Health and Economic Outcomes Associated with Polio Vaccine Policy Options: 2019-2029.

The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart OPV use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.

An Updated Economic Analysis of the Global Polio Eradication Initiative.

Despite a strong global commitment, polio eradication efforts continue now more than 30 years after the 1988 World Health Assembly resolution that established the Global Polio Eradication Initiative (GPEI), and 20 years after the original target of the year 2000. Prior health economic analyses estimated incremental net benefits of the GPEI of 40-50 billion in 2008 U.S. dollars (US$2008, equivalent to 48-59 billion US$2019), assuming the achievement of polio eradication by 2012. Given the delays in achieving polio eradication and increased costs, we performed an updated economic analysis of the GPEI using an updated integrated global model, and considering the GPEI trajectory as of the beginning of 2020. Applying similar methods and assuming eradication achievement in 2023, we estimate incremental net benefits of the GPEI of 28 billion US$2019, which falls below the prior estimate. Delays in achieving polio eradication combined with the widescale introduction of relatively expensive inactivated poliovirus vaccine significantly increased the costs of the GPEI and make it less cost-effective, although the GPEI continues to yield expected incremental net benefits at the global level when considered over the time horizon of 1988-2029. The overall health and financial benefits of the GPEI will depend on whether and when the GPEI can achieve its goals, when eradication occurs, the valuation method applied, and the path dependence of the actions taken. Reduced expected incremental net benefits of the GPEI and the substantial economic impacts of the COVID-19 pandemic pose large financial risks for the GPEI.

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.

Potential Future Use, Costs, and Value of Poliovirus Vaccines.

Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated poliovirus vaccine (IPV). With the Global Polio Eradication Initiative (GPEI) continuing to extend its timeline for ending the transmission of all wild polioviruses and to introduce new poliovirus vaccines, the polio vaccine supply chain continues to expand in complexity. The increased complexity leads to significant uncertainty about supply and costs. Notably, the strategy of phased OPV cessation of all three serotypes to stop all future incidence of poliomyelitis depends on successfully stopping the transmission of all wild polioviruses. Countries also face challenges associated with responding to any outbreaks that occur after OPV cessation, because stopping transmission of such outbreaks requires reintroducing the use of the stopped OPV in most countries. National immunization program leaders will likely consider differences in their risks and willingness-to-pay for risk reduction as they evaluate their investments in current and future polio vaccination. Information about the costs and benefits of future poliovirus vaccines, and discussion of the complex situation that currently exists, should prove useful to national, regional, and global decisionmakers and support health economic modeling. Delays in achieving polio eradication combined with increasing costs of poliovirus vaccines continue to increase financial risks for the GPEI.

Valuing the cost of improving Chilean primary vaccination: a cost minimization analysis of a hexavalent vaccine.

BACKGROUND: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy. METHODS: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26). RESULTS: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme. CONCLUSIONS: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.

Projection of Costs of Polio Eradication Compared to Permanent Control.

Despite increased efforts and spending toward polio eradication, it has yet to be eliminated worldwide. We aimed to project economic costs of polio eradication compared to permanent control. We used historical Financial Resource Requirements from the Global Polio Eradication Initiative, as well as vaccination and population data from publicly available sources, to project costs for routine immunization, immunization campaigns, surveillance and laboratory resources, technical assistance, social mobilization, treatment, and overhead. We found that cumulative spending for a control strategy would exceed that for an eradication strategy in 2032 (range, 2027-2051). Eradication of polio would likely be cost-saving compared to permanent control.

Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

Socioeconomic factors associated with full childhood vaccination in Bangladesh, 2014.

OBJECTIVES: Childhood vaccination in Bangladesh has improved, but there is room for improvement. This study estimated full immunization coverage in Bangladeshi children and characterized risk factors for incomplete immunization. METHODS: Using the 2014 Bangladesh Demographic and Health Survey (DHS), full vaccination of children aged 12 to 24 months was examined; this was defined as the receipt of one dose of bacillus Calmette-Guérin (BCG), three doses of pentavalent vaccine, three doses of oral polio vaccine (OPV), and one dose of measles-containing vaccine (MCV). Associations between full vaccination and selected risk factors were assessed by logistic regression. RESULTS: Overall, 83% of children were fully vaccinated. BCG had the highest completion (97%), followed by OPV (92%), pentavalent vaccine (91%), and MCV (85%). Full vaccination coverage ranged from 64.4% in Sylhet to 90.0% in Rangpur and was lowest among non-locals of all regions (78.4%). Children who were in the lowest wealth quintile, who had mothers without antenatal care visits, or who had mothers without autonomy in healthcare decision-making were less likely to be fully vaccinated. CONCLUSIONS: Overall, full vaccination of children is high, but varies by vaccine type. Disparities still exist by wealth and by region. Maternal access to care and autonomy in healthcare decision-making are associated with higher vaccination coverage.

