Cholera vaccine

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Cholera vaccine
Dukoral package vaccine vial.jpg
Vaccine description
Target Vibrio cholerae
Vaccine type Inactivated
Clinical data
Trade names Dukoral, Vaxchora, others
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A cholera vaccine is a vaccine that is effective at reducing the risk of contracting cholera. [10] The recommended cholera vaccines are administered orally to elicit local immune response in the gut where the intestinal cells produce antibodies against the cholera microbe. This immune response 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% protection, which decreases to approximately 60% 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 % (known as herd immunity). [10]

Contents

The World Health Organization (WHO) 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 cholera vaccine are generally considered safe for the majority of the population. [10] These vaccines were shown to be safe in pregnancy and in those with poor immune function. [10] The main side effects which could be experienced includes mild abdominal pain or diarrhea may occur. [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]

These vaccines 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]

Medical use

In the late 20th 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. [19] The Dukoral vaccine, which combines formalin- and heat-killed whole cells of Vibrio cholerae O1 and a recombinant cholera toxin B subunit, was licensed in 1991 and has been used widely, mainly for travellers. [10] The Shanchol bivalent vaccine, which combines the O1 and O139 serogroups, was originally developed in Vietnam under the name mORCVAX in 1997 and given in 20 million doses in Vietnam's public health programme during the following decade through targeted mass vaccination of school-aged children in cholera endemic regions. [10]

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.

The observed vaccine specific protection with two doses of the oral vaccine was 58–76%. [21] Herd immunity can multiply the effectiveness of vaccination. [10] 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.

As of 2013, the WHO established a revolving stockpile, initially of only 2 million oral cholera vaccine doses. [22] With donations from mainly the GAVI Alliance the stockpile has progressively expanded to now more than 40 million doses per year. [23] [24] It consists mainly of the Euvichol-Plus oral cholera vaccine being produced in South Korea. In total more than 150 million doses from the stockpile have been given in mass campaigns against both epidemic and endemic cholera in more than 25 cholera afflicted countries. A set goal of WHO's Global Task Force for Cholera Control (GTFCC) is, by using oral cholera vaccine and other available tools, by 2030 to have reduced cholera deaths by more than 90% and stopped transmission globally.  

Oral

Dukoral: vial of inactivated vaccine with packet of sodium bicarbonate buffer Dukoral vial bicarb.jpg
Dukoral: vial of inactivated vaccine with packet of sodium bicarbonate buffer

The oral vaccines are generally of two forms: inactivated and attenuated. [25]

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. [26]

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. [10]

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] [27] [14]

In 2024, the Euvichol-S vaccine, an optimized version of Euvichol-Plus, received WHO prequalification. This streamlined formulation is designed to maintain effectiveness while reducing production costs, significantly boosting the global oral cholera vaccine supply to 50 million doses, up from 38 million. This increase addresses the growing demand amid rising cholera outbreaks since 2021. [28]

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 the inactivated and attenuated oral vaccines available are generally safe. [10] Some of the common side effects include mild abdominal pain or diarrhea. [10] They are safe in pregnancy and in those with poor immune function. [10]

History of development

Cholera vaccinations by a Guinean nurse using a jet injector in Ziguinchor, Senegal, 1973 ASC Leiden - Coutinho Collection - G 01 - Ziguinchor, Senegal - Cholera vaccinations by Guinean nurse - 1973.tif
Cholera vaccinations by a Guinean nurse using a jet injector in Ziguinchor, Senegal, 1973

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

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

Society and culture

In 2016, the US Food and Drug Administration (FDA) approved Vaxchora, [15] [14] [27] a single-dose oral vaccine to prevent cholera for travelers. As of June 2016, Vaxchora is the only FDA-approved vaccine for the prevention of cholera. [27]

Economics

The cost to immunize against cholera is between US$0.10 and $4.00 per vaccination. [38]

The Vaxchora vaccine can cost more than $250. [39]

Related Research Articles

<span class="mw-page-title-main">Cholera</span> Bacterial infection of the small intestine

Cholera is an infection of the small intestine by some strains of the bacterium Vibrio cholerae. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Vomiting and muscle cramps may also occur. Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance. This may result in sunken eyes, cold skin, decreased skin elasticity, and wrinkling of the hands and feet. Dehydration can cause the skin to turn bluish. Symptoms start two hours to five days after exposure.

<i>Vibrio cholerae</i> Species of bacterium

Vibrio cholerae is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimp, and other shellfish. Some strains of V. cholerae are pathogenic to humans and cause a deadly disease called cholera, which can be derived from the consumption of undercooked or raw marine life species or drinking contaminated water.

