Vaccine-associated Paralytic Poliomyelitis Cases Research Articles

Surveillance of acute flaccidparalysis and poliomyelitison some territories of Russia and South Vietnam. Part 1. Polioviruses and paralysis

The epidemiological and etiological aspects of poliomyelitis and acute flaccid paralysis (AFP) in Russia and Vietnam were analysed and compared. The polio-free status is maintained on 14 territories of Russia and 29 provinces of South Vietnam. The quality of epidemiological and virological surveillance for acute flaccid paralysis is in accordance with the requirements of the national and international polio surveillance systems. All AFP cases were revealed, registered, reported and investigated in both countries. The percentage of poliovirus isolation from 2492 samples collected from patients with acute flaccid paralysis and contact persons in different years in Russia ranged from 1.30.89 to 9.80.79. In South Vietnam, 2143 samples from patients with acute flaccid paralysis were investigated. In Russia and Vietnam, we isolated vaccine polioviruses of all three types with predominance of type 3 polioviruses (63% and 50%, respectively) in both countries. From AFP patients in Russia and Vietnam, polioviruses were isolated in 4.9% and 1.0% studied samples, respectively. Some VDPV strains were revealed on the territories of Russia and South Vietnam. Here, we describe five cases of vaccine-associated paralytic poliomyelitis registered in Russia and two cases of AFP caused by VDPV type 2 reported in Vietnam. To prevent the risk of developing vaccine-associated paralytic poliomyelitis, it is indispensable to ensure high-quality surveillance for acute flaccid paralysis, maintain 95% polio vaccine pediatric coverage and strictly comply with sanitary legislation, including the National Vaccination Schedule when vaccinating children, to improve virological surveillance of polioviruses using classical and new virological and molecular methods and to continue research on poliomyelitis, including development of new safe and effective poliovirus vaccines able to induce both humoral and mucosal immunity. The systematic control of adequate polio vaccination is indispensable in order to prevent transmission of imported wild polioviruses into polio free countries as well as circulation of vaccine-derived polioviruses worldwide.

Genetic Characterization of Novel Oral Polio Vaccine Type 2 Viruses During Initial Use Phase Under Emergency Use Listing - Worldwide, March-October 2021.

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL.

Untranslated region-5’ and viral protein 1-based genetic stability analysis of bulk polio in Indonesia 2010-2019

Cases of vaccine-associated paralytic poliomyelitis (VAPP) continued increasingly from 2010-2019 in the world. Oral polio vaccine (OPV) is the live attenuated virus-based vaccine that could genetically revert to neurovirulent during the vaccine production process or when the virus replicates in the human body. The poliovirus neurovirulence is determined by the UTR-5' region and VP1 coding region. UTR-5' played a role in protein translation and VP1 was responsible for the immunogenicity of the virus. Some reported mutations in UTR-5' and VP1 could affect the neurovirulence of poliovirus. In this study, we analyzed the genetic stability of the UTR-5' and VP1 in the bulk of OPV types -1 and -3 produced in 2010 - 2019. The results of the analysis of UTR-5' sequences in Sabin strain types-1 and -3 and VP1 sequences on Sabin virus type 1 did not show any mutations. Meanwhile, the VP1 sequences in Sabin strain type 3 showed nucleotide mutation C2493U that caused the substitution amino acid Thr6Ile amino acid in all samples of the type 3 bulk polio test. Based on the results of in silico analysis, this mutation in VP1 did not contribute significantly to the neurovirulence of the virus.

Enlightment of routine vaccination under the prevention and control of COVID-19 based on the circulating event of type Ⅲ vaccine-derived poliovirus in Shanghai

Since the Global Polio Eradication Initiative was launched by the World Health Assembly in 1988, significant progress has been made in global polio prevention and control. But the occurrence of vaccine-associated paralytic poliomyelitis cases and vaccine-derived poliovirus related cases have become a major challenge during the post-polio era. While coronavirus disease 2019(COVID-19) has brought serious disease burden and economic burden to all countries in the world, prevention and control of vaccine-preventable infectious diseases such as polio should not be neglected under the background of the global common fight against COVID-19. Taking the type Ⅲ VDPV cycle event in Shanghai as an example, the paper discussed how to do a good job of routine inoculation under the prevention and control of COVID-19 to strictly prevent the outbreak of vaccine-preventable infectious diseases.

Cost-Effectiveness of Three Poliovirus Immunization Schedules in Shanghai, China.

