Use Of Oral Poliovirus Vaccine Research Articles

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.

Circulating vaccine-derived polioviruses: current state of knowledge.

Within the past 4 years, poliomyelitis outbreaks associated with circulating vaccine-derived polioviruses (cVDPVs) have occurred in Hispaniola (2000-01), the Philippines (2001), and Madagascar (2001-02). Retrospective studies have also detected the circulation of endemic cVDPV in Egypt (1988-93) and the likely localized spread of oral poliovirus vaccine (OPV)-derived virus in Belarus (1965-66). Gaps in OPV coverage and the previous eradication of the corresponding serotype of indigenous wild poliovirus were the critical risk factors for all cVDPV outbreaks. The cVDPV outbreaks were stopped by mass immunization campaigns using OPV. To increase sensitivity for detecting vaccine-derived polioviruses (VDPVs), in 2001 the Global Polio Laboratory Network implemented additional testing requirements for all poliovirus isolates under investigation. This approach quickly led to the recognition of the Philippines and Madagascar cVDPV outbreaks, but of no other current outbreaks. The potential risk of cVDPV emergence has increased dramatically in recent years as wild poliovirus circulation has ceased in most of the world. The risk appears highest for the type 2 OPV strain because of its greater tendency to spread to contacts. The emergence of cVDPVs underscores the critical importance of eliminating the last pockets of wild poliovirus circulation, maintaining universally high levels of polio vaccine coverage, stopping OPV use as soon as it is safely possible to do so, and continuing sensitive poliovirus surveillance into the foreseeable future. Particular attention must be given to areas where the risks for wild poliovirus circulation have been highest, and where the highest rates of polio vaccine coverage must be maintained to suppress cVDPV emergence.

Retrospective analysis of a local cessation of vaccination against poliomyelitis: a possible scenario for the future.

The global eradication of poliomyelitis will require substantial changes in immunization practices. One of the proposed scenarios includes cessation of vaccination with live oral poliovirus vaccine (OPV) and the creation of an OPV stockpile for emergency response in case of the reintroduction of poliovirus into circulation. We describe here a retrospective analysis of the cessation of OPV usage in a region of the Byelorussian Republic of the former Soviet Union in 1963 to 1966. During this period, a widespread circulation and evolution of independent lineages of vaccine-derived polioviruses took place in the region. Some of these lineages appeared to originate from OPV given to 40 children in the community during this period of essentially no vaccinations. The data demonstrate very high risks associated with both the local cessation of OPV vaccination and the proposed use of OPV to control a possible reemergence of poliovirus in the postvaccination period. The high transmissibility of OPV-derived viruses in nonimmune population, documented here, and the known existence of long-term OPV excretors should be also considered in assessing risks of the synchronized global cessation of OPV usage.

Parental opinions regarding poliomyelitis immunizations.

The successful eradication of poliomyelitis in the United States has primarily been due to the use of oral poliovirus vaccine (OPV). However, because of the risk of vaccine-associated paralytic poliomyelitis with OPV, the use of inactivated poliovirus vaccine (IPV) has become the accepted option. We performed a cross-sectional survey of parents of children less than 18 months of age to determine parental preference regarding poliomyelitis vaccine options. Parents were asked questions about their knowledge regarding poliomyelitis and available vaccines. Parents were also given information about the risks and benefits of the 3 immunization options (all OPV, all IPV, and sequential IPV/OPV) and then asked to choose among the 3 schedules. We distributed 146 questionnaires, with an 88% response rate. Parents were, on average, 22 years old and had 12 years of education. Fifty-eight percent of parents thought that decisions regarding vaccine choices should be made by the physician and caregiver together. However, when given the choice, 41 % could not decide among the different vaccine options. One quarter (25%) chose the all OPV, 13% the all IPV, and 21% the sequential IPV/OPV schedule. Older parents were more likely to choose the all IPV schedule (p=0.042). There was no correlation with the parental level of education. More studies are required to determine if further education will empower urban parents to be more active participants in the medical decision process.

