Nearing the end: The final stages of polio eradication

Once responsible for the paralysis of hundreds of thousands of children annually, poliovirus has largely been brought under control through decades of national and international immunization programs. More than 2.5 billion children have received polio vaccinations since the Global Polio Eradication Initiative was launched in 1988, and transmission of wild poliovirus has been interrupted in all but two countries.

Photo by Vertefeuille JF

Despite the estimated 99.9% reduction in cases, however, a substantial effort is still required to achieve true eradication and ensure that the disease does not resurface

“Because we are so close now to entrapping wild poliovirus (WPV) transmission, there is a feeling that we have done the job, and a high risk that the global community [may decide] that we don’t need to focus on this anymore,” Michel Zaffran, MEng, director of polio eradication at WHO and the Global Polio Eradication Initiative (GPEI), told Infectious Disease News. “It’s very important that we maintain the momentum, not only from a technical implementation perspective, but also from an advocacy and financial support perspective.”

Infectious Disease News spoke with several experts about recent developments in polio eradication and the final challenges facing the global campaign.

Decades of international cooperation

International efforts to eradicate poliovirus began in the late 1970s when members of Rotary International organized a 5-year campaign to immunize approximately 6.5 million children in the Philippines, John L. Sever, MD, PhD, professor emeritus of pediatrics at the Children’s National Medical Center and vice chair of Rotary International’s PolioPlus Committee, told Infectious Disease News. Following this and other vaccination efforts in the Americas that were supported by the Pan American Health Organization (PAHO), Rotary launched the PolioPlus program in 1985 with the initial goal of eradicating the disease globally by 2005.

According to Zaffran, seeing the successes of Rotary and PAHO led the World Health Assembly to launch the GPEI, a multi-agency eradication initiative spearheaded by WHO, Rotary, CDC, the United Nations Children’s Fund (UNICEF) and later the Bill and Melinda Gates Foundation. Immunization programs driven by the partnership since its inception have been largely successful: Regional Certification Commissions have declared the Americas, Europe, the Western Pacific and South East Asia free of circulating poliovirus, and WPV type 2 was declared globally eradicated in September 2015 by the Global Commission for the Certification of the Eradication of Poliomyelitis. In addition, according to weekly monitoring data reported by the GPEI, transmission in Nigeria and the African Region was interrupted in 2014; WPV type 3 has not been detected since 2012; paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) was only reported in seven countries in 2015; and transmission of WPV in 2016 has been limited to 17 cases in Afghanistan and Pakistan alone, as of July 6, 2016.

“The World Health Assembly set a goal to eradicate polio in the world by the year 2000, so we are 16 years behind our goal — but we’ve made tremendous progress,” Walter A. Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University School of Medicine, told Infectious Disease News. “The goal is to interrupt transmission of WPV type 1 in Pakistan and Afghanistan this year, as the total WPV case count for these countries is at a record low thus far in 2016 compared to the same time period in prior years.”

The modern immunization campaign

The composition of eradication campaigns has been transformed since their inception. Early efforts were supplemented by a country’s regular immunization program, Sever said, with the efforts of Rotarians and other volunteers primarily focused on supplying polio vaccines, staffing immunization facilities and encouraging social mobilization.

“For many early social mobilization campaigns I went to — not only in Latin America, but in India, for example — they would have parades in the streets, bands, big celebrations about how this is going to happen,” Sever said. “They would have, and still do have, a lot of speakers on mopeds or small vehicles telling the people about the immunization, why it was happening, that it was safe and where they could take their children. From there, it expanded to going from house to house to be sure that we immunized the children.”

The immunization campaign has also greatly increased in scale, with the GPEI’s most recent financing documents indicating $1.4 billion in planned operational costs for 2016 and more than $3.6 billion between 2016 and 2019. According to the GPEI’s 2013-2018 strategy document, much of this funding is split between four key components of the campaign: routine immunization, supplementary immunization activities (SIAs), surveillance and targeted mop-up campaigns.

