| disease | Cholera |
| alias | Disease No. 2, Cholera |
Cholera is an acute intestinal infectious disease caused by Vibrio cholerae, with varying clinical manifestations. Severe cases typically present with intense vomiting and diarrhea, dehydration, microcirculatory failure, metabolic acidosis, and acute renal failure. It is highly fatal if untreated and classified as a Class A infectious disease. Previously, infections caused by the classical biotype of Vibrio cholerae were termed "cholera," while those caused by the El Tor biotype were called "paracholera." However, since the two biotypes are nearly identical morphologically and serologically, with similar clinical presentations and prevention measures, distinguishing them as cholera and paracholera is unnecessary. The disease is now uniformly referred to as cholera. The fifth and sixth global pandemics were associated with the classical biotype, while the seventh originated from the endemic El Tor biotype in Indonesia and persists to this day. In 1992, outbreaks in India and Bangladesh were confirmed to be caused by a new serotype, designated O139. This strain has since spread to Pakistan, Sri Lanka, Thailand, Nepal, China's Hong Kong, as well as Europe and America, potentially signaling the onset of an eighth pandemic.
bubble_chart Epidemiology
Patients and carriers are the sources of cholera pestilence. The vomit and diarrhea of typical patients contain a large number of bacteria, with each milliliter of feces containing 107 to 109 vibrios, which plays an important role in the spread of the disease. Mild cases are easily overlooked, and healthy carriers are difficult to detect, both of which pose significant risks as sources of pestilence. Incubatory carriers do not yet exhibit vomiting or diarrhea, and convalescent carriers generally excrete bacteria for a short period, making their role as sources of pestilence secondary. Marine crustaceans can harbor El Tor vibrios on their surfaces; these vibrios secrete chitinase, breaking down chitin for nutrients and surviving long-term. Consumption of contaminated seafood can lead to cholera outbreaks. Experimental observations show that El Tor vibrios ingested by artificially raised loaches and eels can grow and multiply within these hosts before being excreted into water. Thus, loaches and eels can serve as reservoirs for vibrios, spreading pathogens and causing cholera outbreaks.
The disease is primarily transmitted through water, but contaminated food, hands, and flies also play a role in its spread.People of all ages and genders are susceptible to the disease. In newly affected areas, adults are more susceptible than children; in endemic regions, children have higher incidence rates than adults, whose resistance to infection increases with rising antibody titers against cholera vibrios. Recurrent severe infections are rare. Volunteers experimentally infected with cholera vibrios exhibit high resistance to reinfection, lasting at least three years. Immunity from initial infection with classical cholera vibrios (100% protection) is stronger than that from El Tor vibrios (90% protection). Although cholera patients may retain protective immunity against new infections for several years, intestinal antibodies against cholera toxins and bacteria persist for only a few months.
1. Morphological Staining: Cholera vibrio is Gram-negative, with a body length of 1.5–2.0 μm and a width of 0.3–0.4 μm, curved like a comma, and possesses a single polar flagellum that is 4–5 times the length of the bacterial body.
The bacterium is highly motile, exhibiting darting movements observable in dark-field suspensions, and feces can be used for direct smear examination.
2. Culture Characteristics: Cholera vibrio proliferates rapidly in alkaline (pH 8.8–9.0) broth or peptone water, forming a transparent bacterial membrane on the surface. After overnight culture on nutrient agar or meat extract agar, the colonies appear large, translucent, and grayish. The bacterium thrives on selective media, commonly including bile salt agar, thiosulfate-citrate-bile salts-sucrose (TCBS) medium, and tellurite agar.
