Cholera: Treatment and prevention

INTRODUCTION — Cholera is a life-threatening diarrheal illness caused by cholera toxin-producing strains of Vibrio cholerae.

Issues related to treatment and prevention of cholera will be reviewed here. Other issues related to cholera are discussed separately. (See "Cholera: Epidemiology, clinical features, and diagnosis".)

TREATMENT

Absence of severe malnutrition — Fluid management is the cornerstone of cholera treatment [1,2]. Administration of appropriate rehydration therapy reduces the mortality of severe cholera from >10 percent to <0.5 percent [1].

Antibiotics are an adjunctive therapy for patients with moderate to severe volume depletion.

Ensuring adequate nutrition is important for all patients; children may also benefit from supplementation of certain micronutrients.

Fluid management — Fluid management is guided by assessment of volume depletion and ongoing fluid losses.

Assessment of fluid loss — Volume status may be determined by assessment of the mental status, eyes, mouth, and skin (table 1). Based on physical findings, the degree of volume depletion can be categorized by World Health Organization (WHO) criteria as no dehydration (<5 percent of body weight), some dehydration (5 to 10 percent of body weight), or severe dehydration (>10 percent of body weight).

Cholera cots are useful for estimating stool volume losses (picture 1); if these are not available, ongoing losses may be estimated at 10 to 20 mL/kg of body weight for each episode of diarrhea or vomiting.

Fluid resuscitation — The type and quantity of fluids to administer is determined by the level of volume depletion (table 1) and an assessment of ongoing fluid losses (algorithm 1).

The most common error in caring for patients with cholera is underestimating the amount of fluid needed to correct volume depletion and replace ongoing losses. Patients with cholera typically present with more severe volume depletion, have more rapid fluid losses (typically 10 to 20 mL/kg/hour), and have proportionally greater stool electrolyte losses than patients with non-cholera gastroenteritis [3,4].

Issues related to fluid repletion for adults and children with acute diarrhea are discussed further separately. (See "Approach to the adult with acute diarrhea in resource-limited settings", section on 'Rehydration' and "Approach to the child with acute diarrhea in resource-limited settings", section on 'Fluid and electrolytes'.)

●No dehydration (<5 percent) or some dehydration (5 to 10 percent)

•Clinical approach – Use of oral rehydration solution (ORS):

-For patients with no dehydration, ORS should be administered to replace ongoing losses (table 2 and algorithm 1).

-For patients with some dehydration, ORS should be administered to correct the fluid deficit (table 3), then continued for replacement of ongoing losses (table 2 and algorithm 1).

ORS is as effective as and more practical than intravenous fluid repletion in this setting (see "Oral rehydration therapy", section on 'Efficacy').

Indications for intravenous hydration include:

-Patients with profound vomiting (more than three times in one hour) or ongoing stool losses; in such cases, administration of intravenous therapy in conjunction with ORS may be warranted to prevent progression to severe dehydration.

-Patients who are unable to drink because of vomiting or altered mental status.

•ORS formulation – Types of ORS are summarized in the table (table 2).

The WHO recommended use of a reduced osmolar glucose-based ORS in 2002; other formulations include a rice-based formulation (using rice powder rather than glucose) or home-made ORS (using sugar, salt, and clean water).

Use of the WHO 2002 formulation has been shown to reduce stool output, vomiting, and the need for supplemental intravenous fluids [5]. Among patients with cholera, subclinical hyponatremia is common with this ORS formulation, but rates of symptomatic hyponatremia do not appear to be significantly increased [6].

Rice-based ORS has been demonstrated to reduce the duration of diarrhea and stool losses in severe cholera; however, it is more complex to prepare [7].

Additional details related to ORS are discussed further separately. (See "Oral rehydration therapy", section on 'Commercial and standard oral rehydration solutions'.)

●Severe dehydration (>10 percent) – For patients with severe dehydration, intravenous fluids should be administered urgently (algorithm 1).

•Fluid quantity – For patients ≥1 year of age without severe malnutrition, a fluid volume of 100 mL/kg should be administered over three hours; an initial volume of 30 mL/kg should be given over the first 30 minutes.

