Hepatitis E Seroprevalence and Seroconversion. Part 5
A secondary objective of this study was to assess the predeployment prevalence of anti‐HEV among service members. Our finding of low anti‐HEV seroprevalence was surprising. Although this rate is consistent with initial reports of anti‐HEV prevalence in the United States, which were 0.4%–2.3%, our rate was considerably lower than those reported in more recent studies. Previous studies among US blood donors reported seroprevalence rates of 18.3% and 21.3%. A study by Kuniholm et al reported a seroprevalence of HEV of 21% among a general civilian noninstitutionalized US population from 1988 through 1994.
We postulate several reasons for this marked difference between the findings of recent studies among the general US population and those of our study. First, there is the possibility that the assays used in these other studies led to an overestimation of the prevalence of HEV in the US population or that the WRAIR assay underestimated this prevalence. The WRAIR assay was specifically developed to improve seroepidemiology and identification of hepatitis E infections and underwent multiple validation steps. It has been reported to have greater sensitivity to low levels of anti‐HEV than commercially available assays and to have 100% specificity in a healthy population. However, one study did find that in an outbreak setting, the sensitivity of the WRAIR test among asymptomatic and symptomatic individuals was less than that of some commercially available assays. In addition, there are differences between the WRAIR assay and other assays in the dilution of test samples and the resulting positive cutoff values. The assay used in the study by Kuniholm et al had a serum dilution of 1:200, compared with a serum dilution of 1:1000 for the WRAIR assay.
The WRAIR assay used a cutoff value that was 15–25 times higher than the cutoff values used with the other assays. If shifting of the WRAIR assay cutoff value from 20 WRAIR U/mL to 15, 10, 5, or 3 WRAIR U/mL was verified, then the resulting seroprevalence estimates in this study would be 1.7%, 2.9%, 8.0%, or 17.1%, respectively. Using a lower cutoff value of 15 or 10 did not result in meaningful increases in seroprevalence. However, when one‐quarter and approximately one‐sixth of the original cutoff value were used, the seroprevalence increased to those of similar estimates seen in other studies. This supports the idea that different cutoff values may be driving some of the differences we see between these assays, but without direct comparisons between the assays in a variety of settings, it is difficult to determine the true source of these differences.