Genomic aspects of cholera and its relevance to cholera control

Abstract

Toxigenic Vibrio cholerae belonging to serogroups O1 or O139 are water and food borne pathogens that cause the disease cholera. The fifth and sixth pandemics of cholera were caused by the classical biotype while the current seventh pandemic is caused by the El Tor biotype, which has now completely replaced the classical biotype. Molecular studies have further defined three new variants of El Tor V. cholerae O1 associated with cholera. The three variants are i) the Matlab variants which could not be biotyped by conventional methods since they had a combination of both classical and El Tor traits, ii) altered El Tor O1 strains which displayed typical traits of the El Tor biotype but carried the classical CTX prophage and iii) altered O1 El Tor isolates which harbored ctxB of classical origin. The altered El Tor variants produce higher quantities of cholera toxin as compared to the prototype El Tor and classical biotypes. The current pandemic caused by the El Tor biotype has shown subtle but distinct changes in the epidemiology and clinical presentation of the disease and also in the virulence and molecular traits. There has also been a change in the epidemiology of the disease with the burden of disease dominating in the under 5 year age group particularly in cholera endemic areas of south east Asia. Another unusual trend recently witnessed is the protracted nature of cholera outbreaks with high case fatality. Single nucleotide polymorphisms in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates show that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves, and identified several transcontinental transmission events. From the studies on the genomes of V. cholerae, two facts have emerged. One is that variants of V. cholerae O1 emerge in cholera hyper endemic areas due to the intense transmission. The other fact is that all the three new waves of the El Tor variants originated from the Bay of Bengal area. Taken together, genomic studies point to the adoption of intense cholera control programs in the cholera endemic Bay of Bengal area as a strategy to eliminate cholera in these endemic areas and thereby abort the emergence and spread of cholera over the region and the globe.