Introduction

Live, attenuated bacterial vaccine containing Vibrio cholerae strain CVD 103-HgR derived from V. cholerae serogroup O1. Other cholera vaccines (e.g., oral inactivated vaccine containing whole-cell V. cholerae O1 with recombinant cholera toxin B subunit, oral inactivated vaccine containing whole-cell V. cholerae O1 and O139) may be available in other countries.

Uses for Cholera Vaccine Live Oral

Prevention of Cholera Infection

Prevention of disease caused by V. cholerae serogroup O1 in adults 18 through 64 years of age traveling to cholera-affected areas.

Cholera is an acute, intestinal infection caused by toxigenic V. cholerae and may be associated with sudden onset of profuse watery diarrhea and rapid progression to volume depletion, severe dehydration, hypovolemic shock, and death. Many individuals with V. cholerae infection are asymptomatic or have only mild to moderate disease; 10–20% of infected individuals develop severe disease and potentially fatal dehydration. Transmitted principally by ingestion of water and/or food contaminated with feces from individuals with V. cholera infection and generally occurs in countries that lack clean drinking water or proper sanitation. Although more than 200 V. cholerae serogroups identified, only toxigenic strains of V. cholerae serogroups O1 and O139 have been associated with cholera epidemics; serogroup O1 is the leading cause of cholera worldwide.

Cholera is uncommon in US, but endemic in approximately 50–60 countries, principally in less well-developed areas of the world that have poor sanitation and primitive water systems (e.g., areas of Africa, South and Southeast Asia, the Caribbean). In 2015, 172,454 cases (including 1304 fatalities) were reported in 42 different countries. However, many cases unreported and it has been estimated that up to 3–4 million cholera cases (up to 95,000–143,000 fatalities) may occur annually worldwide. Large cholera epidemic began in Haiti in 2010 following a devastating earthquake; CDC states cholera likely to persist at endemic levels in Haiti for the foreseeable future and sporadic cases may continue be associated with travel to and from Caribbean countries, including Haiti, the Dominican Republic, and Cuba.

During 2001–2013, there were 123 confirmed cases of cholera in the US in individuals who had been traveling abroad. Risk of acquiring cholera is highest in those traveling to countries where cholera is endemic or epidemic, and is especially high in travelers who drink untreated water, eat raw or poorly cooked food (especially seafood), or do not follow proper hygiene recommendations while in cholera endemic or outbreak settings. Individuals at increased risk for poor clinical outcome if infected with toxigenic V. cholerae include those without rapid access to medical care and rehydration therapy; those with certain chronic medical conditions (e.g., immunosuppression, cardiovascular disease, renal disease); those with low gastric acidity related to antacid therapy, partial gastrectomy, or other causes; those with blood type O; and pregnant women.

For US travelers, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) recommends cholera vaccine live oral for adults 18 through 64 years of age who will be at increased risk of exposure to toxigenic V. cholerae O1 because they will be traveling to areas with active cholera transmission. These areas are defined as a province, state, or other administrative subdivision within a country with endemic or epidemic cholera caused by toxigenic V. cholerae O1. This includes areas that have had cholera activity within the past year and are prone to recurrence of cholera epidemics; does not include areas with only rare imported or sporadic cholera cases.

ACIP states that routine use of cholera vaccine is not recommended for most travelers from the US since the majority do not visit areas with active cholera transmission and, therefore, are at low risk of exposure to toxigenic V. cholerae.

Efficacy for prevention of cholera not established in individuals living in cholera-affected areas or in individuals who have preexisting immunity because of previous exposure to V. cholerae or previous vaccination with a cholera vaccine.

Has not been shown to provide protection against disease caused by V. cholerae serogroup O139 or other non-O1 serogroups.

All travelers to cholera-affected areas should follow safe food and water precautions and proper sanitation and personal hygiene measures, regardless of vaccination status. If severe diarrhea develops, traveler should seek prompt medical attention, particularly fluid replacement therapy.

The most recent information regarding geographic areas where cholera is actively being transmitted and additional information on vaccination and other precautions for prevention of cholera are available from CDC at [Web] and [Web].

