Cholera

Cholera is an acute, severe intestinal infectious disease caused by Vibrio cholerae. It has an abrupt onset and rapid transmission, and is a major cause of diarrhea across most of Asia and Africa. It is an internationally quarantinable disease and a Class A infectious disease in China. Typical patients develop dehydration and muscle cramps due to severe diarrhea and vomiting; severe cases may progress to peripheral circulatory failure and acute renal failure. Mild cases predominate in general, and carriers are also common, but severe and typical cases may be fatal if treatment is not timely.

Common Symptoms

Water loss; lowered blood pressure; explosive watery diarrhea; tenesmus; restlessness; dizziness; fatigue; dehydration; thready rapid pulse

Causes and Pathogenesis

The etiology of cholera mainly involves three major aspects: Vibrio cholerae is the pathogen, the source of infection is patients and carriers, and waterborne transmission is the most important route. Receptors for cholera enterotoxin exist on the brush border of small intestinal epithelial cells; disease occurs when large amounts of water and electrolytes bind irreversibly to surface gangliosides. Etiology of cholera: Vibrio cholerae has two biotypes, namely the classical biotype and the El Tor biotype. 1. Source of infection: The source of cholera infection is patients and carriers. 2. Transmission route: Both biotypes of cholera can be transmitted through water, food, flies, and everyday contact. Waterborne transmission is the most important route. 3. Susceptible population: People of all races, sexes, and ages are generally susceptible to cholera. Pathogenesis: 1. Pathogenesis: Whether a person develops disease after ingesting Vibrio cholerae mainly depends on the body's immunity and the amount of vibrio ingested. If the body can secrete normal gastric acid without dilution, it can kill a certain number of Vibrio cholerae without developing disease. After oral live vaccination, specific IgM, IgG, and IgA antibodies in the intestine can also prevent vibrio from adhering to the intestinal wall and thereby avoid disease. However, prior subtotal gastrectomy reducing gastric acid secretion, large amounts of water or food diluting gastric acid, or ingesting a quantity of Vibrio cholerae exceeding 10^8 to 10^9, can all cause disease. After reaching the intestine through the stomach, Vibrio cholerae crosses the mucus layer of the intestinal mucosa by means of flagellar motility and proteases produced by the vibrio; under the action of TcpA and vibrio hemagglutinin (HA), it adheres to the brush border of epithelial cells in the upper small intestine without invading the submucosa. In the alkaline environment of the small intestine, Vibrio cholerae multiplies in large numbers and produces cholera enterotoxin. When the enterotoxin contacts the intestinal mucosa, its B subunit recognizes and binds to receptors on intestinal epithelial cells; this receptor is ganglioside. The enzymatically active A subunit then enters the intestinal mucosal cells, where it transfers ADP-ribose from nicotinamide adenine dinucleotide (NAD) to the target protein GTPase and binds to it, thereby inhibiting GTPase activity. This causes adenylate cyclase to be persistently activated, continuously converting adenosine triphosphate into cyclic adenosine monophosphate (cAMP). When intracellular cAMP concentration rises, it stimulates intestinal crypt cells to hypersecrete water, chloride, and bicarbonate, while inhibiting the absorption of sodium and chloride by intestinal villus cells, causing water and sodium chloride to accumulate in the intestinal lumen and thereby producing severe watery diarrhea. Cholera enterotoxin also stimulates intestinal mucosal goblet cells to secrete more mucus, so that the watery stool contains large amounts of mucus; in addition, the dehydration caused by diarrhea reduces bile secretion, so the diarrheal stool may become "rice-water" like. Apart from enterotoxin, endotoxin and the hemolysins, enzymes, and other metabolites produced by Vibrio cholerae also play a certain pathogenic role. 2. Pathophysiology: (1) Water and electrolyte disturbance: Due to severe vomiting and diarrhea, cholera patients lose large amounts of water and electrolytes, leading to dehydration and electrolyte disturbance. Patients with severe dehydration may develop circulatory failure; if rehydration is not timely and shock is prolonged, acute renal failure may further result. Although the fluid lost by cholera patients is isotonic, its potassium content is 4 to 6 times that of serum potassium, while sodium and chloride are slightly lower than in serum; therefore, during rehydration therapy, potassium should be supplemented promptly when the patient is urinating, otherwise severe hypokalemia may cause arrhythmia and may also cause degeneration of renal tubular epithelial cells, further aggravating renal failure. (2) Metabolic acidosis: Large amounts of bicarbonate are lost through diarrhea. In addition, peripheral circulatory failure due to dehydration causes tissue hypoxia and anaerobic metabolism, resulting in excessive lactic acid production that worsens metabolic acidosis. Acute renal failure with failure to excrete metabolic acids is also a cause of acidosis. 3. Pathological anatomy: The main pathological change of this disease is severe dehydration, with no severe parenchymal organ damage. Findings include dry skin, dehydration of subcutaneous tissue and muscles, shrinkage of organs such as the heart, liver, and spleen due to dehydration, dilation of glomerular and renal interstitial capillaries, possible degeneration and necrosis of renal tubules, and only nonspecific infiltration of the small intestinal mucosa.