For patients <1 year of age without severe malnutrition, a fluid volume of 100 mL/kg should be administered over six hours; an initial volume of 30 mL/kg should be given over the first 30 minutes.

In the first 24 hours of treatment, patients with severe cholera typically require an average of 200 mL/kg of isotonic oral or intravenous fluids and may require more than 350 mL/kg [2].

Issues related to fluid management for children with severe dehydration in the setting of severe malnutrition are discussed separately. (See "Management of complicated severe acute malnutrition in children in resource-limited settings".)

•Fluid formulation – Intravenous Ringer's lactate is the best commercially available intravenous solution for rehydration of patients with severe dehydration due to cholera, since it includes potassium and sodium bicarbonate — both of which are lost in cholera stools (table 2).

Locally prepared solutions, such as "Dhaka solution" (which contains glucose and more potassium than Ringer's lactate), are available in some cholera-endemic regions; such preparations may mitigate potential complications including hypokalemia, hypoglycemia, and metabolic acidosis.

●Access to rehydration therapy – Access to appropriate rehydration therapy is an important obstacle, particularly during cholera epidemics. For this reason, a community-based response and strategic use of decentralized treatment centers (ie, oral rehydration points) to improve access to treatment are crucial to successful management of cholera outbreaks [8].

Continued monitoring — Volume status should be assessed via physical exam on an ongoing basis (table 1), and the rate of fluid repletion should be adjusted if needed.

Once the fluid volume to replace the estimated initial deficit has been administered, patients should be managed based on the estimated degree of residual volume depletion from ongoing losses. In general, children ≤2 years of age should receive 50 to 100 mL of fluid for each episode of diarrhea or vomiting; children >2 years of age should receive 100 to 200 mL of fluid for each episode. For adults, stool output may be estimated at 10 to 20 mL/kg. Stool output may also be measured by collecting stool using a cholera cot.

In patients treated with proper rehydration, diarrhea is most severe during the first two days and resolves after four to six days [9-11].

Antibiotic therapy

●Use and rationale – Antibiotics are warranted for patients with cholera and moderate to severe dehydration. In such patients, antibiotic therapy can shorten the duration of diarrhea to 48 hours, reduce the volume of stool losses by up to 50 percent, and shorten the duration of stool shedding of V. cholerae from 5 days to 1 or 2 days [12,13]. However, antibiotic therapy has not been demonstrated to control cholera outbreaks [14].

●Clinical approach – Antibiotics may be administered as soon as the patient is able to take oral medications. Antibiotic options include macrolides, fluoroquinolones, and tetracyclines (table 4); selection should be based on availability and local resistance patterns.  

●Drug efficacy and drug resistance

•Tetracyclines – Tetracyclines are the antibiotic class for which there is greatest clinical experience for treatment of cholera infection [12]. In a randomized trial including 246 patients in Bangladesh with severe dehydration and tetracycline-susceptible V. cholerae, the efficacy of doxycycline (single 300 mg dose) and tetracycline (500 mg every 6 hours for 2 days) were comparable with respect to stool output, duration of diarrhea, vomiting, and requirement for ORS [15].

However, resistance to tetracycline and doxycycline is common [16-18]; empiric use of these agents should be limited to settings where ongoing surveillance indicates that most strains are susceptible to this antibiotic class. In regions where tetracycline resistance is common, fluoroquinolones and macrolides are alternative agents; however, fluoroquinolone resistance has also become common in endemic areas [19].

•Fluoroquinolones – Fluroquinolone efficacy is comparable to or greater than tetracycline efficacy for treatment of cholera infection [20-22]. In one randomized trial including 260 adults with V. cholerae O1 or O139 infection in Bangladesh, ciprofloxacin (1000 mg single dose) was effective against both strains, and superior to doxycycline (300 mg single dose) in eradicating organisms from stool [21].

However, decreased fluoroquinolone susceptibility has emerged with increasing use of ciprofloxacin to treat cholera [23,24]. For treatment of patients with cholera due to isolates with decreased fluoroquinolone susceptibility (identified by resistance to nalidixic acid), administration of a three-day regimen has been associated with higher rates of clinical and bacteriologic response than a single-dose regimen [25]. Such nalidixic acid resistant strains remain common among the current pandemic circulating lineage of V. cholerae [26,27].

