Poliomyelitis mainly affects unvaccinated children under five years of age, causing irreversible paralysis or even death. The oral polio vaccine (OPV) contains live attenuated virus, which can, in rare cases, cause a paralysis known as vaccine-associated paralytic polio (VAPP), and also vaccine-derived polioviruses (VDPVs) due to acquired neurovirulence after prolonged duration of replication. The incidence of poliomyelitis caused by wild polio virus (WPV) has declined dramatically since the introduction of OPV and later the inactivated polio vaccine (IPV), however, the cases of paralysis linked to the OPV are currently more frequent than those related to the WPV. Therefore, in 2016, the World Health Organization (WHO) recommended at least one IPV dose preceding routine immunisation with OPV to reduce VAPPs and VDPVs until polio could be eradicated.

To assess the effectiveness, safety, and immunogenicity of sequential IPV-OPV immunisation schemes compared to either OPV or IPV alone.

In May 2019 we searched CENTRAL, MEDLINE, Embase, 14 other databases, three trials registers and reports of adverse effects on four web sites. We also searched the references of identified studies, relevant reviews and contacted authors to identify additional references.

Randomised controlled trials (RCTs), quasi-RCTs, controlled before-after studies, nationwide uncontrolled before-after studies (UBAs), interrupted time series (ITS) and controlled ITS comparing sequential IPV-OPV schedules (one or more IPV doses followed by one or more OPV doses) with IPV alone, OPV alone or non-sequential IPV-OPV combinations.

We used standard methodological procedures expected by Cochrane.

We included 21 studies: 16 RCTs involving 6407 healthy infants (age range 96 to 975 days, mean 382 days), one ITS with 28,330 infants and four nationwide studies (two ITS, two UBA). Ten RCTs were conducted in high-income countries; five in the USA, two in the UK, and one each in Chile, Israel, and Oman. The remaining six RCTs were conducted in middle-income countries; China, Bangladesh, Guatemala, India, and Thailand. We rated all included RCTs at low or unclear risk of bias for randomisation domains, most at high or unclear risk of attrition bias, and half at high or unclear risk for conflict of interests. Almost all RCTs were at low risk for the remaining domains. ITSs and UBAs were mainly considered at low risk of bias for most domains. IPV-OPV versus OPV It is uncertain if an IPV followed by OPV schedule is better than OPV alone at reducing the number of WPV cases (very low-certainty evidence); however, it may reduce VAPP cases by 54% to 100% (three nationwide studies; low-certainty evidence). There is little or no difference in vaccination coverage between IPV-OPV and OPV-only schedules (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.96 to 1.06; 1 ITS study; low-certainty evidence). Similarly, there is little or no difference between the two schedule types for the number of serious adverse events (SAEs) (RR 0.88, 95% CI 0.46 to 1.70; 4 studies, 1948 participants; low-certainty evidence); or the number of people with protective humoral response P1 (moderate-certainty evidence), P2 (for the most studied schedule; two IPV doses followed by OPV; low-certainty evidence), and P3 (low-certainty evidence). Two IPV doses followed by bivalent OPV (IIbO) may reduce P2 neutralising antibodies compared to trivalent OPV (moderate-certainty evidence), but may make little or no difference to P1 or P2 neutralising antibodies following an IIO schedule or OPV alone (low-certainty evidence). Both IIO and IIbO schedules may increase P3 neutralising antibodies compared to OPV (moderate-certainty evidence). It may also lead to lower mucosal immunity given increased faecal excretion of P1 (low-certainty evidence), P2 and P3 (moderate-certainty evidence) after OPV challenge. IPV-OPV versus IPV It is uncertain if IPV-OPV is more effective than IPV alone at reducing the number of WPV cases (very low-certainty evidence). There were no data regarding VAPP cases. There is no clear evidence of a difference between IPV-OPV and OPV schedules for the number of people with protective humoral response (low- and moderate-certainty evidence). IPV-OPV schedules may increase mean titres of P1 neutralising antibodies compared to OPV alone (low- and moderate-certainty evidence), but the effect on P2 and P3 titres is not clear (very low- and moderate-certainty evidence). IPV-OPV probably reduces the number of people with P3 poliovirus faecal excretion after OPV challenge with IIO and IIOO sequences (moderate-certainty evidence), and may reduce the number with P2 (low-certainty evidence), but not with P1 (very low-certainty evidence). There may be little or no difference between the schedules in number of SAEs (RR 0.92, 95% CI 0.60 to 1.43; 2 studies, 1063 participants, low-certainty evidence). The number of persons with P2 protective humoral immunity and P2 neutralising antibodies are probably lower with most sequential schemes without P2 components (i.e. bOPV) than with trivalent OPV or IVP alone (moderate-certainty evidence). IPV (3)-OPV versus IPV (2)-OPV One study (137 participants) showed no clear evidence of a difference between three IPV doses followed by OPV and two IPV doses followed by OPV, on the number of people with P1 (RR 0.98, 95% CI 0.93 to 1.03), P2 (RR 1.00, 95% CI 0.97 to 1.03), or P3 (RR 1.01, 95% CI 0.97 to 1.05) protective humoral and intestinal immunity; all moderate-certainty evidence. This study did not report on any other outcomes.

