Cholera as a disease is a relatively recent emergence on the worldwide scale, originally having been mostly contained to Asia for centuries before wreaking havoc in other continents. It was not until the 19th century that cholera as an epidemic disease spread far beyond its likely origination point in India. However, due to this recency in its worldwide development, cholera is uniquely also noted as being the first disease to have had the current model of epidemiological methods used to track its rampage through London during a cholera epidemic known as the “Broad Street Cholera Outbreak” (9).
Cholera as a disease is caused by the Vibrio cholerae bacteria, which settles in the small intestine of humans and, through a gene occasionally given by a bacteriophage virus, is able to secrete a potent toxin. This toxin initiates a response in the bowels of the human host, causing intense bouts of diarrhea that can often appear a whitish color and is known as “rice water stool”. The diarrhea caused by V. cholerae is also of a greater water concentration than normal diarrhea, which will cause the host to suffer from extreme dehydration (10).
On an individual epidemic scale, cholera generally appears to last up to a decade, but sometimes epidemics last only half of that. This timeframe can be lengthened or shortened by environmental conditions in the area, such as temperature and the presence of plankton. The V. cholerae bacteria has been observed to form a commensalistic relationship with plankton possessing exoskeletons. This relationship allows for the bacteria to survive and proliferate even without human hosts, and even displaying an importance in recycling biologically inaccessible sugar molecules into forms that other organisms can utilize (11).
Introduction: Origin and Transmission
Cholera is an infectious disease of the intestine caused by the bacterium called Vibrio cholerae. Vibrio cholerae is a species of the gram-negative which produces toxic bacteria. There are many serogroups of the cholera bacteria. The Vibrio cholerae serogroups 01 and 0139 are the only two strains of bacteria known to cause the cholera outbreak. These strains produce toxic bacteria that causes the intestine to release a large amount of water which leads to diarrhea and loss of fluids. People can get sick from cholera by drinking contaminated water and food with cholera bacteria. During the 19th century, cholera spread across the world infecting many people. The disease originated from the Ganges delta in India. (14) The first cholera pandemic appeared in India, in 1817 from contaminated rice. (14) The disease spread fast throughout India killing many people. By 1820, the disease spread to Thailand, Indonesia, the Philippines, and China. (14) By 1822, the disease spread to Japan, infecting people on ships. The pandemic of the cholera disease came to an end 6 years after the first pandemic due to a severe winter between 1823-1824. (14) That could have killed the bacteria living in the water. However, there was a second pandemic that came back during 1829, which infected many people in Central Asia and the Middle East. (14) During 1832, the disease made it to the Americans. The pandemic then died out and reappeared throughout many countries for nearly two decades until 1851. (14) Then there were four more cholera pandemics between 1852 and 1923. (14) Unlike other infectious diseases, cholera continues to be a huge health problem worldwide.
Cholera is caused by water contaminated with the bacteria, Vibrio cholerae, that infects the intestines. Other ways V. cholerae can be transmitted is through raw or undercooked seafood, raw or unpeeled fruits and vegetables in areas that Cholera is present, and grains such as rice and millet left at room temperature in areas that Cholera is present. There are currently three different strains of Cholera, two of which are V. cholerae O1 and O139 (3). These cause the majority of outbreaks but do not cause epidemics. The third strand, a newer strand called El Tor, detected in parts of Asia and Africa, has a higher fatality rate (3).Vibrio species are gram-negative aerobic coliform bacteria and are shaped like curved rods with singular pole flagellum (1). Transmitted by the fecal-oral route, cases of V. cholerae can be mild or life-threatening. Although Vibrio species are sensitive to stomach acid, surviving ones move to the bowels where they secrete cholera enterotoxin encoded by a lysogenic bacteriophage called CTXΦ (1). This toxin leads to the rapid onset of liquid accumulation and loss of electrolytes in the body. In the United States, cases of Cholera are very low, but in places like Asia, Africa, and Latin America cases remain endemic from the poor sanitary conditions (2).