Surveillance for poliovirus vaccine adverse events, 1991 to 1998: impact of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine.

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.

Inactivated poliovirus vaccine and the final stages of poliovirus eradication

The use of the inactivated poliovirus vaccine (IPV) will increase before and probably also after the global eradication of the wild type poliovirus. Before eradication, the switch from the use of oral poliovirus vaccine (OPV) to IPV has been due to the better safety record of IPV. Introduction of IPV in the regular immunisation schedules is made easier by the development of several combination vaccines, including IPV. Maternal antibodies and young age, often considered problematic for early initiation of IPV schedules, did not compromise optimal maintenance of seropositivity during infancy or long-term persisting antibody levels in our studies. OPV-derived, potentially pathogenic and transmissible poliovirus strains, excreted by some individuals for years, may present a problem for a blunt stopping of all polio immunisations after eradication. Our recent results suggest that locally excreted IgA might have a role in the elimination of poliovirus infection in the intestinal tissues.

Tetravalent Human-Rhesus Reassortant Rotavirus Vaccine

Tetravalent human-rhesus reassortant rotavirus vaccine (RRV-TV) contains the rhesus rotavirus (RRV) strain MMU 18006, which has serotype G3 specificity, and reassortant rotavirus strains with human serotype G1, G2 and G4 specificity. Rotavirus gastroenteritis in humans is predominantly caused by these 4 serotypes. RRV-TV 4 x 10(4), 4 x 10(5) or 4 x 10(6) plaque-forming units (PFU) per dose induces seroresponse rates (generally defined as a >or=4-fold increase in antibody titre) of 48 to 93% for IgA against RRV and 49 to 90% for neutralising antibodies to RRV after 1 to 3 doses in infants aged >or=4 weeks. Seroresponse rates for neutralising antibodies to human serotypes G1, G2, G3 and G4 are generally lower (2 to 68%). The rates generally increase with sequential doses, but not necessarily with increased vaccine titre. Seroresponse rates appear to be better in older infants than in neonates or infants aged <or=12 weeks. RRV-TV is more immunogenic against human G2, G3 and G4 serotypes than the monovalent serotype G1 human-rhesus reassortant rotavirus vaccine (RRV-S1) and tends to be more immunogenic against G1, G2 and G3 serotypes than the human serotype G1 strain vaccine M37. In most settings, RRV-TV has at least moderate efficacy in reducing the incidence of rotavirus gastroenteritis. Importantly, it protects against severe disease, with efficacy rates of 69 to 100% against very severe rotavirus gastroenteritis in large scale studies in the US, Finland and Venezuela. RRV-TV has similar overall efficacy to RRV-S1, but provides greater protection against gastroenteritis caused by rotavirus strains of serotypes other than G1. The efficacy of RRV-TV is not significantly affected by breast feeding or concurrent use of oral poliovirus vaccine. The only adverse effect with which RRV-TV has been associated is a mild, transient febrile reaction. Limited data from the US and Finland suggest that vaccination with RRV-TV could be cost saving. In conclusion, the incidence of paediatric rotavirus gastroenteritis, particularly severe cases, would be reduced in most settings by the incorporation of RRV-TV into routine childhood immunisation schedules. Further refinements to RRV-TV (and/or development of additional candidate vaccines) may eventually produce even greater protective efficacy. In the meantime, RRV-TV is a significant advance in the prevention of paediatric rotavirus gastroenteritis worldwide.