•Macrolides – Macrolides are also effective for treatment of cholera [23,24,28-30]. In a trial including 128 children with cholera in India, the clinical and bacteriologic efficacy of azithromycin (20 mg/kg single dose) and erythromycin (12.5 mg/kg every six hours for three days) were similar; azithromycin was associated with less vomiting [30].

Some trials have demonstrated greater efficacy with macrolides compared with fluoroquinolones, perhaps because of decreased susceptibility of V. cholerae strains to fluoroquinolones. As an example, in a randomized trial including 195 adults with severe cholera in Bangladesh, azithromycin (1 gram single dose) was superior to ciprofloxacin (1 gram single dose) with regards to clinical efficacy (73 versus 27 percent ceased to have watery stool at 48 hours) and bacteriologic efficacy (78 versus 10 percent eradication of V. cholerae from stools at 48 hours) [24].

Rarely, V. cholerae O1 strains with macrolide resistance have been reported [31].

Most V. cholerae O139 strains and many O1 El Tor strains are resistant to trimethoprim-sulfamethoxazole and furazolidone [18].

Nutrition, vitamins, and minerals

●Nutrition – Eating should resume as soon as possible after the initial fluid deficit is corrected, and breastfeeding of infants should be encouraged in conjunction with oral rehydration solution. Sufficient feeding should be encouraged to prevent malnutrition and facilitate recovery of normal gastrointestinal function [2].

Children with severe malnutrition require an individualized approach to nutritional repletion; this is discussed further separately. (See "Management of complicated severe acute malnutrition in children in resource-limited settings".)

●Vitamins and minerals – Among children with acute diarrhea, zinc and vitamin A supplementation are also important interventions. Zinc supplementation reduces the duration and volume of stool in children with cholera [32]. This is discussed separately. (See "Approach to the child with acute diarrhea in resource-limited settings", section on 'Vitamins and minerals'.)

Presence of severe malnutrition — Children with acute diarrhea and severe malnutrition require an individualized approach to rehydration and nutritional repletion. These issues are discussed further separately. (See "Management of complicated severe acute malnutrition in children in resource-limited settings" and "Persistent diarrhea in children in resource-limited settings".)

Outcomes — Mortality in untreated patients may reach 50 to 70 percent in severe cholera [16,33]. Administration of appropriate rehydration therapy can reduce the mortality of severe cholera to <0.5 percent [34]. In endemic areas, the risk of mortality risk is highest in children (10 times greater than in adults) [35,36].

Early studies suggested a high risk of fetal death associated with cholera during pregnancy (up to 50 percent during the third trimester); subsequent studies have reported a risk of approximately 8 percent [37,38].

PREVENTING TRANSMISSION

●In endemic areas – Cornerstones of cholera prevention include access to safely managed water and appropriate sanitation. In resource-limited settings, these can be difficult to achieve; worldwide, more than 1 in 4 people lack access to safely managed water and 2 out of 5 lack access to safely managed home sanitation [39,40]. Universal safe water and sanitation are urgently needed in many areas of the world.

Smaller-scale interventions to reduce cholera risk include point-of-use water treatment, safe storage of water systems using simple vessels with lids and taps, provision of sanitation facilities (including latrines and flush toilets), and behavior change campaigns targeted at increasing handwashing [1].

Breastfeeding of young infants is protective against cholera and other enteric infections (see "Infant benefits of breastfeeding", section on 'Prevention of illnesses while breastfeeding').

●For travelers – Travelers to regions where cholera is endemic should follow the general precautions for the prevention of travelers' diarrhea [41]. This includes avoidance of tap water, food from street vendors, raw or undercooked seafood, and raw vegetables [42]. Water can be treated with chlorine or iodine, by filtration, or by boiling [43]. (See "Travel advice", section on 'Food and water'.)

VACCINATION

Human immunity

●Immunity following natural infection – V. cholerae O1 infection results in immunity against reinfection and disease [44,45]. In one cohort including more than 4600 patients with cholera detected in Bangladesh between 1991 and 2000, natural infection resulted in 65 percent protection (95% CI, 37-81) relative to age-matched controls over three-year follow-up [45].

●Antibody response – The mechanisms mediating mucosal immunity against V. cholerae are not well understood. The major targets of the human antibody response to V. cholerae O1 consist of the O-specific polysaccharide and cholera toxin [46]. Antibodies that target the O1-specific polysaccharide are likely critical for protection [47]; however, antibodies to cholera toxin appear to play a limited role in protection, since immunization with inactivated cholera toxin provides only short-term immunity [48].

●Correlates of protection – There are no well-established correlates of protection for cholera. Correlates of protection are immunologic markers (following infection or vaccination) associated with a decreased risk of subsequent infection; they can be used to evaluate early vaccine candidates or as proxy measurements of vaccine efficacy in clinical trials.

Vibriocidal antibody titers are imperfect correlates of protection for cholera but have been used as a proxy for efficacy for cholera vaccine-induced protection [49,50]. A combination of several immunologic markers may serve as a better correlation of protection than the vibriocidal antibody [51]; however, thus far such a correlate has not been used to support cholera vaccine approval.

Vaccine formulations and efficacy — The first parenteral whole-cell cholera vaccines were developed shortly after V. cholerae was isolated by Robert Koch in 1883 [52]. The efficacy of these vaccines was approximately 80 percent [53], but they were associated with significant reactogenicity. They fell from favor after clinical trials in Bangladesh in the 1960s demonstrated only short-lived protection [54].

Available vaccines — Available cholera vaccines are summarized in the table.

Inactivated oral cholera vaccines — Inactivated oral cholera vaccines include bivalent killed whole-cell vaccines (WC) and a killed whole cell vaccine with a recombinant B subunit (WC-rBS).

In a meta-analysis (table 5) including seven clinical trials and six observational studies evaluating these vaccines, the average effectiveness of a two-dose series was 76 percent; however, among children <5 years of age the average efficacy was 30 percent [55].

Bivalent WC

●Formulation – Bivalent WC vaccines contain killed whole cells of several biotypes and serotypes of V. cholerae O1 and V. cholerae O139 without supplemental cholera toxin B subunit. They are formulated with heat- and formalin-inactivated V. cholerae strains, including a combination of the O1 Inaba and O1 Ogawa serotypes derived from the Classical and El Tor biotypes, and the now-rare V. cholerae O139 serogroup. There are four available formulations (table 5).

●Use – Two bivalent WC formulations are included in the global stockpile; a third is approved and licensed in Bangladesh, and a fourth is approved and licensed in Vietnam (table 5).

●Efficacy

•Two-dose series – In a meta-analysis including seven clinical trials and six observational studies evaluating the WC-rBS and bivalent WC, the average effectiveness of a two-dose series was 76 percent (95% CI, 62-85); however, among children <5 years of age the average efficacy was 30 percent (95% CI, 15-42) [55].

In randomized trials, the efficacy of bivalent WC has ranged from 53 to 67 percent, with protection persisting for five years among adults but shorter durability among children ≤5 years of age (42 percent at five years) [56-59].

•A single dose confers some benefit – For situations in which the two-dose series cannot be given, a single dose provides some protection for older children and adults. In a randomized trial evaluating Shanchol (single dose), adjusted six-month efficacy was 40 and 63 percent for all and severely dehydrating cholera, respectively, and protection was sustained over at least two years [58,60]. However, there was no evidence of protection in children under five years of age.

•Herd immunity – Use of bivalent WC vaccine confers herd protection. In a cluster-randomized trial in India, more than 66,000 individuals were randomly assigned to receive cholera vaccine or placebo; among placebo recipients, the risk of cholera was inversely related to neighborhood-level vaccine coverage [61].

•Control of outbreak and epidemic cholera – Vaccination with bivalent WC vaccine shortly after the onset of a cholera outbreak provides some protection within the first several months following administration. In a case-control study following a cholera outbreak in Guinea, two doses of Shanchol were associated with an adjusted vaccine effectiveness of 87 percent [62]. In a case-control study in Haiti, a two-dose series was associated with effectiveness of 76 percent over a four-year period; however, for those who received a single dose, effectiveness declined from 79 percent in the first year to no detectable effectiveness by two years after vaccination [63].

