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Cholera
Cholera
Cholera is an acute diarrheal infectious disease caused by Vibrio cholerae contamination of ingested food or water. Each year, there are an estimated 3 to 5 million cholera cases and an additional 100,000 to 120,000 deaths. The peak incidence is in summer, and it can cause diarrhea, dehydration, and even death within hours.
Cholera is caused by Vibrio cholerae. Two serotypes of Vibrio cholerae, O1 and O139, can cause outbreaks. Most outbreaks are caused by Vibrio cholerae type O1, while type O139, first identified in Bangladesh in 1992, is limited to Southeast Asia. Non-O1 non-O139 Vibrio cholerae can cause mild diarrhea but not epidemic. Recently, new mutant strains have been discovered in some parts of Asia and Africa. These strains have been observed to cause more severe cholera disease with higher mortality.
Vibrio cholerae is present in water, and the most common cause of infection is the consumption of water that has been contaminated with patient faeces. Vibrio cholerae can produce cholera toxin, which causes secretory diarrhea, which persists even if you stop eating. Rice-washed faeces are characteristic of cholera.
Disease Profile
According to clinical manifestations, cholera patients can often be divided into typical cases (moderate and severe), atypical cases (mild) and toxic cases (dry cholera), which are described as follows.
1. Typical cases (moderate and severe): have typical symptoms of diarrhea and vomiting. Among them, patients with moderate cholera have diarrhea 10 to 20 times a day, and the stools are watery or “rice swill”, with a large amount and obvious signs of dehydration. . Blood pressure drops, systolic blood pressure is 70 ~ 90mmHg, urine output decreases, 24-hour urine output is less than 500ml. In addition to typical diarrhea (more than 20 times/day) and vomiting, severe patients have severe dehydration and circulatory failure. It is manifested as a thin or unpalatable pulse, a significant drop in blood pressure, and a systolic blood pressure below 70 mmHg or undetectable. The urine output in 24 hours is less than 50ml.
2. Atypical cases (mild): slow onset, diarrhea no more than 10 times a day, loose stools or watery stools, usually not accompanied by vomiting, continuous diarrhea and recovery after 3 to 5 days. No obvious dehydration performance.
3. Poisoning cases (dry cholera): It is characterized by a rapid onset, and has died of circulatory failure before diarrhea and vomiting, so it is also called “dry cholera”. The course of cholera is not long, and mild cases without complications recover within 3 to 7 days on average. In some cases, diarrhea can last for about 1 week, and the recovery period for those complicated with uremia can be extended to more than 2 weeks.
2 The cause of the disease
Vibrio cholerae was discovered by Koch in Egypt during the fifth worldwide cholera pandemic in 1883. In 1905, Cotschlich isolated a special strain of Vibrio cholera from the corpses of pilgrims in Mecca at the El-Tor quarantine station in the Sinai Peninsula, Egypt, and named it El-Tor Vibrio. In 1966, the International Vibrio Nomenclature Committee collectively referred to the two pathogenic Vibrio species discovered successively as the two biotypes of Vibrio cholerae, namely the classical biotype and the Etto biotype. In the seventh world pandemic, the latter gradually replaced the former as the main pathogen of the cholera epidemic.
Vibrio cholerae is 1 to 3 μm long and 0.3 to 0.6 μm wide, and the bacterial body is curved in an arc or comma shape. Fresh specimens are smeared under microscope and arranged like a “fish school”. Gram stain negative, no spores and capsules. One end of the cell has a single flagella, which is active and active. The culture is aerobic, alkali-resistant and acid-resistant, and it grows well on alkaline peptone water or alkaline agar plates at pH 8.8 to 9.0. The flagellar antigens (H) of each group of Vibrio are mostly the same, and only the bacterial antigens (O) are different. According to the bacterial antigen, Vibrio is divided into O1~O6 groups (now increased to 72 groups). Both biotypes of Vibrio cholerae can agglutinate with serum antibodies to antimicrobial antigens and belong to the O1 group.
