- Email: [email protected]
Polio vaccines and the eradication of poliomyelitis
Comment
Polio vaccines and the eradication of poliomyelitis Published Online July 4, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60921-0
AFP/Getty Images
See Articles page 491
454
In The Lancet, Kathleen O’Reilly and colleagues1 describe their findings from a case-control analysis of vaccination history data from children in Pakistan and Afghanistan, in which they estimated the clinical effectiveness of oral monovalent, bivalent, and trivalent poliovirus vaccines (OPVs) specifically related to type 1 poliomyelitis—a topic that might seem esoteric to those outside the poliomyelitis community. However, these results provide an example of the need to tailor immunisation programmes to epidemiological circumstances, particularly where the goal is eradication. In the UK, the incidence of poliomyelitis in the early 1950s ranged from about 1000 to 10 000 people per year—about 1% of the birth cohort.2 By the 1960s, cases of poliomyelitis had been controlled, mainly by the use of the Salk inactivated vaccine, and by the 1970s poliomyelitis was rare or non-existent. The live attenuated vaccines (OPVs) developed by Sabin were used in preference to the Salk inactivated vaccine from the early 1960s in the UK and elsewhere because they were thought to be better able to prevent transmission. Control of poliomyelitis in tropical and less developed countries was more difficult,3 but by the mid-1980s the disease had been eliminated from most of South America, leading the World Health Assembly to pledge the commitment of WHO to the global eradication of poliomyelitis by 2000.4 Although this target was missed, poliomyelitis was eradicated from most countries, and by 2009 there were only four countries that had
never managed to do so: India, Pakistan, Afghanistan, and Nigeria.5 These countries are a reservoir for the reintroduction of the virus into poliomyelitis-free areas, which has occurred repeatedly, for instance from India to Angola; from Nigeria to many of the surrounding countries and also Yemen and Indonesia; from India to Tajikistan, a country in the WHO European region; and from Pakistan to China, a country that pioneered eradication after South America became poliomyelitis free.5 Clearly, if one country has poliomyelitis the whole world is at risk. The immunisation strategies needed to eradicate poliomyelitis depend on epidemiological circumstances. In developed countries, the seasonality of infection meant that routine immunisation at a set age was sufficient to reduce the pool of susceptible people during the low season to levels at which virus transmission in the high season was not sustainable.6 In regions where poliomyelitis transmission occurs throughout the year, such as in South America, the strategy for eradication involved mass campaigns directly aimed at reducing the pool of susceptible people and breaking the silent transmission of poliomyelitis, which is one of its characteristic features.7 This strategy proved very successful in most regions of the world. However, poliomyelitis eradication in the four countries that were endemic in 2009 proved more difficult. Poliomyelitis occurs in three serotypes and the live vaccine has been given as a mixture of all three trivalent OPV. The strains compete with each other, and the type 2 component infects and produces immunity at the expense of types 1 and 3; wild type 2 poliomyelitis has been eradicated globally including in the four endemic countries—the last case was identified in October, 1999. The remaining serotypes, 1 and 3, were problematic so long as type 2 was included in the vaccine because of interference between the vaccine strains and, although trivalent OPV remains the vaccine of choice in routine vaccination programmes, monovalent OPV and bivalent OPV preparations were developed for use and are now used in mass campaigns. Findings from studies in India showed that these vaccines were more effective than trivalent OPV;8 the last case of poliomyelitis in India occurred in a 2-year-old girl in West Bengal on Jan 13, 2011.5 This outstanding achievement provides www.thelancet.com Vol 380 August 4, 2012
Comment
