WHAT'S NEW THIS THURSDAY: TEN ON VACCINE DERIVED POLIOVIRUS

Thursday, 16th of August 2012

TEN ON VACCINE DERIVED POLIOVIRUS

To readers new to the subject, posting 10 items on vaccine derived poliovirus may seem like a lot. Or is it? Writing recently in Current Opinion in Virology, Olen Kew places VDPV in its context:

Since its launch in 1988, the World Health Organization's Global Polio Eradication Initiative has reduced worldwide polio incidence by >99%. The most dramatic progress was achieved up to the year 2000, the original eradication target date, but subsequent years have seen only limited progress in preventing the last 1% of cases. . . . Although wild poliovirus type 2 was eradicated in 1999 and wild poliovirus type 3 may be nearing eradication, the continued emergence of circulating vaccine-derived polioviruses, especially type 2, presents ongoing challenges to stopping all poliovirus transmission.

Circulating vaccine derived poliovirus, which passes from person to person for months and even years, poses major challenges to eradicators as the world moves towards final stages of polio eradication endgame. Is the relatively expensive inactivated (Salk) polio vaccine, hitherto rarely used in developing countries, part or all of the solution to cVDPV?

The World Health Organization co-hosted, this May and June, a three day meeting on the subject; those interested can read the presentations from that meeting at

LINK: http://workspace.who.int/sites/polio_work/gpln/default.aspx

USERNAME: ads\poliolab

PASSWORD: polioeradication

Specialists on VDPV can go to www.pubmed.gov and search for vaccine derived polioviruses. Novices can start with the following items, from the Morbidity and Mortality Weekly Report and the Pan African Medical Journal, http://www.panafrican-med-journal.com/content/editorial/12/109/

UPDATE ON VACCINE DERIVED POLIOVIRUSES

Editorial Note below; full text is at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6025a3.htm

The three categories of VDPVs differ in their public health importance. First, cVDPVs [Circulating vaccine derived polioviruses] have recovered the biologic properties of WPVs and have the potential to circulate for years in settings where polio vaccination coverage to prevent that particular type is low. In addition, for each case detected, another 100--1,000 asymptomatic infections occur among susceptible children, as is the case for WPVs (10). Second, iVDPVs [immunodeficient vaccine derived polioviruses]can be excreted for many years by persons with certain primary immunodeficiencies, and some chronic infections are latent. Many persons with prolonged iVDPV infections either spontaneously clear the infections or die from the complications of immunodeficiency. Nonetheless, in the absence of effective antiviral therapy, persons infected with iVDPVs without paralysis are at risk for developing paralytic poliomyelitis and might infect others with poliovirus, posing a risk for outbreaks in areas with low polio vaccination coverage. Third, aVDPVs [ambiguous vaccine derived polioviruses]are heterogeneous; some represent the initial isolates from cVDPV outbreaks, especially in areas with type-specific immunity gaps, and aVDPVs isolated during cVDPV outbreaks of the same serotype might be cVDPVs whose progenitors or progeny were not detected. Other aVDPVs, such as those detected in sewage in Estonia, Finland, and Israel, probably are iVDPVs from latent chronic infections. Still other aVDPVs, especially those with limited divergence, might represent limited spread of OPV virus or the upper limit of OPV divergence in a single normal vaccine recipient or contact.

The detection in Nigeria of numerous isolates with <1% divergence that were ancestral to cVDPV2 lineages (7) prompted a redefinition of VDPV2 for purposes of reporting by the Global Polio Laboratory Network to include isolates with >0.6% divergence and was applied beginning in 2010.

The increased frequency of VDPV detection compared with the previous reporting period (3) is attributable partly to increased surveillance sensitivity and improved laboratory methods. However, for cVDPVs, the most important factor is the growth of type-specific immunity gaps in areas with low routine vaccination, arising from the intensive use of mOPV1 and bOPV in SIAs. These alternative OPV formulations, by eliminating interference from the type 2 OPV strain, are more effective than tOPV in inducing higher levels of population immunity to WPV1 and WPV3. Their use in endemic and outbreak countries has facilitated WPV control. In settings of inadequate routine vaccination coverage with tOPV, conditions develop that favor multiple independent VDPV2 emergences, as occurred in DRC, India, Nigeria, and Somalia. Emergence of cVDPV3 appears to be rare but occurred in areas of low tOPV coverage in Ethiopia after a cVDPV2 emergence in 2008 (3).