Signs and Symptoms:
Although Cholera normally lasts between 1-3 days, host susceptibility and inoculum size can make it last from 3 to 5 days. It also takes between 12 hours and 5 days for Vibrio cholerae to incubate in the body before causing symptoms. After ingestion of an infected common source vector, people generally experience their first symptom within 12 hours to 5 days. Affecting both children and adults, Cholera left untreated can result in death. However, most people are not affected by Vibrio cholerae, and it can go unnoticed, with the bacteria remaining in their feces for approximately 1 to 10 days after infection (4). Some symptoms the infected can expect would be watery diarrhea, nausea and vomiting, dehydration, muscle cramps, and electrolyte imbalance (5).
During the early stages of Cholera, nausea and vomiting are quite common and can last for hours. Diarrhea can cause a major electrolyte imbalance from coming on suddenly and causing as much as 1 liter of fluid lost per hour. It is often a pale milky substance, resembling rice water (5). A loss of 10% or more of body weight indicates severe dehydration and occurs often in cases of Cholera. An electrolyte imbalance is characterized by the rapid loss of minerals in the blood that maintain the balance of fluids in the body (5). This electrolyte imbalance can lead to serious complications such as shock. Shock occurs when a low volume of blood causes a drop in blood pressure and a lack of oxygen resulting in death in a matter of minutes (5).
Following infection of the small intestines by the necessary virulent forms of V. cholerae that carry the cholera toxin-producing gene, the infecting bacteria attempts to attach itself to its host. To facilitate this, V. cholerae produces an enzyme to break apart the slick gastrointestinal mucus that lines the intestinal wall (12). This mucus lining is normally produced by epithelial goblet cells that compose the lining of the intestines in order to facilitate the movement of waste and prevent parasites and pathogens from taking root within the gut. However, the enzyme produced by V. cholerae, a mucinase, destroys the carbohydrate and protein structures within the mucus membrane that allow it to be so effective, thus rendering it useless (13).
Once the protective mucus layer has been removed, most specimens of V. cholerae are able to utilize their possessed flagella to rapidly move towards the exposed intestinal wall. However, other non-standard mutant members of the species do not possess a flagella and have been discovered to have a lesser virulence than members that do possess one (13). Additional projections from the bacterial cell wall known as pili enable the bacteria to attach itself to the epithelial cells that compose the intestinal wall.
After attaching, if the bacteria possesses the gene that allows for the production of the cholera enterotoxin, it will begin to secrete. This toxin, also known as CT or choleragen, acts as a chemical messenger that attaches to epithelial cells and signals the rapid production of cAMP. High levels of cAMP increase the porosity of ion-containing portions of the cells and thus cause for a rapid secretion of ions and water into the intestines. This mechanism of disease causes diarrhea reminiscent of rice water that cholera is well known for, as it has a much higher concentration of water than normal diarrhea (12).
The majority of cholera prevention strategies include immunizing populations with oral cholera vaccines as well as providing clean water and good sanitation to those who do not yet have access to these necessities. Additionally crucial are food hygiene and health education. Communities need to be reminded to practice good hygiene. These include the necessity of consistently washing one’s hands with soap after defecating and before handling or consuming food, as well as the proper preparation and storage of food. In order to identify the first cases of an outbreak and implement controls as soon as feasible, it is critical to strengthen surveillance and early warning systems. Cholera prevention and control involve actions outside the health sector, and collaboration with partners from other industries is crucial. Multi-sectoral cholera control strategies can be created and put into action to bring together all key sectors and create channels of cooperation and communication that are beneficial for reasons other than cholera control (7).
Economic growth, universal access to clean water, and proper sanitation are the long-term answers to cholera control. Providing customized long-term sustainable wash solutions to guarantee the use of safe water, fundamental sanitation, and good hygiene habits in cholera hotspots is one of the actions aimed at improving the environment. Such initiatives help achieve objectives for reducing poverty, hunger, and illiteracy in addition to preventing cholera and a wide range of other water-borne diseases. The Sustainable Development Goals and the wash cholera solutions are complementary (SDG 6).Community engagement refers to including people and communities in the development and delivery of programs. Promoting behaviors like the use of preventative hygiene measures like handwashing with soap, safe food preparation and storage, and appropriate kid feces disposal are all based on local cultural customs and beliefs. funeral customs for victims of cholera to avoid contamination among guests. Community involvement is maintained throughout the epidemic response with improved communication on potential hazards, cholera symptoms, preventative measures to take, when and where to report cases, and to seek emergency medical attention when symptoms arise. The development of programs to address needs, such as where and when to seek care, should involve the communities (8).
