Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh

Background Despite 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 Findings We 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. Conclusions Our 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.

[1]  K Y Liang,et al.  Longitudinal data analysis for discrete and continuous outcomes. , 1986, Biometrics.

[2]  L. Cisneros,et al.  Duration of infection-derived immunity to cholera. , 1981, The Journal of infectious diseases.

[3]  R. Sack,et al.  Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae O139 Bengal with the response in cholera due to Vibrio cholerae O1 , 1995, Clinical and diagnostic laboratory immunology.

[4]  W. Mosley,et al.  The relationship of vibriocidal antibody titre to susceptibility to cholera in family contacts of cholera patients. , 1968, Bulletin of the World Health Organization.

[5]  R. Sack,et al.  Production, characterization, and application of monoclonal antibodies to Vibrio cholerae O139 synonym Bengal , 1994, Clinical and diagnostic laboratory immunology.

[6]  A. Faruque,et al.  Incomplete correlation of serum vibriocidal antibody titer with protection from Vibrio cholerae infection in urban Bangladesh. , 2004, The Journal of infectious diseases.

[7]  M. Mathan,et al.  Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut , 2003, Gut.

[8]  R. Black,et al.  Supplementation with zinc, but not vitamin A, improves seroconversion to vibriocidal antibody in children given an oral cholera vaccine. , 2003, The Journal of infectious diseases.

[9]  David A. Sack,et al.  Blood Group, Immunity, and Risk of Infection with Vibrio cholerae in an Area of Endemicity , 2005, Infection and Immunity.

[10]  B. Stoll,et al.  Predisposition for cholera of individuals with O blood group. Possible evolutionary significance. , 1985, American journal of epidemiology.

[11]  A. Faruque,et al.  Transcriptional Profiling of Vibrio cholerae Recovered Directly from Patient Specimens during Early and Late Stages of Human Infection , 2005, Infection and Immunity.

[12]  S. Calderwood,et al.  Cholera vaccines. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  Carl-Fredrik Flach,et al.  Broad Up-Regulation of Innate Defense Factors during Acute Cholera , 2007, Infection and Immunity.

[14]  M. Asaduzzaman,et al.  The Major Subunit of the Toxin-Coregulated Pilus TcpA Induces Mucosal and Systemic Immunoglobulin A Immune Responses in Patients with Cholera Caused by Vibrio cholerae O1 and O139 , 2004, Infection and Immunity.

[15]  R. Black,et al.  Suppressive effect of zinc on antibody response to cholera toxin in children given the killed, B subunit-whole cell, oral cholera vaccine. , 2004, Vaccine.

[16]  A. Faruque,et al.  Antigen-Specific Immunoglobulin A Antibodies Secreted from Circulating B Cells Are an Effective Marker for Recent Local Immune Responses in Patients with Cholera: Comparison to Antibody-Secreting Cell Responses and Other Immunological Markers , 2003, Infection and Immunity.

[17]  C. F. Fischer Walker,et al.  Micronutrients and diarrheal disease. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[18]  R. Glass,et al.  Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection. , 1985, The Journal of infectious diseases.

[19]  D. Sack,et al.  Rapid diagnosis of cholera by coagglutination test using 4-h fecal enrichment cultures , 1987, Journal of clinical microbiology.

[20]  S. Neoh,et al.  The antigens of Vibrio cholerae involved in the vibriocidal action of antibody and complement. , 1970, The Journal of infectious diseases.

[21]  M U Khan,et al.  Endemic cholera in rural Bangladesh, 1966-1980. , 1982, American journal of epidemiology.

[22]  D. Sack,et al.  Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine. , 1984, The Journal of infectious diseases.

[23]  U. Ramakrishnan Prevalence of micronutrient malnutrition worldwide. , 2002, Nutrition reviews.

[24]  Yunus,et al.  Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up , 1990, The Lancet.