Current and past experiences underscore the importance of robust routine vaccination with tOPV (or, alternatively, inactivated poliovirus vaccine) to prevent VDPV emergence and spread as well as to prevent WPV transmission. In countries with low routine vaccination coverage, closing the immunity gaps to all three poliovirus serotypes by periodic but regular use of tOPV in SIAs is essential to prevent cVDPV emergence (3). Maintenance of sensitive AFP surveillance also is crucial; any temporal and geographic clustering of vaccine-related isolates of the same serotype should prompt further investigation.

CIRCULATING VACCINE DERIVED POLIOVIRUS AND THE POLIO ERADICATION ENDGAME

Robert Davis¹ and Peter F. Wright²

^{1 American Red Cross, Nairobi, Kenya, rdavis@africamail.com}

²Department of Pediatrics, The Geisel School of Medicine at Dartmouth, Lebanon, NH., Peter.F.Wright@hitchcock.org

Also at http://www.panafrican-med-journal.com/content/editorial/12/109/

The world is now in the 24^th year of the Global Polio Eradication Initiative. Halfway through that initiative in 2000, the island of Hispaniola, home to Haiti and the Dominican Republic, saw an outbreak of vaccine derived poliovirus (1). The implications of this outbreak and multiple subsequent isolations of Sabin strains that are estimated to have circulated in communities for a year or more are now causing a reconsideration of the optimal way to achieve polio eradication. These circulating vaccine derived polio viruses, cVDPV, in many cases have regained the virulence and capacity to cause paralytic disease that we associate with wild-type poliovirus (WPV) strains. They, with the prolonged poliovirus vaccine virus shedding seen in some immunodeficient children, iVDPV, have uncovered a serious risk to polio eradication using OPV as our sole weapon.

After the Hispaniola outbreak, retrospective studies of polio stool samples showed that a multiyear cVDPV epidemic had struck Egypt in the 1990s (2), and cVDPV type 2 has persisted for multiple years in Nigeria (3).

Shorter contained cVDPV outbreaks have occurred in many areas of the world, most typically in areas with inadequate vaccine coverage and low strain specific immunity. They have each been interrupted with a renewed effort at increasing OPV coverage. If safe and effective antivirals become available in the next few years, could they serve for ring containment of cVDPV or to treat the identified people with iVDPV?

Surveillance Issues, and the Growing Relevance of Environmental Sampling

If AFP surveillance declines in the final years of eradication and, especially, post-eradication, will environmental sampling be needed on a larger scale? At present it is time-consuming and requires some at least rudimentary sewage system, but in Egypt it was key to documenting persistent cVDPV (4) and to eradication of WPV (5). Environmental surveillance now serves as a useful check on the quality of AFP surveillance and as a tool for detecting VDPV. Its importance will grow in the post-eradication era.

Oral Polio Vaccine, Friend and Enemy

The OPV paradox states that we produce cVDPV by vaccination and we prevent cVDPV by vaccination. The absence of wild type polio from India for over a year speaks to the power of OPV as a tool for polio eradication (6). The paradox does not apply in areas where OPV coverage is high enough to prevent cVDPV introduction. An additional paradox is the rare but well established occurrence of paralytic disease as a direct result of OPV administration. These risks do not apply in countries which have used inactivated poliovirus vaccine (IPV) as their long-standing defense against polio or to the increasing number of countries which after achieving high OPV coverage have switched to IPV.

Bivalent types 1 and 3 OPV (bOPV)

On WHO advice, many countries have adopted a mixed schedule, retaining trivalent types 1, 2, and 3 vaccine (tOPV) for routine and using bOPV for campaigns. The bOPV option, while creating risks of cVDPV, produces higher seroconversion rates for types 1 and 3, both of them still endemic as wild type viruses in the world. While this strategy holds the promise of stopping types 1 and 3 WPV, it also carries risks. Some see continuing type 2 cVDPV transmission in Nigeria as linked to Nigeria’s extensive use of bOPV in campaigns, a measure thought necessary to stop WPV transmission in Africa’s only remaining polio endemic country, while inefficiently administering tOPV in the routine program.

