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Cholera

Disease Details

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Description: Cholera is an acute diarrheal illness caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae.
Type: Cholera is an infectious disease caused by the bacterium Vibrio cholerae. It is not genetically transmitted; instead, it is typically spread through contaminated water or food.
Signs And Symptoms: The primary symptoms of cholera are profuse diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, half a day to five days after ingestion of the bacteria. The diarrhea is frequently described as "rice water" in nature and may have a fishy odor. An untreated person with cholera may produce 10 to 20 litres (3 to 5 US gal) of diarrhea a day. Severe cholera, without treatment, kills about half of affected individuals. If the severe diarrhea is not treated, it can result in life-threatening dehydration and electrolyte imbalances. Estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100. Cholera has been nicknamed the "blue death" because a person's skin may turn bluish-gray from extreme loss of fluids.Fever is rare and should raise suspicion for secondary infection. Patients can be lethargic and might have sunken eyes, dry mouth, cold clammy skin, or wrinkled hands and feet. Kussmaul breathing, a deep and labored breathing pattern, can occur because of acidosis from stool bicarbonate losses and lactic acidosis associated with poor perfusion. Blood pressure drops due to dehydration, peripheral pulse is rapid and thready, and urine output decreases with time. Muscle cramping and weakness, altered consciousness, seizures, or even coma due to electrolyte imbalances are common, especially in children.
Prognosis: If people with cholera are treated quickly and properly, the mortality rate is less than 1%; however, with untreated cholera, the mortality rate rises to 50–60%.For certain genetic strains of cholera, such as the one present during the 2010 epidemic in Haiti and the 2004 outbreak in India, death can occur within two hours of becoming ill.
Onset: The onset of cholera is typically sudden, with symptoms appearing within a few hours to five days after consuming contaminated food or water.
Prevalence: "Nan" is insufficiently clear in the context. However, if you are referring to the term "nan" as found in technical cases (Not a Number or unavailable data), it's important to understand that cholera prevalence can vary significantly by region and time due to factors like access to clean water, sanitation, and public health infrastructure.

If you need specific, up-to-date prevalence data on cholera, I would suggest referring to reports from reputable health organizations such as the World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC).
Epidemiology: Cholera affects an estimated 2.8 million people worldwide, and causes approximately 95,000 deaths a year (uncertainty range: 21,000–143,000) as of 2015. This occurs mainly in the developing world.In the early 1980s, death rates are believed to have still been higher than three million a year. It is difficult to calculate exact numbers of cases, as many go unreported due to concerns that an outbreak may have a negative impact on the tourism of a country. As of 2004, cholera remained both epidemic and endemic in many areas of the world.Recent major outbreaks are the 2010s Haiti cholera outbreak and the 2016–2022 Yemen cholera outbreak. In October 2016, an outbreak of cholera began in war-ravaged Yemen. WHO called it "the worst cholera outbreak in the world". In 2019, 93% of the reported 923,037 cholera cases were from Yemen (with 1911 deaths reported). Between September 2019 and September 2020, a global total of over 450,000 cases and over 900 deaths was reported; however, the accuracy of these numbers suffer from over-reporting from countries that report suspected cases (and not laboratory confirmed cases), as well as under-reporting from countries that do not report official cases (such as Bangladesh, India and Philippines).Although much is known about the mechanisms behind the spread of cholera, researchers still do not have a full understanding of what makes cholera outbreaks happen in some places and not others. Lack of treatment of human feces and lack of treatment of drinking water greatly facilitate its spread. Bodies of water have been found to serve as a reservoir of infection, and seafood shipped long distances can spread the disease.
Cholera had disappeared from the Americas for most of the 20th century, but it reappeared toward the end of that century, beginning with a severe outbreak in Peru. This was followed by the 2010s Haiti cholera outbreak and another outbreak of cholera in Haiti amid the 2018–2023 Haitian crisis. As of August 2021 the disease is endemic in Africa and some areas of eastern and western Asia (Bangladesh, India and Yemen). Cholera is not endemic in Europe; all reported cases had a travel history to endemic areas.
Intractability: Cholera is not considered an intractable disease. It can be effectively managed and treated with timely rehydration and appropriate antibiotic therapy. Preventive measures such as ensuring clean water supply, proper sanitation, and good hygiene practices can significantly reduce the incidence and spread of the disease.
Disease Severity: For cholera, the disease severity is:

