diarrhea, the hallmark symptom of cholera. infection can be spread by eating contaminated food or drinking contaminated water. it also can spread through skin contact with contaminated human feces. not all infection indicate symptoms, only about 1 in 10 people develop diarrhea. the major symptoms include: watery diarrhea, vomiting, rapid heart rate, loss of skin elasticity, low blood pressure, thirst, and muscle cramps. this illness can get serious as it can progress to kidney failure and possible coma. if diagnosed, it can be treated using medications. disease occurrence v. cholerae has an endemic or epidemic occurrence. in countries where the disease has been for the past three years and the cases confirmed are local (within the confines of the country) transmission is considered to be "endemic." alternatively, an outbreak is declared when the occurrence of disease exceeds the normal occurrence for any given time or location. epidemics can last several days or over a span of years. additionally, countries that have an occurrence of an epidemic can also be endemic. the longest standing v. cholerae epidemic was recorded in yemen. yemen had two outbreaks, the first occurred between september 2016 and april 2017, and the second began later in april 2017 and recently was considered to be resolved in 2019. the epidemic in yemen took over 2,500 lives and impacted over 1 million people of yemen. more outbreaks have occurred in africa, the americas, and haiti. preventive measures when visiting areas with epidemic cholera, the following precautions should be observed: drink and use bottled water; frequently wash hands with soap and safe water; use chemical toilets or bury feces if no restroom is available; do not defecate in any body of water and cook food thoroughly. supplying proper, safe water is important. a precaution to take is to properly sanitize. hand hygiene is an essential in areas where soap and water is not available. when there is no sanitation available for hand washing, scrub hands with ash or sand and rinse with clean water. a single dose vaccine is available for those traveling to an area where cholera is common. there is a v. cholerae vaccine available to prevent disease spread. the vaccine is known as the, "oral cholera vaccine" (ocv). there are three types of ocv available for prevention: dukoral®, shanchol™, and euvichol-plus®. all three ocvs require two doses to be fully effective. countries who are endemic or have an epidemic status are eligible to receive the vaccine based on several criteria: risk of cholera, severity of cholera, wash conditions and capacity to improve, healthcare conditions and capacity to improve, capacity to implement ocv campaigns, capacity to conduct m&e activities, commitment at national and local level since may the start of the ocv program to may 2018 over 25 million vaccines have been distributed to countries who meet the above criteria. treatment the basic, overall treatment for cholera is re-hydration, to replace the fluids that have been lost. those with mild dehydration can be treated orally with an oral rehydration solution (ors). when patients are severely dehydrated and unable to take in the proper amount of ors, iv fluid treatment is generally pursued. antibiotics are used in some cases, typically fluoroquinolones and tetracyclines. genome v. cholerae (and vibrionaceae in general) has two circular chromosomes, together totalling 4 million base pairs of dna sequence and 3,885 predicted genes. the genes for cholera toxin are carried by ctxphi (ctxφ), a temperate bacteriophage inserted into the v. cholerae genome. ctxφ can transmit cholera toxin genes from one v. cholerae strain to another, one form of horizontal gene transfer. the genes for toxin coregulated pilus are coded by the vibrio pathogenicity island (vpi), which is separate from the prophage. the larger first chromosome is 3 mbp long with 2,770 open reading frames (orfs). it contains the crucial genes for toxicity, regulation of toxicity, and important cellular functions, such as transcription and translation. the second chromosome is 1 mbp long with 1115 orfs. it is determined to be different from a plasmid or megaplasmid due to the inclusion of housekeeping and other essential genes in the genome, including essential genes for metabolism, heat-shock proteins, and 16s rrna genes, which are ribosomal subunit genes used to track evolutionary relationships between bacteria. also relevant in determining if the replicon is a chromosome is whether it represents a significant percentage of the genome, and chromosome 2 is 40% by size of the entire genome. and, unlike plasmids, chromosomes are not self-transmissible. however, the second chromosome may have once been a megaplasmid because it contains some genes usually