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1) Eradication of Poliovirus: Fighting Fire With Fire
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(See the article by Wasssilak et al., on pages 898–909.)
Endemic wild polioviruses have been eliminated from most of the world, and the number of human paralytic cases has been reduced by >99%, from an estimated annual incidence of >500,000 cases to <2000 cases [1–3]. Circulating wild polioviruses remain endemic in only 2 major locations, Nigeria and a zone extending from northern India west to Pakistan and Afghanistan [1–3]. Furthermore, wild-type 2 poliovirus has been eliminated altogether, with the last documented case reported in northern India in 1999 [4]. These remarkable accomplishments represent a triumph for oral poliovirus vaccine (OPV), composed of attenuated variants of the 3 poliovirus serotypes [5]. OPV is administered by mouth, induces mucosal and humoral immunity, and is relatively inexpensive to produce—attributes that have contributed to its widespread use even in regions with rudimentary health systems.
However, OPV has an Achilles heel. The attenuated variants in the vaccine are rapidly replaced by revertant mutants, even on a single passage through the human intestine [6]. The revertant genotype has been mapped to a limited number of point mutations [7, 8], and revertant viruses can be distinguished genetically from wild polioviruses [8]. OPV vaccinees excrete a mix of viruses, some of which are as paralytogenic as wild polioviruses. These excreted viruses, similar to wild polioviruses, are readily transmitted to contacts of vaccinated infants and children by the fecal-oral route. Therefore, after mass OPV vaccination campaigns, the environment is inundated with a mix of excreted viruses, some of which have the disease potential of wild polioviruses. Therefore, the use of OPV could be considered to be an example of fighting fire with fire.
The dangers of OPV were recognized during early vaccine trials, and one epidemiologist coined the epigram “in like a lamb out like a lion” [9 p. 1214]. On the basis of meticulous surveillance in the United States, vaccine-associated paralytic poliomyelitis was documented both in vaccinees and their immediate contacts [10–14]. However, vaccine-associated paralytic poliomyelitis in contacts was rare and sporadic, occurring at a rate of 1–2 cases per 1,000,000 primary vaccinations. In retrospect, it is likely that vaccine-derived polioviruses (VDPV) did not spread widely in the United States because most susceptible children were vaccinated with OPV, rendering them resistant to virus shed by their vaccinated contacts.
Since 2000, >15 outbreaks of paralytic poliomyelitis caused by circulating VDPV (cVDPV) have been recognized throughout the world [1]. Such outbreaks have shared one epidemiological characteristic. They have occurred in areas where OPV vaccination coverage has been incomplete; thus, >50% of children remained susceptible. Under these circumstances, cVDPV can circulate for many generations, infect large numbers of persons, and cause outbreaks of paralytic poliomyelitis.
The article by Wassilak et al [15] in this issue of the Journal and a companion article [16] describe the most significant of these outbreaks of cVDPV. The Nigerian epidemic, in which type 2 VDPV has caused >300 paralytic cases, began in 2005 and has continued through 2010. Because wild-type 2 poliovirus causes only 1 paralytic case per 2000 infections [1], the Nigerian outbreak might represent >600,000 infections with virulent VDPV.
Under what circumstances did this outbreak occur? First, similar to other outbreaks of cVDPV, the epidemic was concentrated in the northern region of Nigeria, where there were relatively low rates of OPV vaccination [15]. Second, during 2006–2010, most of the vaccination campaigns in Nigeria used either monovalent or, more recently, bivalent vaccine lacking type 2 OPV. The decision to use these formulations was based on an attempt to control wild-type 1 and 3 polioviruses at a time when wild-type 2 had been eliminated. Monovalent and bivalent formulations that omit type 2 OPV are much more effective than is trivalent OPV [17, 18]. In 2009, the dramatic increase in cases due to type 2 cVDPV led to several rounds of trivalent OPV, which may account for the rapid decrease in the number of type 2 cases in 2010. However, this outbreak has not yet been terminated, posing the potential threat of re-introduction of virulent type 2 polioviruses. Because wild-type 1 and 3 polioviruses frequently spread from Nigeria to neighboring countries in Africa, this constitutes a significant contingency [19].
