Oral Cholera Vaccine

The oral Cholera vaccine is a prescription medication belonging to the vaccine class.

The oral cholera vaccine is approved for active immunisation against Vibrio cholerae serogroup O1-related cholera in people one year of age and older, specifically in regions where cholera is endemic or during outbreaks to prevent its spread.

It is not a part of the national immunization programme.

The cholera vaccine is taken orally and causes an immunological reaction after being absorbed into the gastrointestinal tract. Following metabolism, excretion happens gradually through the body's processes in the form of urine and faeces.

The common side effects of the oral cholera vaccine include mild diarrhoea, abdominal pain, nausea, and fatigue.

The Cholera vaccine is available in the form of powder for oral suspension.

Cholera vaccine is available in Bangladesh, India, Haiti, Nepal, Sudan, Guinea, Malawi, Mozambique, South Sudan, and Zambia.

The oral cholera vaccine belonging to the vaccine class is an oral suspension.

The vaccine contains live, attenuated cholera bacteria that multiply in the recipient's digestive system and provide protection. Although the specific immunological mechanisms that protect against cholera remain unclear, a human challenge trial has shown that increased serum vibriocidal antibody levels seen ten days after vaccination corresponds with immunity. This indicates that vibriocidal antibodies are crucial in cholera protection after oral cholera vaccination. Further investigation is required to fully understand the exact immunological processes involved in providing protection against cholera by this vaccine.

The oral cholera vaccine is available as a powder for oral suspension.

Powder for oral suspension: To be administered orally, as applicable.

Oral cholera vaccine can be used as follows:

• To protect individuals travelling to endemic regions.

• To protect high-risk populations, individuals with underlying medical conditions or at high risk should be given immunity.

• To provide prophylaxis in outbreak situations such as during epidemics and also control the spread of cholera outbreaks in affected communities.

The oral cholera vaccine can help support the following health benefits:

• Prevention: If untreated, cholera is a serious and fatal condition. It is mainly transmitted by contaminated water or food and caused by the Vibrio cholerae. The oral cholera vaccine induces the body to develop defences (antibodies) against the bacterium. Individuals visiting places where cholera is frequent are often advised to get this vaccination. However, staying away from contaminated beverages and food while travelling is crucial.
• Vulnerable populations: Children, the elderly, pregnant women, and those with underlying medical issues are some of the groups who are particularly susceptible to cholera. These vaccines are very useful in protecting those at-risk populations. For instance, immunizing pregnant mothers provides their unborn children with passive protection during the crucial first few months of life and protects them from cholera.
• Herd immunity: Public health benefits greatly from extensive cholera vaccinations. The possibility of severe cholera ramifications among them is reduced. It protects the person vaccinated and those individuals with weaker immune systems, children, the elderly, and vulnerable populations, reducing overall cholera transmission. The oral cholera vaccine's administration ultimately results in a decrease in cholera-related morbidity and mortality.
• Control strategy: The effectiveness of public health initiatives is increased when the oral cholera vaccine is incorporated into comprehensive cholera control strategies. It enhances other preventative measures, like better water and sanitation systems and hygiene standards. Immunisation helps to increase the capacity and resource allocation of the healthcare system by lowering the incidence of cholera cases.

Indicated for active vaccination against Vibrio cholerae serogroup O1 illness among individuals aged 2 to 64 years travelling to cholera-affected areas but has not been shown to protect against disease which is caused by V cholerae serogroup O139 or other non-O1 serogroups.

Orally: The cholera vaccine is given by mouth as a single dose. This vaccine is a powder mixed with water before you take it. This vaccine is taken by mouth, and you should avoid eating, drinking, and taking any other medicines by mouth for an hour before and after, as this may make it less effective.

100 mL of a single, oral liquid dose should be administered orally at least ten days before travelling to a cholera-affected region.

The dosage and duration of treatment should be as per the clinical judgement of the treating physician

Oral suspension (after reconstitution)

(Following reconstitution) 100 mL

Lyophilized V cholerae CVD 103-HgR is provided in a foil package with a foil packet containing buffer.

Dosage Adjustment for Adult Patients

To prevent cholera

Adults: 100 mL PO in a single dose at least ten days before any potential cholera exposure

The Cholera vaccine is available in the form of powder for oral suspension.

Oral cholera vaccine should be used to prevent cholera infection in children and individuals at high risk, along with no appropriate dietary restrictions.

