May 12, 2017
Adults between the ages of 18 and 64 years are recommended to receive one dose of the lyophilized CVD 103-HgR (Vaxchora, PaxVax) cholera vaccine before travel to areas with active cholera transmission, according to a recommendations published May 11 in the Morbidity and Mortality Weekly Report. The Advisory Committee on Immunization Practices initially recommended use of the cholera vaccine in June 2016 to prevent cholera in adult travelers to areas with endemic or epidemic cholera.
The live attenuated oral lyophilized CVD 103-HgR, the first and only vaccine approved by the US Food and Drug Administration and licensed for use in the United States, prevents disease caused by Vibrio cholerae bacteria of serogroup O1, which is responsible for more than 99% of global cases. The vaccine does not protect against V cholerae O139, according to the World Health Organization. The vaccine should be administered at least 10 days before travel, according to the US Food and Drug Administration.
"The primary prevention strategy for cholera is consistent access to and exclusive use of safe water and food and frequent handwashing," write Karen K. Wong, MD, from the Centers for Disease Control and Prevention's National Center for Emerging and Zoonotic Infectious Diseases, Atlanta, Georgia, and colleagues. "Nonetheless, travelers to areas of active cholera transmission, which include areas with current or recent endemic or epidemic cholera activity, might be exposed to toxigenic V. cholerae O1 through inadvertent or unexpected means, despite efforts to adhere to prevention measures."
Cholera is endemic in approximately 60 countries and is the source of epidemics, causing approximately 2.9 million cases and 95,000 deaths each year.
Those considered at higher risk for cholera exposure in endemic or epidemic areas include "travelers visiting friends and relatives, health care personnel, cholera outbreak response workers, and persons traveling to or living in a cholera-affected area for extended periods."
The Advisory Committee on Immunization Practices Cholera Vaccine Work Group assessed evidence for the vaccine's safety and efficacy and the epidemiology of cholera worldwide, using clinical trial data from both the current lyophilized CVD 103-HgR and a previous CVD 103-HgR formulation used abroad and discontinued for business reasons unrelated to safety or efficacy. According to findings presented at the August 2015 Advisory Committee on Immunization Practices meeting, the vaccine is 90% effective 10 days after vaccination and 80% effective 3 months after vaccination against severe diarrhea, with no serious adverse events reported in clinical studies. Both formulations induced a vibriocidal antibody response, "the best available correlate of protection against cholera infection," the authors state.
The only adverse event statistically different between groups was mild diarrhea, occurring in 3.8% of vaccine recipients compared with 1.6% of unvaccinated groups.
Overall safety data, however, were limited, given the relatively limited number of people who received the currently available formulation. In addition, there are no data regarding the coadministration of the cholera vaccine with other vaccines.
Furthermore, there are no data are available for safety or efficacy of booster doses of the vaccine or protection duration beyond 3 months.
Vaccine recipients should not have received oral or parenteral antibiotics in the 14 days before vaccine administration; effects of antibiotics taken after vaccination are unknown, according to the authors. Recipients should wait at least 10 days after vaccine administration to take chloroquine. Data are unavailable regarding potential interaction with the oral live-attenuated typhoid vaccine, but taking the typhoid vaccine at least 8 hours after the cholera vaccine may decrease potential interference.
Lyophilized CVD 103-HgR may shed in stool with the potential for transmission to close contacts. A week after administration, 11.1% of recipients had cultures of the vaccine strain in stool, but the strain was not found in any of 28 household contacts of recipients 7 days after vaccination. However, with the previous CVD 103-HgR vaccine, seroconversion was seen in 3.7% of family contacts of vaccine recipients at 9 or 28 days postvaccination.
Although no data exist on using CVD 103-HgR in pregnant or breast-feeding women, "maternal exposure to the vaccine is not expected to result in exposure of the fetus or breastfed infant to the vaccine" because of lack of systemic absorption of the vaccine. "However, the vaccine strain might be shed in stool for =7 days after vaccination, and theoretically, the vaccine strain could be transmitted to an infant during vaginal delivery," the authors write.
Those with history of a severe allergic reaction to components of this or previous cholera vaccines should not receive it. No data exist on the lyophilized CVD 103-HgR vaccine's use in immunocompromised populations; a previous CVD 103-HgR formulation showed lower vibriocidal seroconversion among HIV-positive (58%) individuals than among HIV-negative (71%) ones with no significant differences in adverse events.
The work group summarized the strength of current evidence from randomized controlled trials and observational studies at the February 2016 meeting for outcomes for "prevention of cholera death, life-threatening cholera diarrhea, severe cholera diarrhea, and cholera diarrhea of any severity" and for "induction of vibriocidal antibody response, occurrence of serious and systemic adverse events, and impact on effectiveness of co-administered vaccines and medications." Efficacy evidence was judged to be of type 1 (highly reliable), using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Safety outcome evidence was determined to be type 3.
The research was funded by the Centers for Disease Control and Prevention. The authors have disclosed no relevant financial relationships.