Once the world stops transmission of WPV types 1 and 3 (confined in 2012 to Chad and the three endemic countries of Nigeria, Afghanistan and Pakistan), the remaining problem of cVDPV, especially type 2, could be overcome, in the interim, by systematic and high quality coverage with tOPV or monovalent type 2 OPV. The importance of having an optimal type 2 OPV has led to an effort to develop a safer and more genetically stable type 2 strain.

An OPV to IPV Transition

For countries currently using OPV, several solutions to this problem have been proposed:

Introduction of IPV into the EPI program , while continuing the use of tOPV or bOPV through the Global Polio Eradication Initiative (South Africa and several Latin American countries have recently done this)
Cessation of type 2 OPV, which accounts for most cVDPV, while continuing vaccination with types 1 and 3, using bivalent OPV (bOPV), in both routine and vaccination campaigns.
Discontinuation of all OPV, and continuation of IPV, once cessation of WPV and cVDPV is documented.

All of these solutions will be aided by development of easier and less expensive approaches to the use of IPV so that it can readily be used in routine immunization and mass campaigns. Discontinuation of all OPV is a necessary step on the critical pathway to polio eradication. An interim step of discontinuing all live type 2 vaccine is viewed as highly informative and the safest route to eradication.

Inactivated Polio Vaccine, Savior or Mirage

Polio vaccination policy, especially in industrialized countries, has seen many transitions between OPV and IPV use. The US, for example, used IPV in the ‘50s, before going over to OPV for most vaccinees after 1961. A joint IPV/OPV regimen, used in the ‘90s, was abandoned in 2000 in favor of the straight IPV schedule now in use.

Early adopters of IPV (Sweden and the Netherlands, among others) point to the safety of the product, to its protection of the individual, and to its priming effect. IPV has stopped polio transmission in many countries; the 56 countries now using it exclusively have witnessed rapid disappearance of OPV from their environments.

Individual countries and regions will make decisions about their polio immunization strategy. The 2012 World Health Assembly was a sounding board for broader use of IPV. Concerns about IPV included questions related to cost and sufficient supplies of affordable IPV.
For most developing countries, the use of full-dose IPV by the intramuscular route is too expensive. WHO is now supporting research on multiple solutions leading to affordable IPV product including an intradermal administration of reduced dose (intradermal) IPV through the traditional needles used for BCG vaccination or use of hand-held needle-free injectors. This solution is at least two years from field implementation. Another question is how many doses of IPV would be needed to assure solid immunity. Recent work from Cuba points to a priming effect from a single dose IPV in previously naïve subjects (Resik S, unpublished data). Research on intradermal administration of IPV in fractional doses is informing policy making in this area (8,9) Although IPV has eradicated polio in a number of European countries, we are learning from studies such as these that IPV does not, in those countries, provide as strong mucosal immunity against virus shedding as OPV (although this conclusion is being questioned in the most recent Indian study). Further complicating the full endorsement of IPV are the manufacturing risks associated with production of large quantities of WPVs that are the source of the antigen in the present IPV. A WHO-led initiative is preparing the introduction of IPV made from the attenuated Sabin strains.

An advocacy effort may be necessary to persuade reluctant governments that IPV introduction is a prerequisite for the OPV cessation endorsed in 2008 by the World Health Assembly (WHA Resolution 61.1). In Asia and Africa, only a few countries are current IPV users. For most countries, a technology needs final development and field testing which will permit affordable, safe and effective administration of IPV. Also in development are antiviral drugs that might have a role in interrupting cVDPV circulation.

Will a combined regime of OPV and IPV be the best of both worlds?

