V. cholerae, like other pathogens, requires certain environmental conditions (30 °C temperature, pH 8.5, 15% salinity), to survive and thrive [6]. When encountered with more hostile circumstances, V. cholerae persists for long periods in its aquatic niche in a dormant state, or interacts with tiny planktonic crustaceans and animals, such as oysters and copepods [36,37]. Ocean currents can displace plankton together with attached Vibrios [38].

During the nineteenth century, six pandemics occurred, first at coastlines, while dispersion was achieved through maritime activity. All pandemics were attributed to contaminated water from rivers or swampy waters. Moreover, they started from Bangladesh and were caused by V. cholerae serotype O1 [38,39]. Details about the cholera pandemics are presented in Table 1. During 1926–1960 and in light of improvements in water management, it was assumed that cholera pandemics could be a part of history. However, at the end of the twentieth century, a different spread of a new V. cholerae biotype (El Tor) was observed, causing the seventh pandemic. It started in Indonesia in 1961 and spread to Africa and South America over the next decades [38]. Almost all South American countries were involved during the last pandemic, and climate change seems to have played a role. In South America (from January 1991 in Peru until February 1991 in Ecuador), there was an almost simultaneous appearance of outbreaks at a distance of more than 2100 km. The El-Nino event, which causes phytoplacton blooms due to the confluence of rain and nutrients from land into the warm SST, could explain the geographically distant cholera outbreaks since a large “infectious dose” of V. cholerae may have originated from river overflow [36]. In detail, the infectious dose of 10³ V. cholerae cells could be provided by one copepod as each one usually carries more than 10⁴ V. cholerae cells, and during a plankton bloom, several copepods are contained in a glass of untreated water. In 1992 an outbreak of the new V. cholerae serogroup 0139 caused a large outbreak in India and Southeast Asia [36,39].

The El Niño/Southern Oscillation (ENSO) periodicity has been connected to many cholera outbreaks and is characterized as a ‘powerful natural experiment’ [40]. The extreme weather conditions of higher temperature, increased rainfall, and consequent flooding, associated with one of the strongest ENSO events, which occurred in 1997 and lasted until 1998, may explain the global surge of outbreaks observed between 1997 through 1999 [40]. As Mercedes et al. showed in their study [41], the interannual variability of cholera cases correlates with the ENSO time series. In this regard, climate variability seems to affect disease dynamics. During the last two decades of the 20th century, this strong association between ENSO and cholera accounts for more than 70% of the disease variance [42]. Moreover, other events, such as the Northern Hemisphere Temperature and Atlantic Multidecadal Oscillation, are known to correlate positively with Vibrios abundance [43].

Climate variations may also affect the genetic diversity of strains between epidemics through environmentally driven changes in the expression of virulence factors [44]. Genetic variability of clinical and environmental strains during and between epidemics occurring in the last 20 years in Bangladesh and neighboring countries, as well as clonal variability of toxigenic V. cholera, have been well documented [45,46,47,48]. Environmental factors, such as rainfall, seem to influence serotype selection (between O1 and O139 strains), as shown by Goel et al., in two subsequent epidemics in India [49]. Rainfall, as well as increased salinity and water temperature, enhances V. cholerae biofilm formation, potentially by affecting the expression of genes responsible for vibrio polysaccharide synthesis (vps) [50,51]. Another example is the predominance of the El Tor biotype over the classical one during suboptimal climatic conditions due to its better fitness, owing again to the expression of the vps gene [52]. Moreover, transduction, which can give rise to novel toxigenic clones, is enhanced by certain environmental conditions, including optimal temperature, sunlight, and osmotic conditions [16].