WC-rBS

●Formulation – WC-rBS (Dukoral) contains killed whole cells of several biotypes and serotypes of V. cholerae O1 in addition to recombinant cholera toxin B subunit (the nonenzymatically active portion of cholera toxin which binds to the cell surface receptor). This vaccine is not effective against V. cholerae O139.

●Use – WC-rBS is used primarily for travelers from Canada or Europe to areas of active cholera transmission. It is recommended for individuals ≥2 years of age (table 5). Revaccination is recommended for ongoing exposure. (See "Immunizations for travel", section on 'Indications'.)

Production of WC-rBS is more expensive than production of bivalent WC vaccines (which do not include the recombinant cholera toxin B subunit) (see 'Bivalent WC' above).

●Efficacy

•Two-dose series – In a meta-analysis including seven clinical trials and six observational studies evaluating the WC-rBS and bivalent WC, the average effectiveness of a two-dose series was 76 percent (95% CI, 62- 85); however, among children <5 years of age the average efficacy was 30 percent (95% CI, 15-42) [55].

The precursor to WC-rBS was evaluated in a randomized trial in Bangladesh including more than 62,000 participants randomly assigned to receive B subunit-killed whole cell vaccine (BS-WC), killed whole cell-only vaccine (WC), or placebo (inactivated non-toxigenic Escherichia coli vaccine) [64]. Over a five-year follow-up period, the WC and BS-WC vaccines were associated with protective efficacy of 47 percent and 49 percent, respectively, compared with placebo [64]. Protection waned more rapidly among children <5 years of age who were not protected after two years of follow-up [65].

•Herd immunity – Use of WC-rBS confers herd immunity; among unvaccinated individuals in areas of Bangladesh where local vaccine coverage exceeded 50 percent, a fivefold reduction in the risk of cholera was observed compared with unvaccinated individuals in lower vaccine coverage areas (7 versus 1.47 cases per 1000) [66].

•Outbreak control – The efficacy of WC-rBS has also been evaluated in outbreak settings in Mozambique and Zanzibar [67,68]. In both studies, oral cholera vaccination was undertaken prior to the outbreak, and in both studies, receipt of one or more doses of vaccine was associated with 78 percent protection. Vaccination was equally effective in children ≤5 years and in older individuals [67]. Protection declined rapidly among young children after six months but remained as high as 60 percent in older recipients for two to three years.

Live attenuated oral cholera vaccine

CVD 103-HgR

●Formulation – CVD 103-HgR (Vaxchora) was derived from a Classical O1 Inaba strain by deletion of the active cholera toxin A subunit.

●Use – Issues related to use of CVD 103-HgR are discussed below. (See 'For travelers to high-risk areas' below.)

●Efficacy – In a clinical trial including 197 healthy adult volunteers randomly assigned to receive an oral dose of CVD 103-HgR vaccine or placebo, followed by oral challenge with a V. cholerae O1 strain (10 days after vaccine), diarrhea occurred less frequently among vaccine recipients (5.7 versus 59.1 percent; vaccine efficacy 90 percent) [69]. The vaccine was well tolerated without increased rates of diarrhea, other gastrointestinal complaints, or fever.

CVD 103-HgR was approved for children based on immunogenicity bridging studies; these suggest a similar safety and immunogenicity profile in children [70-73].

Few studies of CVD 103-HgR have been conducted in areas in which cholera is endemic. CVD 103-HgR was evaluated in the 1990s in Indonesia among more than 67,000 individuals age 2 to 41 years of age randomly assigned to receive vaccine or placebo [74]. At four-year follow-up, the efficacy was 14 percent; however, a lower-than-expected incidence of infection was observed [75].

Vaccines in development — Vaccines in development include:

●Hillchol – Hillchol is an inactivated whole-cell vaccine consisting of a formaldehyde-inactivated recombinant V. cholerae strain engineered to expresses the Inaba and Ogawa antigens. Use of a single formaldehyde-inactivated strain is expected to simplify manufacturing and production. Phase I/II studies were reported in 2021 [76].

