However, the use of eggs or cell culture allows for vaccine production in a sterile environment, while first-generation vaccine contains skin bacteria from the animal that the vaccine was grown on. An antitoxin is a blood-based product that 'borrows' immunity from another person or animal to help you fight an infection, once you already have it. Saving Lives, Protecting People, Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Community-Based Planning for a Smallpox Emergency, Help People with Functional, Language, or Cognitive Needs, Sample Alert Messages for Healthcare Providers, Comparison of Reactions for First-Time Vaccinees and Revaccinees, Examples of Major or Take Reactions to Smallpox Vaccination, Administering ACAM2000 Smallpox Vaccine Videos, Specimen Collection and Transport Guidelines for Suspect Smallpox Cases, Specimen Collection and Transport Guidelines for Suspect Smallpox Vaccine Adverse Events, Negative Staining Electron Microscope Protocol for Rash Illness, Packaging and Transporting Infectious Substances, Chart 1: Acute, Generalized Vesicular or Pustular Rash Illness Protocol, Chart 2: Laboratory Testing for Acute, Generalized Vesicular or Pustular Rash Illness, Chart 3: Laboratory Testing for Suspect Smallpox Vaccine Adverse Event (Vaccinia), Chart 4: Laboratory Testing for Environmental Sample, U.S. Department of Health & Human Services. Following the eradication of smallpox, scientists and public health officials determined there was still a need to perform researchusing the variola virus. Four decades on, the . Written accounts from the mid-1500s describe a form of variolation used in China known as insufflation, where smallpox scabs were dried, ground and blown into the nostril using a pipe. Crucially all of at least four whom Jenner deliberately inoculated with smallpox virus resisted it. People who survived usually had scars, which were sometimes severe. Glycerine was sometimes used simply as a diluent by some continental vaccine producers. Through all this, the United States and the Soviet Union worked in rare solidarity. The first vaccine was developed to protect against smallpox, a deadly disease that killed thousands of people until the 1800s. Find out who should get smallpox vaccine. Baden followed in 1809, Prussia in 1815, Wrttemberg in 1818, Sweden in 1816, England in 1867 and the German Empire in 1874 through the Reichs Vaccination Act. [144], The word "vaccine" is derived from Variolae vaccinae (i.e. You can review and change the way we collect information below. Other vaccine material was not reliably derived from cowpox, but from other skin eruptions of cattle. [94]:26267 Despite some concern about the safety of vaccination the mortality using carefully selected vaccine was close to zero, and it was soon in use all over Europe and the United States. It was organised and co-ordinated by a World Health Organization (WHO) unit, set up and headed by Donald Henderson. You are a medical researcher working for Pfizer, which has developed a new meningococcal vaccine. The children or young patients play together all the rest of the day and are in perfect health till the eighth. By the 1950s, advances in production techniques meant that heat-stable, freeze-dried smallpox vaccines could be stored without refrigeration. Rahima was the last known person to have had naturally acquired smallpox in the world. This consisted of transferring to healthy people small amounts of material from smallpox sores, resulting in milder forms of illness and much lower mortality than natural infection. There are now only two locations that officially store and handle variola virus under WHO supervision: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (VECTOR Institute) in Koltsovo, Russia. [23] Egg-based vaccine was also used widely in Brazil, New Zealand, and Sweden, and on a smaller scale in many other countries. Modern research suggests Jenner was trying to distinguish between effects caused by what would now[when?] [13] After the September 11 attacks in 2001, many governments began building up vaccine stockpiles again for fear of bioterrorism. