The cost-effectiveness of alternative polio immunization policies in South Africa

AIMS: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. METHODS: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. CONCLUSIONS: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39.     

A developing country perspective on vaccine-associated paralytic poliomyelitis

When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin.     

Imported vaccine-associated paralytic poliomyelitis--United States, 2005

Paralytic poliomyelitis is rare in the United States because of the success of universal childhood immunization and the Global Polio Eradication Initiative. Poliovirus vaccine was introduced in the 1950s. Since then, the United States has eliminated indigenous wild poliovirus transmission, controlled imported wild poliovirus cases, and, through a vaccine policy change (i.e., from live, attenuated oral polio vaccine [OPV] to inactivated polio vaccine [IPV]), eliminated vaccine-associated paralytic polio (VAPP) cases. The most recent VAPP case occurred in 1999. The primary risk for paralytic polio for U.S. residents is through travel to countries where polio remains endemic or where polio outbreaks are occurring. This report describes the first known occurrence of imported VAPP in an unvaccinated U.S. adult who traveled abroad, where she likely was exposed through contact with an infant recently vaccinated with OPV. This case highlights the previously unrecognized risk for paralytic polio among unvaccinated persons exposed to OPV during travel abroad.     

PER.C6 cells as a serum-free suspension cell platform for the production of high titer poliovirus: A potential low cost of goods option for world supply of inactivated poliovirus vaccine

There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries.     

End phase challenges of poliomyelitis eradication programme realization

The progress of poliomyelitis eradication programme realization, the implementation schedule and strategies for the future, are summarised based on publications of the World Health Organisation. During the following two years wild poliovirus strains should be globally eradicated. This means that potentially in 2010 the global eradication of wild polioviruses will be certified. To eradicate poliomyelitis, cessation of the oral polio vaccine (OPV) is necessary, since the vaccine strains produce cases of vaccine-associated paralytic poliomyelitis (VAPP) and cases of poliomyelitis caused by circulating vaccine-derived poliovirus (cVDPV). However, the WHO plan to stop immunization with OPV and the immunization with inactivated polio vaccine (IPV) shortly after, is alarming in the present situation. The article describes the measures undertaken to prevent or minimise the risk of reintroduction of wild poliovirus strains, which is potentially associated with WHO plan of action.     

World wide experience with inactivated poliovirus vaccine

As part of the global poliovirus eradication strategy, oral poliovirus vaccine (OPV) has successfully contributed to reduce polio incidence rates globally. However, because of the OPV-related risks of vaccine associated paralytic poliomyelitis (VAPP) and vaccine-derived polioviruses (VDPVs) OPV cessation is required in order to achieve complete eradication of polio. Inactivated poliovirus vaccine (IPV) is a viable option for incorporation into existing vaccination schedules so as to avoid these risks. Furthermore, the continuation of vaccination with IPV will protect populations in case of re-emergence of wild-type poliovirus from remote locations, laboratory samples, or through bioterrorism. The ability of IPV to prevent poliovirus outbreaks and provide herd protection has been demonstrated in several circumstances and in various settings. This paper reviews clinical experiences with IPV administration and outcomes in various countries in Europe, the Americas, Africa and Asia.     

Poliomyelitis prevention in the United States. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP).

These recommendations of the Advisory Committee on Immunization Practices (ACIP) for poliomyelitis prevention replace those issued in 1997. As of January 1, 2000, ACIP recommends exclusive use of inactivated poliovirus vaccine (IPV) for routine childhood polio vaccination in the United States. All children should receive four doses of IPV at ages 2, 4, and 6-18 months and 4-6 years. Oral poliovirus vaccine (OPV) should be used only in certain circumstances, which are detailed in these recommendations. Since 1979, the only indigenous cases of polio reported in the United States have been associated with the use of the live OPV. Until recently, the benefits of OPV use (i.e., intestinal immunity, secondary spread) outweighed the risk for vaccine-associated paralytic poliomyelitis (VAPP) (i.e., one case among 2.4 million vaccine doses distributed). In 1997, to decrease the risk for VAPP but maintain the benefits of OPV, ACIP recommended replacing the all-OPV schedule with a sequential schedule of IPV followed by OPV. Since 1997, the global polio eradication initiative has progressed rapidly, and the likelihood of poliovirus importation into the United States has decreased substantially. In addition, the sequential schedule has been well accepted. No declines in childhood immunization coverage were observed, despite the need for additional injections. On the basis of these data, ACIP recommended on June 17, 1999, an all-IPV schedule for routine childhood polio vaccination in the United States to eliminate the risk for VAPP. ACIP reaffirms its support for the global polio eradication initiative and the use of OPV as the only vaccine recommended to eradicate polio from the remaining countries where polio is endemic.     

