Risk factors for an emergent VDPV2 to establish a circulating lineage associated with >1 case of poliomyelitis in Nigeria.

<p>Serotype-2 population immunity and DTP3 coverage in districts in the 6-month period when the first AFP case associated with each of the 29 independent VDPV2 emergences in Nigeria during 2004−2014 were reported. Red triangles represent isolates that established circulating lineages, whereas blue circles represent single isolates.</p

Univariable and multivariable analyses of cases (district−6-months where the first AFP case associated with a VDPV2 emergence was detected) vs. controls (district−6-months with no VDPV2 emergence).

<p>Abbreviations: CI, confidence interval; OR, odds ratio; <i>P</i>, p-value. Statistically significant p-values <0.05 are shown in boldface. Borderline significant p-values <0.1 are shown in italics.</p

Illustration of results from the stochastic dynamic mathematical model of VDPV2 emergence and spread.

<p>The model is simulated for 1 year and a population of 10,000 individuals, starting from a VDPV-free equilibrium that includes routine immunisation. OPV2 withdrawal occurs at 6 months (red arrow) and the last tOPV SIA is assumed to occur 4 weeks before this date in agreement with current plans. SIAs are implemented 4 weeks apart. We define the risk of a VDPV2 outbreak after OPV2 withdrawal as the probability of having >200 incident VDPV2 infections during the 6 months following OPV2 cessation. In this illustration, the grey lines represent the number of VDPV infected individuals over time for 20 different simulations of the model assuming 20% routine immunisation coverage and 3 tOPV SIAs with 80% coverage implemented before OPV2 withdrawal.</p

Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014

<div><p>A type 2 vaccine-derived poliovirus (VDPV), differing from the Sabin 2 strain at 8.6% (78/903) of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C). The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg) sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication.</p></div

Amino acid substitutions in the capsid protomer of isolate 44624.

<p>VP1, VP2, VP3 and VP4 are represented as a 3-dimensional structured protomer. The image was generated using the software Swiss-PdbViewer [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152251#pone.0152251.ref024" target="_blank">24</a>], based on X-ray crystallographic analysis of type 2 poliovirus strain Lansing (Protein Data Bank accession number 1EAH.pdb) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0152251#pone.0152251.ref023" target="_blank">23</a>]. Colour codes: Substitutions at known antigenic sites, brown. Substitutions elsewhere, pink. The BC-loop of VP1 is not visible in this model.</p

Alignment of amino acids residues of neutralizing antigenic (NAg) sites for Sabin 2 (GenBank accession number AY184220) and isolate 44624.

<p>Amino acid positions are numbered according to Sabin 2 NAg1 (VP1 88–106), NAg2 (VP2 163–169; VP2 268–270; VP1 220–225), NAg3a (VP3 54–61; VP3 70–74; VP1 286–291) and NA3b (VP2 71–73; VP3 75–79).</p

Analysis of nucleotide differences between the genome of isolate 44624 and Sabin 2.

<p>Analysis of nucleotide differences between the genome of isolate 44624 and Sabin 2.</p

Schematic representation of the genome of recombinant aVDPV 44624, isolated in Brazil.

<p>Non-vaccine sequences (HEV-C species) are represented in light blue. Highly mutated Sabin 2 regions are represented in gray.</p

Recombination events predicted by RDP algorithms for the genome of isolate 44624 and putative parental sequences.

<p>Break points consist of the beginning nucleotide (BN) and the ending nucleotide (EN) of recombination fragment detected in the break point analysis. The figures are for isolate 44624. RDP software considers the major parent as the sequence closely related to that from which the greater part of the recombinant’s sequence may have been derived, and the minor parent is pointed as the sequence closely related to that from which sequences in the proposed recombinant region may have been derived.</p

The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan – 2011–2013

<div><p>Background</p><p>More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection.</p><p>Methods</p><p>Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of ‘orphan viruses’ (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case.</p><p>Findings</p><p>A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011–2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance.</p><p>Interpretation</p><p>Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy.</p></div