A 50% infectious dose (ID50) of 132 Cryptosporidium parvum oocysts was previously determined in serologically negative individuals (ELISA). In this study, 17 healthy adults with pre-existing anti-C. parvum serum IgG were challenged with 500–50,000 oocysts. Infection and diarrhea were associated with the higher challenge doses. The ID50 was 1,880 oocysts, 20-fold higher than in seronegative volunteers. Fecal oocysts were detected in only seven (53.8%) of 13 individuals with clinical cryptosporidiosis, indicating that the host response may effectively decrease the number of oocysts produced. Subjects with the highest absorbances prior to challenge had little to no increase in IgG following challenge, whereas volunteers with lower reactivities showed significant postchallenge increases. This suggests that an upper limit of serum IgG was present in some subjects, while others were further stimulated by an additional exposure. These data indicate that prior exposure to C. parvum provides protection from infection and illness at low oocyst doses.

Cryptosporidium parvum is a recognized cause of diarrheal illness in waterborne outbreaks1–3 and in individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). 4 The increased awareness of cryptosporidiosis in the general population and in specialized settings, such as day care centers, as well as the seriousness of the disease in immunosuppressed individuals have earned Cryptosporidium a place on the list of emerging diseases that are a threat to the public health. 5 Furthermore, no effective chemotherapeutic agent has been demonstrated to prevent or cure C. parvum infections. Thus, there is considerable interest in the development of immunotherapies designed to limit infection. To rationally design such interventions, it is important to understand the major immunologic mechanisms that are operative in self-limited disease. Animals6–8 and humans9 with intact immune systems are typically capable of clearing the parasite within 1–3 weeks after infection. Several studies with experimental animal models have demonstrated that most species are refractory to a second oocyst challenge. 7, 8 Indeed, adult animals exposed to the parasite for the first time are relatively resistant to infection and often have only a transient period of oocyst shedding with few to no symptoms. In contrast, healthy adult volunteers can experience infections and diarrheal illnesses when oocyst challenges are at least one year apart. 10 Many studies in animals11–15 and humans16–19 have documented the presence of antibodies to C. parvum infection. However, these investigations in humans were carried out in serologic surveys or in select persons experiencing diarrhea and only after the infections were diagnosed. Thus, the observations were necessarily limited by the lack of information on the immune status and exposure history prior to the exposure. Also, differences among the studies in antigen preparations used in the testing and definitions of positivity further complicate direct comparisons. In volunteer studies previously published, 20 an anti-C. parvum ELISA was used to identify serologically negative volunteers that were subsequently challenged with known concentrations of oocysts. Following challenge, the serum antibody response was primarily IgM and in some cases IgA.