Cholera Vaccine Live Oral Dosage and Administration

Administration

Oral Administration

Administer orally as a single dose.

Avoid eating or drinking for 60 minutes before and after ingestion of the vaccine.

Provided by the manufacturer in single-dose carton that contains foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component). Reconstitute and mix these 2 components according to manufacturer's instructions to provide an oral suspension containing cholera vaccine live oral. (See Reconstitution under Dosage and Administration.)

Oral suspension must be administered within 15 minutes after preparation. Swallow entire contents of the cup (100 mL) at one time.

After the vaccine is administered, the cup (including any residue remaining in the cup), stirrer, and empty component packets are considered biohazardous materials; handle and dispose of according to standard procedures for medical waste. Use 70% isopropyl alcohol or 10% bleach to clean nondisposable equipment used to prepare the oral suspension and to inactivate any spilled vaccine.

Reconstitution

Remove single-dose carton containing foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component) from freezer. Thawing unnecessary. Use within 15 minutes after removal from frozen storage; do not expose packets to temperatures >27°C. (See Storage under Stability.)

The buffer component must be reconstituted first. Open foil packet of buffer component with scissors and pour contents into a clean disposable cup containing 100 mL of cold or room temperature (5–22°C) purified bottled water; do not use tap water, nonpurified bottled water, or any other beverage or liquid. Effervescence will occur; stir with a disposable stirrer until powder buffer dissolves completely.

After buffer component is dissolved, open foil packet containing lyophilized cholera vaccine (active component) with scissors and pour contents into the cup containing reconstituted buffer. Stir the mixture for at least 30 seconds to form a slightly cloudy suspension that may contain some white particles; lyophilized vaccine may not dissolve completely.

If buffer component and active component are not reconstituted and mixed in proper sequence, discard the vaccine.

Dosage

Adults

Prevention on Cholera Infection

Adults 18 through 64 Years of Age Traveling to Cholera-affected Areas

Administer a single dose of 100 mL of reconstituted oral suspension (see Reconstitution under Dosage and Administration). Give dose ≥10 days before potential exposure to cholera.

Duration of immunity and protection against cholera after a single dose not fully determined (see Duration of Immunity under Cautions). Safety and efficacy of revaccination or booster doses not established; ACIP does not currently recommend use of booster doses.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

Not indicated in geriatric adults ≥65 years of age.

Contraindications

• History of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or to a previous dose of any cholera vaccine.

Warnings/Precautions

Individuals with Altered Immunocompetence

Safety and efficacy not established in immunocompromised individuals. Immunologic response to the vaccine may be diminished in individuals with altered immunocompetence related to disease or immunosuppressive therapy.

ACIP states that individuals with altered immunocompetence generally should not receive live vaccines since these individuals may be at increased risk for adverse reactions to such vaccines and may have diminished or suboptimal immune responses to vaccines.

Transmission of Vaccine Strain of Vibrio cholera

Cholera vaccine live oral contains live, attenuated V. cholerae that may be shed in stool of vaccine recipients for ≥7 days and may be transmitted to close contacts (e.g., household contacts). Total duration of fecal shedding of the V. cholerae vaccine strain after vaccination is unknown.

Fecal shedding of the vaccine strain has been detected as early as day 1 and has been highest on day 7 after vaccination. In one study, 11% of vaccinees shed the vaccine strain in their stools; no evidence that these individuals transmitted the vaccine strain to household contacts.

Because of potential transmission of vaccine strain, vaccinees should take precautions (i.e., thorough and frequent handwashing, especially after bowel movements and before preparing and handling food) for ≥14 days after vaccination.

Caution is advised when considering whether to administer cholera vaccine live oral to individuals with immunocompromised close contacts (e.g., individuals with malignancies or primary immunodeficiencies, individuals receiving immunosuppressive therapy).

Limitations of Vaccine Efficacy

May not protect all vaccine recipients against cholera infection.

Will not provide protection against V. cholerae serogroups not represented in the vaccine (e.g., V. cholerae serogroup O139, other non-O1 serogroups).

