Oral Poliovirus Vaccine Coverage Research Articles

Poliomyelitis in Pakistan: Evolving challenges and way forward

Poliomyelitis, an acute paralytic illness, affects children under the age of five. It is brought on by the Polio Virus (PV), a single-stranded RNA virus that comes in three serotypes (type 1, 2, and 3) which is transmitted by feco-oral route.1,2 Since 1988, there has been a 99.9% decrease in polio cases worldwide because of the World Health Organization's Global Polio Eradication initiative.1 This initiative has played a vital role in eradication of the disease. Pakistan is one of the 2 nations where polio remains as an endemic disease even at the end of 2022, the other being Afghanistan.2
 In 2021, Pakistan reported just 1 case of polio linked to the Wild Poliovirus type 1 (WPV1) against 14 cases from April 1 through July 31, 2022.2 Eleven instances of polio have been reported in the Northwestern Waziristan in 2022, clearly illustrating the loopholes in national policies to completely eradicate the disease despite its goal to immunize 12.6 million children by 2022.2 The goal of the Global Polio Eradication Initiative's (GPEI) current 5-year strategic plan is to interrupt WPV1 transmission by 2023.3
 According to WHO and UNICEF estimates, in Pakistan approximately 83% of infants received three doses of the Oral Poliovirus Vaccine (OPV) and one dose of Inactivated Poliovirus Vaccine (IPV) in 2021. While none of the districts in Baluchistan, Khyber Pakhtunkhwa, and Sindh attained 80% vaccine coverage, 86% districts in Punjab province had >3 dose OPV coverage.4

Response to back-to-back outbreaks of circulating vaccine-derived poliovirus type 2 in two nomadic pastoralist settlements in Oti Region, Ghana-2019

BackgroundThe global switch from trivalent oral poliovirus vaccine (OPV) to bivalent OPV in April 2016 without corresponding co-administration of inactivated poliovirus vaccine (IPV) until June 2018, created a cohort of poliovirus type 2 naïve children with risk of developing vaccine-derived poliovirus type 2 (VDPV2). In November and December 2019, two cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) were confirmed in quick succession through Acute Flaccid Paralysis (AFP) surveillance in two nomadic pastoralist settlements in Oti Region. We investigated to determine the outbreak extent, identify risk factors and implement control and preventive measures.MethodsWe interviewed case-patients’ families, abstracted immunization records, assessed AFP surveillance and conducted rapid OPV and IPV vaccination coverage surveys. Using AFP case definition of any child less than 15 years in the community with sudden onset of paralysis from July to November 2019 (in case-patient 1’s district) and August to December 2019 (in case-patient 2’s district), we conducted active case search. Stool samples from apparently healthy children and close contacts of the case-patients were collected and tested for poliovirus. We conducted environmental assessment of the community to identify potential risk factors.ResultsCase-patient 1 was an eight-year-old female who had taken two doses of OPV while case-patient 2 was an eight-month-old male who had taken three out of required four OPV doses in addition to IPV at seven months. Families of both case-patients had either travelled to or received visitors from areas with confirmed cVDPV2. Of all children surveyed, eight (29.6%) of 27 and three (18.8%) of 16 eligible children in communities of case-patient 1 and 2 respectively had received required four doses of OPV. No AFP case was found in both communities and surrounding settlements. Both communities had no source of potable water and toilet facilities. A stool sample from a contact of case-patient 1 tested positive for cVDPV2.ConclusionOutbreaks of cVDPV2 occurred in insanitary, under-vaccinated nomadic pastoralist settlements in Oti Region. Three rounds of monovalent OPV vaccination campaigns for children under 5 years of age in the districts and region as well as countrywide IPV vaccination campaign for poliovirus type 2 naïve cohort were conducted.

A Health Economic Analysis for Oral Poliovirus Vaccine to Prevent COVID-19 in the United States.