An increase in SST seems to be a critical factor not only for Vibrio persistence but also for the emergence of new Vibrio spp. habitats (Table 2). Data from the Baltic Sea during the last decades have confirmed these warming patterns, which correspond closely with the emergence and spread of Vibrio infections in the area. Furthermore, many reports of Vibrio-associated wound infections were recorded during the warm summers of 1994, 2003, and 2006 when SST exceeded 19 °C for more than three weeks. Baker-Austin et al. [6] showed that climate change has affected aquatic bacterial communities and the emergence of Vibrio disease in temperate areas. The authors explain the variability of Vibrio-related disease using generalized linear models (GLM) by maximum SST and time, concluding in a very strong association between SST and Vibrio cases. Several biological explanations support these results, including increased bacterial replication in high temperatures, temperature mediated pathogenicity of Vibrio spp., and increased leisure activities, such as bathing during such circumstances. Vezzulli et al. [53] also proposed a similar relationship between climate change and Vibrio disease using generalized additive models. Abundance of Vibrio was induced by an increase in SST, up to 1.5 °C during the past 54 years, and this was positively correlated with northern hemisphere temperatures [43,53]. From a different perspective, another study, involving the coastal Bay of Bengal, concluded that the association between SST and cholera could be explained from the presence and dominance of high river discharge [54]. This was proposed after showing that phytoplankton-related chlorophyll and SST were positively correlated during high river discharge and negatively correlated during low river discharge. Based on this finding, the authors suggested that cholera prediction models will benefit from the inclusion of nutrient influx and phytoplankton and zooplankton blooms, in addition to other climatic variables for the early detection of outbreaks. In addition, Lipp et al. [16] highlighted in their review that the likelihood of consuming an infectious dose of Vibrios during community use of untreated water is higher during the bloom of copepods. The association of cholera and commensal copepods could also inform models of early outbreak risk recognition based on SST, surface height, and plankton blooms. High salinity and elevated water temperature could influence the expression of regulatory and virulence genes found in V. cholerae, such as TfoX and the activity of Chi A2 [55]. Increased water temperature enhances V. cholerae growth by decreasing replication time, underlining the importance of environmental conditions and V. cholerae transmission dynamics [16]. Finally, another study found that the number of clinical cases in Bangladesh correlated with an air temperature of more than 28.6 °C and more than 4 hours of sunshine daily [56].

Interestingly, using artificial intelligence applications, it has been shown that cholera cases were associated with periods of low precipitation and higher temperatures. Asadgol and colleagues [57] used artificial neural networks projecting from 2021 to 2050 to study the effect of climate change in cholera disease, using data from 1998 to 2016 of daily cholera infections in Qom city, Iran. A trend towards increasing cholera cases was observed with a significant correlation between low precipitation and cholera infection. Higher temperatures in warmer months could also contribute to this trend [57]. Similar tools, using artificial intelligence methods to model the association between disease cases and environmental conditions, could predict the risk for future outbreaks and thus inform early public health interventions. Other crucial predisposing factors that contribute to the occurrence of cholera outbreaks are rainfall patterns and floodings. After studying an outbreak of cholera in 2015 in South Sudan, investigators analyzed the rainfall patterns using deterministic and stochastic models [58]. They concluded that rainfall patterns are fundamental drivers for a cholera epidemic, and they were able to capture seasonal trends as well as short term seasonal fluctuations. Possible mechanistic ways for this rainfall drive are the increased exposure to contaminated water and contamination with bacteria from open-air defecation sites and overflows. Heavy rainfall and flooding are considered as important as well as common risk factors for cholera outbreaks worldwide during 1995-2005, explaining the global increase in such outbreaks during 1997 and 1999 [38].

Apart from endemic countries, the risk of imported V. cholerae is substantial in non-endemic countries with weak healthcare infrastructure and public health systems. The cholera outbreak in Haiti in 2010, following the large earthquake, was believed to have initiated from an imported strain from South Asia via international personnel [59,60]. However, the outbreak may have resulted in propagation due to favorable environmental conditions since the average temperature and rainfall had been above average around that time and before it began [61]. Notably, disruption of the public health system and lack of access to safe water also contributed to its course. Natural disasters and extreme weather events can cause the breakdown of healthcare infrastructure, jeopardize sanitation systems and access to clean water, and, overall, increase vulnerability to cholera epidemics in endemic regions.