encouragement for eradication efforts in the remaining three countries that have never eradicated the disease. It shows the value of careful examination of the effect of vaccination and the means to optimise the effects of vaccination programmes. O’Reilly and colleagues1 estimate the per-dose effectiveness of monovalent OPV to have been 34·5% (95% CI 16·1–48·9) as compared with 23·4% (10·4–34·6) for bivalent OPV and 12·5% (5·6–18·8) for trivalent OPV, indicating that, where monovalent OPV and bivalent OPV are given in Afghanistan and Pakistan, their effect is consistent with the findings from studies in India where they played such a big part in eradication. However, the number of poliomyelitis cases in these countries has risen in the past few years, suggesting that vaccines are not being delivered. Given the circumstances, this finding might not be surprising but it does imply that if the vaccine could be given, poliomyelitis could be eradicated. There is one additional matter: given that nobody has been infected with wild type 2 poliomyelitis this century, continued inclusion of the type 2 component in vaccines might seem strange. The problem with not including the type 2 component and using bivalent OPV routinely is that the vaccine strains can revert to transmissible forms to cause circulating vaccine-derived poliovirus;9 type 2 circulating vaccine-derived poliovirus is the most common and there have been an uncomfortable number of outbreaks as a result.10 Using a vaccine that does not include the type 2 component is therefore probably risky. Conversely, to immunise against a disease that is only caused by the vaccine seems unsustainable. The last stages of poliomyelitis eradication are interesting and highlight important issues in virus eradication,10 partly because of the silent nature of most infections, which makes the last cases hard to identify, and partly
because of the risks that vaccines based on growth of the virus pose, at however low a level and whether inactivated or live.9–12 The use of suitable vaccines given appropriately is key to the eradication of the last cases attributable to wild type poliovirus but, given what has happened in India, worldwide eradication is possible. Philip D Minor Division of Virology, National Institute of Biological Standards and Control, Health Protection Agency, Potters Bar, South Mimms EN6 3QG, UK [email protected] I declare that I have no conflicts of interest. 1
2
3 4
5 6 7
8 9
10 11 12
O’Reilly KM, Durry E, ul Islam O, et al. The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001–11: a retrospective analysis. Lancet 2012; published online July 4. http://dx.doi.org/10.1016/ S0140-6736(12)60648-5. Office of Health Economics. The price of poliomyelitis, 1963. http:// ohematerials.org/publication_pdfs/Price_of_Poliomyelitis_1963.pdf (accessed May 10, 2012). Jacob TJ. Poliomyelitis in India: prospects and problems of control. Rev Infect Dis 1984; 6 (suppl 2): S438–41. 41st World Health Assembly. Resolution WHA 41.28, 1988. http://www. polioeradication.org/content/publications/19880513_resolution.pdf (accessed May 10, 2012). Global Polio Eradication Initiative. Infected countries. http://www. polioeradication.org/Infectedcountries.aspx (accessed May 10, 2012). Nathanson N. Epidemiologic aspects of poliomyelitis eradication. Rev Infect Dis 1984; 6 (suppl 2): S308–12. Sabin AB. Strategies for elimination of poliomyelitis in different parts of the world with use of oral poliovirus vaccine. Rev Infect Dis 1984; 6 (suppl 2): S391–96. Grassly NC, Wenger J, Durrani S, et al. Protective efficacy of a monovalent type 1 poliovirus vaccine: a case-control study. Lancet 2007, 369: 1356–62. Kew O, Morris-Glasgow V, Landaverde M, et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 2002; 296: 356–59. Minor PD. The polio-eradication programme and issues of the end game. J Gen Virol 2012; 93: 457–74. Nkowane BM, Wassilak SG, Orenstein WA, et al. Vaccine associated paralytic poliomyelitis. United States: 1973 through 1984. JAMA 1987; 257: 1335–40. Nathanson N, Langmuir AD. The Cutter incident: poliomyelitis following formaldehyde-inactivated poliovirus vaccination in the United States during the spring of 1955. II Relationship of poliomyelitis to Cutter vaccine. Am J Hyg 1963; 78: 29–60.
Beyond the bombs: cancer risks of low-dose medical radiation More than a decade ago, Brenner and colleagues’ landmark report1 suggested that radiation doses attributed to paediatric CT scans would lead to a significant number of excess cancer deaths. The risk estimates produced for paediatric CT in that study,1 and subsequent estimates for other medical exposures,2 were derived from risk projection models based on studies of survivors of the atomic bombs in Japan.3,4 www.thelancet.com Vol 380 August 4, 2012
Many differences exist between a CT scan and exposure to an atomic bomb—for example, CT scans are usually focused on a particular part of the body, whereas atomic bomb exposures affected the whole body. Investigators took these differences into account insofar as possible in the models used to estimate CT scan risks, but were the predictions correct? Was there a small yet real cancer risk associated with CT scans?