The occurrence of repeated outbreaks of cVDPV and the magnitude of the Nigerian epidemic have sent a clear message. True eradication can only be achieved with the elimination of all circulating polioviruses. In countries or scontinents where wild polioviruses have been eliminated, there should be a transition from OPV to inactivated poliovirus vaccine. Many industrialized countries have already made this shift, which occurred in the United States during 1998–2000 [14]. Although there is no universal consensus, a number of experts have advocated this strategy [20–27]. Because inactivated poliovirus vaccine is expensive to manufacture and must be injected, this approach is costly. Several donors (including Rotary International and the Bill and Melinda Gates Foundation) have made significant commitments to underwrite this campaign for low-income countries.
Although recent history compels caution, it appears that the world may be on the cusp of elimination of indigenous wild polioviruses. When this goal is achieved, it will then be necessary to terminate the use of OPV if true eradication of circulating polioviruses is to be accomplished.
Footnotes
References
Centers for Disease Control, Prevention. Progress toward interruption of wild poliovirus transmission worldwide, 2009. MMWR Morb Mortal Wkly Rep 2010;59:545-50.
World Health Organization. Progress towards interruption of wild poliovirus transmission worldwide, 2009. Wkly Epidemiol Rec 2010;85:178-84.
. From emergence to eradication: the epidemiology of poliomyelitis deconstructed. Am J Epidemiol 2010. DOI: 10.1093/aje/kwq320.
. Apparent global interruption of wild poliovirus type 2 transmission. MMWR Morb Mortal Wkly Rep 2001;50:222-4.
. Present position of immunization against poliomyelitis with live virus vaccines. Br Med J 1959;1:663-80.
. Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature 1983;314:548-50.
. The molecular biology of poliovaccines. J Gen Virol 1992;73:3065-77.
. Vaccine-derived polioviruses and the endgame strategy for global polio eradication. Annu Rev Microbiol 2005;59:587-635.
. Immunity to poliomyelitis. Br Med J 1963;2:1468-9.
10. 10.↵
. Paralytic disease associated with oral polio vaccines. JAMA 1964;190:41-8.
11. 11.
. Vaccine-associated poliomyelitis in the United States, 1961-1972. Am J Epidemiol 1976;104:202-11.
12. 12.
. Vaccine-associated paralytic poliomyelitis, U.S.A. 1973–1984. JAMA 1987;257:1335-40.
13. 13.
. Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus-associated disease. Clin Infect Dis 1992;14:568-79.
14. 14.↵
. Vaccine policy changes and epidemiology of poliomyelitis in the United States. JAMA 2004;292:1696-701.
15. 15.↵
. Outbreak of type 2 vaccine-derived poliovirus in Nigeria: emergence and widespread circulation in a underimmunized population. J Infect Dis 2010. DOI:10.1093/infdis/JIQ140.
16. 16.↵
. Implications of a circulating vaccine-derived poliovirus in Nigeria. N Engl J Med 2010;362:2360-9.
17. 17.↵
. Effectiveness of immunization against paralytic poliomyelitis in Nigeria. N Engl J Med 2008;359:1666-74.
18. 18.↵
. Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial. Lancet 2010. DOI:10.1016/s0140–6736(10)61230–5.
19. 19.↵
http://www.who.int/csr/don/2010_11_09/en/, Accessed 13 November 2010.
20. 20.↵
. Polio control after certification: major issues outstanding. Bull World Health Organ 2004;82:47-52.
21. 21.
. The role of routine polio immunization in the post-certification era. Bull World Health Organ 2004;82:31-9.
22. 22.
. Vaccine-derived polioviruses. Biologicals 2006;34:103-8.
23. 23.
. Containment of polioviruses after eradication and OPV cessation: characterizing risks to improve management. Risk Anal 2006;26:1449-69.
24. 24.
. A vision of a world without polio: the OPV cessation strategy. Biologicals 2006;34:75-9.
25. 25.
. Vaccination against polio should not be stopped. Nat Rev Microbiol 2007;5:952-8.
26. 26.
. Immunisation against poliomyelitis: moving forward. Lancet 2008;371:1385-7.
27. 27.↵
. The risks, costs, and benefits of possible future global policies for managing polioviruses. Am J Public Health 2008;98:1322-30.
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editor's choice: Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population J Infect Dis. (2011) 203(7): 898-909 doi:10.1093/infdis/jiq140
2) cVDPV in Nigeria
Full text, with figures, is at http://jid.oxfordjournals.org/content/203/7/898.full?etocExpand+
Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population
10. Alex Gasasira3,
12. Pascal Mkanda3,
13. A. J. Williams1,
15. Mark Pallansch1 and
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Abstract
ARTICLEWild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation.