Cholera

Introduction to Cholera Cholera (cholera) is a potent intestinal infectious disease caused by Vibrio cholerae. It is an acute and rapid spread, and is an important cause of diarrhea in most parts of Asia and Africa. It is an international quarantine infectious disease. In China, it belongs to Class A infectious diseases. Typical patients due to severe diarrhea and vomiting can cause dehydration, muscle spasm, severe cases of peripheral circulatory failure and acute renal failure, generally more common in mild cases, more carriers, but severe and typical patients can not be treated in time death. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: fecal-mouth transmission Complications: uremia metabolic acidosis acute pulmonary edema

Cholera cause

Vibrio cholerae infection (95%)

The causes of cholera are mainly divided into three major aspects: Vibrio cholerae is a pathogen, and the source of infection is patients and carriers. Water transmission is the most important route. The brush border of small intestinal mucosal epithelial cells has cholera enterotoxin receptors, and the pathogenesis is that a large amount of water and electrolytes irreversibly bind from surface gangliosides. The cause of cholera: Vibrio cholerae has two biotypes, the classical biotype and the Eto biotype. 1. The source of infection of cholera is the patient and the carrier. 2. Transmission The two biotypes of cholera can be transmitted through water, food, flies and daily life contacts. Water source transmission is the most important way. 3. Susceptible people are generally susceptible to cholera regardless of race, gender and age.

Pathogenesis:

1. Pathogenesis Whether the disease occurs after the human body ingests Vibrio cholerae depends mainly on the immunity of the body and the amount of Vibrio inhaled. If the human body can secrete normal gastric acid and is not diluted, it can kill a certain amount of Vibrio cholerae. Without the onset of disease, if the oral live vaccine is used, the presence of specific IgM, IgG and IgA antibodies in the intestine can also prevent Vibrio from adhering to the intestinal wall and avoiding the onset of the disease, but if the gastric resection is performed, the gastric acid secretion is reduced. Or a large amount of drinking water, a large amount of food to dilute the stomach acid, or the amount of Vibrio cholerae more than 108 ~ 109, can cause the disease, Vibrio cholerae through the stomach after the intestinal tract through the flagellar movement and the protease produced by Vibrio, through The mucus layer on the intestinal mucosa adheres to the brush border of the upper intestinal mucosal epithelial cells under the action of Tcp A and Vibrio cholerae hemagglutinin (HA), and does not invade the intestinal mucosa, in the alkaline environment of the small intestine. Vibrio cholerae multiplies and produces cholera enterotoxin. When the enterotoxin is in contact with the intestinal mucosa, its B subunit recognizes and binds to receptors on intestinal mucosal epithelial cells. This receptor is ganglioside (gangliosi). De), followed by the enzymatically active A subunit into the intestinal mucosal cells, wherein the A subunit is capable of transferring ADP (adenosine diphosphate) ribose from the nicotinamide adenine dinucleotide (NAD) to the target protein guanosine In the triphosphatase (GTPase), and binding to it, the GTPase activity is inhibited, resulting in the continuous activation of adenylate cyclase, which continuously converts adenosine triphosphate into cyclic adenosine monophosphate (cAMP). When the intracellular cAMP concentration is increased, it stimulates the intestinal mucosal crypt cells to secrete excessive water, chloride and carbonate, while inhibiting the absorption of sodium and chloride ions by the intestinal villus cells, so that water and sodium chloride are present. The intestinal lumen accumulates, causing severe watery diarrhea.

Cholera enterotoxin can also promote the secretion of mucus in the intestinal mucosal goblet cells, so that the diarrhea watery sample contains a lot of mucus, in addition to the loss of water caused by diarrhea, so that the secretion of bile is reduced, so the diarrhea feces can become "rice water", except the intestines In addition to toxins, endotoxin and Vibrio cholerae produce hemolysin, enzymes and other metabolites, which also have a certain pathogenic effect.

2. Pathophysiology

(1) Water and electrolyte disorders: cholera patients due to severe vomiting and diarrhea, a large loss of water and electrolytes in the body, resulting in dehydration and electrolyte imbalance, severe dehydration patients may have circulatory failure, if the correction of water loss is not timely, shock time is too long Can further cause acute renal failure, although the fluid lost by cholera patients is isotonic liquid, but the amount of potassium contained in it is 4-6 times that of serum potassium, while sodium and chlorine are slightly lower than serum, so when rehydration treatment, In the case of urine, potassium should be added in time, otherwise severe hypokalemia can lead to arrhythmia; it can also cause degeneration of renal tubular epithelial cells, further aggravating renal failure.