Control of Poliomyelitis in Kuwait

The use of oral poliovirus vaccine (OPV) in the early 1960s marked the beginning of the State's effort in controlling poliomyelitis in Kuwait. During the next two decades, despite the vaccine's availability and use, the disease continued to cause disability and death. However, with the massive and sustained use of the trivalent OPV since 1963G and the introduction of neonatal supplementary immunization with monovalent type 1 (MOPV) in 1976G along with strengthening of the surveillance activities against poliomyelitis, the incidence of the paralytic disease began declining and by the mid-eighties it disappeared altogether. With no cases of paralytic poliomylelitis reported in Kuwait since 1986G, the disease is largely controlled. The epidemiology of poliomyelitis in Kuwait has been examined here in retrospect. The paper profiles about 3 1/2 decades (1958G to 1992G) of efforts that led to this impressive virtual elimination of poliomyelitis. In order to maintain this status and eventually achieve the goal of eradication without the rare occurrence of vaccine-associated paralysis, it is, in our opinion, necessary to adopt an approach of combined vaccination with the inactivated polio vaccine (IPV), preferably in the neonatal age, followed by OPV. Simultaneously, monitoring the presence and circulation of wild poliovirus in the environment and continuous surveillance should be carried out for timely intervention.

Postoutbreak Polio Vaccination Policy in Israel

Sir .—In the unending debate between the proponents of oral polio virus vaccine (OPV) and those favoring the addition or substitution of the now enhanced-potency inactivated polio vaccine (E-IPV), the 1988 Israel poliomyelitis outbreak 1 was cited by Katz 2 in support of continuing, for the time being, the routine use of OPV in the United States. The 15 cases in the Israel outbreak occurred mainly in young adults immunized in the distant past with OPV, in a subdistrict where E-IPV had been used exclusively for several years. We agree with Dr Katz that the spread of wild poliovirus to susceptible people via the under-protected gastrointestinal tracts of E-IPV–vaccinated children was a major factor in the development of the epidemic. Nevertheless, despite wide circulation of wild virus, only a single case of paralytic disease was observed among some 27 000 children who had received E-IPV demonstrating the excellent individual protection

Live attenuated oral poliovirus vaccine.

During 1952-1954, some of the first papers were published on the attenuation of wild poliovirus for vaccine purposes. These efforts soon came to fruition , and large-scale field trials were held in many countries under a variety of conditions. Routine use of live oral poliovirus vaccines ( OPV ) was begun in many countries during the spring of 1960, and vaccines made from the Sabin strains were licensed in the United States in 1961-1962. In the early years of immunization with OPV , vaccines were usually monovalent, but a trivalent vaccine is now used. Throughout the world the introduction and continued proper use of OPV has been followed by a striking decrease in the number of paralytic cases. This dramatic and persistent outcome has stimulated recent discussions on the possible eradication of the disease. This paper reviews the criteria for the selection of vaccine strains that now make up the OPV , thermal stabilization of OPV , safety precautions that are followed in the manufacture of OPV , genetic stability of OPV strains following replication in vaccines and their contacts, and potential incorporation into OPV of totally attenuated polioviruses that can no longer revert to neurovirulence because the regions of the viral genome associated with neurovirulence are deleted or altered.

Observations on the use of oral poliovirus vaccines in the Caribbean and Canada.

Investigations on the use of poliovirus vaccines in the Caribbean and Canada are reviewed. Studies in Trinidad and Tobago in 1963 showed that children who were given two doses of oral poliovirus vaccine responded satisfactorily to the type 2 and type 3 components but poorly to the type 1 component. Studies on poliovirus vaccines in Canada have indicated that both killed and live vaccines are capable of controlling poliomyelitis. Results of studies undertaken in Ontario suggested that the response to a killed vaccine was not entirely satisfactory. The need for continued surveillance for poliomyelitis is emphasized. Action should be taken to review immunization procedures when a single case occurs. Consideration should be given to the use of monovalent vaccines in tropical countries.

Long-term use of oral poliovirus vaccine from Sabin strains in the Soviet Union.

