Live Poliovirus Vaccine Research Articles

Regulations for the Manufacture and Control of Live Poliovirus Vaccine: International Experience and China's Path.

The eradication of poliomyelitis is a landmark achievement in the history of public health, providing strong protection for children's health. The introduction of the Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine is a prerequisite and safeguard for the large-scale production and use of domestically produced live poliovirus vaccines, serving as an indispensable component of vaccine safety. This article, based on archival documents, letters, collections of essays, and oral interviews, examines the historical experience of the development of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine. It contends that the emphasis on localization and the active engagement in international cooperation are critical factors in the swift introduction of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine.

Renegade cellular genetic sequences in stealth adapted viruses: introducing a new era of virology

DNA sequence data have previously been obtained on an African green monkey simian cytomegalovirus (SCMV)-derived stealth adapted virus. The virus was repeatedly cultured from a patient with the chronic fatigue syndrome (CFS). The data reveal not only genetic sequences that are derived from regions of the SCMV genome, but also the unexpected presence of genetic sequences that have originated from portions of the human cellular genome. The SCMV-derived stealth adapted virus has also acquired foreign genetic sequences of bacterial origin. The focus of this article is on the potential mechanism as well as the major biological and clinical ramifications of the primate to human and subsequent human to human viral transmission of genetically unstable renegade cellular genetic sequences. Insight into this topic has come from further analysis of rhesus monkey-derived cellular sequences in the stealth adapted viruses cultured from two other CFS patients and a mixture of both rhesus and human genome-derived cellular sequences in the virus cultured from another CFS patient. The virus acquired monkey cellular sequences are subject to ongoing mutations and can be replaced by human cellular sequences, probably by homologous recombination. There is a genetic basis for many human diseases, including cancers. The potential acquisition of pathogenic cellular sequences by stealth adapted viruses may, therefore, result in some of these genetic diseases becoming infectious. Stealth adapted viruses have been cultured from patients with a range of neurological and psychiatric illnesses, yet their existence is still not officially acknowledged by Public Health officials. The political reluctance to do so stems in part from the clearly implied origins of some stealth adapted viruses from the use of kidney cells from cytomegalovirus contaminated monkeys to produce live polio virus vaccines. It is imperative that the culturing and genetic analyses of stealth adapted viruses be pursued.

Multiplex PCR-based titration (MPBT) assay for determination of infectious titers of the three Sabin strains of live poliovirus vaccine

BackgroundConventional assays to titrate polioviruses usually test serial dilutions inoculated into replicate cell cultures to determine a 50% cytopathic endpoint, a process that is both time-consuming and laborious. Such a method is still used to measure potency of live Oral Poliovirus Vaccine during vaccine development and production and in some clinical trials. However, the conventional method is not suited to identify and titrate virus in the large numbers of fecal samples generated during clinical trials. Determining titers of each of the three Sabin strains co-existing in Oral Poliovirus Vaccine presents an additional challenge.ResultsA new assay using quantitative multiplex polymerase chain reaction as an endpoint instead of cytopathic effect was developed to overcome these limitations. In the multiplex polymerase chain reaction-based titration assay, cell cultures were infected with serial dilutions of test samples, lysed after two-day incubation, and subjected to a quantitative multiplex one-step reverse-transcriptase polymerase chain reaction. All three serotypes of poliovirus were identified in single samples and titers calculated. The multiplex polymerase chain reaction-based titration assay was reproducible, robust and sensitive. Its lower limits of titration for three Sabin strains were 1–5 cell culture 50% infectious doses per ml. We prepared different combinations of three Sabin strains and compared titers obtained with conventional and multiplex polymerase chain reaction-based titration assays. Results of the two assays correlated well and showed similar results and sensitivity. Multiplex polymerase chain reaction-based titration assay was completed in two to 3 days instead of 10 days for the conventional assay.ConclusionsThe multiplex polymerase chain reaction-based titration (MPBT) is the first quantitative assay that identifies and titrates each of several different infectious viruses simultaneously in a mixture. It is suitable to identify and titrate polioviruses rapidly during the vaccine manufacturing process as a quality control test, in large clinical trials of vaccines, and for environmental surveillance of polioviruses. The MPBT assay can be automated for high-throughput implementation and applied for other viruses including those with no cytopathic effect.

Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan

BackgroundOutbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks. MethodsSeronegative children for poliovirus type 2 (PV2) at 22 weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera). ResultsWe analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1–4 respectively. mOPV2 was more immunogenic than tOPV alone (p < 0.001); and OPV in combination with IPV was more immunogenic than OPV alone (p < 0.001). There were 33%, 67%, 20% and 43% PV2 excretors in Groups 1–4 respectively. mOPV2 resulted in more prevalent shedding of PV2 than when tOPV was used (p < 0.001); and tOPV together with IPV resulted in lower excretion of PV2 than tOPV alone (p = 0.046). ConclusionmOPV2 was a more potent vaccine than tOPV. Adding IPV to OPV improved immunological response; adding IPV also seemed to have shortened the duration of PV2 shedding. mIPV2 did not provide measurable improvement of immune response when compared to conventional IPV. WHO recommendation to use mOPV2 as a vaccine of first choice in cVDPV2 outbreak response was supported by our findings.Clinical Trial registry number: NCT02189811.

Support for Polio Vaccine Schedule with Bivalent Oral Poliovirus plus Inactivated Poliovirus Vaccine

The transition to a world without transmission of wild polioviruses involves eliminating use of live oral poliovirus vaccines in favor of inactivated

Evaluation of Vero-cell-derived simian endogenous retrovirus infection in humans by detection of viral genome in clinicopathological samples and commercialized vaccines and by serology of Japanese general population

BackgroundVero cells are used in laboratories for the isolation of viruses and the production of vaccines. Recently, the sequence of simian endogenous retrovirus (SERV) was identified in Vero cells (SERVagm-Vero), with homology to exogenously transmitted, pathogenic simian retroviruses (SRVs). Although SERVagm-Vero was shown to be noninfectious to human cells in vitro, SERV infection in humans is controversial. In this study, we evaluated the status of SERV infection in humans by detecting the viral genome in clinicopathological samples and commercialized vaccines, and with a serological survey of the Japanese general population. MethodsReal-time polymerase chain reaction (PCR) and reverse transcription–PCR were used to detect the SERVagm-Vero genome. We also examined the seroprevalence of SERV in 1000 individuals in the Japanese population with an enzyme-linked immunoabsorbent assay (ELISA) using mixed SERVagm-Vero gag, pol, and env proteins as antigens. ResultsReal-time PCR failed to detect SERVagm-Vero genomic fragments in 783 human clinicopathological samples, and all 13 human cell lines tested were negative for the SERVagm-Vero genome. Thirteen commercialized vaccines, including five Vero-based vaccines, were also negative for the SERVagm-Vero genome on real-time PCR and reverse transcription–PCR. Eight (0.8%) were seropositive on ELISA, and western blotting showed that all eight sera contained anti-pol antibodies. All SERV-seropositive individuals were born before 1965, suggesting that SERV infection in Japan might not be associated with vaccine, because more than 90% of Japanese children born from 1964 to 2012 have received live poliovirus vaccines containing virus produced in Vero cells since the 1980s. ConclusionWe have confirmed that the vaccines we use today are free of SERVagm-Vero. Moreover, SERV infection in humans is very rare and unlikely to be associated with vaccines in the Japanese general population.

Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria.

To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the rate for the wild type due to increased nonsynonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like virus evolution with the molecular clock for VP1 of circulating wild-type strains to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for Sabin-like virus type 1, 210 days for Sabin-like virus type 2, and 390 days for Sabin-like virus type 3. Phylogenetic relationships indicated transient local transmission of Sabin-like virus type 3 and, possibly, Sabin-like virus type 1 during periods of low wild polio incidence. Comparison of Sabin-like virus recombinants with known Nigerian vaccine-derived poliovirus recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin isolate-Sabin isolate and Sabin isolate-non-Sabin enterovirus recombination after accounting for the time from dosing to the time of detection. Our study provides a comprehensive picture of the evolutionary dynamics of the oral polio vaccine in the field. The global polio eradication effort has completed its 26th year. Despite success in eliminating wild poliovirus from most of the world, polio persists in populations where logistical, social, and political factors have not allowed vaccination programs of sustained high quality. One issue of critical importance is eliminating circulating vaccine-derived polioviruses (cVDPVs) that have properties indistinguishable from those of wild poliovirus and can cause paralytic disease. cVDPV emerges due to the genetic instability of the Sabin viruses used in the oral polio vaccine (OPV) in populations that have low levels of immunity to poliovirus. However, the dynamics responsible are incompletely understood because it has historically been difficult to gather and interpret data about evolution of the Sabin viruses used in OPV in regions where cVDPV has occurred. This study is the first to combine whole-genome sequencing of poliovirus isolates collected during routine surveillance with knowledge about the intrahost dynamics of poliovirus to provide quantitative insight into polio vaccine evolution in the field.