COVID‐19 led to a recent high‐profile proposal to reintroduce oral poliovirus vaccine (OPV) in the United States (U.S.), initially in clinical trials, but potentially for widespread and repeated use. We explore logistical challenges related to U.S. OPV administration in 2020, review the literature related to nonspecific effects of OPV to induce innate immunity, and model the health and economic implications of the proposal. The costs of reintroducing a single OPV dose to 331 million Americans would exceed $4.4 billion. Giving a dose of bivalent OPV to the entire U.S. population would lead to an expected 40 identifiable cases of vaccine‐associated paralytic polio, with young Americans at the highest risk. Reintroducing any OPV use in the U.S. poses a risk of restarting transmission of OPV‐related viruses and could lead to new infections in immunocompromised individuals with B‐cell related primary immunodeficiencies that could lead to later cases of paralysis. Due to the lack of a currently licensed OPV in the U.S., the decision to administer OPV to Americans for nonspecific immunological effects would require purchasing limited global OPV supplies that could impact polio eradication efforts. Health economic modeling suggests no role for reintroducing OPV into the U.S. with respect to responding to COVID‐19. Countries that currently use OPV experience fundamentally different risks, costs, and benefits than the U.S. Successful global polio eradication will depend on sufficient OPV supplies, achieving and maintaining high OPV coverage in OPV‐using countries, and effective global OPV cessation and containment in all countries, including the U.S.

Update on Immunodeficiency-Associated Vaccine-Derived Polioviruses - Worldwide, July 2018-December 2019.

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.

Strategic Response to an Outbreak of Circulating Vaccine-Derived Poliovirus Type 2 - Syria, 2017-2018.

Since the 1988 inception of the Global Polio Eradication Initiative (GPEI), progress toward interruption of wild poliovirus (WPV) transmission has occurred mostly through extensive use of oral poliovirus vaccine (OPV) in mass vaccination campaigns and through routine immunization services (1,2). However, because OPV contains live, attenuated virus, it carries the rare risk for reversion to neurovirulence. In areas with very low OPV coverage, prolonged transmission of vaccine-associated viruses can lead to the emergence of vaccine-derived polioviruses (VDPVs), which can cause outbreaks of paralytic poliomyelitis. Although WPV type 2 has not been detected since 1999, and was declared eradicated in 2015,* most VDPV outbreaks have been attributable to VDPV serotype 2 (VDPV2) (3,4). After the synchronized global switch from trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (types 1 and 3) in April 2016 (5), GPEI regards any VDPV2 emergence as a public health emergency (6,7). During May-June 2017, VDPV2 was isolated from stool specimens from two children with acute flaccid paralysis (AFP) in Deir-ez-Zor governorate, Syria. The first isolate differed from Sabin vaccine virus by 22 nucleotides in the VP1 coding region (903 nucleotides). Genetic sequence analysis linked the two cases, confirming an outbreak of circulating VDPV2 (cVDPV2). Poliovirus surveillance activities were intensified, and three rounds of vaccination campaigns, aimed at children aged <5 years, were conducted using monovalent OPV type 2 (mOPV2). During the outbreak, 74 cVDPV2 cases were identified; the most recent occurred in September 2017. Evidence indicates that enhanced surveillance measures coupled with vaccination activities using mOPV2 have interrupted cVDPV2 transmission in Syria.

Update on Vaccine-Derived Polioviruses - Worldwide, January 2016-June 2017.

In 1988, the World Health Assembly launched the Global Polio Eradication Initiative (GPEI) (1). Among the three wild poliovirus (WPV) serotypes, only type 1 (WPV1) has been detected since 2012. Since 2014, detection of WPV1 has been limited to three countries, with 37 cases in 2016 and 11 cases in 2017 as of September 27. The >99.99% decline worldwide in polio cases since the launch of the GPEI is attributable to the extensive use of the live, attenuated oral poliovirus vaccine (OPV) in mass vaccination campaigns and comprehensive national routine immunization programs. Despite its well-established safety record, OPV use can be associated with rare emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (2). VDPVs can also emerge among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) can emerge very rarely among immunologically normal vaccine recipients and their contacts in areas with inadequate OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (3). During January 2016-June 2017, new cVDPV outbreaks were identified, including two in the Democratic Republic of the Congo (DRC) (eight cases), and another in Syria (35 cases), whereas the circulation of cVDPV type 2 (cVDPV2) in Nigeria resulted in cVDPV2 detection linked to a previous emergence. The last confirmed case from the 2015-2016 cVDPV type 1 (cVDPV1) outbreak in Laos occurred in January 2016. Fourteen newly identified persons in 10 countries were found to excrete iVDPVs, and three previously reported patients in the United Kingdom and Iran (3) were still excreting type 2 iVDPV (iVDPV2) during the reporting period. Ambiguous VDPVs (aVDPVs), isolates that cannot be classified definitively, were found among immunocompetent persons and environmental samples in 10 countries. Cessation of all OPV use after certification of polio eradication will eliminate the risk for new VDPV infections.

Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4).

Vaccine-Derived Polioviruses

The attenuated oral poliovirus vaccine (OPV) has many properties favoring its use in polio eradication: ease of administration, efficient induction of intestinal immunity, induction of durable humoral immunity, and low cost. Despite these advantages, OPV has the disadvantage of genetic instability, resulting in rare and sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) and the emergence of genetically divergent vaccine-derived polioviruses (VDPVs). Whereas VAPP is an adverse event following exposure to OPV, VDPVs are polioviruses whose genetic properties indicate prolonged replication or transmission. Three categories of VDPVs are recognized: (1) circulating VDPVs (cVDPVs) from outbreaks in settings of low OPV coverage, (2) immunodeficiency-associated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVDPVs), which cannot be definitively assigned to either of the first 2 categories. Because most VDPVs are type 2, the World Health Organization's plans call for coordinated worldwide replacement of trivalent OPV with bivalent OPV containing poliovirus types 1 and 3.

Clustered lot quality assurance sampling: a pragmatic tool for timely assessment of vaccination coverage

To evaluate oral poliovirus vaccine (OPV) coverage of the November 2009 round in five Northern Nigeria states with ongoing wild poliovirus transmission using clustered lot quality assurance sampling (CLQAS). We selected four local government areas in each pre-selected state and sampled six clusters of 10 children in each Local Government Area, defined as the lot area. We used three decision thresholds to classify OPV coverage: 75-90%, 55-70% and 35-50%. A full lot was completed, but we also assessed in retrospect the potential time-saving benefits of stopping sampling when a lot had been classified. We accepted two local government areas (LGAs) with vaccination coverage above 75%. Of the remaining 18 rejected LGAs, 11 also failed to reach 70% coverage, of which four also failed to reach 50%. The average time taken to complete a lot was 10 h. By stopping sampling when a decision was reached, we could have classified lots in 5.3, 7.7 and 7.3 h on average at the 90%, 70% and 50% coverage targets, respectively. Clustered lot quality assurance sampling was feasible and useful to estimate OPV coverage in Northern Nigeria. The multi-threshold approach provided useful information on the variation of IPD vaccination coverage. CLQAS is a very timely tool, allowing corrective actions to be directly taken in insufficiently covered areas.

VACCINE-DERIVED POLIOVIRUSES AND THE ENDGAME STRATEGY FOR GLOBAL POLIO ERADICATION

As the global eradication of wild poliovirus nears, the World Health Organization (WHO) is addressing challenges unprecedented in public health. The live, attenuated oral poliovirus vaccine (OPV), used for more than four decades to interrupt poliovirus transmission, and the vaccine of choice for developing countries, is genetically unstable. Reversion of the small number of substitutions conferring the attenuated phenotype frequently occurs during OPV replication in humans and is the underlying cause of the rare cases of vaccine-associated paralytic poliomyelitis (VAPP) in OPV recipients and their close contacts. Whereas VAPP has long been recognized, two other adverse events have been identified more recently: (a) long-term excretion of highly evolved vaccine-derived polioviruses (VDPVs) in persons with primary immunodeficiencies, and (b) polio outbreaks associated with circulating VDPVs in areas with low rates of OPV coverage. Developing a posteradication strategy to minimize the risks of VDPV emergence and spread has become an urgent WHO priority.

Circulating vaccine-derived polioviruses: current state of knowledge.

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.

Circulation of Endemic Type 2 Vaccine-Derived Poliovirus in Egypt from 1983 to 1993

From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. Complete genomic sequences of an early (1988) and a late (1993) cVDPV isolate revealed that their 5' untranslated region (5' UTR) and noncapsid- 3' UTR sequences were derived from other species C enteroviruses. Circulation of type 2 cVDPVs occurred at a time of low OPV coverage in the affected communities and ceased when OPV coverage rates increased. The potential for cVDPVs to circulate in populations with low immunity to poliovirus has important implications for current and future strategies to eradicate polio worldwide.