Treatment

Drug therapy, supportive therapy

Preventive Measures

1. Control the source of infection: Promptly identify patients and suspected patients, isolate and treat them, and conduct epidemic source tracing; this is an important step in controlling cholera outbreaks, and China has successful experience in this regard. (1) Establish diarrhea intestinal clinics: All urban hospitals should establish intestinal clinics to receive all diarrhea patients so as to promptly identify patients and suspected patients, isolate and treat them, and report epidemics to prevent spread of the source of infection. (2) Perform stool tests and prophylactic medication on close contacts: Close contacts should undergo stool culture once a day for 2 consecutive days; giving medication after the first stool test can reduce the carrier state. Doxycycline 200 mg as a single dose followed by 100 mg orally the next day is generally used; children 6 mg/(kg·d) for 2 days. Norfloxacin 200 mg 3 times a day for 2 days may also be used. (3) Carry out border health quarantine and domestic traffic quarantine: Once a patient or suspected patient is found, immediately isolate and treat them and thoroughly disinfect vehicles. 2. Cut off transmission routes: Strengthen drinking water disinfection and food management to ensure water safety; good sanitation facilities can significantly reduce the risk of cholera transmission. In areas not yet affected by cholera or where seasonal epidemics have not formed, formulating an effective cholera control plan is the best preparation. Long-term improvement of water supply and sanitation is the best method of cholera prevention. Thoroughly disinfect the excreta of patients and carriers; in addition, eliminate flies and other transmission vectors. 3. Improve population immunity: Whole-cell killed vaccines or toxoid vaccines combined with cholera enterotoxin were formerly used to immunize the population, but are no longer recommended due to low protection rate, short protection duration, and failure to prevent subclinical infection and carriers. Various vaccines developed abroad using genetic engineering technology are currently in expanding trials, including: (1) B subunit-whole cell vaccine (BS-WC): This vaccine consists of inactivated whole Vibrio cholerae cells (WC) and purified cholera enterotoxin B subunit (BS). The WC cell wall contains antigens such as lipopolysaccharide (LPS) and toxin-coregulated pili (TCP), which induce antibacterial antibodies that inhibit Vibrio cholerae colonization in the intestine; the antitoxin antibodies produced by BS neutralize the B subunit of CT, preventing cholera enterotoxin from binding to intestinal mucosal receptors and thus preventing its action. The protection rate of this vaccine is 65% to 85%, with better prevention against classical biotype Vibrio cholerae than against El Tor biotype. (2) Attenuated oral live vaccine (CVD103-HgR): This uses DNA recombination technology to remove 94% of the CTXA gene and recombine it into the classical biotype Vibrio cholerae strain 569B, obtaining the attenuated strain CVD103; then a mercury (Hg) resistance coding gene is introduced into the chromosomal site of hgla, becoming the attenuated strain CVD103-HgR. This vaccine significantly protects against O1 classical and El Tor biotype Vibrio cholerae infection. Taket et al. reported that after a single oral dose of (3 to 5)×10^8 CVD103-HgR vaccine, volunteers achieved 100% protection. Protection is generally believed to last at least 6 months, but animal experiments show this vaccine has no protective effect against O139 Vibrio cholerae. Waldor et al. constructed a VCO139 attenuated strain Bengal3 lacking cell toxin (CT) and toxins such as adenylate cyclase (ACE) zot, but its safety and protective efficacy require further study. (3) Research on O139 vaccines: The capsular lipopolysaccharide of O139 is not only an important virulence factor but also an important protective antigen. Using serum protein as a carrier protein to make O139 capsular lipopolysaccharide vaccine, with EDC or CDAP as an activator injected into mice, can cause mice to produce vibriocidal antibodies. Covalently conjugating O139 capsular lipopolysaccharide with diphtheria toxin can cause mice to produce IgG against capsular polysaccharide, which has vibriocidal effect, while also producing antibodies against diphtheria toxin; this research is still at the animal experiment stage.

Department to Visit

It is recommended to visit the Infectious Diseases department; an appointment can be booked on this platform before the visit.

Warm reminder: The above information is for health science reference only and cannot replace professional medical diagnosis. If you have related symptoms, please seek medical attention at a regular hospital promptly.