Global poliomyelitis eradication

INTRODUCTION — Given the availability of an inexpensive oral polio vaccine (OPV) and the success of the Pan American Health Organization polio eradication program in the Americas, the World Health Assembly resolved in 1988 to eradicate polio globally by 2000 [1]. This goal has proven more challenging than originally foreseen, in part due to poor access to children in the remaining endemic areas, insecurity, deficiencies in program performance, and emergence of circulating oral poliovirus vaccine-derived polioviruses (cVDPV).

Nonetheless, great progress has been made; since 1988, the incidence of paralytic polio worldwide has been reduced by more than 1000-fold, and two of the three naturally occurring (wild-type) poliovirus serotypes no longer circulate. Wild-type 1 poliovirus (WPV1) circulation and disease are limited to only four countries: Pakistan, Afghanistan, Mozambique, and Malawi. However, the number of polio cases caused by type 2 cVDPVs in sub-Saharan Africa, Asia, Europe, and North America now exceed the incidence of WPV1 by an order of magnitude, creating a new front in the battle to eradicate poliomyelitis [2,3].

The long-term strategy of the Global Polio Eradication Initiative is to interrupt transmission of all wild-type and cVDPV viruses, phase out OPV use in a staged manner to reduce the risk of vaccine-associated paralytic poliomyelitis (VAPP) and new cVDPV outbreaks, and introduce inactivated poliovirus vaccine into the routine infant immunization schedule in all countries [4].

Issues related to polio eradication are reviewed here. Issues related to polio infection and routine polio vaccination are discussed separately. (See "Poliomyelitis and post-polio syndrome" and "Poliovirus vaccination".)

GLOBAL ERADICATION PARTNERSHIP — The Global Polio Eradication Initiative partnership was launched in 1988 and is led by six organizations: the World Health Organization, the United States Centers for Disease Control and Prevention, the United Nations Children's Fund, Rotary International, the Bill and Melinda Gates Foundation, and Gavi, the vaccine alliance. The partnership includes many governmental and nongovernmental donors as well as the ministries of health of all affected nations who plan and carry out the program's initiatives, at an overall cost that exceeds $1 billion per year.

ERADICATION STRATEGIES — The goal of the Global Polio Eradication Initiative (GPEI) is to interrupt transmission of naturally occurring (wild type) and vaccine-derived polioviruses by increasing population immunity via deployment of supplemental polio immunization activities (SIAs), in addition to routine infant immunization. The program depends on active surveillance for poliovirus-related acute flaccid paralysis (AFP) cases and detection of polioviruses in sewage (environmental surveillance) [5,6].

Until 2005, trivalent oral polio vaccine (tOPV) was used exclusively for routine immunization and in SIAs due to low cost, ease of administration by non-medical workers, and induction of mucosal immunity that reduces person-to-person and community poliovirus transmission. With the elimination of wild-type 2 poliovirus circulation in 1999, monovalent type 1 and type 3 vaccines (mOPV1 and mOPV3) and bivalent type 1 and 3 (bOPV) vaccine replaced tOPV for many SIAs conducted after 2005 due to superior immunogenicity against poliovirus types 1 and 3 [7].

Dose for dose, inactivated poliovirus vaccine (IPV) results in higher seroconversion rates than OPV in low-income settings, where the burden of enteric pathogens and tropical enteropathy reduces the efficacy of OPV [8-10]. However, IPV costs far more than OPV to produce, requires injection, and induces little or no intestinal immunity compared with OPV. For these reasons, IPV was not included in the program until 2015 prior to replacing tOPV with bOPV in 2016.

Routine immunization — From the 1970s until 2016, most low- and middle-income countries used tOPV in their national childhood immunization programs following the World Health Organization (WHO) Expanded Program on Immunization (EPI) recommended schedule that specifies doses at birth and at 6, 10, and 14 weeks of age [7]. Most high-income countries continue to administer IPV in combination with other childhood vaccines, and some (mostly middle-income) countries deploy a mixed IPV-OPV schedule, including China, which now administers two IPV doses at two and three months of age and two bOPV doses at four months and four years of age [11].

