• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE EPI/GEN/8113 /~' 1 ·' ·t. ( _ t ,.r , , t, . ·"'" ENGLISH ONLY I. REVIEW OF CURRENT STATUS OF . / /'. 11' rtctC ORAL AND INACTIVATED POLIOMYELITIS VACCINES l. 2. 3. Oral poliomyelitis vaccine Inactivated poliomyelitis vaccine Present EPI policy Contents Page 1 2 4 Evidence from routine and special survey sources indicates that transmission of polio- virus and the consequent incidence of paralysis due to poliomyelitis are at levels in many developing countries that are comparable to those experienced in the developed countries during the epidemic years from the 1930s to the 1950s. Poliomyelitis has been effectively controlled in the developed countries by the use of polio vaccines, and such vaccines should be used in the developing countries to achieve the same end. There are two basic forms of poliovirus vaccine available: Live, attenuated virus vaccines (oral); - Inactivated virus vaccines. Inactivated vaccine has been available since 1955 and oral slnce 1960. When used on a wide scale both have been shown to be effective and safe. The choice between them in any set of circumstances must be made, taking into account the following: - Efficacy and safety; - Delivery and administration; - Availability and price. 1. Oral poliomyelitis vaccine This vaccine, as usually formulated, contains live, attenuated poliovirus of serotypes 1, 2 and 3 in titres which take account of the differing ability of these serotypes to compete ln infecting the gut. 1.1 Efficacy and safety 1.1.1 Oral poliomyelitis vaccine has been widely used since 1960. The dramatic and sus- tained reduction in paralytic poliomyelitis seen in the countries of Europe and North America, as well as some countries in Central and South America and East Asia, can in most cases be attributed to this vaccine. 1.1.2 The vaccine stimulates the production of antibodies in the gut and pharynx as well as in the blood. The immunity it produces is therefore identical in character to the permanent immunity produced by virulent wild viruses. The issue of this document does not constitute formal publication. lt should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. 11 ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation Mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. EPI/GEN/81/3 page 2 1.1.3 The colonization of the gut by attenuated viruses establishes a barrier to infection by virulent viruses. This phenomenon is valuable in the management of epidemic poliomyelitis. 1.1.4 The development of gut immunity and the circulation of vaccine viruses within the community, which occurs in some situations, leads to the production of a degree of immunity in the community that is greater than can be accounted for by the proportion of the population that has been directly immunized. There is evidence from developed and developing countries that, when live poliovirus vaccines are used, the incidence of paralytic poliomyelitis and the circulation of wild polioviruses may be markedly reduced well before the whole population has been immunized. This has been particularly well shown in the United Kingdom, the United States and Singapore. 1.1.5 Serological evidence suggests that oral polio vaccines are not as effective in warm as in temperate climates. A number of factors are involved in this phenomenon. There is, however, some evidence suggesting that a population that is consistently well immunized with a potent oral vaccine will be protected from paralytic poliomyelitis despite apparently unsatisfactory serological responses. 1.1.6 There is some evidence that oral vaccines do not produce as reliable a serological response when used in young infants who are still passively protected by maternal antibodies. Further information is required before this can be validated and its importance defined. 1.1.7 Oral polio vaccines are among the safest of vaccines. However, it has been estimated that cases of neurological disease associated with the use of these vaccines occur at the rate of one for every three million vaccinees. In a country where there is any risk from poliomyelitis the vaccine has an excellent risk:benefit ratio. 1.2 Delivery and administration 1.2.1 Oral polio vaccine needs to be kept frozen for long-term storage but with a suitable stabilizer will retain its potency at 2-8°C for as long as 12 months. For the vaccine to remain effective, therefore, there is a need for an efficient cold chain. 1.2.2 The method of administration, by drops directly into the mouth or on a sugar lump or in fruit juice off a spoon, is acceptable to both children and parents. It requires no special skill or equipment. The schedule usually recommended is three doses starting from about the third month of age and spaced 4-8 weeks apart, with a fourth dose 1-2 years later. For convenience the vaccine is usually given at the same time as diphtheria/pertussis/tetanus vaccine (DPT). 1.3 Availability and price Oral polio vaccine is produced in cultures of monkey kidney cells. The methods of produc- tion are well established and the present manufacturers can supply as much vaccine as is likely to be required, without further development. Because the volume produced is so large, the cost is low. Oral vaccine obtained in 1981 through UNICEF will cost US $0.02 per dose. 2. Inactivated poliomyelitis vaccine This vaccine contains polioviruses of all three serotypes which have been killed by formalin. 2.1 Efficacy and safety 2.1.1 Inactivated poliovirus vaccine was the first vaccine to be developed against poliomyelitis. It was highly effective in reducing the incidence of paralytic poliomyelitis in the United States before oral vaccine was introduced, and in Scandinavia and Holland where its continued use has been associated with an incidence of paralytic poliomyelitis approaching zero. When outbreaks have occurred, caused by imported wild poliovirus, they have involved unvaccinated individuals exclusively. EPI/GEN/81/3 page 3 2.1.2 The vaccine is injected and stimulates the production of circulating antibodies which apparently act by preventing the invasion of the central nervous system by wild polioviruses which may infect the pharynx and the gut. As with oral vaccine it is not known whether this immunity, once established, is lifelong or whether reinforcement is required either by further vaccine or by circulating wild viruses. 