Published Online June 7, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60897-6 See Articles page 499
455
Polio vaccines and the eradication of poliomyelitis Published Online July 4, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60921-0
AFP/Getty Images
See Articles page 491
454
In The Lancet, Kathleen O’Reilly and colleagues1 describe their findings from a case-control analysis of vaccination history data from children in Pakistan and Afghanistan, in which they estimated the clinical effectiveness of oral monovalent, bivalent, and trivalent poliovirus vaccines (OPVs) specifically related to type 1 poliomyelitis—a topic that might seem esoteric to those outside the poliomyelitis community. However, these results provide an example of the need to tailor immunisation programmes to epidemiological circumstances, particularly where the goal is eradication. In the UK, the incidence of poliomyelitis in the early 1950s ranged from about 1000 to 10 000 people per year—about 1% of the birth cohort.2 By the 1960s, cases of poliomyelitis had been controlled, mainly by the use of the Salk inactivated vaccine, and by the 1970s poliomyelitis was rare or non-existent. The live attenuated vaccines (OPVs) developed by Sabin were used in preference to the Salk inactivated vaccine from the early 1960s in the UK and elsewhere because they were thought to be better able to prevent transmission. Control of poliomyelitis in tropical and less developed countries was more difficult,3 but by the mid-1980s the disease had been eliminated from most of South America, leading the World Health Assembly to pledge the commitment of WHO to the global eradication of poliomyelitis by 2000.4 Although this target was missed, poliomyelitis was eradicated from most countries, and by 2009 there were only four countries that had
never managed to do so: India, Pakistan, Afghanistan, and Nigeria.5 These countries are a reservoir for the reintroduction of the virus into poliomyelitis-free areas, which has occurred repeatedly, for instance from India to Angola; from Nigeria to many of the surrounding countries and also Yemen and Indonesia; from India to Tajikistan, a country in the WHO European region; and from Pakistan to China, a country that pioneered eradication after South America became poliomyelitis free.5 Clearly, if one country has poliomyelitis the whole world is at risk. The immunisation strategies needed to eradicate poliomyelitis depend on epidemiological circumstances. In developed countries, the seasonality of infection meant that routine immunisation at a set age was sufficient to reduce the pool of susceptible people during the low season to levels at which virus transmission in the high season was not sustainable.6 In regions where poliomyelitis transmission occurs throughout the year, such as in South America, the strategy for eradication involved mass campaigns directly aimed at reducing the pool of susceptible people and breaking the silent transmission of poliomyelitis, which is one of its characteristic features.7 This strategy proved very successful in most regions of the world. However, poliomyelitis eradication in the four countries that were endemic in 2009 proved more difficult. Poliomyelitis occurs in three serotypes and the live vaccine has been given as a mixture of all three trivalent OPV. The strains compete with each other, and the type 2 component infects and produces immunity at the expense of types 1 and 3; wild type 2 poliomyelitis has been eradicated globally including in the four endemic countries—the last case was identified in October, 1999. The remaining serotypes, 1 and 3, were problematic so long as type 2 was included in the vaccine because of interference between the vaccine strains and, although trivalent OPV remains the vaccine of choice in routine vaccination programmes, monovalent OPV and bivalent OPV preparations were developed for use and are now used in mass campaigns. Findings from studies in India showed that these vaccines were more effective than trivalent OPV;8 the last case of poliomyelitis in India occurred in a 2-year-old girl in West Bengal on Jan 13, 2011.5 This outstanding achievement provides www.thelancet.com Vol 380 August 4, 2012
Comment
