Circulation and transmission of clones of Vibrio cholerae during cholera outbreaks

Abstract

Cholera is still a major public health problem. The underlying bacterial pathogen Vibrio cholerae (V. cholerae) is evolving and some of its mutations have set the stage for outbreaks. After V. cholerae acquired the mobile elements VSP I & II, the El Tor pandemic began and spread across the tropics. The replacement of the O1 serotype encoding genes with the O139 encoding genes triggered an outbreak that swept across the Indian subcontinent. The sxt element generated a third selective sweep and most recently a fourth sweep was associated with the exchange of the El Tor ctx allele for a classical ctx allele in the El Tor background. In Kenya, variants of this fourth selective sweep have differentiated and become endemic residing in and emerging from environmental reservoirs. On a local level, studies in Bangladesh have revealed that outbreaks may arise from a nonrandom subset of the genetic lineages in the environment and as the population of the pathogen expands, many novel mutations may be found increasing the amount of genetic variation, a phenomenon known as a founder flush. In Haiti, after the initial invasion and expansion of V. cholerae in 2010, a second outbreak occurred in the winter of 2011-2012 driven by natural selection of specific mutations.

Fig. 1

Map of India detailing the spread of O139 V. cholerae. The dates indicate the first observation of O139 in that city and the arrows represent the likely directions of the spread. From Nair et al. 1994

Fig. 2

Phylogenetic tree based on variable nucleotides. Points at which selective sweeps begin are indicated by the arrows. The right side of the figure indicates the presence of various mobile elements. From Mutreja et al. 2011

Fig. 3

Months in which various clonal complexes appeared in a Highland region including Nairobi, b coastal region, c Semi-arid Northern region, and d Lower Eastern region. Distinct clonal complexes occur simultaneously in different regions, thus the isolates could not have been transported between regions. From Mohamed et al. 2012

Fig. 4

Clonal complex found in Chhatak 2010. The dates of the first observation of each isolate are indicated. Genotypes seen only in isolates from clinic patients have a yellow background, while those in environmental isolates only have a green background and when the genotype was isolated from both patient and environmental sources it had a blue background. From Rashed et al. 2014

Fig. 5

Genetic and population variation in Haiti 2010–2012. Panel a graphs the effective population size with its 95 % confidence limits over time with an overlay of the phylogram reflecting the genetic variation. Panel b graphs the proportion of SNPs that are synonymous (purple) versus those that nonsynonymous (green). In each case, the white line is the mean and the colored area represents the 95 % confidence limits. From Salemi et al. 2014