<span class="mw-page-title-main">Polio vaccine</span> Vaccine to prevent poliomyelitis

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.

<span class="mw-page-title-main">DPT vaccine</span> Combination vaccine

The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus (lockjaw). The vaccine components include diphtheria and tetanus toxoids, and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.

<span class="mw-page-title-main">Influenza vaccine</span> Vaccine against influenza

Influenza vaccines, colloquially known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.

<span class="mw-page-title-main">Mumps vaccine</span> Vaccine which prevents mumps

Mumps vaccines are vaccines which prevent mumps. When given to a majority of the population they decrease complications at the population level. Effectiveness when 90% of a population is vaccinated is estimated at 85%. Two doses are required for long term prevention. The initial dose is recommended between 12 and 18 months of age. The second dose is then typically given between two years and six years of age. Usage after exposure in those not already immune may be useful.

<span class="mw-page-title-main">Hepatitis B vaccine</span> Vaccine against hepatitis B

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people, routine immunization results in more than 95% of people being protected.

<span class="mw-page-title-main">Hepatitis A vaccine</span> Vaccine to prevent hepatitis A

Hepatitis A vaccine is a vaccine that prevents hepatitis A. It is effective in around 95% of cases and lasts for at least twenty years and possibly a person's entire life. If given, two doses are recommended beginning after the age of one. It is given by injection into a muscle. The first hepatitis A vaccine was approved in Europe in 1991, and the United States in 1995. It is on the World Health Organization's List of Essential Medicines.

The rotavirus vaccine is a vaccine used to protect against rotavirus infections, which are the leading cause of severe diarrhea among young children. The vaccines prevent 15–34% of severe diarrhea in the developing world and 37–96% of the risk of death among young children due to severe diarrhea. Immunizing babies decreases rates of disease among older people and those who have not been immunized.

<span class="mw-page-title-main">Rabies vaccine</span> Vaccines to prevent rabies in humans and animals

The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the latent period after exposure to prevent the disease. Transmission of rabies virus to humans typically occurs through a bite or scratch from an infectious animal, but exposure can occur through indirect contact with the saliva from an infectious individual.

<span class="mw-page-title-main">Diphtheria vaccine</span> Vaccine against diphtheria

Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by Corynebacterium diphtheriae. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended at six weeks of age with two additional doses four weeks apart, after which it is about 95% effective during childhood. Three further doses are recommended during childhood. It is unclear if further doses later in life are needed.

<span class="mw-page-title-main">Plague vaccine</span> Vaccine used against Yersinia pestis

Plague vaccine is a vaccine used against Yersinia pestis to prevent the plague. Inactivated bacterial vaccines have been used since 1890 but are less effective against the pneumonic plague, so live, attenuated vaccines and recombinant protein vaccines have been developed to prevent the disease.

<span class="mw-page-title-main">Tick-borne encephalitis vaccine</span> Vaccine against tick-borne encephalitis

Tick-borne encephalitis vaccine is a vaccine used to prevent tick-borne encephalitis (TBE). The disease is most common in Central and Eastern Europe, and Northern Asia. More than 87% of people who receive the vaccine develop immunity. It is not useful following the bite of an infected tick. It is given by injection into a muscle.

<span class="mw-page-title-main">Measles vaccine</span> Vaccine used to prevent measles

Measles vaccine protects against becoming infected with measles. Nearly all of those who do not develop immunity after a single dose develop it after a second dose. When the rate of vaccination within a population is greater than 92%, outbreaks of measles typically no longer occur; however, they may occur again if the rate of vaccination decreases. The vaccine's effectiveness lasts many years. It is unclear if it becomes less effective over time. The vaccine may also protect against measles if given within a couple of days after exposure to measles.

<span class="mw-page-title-main">Rubella vaccine</span> Vaccine used to prevent rubella

Rubella vaccine is a vaccine used to prevent rubella. Effectiveness begins about two weeks after a single dose and around 95% of people become immune. Countries with high rates of immunization no longer see cases of rubella or congenital rubella syndrome. When there is a low level of childhood immunization in a population it is possible for rates of congenital rubella to increase as more women make it to child-bearing age without either vaccination or exposure to the disease. Therefore, it is important for more than 80% of people to be vaccinated. By introducing rubella containing vaccines, rubella has been eradicated in 81 nations, as of mid-2020.

