In the fight to eradicate polio, wastewater environmental surveillance acts as an early warning system. Poliovirus can circulate silently because most infections do not cause paralysis, and infected people can shed virus in their stool without knowing they are infected. Routine sampling of wastewater from communities therefore offers a window into what is happening across an entire community, including virus transmission that would otherwise remain invisible.
In the United Kingdom of Great Britain and Northern Ireland, the poliovirus laboratory at the National Institute for Biological Standards and Control (NIBSC), part of the Medicines and Healthcare products Regulatory Agency (MHRA), operates as a WHO Global Specialized Laboratory for poliovirus. Scientists at NIBSC work across many different parts of the polio eradication programme, detecting polioviruses through clinical and wastewater surveillance, sequencing them to understand where they have come from and how they are spreading, and supporting the development and evaluation of safer polio vaccines. This work is part of a commitment to the Global Polio Eradication Initiative (GPEI), which began in 1988. Led by WHO, it is the largest, internationally coordinated public health initiative to date.
MHRA works closely with the UK Health Security Agency (UKHSA), which in turn transforms information into public health action in the pursuit of a world free from polio.
Wastewater sampling
UKHSA works with water companies to collect monthly wastewater samples from 28 sites in England (United Kingdom). The sites are selected by the UKHSA to include locations most likely to see importations of wild polio or vaccine-derived polio, and in which communities are least protected by vaccination. Wastewater from London is sampled more regularly. Altogether, wastewater surveillance covers around 33% of England’s (United Kingdom) population. The samples are shipped to MHRA and National Health Service Lothian in Edinburgh, Scotland, where scientists conduct routine environmental surveillance for polio. If a poliovirus of concern is detected, sampling and testing can be intensified rapidly.
When the poliovirus laboratory at MHRA receives samples, scientists filter and centrifuge them. This concentrates the samples because the amount of poliovirus present may be extremely small. Material from the wastewater samples can also be used by other colleagues to investigate other viral or bacterial targets, increasing the value obtained from each sample.
Scientists introduce the concentrated samples to special cell cultures that are sensitive to enteroviruses and polioviruses. Using a microscope, scientists monitor the cells for a cytopathic effect – visible damage or destruction of the cell caused by the virus multiplying.
Molecular and genomic testing
If the cell culture does show viral growth, scientists carry out further molecular testing to confirm if it is a poliovirus and determine the specific type. At the MHRA lab, poliovirus is detected in about 10–20% of samples annually. Detections are almost always vaccine-like polioviruses, shed by someone who has received the oral polio vaccine (which uses a weakened, live virus) recently. Scientists sequence the virus to determine how far it has evolved from the vaccine to identify extended transmission and circulation in under-vaccinated communities, which can lead to vaccine-derived poliovirus, is more virulent and could cause disease. On the other hand, the detection of imported wild poliovirus, which still circulates in a few countries outside the WHO European Region, is exceedingly rare, thankfully.
When wild or vaccine-derived poliovirus is detected, scientists trace the genetic linkages of the virus to understand where it may have originated, and to see if it matches strains found elsewhere. MHRA and international partners have been developing poliovirus direct detection methods using nanopore sequencing, which can allow virologists to detect and genetically characterize polioviruses in clinical or environmental samples more directly.
Nanopore technology reads individual strands of DNA (a copy of viruses’ RNA) as they pass through tiny pores. The sequencing instruments can be remarkably compact, which means sophisticated genomic surveillance is no longer restricted to very large sequencing centres.
Capacity building in the wider Region
Within the WHO Global Polio Laboratory Network, made up of highly competent laboratories operating under rigorous WHO quality-assurance processes, MHRA supports laboratories in different parts of the world. This includes training and technical support in virus detection and characterization, genetic sequencing, bioinformatics, quality assurance, interpretation of results and reporting, as well as helping laboratories introduce new approaches, such as next-generation sequencing and direct nanopore sequencing. This support complements the substantial expertise already present within the network and continues as laboratories implement and independently use these methods.
MHRA also develops international standards and reference materials that laboratories and vaccine manufacturers around the world use to make sure vaccines and tests are performing consistently. And, as eradication gets closer, they have an increasingly important role in poliovirus containment – making sure that poliovirus materials that still need to be kept for essential purposes, such as vaccine production, quality control or research, are handled safely.
MHRA provides laboratory expertise and poliovirus genetic analysis and interprets results together with epidemiologists and public health colleagues. Information is rapidly shared through national and international surveillance systems, including the WHO Global Polio Laboratory Network.
Turning data into public health action
If action is required, public health authorities can then focus their surveillance efforts, investigate where transmission may be occurring and, when appropriate, alert local health teams and implement local vaccination measures. UKHSA leads the public health response to turn data into action.
“Testing is one thing, but you need to know what to do when you find something and to have a strong relationship between the public health response and the laboratory,” says Vanessa Saliba, consultant epidemiologist at UKHSA.
Wastewater sampling is a critical component in the global polio eradication initiative, providing early warnings that can inform targeted vaccination drives, allowing public health authorities to act earlier to reduce the risk of further transmission, paralysis and death.
The end game
Thanks to decades of high polio vaccination coverage, the United Kingdom is a polio-free country. The United Kingdom has not recorded an indigenous wild polio case since 1984 and was officially declared polio-free by WHO in 2003. However, until polio is eradicated globally, countries remain at risk of importations leading to silent transmission in under-vaccinated communities until a paralytic case makes it visible – in response, clinical, laboratory and wastewater surveillance are essential for early detection.
“Wastewater allows us to see the virus even when we cannot see the disease. That is particularly important for polio because most infections cause no paralysis,” says Javier Martin, Head of the polio virus laboratory at MHRA.
Globally, polio vaccination programmes have reduced wild poliovirus cases by more than 99%, preventing an estimated 20 million cases of paralysis since the late 1980s. However, barriers to accessing vaccination and the rise of mis- and dis-information globally can lead to gaps in coverage, hindering the final eradication of polio.
“We’re getting there but we mustn’t be complacent given the challenges we are facing globally,” says Vanessa Saliba. “We must not lose the determination and focus to get to the end game.”