DURATION OF SERUM ANTITOXIN RESPONSE FOLLOWING VIBRIO CHOLERAE INFECTION IN NORTH AMERICANS: RELEVANCE FOR SEROEPIDEMIOLOGY1

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Abstract
Because of repeated infections with bacterial enteropathogens elaborating antigenically related enterotoxins, persons living in less-developed areas even where cholera is not endemic have high prevalence and levels of cholera antitoxin. Thus, in less-developed areas, antitoxin is not helpful for the seroepidemiology of cholera. In contrast, since diarrheal infections due to pathogens elaborating cholera-like enterotoxins are rare in industrialized countries, this study reviewed the magnitude and duration of the serum antitoxin response to cholera infections in North Americans to develop guidelines for use of antitoxin as a seroepidemiologic tool to investigate endemic cholera in the United States. Sera of 31 North American volunteers who ingested Vibrio cholerae in the course of vaccine development studies were examined for immunoglobulin G (IgG) antitoxin by microtiter enzyme-linked immunosorbent assay (ELISA). All 31 had significant rises in antitoxin one month after challenge and provided one or more additional specimens 4–25 months post-inoculation. Seven persons had subclinical infection; the remaining 24 experienced diarrhea. Pre-challenge, 7 of 31 volunteers had low levels of antitoxin, i.e., the net optical density (O.D.) of these sera was greater than the mean net O.D. + 3 standard deviations (SD) of a negative control serum pool known to lack antitoxin by two neutralization assays. The mean antitoxin level at one month post-challenge in the 24 clinically ill persons (net O.D. 1.10) was significantly higher than the mean of the individuals with sub clinical infections (mean net O.D. 0.83) (p < 0.03); the mean net O.D. of the former group remained elevated for at least 25 months. It was decided arbitrarily that a serum IgG ELISA net O.D. should equal or surpass 4 times the net O.D. of the negative control (positive/negative(P/N) ratio≥4) to be considered indicative of past clinical cholera infection. Using this stringent criterion, such net O.D. levels were found in no one pie-challenge, in 30 of 31 at one month post-challenge (one subclinical case did not reach this level), and in 20/24 persons tested 4–25 months after clinical cholera infection. The microtiter ELISA test for serum IgG cholera antitoxin represents an important tool for seroepidemiologic investigation of cholera in the United States and other industrialized countries.