3. Generation and Transformation Reactions: Both O1 group cholera vibrio and atypical O1 group cholera vibrio can ferment sucrose and mannose but not arabinose. Non-O1 group cholera vibrio exhibits varying fermentation capabilities for sucrose and mannose. Additionally, the El Tor biotype can decompose glucose to produce acetylmethylcarbinol (i.e., VP test positive). The O139 strain can ferment glucose, maltose, sucrose, and mannose, producing acid but no gas, and does not ferment inositol or arabinose.4. Cholera vibrio dies after drying for 2 hours or heating at 55°C for 10 minutes and is immediately killed by boiling. The bacterium is destroyed within minutes upon contact with 1:2000–3000 mercuric chloride or 1:500000 potassium permanganate and dies within 10 minutes in 0.1% bleach. Cholera vibrio can survive for 4 minutes in normal gastric acid and for several days in untreated feces. In shallow wells with pH 7.6–8.8, classical cholera vibrio survives for an average of 7.5 days, while El Tor cholera vibrio survives for 19.3 days. El Tor vibrio survives for 10–13 days in seawater and deep wells. Foods with sodium chloride concentrations above 4% or sucrose concentrations above 5%, as well as spices, vinegar, and alcohol, are unfavorable for the survival of the bacterium. In refrigerated milk, fresh meat, and aquatic products like shrimp, cholera vibrio survives for 2–4 weeks, 1 week, and 1–3 weeks, respectively; on fresh vegetables stored at room temperature, it survives for 1–5 days. The bacterium can survive for a considerable time on cutting boards and cloth but no more than 2 days on glass, ceramics, plastic, and metal.
5. Antigenic Structure: Cholera vibrio has a heat-stable somatic (O) antigen and a heat-labile flagellar (H) antigen. The H antigen is common to all cholera vibrio species; the O antigen includes both group-specific and type-specific antigens, serving as the basis for classifying cholera vibrio into groups and types. There are over 100 group-specific antigens.
6. Classification: The WHO Diarrhea Control Center divides cholera vibrio into three groups.⑴ O1 group cholera vibrio: Includes the classical biotype (Vibrio cholerae) and the El Tor biotype (Vibrio cholerae EL-Tor biotype). The O1 group has three specific antigens—A, B, and C—where antigen A is common to all O1 strains. The combination of A with B or C antigens divides them into three serotypes: prototype—AC (Inaba), heterotype—AB (Ogawa), and intermediate type—ABC (Hikojima).
(2) Non-O1 group Vibrio cholerae: The flagellar antigen of this group of Vibrio is the same as the O1 group, but the somatic (O) antigen is different and is not agglutinated by the polyvalent serum of O1 group Vibrio cholerae. Based on the differences in O antigens, this group can be divided into 137 serotypes. Previously, it was believed that this group only caused sporadic gastroenteritis diarrhea, and infections by such Vibrio were generally not treated as cholera. However, in 1992, cholera outbreaks occurred in India, Bangladesh, and other regions, and it was later confirmed that the epidemic strain was not agglutinated by the diagnostic sera of the O1 group or the 137 non-O1 group Vibrio cholerae. It was then designated as O139 Vibrio cholerae and recognized as a true cholera pathogen.
⑶ Atypical O1 group Vibrio cholerae: Can be agglutinated by polyvalent O1 group serum, but this group of bacteria does not produce enterotoxin, hence lacks the {|###|}nature of disease.
Vibrio cholerae can produce enterotoxin, neuraminidase, hemagglutinin, and release {|###|}internal toxin after bacterial lysis. Among these, cholera enterotoxin (CT) is difficult to distinguish between classical, ET-Tor, and O139 types.
The human body possesses nonspecific immunity to resist the invasion of *Vibrio cholerae*. Gastric acid plays a major role in this process. Factors such as partial gastrectomy, excessive water intake, or excessive food consumption that dilute gastric acid can reduce resistance to *V. cholerae*. However, even in healthy individuals, ingesting *V. cholerae* in quantities exceeding 108-9 can lead to illness.
Other barriers in the human body, such as intestinal motility, intestinal mucus, enzymes, and bile salts, can be adapted to by *V. cholerae*. Through flagellar movement, mucinase, adhesins, and bacterial chemotaxis, the bacteria successfully adhere to the intestinal mucosal epithelial cells without invading them, continuing to proliferate, after which enterotoxin plays a critical role.