The highest immunity to all three polio types in developing country settings has been seen to a combined regimen of OPV and IPV(9). A number of countries are employing mixed IPV and OPV though it seems an interim step. We are still asking the question of whether OPV vaccination can safely cease without well documented high levels of IPV coverage. Each country that switches from OPV to IPV is another experiment in the feasibility of doing this.

Assumptions for Cessation of Type 2 OPV

The world has detected no type 2 WPV since the last cases were seen in northern India in 1999. If bOPV schedules, with or without IPV, are adopted, then Sabin Type 2 will disappear from circulation. Here, there is a mixed picture, with continued circulation of 1 lineage in Nigeria, but apparent limited (rare) occurrence in other countries and prompt disappearance of many lineages with appropriate use of OPV containing Type 2. Nigeria has detected only one VDPV in 2012 to date (in April).

Challenges of Discontinuing all OPV, while Continuing IPV

Once cessation of circulating VDPV and WPV have been well documented, routine IPV administration will continue in many countries, either as a public health or a national security measure. This will reinforce the need for efficient delivery systems for IPV. While combined vaccines exist which permit simultaneous administration of IPV with DPT, and as hexavalent vaccine with hep B and Hib, some of these include acellular pertussis vaccine, which is not yet accepted in most developing countries. There are product development and licensure issues here, which are likely to involve the GAVI Alliance, current provider of pentavalent vaccine to many African and Asian countries, as a major partner.

Post-Discontinuation of OPV

All countries must agree on the need for cessation of OPV, with sensitive surveillance to show the absence of WPV and VDPV. The elimination of the type 2 OPV component and the switch to IPV require both global policy guidance and consultations with all of the polio community.

Once GPEI, like the Smallpox Eradication Programme before it, ceases to exist, the world must build on its accomplishments. As the world turns its attention towards measles and rubella issues, the surveillance and laboratory networks created for GPEI can serve broader purposes, including, in many countries, integrated disease surveillance and response (IDSR). House to house vaccination strategies developed by GPEI can serve other initiatives as well. The AFP surveillance strategies should not collapse.

The world, especially the industrialized world, has started the withdrawal of Sabin vaccines. The increasing popularity of bOPV in developing countries means that potential transmission of Type 2 VDPV assumes greater importance than before. Here, timely introduction of IPV into the routine immunization schedule is a useful step, as part of the move towards eventual cessation of OPV vaccination.

A global consensus on dropping the type 2 component of OPV is being sought. If OPV 2 can be stopped, probably with IPV use, this will be instructive to the ultimate polio endgame in terms of reducing the risk of cVDPV and overall strategy. It would eliminate a major component of vaccine associated paralytic polio and eliminate the competition of type 2 with other OPV Sabin strains.

References:

1) Kew O, Morris-Glasgow V, Landaverde M, Burns C, Shaw J, Garib Z, André J, Blackman E, Freeman CJ, Jorba J, Sutter R, Tambini G, Venczel L, Pedreira C, Laender F, Shimizu H, Yoneyama T, Miyamura T, van Der Avoort H, Oberste MS, Kilpatrick D, Cochi S, Pallansch M, de Quadros C. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science. 2002 Apr 12;296(5566):356-9

2) Yang CF, Naguib T, Yang SJ, Nasr E, Jorba J, Ahmed N, Campagnoli R, van der Avoort H, Shimizu H, Yoneyama T, Miyamura T, Pallansch M, Kew O. Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993. J Virol. 2003 Aug;77(15):8366-77.

3) Wassilak S, Pate MA, Wannemuehler K, Jenks J, Burns C, Chenoweth P, Abanida EA, Adu F, Baba M, Gasasira A, Iber J, Mkanda P, Williams AJ, Shaw J, Pallansch M, Kew O. Outbreak of type 2 vaccine-derived poliovirus in Nigeria: Emergence and widespread circulation in an underimmunized population. J Infect Dis. 2011 Apr 1;203(7):898-909.

4) Yang CF, Naguib T, Yang SJ, Nasr E, Jorba J, Ahmed N, Campagnoli R, van der Avoort H, Shimizu H, Yoneyama T, Miyamura T, Pallansch M, Kew O. Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993. J Virol. 2003 Aug;77(15):8366-77.