found on plasmids, including a p1 plastid-like origin of replication. bacteriophage ctxφ ctxφ (also called ctxphi) is a filamentous phage that contains the genes for cholera toxin. infectious ctxφ particles are produced when v. cholerae infects humans. phage particles are secreted from bacterial cells without lysis. when ctxφ infects v. cholerae cells, it integrates into specific sites on either chromosome. these sites often contain tandem arrays of integrated ctxφ prophage. in addition to the ctxa and ctxb genes encoding cholera toxin, ctxφ contains eight genes involved in phage reproduction, packaging, secretion, integration, and regulation. the ctxφ genome is 6.9 kb long. ecology and epidemiology the main reservoirs of v. cholerae are aquatic sources such as rivers, brackish waters, and estuaries, often in association with copepods or other zooplankton, shellfish, and aquatic plants. cholera infections are most commonly acquired from drinking water in which v. cholerae is found naturally or into which it has been introduced from the feces of an infected person. cholera is most likely to be found and spread in places with inadequate water treatment, poor sanitation, and inadequate hygiene. other common vehicles include raw or undercooked fish and shellfish. transmission from person to person is very unlikely, and casual contact with an infected person is not a risk for becoming ill.v. cholerae thrives in an aquatic environment, particularly in surface water. the primary connection between humans and pathogenic strains is through water, particularly in economically reduced areas that do not have good water purification systems. nonpathogenic strains are also present in water ecologies. the wide variety of pathogenic and nonpathogenic strains that co-exist in aquatic environments are thought to allow for so many genetic varieties. gene transfer is fairly common amongst bacteria, and recombination of different v. cholerae genes can lead to new virulent strains. a symbiotic relationship between v. cholerae and ruminococcus obeum has been determined. r. obeum autoinducer represses the expression of several v. cholerae virulence factors. this inhibitory mechanism is likely to be present in other gut microbiota species which opens the way to mine the gut microbiota of members in specific communities which may utilize autoinducers or other mechanisms in order to restrict colonization by v. cholerae or other enteropathogens. outbreaks of cholera cause an estimated 120,000 deaths annually worldwide. there has been roughly seven pandemics since 1817, the first. these pandemics first arose in the indian subcontinent and spread. diversity and evolution two serogroups of v. cholerae, o1 and o139, cause outbreaks of cholera. o1 causes the majority of outbreaks, while o139 – first identified in bangladesh in 1992 – is confined to southeast asia. many other serogroups of v. cholerae, with or without the cholera toxin gene (including the nontoxigenic strains of the o1 and o139 serogroups), can cause a cholera-like illness. only toxigenic strains of serogroups o1 and o139 have caused widespread epidemics. v. cholerae o1 has two biotypes, classical and el tor, and each biotype has two distinct serotypes, inaba and ogawa. the symptoms of infection are indistinguishable, although more people infected with the el tor biotype remain asymptomatic or have only a mild illness. in recent years, infections with the classical biotype of v. cholerae o1 have become rare and are limited to parts of bangladesh and india. recently, new variant strains have been detected in several parts of asia and africa. observations suggest these strains cause more severe cholera with higher case fatality rates. natural genetic transformation v. cholerae can be induced to become competent for natural genetic transformation when grown on chitin, a biopolymer that is abundant in aquatic habitats (e.g. from crustacean exoskeletons). natural genetic transformation is a sexual process involving dna transfer from one bacterial cell to another through the intervening medium, and the integration of the donor sequence into the recipient genome by homologous recombination. transformation competence in v. cholerae is stimulated by increasing cell density accompanied by nutrient limitation, a decline in growth rate, or stress. the v. cholerae uptake machinery involves a competence-induced pilus, and a conserved dna binding protein that acts as a ratchet to reel dna into the cytoplasm. there are two models of genetic transformation, sex hypothesis and competent bacteria. gallery diagram of the bacterium, v. cholerae yellow colored (sucrose-fermenting) colonies of vibrio cholerae on tcbs agar. transmission electron microscope image of vibrio cholerae that has been negatively stained.