All other Vibrio species that do not belong to the O1 group are not agglutinative, and are collectively referred to as non-O1 group Vibrio. In 1980, the World Health Organization classified Vibrio cholerae into O1 group Vibrio cholerae, O1 group atypical Vibrio cholerae and non-O1 group Vibrio cholerae, and they were named after this. Scholars have analyzed and studied the bacterial antigens of Vibrio cholerae and found that the O1 group of Vibrio cholerae contains a common specific antigen A and different specific antigens B and C, which are divided into three types, namely the rice leaf type ( Inaba, prototype), containing antigens A, C; Ogawa type (Ogawa, heterotype), containing antigens A, B: Hikojima type (Hikojima, intermediate type), containing antigens A, B and C. In 1992, a typical cholera-like disease caused by non-O1 group Vibrio cholerae occurred in India and other places, and a new serotype Vibrio cholerae was isolated and named O139 Vibrio cholerae.
Vibrio cholerae produces three (types I to III) toxins. Type I toxin is endotoxin, heat-resistant, non-dialyzable, polysaccharide, exists inside the bacteria, can cause the death of guinea pigs and mice, and is toxic to chicken embryos and tissue cells. Type II toxins are exotoxins, namely cholera enterotoxin (enterotoxin) or choleragen. It is heat-labile, can be inactivated at 56°C for 30 minutes, is not acid-resistant, has antigenicity, can stimulate the body to produce neutralizing antibodies, and can produce toxoids after the action of formaldehyde.
Cholera enterotoxin causes the body to secrete a large amount of water and electrolytes from the intestinal glands, resulting in the symptoms of cholera diarrhea. It is a metabolite of Vibrio cholerae in the body’s reproduction.
Vibrio cholerae is not very resistant to warm drying. It is resistant to alkali but not acid, and can survive only 4 minutes in normal gastric acid, and can be fatal in a few minutes in 0.5% carbolic acid. Each liter of water containing 1mg of residual chlorine will kill you in 15 minutes. It is sensitive to common concentrations of disinfectants for intestinal infectious diseases. It will kill you in 10 minutes in 1% bleaching powder solution. Sensitive to doxycycline, streptomycin, tetracycline, co-trimoxazole, norfloxacin and ofloxacin.
Pathogenesis
Patients with cholera have characteristic watery diarrhea that results in a cascade of changes including dehydration and metabolic acidosis. The exotoxin secreted by Vibrio cholerae, which adheres to and colonizes the small intestine, is a major contributor to these changes. Research in recent years has made the original theory go a step further. It is now believed that GM1, the receptor for cholera enterotoxin, exists at the brush border of small intestinal mucosal epithelial cells. It has been shown to be a ganglioside, which is a water-soluble lipid in the cell membrane. The chemical structure of GM1 includes two parts, a hydrophilic carbohydrate and a hydrophobic ganglioside.
The former is a hydrophilic sugar chain, and the latter is a hydrophobic long-chain alkyl group. The lipid-soluble long-chain hydrocarbon groups are embedded in the cell membrane, and the sugar chains are exposed on the cell surface, which can bind together rapidly and irreversibly with cholera enterotoxin (CT). When subunit B of CT binds to GM1, subunit A can penetrate the cell membrane.
CT acts as the first messenger, causing increased synthesis and release of prostaglandins (PGE, etc., second messenger). PGE increases the activity of adenylate cyclase (AC) and catalyzes the conversion of ATP into cyclic adenylate (cAMP, the third messenger), thereby increasing cAMP in the cell membrane and promoting a series of enzymatic reactions in the cell. It promotes the enhancement of cell secretion function, and a large amount of intracellular water and electrolytes are secreted. The increased concentration of cAMP inhibits the absorption of sodium by intestinal villi and actively secretes sodium chloride, resulting in a large loss of water and electrolytes.