Duration of Immunity

Duration of immunity and protection against cholera after vaccination with cholera vaccine live oral not fully determined. Data to date indicate duration of protection after a single dose is at least 3 months. In one study, approximately 90% of vaccinees still had vibriocidal antibody responses 6 months (180 days) after a single dose.

Safety and efficacy of revaccination or booster doses not established.

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained. (See Storage under Stability.)

Do not administer vaccine that has been mishandled or has not been stored at the recommended temperature.

If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether the vaccine is usable.

Specific Populations

Pregnancy

Data not available to date regarding use in pregnant women.

Because cholera vaccine live oral not absorbed systemically following oral administration, vaccination during pregnancy not expected to result in fetal exposure.

Consider that cholera infection is associated with adverse pregnancy outcomes, including fetal death. Also consider that the V. cholerae vaccine strain may be shed in stools of vaccinated mothers for ≥7 days after vaccination and potentially could be transmitted to the infant during vaginal delivery.

Pregnancy registry at 800-533-5899.

Lactation

Data not available to date regarding use in nursing women.

Because cholera vaccine live oral not absorbed systemically following oral administration, exposure to the vaccine not expected in breast-fed infants.

Pediatric Use

Safety and efficacy not established in children and adolescents <18 years of age.

Geriatric Use

Safety and efficacy not established in adults ≥65 years of age.

Common Adverse Effects

Tiredness, headache, abdominal pain, nausea, vomiting, lack of appetite, diarrhea.

Administration

Oral Administration

Administer orally as a single dose.

Avoid eating or drinking for 60 minutes before and after ingestion of the vaccine.

Provided by the manufacturer in single-dose carton that contains foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component). Reconstitute and mix these 2 components according to manufacturer's instructions to provide an oral suspension containing cholera vaccine live oral. (See Reconstitution under Dosage and Administration.)

Oral suspension must be administered within 15 minutes after preparation. Swallow entire contents of the cup (100 mL) at one time.

After the vaccine is administered, the cup (including any residue remaining in the cup), stirrer, and empty component packets are considered biohazardous materials; handle and dispose of according to standard procedures for medical waste. Use 70% isopropyl alcohol or 10% bleach to clean nondisposable equipment used to prepare the oral suspension and to inactivate any spilled vaccine.

Reconstitution

Remove single-dose carton containing foil packet of lyophilized live, attenuated V. cholerae CVD 103-HgR (active component) and foil packet of dry powder buffer (buffer component) from freezer. Thawing unnecessary. Use within 15 minutes after removal from frozen storage; do not expose packets to temperatures >27°C. (See Storage under Stability.)

The buffer component must be reconstituted first. Open foil packet of buffer component with scissors and pour contents into a clean disposable cup containing 100 mL of cold or room temperature (5–22°C) purified bottled water; do not use tap water, nonpurified bottled water, or any other beverage or liquid. Effervescence will occur; stir with a disposable stirrer until powder buffer dissolves completely.

After buffer component is dissolved, open foil packet containing lyophilized cholera vaccine (active component) with scissors and pour contents into the cup containing reconstituted buffer. Stir the mixture for at least 30 seconds to form a slightly cloudy suspension that may contain some white particles; lyophilized vaccine may not dissolve completely.

If buffer component and active component are not reconstituted and mixed in proper sequence, discard the vaccine.

Dosage

Adults

Prevention on Cholera Infection

Adults 18 through 64 Years of Age Traveling to Cholera-affected Areas

Administer a single dose of 100 mL of reconstituted oral suspension (see Reconstitution under Dosage and Administration). Give dose ≥10 days before potential exposure to cholera.

Duration of immunity and protection against cholera after a single dose not fully determined (see Duration of Immunity under Cautions). Safety and efficacy of revaccination or booster doses not established; ACIP does not currently recommend use of booster doses.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

Not indicated in geriatric adults ≥65 years of age.

Vaccines

Data not available regarding concurrent administration with other vaccines, including other vaccines used in travelers (e.g., typhoid vaccine, yellow fever vaccine).

Specific Drugs