Sustained detection of type 2 poliovirus in London sewage between February and July, 2022, by enhanced environmental surveillance

Abstract

Background: The international spread of poliovirus exposes all countries to the risk of outbreaks and is designated a Public Health Emergency of International Concern by WHO. This risk can be exacerbated in countries using inactivated polio vaccine, which offers excellent protection against paralysis but is less effective than oral vaccine against poliovirus shedding, potentially allowing circulation without detection of paralytic cases for long periods of time. Our study investigated the molecular properties of type 2 poliovirus isolates found in sewage with an aim to detect virus transmission in the community.

Methods: We performed environmental surveillance in London, UK, testing sewage samples using WHO recommended methods that include concentration, virus isolation in cell culture, and molecular characterisation. We additionally implemented direct molecular detection and determined whole-genome sequences of every isolate using novel nanopore protocols.

Findings: 118 genetically linked poliovirus isolates related to the serotype 2 Sabin vaccine strain were detected in 21 of 52 sequential sewage samples collected in London between Feb 8 and July 4, 2022. Expansion of environmental surveillance sites in London helped localise transmission to several boroughs in north and east London. All isolates have lost two key attenuating mutations, are recombinants with a species C enterovirus, and an increasing proportion (20 of 118) meet the criterion for a vaccine-derived poliovirus, having six to ten nucleotide changes in the gene coding for VP1 capsid protein.

Interpretation: Environmental surveillance allowed early detection of poliovirus importation and circulation in London, permitting a rapid public health response, including enhanced surveillance and an inactivated polio vaccine campaign among children aged 1-9 years. Whole-genome sequences generated through nanopore sequencing established linkage of isolates and confirmed transmission of a unique recombinant poliovirus lineage that has now been detected in Israel and the USA.

Funding: Medicines and Healthcare products Regulatory Agency, UK Health Security Agency, Bill & Melinda Gates Foundation, and National Institute for Health Research Medical Research Council.

Figure 1

Location of London sewage sites sampled for poliovirus detection The location of type 2 poliovirus isolations in London sewage is shown in maps displaying main sewage treatment works (A) or network treatment works sites (B). Catchment areas were coloured by poliovirus prevalence; areas with sustained type 2 poliovirus detection or high virus concentration if only one sample was tested (samples producing ≥50% of type 2-positive cell flasks) in red; areas with only occasional detection or low virus concentration in yellow (samples producing <50% of type 2-positive cell flasks); and sampling sites with negative results in grey. A sample from TW-IOD site collected on June 20, 2022, produced four type 2-positive cell flasks, but samples collected on June 13 and July 4, 2022, from the same site were negative, so it was coloured in yellow. TW=treatment works. BMR=Brookmill Road. CAT=Cadogan Terrace. CLN=Costons Lane Northolt Lane. EBS=Effra Branch Sewer. FRA=Fraser Road. FSR=Folkstone Road. GCR=Gascoigne Road. GWT=Greenwich Terminal. IOD=Isle of Dogs. MTR=Martaban Road. OBR=Old Bromley Road. RIC=Richford Street. RLH=Rayners Lane Harrow. TWH=Trumpers Way Hanwell. WCH=Waterside Close Hendon. WHI=West Ham Inlet. WRW=Watkin Road Wembley.

Figure 2

Type 2 poliovirus isolations from London sewage samples The number of cell flasks with a positive type 2 isolation result per sample is shown. Date and location of sample collection are indicated in the figure. Eight cell flasks (five with rhabdomyosarcoma plus three with L20B) were infected with each sewage concentrate. Samples with a negative isolation result are not represented but are listed in the appendix (pp 4–5). CAT=Cadogan Terrace. IOD=Isle of Dogs. MTR=Martaban Road. WCH=Waterside Close Hendon.

Figure 3

Tree showing phylogenetic relationship between all 118 type 2 poliovirus isolates by the analysis of whole-genome nucleotide sequences using the maximum likelihood method and Tamura–Nei model The inferred Sabin origin date is shown at the root of the tree. Symbols are coloured by sampling site. Vaccine-derived and Sabin-like viruses are shown as different shapes with vaccine-derived type 2 poliovirus highlighted by an asterisk. Numbers 1–5 in open circles indicate groups of mutations acquired at each stage of virus evolution that are shared by viruses derived from that branch and are described in the appendix (pp 5–6). CAT=Cadogan Terrace. IOD=Isle of Dogs. MTR=Martaban Road. WCH=Waterside Close Hendon.

Figure 4

Estimation of the date of initial vaccination with Sabin 2 The figure represents mean values of the number of capsid mutations from Sabin 2 vaccine strain (GenBank ID AY184220) for each of the 21 type 2-positive samples (with bars indicating standard error of the mean plotted) plotted by date of sample collection. Dashed lines show 95% CI bands of the best-fit line. The data were adjusted to a linear function for the accumulation of nucleotide substitutions (y=0·07871*× − 3507; r²=0·79). The date of initial Sabin 2 infection that led to the type 2 isolates identified in the London sewage was estimated by simple linear regression extrapolating the line for the evolution rate of nucleotide substitutions backwards to 0 capsid substitutions.