Cholera can range from mild, with no symptoms or mild diarrhea, to severe, where it can lead to life-threatening dehydration and shock. Approximately 20% of those infected develop severe symptoms, such as acute, watery diarrhea and vomiting, which can result in rapid loss of body fluids. Prompt treatment with rehydration solutions can significantly reduce the severity and prevent fatalities.
Healthcare Professionals: Disease Ontology ID - DOID:1498
Pathophysiology: Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with Vibrio cholerae bacteria.

Pathophysiology:
1. **Ingestion and Colonization**: After ingestion, V. cholerae survives the acidic environment of the stomach and reaches the small intestine.
2. **Adherence and Toxin Production**: The bacteria adhere to the intestinal mucosa using pili and other adhesins. They then release cholera toxin (CT).
3. **Toxin Mechanism**: Cholera toxin is an AB5 toxin composed of one A subunit and five B subunits. The B subunits bind to GM1 gangliosides on the surface of intestinal epithelial cells, facilitating the entry of the A subunit.
4. **Activation of Adenylate Cyclase**: Inside the cell, the A subunit activates adenylate cyclase, increasing cyclic AMP (cAMP) levels.
5. **Increased Ion Secretion**: Elevated cAMP results in the opening of cystic fibrosis transmembrane conductance regulator (CFTR) channels, leading to excessive secretion of chloride ions and bicarbonate into the intestinal lumen.
6. **Water Loss**: To maintain osmotic balance, water follows the secreted ions into the intestinal lumen, causing severe watery diarrhea, known as "rice-water stools."
7. **Dehydration and Electrolyte Imbalance**: The massive fluid loss leads to dehydration, electrolyte imbalance, and hypovolemic shock if left untreated.

Management involves prompt rehydration, either orally (using oral rehydration salts) or intravenously in severe cases, and antibiotics to reduce the duration of symptoms and bacterial shedding.
Carrier Status: Cholera carriers are individuals who harbor the Vibrio cholerae bacteria without showing symptoms of the disease. These asymptomatic carriers can shed the bacteria in their feces and contaminate water sources, potentially leading to outbreaks. Carrier status can persist for a few days to several months, posing a risk for transmission in areas with poor sanitation.
Mechanism: When consumed, most bacteria do not survive the acidic conditions of the human stomach. The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down protein production. When the surviving bacteria exit the stomach and reach the small intestine, they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive.Once the cholera bacteria reach the intestinal wall, they no longer need the flagella to move. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea. This carries the multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place.The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins, while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis. Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production, which in turn leads to the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae carry a variant of a temperate bacteriophage called CTXφ.
Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria turn off the production of some proteins and turn on the production of other proteins as they respond to the series of chemical environments they encounter, passing through the stomach, through the mucous layer of the small intestine, and on to the intestinal wall. Of particular interest have been the genetic mechanisms by which cholera bacteria turn on the protein production of the toxins that interact with host cell mechanisms to pump chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The chloride and sodium ions create a salt-water environment in the small intestines, which through osmosis can pull up to six liters of water per day through the intestinal cells, creating the massive amounts of diarrhea. The host can become rapidly dehydrated unless treated properly.By inserting separate, successive sections of V. cholerae DNA into the DNA of other bacteria, such as E. coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of the stomach, mucous layers, and intestinal wall. Researchers have discovered a complex cascade of regulatory proteins controls expression of V. cholerae virulence determinants. In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce the toxins, causing diarrhea in the infected person and allowing the bacteria to colonize the intestine. Current research aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize (that is, adhere to the cells of) the small intestine."
Treatment: Continued eating speeds the recovery of normal intestinal function. The WHO recommends this generally for cases of diarrhea no matter what the underlying cause. A CDC training manual specifically for cholera states: "Continue to breastfeed your baby if the baby has watery diarrhea, even when traveling to get treatment. Adults and older children should continue to eat frequently."
Compassionate Use Treatment: Compassionate use treatments and off-label or experimental treatments for cholera include:

1. **Antibiotics:** While not the primary treatment, certain antibiotics may be used in severe cases to reduce the duration of diarrhea and bacterial shedding. Examples include doxycycline, azithromycin, and ciprofloxacin.