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers. Maalin was a hospital cook in Merca, Somalia. [18] Rare side effects include postvaccinal encephalitis and myopericarditis. Also included is an antibody which specifically binds to the proteins and nucleic acid encoding the same, as well as methods of preventing and treating a poxvirus infection using the afore . Smallpox was a highly infectious and deadly disease which killed around 300 million people in the 20th century alone. On October 12, 1977, he rode with two smallpox patients in a vehicle from the hospital to the local smallpox office. Wellcome Library, London via Wikimedia Commons. [69], scarred the wrists, legs, and forehead of the patient, placed a fresh and kindly pock in each incision and bound it there for eight or ten days, after this time the patient was credibly informed. [15], The inoculation technique was documented as having a mortality rate of only one in a thousand. Bensom of Los Angeles used his vacation to mush to native villages in Alaska. At some point in the 1800s, the virus used to make the smallpox vaccine changed from cowpox to vaccinia virus. By 1871, parents could be fined for non-compliance, and then imprisoned for non-payment. The term vaccinia now refers only to the smallpox vaccine,[137] while cowpox no longer has a Latin name. A WHO survey of 59 producers, some of whom used more than one source of vaccine, found that 39 used calves, 12 used sheep and 6 used water buffalo, whilst only 3 made vaccine in cell culture and 3 in embryonated hens' eggs. Early written descriptions also appeared in India in the 7th century and in Asia Minor in the 10th century. Although the truncated protein decreases production of extracellular enveloped virus, animal models have shown that antibodies against other membrane proteins are sufficient for immunity. Smallpox persisted in Canada until 1946, when vaccination campaigns eliminated it. And thanks to a series of programmes designed to eradicate the disease - which involved identifying all cases and their contacts and ensuring that they were all vaccinated - it was eliminated in the second half of the 20th century. [12], Horsepox is extinct in the wild, and the only known sample was collected in 1976. This, a personal initiative by Donald Henderson, was a lapel badge, designed and made by his daughter, formed from the needle shaped to form an "O". All three generations of vaccine are available in stockpiles. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. [72], Stimulated by a severe epidemic, variolation was first employed in North America in 1721. [113], In the late 1940s and early 1950s, Leslie Collier, an English microbiologist working at the Lister Institute of Preventive Medicine, developed a method for producing a heat-stable freeze-dried vaccine in powdered form. [131], The origin of the modern smallpox vaccine has long been unclear,[132] but horsepox was identified in the 2010s as the most likely ancestor. MVA-BN has been approved in the European Union,[7] Canada,[38][39][40] and the United States. Guidance for clinicians", "Frequency of adverse events after vaccination with different vaccinia strains", "Correction: Frequency of Adverse Events after Vaccination with Different Vaccinia Strains", "Vaccinal Infection of the Chorio-Allantoic Membrane of the Chick Embryo", "ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense", "ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile", "Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development", "There's a shortage of monkeypox vaccine. [37] It is safer for immunocompromised patients and those who are at risk from a vaccinia infection. A procedure that had been made compulsory in England and Wales in 1853 was discontinued in 1971. bifurcated needle to administer doses contributed to vaccination efforts. By the time the Intensified Eradication Program began in 1967, smallpox was already eliminated in North America (1952) and Europe (1953). Three-year-old Rahima Banu with her mother in Bangladesh. [12], As the oldest vaccine, the smallpox vaccine has gone through several generations of medical technology. Other symptoms include fever, headache, fatigue, and vomiting. Not everyone was on board with Jenner and his vaccine. [18][19] Many countries have stockpiled first generation smallpox vaccines. In 1959, the World Health Organization (WHO) started a plan to rid the world of smallpox. [43][44][45], LC16m8 is a replicating attenuated strain of vaccinia that is manufactured by Kaketsuken in Japan. Jenner also knew about variolation and guessed that exposure to cowpox could be used to protect against smallpox. [63][64] The first clear reference to smallpox inoculation was made by the Chinese author Wan Quan (14991582) in his Douzhen xinfa () published in 1549. [29] During the smallpox eradication campaign, MVA was considered to be a pre-vaccine that would be administered before a replicating vaccine to reduce the side effects, or an alternative vaccine that could be safely given to people at high risk from a replicating vaccine. More experiments followed, and, in 1801, Jenner published his treatise On the Origin of the Vaccine Inoculation. In this work, he summarized his discoveries and expressed hope that the annihilation of the smallpox, the most dreadful scourge of the human species, must be the final result of this practice.. Smallpox epidemics persisted during the nineteenth century, sometimes occurring on a large scale, such as that in 1870-72 with 42,200 deaths suggesting 200,000 or more cases. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". The attenuated viruses may be replicating or non-replicating. These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. [98], The first state to introduce compulsory vaccinations was the Principality of Lucca and Piombino on September 25, 1806. [66] In China, powdered smallpox scabs were blown up the noses of the healthy. Allan Watt Downie demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox,[11] and vaccinia was subsequently recognized as a separate viral species. [15]:54345 English vaccine was occasionally made in sheep during World War I but from 1946 only sheep were used. In a 2006 predictive analysis of casualties if there were a mass vaccination of the populations of Germany and the Netherlands, it was estimated that a total of 9.8 people in the Netherlands and 46.2 people in Germany would die from uncontrolled vaccinia infection after being vaccinated with the New York City Board of Health strain. This allowed exemption on production of a certificate of conscientious objection signed by two magistrates. Then in the late 18th century a vaccine was discovered. By 1984, England and South Africa had either destroyed their stocks or transferred them to other approved labs. The invention is also directed to a vaccine comprising a nucleic acid encoding such proteins. Courtesy of WHO. [67] According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia. Having heard of local beliefs and practices in rural communities that cowpox Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. [142] Modern Brazilian vaccines with a documented introduction date of 1887, made from material collected in an 1866 outbreak of "cowpox" in France, are more similar to horsepox than other strains of vaccinia. [88] Unfortunately glycerolated vaccine soon lost its potency at ambient temperatures which restricted its use in tropical climates. Rumours circulated at the time that it would turn people into cows. have questioned the possible effectiveness of such a vaccine. Perhaps if I live to return I may, however, have courage to war with them. [140] Because the sample was collected at the end of the smallpox eradication campaign, scientists considered the possibility that horsepox is a strain of vaccinia that had escaped into the wild. As vaccination spread, some European countries made it compulsory. At the first sign of any fever after exposure to smallpox, a person needs to be isolated until it is clear that they do not have smallpox. Over a five year period, you tested the effectiveness of the vaccine to monkeys and then challenging the monkeys with meningitis bacteria. Known stockpiles of the virus are stored for research in one lab in the United States and one in Russia. The patients would then develop a mild case of the disease and from then on were immune to it. [133]:9 Edward Jenner had obtained his vaccine from a cow, so he named the virus vaccinia, after the Latin word for cow. (2003), "A case of severe monkeypox virus disease in an American child: emerging infections and changing professional values"; Michael J. Bennett, War against Smallpox: Edward Jenner and the Global Spread of Vaccination (Cambridge, United Kingdom: Cambridge University Press, 2020), 32. The origin of smallpox is unknown. However, a single-nucleotide deletion truncates membrane protein B5R from a residue length of 317 to 92. Other factors that played an important role in the success of the intensified efforts included the development of the bifurcated needle, the establishment of a case surveillance system, and mass vaccination campaigns. Mandatory smallpox vaccination came into effect in Britain and parts of the United States of America in the 1840s and 1850s, as well as in other parts of the world, leading to the establishment of the smallpox vaccination certificates required for travel. [104] During 179092 Peter Plett, a teacher from Holstein, reported limited results of cowpox inoculation to the Medical Faculty of the University of Kiel. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. Epidemiologists from the Soviet Union and the United States of America worked side by side in the middle of a cold war. Several companies sold off their stockpiles of vaccines manufactured in the 1970s, and production of smallpox vaccines resumed. This was a sharpened two-prong fork designed to hold one dose of reconstituted freeze-dried vaccine by capillarity. They make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nutshell full of the matter of the best sort of small-pox and asks what veins you please to have opened. The Soviet Union provided freeze-dried In 1978, Parker was a medical photographer at Englands Birmingham University Medical School. Vaccine issued by the Government Vaccine Establishment contained 5,000 bacteria per gram, while commercial vaccines contained up to 100,000 per gram. [8][9], The term vaccine derives from the Latin word for cow, reflecting the origins of smallpox vaccination. It began as early as 1350 BCE, with cases being found in the study of Egyptian mummies. These cookies perform functions like remembering presentation options or choices and, in some cases, delivery of web content that based on self-identified area of interests. When there IS a smallpox outbreak, you should get the smallpox vaccine if you are directly exposed to smallpox virus. paravaccinia/milker's nodes), or contaminating bacterial pathogens. WHO also maintains a stockpile of vaccines as an emergency reserve in Switzerland and in several other countries. Through the widespread administration of the smallpox vaccine, doctors declared the smallpox virus "extinct" in the United States in 1952. There are two licensed smallpox vaccines in the United States and one investigational vaccine that may be used in a smallpox emergency. However, Fewster, who had a flourishing variolation practice, may have considered this option but used smallpox instead. The ancient practice of variolation (named for smallpox, also known as variola or la variole) was widely used in Asia and some parts of Africa. The second-generation vaccines are also administered through scarification with a bifurcated needle, and they carry the same side effects as the first-generation vaccinia strain that was cloned. ", "Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus", National Institute of Allergy and Infectious Diseases, "A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN) in 56-80-Year-Old Subjects", "Summary Basis for Regulatory Action Template", "Smallpox and monkeypox vaccine: Canadian Immunization Guide", "Products for Human Use. The resulting variant was designated LC16m8 (Lister clone 16, medium pocks, clone 8). As the World Health Organization launched the Smallpox Eradication Programme in 1959, WHO Member States enhanced their support and cooperation. [146] According to some sources the term was first introduced by Jenner's friend Richard Dunning in 1800.[147]. These cookies may also be used for advertising purposes by these third parties. Phipps remained in perfect health, the first person to be vaccinated against smallpox. He thought vaccination offered no advantage over variolation, but maintained friendly contact with Jenner and certainly made no claim of priority for vaccination when critics attacked Jenner's reputation. To the Editor: In 1947, millions of New Yorkers received smallpox vaccinations, an accomplishment still appropriately held up as an example of public health planing and mobilization. They also offered a reward to anyone who reported a smallpox case. Phipps reacted to the cowpox matter and felt unwell for several days but made a full recovery. A vaccine targeting smallpox led to its eradication (elimination). The main sign of smallpox is a rash that starts as flat red spots that turn into blisters. [87] Jenner also tried to distinguish between 'True' cowpox which produced the desired result and 'Spurious' cowpox which was ineffective and/or produced severe reaction. Could one dose instead of two suffice? [13] However, Sanofi dropped its own vaccine after it acquired Acambis in 2008. With renewed political commitment and the contributions of hundreds of thousands of local surveillance officers and health workers, even regions with nascent health systems and tremendous logistical challenges made remarkable progress. According to the US Centers for Disease Control and Prevention (CDC), "within 3 days of being exposed to the virus, the vaccine might protect you from getting the disease. This encouraged the British Royal Family to take an interest and a trial of variolation was carried out on prisoners in Newgate Prison. [15]:47273,56872 Rubin estimated that it was used to do 200 million vaccinations per year during the last years of the campaign. A cure was never found for smallpox before eradication, with those infected being treated only by cleaning wounds and lessening pain. be recognised as non-infectious vaccine, a different virus (e.g. [94]:29293 Compulsory infant vaccination was regulated by only allowing access to school for those who had been vaccinated. [15]:588. Foster M.D., M.P.H. After drying the ampoules were sealed under nitrogen. [15]:52637 A Global Commission for the Certification of Smallpox Eradication chaired by Frank Fenner examined the evidence from, and visited where necessary, all countries