(2) Metabolic acidosis: due to the loss of a large amount of bicarbonate due to diarrhea, in addition, peripheral circulation failure caused by water loss, tissue anaerobic metabolism due to hypoxia, so excessive production of lactic acid can aggravate metabolic acidosis, acute renal failure It is not able to excrete metabolic acidic substances, which is also the cause of acidosis.

3. Pathological anatomy The main pathological changes of this disease are severe dehydration, the organ damage is not heavy, the skin is dry, the subcutaneous tissue and muscle dehydration, the heart, liver, spleen and other organs are reduced due to dehydration, glomerulus and kidney The capillaries can be seen to dilate, the tubules can be degenerated and necrotic, and the small intestinal mucosa can only see non-specific infiltration.

Cholera prevention

1. Control the source of infection to detect patients and suspected patients in time, conduct isolation treatment, and do a good source search. This is an important link to control the cholera epidemic. In this respect, China has had successful experience.

(1) Establishment of diarrhea intestine clinic: All town hospitals should establish a bowel clinic, and patients with diarrhea in the clinic should be able to detect patients and suspected patients in time, conduct isolation treatment and report on epidemic situation to prevent the spread of infectious agents.

(2) Medication and preventive medication for close contacts: close contact should be carried out for fecal culture examination, once/d for 2 consecutive days, after the first fecal examination, medication can be reduced to reduce carriers, generally applied to Dorsey Cyclin 200mg ton, the next day oral 100mg, children 6mg / (kg · d), even for 2 days, can also be applied norfloxacin 200mg, 3 times / d, and even served for 2 days.

(3) Do a good job in frontier health quarantine and domestic traffic quarantine: Once a patient or suspected patient is found, it should be immediately isolated and thoroughly disinfected.

2. Cut off the route of transmission to enhance drinking water disinfection and food management, ensure water safety, have good sanitation facilities can significantly reduce the risk of cholera transmission, and develop effective plans to control cholera in areas where cholera has not yet invaded and formed seasonal epidemics. It is the best preparation for controlling the prevalence of cholera. Long-term improvement of water supply and sanitation is the best way to prevent cholera. It thoroughly disinfects the excretions of patients and carriers, and should eliminate vectors such as flies.

3. Improve the immunity of the population to immunize the population with the whole bacterial dead vaccine or the toxoid vaccine of cholera enterotoxin. Because of the low protection rate, short protection time, and can not prevent hidden infections and carriers, it has not been recommended. At present, there are a variety of vaccines made and tried by foreign applied genetic engineering technology, and they are still expanding their trials, including:

(1) B subunit-full bacterial vaccine (BS-WC): This is a vaccine consisting of inactivated Vibrio cholerae whole cell (WC) and purified cholera enterotoxin B subunit (BS) The WC cell wall contains antigens such as lipopolysaccharide (LPS) and cholera toxin synergistic pili (TCP), which can induce the body to produce antibacterial antibodies, thereby inhibiting the colonization of Vibrio cholerae in the intestine; while the anti-toxic antibodies produced by BS can be And the B subunit of CT makes cholera enterotoxin unable to bind to intestinal mucosal receptors, but does not play the role of enterotoxin. The protection rate of this bacterin is 65%-85%, which is superior to the classical biotype Vibrio cholerae. Elto biotype Vibrio cholerae.

(2) Attenuated oral live vaccine (CVD10-HgR): This is a DNA recombination technique that removes 94% of the CTXA gene and recombines it into the classical biological Vibrio cholerae strain 569B to obtain the attenuated strain CVD103, which is then introduced. An anti-mercury (Hg)-encoding gene enters the chromosomal site of hgla and becomes an attenuated strain of CVD103-HgR. This vaccine can significantly inhibit the infection of O1 group classical biotype and Elto biotype Vibrio cholerae, Taket et al. Oral (3 ~ 5) × 108, after a single dose of CVD103-HgR bacteria, 100% protection was obtained in volunteers. It is generally believed that the protection lasted for at least 6 months, but animal experiments showed that the vaccine was O139 cholera arc The bacteria have no protective effect. Woldol- et al. have constructed attenuated strain Bengal3 of VCO139, which lacks toxins such as cytotoxin (CT) and adenylyl cyclase (ACE) zot, but its safety and protective ability have yet to be further studied.