Once CT is combined with GM1, the above-mentioned reaction is irreversible, and the natural duration of its effect (diarrhea time) can be clinically as short as a few hours or as long as 7 to 8 days. It is now thought that another group O1 cholera toxin (the gene without CT) and the lysin produced by the Eto biotype may also be causative factors. In addition, the chemotaxis of Vibrio motility flagella and bacterial chemokine receptors with chemokines in the mucosal epithelium is a prerequisite for Vibrio to penetrate the mucus gel. Toxin co-regulatory fimbriae (TCP), a unique colonization factor of Vibrio cholerae, play an important role in pathogenicity.
Due to the loss of a large amount of intestinal fluid due to diarrhea, severe dehydration and electrolyte imbalance occur, blood concentration, and microcirculatory failure. Muscle cramps and low sodium, potassium, calcium, etc., are caused by the loss of large amounts of electrolytes with diarrhea. Loss of bicarbonate, resulting in metabolic acidosis. The reduction of bile secretion makes the vomitus spit-like.
Renal function can be severely impaired due to circulatory failure, insufficient renal blood flow, hypokalemia, and toxins. The main causes of death were hypovolemic circulatory failure and metabolic acidosis. Fluid loss in cholera patients occurs in the entire small intestine, and the amount of fluid loss per unit length is estimated to be the largest in the duodenum and the least in the ileum. There is no evidence of gastric hypersecretion, and intestinal absorption remains normal.
The pathological changes that develop during the course of cholera are often mild, manifesting only as marked reduction of mucus in goblet cells, mild dilatation of intestinal glands and microvilli, and mild edema of the lamina propria. The pathological findings of the patient’s post-mortem anatomy were mainly severe dehydration, rapid stiffness of the corpse, cyanosis of the skin, shrinkage of the fingers, and extreme dryness of the subcutaneous tissue and muscles.
The serosal layer of the gastrointestinal tract is dry, dark red, and the intestines are filled with swill-like liquid, occasionally blood-like, and the intestinal mucosa is inflamed and relaxed, but no ulcers are formed, and there is occasional bleeding. The lymphoid follicles are markedly enlarged, and the gallbladder is filled with viscous bile. Heart, liver, spleen and other organs are more common to shrink. There was no inflammatory change in the kidney, the glomerular and interstitial capillaries were dilated, and the renal tubular epithelium had opacity, swelling, degeneration and necrosis. Other internal organs and tissues may also have changes such as hemorrhage and degeneration.
Epidemiology
1. Source of infection
The source of infection for cholera is the sick and the carriers. Mild patients, latent infections and convalescent carriers play a greater role, and latent infections can be as high as 59% to 75%.
2. The way of transmission
Both biotypes of cholera are transmitted by water, food, flies, and everyday contact. Waterborne transmission is the most important route. Because water is most susceptible to contamination by the excrement of infected people, and Vibrio cholerae survives in water for a long time (usually more than 5 days, up to tens of days), contaminated water can contaminate many raw and cold foods.
The role of food transmission is second only to water, and Vibrio cholerae can survive on food for 1 to 2 weeks or longer. In 1972, there was a food-type outbreak in which more than 40 passengers suffered from cholera due to food contamination on an international civil aviation flight.
In the mountainous areas of Hainan Province, there have been many cases of food poisoning caused by Xiaochuan lb-type Vibrio cholerae because of the funeral dinners held by the mountain people. The role of daily contact and the transmission of flies cannot be ignored, but its transmission ability is far less than the first two factors.
3. Susceptible population
People regardless of race, gender and age are generally susceptible to cholera. Some immunity can be obtained after the disease, but the possibility of re-infection also exists. According to a report in Bangladesh in 1963, the annual reinfection rate was 0.22%, and the interval between two infections was 1.5 to 60 months, indicating that the duration of immunity after the disease was short. The original cholera vaccine (containing 4 billion dead bacteria of Ogawa type and Inaba type per ml) can only induce antibacterial antibodies but not antitoxin antibodies, so the immune effect is not ideal, the new artificial immune preparation is under continuous development.
Clinical Manifestations
Disease Symptoms
Except for a few patients who have short-term (1-2 days) prodromal symptoms such as dizziness, fatigue, abdominal distension and mild diarrhea, the onset is sudden, and the severity of the disease varies, with a considerable number of mild (about 75% of the Etto type). of latent infections and 18% of mild cases).
