Modelling the spread of serotype-2 vaccine derived-poliovirus outbreak in Pakistan and Afghanistan to inform outbreak control strategies in the context of the COVID-19 pandemic.

BACKGROUND: Since July 2019, Pakistan and Afghanistan have been facing an outbreak of serotype-2 circulating vaccine derived poliovirus (cVDPV2) in addition to continued transmission of serotype-1 wild poliovirus (WPV1) and SARS-CoV-2 in 2020. Understanding the risks of cVDPV2 transmission due to pause of global vaccination efforts and the impact of potential vaccination response strategies in the current context of COVID-19 mitigation measures is critical. METHODS: We developed a stochastic, geographically structured mathematical model of cVDPV2 transmission which captures both mucosal and humoral immunity separately and allows for reversion of serotype-2 oral polio vaccine (OPV2) virus to cVDPV2 following vaccine administration. The model includes geographic heterogeneities in vaccination coverage, population immunity and population movement. The model was fitted to historic cVDPV2 cases in Pakistan and Afghanistan between January 2010-April 2016 and July 2019-March 2020 using iterated particle filtering. The model was used to simulate spread of cVDPV2 infection from July 2019 to explore impact of various proposed vaccination responses on stopping transmission and risk of spread of reverted Sabin-2 under varying assumptions of impacts from COVID-19 lockdown measures on movement patterns as well as declines in vaccination coverage. RESULTS: Simulated monthly incidence of cVDPV2 from the best-fit model demonstrated general spatio-temporal alignment with observed cVDPV2 cases. The model predicted substantial spread of cVDPV2 infection, with widespread transmission through 2020 in the absence of any vaccination activities. Vaccination responses were predicted to substantially reduce transmission and case burden, with a greater impact from earlier responses and those with larger geographic scope. While the greatest risk of seeding reverted Sabin-2 was predicted in areas targeted with OPV2, subsequent spread was greatest in areas with no or delayed response. The proposed vaccination strategy demonstrated ability to stop the cVDPV2 outbreak (with low risk of reverted Sabin-2 spread) by February 2021. CONCLUSION: Outbreak response vaccination campaigns against cVDPV2 will be challenging throughout the COVID-19 pandemic but must be implemented urgently when feasible to stop transmission of cVDPV2.

Progress Toward Poliovirus Containment Implementation - Worldwide, 2019-2020.

Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases has declined from 350,000 in 125 countries to 176 in only two countries in 2019 (1). The Global Commission for the Certification of Poliomyelitis Eradication (GCC) declared two of the three WPV types, type 2 (WPV2) and type 3 (WPV3), eradicated globally in 2015 and 2019, respectively (1). Wild poliovirus type 1 (WPV1) remains endemic in Afghanistan and Pakistan (1). Containment under strict biorisk management measures is vital to prevent reintroduction of eradicated polioviruses into communities from poliovirus facilities. In 2015, Member States committed to contain type 2 polioviruses (PV2) in poliovirus-essential facilities (PEFs) certified in accordance with a global standard (2). Member states agreed to report national PV2 inventories annually, destroy unneeded PV2 materials, and, if retaining PV2 materials, establish national authorities for containment (NACs) and a PEF auditing process. Since declaration of WPV3 eradication in October 2019, these activities are also required with WPV3 materials. Despite challenges faced during 2019-2020, including the coronavirus disease 2019 (COVID-19) pandemic, the global poliovirus containment program continues to work toward important milestones. To maintain progress, all WHO Member States are urged to adhere to the agreed containment resolutions, including officially establishing legally empowered NACs and submission of PEF Certificates of Participation.

Progress Toward Polio Eradication - Worldwide, January 2018-March 2020.

Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.

Progress Toward Poliovirus Containment Implementation - Worldwide, 2018-2019.