Cost-effectiveness analysis of changing from live oral poliovirus vaccine to inactivated poliovirus vaccine in Australia

OBJECTIVE: Estimate the economic impact of introducing inactivated poliovirus vaccine (IPV) into the Australian childhood immunisation schedule to eliminate vaccine-associated paralytic poliomyelitis (VAPP). METHODS: Cost-effectiveness of two different four-dose IPV schedules (monovalent vaccine and IPV-containing combination vaccine) compared with the current four-dose oral poliovirus vaccine (OPV) schedule for Australian children through age six years. Model used estimates of VAPP incidence, costs, and vaccine utilisation and price obtained from published and unpublished sources. Main outcome measures were total costs, outcomes prevented, and incremental cost-effectiveness, expressed as net cost per case of VAPP prevented. RESULTS: Changing to an IPV-based schedule would prevent 0.395 VAPP cases annually. At $20 per dose for monovalent vaccine and $14 per dose for the IPV component in a combination vaccine, the change would incur incremental, annual costs of $19.5 million ($49.3 million per VAPP case prevented) and $6.7 million ($17.0 million per VAPP case prevented), respectively. Threshold analysis identified break-even prices per dose of $1 for monovalent and $7 for combination vaccines. CONCLUSIONS: Introducing IPV into the Australian childhood immunisation schedule is not likely to be cost-effective unless it comes in a combined vaccine with the IPV-component price below $10. IMPLICATIONS: More precise estimates of VAPP incidence in Australia and IPV price are needed. However, poor cost-effectiveness will make the decision about switching from OPV to IPV in the childhood schedule difficult.     

A ten-year experience in control of poliomyelitis through a combination of live and killed vaccines in two developing areas.

We describe a successful program of poliomyelitis control using a combination of killed and live polio vaccines over a 10-year period in two developing areas, the West Bank and Gaza, adjacent to a relatively developed country, Israel. During the 1970s, immunization using live trivalent oral polio vaccine (OPV) in these areas covered more than 90 percent of the infant population. Nevertheless, the incidence of paralytic polio continued to be high, with many cases occurring in fully or partially immunized persons. It was thought that this could be due to interference with OPV take by other enteroviruses present in the environment due to poor sanitary conditions in these areas. A new policy combining five doses of OPV with two doses of inactivated polio vaccine (IPV) was adopted and implemented in 1978. In the 10 years since then, immunization coverage of infants increased to an estimated 95 percent and paralytic poliomyelitis has been controlled, despite exposure to wild poliovirus from neighboring countries including an outbreak in Israel in 1988. This experience suggests that wide coverage using the combination of IPV and OPV is an effective vaccination policy that may make eradication of polio possible even in developing areas.     

Parental attitudes toward multiple poliovirus injections following a provider recommendation

OBJECTIVES: Changes to the polio vaccination schedule, first to a sequential inactivated poliovirus/oral poliovirus (IPV/OPV) schedule in 1996 and most recently to an all-IPV schedule, require infants to receive additional injections. Some surveys show parental hesitation concerning extra injections, whereas others show that parents prefer multiple simultaneous injections over extra immunization visits. This study describes parental behavior and attitudes about the poliovirus vaccine recommendations and additional injections at the 2- and 4-month immunization visits. METHODS: Beginning July 1, 1996, providers in eight public health clinics in Cobb and Douglas Counties, Georgia, informed parents of polio vaccination options and recommended the IPV/OPV sequential schedule. A cross-sectional clinic exit survey was conducted from July 15, 1996, to January 31, 1997, with parents whose infants (younger than 6 months) were eligible for a first poliovirus vaccination. RESULTS: Of approximately 405 eligible infants, parents of 293 infants were approached for an interview, and 227 agreed to participate. Of those 227 participants, 210 (92%) parents chose IPV for their infant and 17 (8%) chose OPV. Of greatest concern to most parents was vaccine-associated paralytic polio (VAPP) (155, or 68.3%); the next greatest concern was an extra injection (22, or 9.7%). These parental concerns were unrelated to the number of injections the infant actually received. CONCLUSIONS: After receiving information on polio vaccination options and a provider recommendation, parents overwhelmingly chose IPV over OPV. Concern about VAPP was more common than objection to an extra injection. The additional injection that results from using IPV for an infant's first poliovirus vaccination appears to be acceptable to most parents.     