5) El Bassioni L, Barakat I, Nasr E, de Gourville EM, Hovi T, Blomqvist S, Burns C, Stenvik M, Gary H, Kew OM, Pallansch MA, Wahdan MH. Prolonged detection of indigenous wild polioviruses in sewage from communities in Egypt. Am J Epidemiol. 2003 Oct 15;158(8):807-15.

6) Centers for Disease Control and Prevention (CDC). Progress toward interruption of wild poliovirus transmission - worldwide, January 2011-March 2012. MMWR Morb Mortal Wkly Rep. 2012 May 18;61:353-7.

7) Cuba IPV Study Collaborative Group. Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba. N Engl J Med. 2007 Apr 12;356(15):1536-44.

8) Resik S, Tejeda A, Lago PM, Diaz M, Carmenates A, Sarmiento L, Alemañi N, Galindo B, Burton A, Friede M, Landaverde M, Sutter RW. Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba. J Infect Dis. 2010 May 1;201(9):1344-52.

9) Mohammed AJ, AlAwaidy S, Bawikar S, Kurup PJ, Elamir E, Shaban MM, Sharif SM, van der Avoort HG, Pallansch MA, Malankar P, Burton A, Sreevatsava M, Sutter RW. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med. 2010 Jun 24;362(25):2351-9.

10) WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines. Combined immunization of infants with oral and inactivated poliovirus vaccines: results of a randomized trial in The Gambia, Oman, and Thailand. J. Infect Dis. 1997 Feb;175 Suppl 1:S215-27.

ORAL POLIOVACCINE: WILL IT HELP ERADICATE POLIO OR CAUSE THE NEXT EPIDEMIC?

Abstract below; full text is at http://www.ima.org.il/imaj/ar06may-4.pdf

Background: Poliovirus rapidly evolves by nucleic acid substitutions and genetic recombination with other polioviruses and non-polio enteroviruses. Evolving oral poliovirus (Sabin strains) can rapidly revert to neurovirulence and undergo antigenic alterations.

Objectives: To evaluate the threat of vaccine-derived poliovirus (1¨C15% divergence from the respective Sabin strain) for a poliomyelitis-free population in a country with a long-standing routine vaccination program.

Methods: We characterized genetic and antigenic changes in OPV[1] strains isolated from sewage in Israel and evaluated intestinal immunity by measuring fecal excretion after OPV challenge of vaccinated children.

Results: Characterization of poliovirus from sewage revealed eight type 2 and three type 3 vaccine polioviruses that had replicated and started to evolve (vaccine that replicated and diverged by 0.5 to ¡Ü 1.0%) and nine highly diverged type 2 vaccine-derived polioviruses (1¨C15% divergence from the respective Sabin strain) with 8¨C14% divergence between the years 1998 and 2005. Six of the eleven VRPV[2] uniquely recombined with OPV and/or NPEV[3]. The nine VDPV[4] were epidemically related, genotypically neurovirulent, and had 10¨C15 amino acid substitutions in antigenic sites altering their antigenicity, but shared a single recombination. Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months after partial immunization (two doses each of OPV and enhanced inactivated poliovirus) or full immunization (three doses of each) respectively, despite high humoral antibody titers.

Conclusions: Our findings, which show that OPV is excreted for a significant period by children with high humoral immunity, emphasize the long-term potential threat from VDPV in highly vaccinated populations. An adequate immunization program, combined with environmental surveillance, is necessary to prevent poliomyelitis and community transmission of poliovirus.

[1] OPV = oral poliovirus
[2] VRPV = vaccine poliovirus that has replicated and started to evolve but is < 1 % but at least 0.5% diverged from the respective Sabin strain
[3] NPEV = non-polio enterovirus
[4] VDPV = vaccine-derived poliovirus 1¨C15% divergence from the respective Sabin strain

CURRENT POLIO GLOBAL ERADICATION AND CONTROL POLICY OPTIONS: PERSPECTIVES FROM MODELING AND PREREQUISITES FOR ORAL POLIOVIRUS VACCINE CESSATION

Expert Review of Vaccines

April 2012, Vol. 11, No. 4, Pages 449-459

Kimberly M Thompson* and Radboud J Duintjer Tebbens

* Author for correspondence

Abstract below; full text is at http://www.expert-reviews.com/doi/full/10.1586/erv.11.195

As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses.