The WHO Strategic Advisory Group of Experts (SAGE) on immunization recommended introduction of ≥1IPV doses into the EPI schedule in advance of the global, synchronized switch from tOPV to bOPV in April 2016 [4,7]. In most low-income countries, one dose of IPV is given at 14 weeks of age in addition to bOPV at birth and 6, 10, and 14 weeks of age.

Supplemental immunization activities — Routine OPV immunization rates in many regions fall below the threshold required to interrupt poliovirus transmission; therefore, the GPEI relies on SIAs to raise population immunity to polio. SIAs (also known as National Immunization Days and Sub-National Immunization Days) deliver OPV via periodic, highly organized campaigns conducted door to door or at fixed sites within population centers [5]. Typically, a campaign is conducted over a few days and targets all persons of a specified age range (usually <5 years) without regard to prior OPV immunization history. Since 2005, most SIAs have deployed mOPV and, more recently, bOPV. Until 2015, the GPEI conducted multiple bOPV and tOPV campaigns in 30 countries in Africa and Asia. The use of tOPV was discontinued in April 2016.

SIA quality is assessed through independent SIA monitoring protocols developed specifically for this purpose. SIAs are credited with interrupting poliovirus transmission worldwide, and programmatic successes in Africa and Asia are associated with improvements in SIA quality.

Surveillance — Surveillance for poliomyelitis cases consists of detection of AFP cases in children and adolescents ≤15 years of age that are compatible with poliomyelitis [12]. Stool collected from AFP cases and close contacts within 14 days of onset are tested by cell culture in a regional Global Polio Laboratory Network laboratory for the presence of polioviruses and other enteroviruses. Poliovirus isolates are forwarded to reference laboratories for differentiation from oral poliovirus vaccine strains and further characterization. Only a small fraction of AFP cases is confirmed as polio by laboratory testing. In addition, the polio immunization status of every AFP case is recorded as an additional measure of population immunity.

Environmental surveillance for circulating wild-type and vaccine-derived polioviruses by periodic sampling of sewage effluents has been expanded in many high-risk areas to supplement AFP surveillance [13]. As fewer polio cases are detected by AFP surveillance, environmental surveillance activities are expanding in high-risk areas in Africa and Asia. Environmental surveillance has also proven valuable in other locations including Israel where WPV1 circulation was detected in the absence of poliomyelitis cases in 2013 [14].

In 2022, more than 100 genetically related type 2 Sabin vaccine viruses were isolated in sewer systems in London, New York state, and Israel [15,16]. In London and New York, these isolates were found in wastewater at multiple locations, and RNA sequencing classified some as cVDPV, confirming circulation of virulent polioviruses within these populations. As of November 2022, one AFP case has been identified during this outbreak, a young male residing in an under-immunized religious community in Rockland County, New York. Public health authorities responded by reviewing routine childhood immunization rates and encouraging IPV vaccination in affected populations.

Mop-up activities — Mop-up campaigns are door-to-door SIAs that are carried out in focal areas where the virus is known or suspected to still be circulating. Priority areas include those where polio cases have been found over the previous three years and where access to healthcare is difficult. Other criteria include high population density, high population mobility, poor sanitation, and low routine immunization coverage.

CHALLENGES TO ERADICATION

Operational challenges — Polio eradication has encountered numerous challenges, including variable commitment from national authorities, religious and cultural opposition, inadequate funding, poor campaign quality, surveillance gaps, and slow response to outbreaks [17]. In addition, extremist groups perpetrating violence against oral poliovirus vaccine (OPV) campaign workers in the remaining endemic areas deny access to hundreds of thousands of unvaccinated children.

