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Polio vaccine

Polio vaccine is a vaccine 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.

Medical uses
's national symbol of public health, the "Wellbee", encouraging the public to receive an oral polio vaccine. Interruption of person-to-person transmission of the virus by vaccination is important in global polio eradication. This is because no long-term carrier state exists for poliovirus in individuals with normal immune function, polio viruses have no non-primate reservoir in nature, and the survival of the virus in the environment for an extended period appears to be remote. The two types of vaccine are inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Inactivated When the IPV (injection) is used, 90% or more of individuals develop protective antibodies to all three serotypes of poliovirus after two doses, and at least 99% are immune following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to protect for many years. IPV replaced the oral vaccine in many developed countries in the 1990s mainly due to the (small) risk of vaccine-derived polio in the oral vaccine. Attenuated Oral polio vaccines are easier to administer than IPV, as they eliminate the need for sterile syringes, so are more suitable for mass vaccination campaigns. OPV also provided longer-lasting immunity than the Salk vaccine, as it provides both humoral immunity and cell-mediated immunity. One dose of trivalent OPV produces immunity to all three poliovirus serotypes in roughly 50% of recipients. Taken together, these advantages have made it the favored vaccine of many countries, and it has long been preferred by the global eradication initiative. The primary disadvantage of OPV derives from its inherent, if small, risks. As an attenuated but active virus, it can induce vaccine-associated paralytic poliomyelitis (VAPP) in roughly one individual per every 2.7million doses administered. Until recent times, a trivalent OPV containing all three viral strains was used, and had nearly eradicated polio infection worldwide. With the complete eradication of wild poliovirus type2 this was phased out in 2016 and replaced with bivalent vaccine containing just types 1 and 3, supplemented with monovalent type2 OPV in regions where cVDPV type 2 was known to circulate. A novel OPV2 vaccine (nOPV2), which has been genetically modified to reduce the likelihood of disease-causing activating mutations, was granted emergency licencing in 2021, and subsequently full licensure in December 2023. This has greater genetic stability than the traditional oral vaccine and is less likely to revert to a virulent form. Schedule In countries with endemic polio or where the risk of imported cases is high, the WHO recommends OPV vaccine at birth followed by a primary series of three OPV doses and at least one IPV dose starting at 6 weeks of age, with a minimum of 4 weeks between OPV doses. In countries with more than 90% immunization coverage and low risk of importation, the WHO recommends one or two IPV doses starting at two months of age followed by at least two OPV doses, with the doses separated by 4–8 weeks depending on the risk of exposure. In countries with the highest levels of coverage and the lowest risks of importation and transmission, the WHO recommends a primary series of three IPV injections, with a booster dose after an interval of six months or more if the first dose was administered before two months of age. ==Side effects==
Side effects
The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. They are generally safe to be given to pregnant women and those who have HIV/AIDS, but are otherwise well. Vaccine-associated paralytic polio A potential adverse effect of the Sabin OPV is caused by its known potential to recombine to a form that causes neurological infection and paralysis. The Sabin OPV results in vaccine-associated paralytic poliomyelitis (VAPP) in around one individual per every 2.7million doses administered, with symptoms identical to wild polio. Contamination concerns In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, pleural and peritoneal mesothelioma, and some types of non-Hodgkin lymphoma. However, SV40 has not been determined to cause these cancers. SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963; In 1998, the National Cancer Institute undertook a large study, using cancer case information from the institute's SEER database. The published findings from the study revealed no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy. The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus from chimpanzees to humans, causing HIV/AIDS. These hypotheses, however, have been conclusively refuted. often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria and several other African nations without necessary information, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine. ==Manufacture==
Manufacture
Inactivated The Salk vaccine, IPV, is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. Attenuated candy OPV is an attenuated vaccine, produced by the passage of the virus through nonhuman cells at a subphysiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Other groups, led by Hilary Koprowski and H.R. Cox, developed their attenuated vaccine strains. In 1958, the NIH created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio while retaining a low incidence of neuropathogenicity in monkeys. Large-scale clinical trials performed in the Soviet Union in the late 1950s to early 1960s by Mikhail Chumakov and his colleagues demonstrated the safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. which alters stem-loop structures and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965, about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much-reduced levels following the introduction of the Salk vaccine. OPV is usually provided in vials containing 10–20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics—neomycin and streptomycin—but does not contain preservatives. ==History==
History
