Cholera Treatment & Management

Updated: Jun 22, 2017
  • Author: Sajeev Handa, MBBCh, BAO, LRCSI, LRCPI; Chief Editor: Russell W Steele, MD  more...
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Treatment

Approach Considerations

Rehydration is the first priority in the treatment of cholera. Rehydration is accomplished in 2 phases: rehydration and maintenance.

The goal of the rehydration phase is to restore normal hydration status, which should take no more than 4 hours. Set the rate of intravenous infusion in severely dehydrated patients at 50-100 mL/kg/hr. Lactated Ringer solution is preferred over isotonic sodium chloride solution because saline does not correct metabolic acidosis

The goal of the maintenance phase is to maintain normal hydration status by replacing ongoing losses. The oral route is preferred, and the use of oral rehydration solution (ORS) at a rate of 500-1000 mL/hr is recommended.

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Treatment Guidelines

The World Health Organization (WHO) guidelines for the management of cholera are practical, easily understood, and readily applied in clinical practice (see Table 7). These guidelines can be used for the treatment of any patient with diarrhea and dehydration. Diagnosis of cholera is not required to initiate hydration therapy.

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Cholera Cots

In areas where cholera is endemic, cholera cots have been used to assess the volume of ongoing stool losses. A cholera cot is a cot covered by a plastic sheet with a hole in the center to allow the stool to collect in a calibrated bucket underneath.

Use of such a cot allows minimally trained health workers to calculate fluid losses and replacement needs. The volume of stool is measured every 2-4 hours, and the volume of fluid administered is adjusted accordingly.

In the initial phase of therapy, urine losses account for only a small proportion of fluid losses, and the amount of fluid in the bucket is an adequate reflection of stool losses. With rehydration, urine should be collected separately, so that a vicious circle of increasing urine output and overhydration can be avoided.

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Rehydration

The WHO has provided recommendations for fluid replacement in patients with dehydration [16] (see Table 2). The recommendations include recommendations for fluid replacement for severe hydration, some dehydration, and no dehydration.

Severe dehydration

Administer intravenous (IV) fluid immediately to replace fluid deficit. Use lactated Ringer solution or, if that is not available, isotonic sodium chloride solution. If the patient can drink, begin giving oral rehydration salt solution (ORS) by mouth while the drip is being set up; ORS can provide the potassium, bicarbonate, and glucose that saline solution lacks.

For patients older than 1 year, give 100 mL/kg IV in 3 hours—30 mL/kg as rapidly as possible (within 30 min) then 70 mL/kg in the next 2 hours. For patients younger than 1 year, administer 100 mL/kg IV in 6 hours—30 mL/kg in the first hour then 70 mL/kg in the next 5 hours.

Monitor the patient frequently. After the initial 30 mL/kg has been administered, the radial pulse should be strong and blood pressure should be normal. If the pulse is not yet strong, continue to give IV fluid rapidly. Administer ORS solution (about 5 mL/kg/h) as soon as the patient can drink, in addition to IV fluid.

Reassess the hydration status after 3 hours (infants after 6 h), using Table 1. In the rare case that the patient still exhibits signs of severe dehydration, repeat the IV therapy already given. If signs of some dehydration are present, continue as indicated below for some dehydration. If no signs of dehydration exist, maintain hydration by replacing ongoing fluid losses.

Routes for parenteral rehydration

Accessing a peripheral vein is relatively easy, despite the severe dehydration. If a peripheral vein is not readily accessible, scalp veins have been used for initial rehydration. As the vascular volume is reestablished, a larger needle or catheter can be introduced in a peripheral vein.

Intraosseous routes have been used successfully in young children when veins cannot be accessed. The intraperitoneal route has been tried, but is not recommended.

ORS solution can be administered via nasogastric tube if the patient has some signs of dehydration and cannot drink or if the patient has severe dehydration and IV therapy is not possible at the treatment facility.

Overhydration

A risk of overhydration exists with intravenous fluids; it usually first manifests as puffiness around the eyes. Continued excessive administration of intravenous fluids can lead to pulmonary edema and has been observed even in children with normal cardiovascular reserve. Thus, it is important to monitor patients who are receiving intravenous rehydration hourly. Serum-specific gravity is an additional measure of the adequacy of rehydration.