●Cholera conjugate vaccine – Cholera conjugate vaccine consists of the V. cholerae O1-Inaba specific polysaccharide linked to a recombinant tetanus toxoid heavy chain fragment-carrier protein; this approach may overcome the limited immunogenicity of current vaccines in young children. Scalable production was described in 2021 [77].

●PanChol – PanChol is a live attenuated vaccine engineered from a 2010 V. cholerae O1 isolate from Haiti; in an animal model, it induced protection within days of vaccination [78].

Use of vaccines for cholera control — Cholera occurs primarily in settings where there is inadequate access to clean water and sanitation; this includes endemic infection (which typically occurs among young children) as well as outbreak or epidemic settings (which often occur in the setting of natural or humanitarian disasters, among adults as well as children). (See "Cholera: Epidemiology, clinical features, and diagnosis", section on 'Epidemiology'.)

●Available vaccines – Two bivalent WC vaccines, Shanchol and Euvichol-Plus, are used in outbreaks and cholera-endemic countries [1]. Production of Shanchol ceased in 2023. Euvichol has been replaced with Euvichol-Plus, which is packed in plastic containers to facilitate administration by squirting vaccine directly into the mouth. (See 'Bivalent WC' above.)

●Control of endemic cholera – Expanding vaccine use for control of endemic cholera is a core component of the World Health Organization (WHO) effort to reduce the global mortality due to cholera by 90 percent between 2017 and 2030 [79]. However, ongoing shortages in the global supply of oral cholera vaccines have limited access to vaccines for this purpose [80].

●Control of outbreak and epidemic cholera – Forms of vaccination campaigns for outbreak or epidemic control include preventive and reactive:

•Preventive campaigns – The goal of a preventive vaccination campaign is to avert a cholera outbreak in a high-risk setting. As an example, a vaccination campaign conducted among Rohingya refugees and the surrounding Cox's Bazar district in Bangladesh effectively averted cholera [81,82].

•Reactive campaigns – The goal of a reactive campaign is to limit spread in the context of an ongoing outbreak or epidemic. After introduction of cholera in Haiti in 2010, a reactive vaccination campaign was credited with reducing cholera transmission in Haiti to the point where it was considered eradicated; no cases of cholera occurred between 2019 and early 2022 [83].

Cholera reemerged in Haiti in fall 2022. Based on molecular genomic evidence, reemergence was caused by a direct descendant of the same V. cholerae strain that was introduced in 2010 [84], suggesting that the pathogen may be sustained for prolonged periods by in environmental reservoirs or via transmission episodes which evade detection.

Vaccination following onset of an epidemic is effective in reducing the risk of cholera [62]. A single dose of bivalent WC provides some protection and can be used in the setting of a vaccine shortage or if a second dose is not feasible or during a vaccine shortage [85].

Countries can apply to the global stockpile for preventive or reactive vaccine campaigns; however, demand still outstrips supply.

●Vaccine availability – Vaccine shortages are a limiting factor in cholera control efforts; vaccine production must be increased, including manufacturing in endemic countries [86].

A global cholera vaccine stockpile of bivalent WC was started in 2013; use of this vaccine supply is intended for cholera control in outbreaks, humanitarian crises, and settings with endemic cholera. The stockpile is funded by Gavi, the Vaccine Alliance; emergency deployment from the stockpile is coordinated by an International Coordinating Group (ICG) with WHO serving as the secretariat. Between 2013 and 2017, nearly 17 million vaccine doses were shipped to 18 countries [81].

In 2022, Gavi and the ICG approved production of more than 36 million cholera vaccine doses for preventive and reactive cholera vaccine campaigns; however, only 25.5 million vaccine doses were produced [87]. As a result, in October 2022, the ICG decided to limit all approved reactive oral cholera vaccine campaigns to a single dose, while other pending vaccination campaigns were halted due to an insufficient vaccine supply [88].

