Eye on ID

Approaching polio eradication: Endgame hiccups

It has now been 30 years since the official worldwide launch of the Global Polio Eradication Initiative, or GPEI, in 1988. At the time of the launch of the GPEI, estimates of the toll of polio were higher than 350,000 cases per year. It was believed that eradication would be “easy” with the widespread use of the trivalent oral polio vaccine, which includes live-attenuated vaccine viruses of polio type 1, type 2 and type 3.

Marjorie P. Pollack
Donald Kaye

The Pan American Health Organization began an eradication initiative in 1985, and by 1991 had interrupted transmission of the wild poliovirus (WPV) in the Americas region. The last known case of polio due to WPV type 2 (WPV2) occurred in India, with onset in October 1999, and the last known case of polio due to WPV type 3 (WPV3) occurred in Nigeria in November 2012 — both major successes in the polio eradication effort. Global eradication of WPV2 was declared on Sept. 20, 2015.

Now, there are three remaining countries in the world that have not interrupted transmission of WPV — Afghanistan, Pakistan and Nigeria. All three countries are experiencing civil unrest in which anti-government groups are preventing vaccination efforts, a problem compounded by public mistrust of vaccination, with some believing that the vaccines are part of a Western plot to sterilize children, along with other such deterrent stories. In addition, there has been violence against the vaccinators resulting in fatalities and serious injuries in all three countries.

The oral polio vaccine (OPV) has been considered an ideal vaccine to use for the eradication effort. It is inexpensive and can be easily administered by mouth as drops by health workers who do not require a high level of training or skill. The vaccine also produces intestinal immunity, thereby blocking transmission of WPV, and confers immunity to unvaccinated individuals. In the early days of the eradication efforts (back in the 1980s and 1990s), vaccine-associated paralytic polio cases were known to occur in OPV recipients and their contacts. The estimated rate of occurrence ranged from 1 per 700,000 to 1 per 3.4 million first doses administered for vaccine recipients and less than half of that for contacts of vaccine recipients.

To complicate matters further, during the eradication effort, a new classification of polioviruses was identified. These viruses belonged to a group known as vaccine-derived polioviruses (VDPV). VDPVs are OPV virus strains that are more than 1% divergent from the corresponding OPV strain in the complete VP1 genomic region (the major capsid protein). The VDPVs were further subdivided into three different groups (see Table 1) — circulating vaccine-derived polioviruses (cVDPVs), immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and ambiguous vaccine-derived polioviruses (aVDPVs).

Hence, some of the very same traits that made OPV an ideal vaccine for the eradication effort — namely, its ability to vaccinate more individuals than the actual intended recipients of the vaccine — became a liability during outbreaks of paralytic poliolike disease associated with cVDPVs. Initial eradication efforts targeted WPVs, and multiple rounds of mass vaccination over the years worked. However, in some countries, “fatigue” set in, and vaccination coverage dropped below levels sufficient to prevent continued circulation of the vaccine viruses, setting up the ideal environment for development of the cVDPVs. Putting this into perspective, preliminary data from polio surveillance activities for 2017 indicate that there was a total of 22 WPV-associated cases of polio worldwide coming from two countries — Afghanistan and Pakistan — and 95 cases of cVDPV type 2 (cVDPV2) reported from two countries — Syria and the Democratic Republic of the Congo (see Table 2). Hence, the polio eradication effort is now aimed at eradication of both WPV and cVDPVs. Of the cVDPVs, cVDPV2 has been the most frequently associated with outbreaks (90% of cVDPVs isolated are cVDPV2), leading to the decision to remove OPV type 2 (OPV2) from the vaccine and instead use bivalent OPV (bOPV), made of OPV type 1 (OPV1) and OPV type 3 (OPV3), a change that was implemented in April 2016. But removal of OPV2 from vaccines used in the routine immunization programs and the catch-up vaccination activities have not completely removed OPV2 from use because monovalent OPV2 (mOPV2) has been used to interrupt transmission of cVDPV2 when it was identified in outbreaks, including those in Syria and the Democratic Republic of the Congo in 2017. This created a conundrum: adding more mOPV2 into an environment with low vaccination coverage and potentially setting up a cycle of recurrence of cVDPV2.

All countries were required by WHO to introduce at least one dose of trivalent inactivated polio vaccine into their routine immunization schedules by April 2016.

Source: Shutterstock

In addition to the removal of OPV2 from immunization programs, WHO recommended that all countries using only OPV be required to introduce at least one dose of trivalent inactivated polio vaccine (IPV) into their routine schedules by April 2016, thereby mitigating the effects of removing OPV2. Unfortunately, global production of IPV did not scale up to match its increased use, leading to a shortage of the vaccine. But the switch to bOPV did occur on schedule.

So, the good news was that 2017 was the year with the lowest ever reported cases of WPV-associated disease in history. But the not-so-good news was that 2017 had some of the highest numbers of cases of cVDPV since Nigeria reported 154 in 2009.