Some dehydration

Administer ORS solution according to the amount recommended in Table 3. WHO ORS contains the following:

  • Sodium – 75 mmol/L
  • Chloride – 65 mmol/L
  • Potassium – 20 mmol/L
  • Bicarbonate – 30 mmol/L
  • Glucose – 111 mmol/L

A homemade equivalent is 6 teaspoons of sugar and one half teaspoon of salt in a liter of water; a half cup of orange juice or some mashed banana can provide potassium. [17]

Use the patient's age only when weight is unknown. The approximate amount of ORS required (in mL) also can be calculated by multiplying the patient's weight (in kg) times 75.

If the patient passes watery stools or wants more ORS solution than shown, give more. Monitor the patient frequently to ensure that the ORS solution is taken satisfactorily and to identify patients with profuse ongoing diarrhea who require closer monitoring.

Reassess the patient after 4 hours, using Table 1. In the rare case where signs of severe dehydration have appeared, rehydrate for severe dehydration, as above. If some dehydration is still present, repeat the procedures for some dehydration and start to offer food and other fluids. If no signs of dehydration are present, maintain hydration by replacing ongoing fluid losses.

Most patients absorb enough ORS solution to achieve rehydration, even when they are vomiting. Vomiting usually subsides within 2-3 hours, as rehydration is achieved.

Urine output decreases as dehydration develops and may cease. It usually resumes within 6-8 hours after starting rehydration. Regular urinary output (ie, every 3-4 h) is a good sign that enough fluid is being given.

No signs of dehydration

Patients who have no signs of dehydration when first observed can be treated at home. Give these patients ORS packets to take home, enough for 2 days. Demonstrate how to prepare and give the solution. The caretaker should give the patient the amount of ORS solution shown in Table 4.

Instruct the patient or the caretaker to return if any of the following signs develop:

  • Increased number of watery stools
  • Eating or drinking poorly
  • Marked thirst
  • Repeated vomiting
  • Any signs indicating other problems (eg, fever, blood in stool)
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Maintenance of Hydration

Maintain hydration of patients presenting with severe or some dehydration. Replace ongoing fluid losses until diarrhea stops.

When a patient who has been rehydrated with IV fluid or ORS solution is reassessed and has no signs of dehydration, continue to administer ORS solution to maintain normal hydration. The aim is to replace stool losses as they occur with an equivalent amount of ORS solution. See Table 5 .

The amount of ORS solution required to maintain hydration varies greatly among patients, depending on the volume of stool passed. It is highest in the first 24 hours of treatment and is especially large in patients who present with severe dehydration. In the first 24 hours, the average requirement of ORS solution in such patients is 200 mL/kg, but some patients may need as much as 350 mL/kg.

Continue to reassess the patient for signs of dehydration at least every 4 hours to ensure that enough ORS solution is being taken. Patients with profuse ongoing diarrhea require more frequent monitoring. If signs of some dehydration are detected, the patient should be rehydrated as described earlier, before continuing with treatment to maintain hydration.

A few patients, whose ongoing stool output is very large, may have difficulty in drinking the volume of ORS needed to maintain hydration. If these patients become tired, vomit frequently, or develop abdominal distension, ORS solution should be stopped and hydration should be maintained intravenously with lactated Ringer solution or isotonic sodium chloride solution, administering 50 mL/kg in 3 hours. After this is done, resuming treatment with ORS solution is usually possible.

Keep the patient under observation, if possible, until diarrhea stops or is infrequent and of small volume. This is especially important for any patient presenting with severe dehydration. If a patient must be discharged from the hospital before diarrhea has stopped, show the caretaker how to prepare and give ORS solution, and instruct the caretaker to continue to give ORS solution, as above. Also instruct the caretaker to return the patient to the hospital if any signs of danger appear.

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Antibiotic Treatment

An effective antibiotic can reduce the volume of diarrhea in patients with severe cholera and shorten the period during which V cholerae O1 is excreted. In addition, it usually stops the diarrhea within 48 hours, thus shortening the period of hospitalization. Whenever possible, antibiotic therapy should be guided by susceptibility reports.