encouragement for eradication efforts in the remaining three countries that have never eradicated the disease. It shows the value of careful examination of the effect of vaccination and the means to optimise the effects of vaccination programmes. O’Reilly and colleagues1 estimate the per-dose effectiveness of monovalent OPV to have been 34·5% (95% CI 16·1–48·9) as compared with 23·4% (10·4–34·6) for bivalent OPV and 12·5% (5·6–18·8) for trivalent OPV, indicating that, where monovalent OPV and bivalent OPV are given in Afghanistan and Pakistan, their effect is consistent with the findings from studies in India where they played such a big part in eradication. However, the number of poliomyelitis cases in these countries has risen in the past few years, suggesting that vaccines are not being delivered. Given the circumstances, this finding might not be surprising but it does imply that if the vaccine could be given, poliomyelitis could be eradicated. There is one additional matter: given that nobody has been infected with wild type 2 poliomyelitis this century, continued inclusion of the type 2 component in vaccines might seem strange. The problem with not including the type 2 component and using bivalent OPV routinely is that the vaccine strains can revert to transmissible forms to cause circulating vaccine-derived poliovirus;9 type 2 circulating vaccine-derived poliovirus is the most common and there have been an uncomfortable number of outbreaks as a result.10 Using a vaccine that does not include the type 2 component is therefore probably risky. Conversely, to immunise against a disease that is only caused by the vaccine seems unsustainable. The last stages of poliomyelitis eradication are interesting and highlight important issues in virus eradication,10 partly because of the silent nature of most infections, which makes the last cases hard to identify, and partly
because of the risks that vaccines based on growth of the virus pose, at however low a level and whether inactivated or live.9–12 The use of suitable vaccines given appropriately is key to the eradication of the last cases attributable to wild type poliovirus but, given what has happened in India, worldwide eradication is possible. Philip D Minor Division of Virology, National Institute of Biological Standards and Control, Health Protection Agency, Potters Bar, South Mimms EN6 3QG, UK [email protected] I declare that I have no conflicts of interest. 1
2
3 4
5 6 7
8 9
10 11 12
O’Reilly KM, Durry E, ul Islam O, et al. The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001–11: a retrospective analysis. Lancet 2012; published online July 4. http://dx.doi.org/10.1016/ S0140-6736(12)60648-5. Office of Health Economics. The price of poliomyelitis, 1963. http:// ohematerials.org/publication_pdfs/Price_of_Poliomyelitis_1963.pdf (accessed May 10, 2012). Jacob TJ. Poliomyelitis in India: prospects and problems of control. Rev Infect Dis 1984; 6 (suppl 2): S438–41. 41st World Health Assembly. Resolution WHA 41.28, 1988. http://www. polioeradication.org/content/publications/19880513_resolution.pdf (accessed May 10, 2012). Global Polio Eradication Initiative. Infected countries. http://www. polioeradication.org/Infectedcountries.aspx (accessed May 10, 2012). Nathanson N. Epidemiologic aspects of poliomyelitis eradication. Rev Infect Dis 1984; 6 (suppl 2): S308–12. Sabin AB. Strategies for elimination of poliomyelitis in different parts of the world with use of oral poliovirus vaccine. Rev Infect Dis 1984; 6 (suppl 2): S391–96. Grassly NC, Wenger J, Durrani S, et al. Protective efficacy of a monovalent type 1 poliovirus vaccine: a case-control study. Lancet 2007, 369: 1356–62. Kew O, Morris-Glasgow V, Landaverde M, et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 2002; 296: 356–59. Minor PD. The polio-eradication programme and issues of the end game. J Gen Virol 2012; 93: 457–74. Nkowane BM, Wassilak SG, Orenstein WA, et al. Vaccine associated paralytic poliomyelitis. United States: 1973 through 1984. JAMA 1987; 257: 1335–40. Nathanson N, Langmuir AD. The Cutter incident: poliomyelitis following formaldehyde-inactivated poliovirus vaccination in the United States during the spring of 1955. II Relationship of poliomyelitis to Cutter vaccine. Am J Hyg 1963; 78: 29–60.
Beyond the bombs: cancer risks of low-dose medical radiation More than a decade ago, Brenner and colleagues’ landmark report1 suggested that radiation doses attributed to paediatric CT scans would lead to a significant number of excess cancer deaths. The risk estimates produced for paediatric CT in that study,1 and subsequent estimates for other medical exposures,2 were derived from risk projection models based on studies of survivors of the atomic bombs in Japan.3,4 www.thelancet.com Vol 380 August 4, 2012
Many differences exist between a CT scan and exposure to an atomic bomb—for example, CT scans are usually focused on a particular part of the body, whereas atomic bomb exposures affected the whole body. Investigators took these differences into account insofar as possible in the models used to estimate CT scan risks, but were the predictions correct? Was there a small yet real cancer risk associated with CT scans?
Published Online June 7, 2012 http://dx.doi.org/10.1016/ S0140-6736(12)60897-6 See Articles page 499
455