Routine immunization involves improving the distribution of either oral polio vaccine (OPV) or inactivated polio vaccine (IPV) through a national immunization program. SIAs are additional mass-vaccination campaigns run multiple times a year to vaccinate all children aged younger than 5 years, regardless of vaccination status, in order to catch those who are unprotected or only partially protected.

“These SIAs — which are frequently national but could be subnational — occur at least two times a year in some countries, and in countries trying to terminate polio transmission it may occur as frequently as biweekly in the high-risk areas,” Orenstein said.

A region’s surveillance networks identify children with acute flaccid paralysis (AFP) and test stool samples to confirm and distinguish the presence of wild or vaccine-derived poliovirus. Recently published data from a 2013 outbreak demonstrated the sensitivity benefits of extending these tests to a case’s close contacts. Environmental surveillance of local sewage also is implemented to identify circulating virus, and in recent years this approach has become increasingly important to confirm that many areas are truly polio-free, Zaffran said. Data from these various surveillance methods are then used to develop door-to-door, mop-up campaigns targeting areas where poliovirus is known or suspected to be circulating.

According to John F. Vertefeuille, PhD, MHS, chief of the CDC’s polio eradication branch and incident manager for the CDC’s emergency polio response, these interconnected processes represent a substantial logistical challenge that continues to test local and international health infrastructures.

“It’s a pretty incredible sight to see from the ground up a country that is on the brink of interrupting viral transmission of polio,” Vertefeuille told Infectious Disease News. “It’s thousands of vaccinators reporting to hundreds of field supervisors who are then feeding information into the district, the regional and national health offices. The actions that countries are taking right now are making sure that all of their management systems, accountability and logistic systems actually function in a way that can get the vaccine where it’s needed, get a very precise measurement of how they’ve done, and then make corrections in a very short period.”

Novel strategies bolster eradication

Although these four components are at the core of a country’s eradication campaign, Vertefeuille said the continuing development of supplemental strategies and new technologies has been critical to the global partnership’s successes.

“Even though we are near the possible interruption of wild virus, we still see innovations in improving vaccines and laboratory techniques, and also programmatic improvements such as improving transparency, accountability and local ownership of the polio program,” Vertefeuille said. “It’s really important to understand that the closer we get to actually interrupting transmission, the more energy and focus goes into these innovations. We continue to learn, and we continue to try and make the program even better than it is.”

One such innovation is the adoption of satellite mapping and mobile GPS technologies. According to a study published last year by Kebba Touray, of the WHO Country Representative Office in Abuja, Nigeria, and colleagues, outfitting vaccination teams with GPS-enabled smartphones allows campaign organizers to better coordinate efforts and improve coverage. Because many communities may be nomadic due to civil unrest or cultural traditions, Zaffran explained, pockets of circulating poliovirus could be missed by standard census techniques.

“In northern Nigeria, for instance, to ensure that we had a good mapping of the population and settlements, we used satellite imaging to better understand where the villages are and also how to prioritize distribution and visits by the vaccinators,” Zaffran said. “The same also was done to map out the Bihar state of India. This was necessary to better understand those populations that don’t necessarily have regular access to the health systems and would otherwise be isolated. These people need to be vaccinated to ensure that there is no virus remaining.”

Apoorva Mallya, MBA, senior program officer on the polio team at the Bill and Melinda Gates Foundation, pointed to the development of emergency operation centers as another pivotal innovation. Implemented within the national and provincial hubs of Nigeria, Pakistan and Afghanistan, these planning facilities “provided a forum whereby partners and government can sit together, look at all of the data in real time in a very efficient way ... and be able to make joint decisions, identify gaps and develop timely solutions,” he told Infectious Disease News.

To limit new cases of cVDPV, recent adjustments have been made to vaccines distributed throughout affected countries. Beginning April 17, 155 countries participated in a synchronized global switch-over from trivalent OPV to a bivalent formulation that removed type 2 poliovirus. Deemed the largest vaccine rollout in history by WHO, the switch not only prevents paralytic polio caused by the now eradicated type 2 poliovirus, but also improves the vaccine’s overall efficacy.