IPV-OPV compared to OPV may reduce VAPPs without affecting vaccination coverage, safety or humoral response, except P2 with sequential schemes without P2 components, but increase poliovirus faecal excretion after OPV challenge for some polio serotypes. Compared to IPV-only schedules, IPV-OPV may have little or no difference on SAEs, probably has little or no effect on persons with protective humoral response, may increase neutralising antibodies, and probably reduces faecal excretion after OPV challenge of certain polio serotypes. Using three IPV doses as part of a IPV-OPV schedule does not appear to be better than two IPV doses for protective humoral response. Sequential schedules during the transition from OPV to IPV-only immunisation schedules seems a reasonable option aligned with current WHO recommendations. Findings could help decision-makers to optimise polio vaccination policies, reducing inequities between countries.

Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule.

Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored.

Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar.

A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

In the United States during the 1950's, polio was on the forefront of every provider and caregiver's mind. Today, most providers in the United States have never seen a case. The Global Polio Eradication Initiative (GPEI), which began in 1988 has reduced the number of cases by over 99%. The world is closer to achieving global eradication of polio than ever before but as long as poliovirus circulates anywhere in the world, every country is vulnerable. The global community can support the polio eradication effort through continued vaccination, surveillance, enforcing travel regulations and contributing financial support, partnerships and advocacy.

With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models.

Vaccinology today is a rapidly changing specialty of medical science where new developments are regularly taking place. There is a need to review/revise recommendations about existing vaccines in the light of recent information.

Following an IAPCOI meeting in December 2011, a draft statement was prepared and circulated among the meeting participants to arrive at a consensus.

To review and issue recommendations on the recent contentious issues pertaining to rotavirus, Hib, and pneumococcal conjugate vaccines, and to revise recommendations for 2012 Immunization timetable for pediatricians in office practice.

IAPCOI abolished the earlier categorization of vaccines in four categories. On rotavirus, the committee stresses the need of having more data on disease burden in India. Further, there is a need to optimize use of rotavirus vaccines in India to achieve higher yields in term of protective efficacy. For the want of adequate data, the committee is not able to issue any specific recommendation on the suitability of a particular rotavirus vaccine (monovalent vs multivalent) for the country. The committee also acknowledges a small risk of acute intussusception following use of current generation of rotavirus vaccines and recommends inclusion of the history of intussusception in the past as an absolute contraindication. The committee concludes that there are no safety concerns of Hib vaccines as reported frequently in lay media. On the disease burden of pneumococcal diseases, the committee concludes that there is a need of conducting more community based studies to gather more evidence. Similarly, the data on prevalence of different pneumococcal serotypes in the country is sparse and limited to few hospital based studies. There is need of establishing real-time multisite pneumococcal disease surveillance in the country. Due to scarcity of data on the prevalence of pneumococcal serotypes and non-typeable hemophilus influenza (NTHi) in India, it is difficult to comment on the superiority of one pneumococcal conjugate vaccine over other. The committee also revised the recommendations for the year 2012.

Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and has been reduced to near elimination, all within the span of documented medical history. Nevertheless, effective vaccinations, global surveillance network, development of accurate viral diagnosis prompted the historical challenge, global polio eradication initiative (GPEI). Environmental surveillance of poliovirus means monitoring of wild polio virus (WPV) and vaccine derived polio virus (cVDPV) circulation in human populations by examining environmental specimens supposedly contaminated by human feces. The rationale for surveillance is based on the fact that PV-infected individuals, whether presenting with disease symptoms or not, shed large amounts of PV in the feces for several weeks. As the morbidity: infection ratio of PV infection is very low, and therefore this fact contributes to the sensitivity of poliovirus surveillance, which under optimal conditions can be better than that of the standard acute flaccid paralysis (AFP) surveillance. The World Health Organization (WHO) has included environmental surveillance of poliovirus in the new Strategic Plan of the Global Polio Eradication Initiative for years 2010-2012 to be increasingly used in PV surveillance, supplementing AFP surveillance and the strategic advisory group of experts on immunization (SAGE) recommended a switch from tOPV-bOPV to remove the threat of cVDPV2 and to accelerate the elimination of WPV type 1 and 3 as bOPV is a more immunogenic vaccine and to introduce one dose of IPV in their vaccination schedule prior to OPV cessation.

Estimate the economic impact of introducing inactivated poliovirus vaccine (IPV) into the Australian childhood immunisation schedule to eliminate vaccine-associated paralytic poliomyelitis (VAPP).

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.

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.

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.

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.

The elimination of wild-virus-associated poliomyelitis in the Western Hemisphere in 1991 and rapid progress in global polio eradication efforts changed the risk-benefit ratio associated with the exclusive use of oral poliovirus vaccine (OPV) for routine immunization. These changes, plus the November 1987 development of an enhanced-potency inactivated poliovirus vaccine (IPV), which poses no risk of vaccine-associated paralytic poliomyelitis (VAPP), resulted in a change in polio immunization policy in the United States. In September 1996, the Centers for Disease Control and Prevention recommended that IPV replace OPV for the first 2 doses in a sequential poliovirus vaccine schedule. The Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system for adverse events after receipt of any US-licensed vaccine, is used to monitor postlicensure vaccine safety. Postlicensure surveillance of vaccines is important to identify new, rare, or delayed-onset adverse reactions not detected in prelicensure clinical trials or when new vaccine schedules are adopted. Through continual monitoring of adverse events and identification of potential vaccine risks, VAERS can serve as an important resource to ensure continued public acceptance of vaccines. We compared VAERS reports after the receipt of IPV to reports after OPV in infants from 1991 through 1998. Comparisons included reports listing IPV and OPV coadministered with other vaccines.

Annual reporting rates per 100 000 doses distributed within 3 severity categories (fatal, nonfatal serious, less serious) were examined. Distributions of severity categories by vaccine type, age, and time period (pre- and postrecommendation) were constructed. Safety profiles (distribution of 21 symptom groupings) for IPV and OPV reports were compared. Analysis was restricted to reports for infants 1 to 3 months old and 4 to 6 months old, corresponding generally to first- and second-dose recipients. Any notable increase in a severity or safety category for IPV compared with OPV was followed up by examining the frequency of specific symptoms, reporting source, and date of vaccination. An important limitation of VAERS is that reports do not necessarily represent adverse events caused by vaccines. In many cases, the events are temporal associations only.