The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV): facts, experiences and lessons learned from the south-south zone; Nigeria, April 2016.

BACKGROUND: The globally synchronized switch from trivalent Oral Polio Vaccine (tOPV) to bivalent Oral Polio Vaccine (bOPV) took place in Nigeria on April 18th 2016. The country is divided into six geopolitical zones. This study reports the experiences and lessons learned from the switch process in the six states that make up Nigeria's south-south geopolitical zone. METHODS: This was a descriptive retrospective review of Nigeria's switch plan and structures used for implementing the tOPV-bOPV switch in the south-south zone. Nigeria's National Polio Emergency Operation Centre (NPEOC) protocols, global guidelines and reports from switch supervisors during the switch were used to provide background information for this study. Quantitative data were derived from reviewing switch monitoring and validation documents as submitted to the NPEOC RESULTS: The switch process took place in all 3078 Health Facilities (HFs) and 123 Local Government Areas (LGAs) that make up the six states in the zone. A total of $139,430 was used for this process. The 'healthcare personnel' component received the highest budgetary allocation (59%) followed by the 'logistics' component (18%). Akwa Ibom state was allocated the highest number of healthcare personnel and hence received the most budgetary allocation compared to the six states (total healthcare personnel = 458, total budgetary allocation = $17,428). Validation of the switch process revealed that eight HFs in Bayelsa, Cross-River, Edo and Rivers states still possessed tOPV in cold-chain while six HFs in Cross-River and Rivers states had tOPV out of cold-chain but without the 'do not use' sticker. Akwa-Ibom was the only state in the zone to have bOPV and Inactivated Polio Vaccine (IPV) available in all its HFs monitored. CONCLUSION: The Nigerian tOPV-bOPV switch was successful. For future Oral Polio Vaccine (OPV) withdrawals, implementation of the switch plan would be more feasible with an earlier dissemination of funds from global donor organizations, which would greatly aid timely planning and preparations. Increased budgetary allocation to the 'logistics' component to accommodate unexpected hikes in transportation prices and the general inefficiencies with power supply in the country is also advised.

Financial Support to Eligible Countries for the Switch From Trivalent to Bivalent Oral Polio Vaccine-Lessons Learned.

The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) ("the switch") presented an unprecedented challenge to countries. In order to mitigate the risks associated with country-level delays in implementing the switch, the Global Polio Eradication Initiative provided catalytic financial support to specific countries for operational costs unique to the switch. Between November 2015 and February 2016, a total of approximately US$19.4 million in financial support was provided to 67 countries. On average, country budgets allocated 20% to human resources, 23% to trainings and meetings, 8% to communications and advocacy, 9% to logistics, 15% to monitoring, and 5% to waste management. All 67 funded countries successfully switched from tOPV to bOPV during April-May 2016. This funding provided target countries with the necessary catalytic support to facilitate the execution of the switch on an accelerated timeline, and the mechanism offers a model for similar support to future global health efforts, such as the eventual global withdrawal of bOPV.

Resource Needs for the Trivalent Oral Polio to Bivalent Oral Polio Vaccine Switch in Indonesia.

Background: We present an empirical economic cost analysis of the April 2016 switch from trivalent (tOPV) to bivalent (bOPV) oral polio vaccine at the national-level and 3 provinces (Bali, West Sumatera and Nusa Tenggara) for Indonesia's Expanded Program on Immunization. Methods: Data on the quantity and prices of resources used in the 4 World Health Organization guideline phases of the switch were collected at the national-level and in each of the sampled provinces, cities/districts, and health facilities. Costs were calculated as the sum of the value of resources reportedly used in each sampled unit by switch phase. Results: Estimated national-level costs were $46 791. Costs by health system level varied from $9062 to $34 256 at the province-level, from $4576 to $11 936 at the district-level , and from $3488 to $29 175 at the city-level. Estimated national costs ranged from $4 076 446 (Bali, minimum cost scenario) to $28 120 700 (West Sumatera, maximum cost scenario). Conclusions: Our findings suggest that the majority of tPOV to bOPV switch costs were borne at the subnational level. Considerable variation in reported costs among health system levels surveyed indicates a need for flexibility in budgeting for globally synchronized public health activities.