“It turns out that having a type 2 virus in the vaccine interfered with the immunity induction of types 1 and 3,” Orenstein said. “We can get much better immunity induction when we get the type 2 virus out. So now around the world, countries that are using the oral vaccine are only using the bivalent vaccine types 1 and 3.”

As of July 6, 151 countries have submitted a report confirming the validation of trivalent OPV withdrawal, according to the GPEI. Although the switchover will reduce the incidence of vaccine-associated paralytic polio (VAPP), Orenstein said it will be vital to continue transitioning away from OPV altogether.

“The bottom line is that we cannot truly eradicate polio until we eradicate wild viruses and eradicate the use of the oral polio vaccine,” he said.

In pursuit of this goal, WHO announced and initiated plans last year to gradually introduce at least one dose of IPV to countries currently reliant on OPV. IPV carries no risk of VAPP and, according to an analysis of U.S. Vaccine Adverse Event Reporting System data conducted by Orenstein and colleagues, is not associated with any serious adverse events.

The transition to IPV has been limited by supply, Zaffran said, but remains in progress.

“So far, only about 100 of the 126 countries that did not already use it have introduced [IPV] because of vaccine supply shortages,” Zaffran said. “There’s not enough vaccine around for all of the countries but, when vaccine becomes available, all countries will have introduced the inactivated polio virus vaccine into their immunization program. In the meantime, available supply is prioritized to highest risk areas and countries, and we are exploring maximizing use of available supply through innovative methods such as fractional dosing.”

Interruption in remaining regions depends on communication, trust

To achieve complete eradication, Mallya said many of the immunization tactics in current practice will need to be redesigned specifically for Afghanistan and Pakistan.

“Even now, we are using many of the traditional strategies of polio eradication: the mass campaigns, the targeted social mobilization, the frequent reaching of hard-to-reach populations and so forth,” Mallya said. “But in these last areas, we’re realizing that we have to get very local and utilize solutions that are very specific to the local context. It’s not necessarily a complete strategic shift, but it’s more tailoring.”

One of the prevailing complications facing vaccination programs in these regions is armed conflict. In a study published last year, Jonathan Kennedy, PhD, a teaching fellow in international development at University College London, and colleagues identified a direct relationship between the Islamist insurgency and polio incidence from 2012 to 2014. The researchers noted that the insurgents’ actions against vaccinators did not seem to have a religious basis; instead, they appeared to be influenced by reports of counterinsurgency operations masquerading as immunization programs. These operations were verified by the CIA as a means to locate and capture insurgent leaders — including Osama bin Laden — and were confirmed by the White House to be discontinued in 2014.

Orenstein and Sever said violence targeting vaccine providers has been costly for the eradication effort, as well as for the individuals who volunteered to immunize the children of these regions.

“[Vaccination] has been moving forward despite the obstacles, such as more intensive religious opposition or political opposition by certain local leaders,” Sever said. “However, there have been significant setbacks — the assassination of workers and the soldiers there to protect workers during the immunization. So, we honor those people who have given their lives to move this program forward, and the immunization effort is continuing in spite of these significant problems in certain local areas.”

Vertefeuille described the work needed to overcome local distrust as multifaceted. Common strategies involve employing local polio survivors as intermediaries or providing basic medical services alongside vaccination. In addition, data published last year reported increased vaccination successes when cooperating with previously hostile youths affiliated with motorcycle riders, local vigilante groups, motor park touts and youth associations. Such approaches have been successful, Vertefeuille said, but can only succeed with strong relationships at their foundations.

“Gaining and maintaining the trust of communities related to accepting the vaccine is really central to the success of the program,” Vertefeuille said. “I spent a lot of time in the field in Nigeria, and I can say that in 2005 and 2006, there was a lot of distrust of vaccination in general, and polio vaccination in particular. It took a deep change of dialogue with those communities to understand what their concerns were and to provide them information about why this was important ... rather than only relying on mass media approaches such as radio broadcasts.”

Ensuring eradication

Should the transmission of WPV be interrupted this year or in ensuing years, several tasks still will be necessary to achieve true eradication and protect the world from its resurgence.