where smallpox had been endemic. [65] Inoculation for smallpox does not appear to have been widespread in China until the reign era of the Longqing Emperor (r. 15671572) during the Ming Dynasty. Almost two centuries after Jenner hoped that vaccination could annihilate smallpox, the 33rd World Health Assembly declared the world free of this disease on May 8, 1980. WHO poster commemorating the eradication of smallpox in October 1979, which was officially endorsed by the 33rd World Health Assembly on May 8, 1980. She was isolated at home with house guards posted 24 hours a day until she was no longer infectious. Edward Jenner or Benjamin Jesty? Accounts from the 18th century suggest this technique dates back hundreds of years. Laboratories in many countries where smallpox occurred regularly were able to produce more, higher-quality freeze-dried vaccine. In 1714 and 1716, two reports of the Ottoman Empire Turkish method of inoculation were made to the Royal Society in England, by Emmanuel Timoni, a doctor affiliated with the British Embassy in Constantinople,[69] and Giacomo Pylarini. Smallpox can be prevented by smallpox vaccines, also called vaccinia virus vaccines. [15]:588 Lederle Laboratories began selling its Avianized smallpox vaccine in the United States in 1959. [18], First generation vaccines consist of live, unattenuated vaccinia virus. Many people consider smallpox eradication to be the biggest achievement in international public health. Submission #144762", "FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox", "Phase II Trial to Assess Safety and Immunogenicity of Imvamune", "Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox", "Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001", "Vaccines and Related Biological Products Advisory Committee Meeting", "Aventis to Donate Smallpox Vaccine To the U.S. Government's Stockpile", "Emergent BioSolutions Awarded 10-Year HHS Contract to Deliver ACAM2000, (Smallpox (Vaccinia) Vaccine, Live) Into the Strategic", "Bavarian Nordic Announces U.S. FDA Approval of Jynneos (Smallpox and Monkeypox Vaccine, Live, Non-Replicating) for Prevention of Smallpox and Monkeypox Disease in Adults", "HHS Orders 2.5 Million More Doses of JYNNEOS Vaccine For Monkeypox Preparedness", "Clinical guidance for smallpox vaccine use in a postevent vaccination program", "Smallpox eradication: destruction of variola virus stocks", "Plan national de rponse une menace de variole", "Vaiolo delle scimmie, 'abbiamo 5 milioni dosi di vaccino: pronti se servir', "Milestones in history of adult vaccination in Korea", "Edward Jenner and the history of smallpox and vaccination", "The smallpox story: life and death of an old disease", "Smallpox inoculation and the Ottoman contribution: A Brief Historiography", "Black History Month II: Why Wasn't I Taught That? In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox virus. Despite their best efforts, smallpox was still widespread in 1966, causing regular outbreaks across South America, Africa, and Asia. Jenner assumed a causal connection but the idea was not taken up at that time. She worked one floor above the Medical Microbiology Department where staff and students conducted smallpox research. First and second-generation vaccines contain live unattenuated vaccinia virus and can cause serious side effects in a small percentage of recipients, including death in 110 people per million vaccinations. In 1958, the World Health Assembly called for the global eradication of smallpox the permanent reduction to zero cases without risk of reintroduction. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. The physician Valentine Seaman gave his children a smallpox vaccination using a serum acquired from Jenner. Smallpox was gradually wiped out in the 20th century. [49] Aventis Pasteur discovered a stockpile from the 1950s and donated it to the U.S. The smallpox vaccine is the first vaccine to be developed against a contagious disease. The authors of the official World Health Organization (WHO) account Smallpox and its Eradication assessing Jenner's role wrote:[15]:264. Smallpox was a terrible disease. They agreed to reduce the number of laboratories holding stocks of variola virus to only four locations. