Frequently Asked Questions
Below are answers to some common questions about cholera and oral cholera vaccines (OCV). Please use the links in the right sidebar to navigate between FAQ categories. In addition to the information below, an excellent source of general cholera information is the CDC cholera FAQ website.
Cholera is an acute diarrheal disease that in severe cases rapidly leads to dehydration and death if appropriate treatment is not provided immediately.
Cholera is a disease in which the bacterium Vibrio cholerae colonizes the small intestine and produces a toxin which leads to massive secretion of water and salts. This huge amount of fluid from the intestinal cells is much more than the intestine can reabsorb and so the fluid comes pouring out as watery diarrhea. The loss of fluids is so great that the patient can quickly become severely dehydrated, go into shock, and die within a few hours. The diarrhea fluid is teeming with huge numbers of the bacteria and these can rapidly spread to others, leading to epidemics.
Cholera patients commonly present with diarrhea and vomiting. In severe cases, diarrhea is voluminous, resulting in dehydration and shock within a few hours.
Symptoms can range from mild diarrhea to very severe diarrhea. Severe cases are generally accompanied with severe vomiting, weakness, and shock. Muscle cramps in the legs and arms are also common because of the electrolyte imbalance. With shock, the patient may lose consciousness and this may lead to death.
The causative organism, Vibrio cholerae, is a gram-negative, comma-shaped bacillus known to have more than 200 serogroups. Only serogroups O1 and O139 have been associated with epidemics.
The causative bacterium (Vibrio cholerae) produces a toxin called cholera toxin which stimulates adenylate cyclase, increasing the level of intracellular cycline AMP, which leads to the fluid secretion from intestinal cells that is much faster than it can be reabsorbed. Thus, the disease is actually caused by the toxin rather than the bacteria itself.
Cholera transmission occurs where there is unsafe water and poor sanitation. In areas where cholera is common, children aged <5 years have the highest rates of infection, but all age groups are at risk. Household contacts of cholera patients are at increased risk of developing the disease.
Ingestion of fecally contaminated water is the most common source of transmission of cholera; therefore, it can easily spread in highly populated communities where access to clean water and sanitation are poor and when hygiene is compromised by insufficient hand washing and during food preparation. Cholera may also be transmitted via contaminated shellfish and food.
Most cholera infections (about 80%) are mild or unapparent. Among those who are infected, some develop severe dehydration from profuse, acute, watery diarrhea.
After an incubation period of 1-3 days, about 20% will develop diarrhea which may be severe, along with severe vomiting. As the illness progresses, the stools become like water with little flecks of mucus (called rice-water stool). The diarrhea is usually painless and may have a fishy smell. Patients may also have severe muscle cramps and spasms which can be very painful.
If a large enough dose of the bacteria is ingested and survives the acidity of the stomach, the bacteria then colonize the small intestine where they release cholera toxin. This toxin triggers mechanisms which eventually leads to massive purging of electrolyte-rich fluid in the small intestine that exceeds the absorptive capacity of the colon and is expelled as diarrhea. This loss of fluid and depletion of electrolytes can lead to rapid dehydration.
After ingestion of a large enough dose of the bacteria that are able to survive the gastric acidity, the Vibrio organisms then colonize mucosal cells of the small intestine. During this time, the organisms release cholera toxin that bind to the small intestinal epithelial cells. The release of the A subunit of the cholera toxin stimulates the enzyme system of the intestinal cells leading to the increase in chloride secretion by the crypt cells, which in turn leads to inhibition of absorption of sodium and chloride by the microvilli. These events eventually lead to massive purging of electrolyte-rich isotonic fluid in the small intestine that exceeds the absorptive capacity of the colon, resulting in rapid dehydration and depletion of electrolytes, including sodium, chloride, bicarbonate, and potassium.
The gold standard for diagnosing cholera is bacteriological culture of a stool specimen of a patient with diarrhea.
There are rapid tests (e.g., dipsticks) which are now being developed, and these may assist in surveillance for cholera for areas without bacteriology. The rapid tests sometimes give positive results when the culture is negative, so if there is doubt, a standard culture should be carried out with a few specimens to be sure of the diagnosis. Newer methods, using preincubation in enrichment broth for a few hours, may eliminate these false positives, making these dipstick tests more reliable.
Patients can die in 4 to 18 hours if fluid and electrolyte losses from diarrhea and vomiting are not replaced.
