New polio detection method could enable faster vaccine responses

 

 

A new technique has halved the time it takes to detect polio, potentially enabling swifter vaccine responses to outbreaks and fewer polio infections overall.

By allowing virus samples to be genetically sequenced in the country where the outbreak originated rather than being sent to specialist laboratories abroad, detection times could be reduced from an average of 42 days to 19 days, research in the Democratic Republic of the Congo (DRC) suggests.

“This substantial saving in time could lead to quicker responses and truncate the spread of poliovirus and outbreaks.”

– Dr Alex Shaw, Research Fellow in the School of Public Health at Imperial College London

Polio is caused by a virus that is usually transmitted through contact with infected faeces via contaminated food and water. While many people never show symptoms, the infection can lead to permanent paralysis or death, with babies and young children at greatest risk. Efforts to eradicate polio are ongoing, and WHO has identified delays in detection as a major obstacle towards achieving this, as it plays an essential role in managing outbreaks.

Typically, polio is detected by growing cells that are susceptible to poliovirus in tissue culture flasks, exposing them to viruses collected from stool samples, and then waiting to see if they die. This process usually takes around a week, but the test may be repeated to be certain that a sample really is negative for poliovirus.

Once detected, a technique called quantitative PCR is used to try and determine whether the virus is a vaccine-derived strain, a vaccine-derived virus that has evolved to become more dangerous, or a wild form of poliovirus – with the result affecting the type of response that’s required.

“One of the big problems is that in many countries, including the DRC, the national poliovirus laboratories will ship their samples to a global specialised lab that does the sequencing, rather than doing it themselves,” said Dr Alex Shaw, Research Fellow in the School of Public Health at Imperial College London, UK, who led the new study. “It’s only after you’ve gone through that whole process that you can launch a response, and the longer it takes to get to that response phase, the wider the circulation of the virus will be.

“The cell culture-based method is also not in line with the current containment targets for polio. As we’re approaching eradication, we don’t really want labs growing lots of polioviruses, so the aim is to move away from this type of detection over the next couple of years.”

Shaw is a member of an international effort set up to develop a rapid, non-culture-based method of detecting polio, with support from the Bill and Melinda Gates Foundation. The method they have developed, known as Direct molecular Detection and Nanopore Sequencing (DDNS), works by amplifying and sequencing a specific region of the poliovirus genome that encodes a protein called VP1. “This is the protein that allows poliovirus to attack human cells, so it defines what polio can do, essentially,” Shaw explained.

As well as detecting whether poliovirus is present, this sequence is compared to reference genomes to establish what kind of poliovirus it is. If it is the normal vaccine strain, no further response may be necessary, as it is usual for this harmless form of the virus to be excreted in people’s stools following oral vaccination campaigns. However, detection of wild type poliovirus, or a circulating vaccine derived strain, will usually trigger a targeted vaccination campaign.

DRC was selected as the first country to pilot the new method in, because vaccine-derived polioviruses continue to circulate there, with 502 cases reported in 2022. The Institut National de Recherche Biomédicale (INRB) in Kinshasa also has a lot of experience of disease outbreaks and genomic surveillance, Shaw said: “They are nicely placed to take on this technology, to be able to use and maintain it, and they have the experience to deal with the data that comes out of it.”

INRB scientists were initially trained on how to use the technology over Microsoft Teams, and then spent six months testing the method in parallel with the conventional cell culture-based method, allowing the accuracy of the two methods to be compared.

The research, published in Nature Microbiology, found that the DDNS tests produced a result on average 23 days faster than the standard method, with sequences generated being greater than 99% accurate when compared to those generated by the standard method.

“This substantial saving in time could lead to quicker responses and truncate the spread of poliovirus and outbreaks,” Shaw said. “It could mean you don’t need to vaccinate as big an area, and it is likely to be less costly because you can have more targeted campaigns.”

The next step will be to validate the technique in greater numbers of samples and in additional countries – including Pakistan and Nigeria, where polio continues to circulate. British and INRB scientists are also training colleagues in other countries, in anticipation of the technique eventually being rolled out more widely. For instance, the INRB recently hosted a round of training for scientists from Senegal, Cameroon and Kenya.

Professor Placide Mbala-Kingebeni, a medical doctor and virologist at the INRB, said: “Collaboration and training with our partners has empowered the local team, not only to master and confidently carry out this new technique, but also to transfer the knowledge and skills to other African countries where poliovirus outbreaks are reported regularly.”

By equipping more labs with the skills to carry out genomic sequencing and analysis, Shaw also hopes that countries will be better placed to respond to outbreaks of other diseases, besides polio. “In the long run, ideally, we will eradicate polio,” he said. “At that point the existing polio lab network, which is highly skilled and very well organised, could hopefully be repurposed for other forms of disease surveillance.”