The annual rates of VAERS reports per 100 000 vaccine doses distributed by severity category, 1991 to 1998, were in general similar for reports after IPV compared with those after OPV. The reporting rates for poliovirus vaccine did not increase materially with the shift to IPV usage. The relative frequencies of symptoms in the fatal and nonfatal serious categories for 1998 vaccine administrations were similar to 1997 reports. Severity profiles for IPV and OPV reports in infants 1 to 3 months old and 4 to 6 months old, corresponding to first- and second-dose recipients, were remarkably similar. The frequency of symptoms listed on IPV reports categorized as fatal or serious was examined by age, vaccine combinations, and time period, and the distribution of symptoms was similar for ages 1 to 3 months and 4 to 6 months. In the postrecommendation period, the 10 most frequent symptoms reported with IPV were also reported with OPV in either similar or lower relative frequency. During the postrecommendation period, safety profiles for infants 4 to 6 months old showed a 2.5% higher proportion in the allergic reaction category for IPV than for OPV, but none of the allergic reaction reports indicated anaphylaxis. In general, the distribution of symptom groupings was not markedly different for IPV compared with OPV. No cases of VAPP were reported after the administration of IPV, whereas 5 VAPP cases were reported after the administration of OPV.

Although VAERS is subject to the limitations of most passive surveillance systems, the large number of reports and national coverage provide a unique database for monitoring vaccine safety. There was a marked increase of IPV reports in VAERS after 1996, consistent with implementation of the Advisory Committee on Immunization Practices recommendation for the sequential IPV/OPV poliovirus vaccination schedule. Given the increased use of IPV, a review of potential adverse events in VAERS compared IPV with OPV reports both before and after the introduction of the sequential vaccination schedule. Vaccine safety surveillance indicated no adverse events patterns of potential concern following the use of IPV in infants after the introduction of the sequential vaccination schedule. Ongoing surveillance is documenting a decrease in VAPP. These findings provide useful information to support the Advisory Committee on Immunization Practices recommendation, made in 1999, to shift to an all-IPV schedule.

For 3 decades, vaccination against poliomyelitis has rested mainly on the use of the oral attenuated vaccine (OPV). In countries where wild type poliomyelitis has been successfully controlled by OPV, the rare cases of poliomyelitis that can still be identified occur in vaccinees or their contacts and are caused by vaccine related strains. Over years, data indicating that the inactivated vaccine (IPV) also has the potential to control poliomyelitis and that there are no known risks associated with the use of this vaccine have accumulated. The reasons for changes in vaccine policy in industrialised countries and the situation of the global effort of poliomyelitis immunisation are described. Some of the issues and challenges for the future are reviewed.

Poliomyelitis prevention in the United States has relied virtually exclusively on OPV during the past 30 years. Starting in 1997, a major change in the poliomyelitis vaccination policy occurred, facilitated by substantial progress toward worldwide poliomyelitis eradication. A sequential schedule of IPV followed by OPV became the preferred means to prevent poliomyelitis, although an all-OPV and an all-IPV schedule were considered acceptable alternatives. In 1999, two doses of IPV were recommended to start the primary series, followed by two doses of either poliovirus vaccine. As of January 2000, an all-IPV schedule is currently being implemented in the United States for routine childhood vaccination. Several unusual features are associated with the major public health policy change from an all-OPV to a sequential schedule, including (1) the process of involving a neutral party (i.e., the IOM); (2) the perceived concerns expressed before the change in policy with regard to provider and parent compliance, which could affect the hard-earned gains in raising immunization coverage rates; (3) the ethical issues surrounding the change (e.g., societal versus individual protection) and the influence that a single case of VAPP may have on national policy; (4) the relative lack of importance of cost-effectiveness data; and (5) the weight of progress in the global polio eradication initiative spurring the change in the United States and, increasingly, in other industrialized countries. The IOM assisted in the evaluation of the national poliomyelitis vaccination policy in 1977 and again in 1988. The 1988 review recommended that a sequential IPV-OPV schedule be considered at such time that a combination vaccine becomes available. Also, the IOM raised several important questions. Extensive research to address the questions raised by the IOM had been conducted so that, in 1996, more data were available for the decision-making process. The primary reasons for the change in vaccination policy were (1) the continued occurrence of VAPP in the absence of indigenously acquired wildtype poliovirus-associated paralytic disease, (2) the reduced risk for importation and spread of wild-type poliovirus caused by the progress of the global polio eradication initiative, (3) evidence from vaccine trials that combined IPV-OPV schedules are safe and immunogenic, and (4) maintenance of high levels of population immunity to poliovirus. The global effect of a national change in poliomyelitis vaccination policy was also considered in this policy-making process. Some members of the public health and medical communities raised objections that an increased reliance on IPV in the United States could lead other countries, especially developing countries, to inappropriately abandon OPV and increase reliance on IPV for routine vaccination. Experience from the global smallpox eradication campaign indicated that this scenario was unlikely. The United States ceased vaccinating against smallpox in 1971, 6 years before smallpox was eliminated from the world, without jeopardizing the global smallpox campaign. Subsequently, the effect on the global eradication initiative has been negligible. This article illustrates the potential discrepancy between expressed theoretic concerns about the number of injections and the actual practice once vaccination policy recommendations become the standard of care and that appropriate training and education can overcome these initial concerns. The authors found that compliance with the recommended use of IPV for the first and second doses as part of the sequential schedule was high, independent of socioeconomic status and ethnicity. The need for additional injections did not present a barrier to completion of the recommended childhood immunization schedule. (ABSTRACT TRUNCATED)