Dehydration, electrolyte abnormalities (especially hypokalemia—low potassium concentration in the blood), metabolic acidosis, and hypovolemic shock may occur within 4 to 18 hours if diarrheal and vomiting losses are not replaced.
Adequate rehydration followed by maintenance hydration to replace ongoing fluid loss is the most important treatment. If the patient is severely dehydrated or is in shock, rapid administration of intravenous fluids is needed. Oral rehydration solution (ORS) may be given to patients with mild or moderate dehydration who are able to drink. Rice-based ORS has been shown to be superior to regular ORS for cholera patients and this should be used whenever available. Antibiotic treatment is recommended for patients with severe or moderate dehydration. For children <5 years of age, daily zinc should also be given for 10-14 days.
For patients with severe dehydration, rapid administration of intravenous fluids is needed. Ringers lactate is generally used because it has the appropriate mix of electrolytes which are needed to replace those being lost in the diarrhea stool. Ringers has less potassium than is ideal but this can be compensated by starting ORS as soon as the patient is able to drink. Patients with severe dehydration require large volumes given rapidly—generally 10% of their body weight over 2 to 4 hours. Thus, a 50kg patient needs 5 liters quickly. Additional fluids are needed to keep up with ongoing losses, using either ORS or IVs as tolerated. Patients with cholera should be monitored closely, especially in the first 24 hours of illness as the severe purging and vomiting may continue. Ideally, patients should be placed on cholera cots so that stool outputs can be more easily monitored, and they must be reassessed every 1-2 hours or more frequently if purging continues. There is no restriction on feeding, and small frequent feedings may be continued, if tolerated, during treatment. Antibiotic treatment is recommended for patients with severe or moderate diarrhea and should begin as soon as vomiting stops, which is usually 4-6 hours after initiation of rehydration therapy.
Zinc should be given to children <5 years old as soon as vomiting stops. Zinc supplementation has been shown to shorten the duration of diarrhea and reduce diarrhea episodes when given for 10-14 days.
Antibiotics decrease the passage of diarrheal stools, thereby decreasing fluid losses. Antibiotics also result in decreasing the fecal excretion of vibrios. However, some strains of V.cholerae are resistant to certain antibiotics, such that the choice of which antibiotic to use is very important.
Antibiotics reduce the purging by about 50% and shorten the illness by about 50%. This means less time in the hospital and less work for the hospital staff. This is important during outbreaks when hospitals can be overwhelmed with patients. The antibiotic must be appropriate, however, and some strains are resistant to commonly-used antibiotics. Thus, samples should be obtained periodically to determine antibiotic sensitivity to be sure the bacteria have not become resistant. If the strains are sensitive, doxycycline is the preferred antibiotic for both children and adults. If strains are resistant to tetracycline, azithromycin is generally used. Antibiotics also shorten the period of Vibrio excretion and thus limit the spread to the family members.
Cholera will not occur if people have safe water and safe food. Thus, improved water and sanitation is the long term solution to preventing cholera. For many developing countries, this goal is a long way off. In these areas where there is a high risk of cholera, people need to use only safe water, but they should also consider cholera vaccine.
If the cholera vaccine were available in unlimited quantities and were very inexpensive, then most people in developing countries should receive it. Unfortunately, it is in short supply and is not cheap ($1.85 per dose), so it is being used where it will be the most cost effective.
One study has demonstrated that the risk of cholera can be reduced by about 50% if the household water is filtered through sari material. Use of sari filtration is based on the idea that many of the cholera bacteria are attached to plankton and these can be filtered out with the sari material. The bacteria which are not attached to plankton can slip through a sari filter easily. Thus, this method is worthwhile but it is best used with other water purification methods (e.g. chlorination).
Cholera has been reported in much of the developing world, and an estimated 1.4 billion people are said to be at risk of developing cholera in endemic countries alone. In 2012, ~590,000 cholera cases were reported in 58 countries affecting all regions of the world. However, these reports are believed to be underestimates of the burden of cholera and that as many as 1.4 to 4.3 million cases occur annually with 100,000 to 200,000 deaths.
Cholera patients commonly present with diarrhea and vomiting. In severe cases, diarrhea is voluminous, resulting in dehydration and shock within a few hours.
