The polio eradication effort has been a great success--let's finish it and replace it with something even better

The polio eradication campaign has greatly reduced the effects of this disease, but many new challenges have emerged. These challenges include the occurrence of polio outbreaks caused by wild-type polioviruses or circulating vaccine-derived polioviruses (cVDPVs) in areas where vaccination coverage is low, the existence of people who excrete poliovirus persistently, and the inability to know definitely that poliovirus has gone. As a result, there is uncertainty about if, when, and how we can end polio immunisation. In this article, we discuss several scenarios for the future of polio control. Because the emergence of cVDPVs necessitates discontinuing the use of live oral polio vaccine, we propose to strive towards a global coverage of near 100% vaccination against all major childhood infections using combination vaccines that contain inactivated poliovirus vaccine. Such a policy will present multiple challenges.     

Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany

Background  

In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster.     

Study of operational aspects of pulse polio booths during Intensified Pulse Polio Immunisation Campaign in assembly segments of East Delhi

The study was undertaken with the objective of observing operational aspects of 609 pulse polio booths established during Intensified Pulse Polio Campaign in East Delhi on National Immunisation Days (NID) during 2001-2002 through well designed format. The average number of persons present on duty at polio booths was 3.73 against a recommendation of 4 per booth. All the booths had vaccine carriers but some of them were not following the guidelines laid for maintaining the cold chain. One sixth "(15.4%)" of the booths needed fresh supplies of vaccine carrier. There is need for deployment of motivated trained manpower at polio booths to ensure the success of Pulse Polio Campaign. Maintenance of cold chain and quality assurance of vaccine administered to children in the field remain a challenge. More than half (55.7%) booths did not have any volunteer. Absence of volunteers from the community in more than half of the booths warrant for strengthening the linkages between the governmental agencies and the community.     

SV40 and human brain tumors

Persons treated with polio vaccine presumably contaminated with SV40 did not develop more tumors within 20 years after vaccination than did those who had received SV40-free vaccine. Some intracranial tumors, however, might be more frequent among persons who have been treated with contaminated vaccine.     

The “Performance of Rotavirus and Oral Polio Vaccines in Developing Countries” (PROVIDE) Study: Description of Methods of an Interventional Study Designed to Explore Complex Biologic Problems

Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings.     

Isolation of polioviruses from sewage and their characteristics: experience over two decades in Sweden.

Indigenous polio ceased in Sweden in 1962 after 5 years' use of killed polio vaccine. In 1967, it was considered of interest to investigate whether poliovirus was present in the sewage. A method for selective isolation of poliovirus from sewage was developed. The method appeared to increase the yield. The studies were carried out at intervals up to 1990. In 1989-90, the virus isolates were characterized by the use of monoclonal antibodies differentiating between vaccine-like (Sabin-like) and non-vaccine-like strains. Polioviruses of both kinds were isolated throughout the period. Two periods were of special interest. The first was in 1977, when a single, paralytic, type-2 case occurred in Sweden in an unvaccinated sect. The second was in 1984-85 when a type-3 epidemic broke out in Finland, followed by vaccinations of the whole Finnish population with live oral polio vaccine. On both occasions the implicated viruses could be traced to a high degree in sewage in Sweden. The absence of poliovirus isolations from faecal specimens of patients and the isolation of live poliovirus vaccine virus, i.e. a vaccine not used in Sweden, indicate that the virus strains are imported.     

Progress and challenges toward poliomyelitis eradication in Indonesia

Poliomyelitis is one of few diseases that can be eradicated. The virus cannot survive outside the body and effective vaccine is available to protect children and stop transmission. Today, there are 3 million children each year saved by the oral polio vaccine (OPV) and globally the reported cases have declined from 50,000 to 7,000 in 1999. At present, 20 countries may remain at risk of continued transmission, mostly in Africa and Asia. In the region of SEARO, wild poliovirus is still transmitted in India, Nepal and Bangladesh. Efforts to eradicate polio had been made in Indonesia, through a four-pronged strategy; routine immunization, National Surveillance Days (NIDs), surveillance of Acute Onset of Flaccid Paralysis (AFP) cases, and supplementary immunizations. No polio cases have been detected in Indonesia since 1995, but some problem will remain until the whole SEARO region is certified polio-free. Filling the immunization gap and revitalizing the AFP surveillance program are among the highest priority activities.     

Challenges and controversies in immunization safety

No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.     

