Frequently Asked Questions
Below are answers to some common questions about cholera and oral cholera vaccines.
- What is cholera?
Cholera is an acute diarrheal disease caused by the bacterium Vibrio cholerae. In severe cases, loss of so much diarrhea fluid leads rapidly to dehydration and death if appropriate treatment is not provided immediately.
- What are the symptoms of cholera?
Cholera patients commonly present with diarrhea and vomiting. In severe cases, diarrhea is voluminous, resulting in dehydration and shock within a few hours. Although some of the patients will have severe illness, most people infected with Vibrio cholerae will remain asymptomatic or have only mild symptoms but will shed the bacteria in their feces for several days. Of those who develop symptoms, approximately 80% will show no, mild, or moderate symptoms, and the remaining 20% will have severe disease. (The proportions of severe and less severe were calculated from studies in Bangladesh. There may be a higher proportion of severe cases in areas that are not endemic, like in Africa or Haiti.) After an incubation period of 1-3 days, the severe cases will have massive diarrhea and 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. 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 risk of dying.
- What causes cholera and what are the complications?
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 colonizes the small intestine and produces a toxin. The toxin stimulates the enzyme, adenylate cyclase, increasing the level of intracellular cyclic AMP which leads to massive secretion of water and electrolytes from intestinal cells. This huge amount of fluid from the intestinal cells is much more than the intestine can reabsorb and the fluid and the electrolytes (especially, sodium, chloride, potassium and bicarbonate) come 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 loss of potassium leads to hypokalemia and the loss of bicarbonate leads to metabolic acidosis. The diarrhea fluid is teaming with huge numbers of the bacteria. In areas with poor sanitation, these bacteria can spread to others, leading to epidemics.
- Who is most susceptible to cholera?
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. Anyone can get cholera, including healthy people, but certain people have a higher risk. These include persons with decreased gastric acidity (or taking medicines to reduce stomach acid), with blood group “O,” with malnutrition, with an immunocompromised state, or who lack prior immunity.
- How is the disease transmitted?
Ingestion of water contaminated with feces is the most common source of transmission of cholera; therefore, it can easily spread in 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. Although cholera is most often transmitted by the fecal–oral route, in some circumstances, it may also persist in environmental water, independent of human fecal contamination. Thus, some people who eat raw or under-cooked seafood can get cholera from these foods which have Vibrio cholerae attached to their shells.
- Once contracted, how soon can a person die from cholera?
Patients can die in 4 to 24 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 if diarrheal and vomiting losses are not replaced.
- How do you treat someone who has cholera?
Rapid rehydration to correct the dehydration is needed, followed by maintenance hydration to replace ongoing fluid. 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 when intravenous fluids are needed, Ringer’s lactate is generally used because it is the commercially available IV fluid with the most appropriate mix of electrolytes needed to replace the electrolytes being lost in the diarrhea stool. However, Ringer’s has less potassium than is ideal, so patients should also be started on ORS when it is possible for the patient to drink since ORS has more potassium and can provide the additional potassium needed. 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 (also called Watten cots) so that stool outputs can be more easily measured. Patients should be reassessed every 1-2 hours or more frequently if high volume 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.
- How effective are antibiotics in treating cholera and which antibiotics are best?
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, during outbreaks, samples should be obtained periodically to determine antibiotic sensitivity to be sure the bacteria have not become resistant. If the strains are sensitive, single dose 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.
- How many people are affected annually, and how many die?
Cholera has been reported in much of the developing world, and more than 1 billion people are thought to be at risk of cholera in endemic countries alone. In 2019, 31 countries reported a total of 923 037 cases of cholera, including 1911 deaths. However, these reports are believed to underestimate the true burden and the actual number of cases and deaths may be 1.3 to 4 million cases annually with 21,000 to 143,000 deaths. It is likely new estimates will be developed soon.
- What parts of the world are most likely to experience cholera?
