By guest contributors Piero Olliaro and Josephine Bourner Outbreak clinical research presents special challenges, the most pressing one being speed. Long-lasting pandemics…
By guest contributor Dr. Ananda S. Bandyopadhyay, Deputy Director, The Bill & Melinda Gates Foundation
(ES: Environmental Surveillance, OPV2: Oral Polio Vaccine Type 2, AFP: Acute Flaccid Paralysis, cVDPV2: Circulating Vaccine-Derived Poliovirus Type 2, WHO: World Health Organization, AMRO: WHO Region of the Americas, EURO: WHO European Region, SEARO South-East Asia Region)
What is going on?
Polio – a disease many have prematurely consigned to history – made headlines around the world in recent months when the virus was detected in relatively high-income country settings from New York, London, Montreal and Jerusalem. This apparent comeback in polio-free countries has left many questioning the feasibility of eradication. On the contrary, we have never been closer to achieving our goal of a polio-free world: this resurgence only underscores the urgent need for eradication.
When the Global Polio Eradication Initiative (GPEI) was launched in 1988, nearly 1,000 children were being paralyzed with wild poliovirus (WPV) infection across 125 countries every single day. Since then, a concerted effort of health workers, communities, local governments, and global partners such as Rotary International have helped eradicate two of the three serotypes of wild poliovirus (WPV2 and WPV3) and cornered the remaining strain of WPV – type 1 (WPV1) – to small areas of Pakistan and Afghanistan – the last wild polio-endemic countries. The genetic diversity of the remaining chains of WPV1 is also on the decline, indicating the virus might very well be on the verge of being wiped out.
However, this incredible progress is in jeopardy. Due in part to the COVID-19 pandemic, the world has seen a worrying drop in immunization rates over the past few years, creating pockets of under-immunized communities at heightened risk of polio infection and paralysis. Children missing polio vaccinations creates opportunities for polio to re-emerge and spread – as seen in 2022 when WPV1 originating in Pakistan was detected in paralyzed children in Malawi and Mozambique. This episode served as a poignant reminder that as long as polio exists anywhere in the world, it remains a threat to people everywhere.
Persistently under-vaccinated communities are also at risk of outbreaks of vaccine-derived poliovirus (VDPVs). These polio variants evolve from oral polio vaccines (OPVs), which use a weakened form of the virus to protect children from infection and act as a key tool for many countries to stop the spread of polio. When a vaccinated child sheds that weakened virus into the environment, it can help provide indirect protection for the entire community. However, in areas with persistently low immunization coverage, the weakened vaccine virus can circulate over a prolonged period, ultimately regaining the ability to cause paralytic outbreaks that can spread across geographies.
Variant polioviruses are now the main cause of polio outbreaks around the world, with over 600 cases of circulating VDPV type 2 (cVDPV2) reported in 2022. A majority of these cVDPV2 cases have been reported from the Democratic Republic of Congo, Yemen, and Nigeria. The polioviruses detected in sewage samples in the US (which also saw one paralytic case), Canada, the UK, and Israel were also confirmed as cVDPV2 in 2022, demonstrating that poliovirus variants can spread beyond the geographic borders of OPV-using countries through population movement and VDPVs can emerge in high-income settings where OPV is not in use if uniformly high levels of immunity are not maintained in sub-populations.
What do we do about it?
One technological solution to the VDPV situation is the development of OPV strains that are more genetically stable and therefore less likely to evolve into VDPVs. In 2011, a scientific consortium was formed to explore the development of a next-generation vaccine while still maintaining the advantages of existing OPV, such as ease of delivery and intestinal mucosal immunogenicity. As poliovirus serotype 2 strain has been associated with most of the paralytic polio outbreaks of cVDPVs, a new, type 2 OPV was selected as the initial focus of the consortium.
In November 2020, the novel oral polio vaccine type 2 (nOPV2) was authorized under the Emergency Use Listing (EUL) pathway by the World Health Organization (WHO) following positive findings from phase I and phase II studies of safety, reactogenicity, immunogenicity and the desired genetic stability. Rollout of nOPV2 for outbreak response began in March 2021 and since then, more than 580 million doses of nOPV2 have been delivered in 28 countries, with surveillance data from initial field use indicating a high likelihood of success at closing outbreaks with lower risk of seeding the emergence of new ones.
Regardless of which polio vaccine is used to stop an outbreak, there must be high immunization coverage for all children to be protected against paralysis. Following the detection of an environmental sample or confirmation of a case of paralytic polio, outbreak response campaigns must be launched in a timely manner to reach all at-risk communities with vaccines. Coordination transcending geographic borders is also key, which is why countries currently at a high risk of polio spread – such as Pakistan and Afghanistan as well as Malawi, Mozambique, Tanzania, Zambia, and Zimbabwe – are synchronizing campaigns to help ensure that underserved and migrant communities are not missed. Readiness on the regulatory front to use a vaccine under EUL provisions as in the case of nOPV2 and maintaining adequate global supplies of such vaccines will be important in minimizing the risk of spread of polio.
When I began my career in polio eradication, I worked as a surveillance medical officer with the WHO in India and saw both the impact of this terrible disease on children and families as well as the relief and solution in reaching underserved communities with vaccines. Today, India celebrates over a decade free of poliovirus. Its success in the face of overwhelming challenges lays the pathway for the rest of the world to follow. The GPEI’s 2022-2026 eradication strategy uses this experience to improve campaign activities and roll out new tools such as nOPV2. Additional tactics include emphasizing integration of polio vaccination campaigns with the delivery of other essential health services and striving for gender equity among health workers to overcome vaccine hesitancy.
But even with novel tools, proven strategies, and ample experience at hand, political and financial commitments from the global community are paramount if we are to reach every last child with polio vaccines. As evidenced around the world in recent months, polio-free communities are not polio-risk-free. It is incumbent on all countries and partners to step up and reaffirm their support to ending polio for good. Real-world innovations to enable front-line health workers to reach underserved communities with life-saving vaccines hold the key to achieving and sustaining polio eradication.
Acknowledgement: Thanks to Laura Cooper (Bill & Melinda Gates Foundation) for help with data visualization.
About the author:
Dr. Ananda Sankar Bandyopadhyay is the Deputy Director, Technology, Research, and Analytics on the Polio Team at the Bill & Melinda Gates Foundation coordinates research and development initiatives aimed at achieving and sustaining polio eradication. Ananda grew up in Kolkata, India and completed his medical graduation from Calcutta National Medical College & Hospital with a gold medal and several honors certificates and received his Master of Public Health (MPH) degree in Global Health from Harvard School of Public Health. In his professional career spanning more than 15 years, Ananda has worked in diverse settings and has led disease control efforts across the globe.
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