A case of cholera should be suspected, in accordance with the World Health Organization (WHO), when a patient aged 5 years or older experiences severe dehydration or passes away from acute watery diarrhea, even in a location where the disease is not known to exist, or when a patient aged 2 years or older experiences acute watery diarrhea in a location where the disease is known to exist. Where microbiological facilities are available, the isolation of the Vibrio cholerae organism from stool on selective media, followed by biochemical testing, as well as serogrouping and serotyping with certain antibodies, can be used to confirm V. cholerae infection. Stool enrichment in alkaline peptone water can improve culture sensitivity. Fresh human feces should be examined under 400 darkfield microscopy for vibrio-shaped cells with darting motility that are inhibited with particular antibodies; roughly half of culture-positive stools are positive on dark field microscopy. Cholera can be quickly identified in this way.
Additionally, cholera toxin and V. cholerae O1 and O139 lipopolysaccharide direct stool detection immunoassays have been created. Such assays enable early case detection during an outbreak and can be employed in environments with limited laboratory capability. In comparison to PCR under field settings, one such commercially available dipstick for both O1 and O139-associated cholera has a 97% sensitivity and 71–76% specificity. Dipstick assays may be more accurate at finding V. cholerae in patients who have already had antibiotic treatment (6).
Cholera can cause dehydration if not treated properly. Rehydration therapy is the primary treatment for cholera patients. (15) It refers to the restoration of lost fluids and salts. Rehydration therapy for patients includes adequate volumes of solution of oral rehydration salts, IV fluids if necessary, and electrolytes. When patients with cholera are not treated with rehydration therapy it can lead to death. Antibiotic treatment is used for patients for severe cases of cholera (15). The antibiotic doxycycline is recommended for adults and children. Doxycycline results in rapid recovery and shorter lengths of patients having to stay in the hospital. Zinc treatment can be used for children who have cholera. (15) Children who receive zinc treatment have less diarrhea, stool volume and illness. These treatments are all effective for treating patients with cholera.
Novel Disease Control Plan:
Due to cholera being often seen primarily in less developed countries that have limited sanitation laws in response to economic aspects, water sanitation needs to be looked at when looking for ways to reduce or eliminate cholera outbreaks. However, as proper water pipelines are potentially unavailable in these countries, an efficient wide-scale plan of action will be more difficult to implement. This would require more meticulous planning and consideration with each country and community on an individual basis.
A common belief is that all cholera cases are being reported, however, the World Health Organization says only about 5-10% of all Cholera cases are being reported due to inadequate healthcare and epidemiological surveillance (16). One possible solution would be to involve NATO and other coalitions of countries in signing a document or agreeing on sanctions to provide medical centers, waste treatment facilities, and access to clean water by a certain deadline. Not only does Cholera affect the poor and impoverished countries, but the spread of Cholera to other countries can also become costly hence the need for the deadline. These incentives would push countries lacking in preventative steps to invest for future potential outbreaks, and if these become a requirement, member nations could help fund the sanitation measures for the more impoverished countries.
For example, in Haiti, the Cholera outbreak has continued to spread causing a new need for a $145 million dollar appeal to support humanitarian efforts (16). One effort that can be implemented to help treat water in poor and impoverished countries would be to teach the general public about good water sanitation and treatment practices (17). Chemical purification tablets like iodine and bleach should be made available to the public to utilize to treat their water if treatment and sanitation plants are unable to be installed. Another form of water treatment that can be taught and utilized is the creation of a basic water filtration system, to filter out major particulate matter and then a purification process, such as boiling water for a specific set time period (17). Lastly, the most prudent tool that can be used in combating a cholera outbreak would be to properly equip local and state governments with the tools necessary to detect and fight an early outbreak. This can be in the form of the Cholera kits implemented by the World Health organization, introduced in 2020, the cholera kits 2020 are designed to help prepare for a potential cholera outbreak and to support the first month of the initial response for 100 cases (18).