Following the documentation of the final cases in Afghanistan and Pakistan, Vertefeuille said the region would need to remain polio-free for an additional 3 years before receiving certification, which would then be followed by another global certification process. Throughout this process, countries will need to maintain their AFP and environmental surveillance programs, and continue phasing out OPV in favor of IPV.

“Withdrawal of all live-attenuated polio vaccine ... has not been set yet, though we are already using the experience of this recent switch from trivalent to bivalent OPV to inform how to ensure it can happen quickly when the time is correct,” Vertefeuille said.

In addition, containment programs will need to identify each laboratory or vaccine development center where live virus is being held, and ensure that remaining samples are either destroyed or shipped to facilities that meet containment requirements, according to Orenstein. If any facilities are overlooked, mishandling of the virus could lead to a new outbreak.

“When we produce IPV, we produce it from WPV that is then killed,” he said. “There have been leaks — one as recently as a few years ago in Belgium — of wild virus from laboratories. We have to be very careful, and efforts are also being made to develop effective IPV that are not made from the wild virus.”

The GPEI initiated the first phase of this process after eradication of type 2 WPV, Zaffran said, and has laid out working procedures to ensure these viruses are not released back into the environment.

“Type 2 no longer exists in its wild form and has been removed from the vaccine — we cannot afford to have it come back through accidents caused by laboratories or manufacturers,” Zaffran said. “We’re working with manufacturers and laboratories to make sure that we contain all of the existing virus, or that we destroy them if they don’t need to continue working with them.”

Other measures to prevent a resurgence of cases, Orenstein said, involve identifying and treating a “very limited” population of children and adults with immune deficiencies who could unknowingly be chronically shedding virus, and developing contingencies in case poliovirus is synthesized and used as a bioweapon after eradication.

Planning polio’s legacy

While much of the effort’s endgame strategy focuses on ensuring success, Vertefeuille said it also is important to plan for the years after eradication. Part of this, he explained, is documenting the information gained over decades of polio eradication efforts for future generations.

“The scientific writing, the data, the human interest stories, the history of polio, the social pieces, the community engagement — we take the lessons from these and make sure that they are available to the global community so that we can learn as much as we can from this process,” Vertefeuille said.

The other aspect of “legacy planning” involves repurposing the various infrastructures built throughout the polio eradication effort — the trained personnel, outfitted laboratories and interconnected surveillance systems — for other public health challenges such as measles or malaria. While many of the experts were hopeful that another global health initiative could take up polio’s mantle, Zaffran said the prolonged and costly effort to rid the world of polio has left little international interest in another eradication campaign.

“The amount of resources that has been put into polio cannot immediately be matched by another initiative — there’s no appetite at the moment for the world to launch into another eradication goal,” Zaffran said. “We can anticipate that a new agenda for global health security would be heavily supported by the assets, information systems, surveillance systems and staff that were in place for the polio program, but it’s not ‘one-size-fits-all.’ It’s going to have to be tailored to the country’s needs and the resources that become available.”

Regardless of any logistical difficulties in the post-polio era, Orenstein said the impact of humanity’s symbolic victory over the virus will surpass its immediate public health benefits.

“Success with polio eradication will say that human beings can unite against the common enemy — the poliovirus,” Orenstein said. “It holds potential for trying to deal with other potential health burdens and eradicating them. A victory here will have implications well beyond just getting rid of polio.” – by Dave Muoio

References:

• Global Polio Eradication Initiative. Financial Resource Requirements, 2013-2019. . Accessed June 14, 2016.
• Global Polio Eradication Initiative. Polio Eradication and Endgame Strategic Plan, 2013-2018.. Accessed June 13, 2016.
• 6. Global Polio Eradication Initiative. Polio this week as of 7 June 201. Accessed June 13, 2016
• Iqbal S, et al. Lancet Infect Dis. 2015;doi:10.1016/S1473-3099(15)00059-6.
• Kennedy J, et al. Global Health. 2015;doi:10.1186/s12992-015-0123-y.
• Moturi E, et al. Open Forum Infect Dis. 2016;doi:10.1093/ofid/ofw111.
• Musa A, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv510.
• Pan American Health Organization. First Meeting of the American Regional Commission for Certification of Poliovirus Laboratory Containment and Verification of Polio-free Status, Final Report. . Accessed June 13, 2016.
• Touray K, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv493.