Prospective inactivated or live poliovirus vaccine: effectiveness in the 21st Century

Prospective inactivated or live poliovirus vaccine: effectiveness in the 21st Century

Substandard and/or counterfeit medicines for patients

There has been genuine concern at international levels to address the global scourge of fake medicines. WHO would soon launch a multidisciplinary task force to entangle, apart from health care providers, officials in police, customs and law enforcing agencies.1 Such efforts would fail without the availability of simple but accurate assay formats to assess the potency of medicines. Rather than retrieval to analytical laboratory premises to determine the potency of medicines offered to the masses, on-the-spot quantifications of active ingredients would be fundamental. Recent standardization of a rapid spectrometric analysis to monitor antimalarial formulations would appear to be an affirmative development.2 An identical test menu suited to patients’ homes or the field would assist in detection of poor-quality therapeutic agents. Nevertheless, without any prejudice towards a genuine or fake manufacturing process for any therapeutic agent, it would be crucial to tackle faulty storage of every medicine. Therapeutic agents require constant storage at temperatures ranging from subzero to 4–8 oC, 15–25 oC or 25–30 oC. Electrically operated appliances are indispensable to ensure constant storage at the stipulated temperatures. Natural disasters or extensive power failures adversely affect the potency of the active ingredients. The August 2005 Hurricane Katrina was accompanied by a prolonged power shutdown during which auxiliary power generators ran out of fuel.3 The consequences of similar accidental power shutdowns would be grim for genuine or fake therapeutic agents. The proposed international medical products anti-counterfeiting task force initiative1 would be obliged to point out defective storage and distribution practices in countries where medicines are available freely at the pharmacy sites. In urban Rawalpindi, Pakistan, most drug sellers had fragmentary knowledge regarding drug dispensing and storage. Improper dispensing practices were frequent, while only 10% had a temperature-monitoring device for electrically operated refrigerators. While refrigerators were present in 76% of pharmacy sites, only 4% had any alternative power supply for these appliances.4 The anti-counterfeiting initiative and pharmaceuticals industry should support basic research towards the field stability of common medicines in the adverse environments of disease-endemic areas. Experimental lots of the least stable of the common childhood vaccines, live poliovirus vaccine, have been stabilized by pirodavir and deuterium oxide. Stabilized lots resisted 42 oC temperatures for 10 hours.5 Certainly pre-stabilized, environment-resistant therapeutics, including antimicrobials and anti-infective formulations scrutinized in the field with portable instruments,1 would curtail inadvertent usage of poor-quality authentic drugs. Last but not least, the stipulated storage temperatures of therapeutics should be indicated with distinct symbols on vials or infusions. Universally accepted symbols are mandatory on poisons, inflammables and radioactive substances. Such distinct marks would not increase the cost of therapeutics in any manner. ■

Risk Management in a Polio‐Free World

Inherent in the decision to launch the Global Polio Eradication Initiative in 1988 was the expectation for many people that immunization against poliomyelitis would eventually simply stop, as had been the case with smallpox following its eradication in 1977. However, the strategies for managing the risks associated with a "polio-free" world must be continuously refined to reflect new developments, particularly in our understanding of the live polioviruses in the oral poliovirus vaccine (OPV) and in the international approach to managing potential biohazards. The most important of these developments has been the confirmation in 2000 that vaccine-derived polioviruses (VDPVs) can circulate and cause polio outbreaks, making the use of OPV after interruption of wild poliovirus transmission incompatible with a polio-free world. A comprehensive strategy has been developed to minimize the risks associated with eventual OPV cessation, centered on appropriate long-term biocontainment of poliovirus stocks (whether for vaccine production, diagnosis, or research), the controlled reintroduction of any live poliovirus vaccine (i.e., from an OPV stockpile), and appropriate use of the inactivated poliovirus vaccine (IPV). Although some aspects of this risk management strategy are still debated, there is wide agreement that no strategy would entirely eliminate the potential risks to a polio-free world. The current strategy for risk management in a polio-free world will continue to evolve with better characterization of these risks and the development of more effective approaches both to reduce those risks and to limit their consequences should they occur.