The home of cholera is the area around the Bay of Bengal like Bangladesh and India, but cholera now affects most countries of South and Southeast Asia and most countries of Sub-Saharan Africa. In Sub-Saharan countries, Democratic Republic of Congo and Nigeria report the highest number of cases but many others also have pockets of transmission including Ghana, Benin, Cameroon, Chad, Niger, Ethiopia, Kenya, South Sudan, Uganda, Tanzania, Mozambique, Somalia. In addition, Yemen and other countries in the Middle East have experienced large epidemics. The recent large epidemic in Haiti appears to be over, though it may be too soon to be sure.
- What is a cholera outbreak and is a country considered to be endemic?
An outbreak of cholera occurs when documented cases are seen and there is evidence of ongoing transmission in the area. Outbreaks may occur in endemic or non-endemic areas. According to the World Health Organization, countries are said to be endemic for cholera if cholera cases have been reported in 3 out of the previous 5 years.
- What methods are available for diagnosing the presence of Vibrio cholera?
The gold standard for diagnosing cholera is bacteriological culture of a stool specimen of a patient with diarrhea; however, there are other ways to detect and confirm cholera including rapid diagnostic tests (RDTs) and PCR. RDTs represent a promising tool for early detection of V. cholerae O1 especially in remote areas where laboratory resources are poor or not available. Unfortunately, RDTs sometimes yield a false positive result, but during an outbreak, when several samples test positive, this provided increased confidence that the results are providing the true positive results. Thus, during an outbreak, it is wise to test samples from several patients. In addition to culture and RDTs, PCR is now being used to confirm cases. The PCR can be carried out using stool samples or using a fecal sample placed on filter paper. After drying the paper can be sent to the PCR lab. Even if the outbreak is documented by RDT or PCR, samples should still be sent to the lab for culture since this is needed for antibiotic sensitivity testing.
- How effective is surveillance in containing cholera outbreaks?
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.
- Is cholera a problem for travelers?
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. In the United States, CDC recommends that adults traveling to areas with active cholera transmission get vaccinated with a newly licensed cholera vaccine (Vaxchora). In many other countries, a different vaccine, Dukoral, is available for travelers.
- What is the best way to prevent cholera in areas at risk?
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 ($1.30 per dose), so it is being used strategically where it will be the most cost effective.
- How effective is sari filtration?
One study demonstrated that the risk of cholera in rural Bangladesh was reduced by about 50% when 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).
- What kinds of cholera vaccines are available?
The three WHO-prequalified vaccines are Dukoral (manufactured by Valneva), Shanchol (manufactured by Sanofi in India) and Euvichol (manufactured by Eubiologics in Korea). Euvichol and Shanchol are available through a global stockpile for emergency use and for prevention of cholera in hotspot areas in endemic countries. For poor countries, the cost of these vaccines is subsidized by GAVI. The vaccines are killed whole-cell vaccines containing V. cholerae O1 (classical and El Tor) and V. cholerae O139. The vaccine is packaged in single dose vials and each dose consists of 1.5 ml. It is given orally and the subjects simply swallow the vaccine. Two doses are administered to everyone over the age of 1 year with an interval of at least 14 days between the two doses. Dukoral is very similar to Euvichol and Shanchol, being composed of killed whole cells, but this vaccine contains only the serogroup O1. In addition, it includes the B subunit of the cholera toxin. This additional toxoid antigen stimulates antitoxin immunity as well as antibacterial immunity; however, the B subunit is acid sensitive so it must be given with a buffer. It is widely used in travel clinics, but buffer requirement complicates its administration and makes it impractical for use during vaccine campaigns in developing countries. Vaxchora (manufactured by Emergent) is single dose live oral cholera vaccine available in the United States for persons aged from 2 through 64 years of age traveling to cholera-affected areas. It is being evaluated in developing countries but is not currently being used for cholera control in endemic countries.
- How effective is Shanchol and Euvichol OCV when used in developing countries?
As with other vaccines, these oral cholera vaccines help to reduce the risk of getting the disease by about 65-75%. However, if the coverage rate is high, the effectiveness can be higher than this. This is because 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.
- What strategies are used to deliver killed whole cell OCV in developing countries?