2.1.3 When used on a very wide scale this vaccine has been shown to cause the disap- pearance of wild poliovirus from the community. Under these conditions it thus offers indirect protection by reducing the chances of infection of individuals who have not received vaccine. This mechanism will not, however, protect the unimmunized members of the population if they come into contact with imported wild viruses. 2.1.4 Inactivated vaccine stimulates the production of antibody at all ages, but its ability to do so is affected by the presence of maternal antibody. 2.1.5 Small scale controlled trials in West Africa, using concentrated vaccine, have demonstrated good serological responses in vaccinees. Inactivated vaccine has not yet been used on a large scale in any developing country. Its efficacy in preventing clinical poliomyelitis in developing countries where there may be vaccine handling problems and where coverage may be far from complete is unknown. 2.1.6 Well prepared inactivated poliovirus vaccine is safe. No adverse reactions have yet been reported. The only foreseeable danger lies in that failure of inactivation during manufacture could lead to children being injected with live, virulent poliovirus. 2.2 Delivery and administration 2.2.1 Inactivated polio vaccines require refrigeration but most will retain their 0 potency at 2-8 C fqr more than a year. An efficient cold chain is needed for the reliable storage of this vaccine. 2.2.2 A number of different administration schedules have been used in those developed countries where inactivated vaccine has been extensively employed. All stipulate at least two doses in the first year of life, followed by boosters at various times during the school years. A total of at least four doses is recommended. Recently produced vaccines of high potency are claimed to produce ~dequate and lasting immunity with one or two doses. The long term efficacy of these vaccines has not yet been established. 2.2.3 Although available on its own, inactivated polio vaccine is also available combined with DPT vaccine. The most appropriate dosage and administration schedules for this combined vaccine in developing countries are not yet known. Although inactivated vaccine must be given parenterally, its inclusion with DPT in a quadruple vaccine would preclude any increase in the number of injections that each child received. 2.3 Availability and price 2.3.1 Inactivated vaccines currently available are produced in cultures of monkey kidney cells. Recent developments in tissue culture techniques give promise of more efficient use of primary cells, and the availability of more plentiful supplies from tertiary monkey kidney cells. Vaccines produced on these cells are not yet licensed. WHO Requirements referring to the use of cells in addition to the use of primary monkey kidney cells have been formulated and will become available for vaccine manufacture in the near future. Experiments on vaccine production in vero cells and on more efficient concentration systems also provide the technology for future methods suitable for large scale production. At present, however, inactivated vaccine is not available in the large quantities that would be required for any significant expansion of the number of countries using it. 2.3.2 Because of the present constraints on the methods of production, the cost of inactivated vaccine is high. The current price is in excess of US $0.50 per dose. EPI/GEN/81/3 page 4 3. Present EPI policy . 3.1 It is generally accepted that either oral or inactivated vaccines, when given to a high proportion of the population, will produce a significant decline in the incidence of para- lytic poliomyelitis. Operational conditions in many developing countries, however, preclude the achievement of high levels of coverage in the immediate future. 3.2 Information is not available on several important aspects of vaccine efficacy and use. Work is planned to provide information particularly on: 3.2.1 Optimum dosage and administration schedules. This includes studies on: - the respective roles of gut and blood-borne immunities in the development of individual and herd immunity; ~ the most effective methods for ensuring protection for infants in the early months of life; - the efficacy of giving both oral and inactivated vaccine at different times in the same schedules. 3.2.2 Large scale evaluation of the effect on morbidity from .paralytic poliomyelitis of inactivated and oral vaccines when used under field conditions in developing countries. 3.3 In the light of current knowledge and practices there are four areas in which oral vaccine can be seen as preferable to inactivated for use in current immunization schedules in developing countries: 3.3.1 Oral vaccine has been used extensively and has already proved its value in reducing the incidence of paralytic poliomyelitis in tropical and subtropical developing countries. 3.3.2 It is believed that oral vaccine may reduce the circulation of wild poliovirus and the incidence of paralytic poliomyelitis to an extent disproportionate to the size of the vaccinated group within a population. 3.3.3 Oral polio vaccine is available through UNICEF for use on a large scale without the need for further development of manufacturing methods or capacity. 3.3.4 Oral polio vaccine is, at current prices, cheaper per dose than inactivated vaccine by a factor of at least 25. For these reasons, EPI will continue to propose oral poliomyelitis vaccine as the most appropirate polio vaccine for general use in countries which are either intending to institute polio immunization or which are already using oral vaccine. At the same time, it must be stressed that the results obtained in some developing countries using oral polio vaccine are not as good as could be hoped. As indicated aboye, coordinated research will continue into the optimum methods of preventing poliomyelitis and future decisions will be made in the light of the findings of this work.
• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE EPI/GEN/8113 /~' 1 ·' ·t. ( _ t ,.r , , t, . ·"'" ENGLISH ONLY I. REVIEW OF CURRENT STATUS OF . / /'. 11' rtctC ORAL AND INACTIVATED POLIOMYELITIS VACCINES l. 2. 3. Oral poliomyelitis vaccine Inactivated poliomyelitis vaccine Present EPI policy Contents Page 1 2 4 Evidence from routine and special survey sources indicates that transmission of polio- virus and the consequent incidence of paralysis due to poliomyelitis are at levels in many developing countries that are comparable to those experienced in the developed countries during the epidemic years from the 1930s to the 1950s. Poliomyelitis has been effectively controlled in the developed countries by the use of polio vaccines, and such vaccines should be used in the developing countries to achieve the same end. There are two basic forms of poliovirus vaccine available: Live, attenuated virus vaccines (oral); - Inactivated virus vaccines. Inactivated vaccine has been available since 1955 and oral slnce 1960. When used on a wide scale both have been shown to be effective and safe. The choice between them in any set of circumstances must be made, taking into account the following: - Efficacy and safety; - Delivery and administration; - Availability and price. 1. Oral poliomyelitis vaccine This vaccine, as usually formulated, contains live, attenuated poliovirus of serotypes 1, 2 and 3 in titres which take account of the differing ability of these serotypes to compete ln infecting the gut. 1.1 Efficacy and safety 1.1.1 Oral poliomyelitis vaccine has been widely used since 1960. The dramatic and sus- tained reduction in paralytic poliomyelitis seen in the countries of Europe and North America, as well as some countries in Central and South America and East Asia, can in most cases be attributed to this vaccine. 1.1.2 The vaccine stimulates the production of antibodies in the gut and pharynx as well as in the blood. The immunity it produces is therefore identical in character to the permanent immunity produced by virulent wild viruses. The issue of this document does not constitute formal publication. lt should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. 11 ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation Mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. EPI/GEN/81/3 page 2 1.1.3 The colonization of the gut by attenuated viruses establishes a barrier to infection by virulent viruses. This phenomenon is valuable in the management of epidemic poliomyelitis. 1.1.4 The development of gut immunity and the circulation of vaccine viruses within the community, which occurs in some situations, leads to the production of a degree of immunity in the community that is greater than can be accounted for by the proportion of the population that has been directly immunized. There is evidence from developed and developing countries that, when live poliovirus vaccines are used, the incidence of paralytic poliomyelitis and the circulation of wild polioviruses may be markedly reduced well before the whole population has been immunized. This has been particularly well shown in the United Kingdom, the United States and Singapore. 1.1.5 Serological evidence suggests that oral polio vaccines are not as effective in warm as in temperate climates. A number of factors are involved in this phenomenon. There is, however, some evidence suggesting that a population that is consistently well immunized with a potent oral vaccine will be protected from paralytic poliomyelitis despite apparently unsatisfactory serological responses. 1.1.6 There is some evidence that oral vaccines do not produce as reliable a serological response when used in young infants who are still passively protected by maternal antibodies. Further information is required before this can be validated and its importance defined. 1.1.7 Oral polio vaccines are among the safest of vaccines. However, it has been estimated that cases of neurological disease associated with the use of these vaccines occur at the rate of one for every three million vaccinees. In a country where there is any risk from poliomyelitis the vaccine has an excellent risk:benefit ratio. 1.2 Delivery and administration 1.2.1 Oral polio vaccine needs to be kept frozen for long-term storage but with a suitable stabilizer will retain its potency at 2-8°C for as long as 12 months. For the vaccine to remain effective, therefore, there is a need for an efficient cold chain. 1.2.2 The method of administration, by drops directly into the mouth or on a sugar lump or in fruit juice off a spoon, is acceptable to both children and parents. It requires no special skill or equipment. The schedule usually recommended is three doses starting from about the third month of age and spaced 4-8 weeks apart, with a fourth dose 1-2 years later. For convenience the vaccine is usually given at the same time as diphtheria/pertussis/tetanus vaccine (DPT). 1.3 Availability and price Oral polio vaccine is produced in cultures of monkey kidney cells. The methods of produc- tion are well established and the present manufacturers can supply as much vaccine as is likely to be required, without further development. Because the volume produced is so large, the cost is low. Oral vaccine obtained in 1981 through UNICEF will cost US $0.02 per dose. 2. Inactivated poliomyelitis vaccine This vaccine contains polioviruses of all three serotypes which have been killed by formalin. 2.1 Efficacy and safety 2.1.1 Inactivated poliovirus vaccine was the first vaccine to be developed against poliomyelitis. It was highly effective in reducing the incidence of paralytic poliomyelitis in the United States before oral vaccine was introduced, and in Scandinavia and Holland where its continued use has been associated with an incidence of paralytic poliomyelitis approaching zero. When outbreaks have occurred, caused by imported wild poliovirus, they have involved unvaccinated individuals exclusively. EPI/GEN/81/3 page 3 2.1.2 The vaccine is injected and stimulates the production of circulating antibodies which apparently act by preventing the invasion of the central nervous system by wild polioviruses which may infect the pharynx and the gut. As with oral vaccine it is not known whether this immunity, once established, is lifelong or whether reinforcement is required either by further vaccine or by circulating wild viruses. 