Although poliovirus vaccination is nto new, the recent changes in ACIP recommendations involving polio vaccinations are. Currently, wild type poliovirus has been eliminated in the Western hemisphere, but vaccine-associated cases (VAPP) still occur. The new recommendations are intended to continue providing protection and to eliminate VAPP cases from occurring in vaccinees or close contacts.

Taking into account the global status of polio, it seems evident that the continuing use of oral poliovaccine in all countries is the most obvious and prudent public health policy for the foreseeable future. Possible exceptions might include those countries which are not troubled by the added cost of the inactivated vaccine; whose health services are able to guarantee high levels of vaccine coverage; and which can expect to experience comparatively few importations of wild poliovirus. An important question is whether it is warranted at this time to recommend a combined schedule of inactivated vaccine followed by live vaccine. This implies the addition of at least two inoculations of inactivated vaccine to an already complex vaccination schedule. In most countries, this now includes the administration of three inoculations each of DTP and Haemophilus influenzae as well as one of measles-mumps-rubella vaccine by approximately 12 months of age. Some countries also routinely vaccinate young children against hepatitis B (three additional inoculations). Because most physicians and clinics, as a policy, do not give more than two inoculations at one visit, it implies the need for scheduling additional well-child visits. In the United States, this is a principal factor in the greatly increased estimated costs of such a programme. Experience also shows that as the number of routine visits which are required for vaccination increases, overall vaccination coverage diminishes. The schedule recommended in the United States possesses yet a further problem. Children there would not receive the second dose of oral vaccine until five years of age, thus permitting the accumulation of a large number of preschool children with limited intestinal immunity-a potentially explosive problem were wild virus to be introduced. The inactivated polio vaccine is useful and certainly indicated for the small numbers of persons for whom the live, oral vaccine is contraindicated. However, to use it routinely implies accepting the potential of substantial penalties while reducing but not eliminating, an already extremely small risk of vaccine-associated paralytic illness. From the public health perspective, I therefore argue against the proposition. Copyright 1997 John Wiley & Sons, Ltd.

Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus.

Many countries have made use of inactivated poliovirus vaccine (IPV) in their national poliovirus control programs since 1955. Until 1961 IPV was the only vaccine available for the control of poliovirus, but subsequently many countries opted to use the Sabin attenuated poliovirus vaccine (OPV), which was perceived as more effective in preventing intestinal infection and in ensuring community protection by spreading to unvaccinated contacts of vaccinees. Nevertheless, IPV has remained the vaccine of choice in several countries, where experience has shown that it represents a safe and effective option for disease control. IPV limits subsequent infection of the pharynx and intestine in vaccinees, and is able to control circulation of poliovirus in a vaccinated population, providing effective community protection. Furthermore IPV contains only killed virus and cannot cause vaccine-associated paralytic poliomyelitis as OPV sometimes does. This paper reviews the history of the use of IPV, with emphasis on its efficacy and its ability to safely protect communities in which it is used. As the incidence of poliomyelitis declines new control strategies should take account of the knowledge of the use of poliovirus vaccines acquired since 1955.