(3) Study of O139 vaccine O139 capsular lipopolysaccharide is not only an important virulence factor, but also an important protective antigen. O139 capsular lipopolysaccharide vaccine is prepared by using serum protein as carrier protein, and EDC or CDAP is used as an activator. In mice, the mice can produce Vibrio antibodies, and the covalent binding of O139 capsular lipopolysaccharide to diphtheria toxin can produce IgG against capsular polysaccharides, which has an antibacterial effect and can also be produced. This study is still in the animal experiment phase for antibodies to diphtheria toxin.

Cholera complications Complications Uremia Metabolic acidosis Acute pulmonary edema

(1) Renal failure due to shock not being corrected in time and hypokalemia, manifested as decreased urine output and azotemia, severe cases of urinary closure, death due to uremia.

(B) acute pulmonary edema metabolic acidosis can lead to high blood circulation, the latter is also aggravated by the addition of a large amount of alkali-free saline.

(3) Other hypokalemia syndrome, arrhythmia and abortion.

Symptoms of cholera Common symptoms Explosive watery diarrhea, fatigue, dizziness, irritability, blood pressure, urgency, heavy pulse, fine green urine, dehydration, dehydration

The incubation period of the disease is several hours, the elderly are 3 to 6 days, usually 1 to 3 days, the diseases caused by classical biotypes and O139 Vibrio cholerae are more serious; the symptoms caused by the El Torcobacter cholerae More light, more asymptomatic pathogen carriers, typical patients with sudden onset, a small number of patients 1 to 2 days before the onset of symptoms may have dizziness, fatigue or mild diarrhea.

1. The course of a typical case can be divided into three phases.

(1) vomiting and diarrhea: start with severe diarrhea, followed by vomiting, generally no fever, only a few have low fever.

1 diarrhea: diarrhea is the first symptom of the disease, characterized by no urgency and heavy feeling, most without abdominal pain, consciously light after defecation, a small number of patients have abdominal pain, individual cases may have paroxysmal abdominal cramps, discharged feces It is yellow and thin at the beginning, and then it is watery. It is more common with yellow water. The severe diarrhea discharges the white turbid "rice water" stool. If there is intestinal bleeding, the stool is discharged and the bleeding is more. It is tar-like, and it is more common in Erto biotypes of Vibrio cholerae. The number of diarrhea varies from several times to dozens of times a day. In severe cases, it is incontinence.

2 vomiting: generally occurs after diarrhea, without nausea, mostly jet vomiting, vomit is initially food in the stomach, followed by watery, severe cases can also vomit "rice water" sample, similar to the nature of feces, light No vomiting.

(2) Dehydration period: due to severe vomiting and diarrhea, a large amount of water and electrolytes are lost in the body, resulting in dehydration, electrolyte imbalance and metabolic acidosis. In severe cases, circulatory failure occurs, and the duration of the disease depends mainly on whether the treatment is timely. And correct or not, usually hours to 2 to 3 days.

1 dehydration: can be divided into light, medium and heavy three degrees, mild dehydration, visible skin mucous membrane dry, skin elasticity is poor, generally about 1000ml of water loss, children 70 ~ 80mL / kg body weight; moderate dehydration, see skin elasticity is poor, Eye socket depression, mild hoarseness, decreased blood pressure and decreased urine output, loss of water 3000 ~ 3500ml, children 80 ~ 100ml / kg body weight; severe dehydration, dry skin wrinkles, no elasticity, hoarseness, and visible eyelid depression, two Deep cheeks, indifferent or unclear "cholera face", circulatory failure and acidosis, if not actively rescued, can be life-threatening, severe dehydration patients about dehydration 4000ml, children 100 ~ 120ml / kg body weight, dehydration points See Table 1.

2 Circulatory failure: water loss shock caused by severe water loss, clinical manifestations: When the blood volume is significantly reduced, the limbs are cold, the pulse is fine, and even can not be touched, the blood pressure drops or can not be measured, and then because of the brain Insufficient blood supply, cerebral hypoxia and disturbance of consciousness, began to be irritated, then sluggish, sleepy and even coma.

3 uremia acidosis: clinical manifestations of increased breathing, severe in addition to the emergence of Kussmaul (Kussmaul) breathing, may have consciousness disturbances, such as lethargy, feeling dull or even coma.

