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ESTIMATING THE EXTENT OF VACCINE-DERIVED POLIOVIRUS INFECTION

Monday, 24th of October 2011

• ESTIMATING THE EXTENT OF VACCINE-DERIVED POLIOVIRUS INFECTION

‘Although only 114 virologically-confirmed paralytic cases were identified in the eight cVDPV outbreaks [reviewed], 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.’

Abstract and introduction, below. Full text, with figures, is at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003433

Public Library of Science

Open Access Research Article

Estimating the Extent of Vaccine-Derived Poliovirus Infection

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.

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.

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.

Alison Wringe1*, Paul E. M. Fine1, Roland W. Sutter2, Olen M. Kew3

1 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England, 2 Polio Eradication Department, World Health Organization, Geneva, Switzerland, 3 Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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.

Citation: Wringe A, Fine PEM, Sutter RW, Kew OM (2008) Estimating the Extent of Vaccine-Derived Poliovirus Infection. PLoS ONE 3(10): e3433. doi:10.1371/journal.pone.0003433

Editor: Jose Esparza, Bill & Melinda Gates Foundation, United States of America

Received: July 9, 2008; Accepted: September 1, 2008; Published: October 29, 2008

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.

Funding: This work was supported by the Polio Eradication Initiative of the World Health Organisation.

Competing interests: The authors have declared that no competing interests exist.

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

Introduction 

Much of the success of the Polio Eradication Initiative (PEI) to date can be attributed to massive use of oral polio vaccine (OPV), administered through routine immunisation services and supplementary immunisation activities in the form of National Immunisation Days (NIDs) and subnational immunisation days (sNIDs) in over 100 countries since 1988. Though it is a powerful tool for preventing poliomyelitis, OPV has two disadvantages. In addition to carrying a low risk of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees or their close contacts, it is now known that vaccine viruses can be serially transmitted through human hosts, and may revert genetically towards wild-type transmissibility and virulence.

The degree of genetic change in vaccine-derived polioviruses (VDPV) is routinely assessed by determining the number of nucleotide substitutions in the VP1 gene, relative to the sequence of the Sabin vaccine viruses, and typically occurs at a rate of approximately 1% per annum[1]–[4]. A virus is defined as a VDPV if it has ≥1% divergence in the VP1 sequence compared to the corresponding Sabin strain. The prefix c is used to denote “circulating” (two or more clinical cases), and i for VDPV excreted by immunodeficient individuals[5], [6]. The prefix a (for “ambiguous”) is used to describe VDPV isolates from persons with no known immunodeficiency or environmental isolates whose ultimate source has not been identified[5].

Eight outbreaks attributable to cVDPV have so far been fully documented: in Hispaniola, Indonesia, Egypt, Madagascar (×2), Philippines, China and Cambodia, resulting in a total of 114 virologically-confirmed (and an unknown number of undiagnosed or unreported) cases[1], [7]–[13]. Two further cVDPV outbreaks were under investigation as this manuscript was submitted, including 5 virologically-confirmed (VC) cases in Myanmar and approximately 130 VC cases in Nigeria and Niger[14]. Single cases of acute flaccid paralysis (AFP) attributable to VDPV have been reported in several other settings[6], [7], [14]–[17] and single VDPV isolates have also been identified in environmental samples and in healthy contacts of AFP cases[7], [14], [18]–[20]

Spread of VDPV infection is likely to be a function of virus transmissibility, population immunity levels, and other population characteristics such as density, socio-economic status, sanitation levels and hygiene-related behaviour, ascertainment efficiency of infection and/or cases, the nature and scope of response activities, and chance. Both the transmissibility and virulence (as measured by the case-to-infection ratio) of VDPVs are difficult to define, as they change over time. These properties take on particular importance as the PEI approaches its final stages.

As part of the plan to discontinue OPV after wild poliovirus (WPV) eradication, there is discussion of vaccine stockpiles, and response strategies to manage any polio outbreaks in the “post-certification” era[21], [22]. Among potential outbreak threats is the possibility that VDPV strains may persist after OPV is discontinued, or as a consequence of the re-introduction of OPV into susceptible populations later, from residual vaccine stores or vaccine manufacturers[23]. Outbreak response strategies should therefore include methods for estimating the likely geographic spread of VDPV infection prior to and during an outbreak, so that vaccination and other response activities cover an appropriate area. Furthermore, stockpiles of OPV, and in particular monovalent OPV (mOPV), have been proposed for future polio outbreak response[22]. The risks associated with such interventions include the potential spread of mOPV-derived VDPV in susceptible populations. Information on the potential spread of VDPV in different contexts will be helpful for developing policies to deal with any such eventualities.

There has been little discussion of the geographic spread of cVDPV outbreak strains, or of the numbers of infections associated with these and other reported VDPV episodes. In this paper, we develop lines of argument to infer the extent of VDPV spread in outbreak populations. We apply the reasoning to data from three of the largest reported cVDPV outbreaks (Hispaniola, Indonesia and Egypt) in order to give crude estimates of the potential numbers of individuals infected with VDPV in each of these settings. We then summarise findings for five smaller cVDPV outbreaks (Madagascar (×2), Philippines, China and Cambodia), and discuss individual VDPV isolates, including iVDPV, and their implications for vaccine-derived virus spread.