Cholera enterotoxin consists of two subunits, A and B. The toxin-active subunit A can be further divided into two polypeptides, A1 and A2, linked by disulfide bonds, with molecular weights of 23–24kD and 5–6kD, respectively. Subunit B has five parts, each with a molecular weight of 11.6kD, which can individually bind to the receptor (Gm1 ganglioside) on the brush border membrane of intestinal mucosal epithelial cells. After subunit B binds to the intestinal mucosal cells, subunit A detaches from the entire toxin molecule and migrates to the inner side of the cell membrane. The A1 portion is released into the cytoplasm, activating adenylate cyclase, which converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). The accumulation of large amounts of cAMP in the mucosal cells acts as a second messenger, stimulating crypt cells to secrete chloride ions and possibly bicarbonate ions while inhibiting the normal absorption of chloride and sodium ions by villous cells. Due to enhanced secretion and reduced absorption in the intestinal mucosa, a large volume of intestinal fluid accumulates in the lumen, resulting in the characteristic profuse watery diarrhea of the disease.
The internal toxin of *V. cholerae* is derived from the bacterial cell wall, is heat-stable, and carries the specific O-antigen of the vibrio, but it has little relevance to the pathogenesis of cholera. Enzymes (e.g., mucinase), metabolic products, or other toxins (e.g., vascular permeability factor, hemolysin) produced by the vibrio can cause certain harmful effects on the human body.
Profuse diarrhea and vomiting lead to massive loss of water and electrolytes, rapidly causing severe dehydration and resulting in microcirculatory failure. The loss of potassium, sodium, calcium, and chloride can lead to muscle rigidity, hyponatremia, hypokalemia, and hypocalcemia. Due to reduced bile secretion, the intestinal fluid contains large amounts of water, electrolytes, and mucus, giving the vomitus and stool a rice-water appearance. The loss of bicarbonate results in metabolic acidosis. Renal ischemia caused by circulatory failure, hypokalemia, and the direct effects of toxins on the kidneys can lead to renal impairment or failure.
bubble_chart Pathological Changes
Pathological examination revealed that the biopsy of the patient's small intestine showed only mild inflammation. The villous cells exhibited deformed microvilli or large pseudopod-like cytoplasmic protrusions without microvilli, extending from the apical cell surface into the intestinal lumen. Crypt cells also displayed pseudopod-like protrusions extending into the crypt cavity. The epithelial cells showed mitochondrial swelling with cristae disappearance, an increased number of Golgi vesicles, and dilation and vesiculation of the endoplasmic reticulum. The main pathological changes in deceased patients were severe dehydration: early onset of rigor mortis, dry and cyanotic skin, withered subcutaneous tissue and muscles. The visceral serosa appeared dull, the intestines were filled with rice-water-like fluid, and the gallbladder was filled with thick bile. The heart, liver, spleen, and other organs were found to be shrunken. The glomeruli and interstitial capillaries were dilated, with renal tubules showing cloudy swelling, degeneration, and necrosis. Other organs also exhibited hemorrhage, degeneration, and other changes.
bubble_chart Clinical Manifestations
The incubation period is 1 to 3 days, with the shortest being a few hours and the longest up to 7 days. Most cases have an acute onset, while a few may experience prodromal symptoms such as dizziness, fatigue, abdominal distension and fullness, and grade I diarrhea 1 to 2 days before the onset of illness. Diseases caused by the classical biotype and O139 Vibrio cholerae tend to have more severe symptoms, whereas those caused by the El Tor type are often milder, with many asymptomatic cases.
(1) Typical Cases The course of the disease is divided into three stages.
1. Diarrhea and Vomiting Stage The vast majority of patients begin with acute diarrhea and vomiting. The diarrhea is painless, though a few patients may experience abdominal pain due to rectus muscle spasms, without tenesmus. Initially, the stool is muddy or watery with fecal matter, but it quickly turns into rice-water-like or colorless, transparent watery stool, odorless with a faintly sweet or fishy smell, containing large amounts of flaky mucus. A few severe cases may occasionally have bloody stools, appearing like meat-washing water or even tar-like, more commonly seen in cases caused by the El Tor type. The stool volume is large, often exceeding 1000ml per episode, with more than ten episodes per day, sometimes even too numerous to count. Vomiting usually occurs after diarrhea, often projectile and continuous, starting with gastric contents and later turning into clear, watery fluid. In severe cases, it may resemble "rice-water," while mild cases may not involve vomiting. This stage lasts from a few hours to 1–2 days.