In Shanghai, China, a polio immunization schedule of four inactivated polio vaccines (IPV) has been implemented since 2020, replacing the schedules of a combination of two IPVs and two bivalent live attenuated oral polio vaccines (bOPV), and four trivalent live attenuated oral polio vaccines (tOPV). This study aimed to assess the cost-effectiveness of these three schedules in infants born in 2016, in preventing vaccine-associated paralytic poliomyelitis (VAPP). We performed a decision tree model and estimated incremental cost-effectiveness ratio (ICER). Compared to the four-tOPV schedule, the two-IPV-two-bOPV schedule averted 1.2 VAPP cases and 16.83 disability-adjusted life years (DALY) annually; while the four-IPV schedule averted 1.35 VAPP cases and 18.96 DALY annually. Consequently, ICERVAPP and ICERDALY were substantially high for two-IPV-two-bOPV (CNY 12.96 million and 0.93 million), and four-IPV (CNY 21.24 million and 1.52 million). Moreover, net monetary benefit of the two-IPV-two-bOPV and four-IPV schedules was highest when the cost of IPV was hypothesized to be less than CNY 23.75 or CNY 9.11, respectively, and willingness-to-pay was hypothesized as CNY 0.6 million in averting one VAPP-induced DALY. IPV-containing schedules are currently cost-ineffective in Shanghai. They may be cost-effective by reducing the prices of IPV, which may accelerate polio eradication in Chinese settings.

Primary immunodeficiency masks: A clinical case of vaccine-associated paralytic poliomyelitis

Human inborn immune-related errors comprise a heterogeneous group of rare genetically determined diseases of the immune system caused by loss or gain of function mutations altering relevant protein functions. The 2019 International Union of Immunological Societies recently proposed the classification for such pathologies now comprising 406 distinct disorders with 430 different gene defects. Predominantly antibody deficiencies represent most common group of human inborn immune-related errors, which diagnostics poses uneasy challenge for general practitioner due to a broad range of their clinical manifestations, such as infection, allergy, autoimmunity and malignancy. In addition, patients with human immune-related inborn errors may develop a vaccine-associated disease after administering live vaccines in accordance with the Russia-wide National Vaccine Schedule. Most common among vaccine-associated diseases are vaccine-associated paralytic poliomyelitis, vaccine-associated encephalitis (1 case per 1 000 000 doses of measles, rubella, varicella vaccine), vaccine-associated meningitis (1 case per 250 000 – 500 000 doses of mumps vaccine) as well as adverse effects related to BCG immunization: local (infiltration, cold abscess – 8.6 case per 100,000 vaccinated patients) and disseminated complications (BCG lymphadenitis – 15.5 case per 100 000 vaccinated patients, BCG osteitis – 3.5 case per 100 000 vaccinated patients). Vaccine-associated paralytic poliomyelitis in vaccinated patients occurs after the first, second and rarely third oral polio vaccine dose inoculation. Incidence rate for vaccineassociated paralytic polio after 1 and 3 oral vaccine inoculation ranges from 1 case per 700 000 vaccine doses to 1 case per 3 500 000, respectively. Vaccine-associated paralytic poliomyelitis mainly emerges due to inborn mutations related to humoral immunity after primary vaccination with oral polio vaccine or close contact of unvaccinated patients with subjects vaccinated with oral polio vaccine. Here, we describe a clinical case of vaccine-associated paralytic poliomyelitis in patient with primary immunodeficiency. Our is aimed at emphasizing importance of immunological alertness with regard to detecting primary immunodeficiencies and timely apply a replacement therapy prior to verifying type of immunodeficiency.

Vaccineassociated paralytic poliomyelitis and acute flaccid paralysis on some territories of Russia during 20 years

Aim: Analysis of the morbidity of vaccine-associated paralytic poliomyelitis and acute flaccid paralysis and the results of virological investigation of the patients on 14 territories of the Russian Federation in 1998-2017. Materials and methods: We investigated nearly 3000 stool samples from paralytic patients and contact persons. Isolation and identification of polioviruses were performed according to WHO recommendations with the help of cell lines RD and L20B. We conducted the sequencing of the genome fragments VP3-VP1, VP1-2A and full sequencing of genome region VP1 of 45 poliovirus strains. Results: From 1998 till 2017 1257 cases of acute flaccid paralysis were registered on 14 territories of Russia, 15 cases of which (1,2%) were classified as vaccine-associated paralytic poliomyelitis. From these patients 9 children were non vaccinated and 6 children received from one to four doses of oral poliomyelitis vaccine. The percentage of the detection of polioviruses from the patients and contact persons in different years was not equal and constituted from 3, 4±0,89% to 9, 5±0,79%. All in all from the patients with acute flaccid paralysis and contact persons we isolated 191 polioviruses, 60 of them belonged to type 1, 55 polioviruses were identified as types 2 and 76 as type 3. Some cases of vaccine-associated paralytic poliomyelitis are described in the article; polioviruses were isolated from all these patients. The sequencing of the genome fragments of 45 poliovirus strains showed that the majority of them had the nucleotide substitutions including neurovirulent substitutions. Conclusion:In order to prevent the risk of the appearance of vaccine-associated paralytic poliomyelitis it is necessary to maintain the high quality of surveillance of poliomyelitis and acute flaccid paralysis, to ensure the 95% coverage of children with poliomyelitis vaccine, to minimize the cases of groundless delays of vaccination according to medical recommendations and parents’ refusals to vaccinate children against poliomyelitis and to respect strictly the National calendar of vaccination.