Among the three wild poliovirus (WPV) types, type 2 (WPV2) was declared eradicated globally by the Global Commission for the Certification of Poliomyelitis Eradication (GCC) in 2015. Subsequently, in 2016, a global withdrawal of Sabin type 2 oral poliovirus vaccine (OPV2) from routine use, through a synchronized switch from the trivalent formulation of oral poliovirus vaccine (tOPV, containing vaccine virus types 1, 2, and 3) to the bivalent form (bOPV, containing types 1 and 3), was implemented. WPV type 3 (WPV3), last detected in 2012 (1), will possibly be declared eradicated in late 2019.* To ensure that polioviruses are not reintroduced to the human population after eradication, World Health Organization (WHO) Member States committed in 2015 to containing all polioviruses in poliovirus-essential facilities (PEFs) that are certified to meet stringent containment criteria; implementation of containment activities began that year for facilities retaining type 2 polioviruses (PV2), including type 2 oral poliovirus vaccine (OPV) materials (2). As of August 1, 2019, 26 countries have nominated 74 PEFs to retain PV2 materials. Twenty-five of these countries have established national authorities for containment (NACs), which are institutions nominated by ministries of health or equivalent bodies to be responsible for poliovirus containment certification. All designated PEFs are required to be enrolled in the certification process by December 31, 2019 (3). When GCC certifies WPV3 eradication, WPV3 and vaccine-derived poliovirus (VDPV) type 3 materials will also be required to be contained, leading to a temporary increase in the number of designated PEFs. When safer alternatives to wild and OPV/Sabin strains that do not require containment conditions are available for diagnostic and serologic testing, the number of PEFs will decrease. Facilities continuing to work with polioviruses after global eradication must minimize the risk for reintroduction into communities by adopting effective biorisk management practices.

Facility-Associated Release of Polioviruses into Communities-Risks for the Posteradication Era.

The Global Polio Eradication Initiative continues to make progress toward the eradication target. Indigenous wild poliovirus (WPV) type 2 was last detected in 1999, WPV type 3 was last detected in 2012, and over the past 2 years WPV type 1 has been detected only in parts of 2 countries (Afghanistan and Pakistan). Once the eradication of poliomyelitis is achieved, infectious and potentially infectious poliovirus materials retained in laboratories, vaccine production sites, and other storage facilities will continue to pose a risk for poliovirus reintroduction into communities. The recent breach in containment of WPV type 2 in an inactivated poliovirus vaccine manufacturing site in the Netherlands prompted this review, which summarizes information on facility-associated release of polioviruses into communities reported over >8 decades. Successful polio eradication requires the management of poliovirus containment posteradication to prevent the consequences of the reestablishment of poliovirus transmission.

Progress Toward Poliovirus Containment Implementation - Worldwide, 2017-2018.

Substantial progress has been made since the World Health Assembly (WHA) resolved to eradicate poliomyelitis in 1988 (1). Among the three wild poliovirus (WPV) types, type 2 (WPV2) was declared eradicated in 2015, and type 3 (WPV3) has not been reported since 2012 (1). In 2017 and 2018, only Afghanistan and Pakistan have reported WPV type 1 (WPV1) transmission (1). When global eradication of poliomyelitis is achieved, facilities retaining poliovirus materials need to minimize the risk for reintroduction of poliovirus into communities and reestablishment of transmission. Poliovirus containment includes biorisk management requirements for laboratories, vaccine production sites, and other facilities that retain polioviruses after eradication; the initial milestones are for containment of type 2 polioviruses (PV2s). At the 71st WHA in 2018, World Health Organization (WHO) Member States adopted a resolution urging acceleration of poliovirus containment activities globally, including establishment by the end of 2018 of national authorities for containment (NACs) to oversee poliovirus containment (2). This report summarizes containment progress since the previous report (3) and outlines remaining challenges. As of August 2018, 29 countries had designated 81 facilities to retain PV2 materials; 22 of these countries had established NACs. Although there has been substantial progress, intensification of containment measures is needed.

Type 2 Poliovirus Detection after Global Withdrawal of Trivalent Oral Vaccine.

BACKGROUND: Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses. METHODS: We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine-derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2. RESULTS: The prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries. CONCLUSIONS: High population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.).

Global Polio Eradication - Way Ahead.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis by the year 2000. Although substantial progress was achieved by 2000, global polio eradication proved elusive. In India, the goal was accomplished in 2011, and the entire South-East Asia Region was certified as polio-free in 2014. The year 2016 marks the lowest wild poliovirus type 1 case count ever, the lowest number of polio-endemic countries (Afghanistan, Nigeria and Pakistan), the maintenance of wild poliovirus type 2 eradication, and the continued absence of wild poliovirus type 3 detection since 2012. The year also marks the Global Polio Eradication Initiative (GPEI) moving into the post-cessation of Sabin type 2, after the effort of globally synchronized withdrawal of Sabin type 2 poliovirus in April 2016. Sustained efforts will be needed to ensure polio eradication is accomplished, to overcome the access and security issues, and continue to improve the quality and reach of field operations. After that, surveillance (the "eyes and ears") will move further to the center stage. Sensitive surveillance will monitor the withdrawal of all Sabin polioviruses, and with facility containment, constitute the cornerstones for eventual global certification of wild poliovirus eradication. An emergency response capacity is essential to institute timely control measures should polio still re-emerge. Simultaneously, the public health community needs to determine whether and how to apply the polio-funded infrastructure to other priorities (after the GPEI funding has stopped). Eradication is the primary goal, but securing eradication will require continued efforts, dedicated resources, and a firm commitment by the global public health community.