2. Dehydration Stage Due to frequent diarrhea and vomiting, large amounts of water and electrolytes are lost, leading to rapid dehydration and microcirculatory failure. Patients appear apathetic, with a dull or dysphoric expression, and children may experience unconsciousness. Symptoms include thirst, hoarseness, rapid breathing, tinnitus, sunken eyeballs, deeply hollowed cheeks, dry lips, cool skin, loss of elasticity, and wrinkled fingers. Muscle cramps are common, particularly in the gastrocnemius and rectus muscles. The abdomen becomes boat-shaped with a doughy feel. The pulse is thready and rapid or even imperceptible, with low blood pressure. Body temperature drops, with normal rectal temperature in adults but often elevated in children. This stage typically lasts from a few hours to 2–3 days.
3. Stage of Convalescence Once dehydration is promptly corrected, most symptoms disappear, and the patient recovers. Diarrhea decreases or stops entirely. The voice returns, skin becomes moist, and urine output increases. About one-third of patients may experience reactive fever, and a very few, especially children, may develop high fever.
(2) Clinical Types Based on clinical manifestations, cholera can be divided into five types.
1. Asymptomatic Type No symptoms appear after infection, but the patient becomes a carrier, known as a contact or healthy carrier. The carrier state usually lasts 5–10 days, though in some individuals, it may persist for months or years, becoming chronic.
2. Mild Type Patients feel slightly unwell, with diarrhea occurring several times a day and loose stools. Generally, there is no vomiting or signs of dehydration. Blood pressure and pulse remain normal, plasma specific gravity ranges between 1.026 and 1.030, and urine output does not significantly decrease.
3. Moderate Type Vomiting and diarrhea occur more frequently, up to 10–20 times a day. Stools are rice-water-like, with some degree of dehydration. Blood pressure drops (systolic pressure 9.31–12 kPa or 90–70 mmHg), the pulse is thready and rapid, plasma specific gravity is 1.031–1.040, and 24-hour urine output is below 500ml.
4. Severe Type Frequent vomiting and diarrhea lead to severe dehydration. Blood pressure is very low or even unmeasurable, the pulse is rapid and weak, often imperceptible, plasma specific gravity exceeds 1.041, and urine output is minimal or absent.
5. Fulminant Type Also known as dry cholera, it is extremely rare. The onset is abrupt, and death from circulatory failure occurs before diarrhea and vomiting manifest.
bubble_chart Auxiliary Examination
(1) Blood Test Elevated red blood cells and hemoglobin, white blood cell count 10-20×109/L (10,000-20,000/mm3) or higher, with increased neutrophils and large mononuclear cells. Serum potassium, sodium, chloride, and carbonate levels decrease, blood pH drops, and urea nitrogen rises. Before treatment, serum potassium may remain within the normal range due to the outward shift of intracellular potassium ions. However, after correcting acidosis, potassium ions move back into the cells, leading to hypokalemia.
(2) Urine Test A small number of patients may show protein, red and white blood cells, and casts in their urine.
(3) Pathogen Examination
1. Routine Microscopy Mucus and a small number of red and white blood cells may be observed.
2. Stained Smear A Gram-stained smear of feces or early culture reveals Gram-negative, slightly curved vibrios.
3. Hanging Drop Test Fresh feces examined under hanging drop or dark-field microscopy show highly motile, darting vibrios.
4. Motility Inhibition Test Take watery stool from an acute-phase patient or the surface growth of an alkaline peptone water enrichment culture after about 6 hours. First, observe motility under dark-field microscopy. If darting motility is observed, add a drop of O1 polyvalent serum. If the vibrios are O1 group *Vibrio cholerae*, they will agglutinate and motility will cease due to antigen-antibody interaction. If motility is not inhibited by O1 serum, repeat the test with O139 serum.