Vaccine-associated paralytic poliomyelitis in the Russian Federation in 1998–2014

ObjectivesDifferent polio vaccination schemes have been used in Russia: oral polio vaccine (OPV) was used in 1998–2007 and inactivated polio vaccine (IPV) followed by OPV in 2008–2014. This article presents the characteristics of vaccine-associated paralytic poliomyelitis (VAPP) cases in Russia during this period. MethodsVAPP cases were identified through the acute flaccid paralysis surveillance system, classified by the National Expert Classification Committee. Criteria for a ‘recipient VAPP’ (rVAPP) case were poliomyelitis symptoms 6–30days after OPV administration, isolation of the vaccine virus, and residual paralysis 60days after disease onset. Unvaccinated cases with a similar picture 6–60days after contact with an OPV recipient were classified as ‘contact VAPP’ (cVAPP) cases. ResultsDuring 1998–2014, 127 VAPP cases were registered: 82 rVAPP and 45 cVAPP. During the period in which only OPV was used, rVAPP cases prevailed (73.8%); cases of rVAPP were reduced during the sequential scheme period (15%). Poliovirus type 3 (39.5%) and type 2 (23.7%) were isolated more often. Vaccine-derived poliovirus types 1, 2, and 3 were isolated from three cases of cVAPP. The incidence of VAPP cases was higher during the period of OPV use (1 case/1.59 million OPV doses) than during the sequential scheme period (1 case/4.18 million doses). ConclusionThe risk of VAPP exists if OPV remains in the vaccination schedule.

Introduction of Inactivated Poliovirus Vaccine and Impact on Vaccine-Associated Paralytic Poliomyelitis - Beijing, China, 2014-2016.

When included in a sequential polio vaccination schedule, inactivated polio vaccine (IPV) reduces the risk for vaccine-associated paralytic poliomyelitis (VAPP), a rare adverse event associated with receipt of oral poliovirus vaccine (OPV). During January 2014, the World Health Organization (WHO) recommended introduction of at least 1 IPV dose into routine immunization schedules in OPV-using countries (1). The Polio Eradication and Endgame Strategic Plan 2013-2018 recommended completion of IPV introduction in 2015 and globally synchronized withdrawal of OPV type 2 in 2016 (2). Introduction of 1 dose of IPV into Beijing's Expanded Program on Immunization (EPI) on December 5, 2014 represented China's first province-wide IPV introduction. Coverage with the first dose of polio vaccine was maintained from 96.2% to 96.9%, similar to coverage with the first dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP) (96.5%-97.2%); the polio vaccine dropout rate (the percentage of children who received the first dose of polio vaccine but failed to complete the series) was 1.0% in 2015 and 0.4% in 2016. The use of 3 doses of private-sector IPV per child decreased from 18.1% in 2014, to 17.4% in 2015, and to 14.8% in 2016. No cases of VAPP were identified during 2014-2016. Successful introduction of IPV into the public sector EPI program was attributed to comprehensive planning, preparation, implementation, robust surveillance for adverse events after immunization (AEFI), and monitoring of vaccination coverage. This evaluation provided information that helped contribute to the expansion of IPV use in China and in other OPV-using countries.

Vaccine-associated paralytic poliomyelitis in Russian Federation during the period of changes in vaccination schedule (2006-2013 y.y.)