2.1.3 When used on a very wide scale this vaccine has been shown to cause the disap- pearance of wild poliovirus from the community. Under these conditions it thus offers indirect protection by reducing the chances of infection of individuals who have not received vaccine. This mechanism will not, however, protect the unimmunized members of the population if they come into contact with imported wild viruses. 2.1.4 Inactivated vaccine stimulates the production of antibody at all ages, but its ability to do so is affected by the presence of maternal antibody. 2.1.5 Small scale controlled trials in West Africa, using concentrated vaccine, have demonstrated good serological responses in vaccinees. Inactivated vaccine has not yet been used on a large scale in any developing country. Its efficacy in preventing clinical poliomyelitis in developing countries where there may be vaccine handling problems and where coverage may be far from complete is unknown. 2.1.6 Well prepared inactivated poliovirus vaccine is safe. No adverse reactions have yet been reported. The only foreseeable danger lies in that failure of inactivation during manufacture could lead to children being injected with live, virulent poliovirus. 2.2 Delivery and administration 2.2.1 Inactivated polio vaccines require refrigeration but most will retain their 0 potency at 2-8 C fqr more than a year. An efficient cold chain is needed for the reliable storage of this vaccine. 2.2.2 A number of different administration schedules have been used in those developed countries where inactivated vaccine has been extensively employed. All stipulate at least two doses in the first year of life, followed by boosters at various times during the school years. A total of at least four doses is recommended. Recently produced vaccines of high potency are claimed to produce ~dequate and lasting immunity with one or two doses. The long term efficacy of these vaccines has not yet been established. 2.2.3 Although available on its own, inactivated polio vaccine is also available combined with DPT vaccine. The most appropriate dosage and administration schedules for this combined vaccine in developing countries are not yet known. Although inactivated vaccine must be given parenterally, its inclusion with DPT in a quadruple vaccine would preclude any increase in the number of injections that each child received. 2.3 Availability and price 2.3.1 Inactivated vaccines currently available are produced in cultures of monkey kidney cells. Recent developments in tissue culture techniques give promise of more efficient use of primary cells, and the availability of more plentiful supplies from tertiary monkey kidney cells. Vaccines produced on these cells are not yet licensed. WHO Requirements referring to the use of cells in addition to the use of primary monkey kidney cells have been formulated and will become available for vaccine manufacture in the near future. Experiments on vaccine production in vero cells and on more efficient concentration systems also provide the technology for future methods suitable for large scale production. At present, however, inactivated vaccine is not available in the large quantities that would be required for any significant expansion of the number of countries using it. 2.3.2 Because of the present constraints on the methods of production, the cost of inactivated vaccine is high. The current price is in excess of US $0.50 per dose. EPI/GEN/81/3 page 4 3. Present EPI policy . 3.1 It is generally accepted that either oral or inactivated vaccines, when given to a high proportion of the population, will produce a significant decline in the incidence of para- lytic poliomyelitis. Operational conditions in many developing countries, however, preclude the achievement of high levels of coverage in the immediate future. 3.2 Information is not available on several important aspects of vaccine efficacy and use. Work is planned to provide information particularly on: 3.2.1 Optimum dosage and administration schedules. This includes studies on: - the respective roles of gut and blood-borne immunities in the development of individual and herd immunity; ~ the most effective methods for ensuring protection for infants in the early months of life; - the efficacy of giving both oral and inactivated vaccine at different times in the same schedules. 3.2.2 Large scale evaluation of the effect on morbidity from .paralytic poliomyelitis of inactivated and oral vaccines when used under field conditions in developing countries. 3.3 In the light of current knowledge and practices there are four areas in which oral vaccine can be seen as preferable to inactivated for use in current immunization schedules in developing countries: 3.3.1 Oral vaccine has been used extensively and has already proved its value in reducing the incidence of paralytic poliomyelitis in tropical and subtropical developing countries. 3.3.2 It is believed that oral vaccine may reduce the circulation of wild poliovirus and the incidence of paralytic poliomyelitis to an extent disproportionate to the size of the vaccinated group within a population. 3.3.3 Oral polio vaccine is available through UNICEF for use on a large scale without the need for further development of manufacturing methods or capacity. 3.3.4 Oral polio vaccine is, at current prices, cheaper per dose than inactivated vaccine by a factor of at least 25. For these reasons, EPI will continue to propose oral poliomyelitis vaccine as the most appropirate polio vaccine for general use in countries which are either intending to institute polio immunization or which are already using oral vaccine. At the same time, it must be stressed that the results obtained in some developing countries using oral polio vaccine are not as good as could be hoped. As indicated aboye, coordinated research will continue into the optimum methods of preventing poliomyelitis and future decisions will be made in the light of the findings of this work.
• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE EPI/GEN/8113 /~' 1 ·' ·t. ( _ t ,.r , , t, . ·"'" ENGLISH ONLY I. REVIEW OF CURRENT STATUS OF . / /'. 11' rtctC ORAL AND INACTIVATED POLIOMYELITIS VACCINES l. 2. 3. Oral poliomyelitis vaccine Inactivated poliomyelitis vaccine Present EPI policy Contents Page 1 2 4 Evidence from routine and special survey sources indicates that transmission of polio- virus and the consequent incidence of paralysis due to poliomyelitis are at levels in many developing countries that are comparable to those experienced in the developed countries during the epidemic years from the 1930s to the 1950s. Poliomyelitis has been effectively controlled in the developed countries by the use of polio vaccines, and such vaccines should be used in the developing countries to achieve the same end. There are two basic forms of poliovirus vaccine available: Live, attenuated virus vaccines (oral); - Inactivated virus vaccines. Inactivated vaccine has been available since 1955 and oral slnce 1960. When used on a wide scale both have been shown to be effective and safe. The choice between them in any set of circumstances must be made, taking into account the following: - Efficacy and safety; - Delivery and administration; - Availability and price. 1. Oral poliomyelitis vaccine This vaccine, as usually formulated, contains live, attenuated poliovirus of serotypes 1, 2 and 3 in titres which take account of the differing ability of these serotypes to compete ln infecting the gut. 1.1 Efficacy and safety 1.1.1 Oral poliomyelitis vaccine has been widely used since 1960. The dramatic and sus- tained reduction in paralytic poliomyelitis seen in the countries of Europe and North America, as well as some countries in Central and South America and East Asia, can in most cases be attributed to this vaccine. 1.1.2 The vaccine stimulates the production of antibodies in the gut and pharynx as well as in the blood. The immunity it produces is therefore identical in character to the permanent immunity produced by virulent wild viruses. The issue of this document does not constitute formal publication. lt should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. 11 ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation Mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. EPI/GEN/81/3 page 2 1.1.3 The colonization of the gut by attenuated viruses establishes a barrier to infection by virulent viruses. This phenomenon is valuable in the management of epidemic poliomyelitis. 1.1.4 The development of gut immunity and the circulation of vaccine viruses within the community, which occurs in some situations, leads to the production of a degree of immunity in the community that is greater than can be accounted for by the proportion of the population that has been directly immunized. There is evidence from developed and developing countries that, when live poliovirus vaccines are used, the incidence of paralytic poliomyelitis and the circulation of wild polioviruses may be markedly reduced well before the whole population has been immunized. This has been particularly well shown in the United Kingdom, the United States and Singapore. 1.1.5 Serological evidence suggests that oral polio vaccines are not as effective in warm as in temperate climates. A number of factors are involved in this phenomenon. There is, however, some evidence suggesting that a population that is consistently well immunized with a potent oral vaccine will be protected from paralytic poliomyelitis despite apparently unsatisfactory serological responses. 1.1.6 There is some evidence that oral vaccines do not produce as reliable a serological response when used in young infants who are still passively protected by maternal antibodies. Further information is required before this can be validated and its importance defined. 1.1.7 Oral polio vaccines are among the safest of vaccines. However, it has been estimated that cases of neurological disease associated with the use of these vaccines occur at the rate of one for every three million vaccinees. In a country where there is any risk from poliomyelitis the vaccine has an excellent risk:benefit ratio. 1.2 Delivery and administration 1.2.1 Oral polio vaccine needs to be kept frozen for long-term storage but with a suitable stabilizer will retain its potency at 2-8°C for as long as 12 months. For the vaccine to remain effective, therefore, there is a need for an efficient cold chain. 1.2.2 The method of administration, by drops directly into the mouth or on a sugar lump or in fruit juice off a spoon, is acceptable to both children and parents. It requires no special skill or equipment. The schedule usually recommended is three doses starting from about the third month of age and spaced 4-8 weeks apart, with a fourth dose 1-2 years later. For convenience the vaccine is usually given at the same time as diphtheria/pertussis/tetanus vaccine (DPT). 1.3 Availability and price Oral polio vaccine is produced in cultures of monkey kidney cells. The methods of produc- tion are well established and the present manufacturers can supply as much vaccine as is likely to be required, without further development. Because the volume produced is so large, the cost is low. Oral vaccine obtained in 1981 through UNICEF will cost US $0.02 per dose. 2. Inactivated poliomyelitis vaccine This vaccine contains polioviruses of all three serotypes which have been killed by formalin. 2.1 Efficacy and safety 2.1.1 Inactivated poliovirus vaccine was the first vaccine to be developed against poliomyelitis. It was highly effective in reducing the incidence of paralytic poliomyelitis in the United States before oral vaccine was introduced, and in Scandinavia and Holland where its continued use has been associated with an incidence of paralytic poliomyelitis approaching zero. When outbreaks have occurred, caused by imported wild poliovirus, they have involved unvaccinated individuals exclusively. EPI/GEN/81/3 page 3 2.1.2 The vaccine is injected and stimulates the production of circulating antibodies which apparently act by preventing the invasion of the central nervous system by wild polioviruses which may infect the pharynx and the gut. As with oral vaccine it is not known whether this immunity, once established, is lifelong or whether reinforcement is required either by further vaccine or by circulating wild viruses. 