4 muscle spasm: This is vomiting, diarrhea causes a large amount of salt loss, severe hyponatremia causes gastrocnemius and rectus abdominis tendon, clinical manifestations of pain in the ankle area and muscle rigidity.

5 hypokalemia: diarrhea causes a large loss of potassium salt, blood potassium can be significantly reduced, clinical manifestations of weakened muscle tone, knee reflexes disappear or disappear, abdominal distension, can also occur.

(3) Recovery period or reaction period: diarrhea is stopped, most patients lose symptoms after dehydration correction, urine volume increases, and physical strength gradually recovers, but in a few cases, endotoxin remaining in the intestinal lumen is absorbed into the bloodstream due to improvement of blood circulation. It can cause fever of different severity. Generally, the patient's body temperature is as high as 38 ~ 39 ° C, and it will subside after 1 to 3 days.

2. The clinical type can be divided into light, medium and heavy according to the degree of water loss, blood pressure and urine volume.

(1) Light type: slow onset, diarrhea no more than 10 times / d, for loose or dilute watery stools, generally without vomiting, sustained diarrhea after 3 to 5 days to recover, no significant dehydration.

(2) medium (typical): typical diarrhea and vomiting symptoms, diarrhea up to 10 ~ 20 times / d, for water samples or "rice water" sample, the amount is large, so there are obvious signs of water loss, blood pressure, shrinkage The pressure is only 9.31 to 12 kPa (70 to 90 mmHg), the amount of urine is reduced, and the amount of urine is 500 ml/24 hours or less.

(3) Heavy: In addition to typical diarrhea and vomiting symptoms, patients have severe water loss, resulting in circulatory failure, which is characterized by rapid or inaccessible pulse, blood pressure drop, systolic blood pressure below 9.31 kPa (70 mmHg) or can not be measured The urine volume is 50mL/24h or less.

In addition to the above three clinical types, there is a rare violent or poisoning type, also known as "cholera sicca", this type of onset is rapid, no symptoms of diarrhea and vomiting, ie rapid entry into toxic He died in shock.

Cholera check

1. Blood routine and biochemical examination can cause blood concentration due to water loss, red blood cell count is increased, hemoglobin and hematocrit are increased, white blood cells can reach 10×109/L or more, and neutrophils and monocytes increase and count. During the water period, serum sodium, potassium and chlorine were all reduced, urea nitrogen and creatinine were increased, and hydrogen carbonate ions were decreased.

2. Urine routine can have a small amount of protein, microscopic examination has a little red blood cells, white blood cells and casts.

3. Fecal examination

(1) routine microscopic examination: visible mucus and a little red blood cells, white blood cells.

(2) Smear staining: Take the feces or early culture smear for Gram staining microscopy, showing Gram-negative slightly curved Vibrio, no spores, no capsule, and O139 Vibrio cholerae can produce capsules In addition, the other is the same as the O1 group of Vibrio cholerae.

(3) hanging drop inspection: fresh feces for hanging drop or dark field microscopy, visible lively shuttle-like Vibrio.

(4) Braking test: take the watery stool of the acute phase patient or the surface growth of the alkaline sputum water enrichment culture for about 6h, first for dark field microscopy, observe the power, if there is a shuttle-like moving object, then join O1 subgroup multi-valent serum 1 drop, if O1 group Vibrio cholerae, due to antigen-antibody action, it will be agglomerated, vibrio movement will stop, such as adding O1 group Vibrio cholerae serum, can not stop the movement, should use O139 Vibrio cholerae serum re-test.

(5) Enrichment culture: All the suspected cholera patients' feces should be used for enrichment culture except for microscopic examination. The feces should be taken before the use of antibiotics, and should be sent to the laboratory for cultivation as soon as possible. The base is generally made up of alkaline protein peptone at pH 8.4, and the surface can form a membrane after 6 to 8 hours of incubation at 36-37 ° C. At this time, it should be further isolated and cultured, and subjected to dynamic observation and braking test, which will help to improve. Detection rate and early diagnosis.

(6) Isolation and culture: commonly used gentamicin agar plate or alkaline agar plate, the former is a strong selective medium, 36-37 ° C culture 8 ~ 10h Vibrio cholerae can produce small colonies, the latter need to cultivate 10 ~20h, select suspicious or typical colonies, apply anti-serum of Vibrio cholerae O antigen for slide agglutination test, if it is positive, report it. In recent years, foreign countries have also applied DNA probe of cholera toxin gene for colony hybridization. Rapid identification of virulent O1 Vibrio cholerae.

