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CSU 98/2011: TWO ON CIRCULATING VACCINE DERIVED POLIOVIRUS

Sunday, 20th of February 2011

 

1)              Eradication of Poliovirus: Fighting Fire With Fire

1. 1.   Neal Nathanson 

+ Author Affiliations

1. 1.    Global Health Programs, School of Medicine, University of Pennsylvania, Philadelphia
2. Reprints or correspondence: Neal Nathanson, MD, Global Health Programs, School of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6021 (nathansn@upenn.edu).

(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.

 

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Footnotes

• Potential conflicts of interest: none reported.
• Received November 15, 2010.
• Accepted November 16, 2010.

• ·         © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

 

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Abstract/FREE Full Text

MAJOR ARTICLES AND BRIEF REPORTS - VIRUSES:

• Steven Wassilak,
• Muhammad Ali Pate,
• Kathleen Wannemuehler,
• Julie Jenks,
• Cara Burns,
• Paul Chenoweth,
• Emmanuel Ade Abanida,
• Festus Adu,
• Marycelin Baba,
• Alex Gasasira,
• Jane Iber,
• Pascal Mkanda,
• A. J. Williams,
• Jing Shaw,
• Mark Pallansch,
• and Olen Kew

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

1. 1.   Steven Wassilak1,
2. 2.   Muhammad Ali Pate2,
3. 3.   Kathleen Wannemuehler1,
4. 4.   Julie Jenks1,
5. 5.   Cara Burns1,
6. 6.   Paul Chenoweth1,
7. 7.   Emmanuel Ade Abanida2,
8. 8.   Festus Adu4,
9. 9.   Marycelin Baba5,

10. Alex Gasasira3,

11. Jane Iber1,

12. Pascal Mkanda3,

13. A. J. Williams1,

14. Jing Shaw1,

15. Mark Pallansch1 and

16. Olen Kew1

+ Author Affiliations

1. 1.    ¹Centers for Disease Control and Prevention, Atlanta, Georgia
2. 2.    ²National Primary Health Care Development Agency
3. 3.    ³World Health Organization, Nigeria, Abuja
4. 4.    ⁴Department of Virology, College of Medicine, University of Ibadan
5. 5.    ⁵University of Maiduguri Teaching Hospital, Maiduguri, Nigeria
6. Reprints or correspondence: Steven Wassilak, MD, 1600 Clifton Rd. N.E., Mail Stop E-05, Atlanta, GA 30333 (sgw1@cdc.gov).

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.