Yet another hiccup occurred in recent years following the addition of environmental sampling for polioviruses, which includes the sampling of sewage to detect both WPV and cVDPV, indicative of circulation of the viruses in the community. In February 2013, there were positive environmental samples for WPV type 1 (WPV1) identified in southern Israel — a country that used IPV exclusively. Over the subsequent months, environmental samples were positive going in a northerly direction. No cases of paralytic polio were associated with this circulation of WPV1 (a testimony to the efficacy of the vaccination program using IPV exclusively, but at the same time showing the lowered protection against transmission of WPV by individuals vaccinated with IPV). Looking closely at results during 2017, both Afghanistan and Pakistan reported almost weekly WPV1-positive environmental samples, often in areas with no identified acute paralytic cases. In some instances, cases were confirmed in the ensuing weeks following isolation of the environmental samples, but in other instances, no cases were identified. So, although there were only 22 cases of WPV-associated disease confirmed during 2017 (all from Pakistan and Afghanistan), the identification of WPV1 in sewage samples is indicative of continued circulation of poliovirus. But a question remains: How many other countries are conducting regular environmental sampling, especially those countries considered to be “high risk” — areas where there is civil unrest, and where vaccination coverage has dropped because the circulation of poliovirus is presumed to have been interrupted (with no cases identified in a minimum of 3 years)?

To be a devil’s advocate here, is defining 3 years without a case sufficient time to declare a country free of poliovirus transmission when there are areas demonstrated through the retrospectoscope to have had silent transmission of poliovirus for 5 years? Is there any certainty that there is no circulation of either WPVs or cVDPVs in these areas? Is there sufficient environmental sampling in relatively high-risk countries — especially those with areas of civil unrest and difficult access due to safety concerns?

And lastly, another potential impending hiccup has been reported: In an article published in The Conversation on Jan. 25, Oyewale Tomori, DVM, PhD, vice-chancellor of Redeemer’s University in Nigeria, mentioned a “new round” of antivaccination rumors in Nigeria. The impact of the vaccination boycott in Nigeria from 2003 to 2005 led to a major increase in polio transmission in Nigeria, as well as spread of WPV from Nigeria to 18 countries that had been polio-free for 1 or more years, including countries outside of Africa. It is now only 1.5 years since the last identification of WPV1-associated polio in Nigeria, related to circulation in a geographic area of civil unrest with sequestered populations that could not be reached by vaccination activities.

So, the question remains, what will it take to overcome these hiccups and effectuate eradication of both WPV and cVDPVs ... global eradication of all polioviruses?

Disclosures: Kaye and Pollack report no relevant financial disclosures.

It has now been 30 years since the official worldwide launch of the Global Polio Eradication Initiative, or GPEI, in 1988. At the time of the launch of the GPEI, estimates of the toll of polio were higher than 350,000 cases per year. It was believed that eradication would be “easy” with the widespread use of the trivalent oral polio vaccine, which includes live-attenuated vaccine viruses of polio type 1, type 2 and type 3.

Marjorie P. Pollack
Donald Kaye

The Pan American Health Organization began an eradication initiative in 1985, and by 1991 had interrupted transmission of the wild poliovirus (WPV) in the Americas region. The last known case of polio due to WPV type 2 (WPV2) occurred in India, with onset in October 1999, and the last known case of polio due to WPV type 3 (WPV3) occurred in Nigeria in November 2012 — both major successes in the polio eradication effort. Global eradication of WPV2 was declared on Sept. 20, 2015.

Now, there are three remaining countries in the world that have not interrupted transmission of WPV — Afghanistan, Pakistan and Nigeria. All three countries are experiencing civil unrest in which anti-government groups are preventing vaccination efforts, a problem compounded by public mistrust of vaccination, with some believing that the vaccines are part of a Western plot to sterilize children, along with other such deterrent stories. In addition, there has been violence against the vaccinators resulting in fatalities and serious injuries in all three countries.

The oral polio vaccine (OPV) has been considered an ideal vaccine to use for the eradication effort. It is inexpensive and can be easily administered by mouth as drops by health workers who do not require a high level of training or skill. The vaccine also produces intestinal immunity, thereby blocking transmission of WPV, and confers immunity to unvaccinated individuals. In the early days of the eradication efforts (back in the 1980s and 1990s), vaccine-associated paralytic polio cases were known to occur in OPV recipients and their contacts. The estimated rate of occurrence ranged from 1 per 700,000 to 1 per 3.4 million first doses administered for vaccine recipients and less than half of that for contacts of vaccine recipients.

To complicate matters further, during the eradication effort, a new classification of polioviruses was identified. These viruses belonged to a group known as vaccine-derived polioviruses (VDPV). VDPVs are OPV virus strains that are more than 1% divergent from the corresponding OPV strain in the complete VP1 genomic region (the major capsid protein). The VDPVs were further subdivided into three different groups (see Table 1) — circulating vaccine-derived polioviruses (cVDPVs), immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and ambiguous vaccine-derived polioviruses (aVDPVs).