The development of serum and nasopharyngeal antibody response, as well as the magnitude and temporal pattern of fecal shedding of vaccine and revertant polio-viruses, have been examined in infants previously immunized with one or more doses of orally administered live attenuated poliovaccine, enhanced potency inactivated polio-vaccine, or both. The nature of serum immune response appears to be similar after either immunization schedule, although the antibody titers are quantitatively higher after two doses of EP-IPV than those observed after a similar schedule with OPV. Highest antibody activity is generally detected in subjects immunized with a combination of EP-IPV followed by OPV. ELISA antibody activity in the nasopharynx was regularly detected after either form of immunization. However, neutralizing and VP3 poliovirus virion protein-specific antibody responses in the nasopharynx were consistently observed in subjects immunized with OPV or EP-IPV followed by OPV. Subjects immunized with EP-IPV alone exhibit significantly lower or absent neutralizing or VP3-specific responses. The nucleic acid sequences of the purified RNA obtained from all virus isolates have also been examined in the 5' noncoding region by dideoxy-sequencing to determine whether the viruses shed represent revertants (vaccine), non-revertants, or both. The frequency and duration of vaccine virus shedding appears to be similar in both immunization schedules. Revertant virus shedding was not demonstrated 30 days after immunization with OPV alone. However, shedding of revertants was detected for as long as 60 days in some subjects previously immunized with EP-IPV. The duration of shedding of revertant virus differed with different serotypes and different immunization regimens. Prior immunization with one or more doses of OPV reduced the length of shedding of revertant virus. Significantly, however, prior immunization with one or more doses of EP-IPV was not associated with reduced shedding of revertant virus types. Based on these observations and a number of other epidemiologic data summarized in this review, it is clear that both OPV and EP-IPV when used alone are highly effective and safe in inducing effective immunity to polio-virus and in the eradication of poliomyelitis. While the combination schedule employing EP-IPV followed by OPV should result in a decline of vaccine-associated paralytic (VAP) disease in OPV recipients, such immunization schedules may have little or no impact on the development of VAP in susceptible contacts. Furthermore, the logistics and the cost of combination schedules must be considered before current recommendations based on the use of OPV or EP-IPV alone are revised.

The control of poliomyelitis remains a provocative challenge. Alternative vaccination schedules, continuing research toward better vaccines, and ongoing international scientific, epidemiologic, and economic collaboration may make it possible to provide effective immunization for all children of the world and eventually may eradicate poliomyelitis worldwide, a goal set forward by the Expanded Programme on Immunization of the World Health Organization.

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.

An outbreak of 9 cases of paralytic poliomyelitis and 1 non-paralytic case occurred in Finland between August, 1984, and January, 1985, after two decades of freedom from the disease attributable to a successful immunisation programme. During the outbreak poliovirus type 3 was isolated from the patients, from about 15% of healthy persons tested, and from sewage water. At least 100 000 persons were estimated to have been infected. With 1.5 million extra doses of inactivated poliovirus vaccine to children under 18 years of age and an oral poliovirus vaccine campaign covering about 95% of the entire population in February-March, 1985, the outbreak was halted in February, 1985. Impaired herd immunity to the epidemic strain of poliovirus type 3, which differed from the type 3 vaccine strains in both immunological and molecular properties, was important in the emergence of this outbreak. The inactivated poliovaccine that had been used in the vaccination programme was relatively weakly immunogenic, especially as regards the type 3 component. Whether continuous antigenic variation of poliovirus type 3 has wider epidemiological implications is not known.