5. Enrichment Culture All suspected cholera patient stool samples should undergo enrichment culture in addition to microscopy. Stool samples should be collected before antibiotic use and delivered to the laboratory as quickly as possible for culture. The enrichment medium is typically alkaline peptone water at pH 8.4, incubated at 36–37°C for 6–8 hours until a bacterial membrane forms on the surface. Further isolation culture, motility observation, and inhibition testing should then be performed to improve detection rates and enable early diagnosis.
6. Isolation Culture Gentamicin agar plates or alkaline agar plates are commonly used. The former is a highly selective medium, where *Vibrio cholerae* forms small colonies after 8–10 hours of incubation at 36–37°C. The latter requires 10–20 hours. Select suspicious or typical colonies and perform a slide agglutination test using *Vibrio cholerae* "O" antigen antiserum. A positive result can be reported. Recently, DNA probes targeting cholera toxin genes have been used abroad for colony hybridization, enabling rapid identification of toxigenic O1 group *Vibrio cholerae*.
7. PCR Testing Recently, PCR technology has been applied abroad for rapid cholera diagnosis. By identifying the cholera toxin gene subunit CtxA and the toxin-coregulated pilus gene (TcpA) in PCR products, cholera strains can be distinguished from non-cholera vibrios. Further differentiation between classical biotype and El Tor biotype *Vibrio cholerae* is based on variations in the TcpA gene DNA sequence. Results can be obtained within 4 hours, reportedly detecting fewer than 10 *Vibrio cholerae* per mL of alkaline peptone water.
8. Differentiation Tests The differentiation between classical biotype, El Tor biotype, and O139 *Vibrio cholerae* is shown in Table 11-25.
Table 11-25 Differentiation of Classical, El Tor, and O139 *Vibrio cholerae*
| Test | Classical | El Tor | O139 |
| Group VI Cholera Phage Lysis Test (106 particles/unit) | + | -(+) | - |
| Group V cholera phage lysis test | - | + | - |
| Polymyxin B sensitivity test | + | -（+） | - |
| Chicken serum agglutination test V-P test | -（+） | +（-） | + |
| V-P test | - | +（-） | + - |
| Sheep red blood cell hemolysis test | - | +（-） | + |
| 0/129 vibrio inhibition test (diaminodipropyl disc sensitivity test) | + | + | - |
| 01group serum agglutination test | + | + | - |
| 0139serum agglutination test | - | - | + |
(1) Diagnostic Criteria: A diagnosis of cholera can be made if any of the following conditions are met.
1. Presence of diarrhea symptoms with a positive stool culture for Vibrio cholerae.
2. During a cholera epidemic, in an affected area, the presence of typical cholera symptoms such as diarrhea and vomiting, rapidly progressing to severe dehydration, circulatory failure, and muscular rigidity. Even if stool culture does not detect Vibrio cholerae, but no other cause is found. If conditions permit, a paired serum agglutinin test can be performed; a fourfold rise in titer confirms the diagnosis.
3. During source investigation, individuals who exhibit diarrhea symptoms within 5 days before a positive stool culture can be diagnosed as mild cholera.
(2) Suspected Diagnosis: A suspected case is defined as follows.
1. The first case presenting with typical cholera symptoms before pathogen confirmation.
2. During a cholera epidemic, individuals with a clear history of contact with cholera patients who develop diarrhea and vomiting symptoms without other identifiable causes.
Suspected cases should be isolated and disinfected, reported as suspected cholera cases, and undergo daily stool cultures. If two consecutive stool cultures are negative, the diagnosis can be ruled out, and a revised report should be issued.