Antibiotic treatment is indicated for severely dehydrated patients who are older than 2 years. Begin antibiotic therapy after the patient has been rehydrated (usually in 4-6 h) and vomiting has stopped. No advantage exists to using injectable antibiotics, which are expensive. No other drugs should be used in the treatment of cholera. Antimicrobial agents typically are administered for 3-5 days (see Table 6). However, single-dose therapy with tetracycline, doxycycline, furazolidone, or ciprofloxacin has been shown effective in reducing the duration and volume of diarrhea. Because single dose doxycycline has been shown to be as effective as multiple doses of tetracycline, this has become the preferred regimen.

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Fluid Replacement for Dehydration

Table 2. Fluid Replacement for Dehydration (Open Table in a new window)

Severe dehydration Intravenous (IV) drips of Ringer Lactate or, if not available, normal saline and oral rehydration salts as outlined below
  • 100 mL/kg in 3-h period (in 6 h for children < 1 y)
  • Start rapidly (30 mL/kg within 30 min, then slow down)
  • Total amount for first 24 h: 200 mL/kg
Some dehydration Oral rehydration salts (amount in first 4 h)
  • Infants < 4 mo (< 5 kg): 200–400 mL
  • Infants 4–11 mo (5–7.9 kg): 400–600 mL
  • Children 1–2 y (8–10.9 kg): 600–800 mL
  • Children 2–4 y (11–15.9 kg): 800–1200 mL
  • Children 5–14 y (16–29.9 kg): 1200–2200 mL
  • Patients >14 y (≥30 kg): 2200–4000 mL
No dehydration Oral rehydration salts
  • Children < 2 y: 50–100 mL, up to 500 mL/day
  • Children 2–9 y: 100–200 mL, up to 1000 mL/day
  • Patients >9 y: As much as wanted, up to 2000 mL/day
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Oral Rehydration During First 4 Hours

Table 3. Approximate Amount of Oral Rehydration Solution to Administer in the First 4 Hours (Open Table in a new window)

Age < 4 mo 4-11 mo 12-23 mo 2-4 y 5-14 y ≥15 y
Weight < 5 kg 5-7.9 kg 8-10.9 kg 11-15.9 kg 16-29.9 kg ≥30 kg
ORS solution in mL 200-400 400-600 600-800 800-1200 1200-2200 2200-4000
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Oral Rehydration for Home Administration

Table 4. Estimate of Oral Rehydration Solution Packets to Be Administered at Home (Open Table in a new window)

Age Amount of Solution After Each Loose Stool ORS Packets Needed
< 24 mo 50-100 mL Enough for 500 mL/d
2-9 y 100-200 mL Enough for 1000 mL/d
≥10 y As much as is wanted Enough for 200 mL/d
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Oral Replacement Solution for Hydration Maintenance

Table 5. Oral Replacement Solution for Maintenance of Hydration (Open Table in a new window)

Age Amount of Solution After Each Loose Stool
< 24 mo 100 mL
2-9 y 200 mL
≥10 y As much as is wanted
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Antimicrobial Therapy for Cholera

Table 6. Antimicrobial Therapy Used in the Treatment of Cholera* (Open Table in a new window)

Antibiotic Single Dose (PO) Multiple Dose (PO)
Doxycycline 7 mg/kg; not to exceed 300 mg/dose 2 mg/kg bid on day 1; then 2 mg/kg qd on days 2 and 3; not to exceed 100 mg/dose
Tetracycline 25 mg/kg; not to exceed 1 g/dose 40 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Furazolidone 7 mg/kg; not to exceed 300 mg/dose 5 mg/kg/d divided qid for 3 d; not to exceed 400 mg/d
Trimethoprim and sulfamethoxazole Not evaluated < 2 months: Contraindicated



≥2 months: 5-10 mg/kg/d (based on trimethoprim component) divided bid for 3 d; not to exceed 320 mg/d trimethoprim and 1.6 g/d of sulfamethoxazole



Ciprofloxacin§ 30 mg/kg; not to exceed 1 g/dose 30 mg/kg/d divided q12h for 3 d; not to exceed 2 g/d
Ampicillin Not evaluated 50 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Erythromycin Not evaluated 40 mg/kg/d erythromycin base divided tid for 3 d; not to exceed 1 g/d
* Antimicrobial therapy is an adjunct to fluid therapy of cholera and is not an essential component. However, it reduces diarrhea volume and duration by approximately 50%. The choice of antibiotics is determined by the susceptibility patterns of the local strains of V cholerae O1 or O139.