There are currently three strategies when using OCV. These include:
1) emergency use to control an ongoing outbreak
2) emergency use to prevent an outbreak during humanitarian emergencies when cholera risk is high
3) preventive use of OCV for people living in areas determined to be hotspots. Vaccine is available through the IGC (Interagency Coordinating Group) for the first two situations and through the Global Task Force for Cholera Control for the third situation. Currently, Euvichol and Shanchol are not available for purchase on the private market.
- How many doses of killed whole cell OCV are needed, and what is the recommended schedule to receive each dose?
Immunization consists of two doses of oral vaccine. The two doses are given with an interval of 2 to 6 weeks. However, it now appears that the interval between doses can be much longer depending on the logistics locally. In some situations, a longer interval (up to 6 months or longer) may be logistically more convenient and is also acceptable.
- How important is it to receive the second dose of killed whole cell OCV?
Two doses are recommended since this provides optimal protection. Even so, the first dose provides significant protection until the second dose is given. During an outbreak, simulations show that giving a single dose to twice as many people prevents more cases than two doses to half as many people. One study in Bangladesh showed that a single dose offered protection to older children and adults that was sustained for at least 2 years; however, it did not protect young children <5 years. The general consensus is that two doses should be used for most situations, however, the timing of the second dose can be quite flexible.
- How many days after vaccination does it take to establish protection against cholera?
People develop protection against cholera approximately 10 days after receiving the vaccine.
- Does the killed whole cell oral cholera vaccine need to be taken separately from the oral polio vaccine?
It seems likely that the two vaccines can be given at the same time. Studies are underway to validate this recommendation.
- After being vaccinated, why should a person continue to take precautions with clean water, sanitation, and hygiene?
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 despite 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.
- Does the killed whole cell oral OCV have any side effects? How safe is the vaccine?
Extensive safety studies have been conducted and there have been no serious adverse events associated with the vaccine. A few people experience some mild stomach discomfort, but these symptoms occurred in subjects receiving a placebo as well. The vaccine has now been given to millions of people and there continues to be no evidence of safety issues. OCV is safe for women who are pregnant. There is no increased risk to the mother or the fetus. Also, pregnant women are more vulnerable to cholera, so these people should be included for vaccination whenever possible.
- How much vaccine is available?
The supply of killed whole cell OCV, but the supply has been increasing. Between 2013 and 2019, 58 million OCV doses have been used for emergency and preventive campaigns. Each year, about 25 million doses are now being produced.
- Can oral cholera vaccine be used together with water, sanitation, and hygiene programs?
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 hygiene and sanitation (WASH) and the provision of high-quality medical care for those who do develop cholera. In the past, there was a concern that if a cholera vaccine campaign was implemented, that this would interfere with WASH interventions. There was concern that the logistical and resource requirements of the two programs might compete; however, experience with vaccine campaigns have demonstrated that this concern is not warranted. In fact, with careful planning, the types of activities can reinforce each other.
- How much does oral cholera vaccine cost per dose?
The current price for Euvichol-plus when purchased through the UN system is $1.30 per dose. When Dukoral is provided through travel clinics, the price of Dukoral is much higher.
- When attempting to control a cholera outbreak, how should donors distribute the funding resources between programs for safe water and programs for vaccine? 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. Integration of vaccine and safe water programs begins with donors providing humanitarian funding for cholera control.
- Where can I find more information on cholera?
Here are some additional links for cholera.
- Global Task Force on Cholera Control: https://www.gtfcc.org/
- World Health Organization: https://www.who.int/news-room/fact-sheets/detail/cholera
- Centers for Disease Control and Prevention: https://www.cdc.gov/cholera/index.html
- UNICEF: https://sites.unicef.org/cholera/
- United Nations Office for the Coordination of Humanitarian Affairs: https://reliefweb.int/
- Cholera Platform: https://www.plateformecholera.info/
- European Centre for Disease Prevention and Control: https://www.ecdc.europa.eu/en/cholera
- To learn about recent cholera outbreaks: https://promedmail.org/