The clinical manifestations of typical cholera can also be caused by non-O1 group Vibrio and enterotoxigenic Escherichia coli (ETEC). In the former, most patients experience diarrhea accompanied by severe abdominal pain and fever; 1/4 of patients have bloody stools. Diarrhea caused by ETEC generally has a shorter course. Differentiation between these and cholera relies on pathogen testing. Cholera should be distinguished from various bacterial food poisonings, such as those caused by Staphylococcus aureus, Proteus, Bacillus cereus, and Vibrio parahaemolyticus. These food poisonings typically have an acute onset, often affecting groups who consumed the same food, with vomiting preceding diarrhea, paroxysmal abdominal pain before defecation, and stools that are usually yellow and watery, occasionally containing pus or blood. If stools resemble meat-wash water or dysentery-like, bacterial dysentery must be ruled out. The latter is often accompanied by abdominal pain and tenesmus, with scanty, pus-and-blood-containing stools. Acute arsenic poisoning primarily manifests as acute gastroenteritis, with stools appearing yellow or grayish-white and watery, often bloody. Severe cases may present with reduced urine output, anuria, or circulatory failure. Diagnosis is confirmed by detecting arsenic in stool or vomitus.
bubble_chart Treatment Measures
Including strict isolation, fluid replacement, antibacterial treatment, and symptomatic management.
(1) Isolation Confirmed and suspected cases should be isolated separately, and their excreta must be thoroughly disinfected. Patients can only be released from isolation after symptoms have resolved and stool cultures have tested negative twice consecutively.
(2) Fluid Replacement
1. Intravenous Fluid Replacement Typically, a 541 solution is chosen, which closely matches the electrolyte concentration lost by the patient. Each liter contains 5g NaCl, 4g NaHCO3, and 1g KCl. To prevent hypoglycemia, 20ml of 50% glucose is often added. To prepare, use 500ml of 0.9% NaCl, 300ml of 1.4% NaHCO3, 10ml of 10% KCl, and 140ml of 10% glucose in the specified ratio.
The electrolyte content of various fluids and the electrolyte levels in patient stool are shown in Table 11-26.
Table 11-26 Electrolyte Content in Replacement Fluids and Comparison with Stool and Plasma Levels (Concentration mmol/L)
| Sodium | Potassium | Chloride | Base (Bicarbonate) | Glucose | Remarks | ||
| 541 Solution | 134 | 13 | 99 | 48 | Each liter contains 5g sodium chloride, 4g sodium bicarbonate*, and 1g potassium chloride | ||
| Diarrhea Treatment Solution | 118 | 13 | 83 | 48 | 44.8 | Each liter contains 8g glucose, 4g sodium chloride, 6.5g sodium acetate, and 1g potassium chloride | |
| Ringer’s Lactate Solution | 131 | 5 | 111 | 29 | This solution also contains 2mmol/L calcium and is used for early rapid fluid replacement | ||
| 2:1 Saline-Alkali Solution | 154 | - | 103 | 51 | Alkali solution can use bicarbonate or lactate | ||
| Oral Rehydration Solution | 93 | 21 | 80 | 30 | 11.2 | Each liter contains 20g glucose, 3.5g sodium chloride, 2.5g sodium bicarbonate, and 1.5g potassium chloride | |
| Patient Stool Composition | Adult | 135 | 15 | 100 | 45 | Daily stool volume ≥50ml/kg | |
| Children | 105 | 25 | 90 | 30 | |||
| Normal plasma content | 136 | 3.8 | 98 | 24 | |||
| ～148 | ～5.0 | ～106 | ～32 | ||||
*Bicarbonate can be replaced with acetate (more stable)
The volume and rate of intravenous fluid infusion depend on the degree of dehydration. The 24-hour fluid replacement volume is determined by the severity of the condition. For grade I dehydration, oral rehydration is the primary method. If vomiting prevents oral intake, intravenous fluid replacement of 3000～4000ml/day should be administered, with an initial rapid rate of 5～10ml/minute in the first 1～2 hours. For grade II dehydration, fluid replacement of 4000～8000ml/day is required, with rapid infusion in the first 1～2 hours until blood pressure and pulse return to normal, then reduced to 5～10ml/minute. For grade III dehydration, daily fluid replacement of 8000～12000ml is needed, administered through two intravenous lines, initially at 40～80ml/minute, then reduced to 20～30ml/minute until shock is corrected, and further adjusted until dehydration is resolved.