In a generic sense, vaccination works by priming the immune system with an "immunogen". Stimulating immune response, by use of an infectious agent, is known as immunization. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community. 1930s In the early 1930s, Maurice Brodie led a team from the public health laboratory of the city of New York, while John A. Kolmer collaborated with the Research Institute of Cutaneous Medicine in Philadelphia. Kolmer's live vaccine Kolmer began his vaccine development project in 1932 and ultimately focused on producing an attenuated or live virus vaccine. Inspired by the success of vaccines for rabies and yellow fever, he hoped to use a similar process to denature the polio virus. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin", Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self-experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. Kolmer's first formal presentation of results did not come about until November 1935, when he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. ultimately finding a solution of formaldehyde to be the most effective. By 1 June 1934, Brodie was able to publish his first scholarly article describing his successful induction of immunity in three monkeys with inactivated poliovirus. Through continued study on an additional 26 monkeys, Brodie ultimately concluded that administration of live virus vaccine tended to result in humoral immunity, while administration of killed virus vaccine tended to result in tissue immunity. declared the vaccine safe. At this time, very little oversight of medical studies occurred and the ethical treatment of study participants largely relied upon moral pressure from peer academic scientists. Both Kolmer and Brodie were called to present their research at the Annual Meeting of the American Public Health Association in Milwaukee, Wisconsin, in October 1935. 1948 A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that a few unused tubes. He retrieved a sample of mouse brain infected with poliovirus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow, but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their efforts with a Nobel Prize in Physiology or Medicine. Other important advances that led to the development of polio vaccines included the identification of three poliovirus serotypes (poliovirus type 1 – PV1, or Mahoney; PV2, Lansing; and PV3, Leon), the finding that before paralysis, the virus must be present in the blood, and the demonstration that administration of antibodies in the form of gamma globulin protects against paralytic polio. 1950–1955 During the early 1950s, polio rates in the U.S. were above 25,000 annually; in 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year, with deaths in those years numbering 3,200 and 1,400. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski of the Wistar Institute in Philadelphia, who tested the first successful polio vaccine, in 1950. On 27 February 1950, Koprowski's live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village, an institution for physically and mentally disabled people located in New York. After the child had no side effects, Koprowski enlarged his experiment to include 19 other children. Jonas Salk himself, in 1957 at the University of Pittsburgh, where his team had developed the vaccine circa 1961 for the National Polio Immunization Program The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in JAMA. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and eventually involved 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio. Soon after Salk's vaccine was licensed in 1955, children's vaccination campaigns were launched. In the U.S., following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States. A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute in Paris had also announced an effective polio vaccine. Safety incidents In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with the Salk polio vaccine from the Cutter pharmaceutical company, with the paralysis starting in the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 409,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 260 cases of polio, killing 11. 1961 (right) with Robert Gallo, circa 1985 At the same time that Salk was testing his vaccine, both Albert Sabin and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people. Koprowski in the Congo and Poland. Sabin's oral vaccine using live virus came into commercial use in 1961. 1987 An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there. In some countries, a fifth vaccination is given during adolescence. containing IPV was approved for use in the United States. and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin and Mikhail Chumakov (Sabin-Chumakov vaccine). After 1990 Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country. Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occur, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the Middle East, with Pakistan, Syria, and Cameroon advising vaccinations to outbound travellers. Polio vaccination programs have been resisted by some people in Pakistan and Afghanistan – the two countries with remaining wild polio cases as of 2020. Almost all Muslim religious and political leaders have endorsed the vaccine, but a fringe minority believes that the vaccines are secretly being used for the sterilisation of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and skepticism of vaccinations has consequently slowed down the polio eradication process within the two remaining endemic countries. == Travel requirements ==
Travel requirements
Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks. Most requirements apply only to travel to or from so-called 'polio-endemic', 'polio-affected', 'polio-exporting', 'polio-transmission', or 'high-risk' countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from 'key at-risk countries', which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea. ==Society and culture==
Society and culture
Cost , the Global Alliance for Vaccines and Immunization supplies the inactivated vaccine to developing countries for as little as (about ) per dose in 10-dose vials. Misconceptions A misconception has been present in Pakistan that the polio vaccine contains haram ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa province. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally. == References ==
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