Research Article: Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data

Date Published: October 4, 2016

Publisher: Public Library of Science

Author(s): Margarita Pons-Salort, Natalie A. Molodecky, Kathleen M. O’Reilly, Mufti Zubair Wadood, Rana M. Safdar, Andrew Etsano, Rui Gama Vaz, Hamid Jafari, Nicholas C. Grassly, Isobel M. Blake, Cecile Viboud

Abstract: BackgroundGlobal withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s).Methods and FindingsIn August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004–30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model.Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008–2009 and 2012–2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%–100%] in Nigeria and 84% [95% uncertainty interval 77%–91%] in Pakistan) had >70% population immunity among children <36 mo old. Districts with lower immunity were clustered in northeastern Nigeria and northwestern Pakistan. The accuracy of immunity estimates was limited by the small numbers of non-polio AFP cases in some districts, which was reflected by large uncertainty intervals. Forecasted improvements in immunity for April 2016 were robust to the uncertainty in estimates of baseline immunity (January–June 2015), vaccine coverage, and vaccine efficacy.ConclusionsImmunity against serotype-2 poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization.

Partial Text: A key milestone towards polio eradication is the global withdrawal of all live-attenuated oral poliovirus vaccines (OPVs) [1]. OPVs have played an instrumental role in the Global Polio Eradication Initiative (GPEI), and their use has largely contributed to the >99% reduction of annual poliomyelitis cases since the start of the programme in 1988 [1]. Historically, the GPEI has recommended the use of OPV—mainly trivalent OPV (tOPV), which protects against all three poliovirus serotypes—because of its low cost, ease of administration (oral), ability to induce a strong intestinal mucosal immune response, and potential to indirectly immunise secondary contacts. Until April 2016, tOPV was used in 155 countries, primarily through routine immunisation (RI) programmes [1] (administering three doses most commonly at 6, 10, and 14 wk) and additionally in mass supplementary immunisation activities (SIAs) to increase population immunity in settings where there is poliovirus transmission and RI coverage is low. Although OPV has served the GPEI well, the vaccine is genetically unstable, and its use carries some risks [2]. On very rare occasions, OPV may cause vaccine-associated paralytic poliomyelitis (VAPP), at a low rate of about 1–2 cases of VAPP per million primary immunisations [3]. Moreover, OPV viruses shed from vaccinees and their contacts may lose their attenuating mutations, regain transmissibility and neurovirulence, and result in outbreaks of vaccine-derived poliovirus (VDPV) poliomyelitis similar to those observed for wild polioviruses [4].

In April 2016, OPV2 was globally and synchronously withdrawn from 155 countries within a 2-wk period. This unprecedented global public health intervention is a key milestone of the polio eradication programme for complete eradication of poliomyelitis due to serotype 2. OPV2 withdrawal will lead to cohorts of unimmunised children at risk of developing serotype-2 poliomyelitis if there is subsequent exposure, and, therefore, efforts to interrupt transmission of any cVDPV2 were required before OPV2 withdrawal. In this context, information on the levels of serotype-2 population immunity at the time of the OPV2 withdrawal and during the preceding months was essential to assess such risk, and perhaps adapt the tOPV SIA plans if the levels of population immunity were considered too low. In August 2015, we estimated population immunity in the two highest risk countries, Nigeria and Pakistan, at the subnational level for January–June 2015 and projected immunity to April 2016. Interpretation of immunity levels was provided through analysis of a decade of spatio-temporal trends of estimated population immunity and incidence of reported cVDPV2 poliomyelitis in both of these countries.



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