Individuals with Le(a+b−) Blood Group Have Increased Susceptibility to Symptomatic Vibrio cholerae O1 Infection

Mohammad Arifuzzaman,Mohammad Arif Rahman,Firdausi Qadri,Regina C Larocque,Taufiqur Rahman Bhuiyan,Fahima Chowdhury,Ashraful I Khan,Stephen B Calderwood,Edward T Ryan,Rasheduzzaman Rashu,Tanvir Ahmed,Jason B Harris,Joseph M Vinetz

doi:10.1371/journal.pntd.0001413

Abstract

BackgroundHuman genetic factors such as blood group antigens may affect the severity of infectious diseases. Presence of specific ABO and Lewis blood group antigens has been shown previously to be associated with the risk of different enteric infections. The aim of this study was to determine the relationship of the Lewis blood group antigens with susceptibility to cholera, as well as severity of disease and immune responses to infection.MethodologyWe determined Lewis and ABO blood groups of a cohort of patients infected by Vibrio cholerae O1, their household contacts, and healthy controls, and analyzed the risk of symptomatic infection, severity of disease if infected and immune response following infection.Principal FindingsWe found that more individuals with cholera expressed the Le(a+b−) phenotype than the asymptomatic household contacts (OR 1.91, 95% CI 1.03–3.56) or healthy controls (OR 1.90, 95% CI 1.13–3.21), as has been seen previously for the risk of symptomatic ETEC infection. Le(a–b+) individuals were less susceptible to cholera and if infected, required less intravenous fluid replacement in hospital, suggesting that this blood group may be associated with protection against V. cholerae O1. Individuals with Le(a–b−) blood group phenotype who had symptomatic cholera had a longer duration of diarrhea and required higher volumes of intravenous fluid replacement. In addition, individuals with Le(a–b−) phenotype also had lessened plasma IgA responses to V. cholerae O1 lipopolysaccharide on day 7 after infection compared to individuals in the other two Lewis blood group phenotypes.ConclusionIndividuals with Lewis blood type Le(a+b−) are more susceptible and Le(a–b+) are less susceptible to V. cholerae O1 associated symptomatic disease. Presence of this histo-blood group antigen may be included in evaluating the risk for cholera in a population, as well as in vaccine efficacy studies, as is currently being done for the ABO blood group antigens.

Highlights

Cholera continues to cause severe diarrheal illness in people with inadequate public health who live in resource-limited settings
Individuals with Lewis blood type Le(a+b2) are more susceptible and Le(a–b+) are less susceptible to V. cholerae O1 associated symptomatic disease. Presence of this histo-blood group antigen may be included in evaluating the risk for cholera in a population, as well as in vaccine efficacy studies, as is currently being done for the ABO blood group antigens
Saliva specimens were obtained at one time point from 283 healthy individuals who were from an urban setting and in a similar socio-economic status as the index patients, to determine the distribution of the Lewis blood group antigens in the general population

Summary

Introduction

Cholera continues to cause severe diarrheal illness in people with inadequate public health who live in resource-limited settings. Cholera is endemic in countries in Asia and Africa, with new outbreaks reported each year in several countries including, most recently, in Zimbabwe and Haiti [1,2]. Human genetic factors such as blood group antigens may affect the severity of infectious diseases. Presence of specific ABO and Lewis blood group antigens has been shown previously to be associated with the risk of different enteric infections. The aim of this study was to determine the relationship of the Lewis blood group antigens with susceptibility to cholera, as well as severity of disease and immune responses to infection

Objectives

Methods

Results

Discussion

Conclusion