Tetracycline and doxycycline can discolor permanent teeth of children younger than 8 years. However, the risk is small when these drugs are used for short courses of therapy, especially if used in a single dose.



Single-dose therapy of these drugs has not been evaluated systematically in children, and recommendations are extrapolated from experience in adults.



§ Fluoroquinolones (eg, ciprofloxacin) are not approved in the United States for use in persons younger than 18 years. When given in high doses to juvenile animals, they cause arthropathy. Clinical experience indicates that this risk is very small in children when used for short courses of therapy.



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WHO Guidelines for Cholera Management

Table 7. WHO Guidelines for Cholera Management (Open Table in a new window)

Steps in the treatment of a patient with suspected cholera are as follows:
1. Assess for dehydration (see Table 1)
2. Rehydrate the patient and monitor frequently, then reassess hydration status
3. Maintain hydration; replace ongoing fluid losses until diarrhea stops
4. Administer an oral antibiotic to the patient with severe dehydration
5. Feed the patient
More detailed guidelines for the treatment of cholera are as follows:
  • Evaluate the degree of dehydration upon arrival
  • Rehydrate the patient in 2 phases; these include rehydration (for 2-4 h) and maintenance (until diarrhea abates)
  • Register output and intake volumes on predesigned charts and periodically review these data
  • Use the intravenous route only (1) during the rehydration phase for severely dehydrated patients for whom an infusion rate of 50-100 mL/kg/h is advised, (2) for moderately dehydrated patients who do not tolerate the oral route, and (3) during the maintenance phase in patients considered high stool purgers (ie, >10 mL/kg/h)
  • During the maintenance phase, use oral rehydration solution at a rate of 800-1000 mL/h; match ongoing losses with ORS administration
  • Discharge patients to the treatment center if oral tolerance is greater than or equal to 1000 mL/h, urine volume is greater than or equal to 40 mL/h, and stool volume is less than or equal to 400 mL/h.
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Diet

Resume feeding with a normal diet when vomiting has stopped. Continue breastfeeding infants and young children.

Malnutrition after infection is not a major problem, as it is after infection with Shigella species or rotavirus diarrhea. The catabolic cost of the infection is relatively low, anorexia is neither profound nor persistent, and intestinal enzyme activity remains intact after infection; hence, intestinal absorption of nutrients is near normal.

There is no reason to withhold food from cholera patients.

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Deterrence/Prevention

The current response to cholera outbreaks tends to be reactive, in the form of an emergency response. Although this approach prevents many deaths, it fails to prevent cases of cholera.

Rapid identification of cases in children and adults and prompt treatment will limit further spread of the disease. Water can be made safer to drink by boiling or adding chlorine, although both methods are expensive and difficult to implement during epidemics.

Sensitive surveillance and prompt reporting contribute to the rapid containment of cholera epidemics. In many endemic countries, cholera is a seasonal disease, occurring every year usually during the rainy season. Surveillance systems can provide an early alert to outbreaks, which should lead to a coordinated response and assist in the preparation of preparedness plans.

A multisectoral and coordinated approach is paramount to efficiently control a cholera outbreak. Key sectors to be involved are health, water and sanitation, fishery and agriculture, and education.

Cholera is usually transmitted through fecally contaminated water or food. Outbreaks can occur sporadically in any part of the world where water supply, sanitation, food safety, and hygiene are inadequate. WHO recommends improvements in water supply and sanitation as the most sustainable approach for protecting against cholera and other waterborne epidemic diarrheal diseases. However, such an approach is unrealistic for the many impoverished populations most affected by cholera.

Outbreaks can be mitigated and case-fatality rates can be reduced by means of several other measures, many of which are suitable for community participation. Human behaviors related to personal hygiene and food preparation contribute greatly to the occurrence and severity of outbreaks. Education on specific hygiene practices is important in the prevention of cholera.

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Vaccines

Difficulties in implementing public health and personal preventive practices have stimulated the century-long search for vaccines. Experience with the parenteral vaccine has been disappointing. Because of a better understanding of the immune response to natural infection, researchers now know that the oral route of administration is better.

