CDC Issues New Cholera Vaccine Recommendations for Children, Adolescents

The Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention (CDC) has released new recommendations for use of the cholera vaccine. These recommendations were published in Morbidity and Mortality Weekly Report.

Cholera is an acute gastrointestinal illness caused by Vibrio cholerae and is associated with watery diarrhea. Without proper treatment, cholera can be severe or fatal. It is most commonly caused by ingestion of water or food contaminated by toxigenic V cholerae subgroup O1. Person-to-person transmission is rare but may occur in areas with inadequate sanitation practices. Symptoms present hours to days following infection onset.

Cholera is endemic in approximately 50 countries. There are 1.3 to 4.0 million individuals diagnosed with cholera and 21,000 to 143,000 cholera-associated deaths worldwide each year. Individuals living in the US are primarily at risk for contracting cholera during travel to cholera-endemic regions. Of note, 88% of the 64 reported diagnoses of cholera among US patients between 2012 and 2018 were associated with travel.

The cholera vaccine, lyophilized CVD 103-HgR (CVD 103-HgR), is a live attenuated oral vaccine that was approved in 2016 for US adults aged 18 to 64 years, with approval later extended to children and adolescents (age, 2-17 years) in 2020. Four other oral cholera vaccines have been prequalified by the World Health Organization, but none are available in the US.

For adults aged between 18 and 45 years, the CVD 103-HgR vaccine is estimated to be 90% effective against moderate to severe diarrhea (defined as fecal output >3 L) 10 days following vaccination and 80% effective at 3 months. The current formulation of the CVD 103-HgR vaccine was found to induce a 4-fold or higher increase in serum vibriocidal antibody titers in more than 93% of vaccine recipients at day 11 following vaccination, including in those aged between 2 and 17 years and 18 and 45 years.

No serious vaccine-related adverse events have been reported among vaccine recipients aged between 2 and 64 years. Results of a clinical trial conducted among adults aged 18 to 45 years showed that cholera vaccine vs placebo recipients were more likely to report fatigue, headache, nausea or vomiting, and diarrhea following vaccination. Similar results were observed in a clinical trial conducted among children and adolescents aged 2 to 17 years, with more reports of fatigue, headache, abdominal pain, and lack of appetite among vaccine vs placebo recipients.

The ACIP recommends that all US individuals (age, 2 -64 years) who travel to cholera-affected areas receive the CVD 103-HgR vaccine. An affected area was defined as any area in which cholera caused by V cholerae subgroup 01 has been endemic or epidemic within the past year.

The vaccine should be administered at least 10 days or earlier prior to travel. Individuals should avoid food and beverage for 60 minutes prior to and following vaccination receipt. The vaccine is prepared by dissolving the packaged buffer sachet in 100 mL of noncarbonated and nonflavored bottled water that is either cold or at room temperature water. Once mixed, the reconstituted buffer solution should be consumed in its entirety, except in the case of individuals aged 2 to 5 years for whom consumption of half of the vaccine volume is recommended. For children and adolescents aged 2 to 17 years, stevia (1 g) or table sugar (1-4 g) may be added to improve vaccine palatability. The cholera vaccine should not be mixed with food or beverage, and tap water cannot be used as the chlorine content affects vaccine viability.

The coadministration of the CVD 103-HgR vaccine with antibiotics may diminish the effectiveness of the vaccine. The optimal time for the coadministration of the vaccine with antibiotics remains unknown. The vaccine package insert states that CVD 103-HgR should not be administered among patients who have received oral or parenteral antibiotics within the 14 days prior to vaccination.

For patients traveling to areas where the use of antimalarials is recommended, the vaccine manufacturer recommends that administration occur at least 10 days prior to starting chloroquine; however, the optimal time for administration remains unknown.

There are no available data about CVD 103-HgR vaccination during pregnancy or while breastfeeding. However, the live attenuated bacterial vaccine is not absorbed systemically or expected to cause bacterial exposure to the fetus or a breastfeeding infant.

Bacterial shedding in stool may occur for 7 days or more following vaccination. To avoid bacterial transmission, the manufacturer recommends that vaccinated individuals wash their hands vigorously after toilet use for at least 14 days.

No published data are available in regard to vaccine-induced protection against cholera beyond 3 months after vaccination receipt, nor are there any data available about the efficacy of booster vaccine doses.

The guideline authors concluded, “As new information becomes available on cholera epidemiology and cholera vaccines, ACIP and CDC will review and revise these recommendations as indicated.”