Master Thesis: Is enterovirus D68 the new polio? Global prevalence and potential for paralysis call for increased surveillance

Over the past decade, enterovirus D68, an emerging respiratory virus, has continued to assert itself as a significant global public health concern, causing severe respiratory disease and polio-like paralysis.

In humans, enterovirus D68 (EV-D68) causes respiratory disease and in rare cases a polio-like paralytic syndrome. EV-D68 was rarely reported for more than 50 years, until a large, international-level outbreak in 2014. Hereafter, EV-D68 was associated with epidemics recurring in even-numbered years. Following the COVID-19 pandemic, its pattern seems to have shifted to yearly outbreaks. In her master’s thesis, Aurora Hirvonen analyzed the frequency of EV-D68 infections in the global population over the last decade and looked into the ability of EV-D68 to cause severe respiratory infection and neurological disease.  

Ten years of trouble

The findings of the thesis confirm a sustained circulation of EV-D68 over the last ten years in all continents of the world. The cumulative count EV-D68 cases reached over 5700, but it is probably a gross underestimation of its true burden. In terms of trends, the distinct every-even-year pattern of the virus became evident. It was clearer in the northern hemisphere but could be still captured in the global south.  

Even though, 2020 was an even year, it was marked by an unusually low number of EV-D68 notifications by all regions due to the COVID-19 pandemic. Hirvonen explains this was mostly likely the result of three things: the dominating presence of SARS-CoV-2 at the time, the introduction of non-pharmaceutical intervention to control SARS-CoV-2 transmission and the limited testing of other viruses beyond SARS-CoV-2.

Coming out of the COVID-19 pandemic, the pattern of EV-D68 circulation remained a bit unclear. The proposed shift to yearly epidemics remained speculative and was driven by distinct geographical differences. For example, Europe was more conformed to this shift while North America picked up the previous biennial trend. Hirvonen attributes this ambiguity to a lower number of publications in the post-pandemic time.  

Old and new horizons

Other epidemiological details revealed that EV-D68 was still associated with severe respiratory illness and AFP, primarily in children under the age of five, but increasingly in adults. In addition, the spectrum of EV-D68-associated symptoms had widened since the first pivotal outbreak in 2014 and often overlapped with other similar viruses. This tells us how EV-D68 cannot be distinguished by its clinical presentation alone and a strong diagnostic tool is required for the specific detection of the virus.

Why is this important? Hirvonen makes it clear that timely diagnosis and effective surveillance can be the determining factors between a contained infection and complex paralytic case. Patients who progress to AFP have a poor clinical prospect to full recovery often requiring long-term ventilatory support. In this sense, the storyline of EV-D68 is very similar to that of poliovirus a century ago, hence the denomination “new polio”.

A polio eradication blueprint also for EV-D68

We can reapply many key activities from the polio eradication strategy also to EV-D68 surveillance. First, the prime focus for the future should become the establishment of a platform for the accurate diagnosis of EV-D68. Regardless of the severity of the disease and irreversible damage, none exist on the market.

Secondly, the cultivation of strategies for preventing and treating EV-D68 are necessary. The polio vaccine was the cornerstone of the global polio eradication efforts, and the same should translate for EV-D68. Currently, prevention measures for EV-D68 are lacking, and treatment still relies on relieving patient symptoms. Fortunately, a glimmer of hope has come from an EV-D68-specific agent now in clinical trials.

Next, the testing of correct samples allows for correct identification. Polio has been traditionally detected by analyzing the stool of AFP-affected individuals. However, EV-D68 is poorly detected in this type of sample and is much more abundant in respiratory samples. “When an individual presents with paralysis, a stool sample is automatically taken to exclude polio. If they do not find polio, the cause is not further investigated. We know it could be EV-D68, but stool is not the correct sample for this type of virus.” says Hirvonen. She continues by noting that the easiest solution would be to include respiratory samples in the already existing and well-functioning AFP surveillance in place for polio – two birds with one stone.

Finally, in this journey, robust international collaboration should not be forgotten. It can facilitate the process, embrace under-resourced regions, and account for geographical variations. In the long term, enhanced, multifaceted and harmonized surveillance will be reflected in more reliable estimates of EV-D68 cases and the ameliorated global burden of EV-D68 and associated neurological disease.

The dissertation was an update to a previous systematic literature review, conducted by Holm-Hansen et al. (2016) covering the global emergence of EV-68 and the major EV-D68 outbreak in 2014. Published work was reviewed from 2015 to 2024.

The thesis Global prevalence of enterovirus D68 over the last decade – a systematic review can be read from the Theseus repository.

Further information

Aurora Hirvonen
Master’s degree programme in Global Health and Crisis Management