疫苗相关麻痹型脊髓灰质炎对IPV疫苗选择的影响

摘要:在全球消除脊髓灰质炎（脊灰）的进程稳步推进的大背景下,随着口服脊髓灰质炎减毒活疫苗（Oral Polio Vaccine,OPV）的继续使用,疫苗相关麻痹型脊髓灰质炎（Vaccine-associated Paralytic Poliomyelitis,VAPP）越来越受到人们的关注,VAPP在国内外的发病情况不容忽视。WHO估计全球每年约有250～500例VAPP发生,国内的估算数字是76～161例,其中首剂次疫苗VAPP发生率较高。在疫苗选择上,灭活的脊髓灰质炎疫苗（IPV）最大的优点是能够避免VAPP的发生,但成本效益分析结果并不支持引入IPV。尽管如此,为了消除VAPP的危害,一些发达国家已率先使用IPV疫苗,同时一些发展中国家采用IPV/OPV序贯程序。因此,基于当前我国维持无脊灰的现状,VAPP所带来的公共卫生问题是决定选择IPV疫苗的重要因素,在可承担的价格空间上,IPV疫苗可作为首选疫苗推荐,也可先行引入IPV/OPV序贯程序。     

The role of routine polio immunization in the post-certification era

The role of routine vaccination against poliomyelitis for the post-certification era remains an important area for policy decision-making. Two critical decisions need to be taken: first, to continue or discontinue vaccination with the live attenuated oral poliovirus vaccine (OPV); and second, if OPV is to be discontinued, whether vaccination with inactivated poliovirus vaccine (IPV) is needed. Four potential vaccination scenarios can be constructed: stop all polio vaccination; continue with current vaccination policies (OPV, IPV, or sequential schedule); discontinue OPV, but continue IPV universally; or discontinue OPV, but continue IPV in selected countries. All possible scenarios require continued investments in a surveillance and response strategy, including a stockpile of polio vaccine. Continuing vaccination would limit the savings that could be applied to the control of other health priorities. This report reviews the key issues associated with each scenario, highlights the advantages and disadvantages of each scenario, and outlines the major challenges for policy decision-making.     

脊髓灰质炎疫苗应用现状及免疫策略进展

1988年,全球消灭脊髓灰质炎（脊灰）倡议行动启动以来,取得了重大进展。2012年,全球报告脊灰223例,较2011年减少〉60%,本土脊灰流行国家减少为尼日利亚、巴基斯坦和阿富汗,脊灰野病毒（Wild Poliovirus,WPV）病例数下降到历史最低水平。但WPV传播仍未被阻断,无脊灰国家/地区仍面临输入WPV的风险。同时,有些国家正面临使用口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）所致疫苗衍生脊灰病毒的风险。目前,不同国家/地区评估各自的脊灰发病风险,依据OPV、脊灰病毒灭活疫苗（Inactivated Poliovirus Vaccine,IPV）的风险和收益,不同国家/地区采用不同的免疫策略：仅使用IPV、序贯使用IPV/OPV和仅使用OPV。2013年,世界卫生组织《全球消灭脊灰终结战略计划》中提出,2014年全球阻断WPV传播,2015年所有国家应至少使用1剂IPV,停用OPV中的Ⅱ型组分;2018年完成消灭WPV证实后,停用OPV。现对OPV和IPV的应用现状以及免疫策略进行简述。     

Adjuvants and inactivated polio vaccine: A systematic review

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV.     

不同序贯程序的脊髓灰质炎灭活疫苗和减毒活疫苗的免疫效果研究

目的 评价脊髓灰质炎灭活疫苗（IPV）和减毒活疫苗（OPV）不同序贯免疫程序的免疫效果。方法 选取月龄≥2月的婴儿,分为1剂IPV和2剂OPV序贯组(I - O - O组)、2剂IPV和1剂OPV序贯组(I - I - O组)、IPV全程(I - I - I组)和OPV全程组(O - O - O),分别在2、3、4月龄时各接种1针,检测并比较各组人群血清中脊髓灰质炎中和抗体几何平均滴度（GMT）及抗体阳转率。结果 在完成基础免疫后,I - O - O 组Ⅰ、Ⅱ、Ⅲ型抗体GMT分别为948.78、930.91、955.08;I - I - O组抗体GMT分别为909.43、1 202.34、1 102.83;I - I - I 组GMT分别为333.02、298.56、411.98,O - O - O组抗体GMT分别为814.42、778.27、658.52;差异均有统计学意义;各组3个型别的抗体阳转率均为98％~100％,差异无统计学意义。接种1针IPV后脊髓灰质炎Ⅰ型、Ⅱ型、Ⅲ型中和抗体GMT分别为21.77、30.89、26.46,抗体阳转率分别为84.1％、91.5％、91.5％;接种第2剂IPV后,Ⅰ型、Ⅱ型、Ⅲ型中和抗体GMT分别69.42、133.89、212.58,抗体阳转率分别为100.0％、100.0％、99.9％。结论 IPV与OPV序贯接种后,对象产生的脊髓灰质炎中和抗体GMT比单独接种3剂IPV或3剂OPV高;不同序贯程序中,接种2剂IPV后抗体保护率较高。为了使机体产生更高的抗体水平并且避免疫苗相关麻痹病例发生,可采用IPV与OPV序贯程序,并以2剂IPV和1剂OPV的序贯程序为佳。     