Overall, a concerted effort amongst as many countries as possible will be required to control the continued rise of cholera epidemics. This will preferably involve the funding of countries with large GDPs, such as the USA and Germany, that will then funnel their money towards the more impoverished countries in the world, who are willing to accept aid. This money will go towards increased water sanitation measures, sewage treatment quality, and public outreach of how to avoid contracting the illness. Once these measures that are currently existent have been made available to all, more research must be conducted towards methods of destroying CTXΦ, the bacteriophage responsible for the virulence of V. cholerae, in a similar fashion to how the smallpox virus was destroyed in 1980.
- Finkelstein, RA. (1996) Cholera, Vibrio cholerae O1 and O139, and Other Pathogenic Vibrios. In: Baron S, editor. Medical Microbiology. 1994;32:2345.
- Faruque, S. M., Albert, J. M., & Mekalanos, J. j. (1998, December 1). Epidemiology, genetics, and ecology of Toxigenic Vibrio cholerae . Microbiology and Molecular Biology Reviews. https://journals.asm.org/doi/abs/10.1128/mmbr.62.4.1301-1314.1998?view=long&pmid=9841673
- Goel, Naveen. (2007) Cholera. The University of Chandigarh. Department of Medicine. http://gmch.gov.in/sites/default/files/documents/Cholera.pdf
- Azman AS, Rudolph KE, Cummings DA, Lessler J. (2013) Infection rates of Vibrio Cholerae. PubMed.66(5):432-8. doi: 10.1016/j.jinf.2012.11.013.
- Mayo Foundation for Medical Education and Research. (2022, December 9). Cholera. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/cholera/symptoms-causes/syc-20355287
- Harris, J. B., LaRocque, R. C., Qadri, F., Ryan, E. T., & Calderwood, S. B. (2012, June 30). Cholera. Lancet (London, England). Retrieved January 31, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3761070/
- World Health Organization. (n.d.). Cholera. World Health Organization. Retrieved February 6, 2023, from https://www.who.int/health-topics/cholera#tab=tab_2
- World Health Organization. (n.d.). Cholera. World Health Organization. Retrieved January 31, 2023, from https://www.who.int/news-room/fact-sheets/detail/cholera
- Lippi D., Gotuzzo E., Caini S. 2016. Cholera. Microbiology Spectrum, 4(4). https://doi.org/10.1128/microbiolspec.PoH-0012-2015
- Centers for Disease Control and Prevention. 2022. Illness and symptoms. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. https://www.cdc.gov/cholera/illness.html
- Constantin de Magny, G., & Colwell, R. R. (2009). Cholera and climate: a demonstrated relationship. Transactions of the American Clinical and Climatological Association, 120, 119–128. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744514/
- Sharmila T, Thomas TA. 2018. Pathogenesis of cholera: Recent prospectives in rapid detection and prevention of cholera. Bacterial Pathogenesis and Antibacterial Control. https://doi.org/10.5772/intechopen.74071
- Almagro-Moreno, S., Pruss, K., & Taylor, R. K. (2015). Intestinal Colonization Dynamics of Vibrio cholerae. PLoS pathogens, 11(5), e1004787. https://doi.org/10.1371/journal.ppat.1004787
- Cholera. (2017). History.https://www.history.com/topics/inventions/history-of-cholera
- Mayo Foundation for Medical Education and Research. (2022, December 9). Cholera. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/cholera/diagnosis-treatment/drc-20355293
- Centers for Disease Control and Prevention. (2022, November 14). Cholera in Africa. Centers for Disease Control and Prevention. Retrieved February 6, 2023, from https://www.cdc.gov/cholera/africa/index.html
- New York State Department of Health. (2018, November). Boil water response-information for the public health professional. https://www.health.ny.gov/environmental/water/drinking/boilwater/response_information_public_health_professional.htm
- World Health Organization (WHO). (2020). Cholera kits 2020. https://www.who.int/emergencies/emergency-health-kits/revised-cholera-kits
- Deen, J., Mengel, M. A., & Clemens, J. D. (2020). Epidemiology of Cholera. Vaccine, 38(1), A31-A40. https://doi.org/10.1016/j.vaccine.2019.07.078
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