The home of cholera is the area around the Bay of Bengal, but cholera now affects most countries of South and Southeast Asia and most countries of Sub-Saharan Africa. Since 2010, it has spread through Haiti, the Dominican Republic, Cuba, and, more recently, Mexico. Occasionally it has been reported in Middle Eastern countries.
According to the WHO, countries are said to be endemic for cholera if cholera cases have been reported in 3 out of the previous 5 years. An outbreak of cholera occurs when a higher than expected number of cases are reported in a given area for a specific period of time. Outbreaks may occur in endemic or non-endemic areas and are more limited in scope compared to epidemics.
In areas at risk for cholera, surveillance is critical so that outbreaks can be detected early and control strategies can be employed.
Improved surveillance is a critical component for cholera control that is missing from many countries with cholera. Since cholera tends to occur in remote areas of poor countries, cases may go undetected until a major outbreak has already begun. Some constraints to carrying out proper surveillance include the lack of good laboratory facilities in these remote locations and the lack of infrastructure to report suspected cases.
Cholera is rare in travelers because they are usually careful about consuming only safe foods and safe water. However, cholera does happen in travelers to developing countries. They have no immunity and are susceptible. Travelers should therefore be advised to drink only safe water and safe food. Travelers from Europe to Cuba have recently been diagnosed with cholera.
Click here for a case report (PDF format) of a traveler to Cuba who contracted cholera.
There are three licensed vaccines for cholera: Dukoral®, Shanchol(TM), and mORCVAX(TM). Dukoral® and Shanchol(TM) are approved (prequalified) by the World Health Organization. These are licensed and available in certain countries. Dukoral® is available in many travel clinics in Europe, as well as many developing countries, but none of these vaccines is licensed in the USA. Shanchol(TM) is beginning to be provided through relief and government agencies to vulnerable persons at risk of cholera. mORCVAX(TM) is licensed in and used in Vietnam; it is very similar to Shanchol(TM).
Travelers who attend travel clinics in countries where Dukoral® is licensed may receive this vaccine. Shanchol(TM) is licensed in India, but is not yet readily available in India. Shanchol(TM) is being distributed by some relief agencies and ministries of health to targeted populations at risk of cholera.
Dukoral® is now widely available in travel clinics in many countries (not the USA) and it was used in a few campaigns to vulnerable people at risk in developing countries. Now, most campaigns conducted by relief agencies use Shanchol(TM) because it is cheaper and logistically easier and is equally effective.
As with other vaccines, oral cholera vaccine helps to reduce the risk of getting the disease should one be exposed. In the case of cholera vaccine, vaccine reduces this risk by about 65-75%.
In addition to reducing the risk to individuals who may be exposed, the vaccine also induces herd protection, meaning that if a large proportion of the population is immunized, the spread of the infection is reduced. This lowers the risk of cholera for persons who may not have received the vaccine, and it also lowers the risk further for those who do receive it.
The WHO recommendations regarding oral cholera vaccine are found in the WHO Position Paper on cholera vaccines published in the Weekly Epidemiological Record on 26 March 2010. A more detailed review of the vaccine was written by an expert group and presented to the WHO Advisory Committee in October 2009 as a Background Paper on the Integrtation of Oral Cholera Vaccines into Global Cholera Control Programs.
In addition, the package inserts provided by the manufacturers of the vaccines also provide helpful information and can be found at these links:
The DOVE project has experts who can advise about cholera and are available to assist in planning for oral cholera vaccine. Please send an email to firstname.lastname@example.org with your request.
Vaccine reduces the risk of getting sick with cholera by 65-75%, and a recent study has found that protection lasts 5 years.
We know the vaccine is effective shortly after getting two doses. Based on immunological tests, it seems likely that protection starts 7 to 10 days after the first dose, but two doses should be used because that is the way it has been given in the clinical trials.
A study will begin soon to determine how effective a single dose will be in preventing cholera.
Currently, the manufacturers caution that there should be two weeks between rounds of oral vaccines for polio and cholera. Whether this is necessary or not is not known. Until we have data to show that there is no interference between the two vaccines, it is best to separate the two vaccines by at least two weeks.
It seems likely that studies will show that the two vaccines can be given at the same time, but there are no studies to show this can be done without interaction.
The vaccine works best if other actions are taken to prevent cholera’s spread. If a person consumes a very large dose of bacteria, this large number of bacteria can overwhelm the intestinal immunity, resulting in the patient developing cholera in spite of being vaccinated. Thus, the vaccine works best when water is as safe as is reasonably possible.