Exceptional Financial Support for Introduction of Inactivated Polio Vaccine in Middle-Income Countries.

In May 2012, the World Health Assembly declared the completion of poliovirus eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. The Polio Eradication and Endgame Strategic Plan 2013-2018 was developed in response to this call and demands that all countries using Oral Polio Vaccine (OPV) only introduce at least 1 dose of Inactivated Polio Vaccine (IPV) into routine immunization schedules by the end of 2015. In November 2013, the Board of Gavi (the Vaccine Alliance) approved the provision of support for IPV introduction in the 72 Gavi-eligible countries. Following analytical work and stakeholder consultations, the IPV Immunization Systems Management Group (IMG) presented a proposal to provide exceptional financial support for IPV introduction to additional OPV-only using countries not eligible for Gavi support and that would otherwise not be able to mobilize the necessary financial resources within the Polio Eradication and Endgame Strategic Plan timelines. In June 2014, the Polio Oversight Board (POB) agreed to make available a maximum envelope of US $45 million toward supporting countries not eligible for Gavi funding. This article describes the design of the funding mechanism that was developed, its implementation and the lessons learned through this process.

Polio Endgame: Lessons Learned From the Immunization Systems Management Group.

The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere.

Progress Toward Containment of Poliovirus Type 2 - Worldwide, 2017.

The Global Polio Eradication Initiative (GPEI) continues to make progress toward the eradication target. Only one of the three serotypes, wild poliovirus (WPV) type 1 (WPV1), is still circulating, and the numbers of cases and countries with endemic transmission are at record lows. With the certification of wild poliovirus type 2 (WPV2) eradication in 2015 and the global replacement of trivalent oral poliovirus vaccine (tOPV) containing Sabin poliovirus types 1, 2, and 3 with bivalent OPV containing only Sabin poliovirus types 1 and 3 during April-May 2016, poliovirus type 2 (PV2) is now an eradicated pathogen. However, in eight countries (Cameroon, Chad, Democratic Republic of Congo, Mozambique, Niger, Nigeria, Pakistan, and Syria), monovalent type 2 OPV (mOPV2) was authorized for large-scale outbreak control after tOPV withdrawal (1). Poliovirus containment, an evolving area of work that affects every country, aims to ensure that all PV2 specimens are safely contained to minimize the risk for reintroducing the virus into communities. This report summarizes the current status of poliovirus containment and progress since the last report (2), and outlines remaining challenges. Within 30 countries, 86 facilities have been designated by the relevant national authorities (usually the Ministry of Health) to become poliovirus-essential facilities for the continued storage or handling of PV2 materials; each country is responsible for ensuring that these facilities meet all biorisk management requirements.

Polio endgame: the global switch from tOPV to bOPV.

Globally, polio cases have reached an all-time low, and type 2 poliovirus (one of three) is eradicated. Oral polio vaccine (OPV) has been the primary tool, however, in rare cases, OPV induces paralysis. In 2013, the World Health Assembly endorsed the phased withdrawal of OPV and introduction of inactivated poliovirus vaccine (IPV) into childhood routine immunization schedules. Type 2 OPV will be withdrawn through a globally synchronized "switch" from trivalent OPV (all three types) to bivalent OPV (types 1 and 3). The switch will happen in 155 OPV-using countries between April 17(th) and May 1(st), 2016. Planned activities to reduce type 2 outbreak risks post-switch include the following: tOPV campaigns to increase type 2 immunity prior to the switch, monovalent OPV2 stockpiling to respond to outbreaks should they occur, containment of both wild and vaccine type 2 viruses, enhanced acute flaccid paralysis (AFP) and environmental surveillance, outbreak response protocols, and ensured access to IPV and bivalent OPV.

Outsourcing vaccine logistics to the private sector: The evidence and lessons learned from the Western Cape Province in South-Africa.