The case for periodic OPV routine vaccination campaigns.

The possibility of periodic routine vaccination campaigns (PRVCs) is introduced in the context of a search for optimal oral poliovirus vaccine (OPV) administration strategies. Like the usual continuous routine vaccination campaign (CRVC), PRVCs target only newborns. However, they are not necessarily implemented continuously in time. Using a dynamic and compartmental polio transmission model in a stochastic context, it is shown that some PRVCs can achieve much greater efficiency than CRVC in terms of probability of wild poliovirus (WPV) eradication, even though they never outperform CRVC in terms of total number of paralytic infections. Moreover, these PRVCs results can be obtained at a lower price than CRVC. It is also shown that, even though PRVCs do not perform better than pulse vaccination campaigns (PVCs) when only epidemiological outputs are valued, they can do so when a cost-benefit analysis is preferred.

An economic analysis of poliovirus risk management policy options for 2013-2052.

BACKGROUND: The Global Polio Eradication Initiative plans for coordinated cessation of oral poliovirus vaccine (OPV) after interrupting all wild poliovirus (WPV) transmission, but many questions remain related to long-term poliovirus risk management policies. METHODS: We used an integrated dynamic poliovirus transmission and stochastic risk model to simulate possible futures and estimate the health and economic outcomes of maintaining the 2013 status quo of continued OPV use in most developing countries compared with OPV cessation policies with various assumptions about global inactivated poliovirus vaccine (IPV) adoption. RESULTS: Continued OPV use after global WPV eradication leads to continued high costs and/or high cases. Global OPV cessation comes with a high probability of at least one outbreak, which aggressive outbreak response can successfully control in most instances. A low but non-zero probability exists of uncontrolled outbreaks following a poliovirus reintroduction long after OPV cessation in a population in which IPV-alone cannot prevent poliovirus transmission. We estimate global incremental net benefits during 2013-2052 of approximately $16 billion (US$2013) for OPV cessation with at least one IPV routine immunization dose in all countries until 2024 compared to continued OPV use, although significant uncertainty remains associated with the frequency of exportations between populations and the implementation of long term risk management policies. CONCLUSIONS: Global OPV cessation offers the possibility of large future health and economic benefits compared to continued OPV use. Long-term poliovirus risk management interventions matter (e.g., IPV use duration, outbreak response, containment, continued surveillance, stockpile size and contents, vaccine production site requirements, potential antiviral drugs, and potential safer vaccines) and require careful consideration. Risk management activities can help to ensure a low risk of uncontrolled outbreaks and preserve or further increase the positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live poliovirus exposure.

Polio inactivated vaccine costs into routine childhood immunization in Brazil.

OBJECTIVE To analyze the costs of vaccination regimens for introducing inactivated polio vaccine in routine immunization in Brazil. METHODS A cost analysis was conducted for vaccines in five vaccination regimens, including inactivated polio vaccine, compared with the oral polio vaccine-only regimen. The costs of the vaccines were estimated for routine use and for the "National Immunization Days", during when the oral polio vaccine is administered to children aged less than five years, independent of their vaccine status, and the strategic stock of inactivated polio vaccine. The presented estimated costs are of 2011. RESULTS The annual costs of the oral vaccine-only program (routine and two National Immunization Days) were estimated at US$19,873,170. The incremental costs of inclusion of the inactivated vaccine depended on the number of vaccine doses, presentation of the vaccine (bottles with single dose or ten doses), and number of "National Immunization Days" carried out. The cost of the regimen adopted with two doses of inactivated vaccine followed by three doses of oral vaccine and one "National Immunization Day" was estimated at US$29,653,539. The concomitant replacement of the DTPw/Hib and HepB vaccines with the pentavalent vaccine enabled the introduction of the inactivated polio without increasing the number of injections or number of visits needed to complete the vaccination. CONCLUSIONS The introduction of the inactivated vaccine increased the annual costs of the polio vaccines by 49.2% compared with the oral vaccine-only regimen. This increase represented 1.13% of the expenditure of the National Immunization Program on the purchase of vaccines in 2011.