Developments in the production and quality control of poliovirus vaccines – Historical perspectives

Using virus grown in monkey kidney cells, Salk and his colleagues developed an inactivated poliovirus vaccine (IPV) in 1952. A large-scale field trial showed the vaccine to be safe and highly immunogenic in children, but soon after the vaccine became generally available in 1955, cases of paralytic disease were reported in recipients. Investigations showed that almost all the cases occurred in children who had received vaccine from one particular manufacturer. Extensive studies attributed the disaster to problems with inactivation. Addition of a Seitz filtration step midway during formalin inactivation and extension of the inactivation period resulted in a safe vaccine. No further paralytic cases were observed following the use of several hundred million doses of this improved vaccine. Thus, IPV was safe and caused a dramatic decline in the incidence of poliomyelitis in countries where it was used. A second generation IPV is produced in fermentors using well-characterized cell strains or continuous cell lines. The major breakthrough in the development of live poliovirus vaccine was the application of tissue culture methods for virus attenuation. By 1959 several candidate live oral poliovirus vaccines (OPV) had been developed. These were clinically tested in millions of individuals and found to be safe and effective. Since the attenuated virus strains developed by Koprowski and Cox were more neurotropic in monkeys than the Sabin strains, only the latter was licensed in the USA in 1961 and endorsed shortly after by the World Health Organization (WHO). The widespread use of Sabin's OPV in many countries hastened the development of International Requirements by WHO for OPV in 1962 to define the criteria that ensured the uniformity of batches produced by different manufacturers. These have been updated continuously in light of new information and quality control procedures. Extensive field trials have shown the risk of OPV associated polio to be less than 0.3 per million doses administered.

Splendid solution Jonas Salk and the conquest of polio

Splendid solution Jonas Salk and the conquest of polio

Nine-Year-Old Girl With Lymphangiectasia and Chest Pain

Nine-Year-Old Girl With Lymphangiectasia and Chest Pain

The Spatial Dynamics of Poliomyelitis in the United States: From Epidemic Emergence to Vaccine-Induced Retreat, 1910–1971

This article seeks to advance an understanding of the spatial dynamics of one of the great emergent viral diseases of the twentieth century—poliomyelitis. From an apparently rare clinical condition occurring only sporadically or in small outbreaks before the late nineteenth century, poliomyelitis had, by the early 1950s, developed into a globally distributed epidemic disease. But, from 1955, continued growth was suddenly and dramatically reversed by the mass administration of inactivated (killed) and live (attenuated) poliovirus vaccines. After almost half a century of vaccine control, the world now stands on the brink of the global eradication of the disease. Against this background, the article draws upon information included in the U.S. Public Health Service'sPublic Health Reports and the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report to examine the spatial dynamics of poliomyelitis during the phases of epidemic emergence (1910–1955) and vaccine-induced retreat (1955–1971) in the United States. It is shown that epidemic emergence was accompanied by shifts in the spatial center of activity from early diffusion poles in the northeastern states, to the western seaboard, and then finally to cover all the states of the Union. This was accompanied by accelerating epidemic propagation. The introduction of mass vaccination from the mid-1950s realigned spatial transmission of the disease, producing increased spatial volatility in the geographical center of activity and heightened dependence of epidemic outbreaks upon endemic reservoirs in the most populous states. Finally, the empirical results are generalized to suggest that the emergence and reemergence of many infectious diseases is a distinctively geographical process.

Special article: Polio: Its history and its eradication

Poliomyelitis has a long history, dating back at least to the Egyptian eighteenth dynasty (1580-1350 BC). In 1835, the first account of an outbreak of the disease was described by John Badham, and in 1840, Jacob von Heine, a German orthopedist, provided the first description indicating the spinal cord as the primary site of the paralytic form of the disease. During the late 19th and early 20th centuries, numerous epidemics began to occur with increasing frequency and severity. Many of these epidemics were accompanied by hysterical reactions. Because the paralyzed patients experienced respiratory compromise, artificial breathing support was needed. One of the devices most effectively used to manage the breathing for paralytic polio patients was the iron lung. In 1949, John Enders, Thomas Weller, and Frederick Robbins showed that poliovirus caused visible damage to primate cells derived from tissues other than those of the nervous system. This technology ultimately provided the means for producing large quantities of standardized poliovirus for the production of the killed vaccine (Salk vaccine, inactivated polio vaccine) and, eventually, the live poliovirus vaccines (Sabin vaccine, oral polio vaccine). The last case of wild strain poliomyelitis in the United States occurred in 1979. In 1998, the national vaccine advisory bodies responsible for recommending immunization began advocating the use of the enhanced inactivated polio vaccine as an alternative to the oral vaccine. Copyright © 2000 by W.B. Saunders Company

