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From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. (8366)
Poliomyelitis was first transmitted to monkeys experimentally in 1908 by Landsteiner and Popper. Soon after this it was observed that monkeys which had survived one attack became resistant to subsequent infection. This suggested the use of serum from human beings who had had poliomyelitis for the treatment of those who had contracted it. A serum derived from convalescent children and adults was introduced for this purpose in 1911 and was extensively used and widely eulogised in the public press for some years. Eventually it was abandoned as useless
Few years later what is called gamma-globulin was introduced as a prophylactic against poliomyelitis and is still used for this purpose among contacts of actual cases of the disease. It will be recalled that Her Majesty the Queen and the Duke of Edinburgh were given this preparation during their Australian tour, on account of an outbreak of poliomyelitis in that country. In the following year 235,000 children were inoculated. The National Advisory Committee conducting the inquiry were of the opinion that "it had no apparent effect on the incidence or severity of paralysis developing in subsequent cases
Flexner and Lewis established a filterable virus as the causal agent in 1909, but more detailed study of this organism was hampered by the fact that monkey's and chimpanzees were for a long time the only susceptible animals in which the disease could be experimentally induced. Later some strains of the virus were adapted to rodents, but this did not prove very helpful, apparently, and the great advances in our knowledge of poliomyelitis during the past few years began with the discovery by Enders, Weller, and Robbins in 1949 that poliomyelitis virus could readily be grown in tissue-cultures. a discovery which won for them the Nobel prize for physiology and medicine in 1954.
As it became more and more clearly realised that animal and human sera were quite ineffective and that little progress could be expected in this direction, attention was directed towards the production of a vaccine which might prove successful in preventing the disease. The chief difficulty was to find a culture-medium in which the virus would multiply. As is well known, unlike bacteria which will grow on a simple medium such as potato, blood or agar in a test-tube, viruses require a living tissue for their development. After many years of research involving the use of many thousands of monkeys, it was found possible to grow the virus in brain tissue derived from humans, monkeys and certain rodents
Also, it was realized, a vaccine prepared from such material would hold the frightful danger of causing an allergic inflammation of the brain which might well he even worse than the disease it was designed to present. It was in l949 that a team of Harvard research workers headed by Finders reported that they had succeeded in growing polio virus in the kidney tissue of rhesus monkeys.
It was already known that there were three main types of virus: (I) Brunhilde. (2) Lansing, and (3) Leon. but Dr. Salk and his associates isolated and typed 74 strains. By 1952, after he had made experimental vaccines and tested them on monkeys, he was satisfied he had produced one safe enough to be given to human beings.
THE SALK VACCINE
The story begins with the trapping of rhesus monkeys in large numbers in the N. Indian State of Uttar Pradesh. They are stuffed into cages and carried on shoulder-poles to Lucknow. A train journey of 260 miles takes them to New Delhi whence a transport plane carries them the 4.000 miles to London Airport. From London another plane transports them another 3,000 miles across the Atlantic to New York, whence they travel in trucks for a final 700 miles to Okatie Farms in South Carolina. The Okatie Farms, may receive 5,000 monkeys a month, the supply never catches up with the demand. After 21 days for rigorous health checks, they are on their way to laboratories in Toronto, Pittsburgh, Detroit and Berkeley, California.
It was at the University of Pittsburgh's Virus Research Lab' that the bulk of the work in research was carried out and the vaccine initially produced. Dr Salk, who pursues his investigations here, has behind him 81 million dimes, contributed by the National Foundation for Infantile Paralysis Inc, to spend on this enterprise. This is part of the three billion dimes subscribed by the public to the National Foundation.
HOW THE VACCINE IS MANUFACTURED
Let us take, as an example, the University of Toronto Medical Research Laboratories. Some 50 to 65 monkeys will be used in a single morning. Under an anaesthetic a surgeon removes the kidneys, after which the monkey is killed by an overdose of ether. Then the kidneys are cut into tiny pieces and placed in glass bottles with a special nutrient solution devised by Dr. Salk. These bottles are then rocked in a mechanical machine for six days in an incubator to stimulate the growth of the kidney cells.
At this stage fluid containing live polio virus is introduced and the bottles again rocked. After about four days the virus has multiplied a thousand fold in the kidney cells and is now chilled in 21 gallon bottles ready for transportation from Toronto to Eli Lilly & Co, and Parke, Davis & Co. There the brew is filtered free from the kidney cells (which might cause nephritis if injected into a human being) and diluted with formaldehyde to kill the virus.
As we have already seen, there are three main strains of polio virus, against all of which there is need for protection. Consequently three tankfuls each containing one type of virus, cultivated and killed in the above manner, are mixed together. After neutralising the formaldehyde with sodium bisulphite there begins a month-long process of testing to see if the vaccine is safe for injection into human beings. This necessitates inoculations into live monkeys, rabbits, guinea-pigs and mice. These tests are carried out simultaneously, on each batch issued, by Dr. Salk's laboratories and by the National Institute of Health at Bethesda, Maryland. Having passed the final tests the vaccine is distributed in little glass bottles for inoculation into children.