2.1.3 When used on a very wide scale this vaccine has been shown to cause the disap- pearance of wild poliovirus from the community. Under these conditions it thus offers indirect protection by reducing the chances of infection of individuals who have not received vaccine. This mechanism will not, however, protect the unimmunized members of the population if they come into contact with imported wild viruses. 2.1.4 Inactivated vaccine stimulates the production of antibody at all ages, but its ability to do so is affected by the presence of maternal antibody. 2.1.5 Small scale controlled trials in West Africa, using concentrated vaccine, have demonstrated good serological responses in vaccinees. Inactivated vaccine has not yet been used on a large scale in any developing country. Its efficacy in preventing clinical poliomyelitis in developing countries where there may be vaccine handling problems and where coverage may be far from complete is unknown. 2.1.6 Well prepared inactivated poliovirus vaccine is safe. No adverse reactions have yet been reported. The only foreseeable danger lies in that failure of inactivation during manufacture could lead to children being injected with live, virulent poliovirus. 2.2 Delivery and administration 2.2.1 Inactivated polio vaccines require refrigeration but most will retain their 0 potency at 2-8 C fqr more than a year. An efficient cold chain is needed for the reliable storage of this vaccine. 2.2.2 A number of different administration schedules have been used in those developed countries where inactivated vaccine has been extensively employed. All stipulate at least two doses in the first year of life, followed by boosters at various times during the school years. A total of at least four doses is recommended. Recently produced vaccines of high potency are claimed to produce ~dequate and lasting immunity with one or two doses. The long term efficacy of these vaccines has not yet been established. 2.2.3 Although available on its own, inactivated polio vaccine is also available combined with DPT vaccine. The most appropriate dosage and administration schedules for this combined vaccine in developing countries are not yet known. Although inactivated vaccine must be given parenterally, its inclusion with DPT in a quadruple vaccine would preclude any increase in the number of injections that each child received. 2.3 Availability and price 2.3.1 Inactivated vaccines currently available are produced in cultures of monkey kidney cells. Recent developments in tissue culture techniques give promise of more efficient use of primary cells, and the availability of more plentiful supplies from tertiary monkey kidney cells. Vaccines produced on these cells are not yet licensed. WHO Requirements referring to the use of cells in addition to the use of primary monkey kidney cells have been formulated and will become available for vaccine manufacture in the near future. Experiments on vaccine production in vero cells and on more efficient concentration systems also provide the technology for future methods suitable for large scale production. At present, however, inactivated vaccine is not available in the large quantities that would be required for any significant expansion of the number of countries using it. 2.3.2 Because of the present constraints on the methods of production, the cost of inactivated vaccine is high. The current price is in excess of US $0.50 per dose. EPI/GEN/81/3 page 4 3. Present EPI policy . 3.1 It is generally accepted that either oral or inactivated vaccines, when given to a high proportion of the population, will produce a significant decline in the incidence of para- lytic poliomyelitis. Operational conditions in many developing countries, however, preclude the achievement of high levels of coverage in the immediate future. 3.2 Information is not available on several important aspects of vaccine efficacy and use. Work is planned to provide information particularly on: 3.2.1 Optimum dosage and administration schedules. This includes studies on: - the respective roles of gut and blood-borne immunities in the development of individual and herd immunity; ~ the most effective methods for ensuring protection for infants in the early months of life; - the efficacy of giving both oral and inactivated vaccine at different times in the same schedules. 3.2.2 Large scale evaluation of the effect on morbidity from .paralytic poliomyelitis of inactivated and oral vaccines when used under field conditions in developing countries. 3.3 In the light of current knowledge and practices there are four areas in which oral vaccine can be seen as preferable to inactivated for use in current immunization schedules in developing countries: 3.3.1 Oral vaccine has been used extensively and has already proved its value in reducing the incidence of paralytic poliomyelitis in tropical and subtropical developing countries. 3.3.2 It is believed that oral vaccine may reduce the circulation of wild poliovirus and the incidence of paralytic poliomyelitis to an extent disproportionate to the size of the vaccinated group within a population. 3.3.3 Oral polio vaccine is available through UNICEF for use on a large scale without the need for further development of manufacturing methods or capacity. 3.3.4 Oral polio vaccine is, at current prices, cheaper per dose than inactivated vaccine by a factor of at least 25. For these reasons, EPI will continue to propose oral poliomyelitis vaccine as the most appropirate polio vaccine for general use in countries which are either intending to institute polio immunization or which are already using oral vaccine. At the same time, it must be stressed that the results obtained in some developing countries using oral polio vaccine are not as good as could be hoped. As indicated aboye, coordinated research will continue into the optimum methods of preventing poliomyelitis and future decisions will be made in the light of the findings of this work.
• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE EPI/GEN/8113 /~' 1 ·' ·t. ( _ t ,.r , , t, . ·"'" ENGLISH ONLY I. REVIEW OF CURRENT STATUS OF . / /'. 11' rtctC ORAL AND INACTIVATED POLIOMYELITIS VACCINES l. 2. 3. Oral poliomyelitis vaccine Inactivated poliomyelitis vaccine Present EPI policy Contents Page 1 2 4 Evidence from routine and special survey sources indicates that transmission of polio- virus and the consequent incidence of paralysis due to poliomyelitis are at levels in many developing countries that are comparable to those experienced in the developed countries during the epidemic years from the 1930s to the 1950s. Poliomyelitis has been effectively controlled in the developed countries by the use of polio vaccines, and such vaccines should be used in the developing countries to achieve the same end. There are two basic forms of poliovirus vaccine available: Live, attenuated virus vaccines (oral); - Inactivated virus vaccines. Inactivated vaccine has been available since 1955 and oral slnce 1960. When used on a wide scale both have been shown to be effective and safe. The choice between them in any set of circumstances must be made, taking into account the following: - Efficacy and safety; - Delivery and administration; - Availability and price. 1. Oral poliomyelitis vaccine This vaccine, as usually formulated, contains live, attenuated poliovirus of serotypes 1, 2 and 3 in titres which take account of the differing ability of these serotypes to compete ln infecting the gut. 1.1 Efficacy and safety 1.1.1 Oral poliomyelitis vaccine has been widely used since 1960. The dramatic and sus- tained reduction in paralytic poliomyelitis seen in the countries of Europe and North America, as well as some countries in Central and South America and East Asia, can in most cases be attributed to this vaccine. 1.1.2 The vaccine stimulates the production of antibodies in the gut and pharynx as well as in the blood. The immunity it produces is therefore identical in character to the permanent immunity produced by virulent wild viruses. The issue of this document does not constitute formal publication. lt should not be reviewed, abstracted or quoted without the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. 11 ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation Mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. EPI/GEN/81/3 page 2 1.1.3 The colonization of the gut by attenuated viruses establishes a barrier to infection by virulent viruses. This phenomenon is valuable in the management of epidemic poliomyelitis. 1.1.4 The development of gut immunity and the circulation of vaccine viruses within the community, which occurs in some situations, leads to the production of a degree of immunity in the community that is greater than can be accounted for by the proportion of the population that has been directly immunized. There is evidence from developed and developing countries that, when live poliovirus vaccines are used, the incidence of paralytic poliomyelitis and the circulation of wild polioviruses may be markedly reduced well before the whole population has been immunized. This has been particularly well shown in the United Kingdom, the United States and Singapore. 1.1.5 Serological evidence suggests that oral polio vaccines are not as effective in warm as in temperate climates. A number of factors are involved in this phenomenon. There is, however, some evidence suggesting that a population that is consistently well immunized with a potent oral vaccine will be protected from paralytic poliomyelitis despite apparently unsatisfactory serological responses. 1.1.6 There is some evidence that oral vaccines do not produce as reliable a serological response when used in young infants who are still passively protected by maternal antibodies. Further information is required before this can be validated and its importance defined. 1.1.7 Oral polio vaccines are among the safest of vaccines. However, it has been estimated that cases of neurological disease associated with the use of these vaccines occur at the rate of one for every three million vaccinees. In a country where there is any risk from poliomyelitis the vaccine has an excellent risk:benefit ratio. 1.2 Delivery and administration 1.2.1 Oral polio vaccine needs to be kept frozen for long-term storage but with a suitable stabilizer will retain its potency at 2-8°C for as long as 12 months. For the vaccine to remain effective, therefore, there is a need for an efficient cold chain. 1.2.2 The method of administration, by drops directly into the mouth or on a sugar lump or in fruit juice off a spoon, is acceptable to both children and parents. It requires no special skill or equipment. The schedule usually recommended is three doses starting from about the third month of age and spaced 4-8 weeks apart, with a fourth dose 1-2 years later. For convenience the vaccine is usually given at the same time as diphtheria/pertussis/tetanus vaccine (DPT). 1.3 Availability and price Oral polio vaccine is produced in cultures of monkey kidney cells. The methods of produc- tion are well established and the present manufacturers can supply as much vaccine as is likely to be required, without further development. Because the volume produced is so large, the cost is low. Oral vaccine obtained in 1981 through UNICEF will cost US $0.02 per dose. 2. Inactivated poliomyelitis vaccine This vaccine contains polioviruses of all three serotypes which have been killed by formalin. 2.1 Efficacy and safety 2.1.1 Inactivated poliovirus vaccine was the first vaccine to be developed against poliomyelitis. It was highly effective in reducing the incidence of paralytic poliomyelitis in the United States before oral vaccine was introduced, and in Scandinavia and Holland where its continued use has been associated with an incidence of paralytic poliomyelitis approaching zero. When outbreaks have occurred, caused by imported wild poliovirus, they have involved unvaccinated individuals exclusively. EPI/GEN/81/3 page 3 2.1.2 The vaccine is injected and stimulates the production of circulating antibodies which apparently act by preventing the invasion of the central nervous system by wild polioviruses which may infect the pharynx and the gut. As with oral vaccine it is not known whether this immunity, once established, is lifelong or whether reinforcement is required either by further vaccine or by circulating wild viruses. 