ESTIMATING THE EXTENT OF VACCINE-DERIVED POLIOVIRUS

PLoS ONE. 2008; 3(10): e3433.

Published online 2008 October 29.

Abstract below; full text is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570794/?tool=pubmed

Estimating the Extent of Vaccine-Derived Poliovirus Infection

Alison Wringe,1,* Paul E. M. Fine,1 Roland W. Sutter,2 and Olen M. Kew3

1Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England

2Polio Eradication Department, World Health Organization, Geneva, Switzerland

3Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

* E-mail: alison.wringe@lshtm.ac.uk

Conceived and designed the experiments: PEMF RWS OMK. Analyzed the data: AW PEMF RWS OMK. Wrote the paper: AW. Contributed to drafting and revising the manuscript: PEMF RWS OMK.

Jose Esparza, Editor

Received July 9, 2008; Accepted September 1, 2008.

Copyright This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

This article has been cited by other articles in PMC.

Abstract

Background

Eight outbreaks of paralytic polio attributable to circulating vaccine-derived poliovirus (cVDPV) have highlighted the risks associated with oral poliovirus vaccine (OPV) use in areas of low vaccination coverage and poor hygiene. As the Polio Eradication Initiative enters its final stages, it is important to consider the extent to which these viruses spread under different conditions, so that appropriate strategies can be devised to prevent or respond to future cVDPV outbreaks.

Methods and Findings

This paper examines epidemiological (temporal, geographic, age, vaccine history, social group, ascertainment), and virological (type, genetic diversity, virulence) parameters in order to infer the numbers of individuals likely to have been infected in each of these cVDPV outbreaks, and in association with single acute flaccid paralysis (AFP) cases attributable to VDPVs. Although only 114 virologically-confirmed paralytic cases were identified in the eight cVDPV outbreaks, it is likely that a minimum of hundreds of thousands, and more likely several million individuals were infected during these events, and that many thousands more have been infected by VDPV lineages within outbreaks which have escaped detection.

Conclusions

Our estimates of the extent of cVDPV circulation suggest widespread transmission in some countries, as might be expected from endemic wild poliovirus transmission in these same settings. These methods for inferring extent of infection will be useful in the context of identifying future surveillance needs, planning for OPV cessation and preparing outbreak response plans.

ROLE OF ENVIRONMENTAL POLIOVIRUS SURVEILLANCE IN GLOBAL POLIO ERADICATION AND BEYOND

Epidemiol Infect. 2012 Jan;140(1):1-13. Epub 2011 Aug 18.

Hovi T, Shulman LM, van der Avoort H, Deshpande J, Roivainen M, DE Gourville EM.

Source

National Institute for Health and Welfare, Mannerheimintie 166, Helsinki, Finland. tapani.hovi@thl.fi

Abstract below; full text is available to subscribers.

Environmental poliovirus surveillance (ENV) means monitoring of poliovirus (PV) transmission in human populations by examining environmental specimens supposedly contaminated by human faeces. The rationale is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the faeces for several weeks. As the morbidity:infection ratio of PV infection is very low, this fact contributes to the sensitivity of ENV which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization has included ENV in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance. In this paper we review the feasibility of using ENV to monitor wild PV and vaccine-derived PV circulation in human populations, based on global experiences in defined epidemiological situations.

CIRCULATING VACCINE-DERIVED POLIOVIRUS IN NIGERIA

Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria

Helen E. Jenkins, M.Sc., R. Bruce Aylward, M.D., Alex Gasasira, M.B., Ch.B., Christl A. Donnelly, Sc.D., Michael Mwanza, B.Comm., Jukka Corander, Ph.D., Sandra Garnier, B.Sc., Claire Chauvin, R.N., M.P.H., Emmanuel Abanida, M.P.H., Muhammad Ali Pate, M.D., Festus Adu, D.V.M., Ph.D., Marycelin Baba, Ph.D., and Nicholas C. Grassly, D.Phil.