<span class="mw-page-title-main">Yellow fever vaccine</span> Vaccine that protects against yellow fever

Yellow fever vaccine is a vaccine that protects against yellow fever. Yellow fever is a viral infection that occurs in Africa and South America. Most people begin to develop immunity within ten days of vaccination and 99% are protected within one month, and this appears to be lifelong. The vaccine can be used to control outbreaks of disease. It is given either by injection into a muscle or just under the skin.

<span class="mw-page-title-main">Tetanus vaccine</span> Vaccines used to prevent tetanus

Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence.

Dengue vaccine is a vaccine used to prevent dengue fever in humans. Development of dengue vaccines began in the 1920s, but was hindered by the need to create immunity against all four dengue serotypes. As of 2023, there are two commercially available vaccines, sold under the brand names Dengvaxia and Qdenga.

<span class="mw-page-title-main">Vaccine ingredients</span> Ingredients used in a vaccine dose

A vaccine dose contains many ingredients very little of which is the active ingredient, the immunogen. A single dose may have merely nanograms of virus particles, or micrograms of bacterial polysaccharides. A vaccine injection, oral drops or nasal spray is mostly water. Other ingredients are added to boost the immune response, to ensure safety or help with storage, and a tiny amount of material is left-over from the manufacturing process. Very rarely, these materials can cause an allergic reaction in people who are very sensitive to them.

Jan Roland Holmgren is a Swedish physician, microbiologist, immunologist, and vaccinologist, known for his research on cholera and mucosal immunology, specifically, for his leadership in developing "the world's first effective oral cholera vaccine".