In response, the Global Polio Eradication Initiative has improved supplementary immunization activity (SIA) planning, conduct, and monitoring, enhanced acute flaccid paralysis surveillance, and initiated environmental surveillance in high-risk areas. The program now integrates polio vaccination with routine immunization and other key health interventions, engaged government, traditional, and religious leaders at all levels, aggressively supported social mobilization teams to improve communication and advocacy locally, and introduced innovations designed to improve polio vaccine delivery, such as satellite global positioning system mapping and creation of immunization stations at transit points during population movements.

Low OPV efficacy — The high burden of enteric pathogens can reduce seroconversion rates to less than 20 percent per OPV dose in some locations, leaving many children who have received multiple doses still susceptible to polio [8,18,19]. The elimination of naturally occurring type 2 polioviruses allowed for a partial solution to this problem: deployment of monovalent type 1 vaccine and bivalent types 1 and 3 vaccine in SIAs, which induces improved immune responses to type 1 and type 3 polioviruses by removing the interfering type 2 OPV viruses from the formulation [20]. The monovalent and bivalent formulations were instrumental in control of polio in India.

Vaccine-derived polioviruses — Another challenge is circulation of vaccine-derived polioviruses (VDPVs); this was first recognized during an outbreak of poliomyelitis caused by a poliovirus derived from type 1 OPV vaccine occurring on the island of Hispaniola in 2000 [21]. The availability of viral genetic sequencing subsequently uncovered other circulating vaccine-derived poliovirus (cVDPV) outbreaks including extensive transmission of a type 2 VDPV virus in Egypt in the 1980s and periodic outbreaks caused by all three OPV types in multiple locations with low population immunity that permits ongoing person-to-person transmission [21,22]. (See "Poliomyelitis and post-polio syndrome", section on 'Epidemiology'.)

By convention, VDPV viruses diverge by ≥1.0 percent in the VP1 coding region compared with the parent OPV strains (≥0.6 percent for type 2), signifying ongoing transmission for ≥6 to 12 months. Since 2005, more than 80 percent of cases occurring during cVDPV outbreaks have been caused by type 2 OPV virus.

In addition, prolonged OPV virus replication in individuals with inherited B cell immunodeficiencies has rarely been associated with excretion of VDPV viruses (immunodeficiency-associated VDPVs) [23].

The recognition of VDPVs dictates that all OPV use will need to cease to achieve full polio eradication.

PROGRESS — Between 1988 and 2013, the annual global incidence of poliomyelitis fell by >99.9 percent (from more than 350,000 cases to fewer than 1000 cases). Since 2012, all naturally occurring wild type cases have been caused by wild-type 1 poliovirus (WPV1).

India was certified by the World Health Organization in 2014 to have eradicated polio, a monumental achievement by a country that once harbored 85 percent of the global polio burden. In August 2020, the World Health Organization (WHO) declared Africa free of wild-type polio following four years without evidence of transmission. However, a new WPV1 case emerged in Malawi in November 2021, followed by eight cases in Mozambique, where circulation continues as of November 2022. The new African cases are genetically related to contemporary WPV1 viruses in Pakistan [2,3,24]. Worldwide, the annual number of reported WPV1 cases reached an historic low of only two cases in 2021 before rebounding in 2022 in the wake of the coronavirus pandemic.

Synchronized global withdrawal of oral poliovirus vaccine (OPV) began with removal of type 2 OPV from the trivalent vaccine in April 2016. Within two months, the prevalence of serotype 2 poliovirus in surveyed stool samples declined from 3.9 to 0.2 percent, and the detection rate in sewage samples declined from 71 to 13 percent [25]. Initially, as expected, a small number of VDPV2 outbreaks were identified and thought to have originated from tOPV2 use prior to the "switch" to bOPV [3].