N Engl J Med 2010; 362:2360-2369June 24, 2010

Abstract below; full text, with figures is at http://www.nejm.org/doi/full/10.1056/NEJMoa0910074#t=article

The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV).

Methods

We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared.

Results

No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV.

Conclusions

The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge.

AN OUTBREAK OF POLIOMYELITIS CAUSED BY TYPE 1 VACCINE-DERIVED POLIOVIRUS IN CHINA

J Infect Dis. (2006) 194 (5): 545-551. doi: 10.1086/506359

Abstract below; full text is at http://jid.oxfordjournals.org/content/194/5/545.long

Background In May–July 2004, type 1 vaccine-derived poliovirus (VDPV) was isolated from 2 case patients with polio and a contact of a third case patient in Guizhou Province

MethodsWe conducted a field investigation of the outbreak, characterized outbreak isolates, and retrospectively reviewed national polio surveillance data for other VDPVs

ResultsCase patients were unimmunized children, 0.9–3.2 years old, living in 2 villages 40 km apart. Immunization coverage in the affected villages was very low. Isolates differed from the Sabin 1 type by 9–11 VP1 nucleotides (1.0%–1.2%); which indicated, on the basis of known rates of mutation of Sabin strains, that they had been circulating for <1 year. A province-wide immunization response targeting all children <5 years old was initiated in August, and the strain has not been isolated since. During 1997–2004, 10 VDPV strains (5 of type 2, 3 of type 1, and 2 of type 3) were isolated from >50,000 children with acute flaccid paralysis and their contacts; 8 (80%) were found in southern provinces, and 9 (90%) spontaneously disappeared.

ConclusionThis is the first polio outbreak in China in over a decade and the first due to VDPV. The short duration of circulation demonstrates the rapidity with which attenuated Sabin strains can revert to a wild phenotype. One to two VDPVs have been identified each year, primarily in densely populated subtropical regions of southern China. This outbreak highlights the need to consider risks of paralysis from vaccine-derived strains in development of national poliomyelitis immunization policy .

VACCINE-DERIVED POLIOMYELITIS 12 YEARS AFTER INFECTION IN MINNESOTA

Aaron S. DeVries, M.D., M.P.H., Jane Harper, M.S., Andrew Murray, M.P.H., Catherine Lexau, Ph.D., M.P.H., Lynn Bahta, B.S.N., Jaime Christensen, B.S., Elizabeth Cebelinski, B.S., Susan Fuller, M.B.S., Susan Kline, M.D., M.P.H., Gregory S. Wallace, M.D., M.P.H., Jing H. Shaw, M.D., Cara C. Burns, Ph.D., and Ruth Lynfield, M.D.

N Engl J Med 2011; 364:2316-2323June 16, 2011

Abstract below; full text is at http://www.nejm.org/doi/full/10.1056/NEJMoa1008677

A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.

RECOMBINATION BETWEEN POLIOVIRUS AND COXSACKIE A VIRUSES OF SPECIES C: A MODEL OF VIRAL GENETIC PLASTICITY AND EMERGENCE

Viruses. 2011 August; 3(8): 1460–1484.

Nicolas Combelas,1,2 Barbara Holmblat,1,2 Marie-Line Joffret,1,2 Florence Colbère-Garapin,1,2 and Francis Delpeyroux1,2,*

1 Biologie des Virus Entériques, Institut Pasteur, 75724 Paris-cedex 15, France; E-Mails: nicolas.combelas@pasteur.fr (N.C.); Email: barbara.holmblat@pasteur.fr (B.H.); Email: marie-line.joffret@pasteur.fr (M.-L.J.); Email: florence.colbere-garapin@pasteur.fr (F.C.-G.)

2 INSERM U994, Institut National de Santé et de La Recherche Médicale, 75724 Paris-cedex 15, France

*Author to whom correspondence should be addressed; E-Mail: francis.delpeyroux@pasteur.fr .

Abstract below; full text is at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185806/?tool=pubmed

Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV), an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs), which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C), in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.