Poliomyelitis in Oman. II. Toward eradication

In the past decade, the Sultanate of Oman has experienced three outbreaks of paralytic poliomyelitis--a widespread polio type 1 epidemic in 1988/1989, four cases of polio type 3 in three different regions in 1991, and a localized type 1 outbreak in 1993. The lessons learnt from each of these epidemics have guided us to modify and improve our polio eradication activities. Currently, these activities include administration of five primary and three booster doses of trivalent oral polio vaccine, yearly national immunization campaigns (NIDs) since 1995 with coverage of >90%, localized immunization campaigns, acute flaccid paralysis (AFP) surveillance which involves reporting of all cases by facsimile to the Department of Surveillance within 24 h of detecting a case and weekly zero reporting from 22 sentinel sites, and virological testing of stool specimens of all AFP cases and their close contacts at the national, World Health Organization accredited laboratory. The cumulative success of these activities has resulted in Oman being free from polio for the past 6 years. However, the possibility of importation of wild poliovirus, particularly from southern and western Asia still exists.     

Eradicating polio: today's challenges and tomorrow's legacy

Since its launch in 1988, the Global Polio Eradication Initiative has grown into one of the largest international health efforts in history, operating in every country and area in the world. The burden of polio disease has been reduced by over 99%, and the number of countries with indigenous virus has fallen from more than 125 to just four. As importantly, a strong surveillance and laboratory infrastructure has been established for vaccine-preventable diseases (including measles, tetanus, yellow fever, rubella and Japanese encephalitis), and a massive investment has been made in the physical infrastructure and human resources needed to deliver routine immunizations and other health services in developing countries. Between 2000 and 2003, new challenges to polio eradication emerged, threatening the interruption of the transmission of wild poliovirus globally and the eventual elimination of any residual polio disease as the result of the continued use of oral polio vaccines. By the end of 2005, a range of solutions had been developed to address these late challenges, including two new monovalent oral polio vaccines, new and robust international standards for the response to polio outbreaks, and renewed political commitment across the countries that remain infected. As importantly, a comprehensive strategy had been established for managing the long-term risks of paralytic polio, centred, ironically, on the eventual elimination from routine immunizations of the vaccine that is still central to the success of the global eradication effort.     

Seronegativity to polio viruses among previously immunized adult candidates to solid organ transplantation

In the current effort to eliminate polio from the world, it is important to recognize and vaccinate susceptible groups, especially immunocompromised patients living in countries where attenuated polio vaccine is still used. In this report, we describe the frequency of protective antibodies in a small sample of adult SOT candidates in whom previous vaccination could be ascertained. Patients included in this report were selected among the participants of an ongoing prospective study carried out at the Reference Center for Special Immunobiologicals of the Evandro Chagas National Institute of Infectious Diseases in Rio de Janeiro, Brazil. Among the first 100 patients enrolled in this study, only seven adult SOT candidates had proven polio vaccination at childhood. Three of these seven patients (43%) had no protective antibody titers to one or more poliovirus subtype before solid organ transplant. Proven childhood vaccination against polio does not reliably provide lifelong protective antibody titers for adult SOT candidates and should not be used as a criterion to analyze the need for vaccination in this population.     

Sabin monovalent oral polio vaccines: review of past experiences and their potential use after polio eradication.

After global eradication of polio is achieved, there will be a need for stockpiles of vaccine to combat potential outbreaks of poliomyelitis caused by (1) unforeseen release of polioviruses, (2) continued circulation of vaccine-derived strains, or (3) prolonged replication of polioviruses in immunodeficient persons. We conducted a review of the literature to document the immunogenicity and safety of monovalent Sabin vaccines, considered ideal candidates for these situations. The National Library of Medicine archives were searched for the keywords "polio," "monovalent," and "vaccine." Seroconversion rates for monovalent Sabin type 1 ranged from 53% to 100% (median, 95%); for type 2, 77%-100% (median, 93%); and for type 3, 52%-100% (median, 85%). The risk of vaccine-associated poliomyelitis per million persons vaccinated ranged from.05 to 0.99 (type 1), 0-0.65 (type 2), and 1.18-8.91 (type 3). Single-dose monovalent Sabin vaccines are highly immunogenic and safe and should be considered for stockpiles of vaccine to provide an effective response to potential outbreaks of poliomyelitis in the post-eradication period.     

Erythema multiforme minor following vaccination with paediatric vaccines

We present 2 cases of erythema multiforme following a combined tetanus and diphtheria revaccination and a combined diphtheria, tetanus, acellular pertussis inactivated polio and Haemophillus influenzae type B vaccine respectively, suggesting vaccines containing diphtheria and tetanus toxoids as a potential precipitating factor to erythema multiforme.     

Immunomodulatory vaccination in autoimmune disease.

The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously.     

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age

OBJECTIVE: The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS: Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 mug/mL or greater and 1.0 mug/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS: The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine.     