Success in control of poliomyelitis in the USSR has been achieved after mass immunization with oral polio vaccine ( OPV ) manufactured from attenuated Sabin strains. Procedures for large-scale production of the OPV have been developed by Soviet researchers with the leadership of Chumakov and Smorodintsev , and the safety and efficacy of the vaccine have since been demonstrated. A mass immunization program was initiated in the USSR in 1959 and completed in 1960, covering 77.5 million people or 36.7% of the entire population. This immunization campaign resulted in a sharp decrease in the incidence of poliomyelitis: from 10.6 per 100,000 population in 1958 to 0.43 in 1963. Beginning in 1964 the incidence remained at a level of 0.01-0.1 per 100,000 population. At present the vaccination schedule consists of three basic vaccinations given to infants. Over 20 years of experience with OPV in the USSR has shown that this vaccine is a safe and efficient preparation.

Strategies for elimination of poliomyelitis in different parts of the world with use of oral poliovirus vaccine.

Since its first mass use in 1960, oral polio vaccine ( OPV ) has largely eliminated paralytic poliomyelitis from temperate-climate and subtropical regions of the world that have good health services and a combined total population of almost 2,000 million people. The various strategies used in these countries have been highly successful even where, as in the USA, large numbers of children received no vaccine or only a single dose of OPV . During the period of 1981-1982, only 2.8 cases per 100 million total population per year were reported in the USA. The main challenge in the present era is the economically undeveloped tropical and subtropical regions with inadequate health services that are inhabited by more than half of the world population, where recent surveys for residual paralysis due to poliomyelitis have shown that the incidence of the disease has been higher than it was in the USA and other predominantly temperate-climate countries before the vaccine era. The problem in these countries is that the majority of children receive no vaccine and that the extensive year-round dissemination of virulent polioviruses requires a different strategy of vaccination from that used in the temperate-climate countries. The special point about the annual mass vaccinations with OPV for all children younger than three, four, or five years of age-which have proven highly successful in Cuba (for the past 20 years), in Brazil (during the past three years), and recently also in Mexico-is that all the children are usually vaccinated within one or two days, which quickly breaks the chain of transmission of the virulent viruses, and the annual campaigns create and maintain the maximum number of children with resistant intestinal tracts.

Eradication of poliomyelitis in the United States.

Mass immunization with oral poliovirus vaccine (OPV) was begun in the United States in 1963, and the least natural outbreak of poliomyelitis occurred in 1972. Since immunization programs fail to reach the total population, eradication has been achieved in the presence of a residual susceptible population of at least 5% (2-5 million children under the age of 15 years). It is proposed that the fade-out of wild polioviruses is explained by their disappearance during the winter, a low point in the yearly cycle of the virus. In the post-eradication era, the continued presence of millions of susceptible children and adults presents a constant potential hazard. Every effort should be made to maintain maximal levels of immunization with oral poliovirus vaccine and to prevent the reintroduction of wild polioviruses into the United States.

PROBLEMS IN THE DEVELOPMENT AND USE OF ORAL POLIOVIRUS VACCINE.

I am highly honored to be one of the recipients of the Oscar B. Hunter Memorial Award. The esteem of one's colleagues is the greatest reward for a scientist. For the scientist realizes, as Aristotle pointed out long ago, that each one at best can add but a little to our knowledge of Nature, and that the real grandeur arises only from all the assembled facts.

Oral Vaccine: Associated Paralytic Poliomyelitis, 1962

UNTIL RECENTLY, there was almost universal agreement that living, attenuated, oral poliovirus vaccine (OPV) composed of the Sabin strains is safe, both to the primary vaccinee and to his contacts. This reputation for safety was won on the basis of the use of OPV in millions of persons in the US and many other countries. Although the thoroughness of routine reporting of morbidity and of special surveillance for possible vaccine-induced cases of paralytic poliomyelitis differed greatly among the various programs, no evidence had been adduced to show that this vaccine, composed of these strains, had ever caused the disease it was designed to prevent. From July through November, 1962, a small number of cases which had followed the use of oral vaccine came to light and they have cast some doubt on the safety of OPV in adult vaccinees. This cluster of cases was intensively studied and discussed in