Date Published: April 9, 2008
Publisher: Public Library of Science
Author(s): Jason B. Harris, Regina C. LaRocque, Fahima Chowdhury, Ashraful I. Khan, Tanya Logvinenko, Abu S. G. Faruque, Edward T. Ryan, Firdausi Qadri, Stephen B. Calderwood, Albert I. Ko
Abstract: BackgroundDespite recent progress in understanding the molecular basis of Vibrio cholerae pathogenesis, there is relatively little knowledge of the factors that determine the variability in human susceptibility to V. cholerae infection.Methods and FindingsWe performed an observational study of a cohort of household contacts of cholera patients in Bangladesh, and compared the baseline characteristics of household members who went on to develop culture-positive V. cholerae infection with individuals who did not develop infection. Although the vibriocidal antibody is the only previously described immunologic marker associated with protection from V. cholerae infection, we found that levels of serum IgA specific to three V. cholerae antigens—the B subunit of cholera toxin, lipopolysaccharide, and TcpA, the major component of the toxin–co-regulated pilus—also predicted protection in household contacts of patients infected with V. cholerae O1, the current predominant cause of cholera. Circulating IgA antibodies to TcpA were also associated with protection from V. cholerae O139 infection. In contrast, there was no association between serum IgG antibodies specific to these three antigens and protection from infection with either serogroup. We also found evidence that host genetic characteristics and serum retinol levels modify susceptibility to V. cholerae infection.ConclusionsOur observation that levels of serum IgA (but not serum IgG) directed at certain V. cholerae antigens are associated with protection from infection underscores the need to better understand anti–V. cholerae immunity at the mucosal surface. Furthermore, our data suggest that susceptibility to V. cholerae infection is determined by a combination of immunologic, nutritional, and genetic characteristics; additional factors that influence susceptibility to cholera remain unidentified.
Partial Text: Vibrio cholerae causes a spectrum of infection in humans ranging from asymptomatic colonization to severe secretory diarrhea. V. cholerae is differentiated serologically by the O antigen of its lipopolysaccharide (LPS); the vast majority of human cholera is caused by the O1 and O139 serogroups. The O1 serogroup of V. cholerae is classified into two biotypes (classical and El Tor), and two major serotypes (Inaba and Ogawa) . In the 1960s, the V. cholerae O1 El Tor biotype emerged as a major cause of cholera, ultimately replacing the classical biotype. In 1992, the V. cholerae O139 serogroup first appeared, and after briefly predominating in South Asia, now persists in this region, but at much lower levels than V. cholerae O1 El Tor.
An improved understanding of factors that influence host susceptibility to cholera may aid in the development and implementation of an effective vaccination program. In this study, we identified novel immunologic markers that predict protection from V. cholerae infection in a population in Bangladesh, as well as other host characteristics that modify susceptibility.