Characteristics of the immune response to poliovirus virion polypeptides after immunization with live or inactivated polio vaccines

Groups of infants were immunized with high-potency, inactivated polio vaccine (IPV) or live, attenuated oral polio vaccine (OPV) and studied for antibody responses to whole virus and polypeptides VP1, VP2, and VP3. Both vaccines induced neutralizing and enzyme-linked immunosorbent assay (ELISA) IgG to the whole virus, IgG antibody to VP1 and VP3, and similar secretory IgA to VP1 and VP2 in the nasopharyngeal secretions (NPS) without any VP3 response. Virus-specific neutralizing activity in NPS was observed in 70% of subjects receiving OPV and in only 26.7% of subjects receiving IPV. ELISA antibody also appeared to be lower in IPV than in OPV subjects. These observations suggest that specific ELISA antibody to poliovirus virion proteins can be frequently induced in the secretory sites, by OPV as well as by IPV. Neutralizing antibody response in the NPS appeared, however, to be more effectively induced by OPV than by the high-potency IPV.     

Strategy for controlling poliomyelitis in Mexico: greater vaccination coverage of children less than 1 year of age

In spite of the widespread use of oral poliovirus vaccine, some countries have not achieved an optimal control of poliomyelitis. According to Sabin, this fact is due to a lack of immunization coverage of children under one year of age. In this study, the relationship between the general morbidity rate for polio and vaccination coverage of children under one year of age, in people protected by the Mexican Institute of Social Security, is analyzed. There is a negative correlation between these two variables: the lesser the coverage, the greater the rates. There is also a correlation between the rate of polio and the rate of polio for the year prior to each of the years of the study period. In a multiple regression model, both the coverage and the rate for the previous year were significantly correlated with the rate of polio. In order to get an optimum control of this disease, it is advantageous to consider that it is not enough to increase the coverage but that this coverage must be opportune, i.e., in the first year of life.     

Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines.

Oral polio vaccine (OPV) is recommended for routine immunization in the United States in part because of its ability to induce intestinal and pharyngeal immunity to reinfection. Mucosal immunity produced by OPV and enhanced-potency inactivated polio vaccine (E-IPV) was compared by challenging vaccines with type 1 OPV. Fewer OPV (25%) than E-IPV (63%) vaccinees excreted OPV virus in stool after challenge. The mean stool virus titer was higher and the duration of shedding longer among E-IPV excreters. Only one E-IPV and three OPV vaccinees shed virus in the pharynx after challenge. Prechallenge serum neutralizing antibody levels were not statistically different among E-IPV vaccinees who did and did not shed virus; these levels were much higher than those of OPV vaccinees. Poliovirus-specific IgA levels in stool did not correlate with viral excretion. E-IPV was less effective than OPV in preventing and limiting intestinal infection, even though it induced higher postvaccination serum antibody levels.     

Annual cluster (pulse) immunization experience in villages near Sevagram, India

This simple study was undertaken in a 'Third World' rural area to find an appropriate strategy for mass vaccination. The low priority given to preventive health requirements, coupled with a lack of awareness of possible benefits, inaccessibility of vaccination facilities and misconceptions about vaccination, prevent poor, illiterate villagers from reaping these benefits. The 'cluster approach', utilizing locally available manpower, has been attempted. Availability of an immunization facility, free of charge, in a village, when required proved essential for wide coverage. Some 75.2% of children received three doses of polio vaccine, and 43.22% received five doses, in a total of five visits. With an additional (6th) visit, the figures rose to 80.66% receiving three doses and 55.06% receiving five doses. Results with single dose measles vaccine reached 95%. The reasons for defaulters have been investigated and remedial measures suggested. For five doses of polio vaccine the total man-hour requirement was 79 h, of which skilled manpower was employed for only 3 h, while the major share (33 h) fell to the village-level health worker. We consider that the 'cluster approach' is replicable and that it produces satisfactory results.     

Oral polio vaccines have not yet covered West Africa: survey of immunization coverage conducted in Niger

Following the re-emergence of polio in West Africa, an investigation was conducted on the occasion when transients gather for the festival in Niger, where the oral polio vaccine (OPV) and BCG coverage among children under the age of 5 years can be evaluated. A total of 259 children were investigated, including 186 from settled families and 73 from unsettled families. OPV coverage was found to be as low as 32.4%, and 61.8% of all participants in the study had not received both OPV and BCG. There were more children who had not received the OPV in unsettled families than in settled families. As there are still unvaccinated children in Niger, polio continues to occur among them. Moreover, outbreaks can transfer to more densely-populated areas, causing much larger outbreaks. To stop the chain of transmission, it is essential to reconsider the strategy of mass vaccination in order to cover all children thoroughly, including transients.