However, ongoing use of monovalent (mOPV2) in response to VDPV2 outbreaks carries an increasing risk of seeding new VDPV2 outbreaks in the context of growing cohorts of infants and children without immunity to type 2 poliovirus. Between 2017 and November 2022, VDPV2 transmission has been reported in 46 countries causing more than 2600 acute flaccid paralysis cases. Sub-Saharan African countries are most affected, but AFP cases have also occurred in Syria, Afghanistan, Pakistan, Tajikistan, China, Philippines, and the United States. Some outbreaks have been controlled by deployment of mOPV2 vaccine in campaigns, but others continue to spread in susceptible populations representing a major challenge to the eradication program given the extent of spread and limited supply of mOPV2 vaccine [3]. In response, a novel OPV2 vaccine, designed to be genetically stable and less likely to generate VDPV2 viruses, received a WHO Emergency Use Listing in November 2020 and has since been deployed in 21 countries [26,27].

ENDGAME STRATEGY — Because of an uncertain risk of circulating vaccine-derived poliovirus (cVDPV) reemergence from residual oral poliovirus type 2 circulation and from immunodeficient, long-term VDPV excretors, two inactivated poliovirus vaccine (IPV) doses at 14 weeks and 9 months of age have been added to the recommended Expanded Program on Immunization (EPI) schedule for oral polio vaccine (OPV)-using countries in addition to routine bivalent OPV (bOPV) doses at 6, 10, and 14 weeks of age [28]. This schedule provides seroconversion rates ≥97 percent for all three poliovirus serotype by nine months of age [29-31].

Conventional wisdom associates intestinal mucosal immunity, which reduces poliovirus excretion and person-to-person transmission, to OPV alone. However, studies in India have shown that IPV administered to children previously given OPV boosts both humoral neutralizing antibody and intestinal mucosal immunity as measured by bivalent OPV challenge [32,33].

Although virtually all high-income and many middle-income countries have eliminated polio with IPV alone, it is questionable whether similar success can be achieved in locations challenged by crowding and poor sanitation. Experience in Israel with prolonged detection of type 1 polioviruses in sewage effluents has generated substantial concern that IPV-induced intestinal immunity may not prevent silent transmission despite high immunization rates, and that infection could spread extensively before the first clinical case is detected [34].

Assuming success of the eradication program, all countries will rely on IPV alone to prevent poliovirus after total OPV withdrawal [4]. In April 2017, the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) recommended that countries currently using bOPV plan to replace all OPV with 2 IPV doses at 14 weeks and approximately 9 months of age. Furthermore, SAGE recommended that IPV continue to be included in routine immunization schedules for a minimum of 10 years following certification of eradication. How long IPV vaccination will continue thereafter will be based on projected risk of recurrent polio, cost, and feasibility. The availability of affordable standalone IPV and IPV-containing combination vaccines will continue to guide the IPV market during this period.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Polio".)

SUMMARY

●The Global Polio Eradication Initiative (GPEI) partnership is led by five organizations: the World Health Organization, the United States Centers for Disease Control and Prevention, the United Nations Children's Fund, Rotary International, the Bill and Melinda Gates Foundation, and Gavi, the vaccine alliance. (See 'Global eradication partnership' above.)

●The GPEI deploys four strategies: routine infant immunization, supplementary immunization campaigns in many middle- and low-income countries, surveillance for acute flaccid paralysis, and mop-up campaigns. (See 'Eradication strategies' above.)

●The annual global incidence of poliomyelitis has fallen by >99.9 percent from more than 350,000 cases when the GPEI was launched in 1988 to 361 cases, including circulating vaccine-derived poliovirus (cVDPV) cases, in 2021. (See 'Progress' above.)

●Two countries have never eliminated polio: Pakistan and Afghanistan. More than 40 countries have experienced reintroduction of wild-type 1 poliovirus (WPV1) polio from endemic areas or spread of cVDPV viruses because of low population immunity. (See 'Challenges to eradication' above.)

●The GPEI "endgame" strategy calls for cessation of circulation of wild-type poliovirus and type 2 circulating vaccine-derived poliovirus, replacement of trivalent oral polio vaccine with bivalent oral polio vaccine for an interim period after April 2016, introduction of inactivated polio vaccine for routine childhood immunization, and eventual discontinuation of all oral poliovirus vaccine use once complete eradication of all types is certified by the World Health Organization. (See 'Endgame strategy' above.)