Development of a transgenic mouse neurovirulence test for oral poliovirus vaccine: international collaborative study 1993–1999

The neurovirulence safety of oral live poliovirus vaccine (OPV) has been tested in monkeys, because only primates are sensitive to all three types of poliovirus. The genetic engineering of transgenic mice susceptible to poliovirus led to studies on the suitability of these mice for a neurovirulence test of OPV. A WHO international collaborative study started with type-3 OPV in 1993 and was completed in 1999. The study produced a voluminous set of data proving that the TgPVR21 mice, inoculated with OPV samples into the lumbar cord, provided a test for neurovirulence of OPV as sensitive and reproducible as the monkey test. A statistical decision model for acceptance/rejection of type-3 vaccines using the transgenic mouse test has been developed. The mouse neurovirulence test showed a number of essential advantages over the monkey test. This is the first example of a successful introduction of transgenic animals into control of biologicals. In October 1999, the WHO Expert Committee on Biological Standardization approved TgPVR21 mice as alternative to the monkey model for neurovirulence testing of OPV type 3. A final step of the collaborative study with OPV types 1 and 2 is in progress, and data obtained so far are promising. Two breeding stations for production of TgPVR21 mice are being established in Asia and Europe.

Immunization in Hematopoietic Cell Transplantation

Our manuscript discusses recommendations about immunization in patients with hematopoietic cell transplantation (HCT). Each of the commonly administered vaccines is reviewed, current knowledge summarized, and areas for additional studies are presented. Some general concepts emerge. Live vaccines represent special risks, and the risks and benefits for each vaccine must be carefully assessed. Live poliovirus vaccine is contraindicated in all immunocompromising conditions, but an acceptable, alternative inactivated vaccine is widely available. Live measles and varicella vaccines have specific indications in HCT recipients, but caution should be exercised in their use. Inactivated vaccines can be generally regarded as safe in immunocompromised individuals, but immunogenicity and potential for protection vary by condition and severity of disease. Immunization appears to succeed best when vaccines can be administered before anticipated immunocompromise or after immunosuppression has ended. Booster doses of vaccine may be indicated in some circumstances where failure of response occurs. Priming of the donor with vaccine prior to harvest also may be an effective method to enhance the immune response in HCT recipients. We should also remember that household exposure to vaccine-preventable diseases poses a risk. Strategies that encourage immunization of susceptible household contacts may partially compensate for poor response to vaccines in the immunodeficient patient.

Parental knowledge and choice regarding live and inactivated poliovirus vaccines.

Concern about the 8 to 10 cases per year of vaccine-associated paralytic poliomyelitis caused by the live oral poliovirus vaccine (OPV) has led to revised guidelines for immunization of children in the United States. The use of inactivated poliovirus vaccine (IPV) at 2 and 4 months of age could require administration of 3 injections per visit until combination products are available. To determine parents' knowledge of poliovirus vaccines and the choices they would make between IPV and OPV. Parents of 240 children aged 2 weeks to 18 months under the care of 10 private pediatricians in the Baltimore, Md, metropolitan area were interviewed prior to the announcement of revised advisory committee guidelines. The majority (62.5%) of respondents were not aware that 2 poliovirus vaccines are available. After reviewing standardized information about the vaccines and 2 alternate schedules, most (75%) parents would consult someone (primarily their physician) before making a final choice of a vaccine schedule. If parents made the choice without consulting anyone else, 61.3% would choose to have their child receive IPV and 3 injections per visit as compared with an all-OPV schedule and 2 injections per visit. Inactivated poliovirus vaccine was preferred by most parents because it would reduce the risk for vaccine-associated paralytic poliomyelitis. Oral poliovirus vaccine was preferred by 37.9% of parents primarily because it was given orally. If the number of injections at each visit was the same for both vaccines, 76.3% of parents would choose the IPV schedule, and if the number of injections was reduced to 2 by combining IPV with another vaccine, 87.9% of parents would choose IPV. The number of injections per visit is an important issue, but a majority of parents would choose to have their children receive extra injections to prevent the low risk for vaccine-associated paralytic poliomyelitis.

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo ( N=7) or vaccine ( N=7) conditions. All control subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced γ-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

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.