Massive outbreak of poliomyelitis caused by type-3 wild poliovirus in Angola in 1999.

The largest outbreak of poliomyelitis ever recorded in Africa (1093 cases) occurred from 1 March to 28 May 1999 in Luanda, Angola, and in surrounding areas. The outbreak was caused primarily by a type-3 wild poliovirus, although type-1 wild poliovirus was circulating in the outbreak area at the same time. Infected individuals ranged in age from 2 months to 22 years; 788 individuals (72%) were younger than 3 years. Of the 590 individuals whose vaccination status was known, 23% had received no vaccine and 54% had received fewer than three doses of oral poliovirus vaccine (OPV). The major factors that contributed to this outbreak were as follows: massive displacement of unvaccinated persons to urban settings; low routine OPV coverage; inaccessible populations during the previous three national immunization days (NIDs); and inadequate sanitation. This outbreak indicates the urgent need to improve accessibility to all children during NIDs and the dramatic impact that war can have by displacing persons and impeding access to routine immunizations. The period immediately after an outbreak provides an enhanced opportunity to eradicate poliomyelitis. If continuous access in all districts for acute flaccid paralysis surveillance and supplemental immunizations cannot be assured, the current war in Angola may threaten global poliomyelitis eradication.

Progress toward Poliomyelitis Eradication—Africa, 1996

In 1988, the World Health Assembly established a goal of eradicating poliomyelitis worldwide by the year 2000. The four strategies recommended by the World Health Organization (WHO) for polio eradication are 1) achieving and maintaining high routine vaccination coverage levels among children aged < 1 year with at least three doses of oral poliovirus vaccine (OPV); 2) developing sensitive systems of epidemiologic and laboratory surveillance, including establishing acute flaccid paralysis (AFP) surveillance; 3) administering supplementary doses of OPV to all young children (usually those aged < 5 years) during National Immunization Days (NIDs) to rapidly interrupt wild poliovirus transmission; and 4) conducting "mopping-up" vaccination campaigns--localized campaigns targeting high-risk areas where poliovirus transmission is most likely to persist at low levels. Eradicating polio from Africa remains one of the major challenges to global eradication by the target date. This report summarizes progress achieved in 1996 toward polio eradication in Africa with the implementation of supplemental vaccination activities; the reported OPV coverage during the NIDs or Subnational Immunization Days (SNIDs) was > 80% in the target age group in most countries, and the estimated cost was $0.50 per child vaccinated during NIDs.

Current status of polio eradication in Southern Africa.

During the 1990s, poliomyelitis transmission in 11 mainland and island nations of southern Africa appeared relatively low. However, the implementation of specific strategies recommended by the World Health Organization for eradicating polio in southern Africa began only in 1994. In 1995, oral poliovirus vaccine coverage (three doses) among infants was > or = 75% in all but 4 countries. National immunization days (NIDs) to control polio outbreaks were carried out in Namibia in 1994 and 1995. Angola, Botswana, and South Africa carried out subnational NIDs in 1995. All countries in southern Africa except Madagascar planned NIDs in 1996. Epidemiologic surveillance of acute flaccid paralysis (AFP) and laboratory surveillance of wild poliovirus was launched after nationwide training workshops in 7 mainland countries and is planned in the remaining countries by the end of 1996. Analysis of recommended performance indicators of AFP surveillance shows that substantial progress was made during 1994-1995, and the prospects for the certification of polio-free status in southern Africa on target appear good.

Update: Mass Vaccination With Oral Poliovirus Vaccine—Asia and Europe, 1996

In 1995, a group of 18 geographically contiguous countries in Europe, Central and South Asia, and the Middle East cooperated in conducting coordinated National Immunization Days (NIDs) with oral poliovirus vaccine (OPV). The World Health Organization (WHO) had designated this effort "Operation MECACAR" (MEditerranean, CAucasus, and Central Asian Republics). Operation MECACAR was repeated in 1996 with the addition of the Russian Federation. This report describes OPV coverage achieved during the mass vaccination campaign in 1996 and summarizes the impact of the NIDs on poliomyelitis incidence during 1995, and the first 6 months of 1996.