In pediatric patients, stool sodium content is lower and potassium content is higher, dehydration is more severe, and the condition progresses more rapidly, making them prone to hypoglycemia, unconsciousness, cerebral edema, and hypokalemia. Therefore, timely correction of dehydration and potassium supplementation are essential. For mild cases, the 24-hour fluid replacement volume is 100～150ml/kg. For moderate and severe cases, intravenous fluid replacement is 150～200ml/kg and 200～250ml/kg, respectively, using 541 solution. Infants may require appropriately increased amounts. In the first 15 minutes, children over 4 years old should receive 20～30ml/minute, while infants should receive 10ml/minute. Based on plasma specific gravity, for every 0.001 increase, infants should receive 10ml/kg of fluid replacement, with 40% of the total volume administered within 30 minutes and the remainder over 3～4 hours.
The rapid correction of metabolic acidosis with alkaline agents is also a critical factor for successful treatment. Sodium bicarbonate can quickly correct acidosis, while lactate and acetate achieve gradual correction within 1～2 hours. Potassium salts should also be supplemented promptly and appropriately, either intravenously or orally. Each 1000ml of intravenous fluid should contain 10～15mEq of potassium chloride. For oral solutions, each 1000ml of water should contain 100g each of potassium acetate, potassium citrate, and potassium bicarbonate. Adults should take 10ml three times daily, while children should receive appropriately reduced doses.
2. Oral Rehydration For cholera patients, sodium chloride solution cannot be absorbed after oral administration, but potassium salts and carbonates can be absorbed. The ability to absorb glucose remains unchanged, and glucose can promote the absorption of sodium chloride and water. Therefore, oral rehydration can be administered to mild and moderate cases, while severe cases should first receive intravenous rehydration. After shock is corrected and the condition improves, oral rehydration can then be adopted. There are many oral rehydration formulations, all of which are largely similar. The rehydration solution is warmed before oral intake or administered via a nasogastric tube. In the first 6 hours, the oral fluid intake for adults is 700ml/hour, and for children, it is 15–25ml/kg per hour. The intake can be appropriately increased if diarrhea is severe. Subsequently, the fluid volume is calculated as 1.5 times the output volume every 6 hours. Vomiting is not a contraindication for oral rehydration, but the vomitus volume should be included in the total fluid calculation. Bicarbonate can be replaced by citrate, which is more stable, less prone to deliquescence, and also has a good acid-correcting effect while promoting sodium ion absorption in the small intestine. Sucrose can also be used as a substitute for glucose with satisfactory therapeutic effects, though the required amount of sucrose is twice that of glucose. Glycine can also enhance the absorption of water and electrolytes and may be added to oral rehydration solutions, with 110mmol of glycine per 1000ml of solution. Patients treated with glycine show significant reductions in stool volume, duration of diarrhea, and oral fluid intake.
(3) Antibacterial Therapy Antibacterial drugs can shorten the course of the disease and reduce the frequency of diarrhea after controlling the pathogens. However, they are only used as adjunctive therapy to fluid therapy. In recent years, tetracycline-resistant strains have been discovered, but they remain sensitive to doxycycline. Currently commonly used drugs: compound formula sulfamethoxazole, each tablet contains trimethoprim (TMP) 80mg, sulfamethoxazole (SMZ) 40mg, adults take 2 tablets each time, twice a day. For children, 30mg/kg, divided into two oral doses. Doxycycline: adults take 200mg each time, twice a day; children take 6mg/kg per day, divided into two oral doses. Norfloxacin: adults take 200mg each time, three times a day; or ciprofloxacin: adults take 250–500mg each time, twice a day orally. Any one of the above drugs can be selected and taken continuously for 3 days. For those who cannot take oral medications, ampicillin can be administered intramuscularly or intravenously.
(4) Symptomatic Treatment
1. Correcting Acidosis In addition to the infusion of 541 solution, severe patients may also require the use of 5% sodium bicarbonate to correct acidosis based on CO2 combining power.
2. Correcting Hypokalemia For patients who develop hypokalemia during fluid replacement, potassium chloride should be administered intravenously, with the concentration generally not exceeding 0.3%. Grade I hypokalemia patients can take oral potassium supplements.