1. Incubation period
Most are 1 to 2 days, but can be as short as a few hours or as long as 5 to 6 days.
2. Diarrhea period
In most cases, severe diarrhea followed by vomiting, and in individual cases, vomiting followed by diarrhea. Diarrhea is painless and tenesmus. The daily bowel movements can range from several to dozens of times, or even frequently uncountable. The nature of the stool was initially watery and watery, with a large amount, and turned into a swill-like stool. Bloody stools were present in a few cases. Vomiting is jet-like, the frequency is small, and it is gradually swill-like, and some cases are accompanied by nausea. The rectal temperature can reach 37.2℃～38.5℃. This period lasts for several hours, no more than 2 days. There are reports of O139 Vibrio invading the bloodstream and causing bacteremia/septicemia, but it has not been ruled out whether it is an accidental phenomenon.
3. Dehydration and collapse period
The following clinical manifestations can occur due to loss of water and electrolytes due to severe diarrhea and vomiting.
1. General manifestations: restless demeanor, panic or indifference, sunken eye sockets, hoarse voice, thirst, extremely dry lips and tongue, shriveled, clammy skin and loss of elasticity, wrinkled fingerprints, sunken abdomen in a boat-like shape, and decreased body surface temperature .
2. Circulatory failure: Due to moderate or severe dehydration, the blood volume is significantly reduced and the blood is extremely concentrated, resulting in circulatory failure. The patient is extremely weak, unconscious, blood pressure drops, the pulse is thin and fast, the heart sound is weak and the heart rate is fast.
Blood tests may show increased red blood cells, hemoglobin, plasma protein and plasma specific gravity, increased blood viscosity, decreased renal blood flow and decreased glomerular filtration pressure due to dehydration and circulatory failure, resulting in oliguria or anuria, Increased urine specific gravity (above 1.020). If the daily urine output is less than 400ml, the excretion of organic acids and nitrogen products in the body will be hindered, so the blood urea nitrogen or non-protein nitrogen, creatinine will increase, and the carbon dioxide binding capacity will decrease, resulting in prerenal hyperazotemia.
3. Electrolyte balance disorder and metabolic acidosis: Severe diarrhea and vomiting can cause serious loss of blood electrolytes after losing a lot of water and electrolytes. The concentrations of sodium and chloride ions in the feces of patients are slightly lower than those in plasma, while potassium and bicarbonate ions are higher than those in plasma, but the sum of cations and anions in feces are equal to those in plasma, so the dehydration is isotonic.
Before the infusion, due to blood concentration, the plasma sodium, potassium and chloride ion concentrations of the patient are often measured to be normal or close to normal levels, and potassium ions can even increase. Continued infusion of electrolyte-free solutions can immediately cause hemodilution to produce hyponatremia and hypokalemia. Sodium deficiency can cause muscle spasm (most commonly the gastrocnemius and rectus abdominis), hypotension, low pulse pressure, and weak pulse.
Potassium deficiency can cause hypokalemia syndrome, manifested as systemic muscle tone reduction, or even muscle paralysis, loss of tendon reflexes, bloating, tachycardia, weakened heart sounds, arrhythmia, abnormal electrocardiogram (prolonged Q-T time, flat T wave). Or inversion, U wave, etc.), potassium deficiency can also cause kidney damage. Metabolic acidosis occurs due to the massive loss of bicarbonate ions. Oliguria and circulatory failure can exacerbate acidosis. Severe acidosis can cause confusion, deep breathing, and a drop in blood pressure.
4. Response period and recovery period
After the dehydration is corrected, the symptoms of most patients disappear and gradually return to normal. The average course of the disease is 3 to 7 days, and a few can last for more than 10 days (mostly elderly patients or those with severe comorbidities). Febrile reactions may occur in some patients, especially in children, which may be due to the absorption of a large number of enterotoxins after circulation improvement. Body temperature can rise to 38 to 39 ° C, which usually subsides after 1 to 3 days.