4. PCR detection Newly applied PCR technology to rapidly diagnose cholera, which distinguishes cholera strain and non-cholesteric Vibrio by identifying the Vibrio cholerae toxin gene subunit CTXA and the toxin synergistic pili gene (TCPA) in the PCR product, and then according to The different DNA sequences of the TCPA gene distinguish between the classical biotype and the Elto biotype Vibrio cholerae, and the results can be obtained within 4 hours. It is said that the sensitivity can detect <10 cells per ml of alkaline peptone water.

5. Rapid diagnosis of cholera Using ELISA method, the anti-purified Vibrio outer membrane protein serum is used to detect Vibrio antigen in feces, which can quickly diagnose cholera without the need for enrichment culture.

6. Identification of the identification of classical biotypes, Elto biotypes and O139 Vibrio cholerae.

7. Serum immunological examination of Vibrio cholerae infection, can produce antibacterial antibodies and anti-enteric toxin antibodies, anti-agglutination antibodies in antibacterial antibodies, generally appear on the fifth day of onset, the disease reaches a peak of 8 to 21 days, serum immunity The examination is mainly used for the retrospective diagnosis of epidemiology and the diagnosis of suspicious patients with negative fecal culture. If the anti-lectin antibody double serum titer is increased by more than 4 times, it has diagnostic significance.

Arrhythmia ECG shows QT prolongation, T wave flat or inverted and U wave appears.

Cholera diagnosis

diagnosis

In cholera-prone areas, any patients with diarrhea and vomiting during the epidemic season should be suspected of cholera and cholera. Therefore, sputum bacteriological examination for cholera exclusion should be performed. Anyone with typical symptoms should be treated with cholera.

1. One of the following diagnostic criteria can be diagnosed as cholera.

(1) There are symptoms of diarrhea, and the culture of feces is positive for Vibrio cholerae.

(2) During the epidemic of cholera, there are typical symptoms of cholera diarrhea and vomiting in the epidemic area, rapid dehydration, circulatory failure and muscle spasm. Although no cholera vibrio is found in the fecal culture, there are no other reasons to investigate. If the condition can be used as a double serum lectin test, the titer of 4 times increase can be diagnosed.

(3) Those with diarrhea symptoms within 5 days before the fecal culture is found to be positive in the source search can be diagnosed as mild cholera.

2. Suspected diagnosis has one of the following

(1) The first case with typical cholera symptoms, the pathogen examination has not been confirmed before.

(2) During the epidemic of cholera, there is a clear history of contact with cholera patients, and vomiting symptoms occur, but no other reasons can be investigated. Suspected patients should be isolated, disinfected, reported as suspected cholera epidemic, and do fecal culture every day. Negative stool culture was negative for 2 consecutive times, which can be used as a negative diagnosis and a revised report on the epidemic situation.

Differential diagnosis

First, the identification of bacterial diarrhea

Bacterial diarrhea is generally caused by non-OI group Vibrio and enterotoxin-producing Escherichia coli (ETEC). Most of the former patients have diarrhea with severe abdominal pain and fever, and 1/4 of the patients have bloody stools. The diarrhea caused by Escherichia coli is generally more severe. Short, the identification of both and cholera depends on the pathogen examination.

Second, cholera should be differentiated from various bacterial food poisoning, such as Staphylococcus aureus, Proteus, Bacillus cereus and accessory hemolysis such as Staphylococcus aureus, Proteus, Bacillus cereus and Vibrio parahaemolyticus A variety of food poisoning onset, acute convulsions often occur collectively, often vomiting and diarrhea, there is paroxysmal abdominal pain before defecation, feces often yellow water, occasionally pus.

Third, if part of the feces is washed with water or dysentery, it needs to be differentiated from bacterial dysentery. The latter is often associated with abdominal pain and urgency, and the amount of feces is small.

4. Identification with acute arsenic poisoning. Acute arsenic poisoning is mainly characterized by acute gastroenteritis. The stool is yellow or gray water, often with blood. In severe cases, urine output is reduced, even urinary closure and circulatory failure, etc., check feces or The arsenic content of vomit can be clearly diagnosed.

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