3. Correcting Shock and Heart Failure A few patients may have their blood volume largely restored after fluid replacement, with skin and mucous membrane dehydration symptoms gradually disappearing, but blood pressure may not return to normal. In such cases, dexamethasone 20–40mg or hydrocortisone 100–300mg can be administered intravenously, along with vasoactive drugs such as dopamine and aramine. If heart failure or pulmonary edema occurs, fluid infusion should be paused or slowed, and cedilanid 0.4mg or strophanthin K 0.25mg mixed with 20ml glucose should be administered slowly intravenously. If necessary, furosemide 20–40mg can be administered intravenously, or pethidine 50mg can be administered intramuscularly for sedation.
4. Anti-Enterotoxin Therapy Currently, chlorpromazine is believed to inhibit the adenylate cyclase of small intestine epithelial cells, and clinical application can alleviate diarrhea. It can be administered orally or intramuscularly at 1–2mg/kg. Coptis Rhizome also has inhibitory effects on enterotoxins and antibacterial properties. Adults can take 0.3g each time, three times a day orally. For children, 50mg/kg, divided into three oral doses.
(1) Controlling the source of pestilence: Timely detection of patients and early isolation and treatment. Close contacts should be strictly quarantined, undergo stool examinations, and receive medication. Stool cultures should be conducted once daily for two consecutive days. Administering medication after each stool examination can reduce carriers. Typically, doxycycline 200mg is administered at draught, followed by 100mg orally the next day. For children, 6mg/kg per day for two days is recommended. Norfloxacin can also be used, 200mg each time, three times daily for two days. Additionally, border health quarantine and domestic transportation quarantine should be enforced. Once a patient or suspected case is identified, immediate isolation and treatment should be initiated, and the means of transportation should be thoroughly disinfected.
(2) Cutting off transmission routes: Strengthen water disinfection and food management, and thoroughly disinfect the excreta of patients and carriers. Furthermore, eliminate vectors such as flies.
(3) Enhancing population immunity: In the past, whole-cell killed vaccines or vaccines combined with cholera enterotoxin toxoids were used to immunize populations. However, due to low protection rates, short duration of protection, and inability to prevent latent infections and carriers, their use is no longer recommended. Currently, several vaccines developed through genetic engineering are being tested abroad and are still in expanded trials, including:
1. B subunit-whole cell vaccine (BS-WC): This vaccine consists of inactivated whole-cell Vibrio cholerae (WC) and purified cholera enterotoxin B subunit (BS). The WC cell wall contains antigens such as lipopolysaccharide (LPS) and cholera toxin-coregulated pilus (TCP), which induce the production of antibacterial antibodies, thereby inhibiting the colonization of Vibrio cholerae in the intestines. The antitoxin antibodies produced by BS can neutralize the B subunit of CT, preventing cholera enterotoxin from binding to intestinal mucosal receptors and thus rendering the enterotoxin ineffective. This vaccine has a protection rate of approximately 65–85%, with better preventive effects against classical biotype Vibrio cholerae than El Tor biotype.
2. Attenuated oral live vaccine CVD103-HgR: Developed using DNA recombination technology, 94% of the CtxA gene was removed and recombined into the classical biotype Vibrio cholerae strain 569B, resulting in the attenuated strain CVD103. A mercury-resistant (Hg) coding gene was then introduced into the HlyA chromosomal site, creating the attenuated strain CVD103-HgR. This vaccine significantly protects against infections by O1 group classical and El Tor biotype Vibrio cholerae. Taket et al. reported that volunteers achieved 100% protection after a single dose of 3–5×108 units of CVD103-HgR. Generally, the protective effect lasts at least six months. However, animal studies indicate this vaccine offers no protection against O139 type Vibrio cholerae.
(1) Renal Failure Caused by untreated shock and hypokalemia, manifested as reduced urine output and azotemia. In severe cases, anuria may occur, leading to death from uremia.
(2) Acute Pulmonary Edema Metabolic acidosis can lead to pulmonary hypertension, which is further exacerbated by the administration of large amounts of non-alkaline saline.
(3) Others Hypokalemic syndrome, arrhythmia, and late abortion, among others.