 

For more information:

• Apoorva Mallya, MBA, can be reached at apoorva.mallya@gatesfoundation.org.
• Walter A. Orenstein, MD, can be reached at worenst@emory.edu.
• John L. Sever, MD, PhD, can be reached at jlsever@comcast.net.
• John F. Vertefeuille, PhD, MHS, can be reached at axj3@cdc.gov.
• Michel Zaffran, MEng, can be reached at zaffranm@who.int.

Disclosures: Orenstein reports consultation with the Bill and Melinda Gates Foundation. Kennedy, Mallya, Sever, Touray, Vertefeuille and Zaffran report no relevant financial disclosures.

What is the best use for polio infrastructure and assets after eradication?

 

Targeting broad health interventions is the best use of existing infrastructure.

The global effort to eradicate polio has always been about much more than the eradication of a single disease. The vast infrastructure of human resources, equipment, technical capacity and public health expertise is already being used to address broader public health needs. Polio-funded staff on the ground spend on average 50% of their time working on activities broader than polio eradication — such as supporting maternal and child health interventions — and have been so far very effective in strengthening routine immunization. In the Bihar state of India, for example, the estimated proportion of children immunized against all vaccine-preventable diseases (over and beyond polio) increased from 20% to almost 80% over the past 15 years, thanks in part to the systematic utilization of the polio network that had been established in the state.

Such benefits need to continue even after polio has been eradicated, but they have to continue in a systematic and integrated manner. The great success of smallpox eradication was that it succeeded in eradicating smallpox — its great failure was that the network established to achieve this success was allowed to subsequently collapse. There is broad consensus that the same cannot be allowed to happen to the polio network.

Integrating this “PolioPlus” capacity into supporting maternal and child health and broader sustainable development goals makes both strategic and operational sense, as it is already happening on the ground, albeit in an ad hoc manner. There is already a broad coalition of partners in place to improve maternal and child health globally. Rotary, a key partner in the polio effort, also has identified maternal and child health as an institutional priority area, together with others such as water and sanitation, crucial to maintaining any improvements we manage to achieve in health outcomes.

It will now be key to institutionalize these activities at the global and regional levels to ensure this great network can support broader maternal and child health interventions, and the systems needed to deliver them, by building on the existing infrastructure. It is the best way to optimize this resource in the long term.

Flavia Bustreo, MD, MSc, is the assistant director-general for family, women’s and children’s health at WHO. Disclosure: Bustreo reports no relevant financial disclosures.

Public health should pursue routine immunization and measles elimination.

Any targeted disease effort must be placed in the context of a broader health systems-strengthening approach, since no one would argue for the establishment of a global infrastructure to benefit only a single disease. This is, of course, also the case with the global polio eradication effort, also known as “PolioPlus.” The “Plus” in the title is indicative of the fact that the polio infrastructure benefits broader public health issues beyond polio, and there is much evidence to support this.

Having said that, there is a natural strategic and operational fit to further utilize the polio infrastructure to systematically support strengthening of routine immunization and measles elimination. Both are pathogens that can be prevented through simple administration of a vaccine, and both are biologically and operationally feasible to eradicate (unlike most diseases).

Most importantly, the polio effort is already greatly strengthening routine immunization and measles elimination efforts. In many countries, detailed polio campaign microplans are used to implement measles campaigns. Trained vaccinators at fixed sites co-administer measles vaccine alongside polio and other vaccines. Surveillance for polio is already helping conduct surveillance for measles and other vaccine-preventable diseases. And the public health benefits of eliminating measles are extremely significant, so from a humanitarian point of view, the elimination of measles globally would be a tremendous achievement.

All of this means that maintaining the polio infrastructure will continue to support the strengthening of routine immunization and measles elimination. Continuing to do so, in a broader health approach, has always been the case.

Peter M. Strebel, MBChB, MPH, is the priority area leader for accelerated disease control in the expanded program on immunization at WHO. Disclosure: Strebel reports no relevant financial disclosures.