2.1.3 When used on a very wide scale this vaccine has been shown to cause the disap- pearance of wild poliovirus from the community. Under these conditions it thus offers indirect protection by reducing the chances of infection of individuals who have not received vaccine. This mechanism will not, however, protect the unimmunized members of the population if they come into contact with imported wild viruses. 2.1.4 Inactivated vaccine stimulates the production of antibody at all ages, but its ability to do so is affected by the presence of maternal antibody. 2.1.5 Small scale controlled trials in West Africa, using concentrated vaccine, have demonstrated good serological responses in vaccinees. Inactivated vaccine has not yet been used on a large scale in any developing country. Its efficacy in preventing clinical poliomyelitis in developing countries where there may be vaccine handling problems and where coverage may be far from complete is unknown. 2.1.6 Well prepared inactivated poliovirus vaccine is safe. No adverse reactions have yet been reported. The only foreseeable danger lies in that failure of inactivation during manufacture could lead to children being injected with live, virulent poliovirus. 2.2 Delivery and administration 2.2.1 Inactivated polio vaccines require refrigeration but most will retain their 0 potency at 2-8 C fqr more than a year. An efficient cold chain is needed for the reliable storage of this vaccine. 2.2.2 A number of different administration schedules have been used in those developed countries where inactivated vaccine has been extensively employed. All stipulate at least two doses in the first year of life, followed by boosters at various times during the school years. A total of at least four doses is recommended. Recently produced vaccines of high potency are claimed to produce ~dequate and lasting immunity with one or two doses. The long term efficacy of these vaccines has not yet been established. 2.2.3 Although available on its own, inactivated polio vaccine is also available combined with DPT vaccine. The most appropriate dosage and administration schedules for this combined vaccine in developing countries are not yet known. Although inactivated vaccine must be given parenterally, its inclusion with DPT in a quadruple vaccine would preclude any increase in the number of injections that each child received. 2.3 Availability and price 2.3.1 Inactivated vaccines currently available are produced in cultures of monkey kidney cells. Recent developments in tissue culture techniques give promise of more efficient use of primary cells, and the availability of more plentiful supplies from tertiary monkey kidney cells. Vaccines produced on these cells are not yet licensed. WHO Requirements referring to the use of cells in addition to the use of primary monkey kidney cells have been formulated and will become available for vaccine manufacture in the near future. Experiments on vaccine production in vero cells and on more efficient concentration systems also provide the technology for future methods suitable for large scale production. At present, however, inactivated vaccine is not available in the large quantities that would be required for any significant expansion of the number of countries using it. 2.3.2 Because of the present constraints on the methods of production, the cost of inactivated vaccine is high. The current price is in excess of US $0.50 per dose. EPI/GEN/81/3 page 4 3. Present EPI policy . 3.1 It is generally accepted that either oral or inactivated vaccines, when given to a high proportion of the population, will produce a significant decline in the incidence of para- lytic poliomyelitis. Operational conditions in many developing countries, however, preclude the achievement of high levels of coverage in the immediate future. 3.2 Information is not available on several important aspects of vaccine efficacy and use. Work is planned to provide information particularly on: 3.2.1 Optimum dosage and administration schedules. This includes studies on: - the respective roles of gut and blood-borne immunities in the development of individual and herd immunity; ~ the most effective methods for ensuring protection for infants in the early months of life; - the efficacy of giving both oral and inactivated vaccine at different times in the same schedules. 3.2.2 Large scale evaluation of the effect on morbidity from .paralytic poliomyelitis of inactivated and oral vaccines when used under field conditions in developing countries. 3.3 In the light of current knowledge and practices there are four areas in which oral vaccine can be seen as preferable to inactivated for use in current immunization schedules in developing countries: 3.3.1 Oral vaccine has been used extensively and has already proved its value in reducing the incidence of paralytic poliomyelitis in tropical and subtropical developing countries. 3.3.2 It is believed that oral vaccine may reduce the circulation of wild poliovirus and the incidence of paralytic poliomyelitis to an extent disproportionate to the size of the vaccinated group within a population. 3.3.3 Oral polio vaccine is available through UNICEF for use on a large scale without the need for further development of manufacturing methods or capacity. 3.3.4 Oral polio vaccine is, at current prices, cheaper per dose than inactivated vaccine by a factor of at least 25. For these reasons, EPI will continue to propose oral poliomyelitis vaccine as the most appropirate polio vaccine for general use in countries which are either intending to institute polio immunization or which are already using oral vaccine. At the same time, it must be stressed that the results obtained in some developing countries using oral polio vaccine are not as good as could be hoped. As indicated aboye, coordinated research will continue into the optimum methods of preventing poliomyelitis and future decisions will be made in the light of the findings of this work.