies to prospectively characterize the clinical course and immunologic responses of young children (<1 year of age) who acquire C. parvum infection to begin to identify potential mechanisms accounting for the subsequent enhanced morbidity observed in field epidemiologic investigations.
Our specific aims are: 1) To examine the systemic immunologic response of children both at the time of initial diagnosis of C. parvum infection and at approximately 9 to 12 months after C. parvum infection. The immunologic responses associated with C. parvum infection will be correlated with both the initial clinical expression of infection, i.e., acute, persistent or chronic diarrhea) and the subsequent clinical course of the children; 2) To investigate the intestinal immunologic response to C. parvum infection; and, 3) To begin to investigate whether infection with different genotypes (i.e., human type or bovine type) of C. parvum correlates with either the initial clinical expression of infection, host immunologic responses and/or the subsequent clinical course of children who acquire C. parvum infection. These studies will provide new data on the acute immunologic responses to C. parvum infection in immunocompetent children; will examine the delayed immunologic function after C. parvum infection; and will begin to identify the nature of the intestinal immunologic responses to natural C. parvum infection. We anticipate that these descriptive pilot studies will enable us to seek R01 funding to pursue mechanistic studies of C. parvum disease pathogenesis.
| Kirkpatrick, B D; Noel, Francine; Rouzier, Patricia D et al. (2006) Childhood cryptosporidiosis is associated with a persistent systemic inflammatory response. Clin Infect Dis 43:604-8 |
| Kirkpatrick, B D; Huston, C D; Wagner, D et al. (2006) Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children. Clin Infect Dis 43:289-94 |
| Kirkpatrick, Beth D; Daniels, Michelle M; Jean, Simone Sonia et al. (2002) Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian children. J Infect Dis 186:94-101 |