2. **Probiotics:** Experimental and off-label, probiotics may help restore the gut microbiota balance disrupted by cholera.

3. **Zinc Supplementation:** There is evidence suggesting that zinc supplements can reduce the severity and duration of diarrhea in children with cholera.

These treatments are often considered on a case-by-case basis, typically when standard treatments like oral rehydration salts (ORS) and intravenous fluids are insufficient or unavailable.
Lifestyle Recommendations: For cholera, lifestyle recommendations include:

1. **Safe Drinking Water**: Ensure that your drinking water is clean. Use bottled water or water that has been boiled, filtered, or treated with chlorine.

2. **Proper Sanitation**: Use proper sanitation techniques, including washing hands with soap and water frequently, especially before eating and after using the toilet.

3. **Hygienic Food Practices**: Eat food that is well-cooked and avoid raw or undercooked fish and shellfish. Peel fruits and vegetables yourself if eating them raw.

4. **Avoiding Contaminated Areas**: Be cautious in areas known for cholera outbreaks. Ensure the environment is clean and avoid swimming in contaminated water.

5. **Vaccination**: If traveling to areas where cholera is prevalent, consider getting vaccinated. Oral cholera vaccines can provide some protection.

6. **Emergency Preparedness**: Keep oral rehydration solutions (ORS) handy to treat dehydration in case of acute cholera symptoms.
Medication: Cholera is primarily treated with rehydration solutions to replace lost fluids and electrolytes. Antibiotics can also be administered to reduce the duration and severity of the illness; common antibiotics include doxycycline, azithromycin, and ciprofloxacin. For severe cases, intravenous fluids may be necessary. Additionally, zinc supplements may be given to children to reduce the duration and severity of diarrhea.
Repurposable Drugs: Currently, there are no widely recognized repurposable drugs specifically for cholera. Treatment typically involves oral rehydration solutions, intravenous fluids, and antibiotics such as doxycycline or azithromycin in severe cases.
Metabolites: Cholera is an infectious disease caused by the bacterium *Vibrio cholerae*. Upon infection, it primarily affects the small intestine and can lead to severe dehydration and electrolyte imbalance due to intense water loss from diarrhea.

In the context of the disease, relevant metabolites produced by *Vibrio cholerae* and the host include:
1. **Cholera Toxin (CT):** A multifunctional protein toxin responsible for the watery diarrhea characteristic of cholera.
2. **cAMP (Cyclic Adenosine Monophosphate):** The intracellular signaling molecule whose levels increase as a result of cholera toxin activity, causing chloride and water secretion into the intestinal lumen.

There is no widely recognized "nan" metabolite specifically associated with cholera. If you meant to refer to "NaN," it is important to note that NaN commonly stands for "Not a Number" in programming and computing contexts, and does not apply to biological metabolite descriptions. If "nan" was a typographical or ambiguous term, please provide further clarification.
Nutraceuticals: Cholera is an acute diarrheal illness caused by infection with the bacterium *Vibrio cholerae*. Nutraceuticals, which are food-derived products with potential health benefits, may help support the immune system and improve gut health, but they cannot cure cholera. Immediate medical treatment is essential for cholera, including rehydration therapy and antibiotics.
Peptides: Cholera is primarily caused by the bacterium Vibrio cholerae. However, in the context of your query, peptides related to cholera could involve antimicrobial peptides (AMPs) that target V. cholerae to mitigate infection. For instance, bacteriocins or synthetic peptides could disrupt bacterial cell membranes.

Nanotechnology (nan) applications in cholera include the use of nanoparticles for rapid diagnostics, drug delivery systems to administer treatment more effectively, and the development of water purification systems to remove V. cholerae from contaminated water sources. Nano-based vaccines are also being researched for improved immune responses against cholera.