Cholera vaccination is no longer officially required for any international traveler, and the International Certificate of Vaccination no longer provides a special section for recording cholera immunization. The risk of an international traveler from a developed country contracting cholera is small (1 case in 500,000 travelers). WHO has identified 3 oral vaccines. These are available in some countries but are used mainly by travelers.

One vaccine consists of a monovalent killed whole-cell V cholerae O1 with purified recombinant B-subunit of cholera toxoid (WC/rBS). Clinical trials have been performed in Bangladesh, Peru, and Sweden. Efficacy trials have shown that this vaccine is safe and confers 85-90% protection during 6 months in all age groups after administration of 2 doses, 1 week apart. In Bangladesh, protection declined rapidly after 6 months in young children but was still about 60% in older children and adults after 2 years.

This vaccine is available in more than 60 countries for adults and children older than 2 years. It was approved for use in the United States in 2006.

Shanchol and ORCVAX are bivalent vaccines that are based on serogroups O1 and O139; however, they do not contain the bacterial toxin B subunit. ORCVAX was originally formulated in Vietnam in 1997 and was modified in 2004. Over 20 million doses have been administered to adults and children in endemic areas of Vietnam. Shanchol is a similar formulation available in India. Shanchol is administered in 2 liquid doses 14 days apart in adults and children older than 1 year. A booster dose is recommended after 2 years. [18]

CVD 103-HgR is a cholera vaccine developed by the Swiss Serum and Vaccine Institute in Berne, Switzerland. This vaccine, although not recognized by the WHO, is available in Europe, Latin America, and, since 1997, Canada. The vaccine is composed of attenuated V cholerae O1 prepared by recombinant DNA. It has been tested in industrialized countries and in developing countries that have endemic, epidemic, and little or no cholera. [19]

The vaccine is highly protective against moderate and severe cholera, and it is very well tolerated and extremely immunogenic. In addition, the rate and extent of vaccine excretion is minimal.

In June, 2016, the FDA approved the CVD 103-HgR cholera vaccine (Vaxchora, PaxVax, Inc) for the prevention of cholera caused by serogroup 01. Also, in June, 2016 the Advisory Committee on Immunization Practices (ACIP) of the CDC voted unanimously to recommend the CVD 103-HgR cholera vaccine (Vaxchora, PaxVax, Inc) for adults aged 18 to 64 years who are traveling to an area of active toxigenic Vibrio cholerae O1 transmission and who have an increased risk for exposure or poor clinical outcome if infected. [20, 21]

The Advisory Committee on Immunization Practices for Use of Cholera Vaccine recommend [22, 23] :

  • Adults between the ages of 18 and 64 yr are recommended to receive one dose of the lyophilized CVD 103-HgR ( Vaxchora, PaxVax) cholera vaccine before travel to areas with active cholera transmission.
  • Vaccine recipients should not have received oral or parenteral antibiotics in the 14 days before vaccine administration.
  • Recipients should wait at least 10 days after vaccine administration to take chloroquine.

According to a 2011 Cochrane review on oral cholera vaccines, currently available vaccines are safe and provide 50-60% efficacy in preventing episodes of cholera in the first 2 years after the primary vaccination schedule. A booster dose may be required after 3 years. [24] At this time, no countries use these vaccines in routine immunization.

A study by Qadri et al assessed the feasibility and protective effect of delivering the vaccine Shanchol through routine government services in urban Bangladesh and evaluated the benefit of adding behavioral interventions to encourage safe drinking water and hand washing along with the vaccination.  The study analyzed 267,270 people, 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioral change, and 80,056 assigned to non-intervention. The study found that vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioral change group. Overall protective effectiveness was 37% in the vaccination group and 45% in the vaccination and behavioral change group. [25, 26]

A study by Matias et al found that immunization with the bivalent oral cholera vaccine (Shanchol) induced antibody secreting cell responses among a cohort of healthy adults in Haiti after a single dose, however, the second dose of vaccine resulted in a minimal response. [27]

A study by Azman et al reported that vaccination campaigns that use a single dose of oral cholera vaccine may be able to prevent more deaths than the standard two-dose campaign when vaccine supplies are limited. [28, 29]

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