In the US the potential for drinking water to be associated with cryptosporidiosis among immunocompetent persons is relevant since most major known outbreaks of cryptosporidiosis involved transmission through contaminated water [10, 11, 15, 16, 21–27]. Additionally, other modes of transmission are of interest because of published reports implicating them (such as food, travel, institution-associated, sexual behavior, etc.) [1, 2, 28–52]. This study was undertaken as the first population-based study in the United States of risk factors for endemic cryptosporidiosis in immunocompetent persons.
The major finding in this study was that travel to another country is a very strong and significant risk factor for cryptosporidiosis transmitted in non-outbreak settings in the San Francisco Bay Area. This is consistent with studies of other enteric pathogens [47, 48]. In fact, intestinal protozoa are the most common infecting organisms identified in travelers with chronic diarrhea; the precise etiology of traveler's diarrhea is unclear but it is believed that duration of stay, hygiene, and level of socioeconomic development in the host country are associated with acquisition of infection . The current study was unable to evaluate any of these factors because of limited sample size, but it was observed that 7 of the 13 cases (50.0%) who traveled outside the United States traveled to Central America or Mexico, compared to one out of three controls (33.3%). This finding is very similar to a laboratory-based survey conducted in the mid-1980s in Canada where 52% of the cases of cryptosporidiosis had traveled to Mexico . There is, however, a possibility that ascertainment bias could be the reason that foreign travel was found to be a significant risk factor in our study. If patients presenting with diarrhea who have traveled recently are more likely to have a fecal sample taken, then this will appear as a risk factor. Since we have no information on the likelihood of diagnosis given travel history in the clinical setting in the Bay Area we were unable to evaluate whether this was indeed the case.
Another important finding of this study is that consumption of tap water without further treatment or processing was not associated with cryptosporidiosis when compared to drinking boiled water. Our data were too few to allow further evaluation of the fact that there was a consistent finding of an increased point estimate for tap water in the adjusted analyses. The adjusted analyses involved the composite variables described in the Methods section with the purpose of constructing the most parsimonious model. The reversion of the odds ratio for water from a protective effect in the univariate analysis to an elevated risk in the multivariate is probably associated with its interaction with travel. Because of the small numbers in this study, this interaction could not be addressed – either by looking at interactions in the model or via a stratified analysis. We do, however, feel that the results in this paper will greatly benefit the design and planning of future studies of cryptosporidiosis particularly with respect to understanding the relationship between water consumption and travel.
A study conducted in South Australia in 1993 using a similar approach found that only water-related risks, i.e. rain and spring water consumption, were significantly associated with cryptosporidiosis . But more powerful, recent studies in the same country found no elevated risk for plain tap water consumption . Given our difficulties in recruitment and sometimes conflicting data, such studies must be done in multiple communities simultaneously to obtain an accurate picture of the local situation. The larger CDC study, which will pool data from all seven EIP sites around the country, may be able to better address the issue of drinking water-related risk factors because of the resulting larger sample size. However, even with a larger dataset, the multi-site study will not be able to clarify the risk of cryptosporidiosis from drinking water specifically for residents of the San Francisco Bay Area.
Our planned sample size, determined by available funding, was for 100 cases and 200 controls. Such a sample size would allow the detection of a difference of 15% in exposure to tap water between cases and controls with 80% power and a 0.05 level of statistical significance. We assumed (based on consumer survey data from the Water Quality Association http://www.wqa.org/) that 70% of the controls used tap water without further treatment. Based on the difference in exposure to tap water that we actually observed (4%), a study would require approximately 2500 cases and 2500 controls to detect a statistically significant difference in the use of tap water. Wide confidence intervals for some of the other point estimates indicate that clinically important findings cannot be conclusively ruled out for residents of the San Francisco Bay Area.
An intriguing observation in this study is that exposures that would generally be considered to increase the risk of cryptosporidiosis, such as contact with fecal matter, exposure to raw or uncooked food items, and animal contact, did not have elevated risks. One theoretical explanation for this was offered by Casemore  who expressed the opinion that long-term, low-level exposures to oocysts in raw vegetables and in unpasteurized products may confer protection by boosting the immune system. The recent Australian studies also found significant protective effects of contact with pets and consumption of uncooked vegetables . Indeed, it is likely that acquisition of specific antibodies and an effective protective cellular immune response requires repeated exposure [48, 57]. Although the exposures in this study were assessed for the two-week risk period prior to the onset date of the case, it is probable that some of these exposures are no different in the long and the short term, which may account for the protective effect. Serologic evaluation of cases and controls for immunity to cryptosporidiosis prior to enrollment may be a worthwhile addition to such case-control studies. Serologic definitions of Cryptosporidium exposure were considered as a potential outcome for the current study, especially for controls, but were not feasible due to resource and logistic constraints. Because symptomatic cryptosporidiosis cases represent only a small fraction of those who may be infected with Cryptosporidium, the conclusions drawn from a study such as ours may not apply to those asymptomatically infected.