It is advised not to eat heavy meals for at least an hour before and an hour after receiving a vaccination to help reduce the chances of vomiting the vaccine or diluting its effectiveness due to ample food intake.

Avoiding unpeeled fruits, raw or undercooked seafood, and untreated or unboiled water are among the food and water safety precautions that should be followed as they significantly raise the risk of cholera infection.

Before and during immunisation, being well-hydrated is essential. Drinking enough water can improve the body's reaction to immunisation and help overall well-being.

Oral cholera vaccine may be contraindicated in the following conditions-

• Hypersensitivity (previous dose of cholera vaccine or any of its components)
• Newborns or infants below two years.
• Severe GI illness
• Severe immunodeficiency due to any cause like HIV, leukaemia, or chemotherapy.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• People with an acute digestive illness with fever should postpone being vaccinated until their condition improves.
• Children with weak immune systems, such as those with HIV/AIDS infection or cancer or who are taking certain drugs, may not respond as well to oral cholera vaccine and may consult a healthcare professional who might suggest modifying the vaccine schedule or giving additional doses to these people to improve protection.

• Although the vaccine is generally safe for pregnant, it should only be administered with a high risk of cholera infection.
• Wash hands often for at least two weeks after receiving this vaccination, especially after using toilets or handling food.

Caution is advised when consuming alcohol with the oral Cholera vaccine.

There is no sufficient scientific evidence regarding the use and safety of the oral cholera vaccine in the breastfeeding population.

Unsafe to use during pregnancy.

There is no sufficient scientific evidence regarding the use and safety of the oral Cholera vaccine in concurrent use with any particular food.

The adverse reactions related to the oral cholera vaccine can be categorized as

• Common: Mild headache, mild tiredness, loose stools, mild nausea/vomiting, mild abdominal pain
• Less common: Severe fever, moderate headache, moderate tiredness, loose stools, moderate nausea/vomiting and moderate abdominal pain
• Rare: Serious allergic reactions (anaphylaxis) and neurological issues

The clinically relevant drug interactions of the oral cholera vaccine are briefly summarized here:

• Immunosuppressants- The immunological response may be suppressed by immunosuppressive treatments such as radiation, antimetabolites, alkylating agents, cytotoxic medicines, and corticosteroids (used in dosages larger than therapeutic doses).
• Other Vaccines- Multiple vaccinations, including the oral cholera vaccine, given at the same time may increase the risk of adverse reactions. To reduce such a risk, medical professionals frequently adhere to vaccination regimens considering the time and space of vaccines.

The common side of the oral Cholera Vaccine includes the following-

• Fatigue
• Headache,
• Pain in the abdomen
• Nausea
• Vomiting
• Loss of appetite
• Diarrhoea
• Fever

Oral Cholera Vaccine should be prudent in the following group of special populations.

• Pregnancy: Due to limited safety data during pregnancy, the oral cholera vaccine is not recommended in pregnant women. The cholera vaccine is not directly absorbed into the bloodstream after oral administration, and fetal exposure is not predicted if taken by a pregnant woman. However, maternal cholera can have a negative impact on pregnancy outcomes, including fetal mortality. The vaccine strain may remain in the mother's stool for up to 7 days, with transmission to the newborn likely during vaginal birth.

• Paediatrics: The oral cholera vaccine is generally safe, with minimal side effects. It provides critical protection against potentially fatal cholera infections, particularly in areas with outbreaks or endemic cholera, decreasing the severity of the disease and its impact on children.

Dosage Adjustment for Paediatric Patients

Cholera Prevention

<2 years: There is no evidence of safety or efficacy.

≥2 years: Administer one dose at least ten days before potential cholera exposure.

50 mL oral for children aged 2 to 6 years;

100 mL oral for children aged more than six years.

• Geriatrics:

There is no sufficient scientific evidence traceable regarding the use and safety of the oral Cholera vaccine for geriatric populations.

• Lactating mothers:

Oral Cholera vaccine administered orally to mothers does not result in systemic absorption, and breastfeeding is unlikely to expose the baby to the vaccine. However, there is no sufficient scientific evidence traceable regarding the use and safety of the Cholera vaccine for lactating mother populations.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

Overdosage of oral cholera vaccine rarely occurs because it is typically administered as a single or double dose according to the recommended schedule by healthcare professionals according to specific or precise dosing guidelines.