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. Second-generation vaccines were grown in chorioallantoic membrane or cell cultures for greater purity, and they were used in some areas during the smallpox eradication campaign. In 1980, WHO declared smallpox officially eradicated: The world and all its people have won freedom from smallpox, which was the most devastating disease sweeping in epidemic form through many countries since earliest times, leaving death, blindness and disfigurement in its wake. [108] Those seeking to enforce compulsory vaccination argued that the public good overrode personal freedom, a view supported by the U.S. Supreme Court in Jacobson v. Massachusetts in 1905, a landmark ruling which set a precedent for cases dealing with personal freedom and the public good. [121], Smallpox vaccine was inoculated by scratches into the superficial layers of the skin, with a wide variety of instruments used to achieve this. Attention was later drawn to Jesty, and he was brought to London in 1802 by critics jealous of Jenner's prominence at a time when he was applying to Parliament for financial reward. A member of the Smallpox Eradication Program team visited every house, public meeting area, school, and healer within 5 miles to ensure the illness did not spread. The Program made steady progress toward ridding the world of this disease, and by 1971 smallpox was eradicated from South America, followed by Asia (1975), and finally Africa (1977). Smallpox vaccine was successfully maintained in cattle starting in the 1840s, and calf lymph vaccine became the leading smallpox vaccine in the 1880s. It was not submitted formally and there is no mention of it in the Society's records. Two months later, in July 1796, Jenner took matter from a human smallpox sore and inoculated Phipps with it to test his resistance. From 1958 to 1977, the World Health Organization (WHO) conducted a global vaccination campaign that eradicated smallpox, making it the only human disease to be eradicated. [144] One of the 18591873 vaccines was identified as a novel strain of horsepox, containing a complete gene from the 1976 horsepox sample that has deletions in vaccinia. [100][101] In Lutheran Sweden, the Protestant clergy played a pioneering role in voluntary smallpox vaccination as early as 1800. [41][42] Clinical trials have found that MVA-BN is safer and just as immunogenic as ACAM2000. Key components of the worldwide smallpox eradication effort included universal childhood immunization programmes in some countries, mass vaccination in others, and targeted surveillance-containment strategies during the end-game. Whole-genome sequencing has revealed that vaccinia is most closely related to horsepox, and the cowpox strains found in Great Britain are the least closely related to vaccinia. [13], Modified vaccinia Ankara (MVA, German: Modifiziertes Vakziniavirus Ankara) is a replication-incompetent variant of vaccinia that was developed in West Germany through serial passage. The Vaccination Act made it compulsory for all children born after August 1st 1853 to have a smallpox vaccine in the first three months of their life. to have been eradicated. For example, if you had a prolonged face-to-face contact with someone who has smallpox. [129] On May 6, the contract was awarded to Bavarian Nordic for their Imvamune vaccine. The invention is directed to a poxvirus vaccine comprising a soluble truncated poxvirus envelope protein. After 572 serial passages, the vaccinia virus had lost over 14% of its genome and could no longer replicate in human cells. Third-generation vaccines are much safer due to the milder side effects of the attenuated vaccinia strains. At the same time the 1898 Vaccination Act banned arm-to-arm vaccination, thus preventing transmission of syphilis by this vaccine. During the 1970s, one vaccine was eliminated. Smallpox vaccine was successfully maintained in cattle starting in the 1840s, and calf lymph vaccine became the leading smallpox vaccine in the 1880s. [62] A method of inducing immunity known as inoculation, insufflation or "variolation" was practiced before the development of a modern vaccine and likely occurred in Africa and China well before the practice arrived in Europe. She immediately rips open that you offer to her with a large needle (which gives you no more pain than a common scratch) and puts into the vein as much venom as can lye upon the head of her needle, and after binds up the little wound with a hollow bit of shell, and in this manner opens four or five veins. [15]:545,550, In a letter about landmarks in the history of smallpox vaccine, written to and quoted from by Derrick Baxby, Donald Henderson, chief of the Smallpox Eradication Unit from 1967 to 1977 wrote; "Copeman and Collier made an enormous contribution for which neither, in my opinion ever received due credit". It was one of the deadliest diseases known to humans, and to date (2016) the only human disease to have been eradicated by vaccination. [123] Easy to use with minimum training, cheap to produce ($5 per 1000), using one quarter as much vaccine as other methods, and repeatedly re-usable after flame sterilization, it was used globally in the WHO Smallpox Eradication Campaign from 1968.
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