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Hence, some of the very same traits that made OPV an ideal vaccine for the eradication effort — namely, its ability to vaccinate more individuals than the actual intended recipients of the vaccine — became a liability during outbreaks of paralytic poliolike disease associated with cVDPVs. Initial eradication efforts targeted WPVs, and multiple rounds of mass vaccination over the years worked. However, in some countries, “fatigue” set in, and vaccination coverage dropped below levels sufficient to prevent continued circulation of the vaccine viruses, setting up the ideal environment for development of the cVDPVs. Putting this into perspective, preliminary data from polio surveillance activities for 2017 indicate that there was a total of 22 WPV-associated cases of polio worldwide coming from two countries — Afghanistan and Pakistan — and 95 cases of cVDPV type 2 (cVDPV2) reported from two countries — Syria and the Democratic Republic of the Congo (see Table 2). Hence, the polio eradication effort is now aimed at eradication of both WPV and cVDPVs. Of the cVDPVs, cVDPV2 has been the most frequently associated with outbreaks (90% of cVDPVs isolated are cVDPV2), leading to the decision to remove OPV type 2 (OPV2) from the vaccine and instead use bivalent OPV (bOPV), made of OPV type 1 (OPV1) and OPV type 3 (OPV3), a change that was implemented in April 2016. But removal of OPV2 from vaccines used in the routine immunization programs and the catch-up vaccination activities have not completely removed OPV2 from use because monovalent OPV2 (mOPV2) has been used to interrupt transmission of cVDPV2 when it was identified in outbreaks, including those in Syria and the Democratic Republic of the Congo in 2017. This created a conundrum: adding more mOPV2 into an environment with low vaccination coverage and potentially setting up a cycle of recurrence of cVDPV2.

All countries were required by WHO to introduce at least one dose of trivalent inactivated polio vaccine into their routine immunization schedules by April 2016.

Source: Shutterstock

In addition to the removal of OPV2 from immunization programs, WHO recommended that all countries using only OPV be required to introduce at least one dose of trivalent inactivated polio vaccine (IPV) into their routine schedules by April 2016, thereby mitigating the effects of removing OPV2. Unfortunately, global production of IPV did not scale up to match its increased use, leading to a shortage of the vaccine. But the switch to bOPV did occur on schedule.

PAGE BREAK

So, the good news was that 2017 was the year with the lowest ever reported cases of WPV-associated disease in history. But the not-so-good news was that 2017 had some of the highest numbers of cases of cVDPV since Nigeria reported 154 in 2009.

Yet another hiccup occurred in recent years following the addition of environmental sampling for polioviruses, which includes the sampling of sewage to detect both WPV and cVDPV, indicative of circulation of the viruses in the community. In February 2013, there were positive environmental samples for WPV type 1 (WPV1) identified in southern Israel — a country that used IPV exclusively. Over the subsequent months, environmental samples were positive going in a northerly direction. No cases of paralytic polio were associated with this circulation of WPV1 (a testimony to the efficacy of the vaccination program using IPV exclusively, but at the same time showing the lowered protection against transmission of WPV by individuals vaccinated with IPV). Looking closely at results during 2017, both Afghanistan and Pakistan reported almost weekly WPV1-positive environmental samples, often in areas with no identified acute paralytic cases. In some instances, cases were confirmed in the ensuing weeks following isolation of the environmental samples, but in other instances, no cases were identified. So, although there were only 22 cases of WPV-associated disease confirmed during 2017 (all from Pakistan and Afghanistan), the identification of WPV1 in sewage samples is indicative of continued circulation of poliovirus. But a question remains: How many other countries are conducting regular environmental sampling, especially those countries considered to be “high risk” — areas where there is civil unrest, and where vaccination coverage has dropped because the circulation of poliovirus is presumed to have been interrupted (with no cases identified in a minimum of 3 years)?

To be a devil’s advocate here, is defining 3 years without a case sufficient time to declare a country free of poliovirus transmission when there are areas demonstrated through the retrospectoscope to have had silent transmission of poliovirus for 5 years? Is there any certainty that there is no circulation of either WPVs or cVDPVs in these areas? Is there sufficient environmental sampling in relatively high-risk countries — especially those with areas of civil unrest and difficult access due to safety concerns?

And lastly, another potential impending hiccup has been reported: In an article published in The Conversation on Jan. 25, Oyewale Tomori, DVM, PhD, vice-chancellor of Redeemer’s University in Nigeria, mentioned a “new round” of antivaccination rumors in Nigeria. The impact of the vaccination boycott in Nigeria from 2003 to 2005 led to a major increase in polio transmission in Nigeria, as well as spread of WPV from Nigeria to 18 countries that had been polio-free for 1 or more years, including countries outside of Africa. It is now only 1.5 years since the last identification of WPV1-associated polio in Nigeria, related to circulation in a geographic area of civil unrest with sequestered populations that could not be reached by vaccination activities.

So, the question remains, what will it take to overcome these hiccups and effectuate eradication of both WPV and cVDPVs ... global eradication of all polioviruses?

Disclosures: Kaye and Pollack report no relevant financial disclosures.