There is no specific antidote or treatment for excessive intake of oral cholera vaccine. Medical attention should be sought immediately when an overdose is suspected, followed by close monitoring for any adverse effects or allergic reactions. Supportive therapy should also be given, addressing any symptoms that persist or worsen. Physical treatment might be added if necessary.

Pharmacodynamics of Oral Cholera vaccine:

The oral cholera vaccine has a potential physiological mechanism that plays a role in its pharmacodynamics, involving its interaction with the immune system.

The oral cholera vaccine stimulates an immunological reaction in the digestive system, which results in the generation of crucial vibriocidal antibodies that protect against cholera. Within the first seven days after immunisation, shedding of the vaccine strain was measured in research, including 53 healthy persons who received the vaccine. According to the findings, 11.3% (95% CI 4.3%, 23.0%) of recipients passed the vaccination in their faeces at some point throughout this period. The most significant percentage of shedding occurred on the seventh day (7.5% [95% CI 2.1%, 18.2%]). Nevertheless, additional research is necessary to thoroughly understand the ramifications of the specific length of vaccination strain shedding, which remains to be seen.

Pharmacokinetics of Oral Cholera vaccine:

• Absorption: The vaccine contains inactivated components of the cholera-causing bacterium Vibrio cholerae. When cholera vaccine is administered orally, it is absorbed in the gastrointestinal system.
• Distribution: The vaccine's components trigger an immunological reaction in the gastrointestinal tract after ingestion. This initiates the process of producing particular antibodies against Vibrio cholerae.
• Metabolic process: The body's tissues, particularly the liver, are where cholera vaccine is metabolised. Depending on specific vaccine components, the exact metabolic pathways might vary.

• Excretion: Metabolised vaccine residues, as well as any unabsorbed components of the vaccine, are eliminated from the body through normal excretory functions, such as urine and faeces.

• McCarty JM, Lock MD, et al. Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45. Vaccine. 2018 Feb 1;36(6):833-840. doi: 10.1016/j.vaccine.2017.12.062. Epub 2018 Jan 6.
• Mahalanabis D, Ramamurthy T, et al. (2009) Randomized placebo-controlled human volunteer trial of a live oral cholera vaccine VA 1.3 for safety and immune response. Vaccine 27: 4850–6.
• Gabutti, Giovanni et al. “Cholera, the Current Status of Cholera Vaccines and Recommendations for Travellers.” Vaccines vol. 8,4 606. 14 Oct. 2020, doi:10.3390/vaccines8040606
• Tacket CO, Losonsky G, Nataro JP, Comstock L, Michalski J, Edelman R, Kaper JB, Levine MM. Initial clinical studies of CVD 112 Vibrio cholerae O139 live oral vaccine: safety and efficacy against experimental challenge. J Infect Dis. 1995 Sep;172(3):883-6. doi: 10.1093/infdis/172.3.883. PMID: 7658089.

• Inform the caregivers of the schedule for administering the oral cholera vaccine doses, emphasizing the benefits of cholera vaccination, including reduced risk of contracting cholera and its potentially severe consequences.
• Inform the vaccination recipient, their parents, or their guardians whether they had any side effects from a prior dosage of the oral cholera vaccine, including the number of doses required and the recommended schedule.
• Inform individuals about the most frequent oral cholera vaccine side effects within seven days after administration (fatigue, headache, stomach discomfort, nausea/vomiting, loss of appetite, and diarrhoea). Encouraging them to immediately report any unexpected or severe responses to the healthcare physician and, whenever applicable, to use reporting systems like the Vaccine Adverse Event Reporting System (VAERS)
• Inform caregivers of the recommended immunization schedule, which usually consists of two or three doses, depending on the vaccine brand. Also, mention the ages at which the doses should be administered and give the Vaccine Information Statements, which must be disclosed before immunization by the National Childhood Vaccine Injury Act of 1986 about the Centres for Disease Control and Prevention (CDC) website (www.cdc.gov/vaccines), these resources are freely accessible.

https://main.mohfw.gov.in/sites/default/files/Universal.pdf

https://www.indianpediatrics.net/oct2014/785 figure1.pdf

http://www.cdc.gov/vaccines/schedules/hcp/index.html

https://www.cdc.gov/cholera/vaccines.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536201/