Vaccine and safe water interventions work synergistically. Safer water improves the effectiveness of the vaccine and the vaccine reduces the number of Vibrio cholerae shed in feces and contaminating environmental water. Thus, when deciding how to control cholera, these are not two competing strategies—they work together.
The vaccine is safe and there have been no serious side effects from it. Being a killed oral vaccine, there is no reason to expect it to be risky. While safe, a few people who have taken the vaccine have noted experiencing a brief period of upset stomach. Also, the taste of Shanchol(TM) is not pleasant.
Extensive safety studies have been conducted and there have been no serious adverse events associated with the vaccine. A few people have experienced some mild stomach discomfort, but these symptoms occurred in subjects receiving a placebo as well. The vaccine has now been given to more than a million people and there continues to be no evidence of safety issues.
Immunization consists of two doses of oral vaccine. The two doses are given with an interval of 2 to 6 weeks.
The schedule using a two week interval was designed to speed the process of immunization as much as possible during campaigns when there is urgency to get people immunized as quickly as possible. For travelers who delay getting the vaccine until shortly before the trip, the two week schedule was appropriate. From an immunological standpoint, a shorter interval may not be as effective since the vaccine stimulates local intestinal immunity and a booster response is better if the interval is not too close together. In some situations, a longer interval (up to 8 weeks) may be logistically more convenient and is also acceptable.
The studies which document vaccine efficacy have used two doses, so we do not know how effective a single dose would be. A study is planned to determine if a single dose will be effective and for how long.
The immune response to the first dose of the vaccine is nearly equal to that of two doses, so there is hope that a single dose will be effective, at least for some duration. However, since we do not have documentation of its effectiveness in a field trial, the utility of a single dose is not known. During campaigns which use two doses of vaccine, it is likely that some protection is induced within 10 days of the first dose even if full protection requires two doses.
Unfortunately, there is a limited supply of vaccine at present (a few million doses per year). Manufacturers are attempting to scale up production to be able to provide it to more people who will benefit.
The low number of doses currently available is a major constraint to its use. Until recently, there was a low demand for the vaccine, so manufacturers were reluctant to increase production. This resulted in a “low demand–low supply” cycle. With the creation of the stockpile at the World Health Organization, this unfortunate cycle will be broken, and it is hoped that other manufacturers will begin production.
When cholera vaccines are being provided to populations at risk of cholera, it is imperative that it be used as part of an overall integrated strategy that includes improved water and sanitation and the provision of high quality medical care for those who do develop cholera. Recent experiences demonstrate that these activities can reinforce each other.
In the past, there was a concern that if a cholera vaccine campaign was implemented, that this would interfere with other interventions such as improved water and sanitation. From a biological standpoint, both types of interventions reduce the threat of cholera, but there was still concern that the logistical and resource requirements of the two programs might compete. Recent experience with vaccine campaigns have demonstrated that this concern is not warranted, and in fact, with careful planning, the types of activities can reinforce each other.
The current price for Shanchol(TM), when purchased through the UN system or through large relief agencies, is $1.85 per dose. The price for Dukoral® through the UN system is significantly higher. When Dukoral® is provided through travel clinics, the price of Dukoral® is much higher.
With increasing production, we anticipate that the price of the vaccine will come down.
Each outbreak must be assessed as to its risk to the population. For outbreaks that can be controlled rapidly with improved safe water, this may be the best strategy. However, for outbreaks that put many people at risk, including vaccine along with safe water will save money as well as lives. The DOVE project consultants can help assess these situations. Please send an email to email@example.com with your request.
Integration of vaccine and safe water programs begins with donors providing humanitarian funding for cholera control.
Vaccine is now available through the stockpile at the World Health Organization.
Decisions about use of cholera vaccine depend on the cholera situation in the country. The DOVE project has a process for assessing the risk of cholera and whether vaccine makes sense for use in given situations. Some countries with a consistently high cholera rate will find that use of vaccine will save money as well as lives. For low risk countries, vaccine may not be cost effective relative to other strategies.
The World Health Organization (WHO) has a stockpile of 2 million doses of vaccine that can be made available very rapidly during emergency situations. The size of the stockpile is expected to increase substantially over the next few years. Countries can access vaccine from the stockpile by applying to WHO through their website.