IT was on April 12th. 1955, the tenth anniversary of President Franklin Roosevelt's death, that the Foundation for Infantile Paralysis told the world, using every possible means of publicity, that the vaccine devised by Dr. Jonas E. Salk was "safe, potent, and efficient." For it was on this day that the eagerly awaited report on the 1954 tests of the vaccine was issued by Dr. Thomas Francis, of Michigan University. who had been entrusted with the task of evaluating the results. At a meeting of 500 doctors and scientists at Ann Arbor. Michigan, Dr. Salk and Dr. Francis made such sweeping claims for the vaccine that nearly every American newspaper declared that Dr. Salk had abolished poliomyelitis.
Only thirteen days after the vaccine had been acclaimed by the whole of the American Press and Radio as one of the greatest medical discoveries of the century, and two days after the English Minister of Health had announced he would go right ahead with the manufacture of the vaccine, came the first news of disaster. Children inoculated with one brand of vaccine had developed poliomyelitis. In the following days more and more cases were reported, some of them after inoculation with other brands of the vaccine
THere has been a long controversy over the question of whether a virus killed by formalin and given intramuscularly or a modified (attenuated live virus given by mouth is likely to he the most effective vaccine. According to the Lancet (May 14. 1955. p. l0l8) "Dr. Jonas Salk and Dr. Albert Sabin have long held opposing views about vaccination against poliomyelitis, but this year it looks as though Sabin may be right. He favours the use of attenuated-virus vaccine given by the natural route of infection (by mouth)."
"Sabin has contended that intramuscular injections of killed vaccine will not confer life-long immunity and that it would he impracticable to re-vaccinate each time the short-lived artificial immunity runs out. If children received such a short-term vaccine, he argues, there would soon be a population of young adults with no protection against poliomyelitis; and as the disease is more severe in adults than in children, a vaccine which confers only a short immunity might eventually result in many severe illnesses when the children grew up."
On the other hand, the whole of Dr. Sabin's claims as to the effectiveness of his vaccine are based upon estimations of the antibodies present (as the result of vaccination) in the blood-serum of the chimpanzees and human "volunteers" taking part in the experiment. The fallacy underlying this method of assessing the degree of immunity induced by vaccination has already been fully described, so that it may justly be argued that the efficiency of the attenuated live vaccine is so far entirely problematical.
IT may be of interest to know what is meant by a modified or attenuated virus. Dr. Sabin found that by passing virulent strains of polio virus through monkey tissue in a rapid succession of cultures a vaccine could be produced which did not produce poliomyelitis when injected directly into the brains of cynomolgus monkeys. It was evident that some change had taken place in the virus which rendered it far less virulent; it is claimed that this modification is permanent and that there is no tendency for the virus to return to its former virulence. In point of fact, the vaccine now being used by Dr. Sabin is prepared by mixing together the modified viruses of all three types: type I having been attenuated by rapid culture in monkey-kidney tissue 33 times; type II. 5I times, and type III, 34 times.(bylyl)
Egypt. "A survey of permanent paralysis due to
poliomyelitis was conducted in Alexandria in July
1976, to obtain an estimate of poliomyelitis incidence,
prior to conducting a national mass vaccination programme of all
children 10 years of age and under
A total of 897 children with
residual paralytic poliomyelitis were found, i.e., 1710
per million children aged 10 years and under. The data
on age at onset of paralysis show that 91.5% occurred
during the first 3 years of life and 97.5% in the 0-4 age
group. Further analysis of the data shows that among
the 264 513 children in the 0-4 age group (i.e., those
born in 1971-75) there was a total of 308 with residual
paralysis (i.e., 1164 per million or an average annual
rate of 233 per million), while among the 219 082
children in the 5-9 age group there was a total of 481
with residual paralysis (i.e., 2200 per million or an
average annual rate of 439 per million), 97.5% of
whom acquired the disease during the first 5 years of
their life, i.e., from about 1966 to 1970. Since the 1960
census in Egypt showed that about 16% of the population
was in the 0-4 age group, one can estimate on
the basis of the clinical survey an average annual
poliomyelitis rate of at least 37 per million total population
during the 1971-75 period and 70 per million
for the 1966-70 period for Alexandria, compared
with reported rates of 23 and 51 per million total population
in Egypt during the same two periods.
effect of vaccination in Egypt is reflected by the
decline in the number of paralytic cases among those
born during the period of 1971-75 compared with the
number in those born in 1966-70 in the Alexandria
survey as well as in the total number of officially
reported cases during these two 5-year periods. Ofosu-
Amaah et al. (8) also noted that the rates of residual
paralysis in urban primary schoolchildren were lower
than in rural primary schoolchildren, while the rates
among children in the middle schools were the same in
the urban and rural areas. They estimated that up to
20% of children in Accra may have received OPV and
suggested that the more widespread use of vaccine in
the urban areas could explain the observed differdifferences.
