With respect to the clinical course of E. bieneusi-infected men, after a mean of 15 months of follow-up, the 18 men with chronic diarrhea retained this pattern, and 2 of the 13 asymptomatic men developed intermittent diarrhea (unpublished data). Histologic findings varied from normal architecture to almost complete effacement of the villous architecture (unpublished data). We do not agree with Orenstein and colleagues' statement correlating parasite burden and the severity of diarrhea. Such a correlation requires a valid and reliable method for assessing parasite burden, which is not currently available. Classifying the degree of mucosal damage on the basis of one or more small biopsy fragments assumes that the lesion is not patchy. We are aware of only one study of the topographic distribution of intestinal microsporidiosis [1] and were unfamiliar with the earlier published abstract describing large-bowel infection with E. bieneusi [2].

We agree that plastic embedding is the best method to process specimens for light microscopy, but we used electron microscopy because of its ready availability. As Orenstein and colleagues [1] previously stated, the detection of microsporidia by light microscopy in slides prepared from paraffin-embedded tissues is difficult because "E. bieneusi organisms are not reliably detected in paraffin sections using a variety of cytochemical stains" [1]. Because the pathologist experiences a learning curve, we decided to learn to recognize organisms on slides from patients known to have microsporidia that was previously diagnosed by electron microscopy. We recognize the shortcomings of attempting to quantify intensity of infection (or parasite burden) using electron microscopy, as stated in our article [3].

From our evidence, we cannot conclude that a relation between diarrhea and Microsporidia does not exist, but only that we did not detect any such relation. It seems likely that, as with many other parasites, a relation exists between the intensity of infection and clinical illness (in this case, diarrhea).