Economics of polio vaccination in the post-eradication era: should OPV-using countries adopt IPV?

The continued use of oral polio vaccine (OPV) poses a threat to polio virus eradication. Stopping all polio vaccination in the post-certification era is no longer considered to be a practical option. Policy makers agree that OPV use must stop immediately after certification. Therefore, the pragmatic alternative is for the OPV-using countries to switch to IPV. This study estimates the cost of switching to IPV, and the cost-effectiveness of this switch. Using data on the number of polio cases and the number of unvaccinated children in different countries of the world, the risks of polio and polio outbreaks have been calculated. The current cost of routine and intensive OPV immunisation is about US $2143 million in the 148 OPV-using countries. Routine use of IPV in these countries should cost US $1246 million. If the current costs of routine and intensive polio immunisation are considered, adopting IPV to replace OPV will not increase the total global cost. Even if the cost of intensive polio immunisation is ignored, cost-effectiveness ratio of adopting IPV remains less than the average GNI per capita of OPV-using countries. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.     

The global introduction of inactivated polio vaccine can circumvent the oral polio vaccine paradox

This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become transmissible circulating vaccine-derived polioviruses (cVDPVs), preventing use of the vaccine in the post-eradication era. This literature review identifies (1) risks of complete cessation of vaccination, (2) barriers and (3) solutions for the introduction of IPV in developing countries. The reviewed literature favours to circumvent the so-called “OPV paradox” by global introduction of IPV.     

Polio eradication in India: some observations

In 1988, the World Health Assembly passed resolution WHA 41.28, which committed the World Health Organization (WHO) to the global eradication of poliomyelitis by the year 2000. In spite of the combined efforts by UNICEF, National Polio Surveillance Project (NPSP), Indian Academy of Pediatrics (IAP) and Rotary International, Polio Free India is still a distant dream.Though oral polio vaccine has succeeded in polio eradication from many countries but there is high incidence of vaccine failure in India.Oral polio vaccine (OPV) has failed to provide full protection to many children who have developed paralytic polio even after taking 10 or more doses of OPV. In some children, OPV has caused paralysis-vaccine associated paralytic polio (VAPP). Number of children developing polio due to vaccine is high and on increase. Reasons for this could be that even immunocompromised children are being administered OPVbecause IPV is not available. Vaccine failure has exaggerated the problem of VAPP. No efforts have been made to find the causes for high incidence of vaccine failure and VAPP.     

Poliomyelitis control in Israel, the West Bank and Gaza Strip: changing strategies with the goal of eradication in an endemic area.

Israel has faced the challenge presented by epidemic poliomyelitis by using different immunization strategies. In the 1950s, inactivated poliovirus vaccine (IPV) helped to reduce the total burden of the disease, but cases continued to occur. Introduction of oral poliovirus vaccine (OPV) in mid-1961 had a dramatic effect in controlling an extensive epidemic of poliomyelitis; however, poliovirus activity and cases continued during the 1970s, and at a low level in the 1980s. A localized outbreak of 15 cases of poliomyelitis in 1988 occurred in an area using enhanced potency IPV (eIPV) only. This led to a revision of poliomyelitis immunization policy. The successful poliomyelitis control in the West Bank and the Gaza Strip using both OPV and IPV since 1978 shows the advantages of a combined approach. This programme was therefore adopted in modified form in the whole of Israel, the West Bank and Gaza. Since late 1988, no cases of poliomyelitis have occurred in any of these three areas, indicating the success of the combined poliomyelitis immunization programme. These experiences may be helpful to other countries, especially those where there is a danger of importation of wild poliovirus, and to prevent vaccine-associated disease. The combined approach provides an additional immunization model in the international effort to eradicate poliomyelitis.