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.

Cholera Toxin B: One Subunit with Many Pharmaceutical Applications

“…Natural disasters (e.g., floods, monsoons, and earthquakes) and poor sanitation are major players in the spread of cholera epidemics. Symptomatic individuals can shed the organism from 2 days to 2 weeks after infection and recently shed organisms (5–24 h after shedding) have hyperinfectivity; in this state the infectious dose is 10 to 100 times lower than non-shed organisms (~10 6 bacteria) [ 4 , 5 ]. This can lead to the rapid spread of cholera in densely populated areas without proper management of patients and their waste.…”

Origins of the current seventh cholera pandemic

“…If these strains had evolved from a population that had been resident in the region for many years, the chance of observing a branch with no SNPs is negligible. This finding indicates that their most recent common ancestor (MRCA) in ∼1902, and thus a representative of oldest known precursor of the seventh-pandemic strain, is not from a longestablished form, but rather is a new strain that had arrived in the Middle East from elsewhere or, alternatively, had undergone a genetic change that enabled it to replace preexisting forms in a selective sweep (28). We suggest that the former is more likely, because Mecca was recognized in the 1850s as a source of cholera, leading to the establishment of quarantine and monitoring of facilities in the region.…”

Molecular tools in understanding the evolution of Vibrio cholerae

“… Stine and Morris (2014) proposed acqisition of a novel genetic element(s) leads to an increase in bacterial fitness which, in turn, causes a selective sweep (a local or global outbreak). The seventh cholera pandemic was suggested to comprise four such selective sweeps.…”

“…Severe fluid loss can lead to death within a day of onset ( Sack et al, 2004 ). To date, seven pandemic outbreaks of cholera have been classified by year of commencement, namely 1817, 1829, 1852, 1861, 1881, 1899, and 1961 ( Stine and Morris, 2014 ). The current seventh pandemic is believed to have originated in Indonesia ( Barua, 1972 ) and continued in other continents, typical of pandemics.…”

“…Earlier pandemics were speculated to have originated in the Ganges Delta region of the Indian subcontinent ( Singh and Mohapatra, 2008 ). In addition to recorded pandemics, many localized outbreaks have also affected regions with severe outcomes, as occurred with re-emergence of cholera in Latin America in 1991 and explosive outbreaks of cholera in Orissa 1999, Dhaka 2006, Zimbabwe 2008, Haiti 2010, and Kenya 2010 ( Singh and Mohapatra, 2008 ; Stine and Morris, 2014 ). All of these events highlight the epidemiological importance of this global disease.…”