References

  1. 1 2 "Vaxchora APMDS". Therapeutic Goods Administration (TGA). 18 September 2023. Retrieved 7 March 2024.
  2. ↑ "Summary for ARTG Entry:94483 Dukoral oral inactivated cholera vaccine liquid vial and buffer granules sachet". Therapeutic Goods Administration (TGA). Retrieved 30 July 2020.
  3. ↑ "Dukoral Product information". Health Canada. 25 April 2012. Retrieved 30 July 2020.
  4. ↑ "Dukoral suspension and effervescent granules for oral suspension, Cholera vaccine (inactivated, oral) – Summary of Product Characteristics (SmPC)". (emc). 7 December 2015. Retrieved 30 July 2020.
  5. ↑ "Vaxchora – cholera vaccine, live, oral kit". DailyMed. 24 October 2018. Retrieved 30 July 2020.
  6. ↑ "Vaxchora – cholera vaccine, live, oral kit". DailyMed. Retrieved 30 July 2020.
  7. ↑ "Eukoral EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 30 July 2020.
  8. ↑ "Vaxchora EPAR". European Medicines Agency (EMA). 30 January 2020. Retrieved 30 July 2020.
  9. ↑ "Vaxchora Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  10. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 "Cholera vaccines: WHO position paper – August 2017". Weekly Epidemiological Record. 92 (34): 477–498. August 2017. hdl: 10665/258764 . PMID   28845659.
  11. 1 2 Graves PM, Deeks JJ, Demicheli V, Jefferson T (August 2010). "Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected)". The Cochrane Database of Systematic Reviews. 2019 (8): CD000974. doi:10.1002/14651858.CD000974.pub2. PMC   6532721 . PMID   20687062.
  12. ↑ Sinclair D, Abba K, Zaman K, Qadri F, Graves PM (March 2011). "Oral vaccines for preventing cholera". The Cochrane Database of Systematic Reviews. 2011 (3): CD008603. doi:10.1002/14651858.CD008603.pub2. PMC   6532691 . PMID   21412922.
  13. 1 2 "Vaxchora (Cholera vaccine, Live, Oral)". U.S. Food and Drug Administration. Archived (PDF) from the original on 1 March 2017. Retrieved 15 March 2017.
  14. 1 2 3 "Vaxchora approval letter" (PDF). U.S. Food and Drug Administration. 10 June 2016. Archived from the original (PDF) on 22 July 2017. Retrieved 30 July 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. 1 2 "Vaxchora". U.S. Food and Drug Administration (FDA). 1 September 2019. Retrieved 28 December 2019.
  16. 1 2 3 Stanberry LR (2009). Vaccines for biodefense and emerging and neglected diseases (1st ed.). Amsterdam: Academic. p. 870. ISBN   978-0-08-091902-7. Archived from the original on 8 September 2017.
  17. ↑ Organization WH (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  18. ↑ Organization WH (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  19. ↑ Harris JB, LaRocque RC, Qadri F, Ryan ET, Calderwood SB (June 2012). "Cholera". Lancet. 379 (9835): 2466–76. doi:10.1016/s0140-6736(12)60436-x. PMC   3761070 . PMID   22748592.
  20. ↑ Oral cholera vaccines in mass immunization campaigns: guidance for planning and use (PDF). World Health Organization. 2010. ISBN   978-92-4-150043-2. Archived (PDF) from the original on 3 September 2014.
  21. ↑ Bi Q, Ferreras E, Pezzoli L, Legros D, Ivers LC, Date K, et al. (October 2017). "Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis". Lancet Infect Dis. 17 (10): 1080–8. doi:10.1016/S1473-3099(17)30359-6. PMC   5639147 . PMID   28729167.
  22. ↑ "Oral cholera vaccine stockpile". World Health Organization. Archived from the original on 12 December 2013. Retrieved 18 December 2013.
  23. ↑ "WHO Doubles Global Supply of Cholera Vaccine". NBC News . 8 January 2016. Archived from the original on 8 January 2016. Retrieved 9 January 2016.
  24. ↑ "GAVI Board Approves Support to Expand Oral Cholera Vaccine Stockpile". The Task Force on Global Health. Archived from the original on 16 December 2013. Retrieved 18 December 2013.
  25. ↑ "Cholera". World Health Organization (WHO). Retrieved 3 May 2024.
  26. ↑ "Dukoral Canadian Product Monograph Part III: Consumer Information" (PDF). Dukoral. Archived from the original (PDF) on 22 August 2016. Retrieved 8 May 2013.
  27. 1 2 3 "FDA approves vaccine to prevent cholera for travelers" (Press release). U.S. Food and Drug Administration (FDA). 10 June 2016. Archived from the original on 18 December 2016.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  28. ↑ "Gavi and UNICEF welcome approval of new oral cholera vaccine". UNICEF (Press release). Retrieved 19 April 2024.
  29. ↑ Barranco C (28 September 2020). "The first live attenuated vaccines". Nature Research.
  30. ↑ Dorsey TA, Harshfield GS (May 1959). "Studies on Control of Fowl Cholera". Agricultural Experiment Station Technical Bulletins (1939–2011).
  31. 1 2 Bornside GH (December 1982). "Waldemar Haffkine's cholera vaccines and the Ferran-Haffkine priority dispute". Journal of the History of Medicine and Allied Sciences. 37 (4): 399–422. doi:10.1093/jhmas/XXXVII.4.399. PMID   6759570.
  32. ↑ Lopez AL, Gonzales ML, Aldaba JG, Nair GB (September 2014). "Killed oral cholera vaccines: history, development and implementation challenges". Therapeutic Advances in Vaccines and Immunotherapy. 2 (5): 123–148. doi:10.1177/2051013614537819. PMC   4144262 . PMID   25177492.
  33. ↑ Hanhart J (2017). Un illustre inconnu. Une biographie du docteur Waldemar Mordekhaï Haffkine[An illustrious stranger. A biography of Doctor Waldemar Mordechaï Haffkine] (in French). Paris: Lichma. ISBN   978-2-912553-84-3.
  34. ↑ Bornside GH (1981). "Jaime Ferran and preventive inoculation against cholera". Bulletin of the History of Medicine. 55 (4): 516–532. JSTOR   44441415. PMID   7039738.
  35. ↑ Hawgood BJ (February 2007). "Waldemar Mordecai Haffkine, CIE (1860–1930): prophylactic vaccination against cholera and bubonic plague in British India". Journal of Medical Biography. 15 (1): 9–19. doi:10.1258/j.jmb.2007.05-59. PMID   17356724. S2CID   42075270.
  36. ↑ "Waldemar Haffkine: The vaccine pioneer the world forgot". BBC News. 11 December 2020. Retrieved 20 January 2021.
  37. ↑ Artenstein AW (2009). Vaccines: A Biography (1 ed.). New York City: Springer Science & Business Media. pp. 89–92. ISBN   978-0-08-091902-7. Archived from the original on 8 September 2017.
  38. ↑ Martin S, Lopez AL, Bellos A, Deen J, Ali M, Alberti K, et al. (December 2014). "Post-licensure deployment of oral cholera vaccines: a systematic review". Bulletin of the World Health Organization. 92 (12): 881–93. doi:10.2471/blt.14.139949. PMC   4264394 . PMID   25552772.
  39. ↑ "New Cholera Vaccine for Adult Travelers". Medscape. 17 April 2017. Archived from the original on 8 September 2017. Retrieved 20 August 2017.

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