The efficiency of official reporting may also be
much higher in Egypt than in Ghana and Burma.(bullwho)
There are two types of polio vaccine in use: the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV). Advantages of OPV compared with IPV are ease of administration (does not need a trained health worker) and the lower cost. The advantage of IPV is that it is not a "live" vaccine (i.e. it is inactivated) and thus carries no risk of vaccine-associated paralysis. Different OPV vaccines (trivalent, bivalent and monovalent) are available, to protect against one or more virus types. The choice of vaccine depends primarily on the prevalence of the three types of virus circulating in the target population. IPV protects against types 1, 2 and 3.
Polio cases have decreased by over 99% since 1988, from an estimated 350 000 cases to just over 1600 in 2009. Only four countries, Afghanistan, India, Nigeria and Pakistan, have never interrupted circulation of the wild poliovirus, although transmission is now limited to small areas within these countries. A further 19 countries, previously polio-free, reported cases and outbreaks due to imported wild poliovirus in 2009.
This report describes a case of acute flaccid paralysis after administration of oral
The report by Strebel et al. (Feb. 23 issue)1 provides support for our ongoing work on the role of the muscle and the participation of the poliovirus receptor in the transport of the poliovirus from the muscle to the motor neurons. The poliovirus receptor, an integral membrane protein with structural characteristics of the immunoglobulin superfamily of proteins,2 is the prerequisite for infection of tissue with the poliovirus. The possible entry of the virus into the central nervous system through muscle prompted us to search for the poliovirus receptor in normal human muscle fibers and motor end plates and in degenerating muscle fibers.(nejm)
In 1921, outbreaks of poliomyelitis plagued America. That summer, a young politician named Franklin Delano Roosevelt was vacationing with his family at their Campobello estate. After an exhausting day fighting a local forest fire, taking a cold swim for relief, and then lounging in his wet swimsuit at home, he went to bed feeling as though he had contracted a cold. In a few days Roosevelt found out he had polio.
In 1957, in an effort to improve upon the killed Salk vaccine, Albert Bruce Sabin began testing a live, oral form of vaccine in which the infectious part of the virus was inactivated (attenuated). This vaccine became available for use in 1963.
The Salk vaccine is given in two intramuscular injections spaced one month apart and requires boosters every 5 years. Because of the way it is inactivated, the vaccine is safe for those with compromised (weakened) immune systems.
The Sabin oral vaccine is given in 3 doses in the first two years of life, and a booster is given when the child starts school. Further boosters are not given unless the patient is exposed to polio or will be traveling to an endemic region. The advantages of a live, oral vaccine are its long-lasting immunity, the prevention of reinfection of the digestive tract, and the lower cost of administering the vaccine orally because sterile syringes and needles are not necessary. However, a major disadvantage is that it cannot be used for patients with compromised immune systems because it is a live virus and can cause disease in these patients
The discovery and use of polio vaccines has all but eliminated polio in the Americas. In 1960, there were 2,525 cases of paralytic polio in the United States. By 1965, there were 61. Between 1980 and 1990, cases averaged 8 per year, and most of those were induced by vaccination! There has not been a single case of polio caused by the wild virus since 1979, with a rare case reported each year from persons coming into the country carrying the virus. In 1994, polio was declared eradicated in all of the Americas.
In 1988, the World Health Organization set a goal of eradication of poliomyelitis from the entire world by the year 2000. This is theoretically possible since the poliovirus is found only in humans, and humans can be immunized. Smallpox was the first disease in history to be eradicated. It seems likely that polio could follow in its footsteps.
Two polio vaccines are used throughout the world to combat poliomyelitis (or polio). The first was developed by Jonas Salk and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated (dead) poliovirus. An oral vaccine was developed by Albert Sabin using attenuated poliovirus. Human trials of Sabin's vaccine began in 1957 and it was licensed in 1962. Because there is no long term carrier state for poliovirus in immunocompetent individuals, polioviruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. Therefore, interruption of person to person transmission of the virus by vaccination is the critical step in global polio eradication. The two vaccines have eradicated polio from most countries in the world, and reduced the worldwide incidence from an estimated 350,000 cases in 1988 to 1,652 cases in 2007.
In the generic sense, vaccination works by priming the immune system with an 'immunogen'. Stimulating immune response, via 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.
Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 - PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to 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.
The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states. A global effort to eradicate polio, led by the World Health Organization, UNICEF, and The Rotary Foundation, began in 1988 and has relied largely on the oral polio vaccine developed by Albert Sabin. The disease was entirely eradicated in the Americas by 1994. Polio was officially eradicated in 36 Western Pacific countries, including China and Australia in 2000. Europe was declared polio-free in 2002. As of 2008, polio remains endemic in only four countries: Nigeria, India, Pakistan, and Afghanistan. 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 occurs, 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.
The Salk vaccine, or inactivated poliovirus 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. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome.
Oral polio vaccine (OPV) is a live-attenuated vaccine, produced by the passage of the virus through non-human cells at a sub-physiological 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 own attenuated vaccine strains. In 1958, the National Institutes of Health 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. Based on these results, the Sabin strains were chosen for worldwide distribution.
There are 57 nucleotide substitutions which 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. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the virus's internal ribosome entry site (or IRES) 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. OPV also proved to be superior in administration, eliminating the need for sterile syringes and making the vaccine more suitable for mass vaccination campaigns. OPV also provided longer lasting immunity than the Salk vaccine.