Cholera vaccine

Cholera vaccine

Vaccine description
Target	Vibrio cholerae
Vaccine type	Inactivated
Clinical data
Trade names	Dukoral, Vaxchora, others
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	AU: B2 [1]
ATC code	J07AE01 (WHO) J07AE02 (WHO) J07AE51 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[1][2] CA: ℞-only / Schedule D[3] UK: POM (Prescription only)[4] US: ℞-only[5][6] EU: Rx-only[7][8][9]
Identifiers
DrugBank	DB11643 Y DB14443 Y
ChemSpider	none
UNII	V9G528E9E0
KEGG	D03530
NY (what is this?)  (verify)

A cholera vaccine is a vaccine that is effective at preventing cholera.^[10] The currently recommended cholera vaccines are administered orally to elicit a protective local mucosal immune response in the gut, which was poorly achieved with the injectable vaccines that were used until the 1970s. The first effective oral cholera vaccine was Dukoral, developed in Sweden in the 1980s. For the first six months after vaccination it provides about 85 percent protection, which decreases to approximately 60 percent during the first two years.^[10][11][12] When enough of the population is immunized, it may protect those who have not been immunized thereby increasing the total protective impact to more than 90 percent (known as herd immunity).^[10]

The World Health Organization (WHO) currently recommends the use of three oral cholera vaccines – Dukoral, Shanchol and Euvichol-Plus – in combination with other measures among those at high risk for cholera.^[10] Two vaccine doses with a 1-6 week interval are typically recommended.^[10] The duration of protection is at least two years in adults and six months in children aged 1–5 years.^[10] A live, attenuated single dose oral vaccine is available for those traveling to an area where cholera is common but is not WHO approved for public health use.^[13][14][15]

The available types of oral vaccine are generally safe.^[10] Mild abdominal pain or diarrhea may occur.^[10] They are safe in pregnancy and in those with poor immune function.^[10] They are licensed for use in more than 60 countries.^[10] In countries where the disease is common, the vaccine appears to be cost effective.^[10]

The first cholera vaccines were developed in the late 19th century.^[16] They were the first widely used vaccine that was made in a laboratory but were largely abandoned in the 1970s due to their then documented reactogenicity and poor efficacy .^[16]

Oral cholera vaccines were first introduced in the 1990s.^[10] It is on the World Health Organization's List of Essential Medicines.^[17][18]

Medical use

In the late twentieth century, oral cholera vaccines started to be used on a massive scale, with millions of vaccinations taking place, as a tool to control cholera outbreaks in addition to the traditional interventions of improving safe water supplies, sanitation, handwashing, and other means of improving hygiene.

The World Health Organization (WHO) recommends both preventive and reactive use of the vaccine, making the following key statements:^[20]

WHO recommends that current available cholera vaccines be used as complements to traditional control and preventive measures in areas where the disease is endemic and should be considered in areas at risk for outbreaks. Vaccination should not disrupt the provision of other high priority health interventions to control or prevent cholera outbreaks.... Reactive vaccination might be considered in view of limiting the extent of large prolonged outbreaks, provided the local infrastructure allows it, and an in-depth analysis of past cholera data and identification of a defined target area have been performed.

Although the vaccine specific protection observed, 60–70 percent, has been described as "moderate", herd immunity can multiply the effectiveness of vaccination. Dukoral has been licensed for children two years of age and older, Shanchol and Euvichol-Plus for children one year of age and older. The administration of the vaccine to adults confers additional indirect protection (herd immunity) also to children.

The WHO as of 2013 established a revolving stockpile, initially of only two million oral cholera vaccine doses.

The oral vaccines are generally of two forms: inactivated and attenuated.^{[citation needed]}

The first developed effective oral cholera vaccine, Dukoral, is a monovalent inactivated vaccine containing killed whole cells of V. cholerae O1 plus additional recombinant cholera toxin B subunit. Bacterial strains of both Inaba and Ogawa serotypes and of El Tor and Classical biotypes are included in the vaccine. Dukoral is taken orally with bicarbonate buffer, which protects the antigens from the gastric acid. The vaccine acts by inducing antibodies against both the bacterial components and CTB. The antibacterial intestinal antibodies prevent the bacteria from attaching to the intestinal wall, thereby impeding colonisation of V. cholerae O1. The anti-toxin intestinal antibodies prevent the cholera toxin from binding to the intestinal mucosal surface, thereby preventing the toxin-mediated diarrhoeal symptoms.^[24]

The two later inactivated oral cholera vaccines recommended by WHO, Shanchol and Euvichol-Plus, have an identical composition, containing killed whole cells of V. cholerae O1 (the same components as in Dukoral) plus formalin-killed V. cholerae O139 bacteria.^{[citation needed]}

A live, attenuated oral vaccine (CVD 103-HgR or Vaxchora), derived from a serogroup O1 classical Inaba strain, was approved for use in travellers by the US FDA in 2016.^[13][25][14]

Injectable

Although rarely in use, the injected cholera vaccines can be effective for people living where cholera is common. While being ineffective in young children, in such areas they can offer some degree of protection in adults and older children for up to six months.^[11]

Side effects

Both of the available types of oral vaccine are generally safe.^[10] Mild abdominal pain or diarrhea may occur.^[10] They are safe in pregnancy and in those with poor immune function.^[10] They are licensed for use in more than 60 countries.^[10] In countries where the disease is common, the vaccine appears to be cost effective.^[10]

History of development

The first cholera vaccines were developed in the late 19th century. There were several pioneers in the development of the vaccine:

• The first known attempt at a cholera vaccine was made by Louis Pasteur and it was aimed at preventing cholera in chickens.^[26] This was the first widely used vaccine that was made in a laboratory.^[16] Later use showed this early cholera vaccine to be ineffective.^[27]
• In 1884, Spanish physician Jaume Ferran i Clua developed a live vaccine he had isolated from cholera patients in Marseilles, and used it that on over 30,000 individuals in Valencia during that year's epidemic. However, his vaccine and inoculation was rather controversial and was rejected by his peers and several investigation commissions,^[28] but it ended up demonstrating its effectiveness and being recognized for it.^[29]
• In 1892, Waldemar Haffkine developed an effective vaccine with less severe side effects, later testing it on more than 40,000 people in the Calcutta area from 1893 to 1896.^[30] His vaccine was accepted by the medical community, and is credited as the first effective human cholera vaccine.^{[28][31][32][33]}
• Finally, in 1896, Wilhelm Kolle introduced a heat-killed vaccine that was significantly easier to prepare than Haffkine's, using it on a large scale in Japan in 1902.^[34]

Oral cholera vaccines were first introduced in the 1990s.^[10]

Society and culture

Legal status

In 2016, the U.S. Food and Drug Administration (FDA) approved Vaxchora,^[15][14][25] a single-dose oral vaccine to prevent cholera for travelers. As of June 2016^[update], Vaxchora was the only FDA-approved vaccine for the prevention of cholera.^[25]

Economics

The cost to immunize against cholera is between US$0.10 and US$4.00 per vaccination.^[35]

The Vaxchora vaccine can cost more than US$250.^[36]

References