For travelers to high-risk areas

●Indications – The United States Centers for Disease Control and Prevention (CDC) recommends vaccination for prevention of cholera in patients age 2 to 64 years of age traveling to an area of active cholera transmission who are at immediate risk of epidemic cholera [70]. An area of active cholera transmission is defined as a region with endemic or epidemic cholera caused by toxigenic V. cholerae O1 and includes areas with cholera activity within the last year that are prone to recurrence of cholera epidemics; it does not include areas where only rare imported or sporadic cases have been reported.

Most people do not travel to areas of active cholera transmission, and most travelers are at extremely low risk for cholera infection. Groups that most warrant vaccination include aid, refugee, and health care workers in endemic and epidemic areas in proximity to displaced populations, especially in crowded camps and urban areas with unsanitary conditions. (See "Immunizations for travel", section on 'Indications'.)

●United States – In the United States, a live attenuated cholera vaccine CVD 103-HgR (Vaxchora) that prevents cholera caused by serotype O1 is available for travelers age 2 to 64 years of age who are at high risk of exposure (table 5) [70]. In 2016, the vaccine was approved by the US Food and Drug Administration (FDA) and recommended by the Advisory Committee on Immunization Practices (ACIP) for adults age 18 to 64; in 2022, the vaccine was further approved by the FDA and recommended by the ACIP to include children and adolescents age 2 to 17 years of age [70]. (See 'CVD 103-HgR' above.)

●Canada and Europe – In Canada and European countries, WC-rBS (Dukoral) is available for prevention of cholera caused by serotype O1 in travelers. (See 'WC-rBS' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute diarrhea in adults" and "Society guideline links: Travel medicine".)

SUMMARY AND RECOMMENDATIONS

●General principles – Cholera is a life-threatening diarrheal illness caused by cholera toxin-producing strains of Vibrio cholerae.

●Management in absence of severe malnutrition (See 'Absence of severe malnutrition' above.)

•Fluid management – Fluid management is the cornerstone of cholera treatment (algorithm 1). The type and quantity of fluids to administer is determined by the level of volume depletion (table 1) and assessment of ongoing losses. (See 'Fluid management' above.)

-For patients with no dehydration, oral rehydration solution (ORS) should be administered to replace ongoing losses (table 2 and algorithm 1).

-For patients with some dehydration, ORS should be administered to correct the fluid deficit (table 2 and table 3), then continued for replacement of ongoing losses (algorithm 1).

-For patients with severe dehydration, intravenous fluids should be administered urgently (algorithm 1).

•Role of antibiotic therapy

-For patients with cholera and moderate to severe dehydration (≥5 percent), we recommend antibiotic therapy (Grade 1B). Individuals with <5 percent dehydration do not require antibiotic therapy.

-Antibiotics may be administered as soon as the patient is able to take oral medications. Antibiotic options include macrolides, fluoroquinolones, and tetracyclines (table 4); selection should be based on availability and local resistance patterns. (See 'Antibiotic therapy' above.)

•Nutrition, vitamins, and minerals – Sufficient feeding should be encouraged. Among children with acute diarrhea, zinc and vitamin A supplementation are also important interventions; this is discussed separately. (See "Approach to the child with acute diarrhea in resource-limited settings", section on 'Vitamins and minerals'.)

●Management in presence of severe malnutrition – Management of children with acute diarrhea and severe malnutrition is discussed further separately. (See "Management of complicated severe acute malnutrition in children in resource-limited settings", section on 'Dehydration' and "Persistent diarrhea in children in resource-limited settings", section on 'Rehydration'.)

●Prevention

•Preventing transmission – Cornerstones of cholera control include access to safely managed water and appropriate sanitation. (See 'Preventing transmission' above.)

•Vaccination

-Available vaccines – Available vaccines are summarized in the table (table 5). They include inactivated (Bivalent killed whole cell-only vaccine [WC], killed whole cell vaccine with a recombinant B subunit [WC-rBS]) and live attenuated (CVD 103-HgR) oral formulations. (See 'Available vaccines' above.)

-Cholera control – In endemic areas, two bivalent WC vaccines are used for control of endemic and outbreak/epidemic cholera. Vaccine shortages are a limiting factor in cholera control efforts. Decisions regarding vaccine implementation should be guided by local public health officials, based in part on vaccine availability. (See 'Use of vaccines for cholera control' above.)