With few exceptions, immunization supply chains in developing countries continue to face chronic difficulties in providing uninterrupted availability of potent vaccines up to service delivery levels, and in the most efficient manner possible. As these countries struggle to keep pace with an ever growing number of vaccines, more and more Ministries of Health are considering options of engaging the private sector to manage vaccine storage, handling and distribution on their behalf. Despite this emerging trend, there is limited evidence on the benefits or challenges of this option to improve public supply chain performance for national immunization programmes. To bridge this knowledge gap, this study aims to shed light on the value proposition of outsourcing by documenting the specific experience of the Western Cape Province of South Africa. The methodology for this review rested on conducting two key supply chain assessments which allowed juxtaposing the performance of the government managed segments of the vaccine supply chain against those managed by the private sector. In particular, measures of effective vaccine management best practice and temperature control in the cold chain were analysed. In addition, the costs of engaging the private sector were analysed to get a better understanding of the economics underpinning outsourcing vaccine logistics. The results from this analysis confirmed some of the theoretical benefits of outsourcing to the private sector. Yet, if the experience in the Western Cape can be deemed a successful one, there are several policy and practice implications that developing countries should be mindful of when considering engaging the private sector. While outsourcing can help improve the performance of the vaccine supply chain, it has the potential to do the reverse if done incorrectly. The findings and lessons learnt from the Western Cape experience can serve as a step towards understanding the role of the private sector in immunization supply chain and logistics systems for developing countries.

Polio endgame: the global introduction of inactivated polio vaccine.

In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses.

Reducing the loss of vaccines from accidental freezing in the cold chain: the experience of continuous temperature monitoring in Tunisia.

Accidental freezing of vaccines is a growing threat and a real risk for national immunization programs when the potency of many vaccines can be compromised if these are exposed to sub-zero temperatures in the cold chain. In Tunisia, this issue is compounded by using sub-standard domestic cold chain equipment instead of equipping the program with medical refrigerators designed specifically for storing vaccines and temperature sensitive pharmaceuticals. Against this backdrop, this paper presents the findings of a demonstration project conducted in Tunisia in 2012 that tested the impact of introducing several freeze prevention solutions to mitigate the risk of accidental freezing of vaccines. The main finding is that, despite the continued use of underperforming domestic refrigerators, continuous temperature monitoring using new technologies combined with other technological interventions significantly reduced the prevalence of accidental exposure to freezing temperatures. These improvements were noticed for cold chain storage at regional, district and health center levels, and during the transport legs that were part of the demonstration conducted in the regions of Kasserine in the South-Eastern part of Tunisia. Subsequent to introducing these freeze prevention solutions, the incidence of freeze alarms was reduced and the percent of time the temperatures dropped below the 2 °C recommended threshold. The incidence of freeze alarms at health center level was reduced by 40%. Lastly, the solutions implemented reduced risk of freezing during transport from 13.8% to 1.7%. Although the solution implemented is not optimal in the longer term because domestic refrigerators are used extensively in district stores and health centers, the risk of accidental freezing is significantly reduced by introducing the practice of continuous temperature monitoring as a standard. The management of the cold chain equipment was strengthened as a result which helps protect the potency of vaccines to the areas of most difficult access.

Optimizing energy for a 'green' vaccine supply chain.

This paper describes an approach piloted in the Kasserine region of Tunisia to increase the energy efficiency of the distribution of vaccines and temperature sensitive drugs. The objectives of an approach, known as the 'net zero energy' (NZE) supply chain were demonstrated within the first year of operation. The existing distribution system was modified to store vaccines and medicines in the same buildings and to transport them according to pre-scheduled and optimized delivery circuits. Electric utility vehicles, dedicated to the integrated delivery of vaccines and medicines, improved the regularity and reliability of the supply chains. Solar energy, linked to the electricity grid at regional and district stores, supplied over 100% of consumption meeting all energy needs for storage, cooling and transportation. Significant benefits to the quality and costs of distribution were demonstrated. Supply trips were scheduled, integrated and reliable, energy consumption was reduced, the recurrent cost of electricity was eliminated and the release of carbon to the atmosphere was reduced. Although the initial capital cost of scaling up implementation of NZE remain high today, commercial forecasts predict cost reduction for solar energy and electric vehicles that may permit a step-wise implementation over the next 7-10 years. Efficiency in the use of energy and in the deployment of transport is already a critical component of distribution logistics in both private and public sectors of industrialized countries. The NZE approach has an intensified rationale in countries where energy costs threaten the maintenance of public health services in areas of low population density. In these countries where the mobility of health personnel and timely arrival of supplies is at risk, NZE has the potential to reduce energy costs and release recurrent budget to other needs of service delivery while also improving the supply chain.