The results of virologic testing of clinical materials and epidemiological analysis of vaccine-associated paralytic poliomyelitis (VAPP) cases obtained in 2006-2013 during AFP surveillance are presented. Among the 2976 cases of AFP 30 cases were vapp. 15 cases were observed in OPV recipients, whereas 15 cases were observed in non-vaccinated contacts. The age of the patients varied from 4 months to 5.5 years (13.6 ± 12.4 months old). Children younger than 1 year constituted 63.3% of the group; boys were dominant (73.3%); 53.3% of children were vaccinated with OPV; the time period between receipt of OPV and onset of palsy was from 2 to 32 days (18.7 ± 8.2). Lower paraparesis was documented in 48.3% of patients; lower monoparesis, in 37.9%; upper monoparesis, in 6.9%; tetraparesis with bulbar syndrome, in 6%. the majority of the patients (85.7%) had an unfavorable premorbid status. The violations of the humoral immunity were found in 73.9% cases: CVID (52.9%), hypogammaglobulinemia (41.2%), selective IgA deficiency (5.9%). In 70.6% cases damage to humoral immunity was combined with poor premorbid status. The most frequently observed (76%, p 0.05) represented the single type of poliovirus – type 2 (44%) and type 3 (32%). All strains were of the vaccine origin, the divergence from the homotypic Sabin strains fell within the region of the gene encoding VP1 protein, which did not exceed 0.5% of nucleotide substitutions except vaccine derived poliovirus type 2 – multiple recombinant (type 2 / type 3 / type 2 / type 1) with the degree of the divergence of 1.44% isolated from 6-month old unvaccinated child (RUS-08063034001). The frequency of the VAPP cases was a total of 1 case per 3.4 million doses of distributed OPV in 2006-2013; 2.2 cases per 1 million of newborns were observed. This frequency decreased after the introduction of the sequential scheme of vaccination (ipv, Opv) in 2008-2013 as compared with the period of exclusive use of OPV in 2006-2007: 1 case per 4.9 million doses, 1.4 cases per 1 million newborns and 1 case per 1.9 million doses, 4.9 cases per 1 million newborns, respectively.

Integrative representations and analyses of vaccine-induced intended protective immunity and unintended adverse events using ontology-based and theory-guided approaches.

While effective preventive vaccines induce intended protective immunity, they also induce unintended adverse events (AEs). Generally speaking, compared to killed, inactivated vaccines and protein vaccines, live attenuated vaccines induce more protective immune responses. However, live attenuated vaccines are also associated with more AEs and even more serious AEs. For example, while live attenuated smallpox vaccines were critical to the eradication of smallpox, approximately 20–30% of smallpox vaccine recipients also experienced with various AEs that range in prevalence and severity [1]. Inter-individual variations in cytokine and AE response after smallpox vaccinations are in part due to genetic variation. For another example, the attenuated oral poliovirus vaccine (OPV) efficiently induces intestinal immunity and durable humoral immunity. However, OPV has the disadvantage of genetic instability, contributing to rare and sporadic cases of vaccine-associated paralytic poliomyelitis and the emergence of genetically divergent vaccine-derived polioviruses [2]. These AEs are worsened in patients with primary immunodeficiencies. These results suggest that the intended protective immune responses and unintended adverse events are correlated and deserve being studied simultaneously.

Health and economic consequences of different options for timing the coordinated global cessation of the three oral poliovirus vaccine serotypes.

BackgroundWorld leaders remain committed to globally-coordinated oral poliovirus vaccine (OPV) cessation following successful eradication of wild polioviruses, but the best timing and strategy for implementation depend on existing and emerging conditions.MethodsUsing an existing integrated global poliovirus risk management model, we explore alternatives to the current timing plan of coordinated cessation of each OPV serotype (i.e., OPV1, OPV2, and OPV3 cessation for serotypes 1, 2, and 3, respectively). We assume the current timing plan involves OPV2 cessation in 2016 followed by OPV1 and OPV3 cessation in 2019 and we compare this to alternative timing options, including cessation of all three serotypes in 2018 or 2019, and cessation of both OPV2 and OPV3 in 2017 followed by OPV1 in 2019.ResultsIf Supplemtal Immunization Activity frequency remains sufficiently high through cessation of the last OPV serotype, then all OPV cessation timing options prevent circulating vaccine-derived poliovirus (cVDPV) outbreaks after OPV cessation of any serotype. The various OPV cessation timing options result in relatively modest differences in expected vaccine-associated paralytic poliomyelitis cases and expected total of approximately 10–13 billion polio vaccine doses used. However, the expected amounts of vaccine of different OPV formulations needed changes dramatically with each OPV cessation timing option. Overall health economic impacts remain limited for timing options that only change the OPV formulation but preserve the currently planned year for cessation of the last OPV serotype and the global introduction of inactivated poliovirus vaccine (IPV) introduction. Earlier cessation of the last OPV serotype or later global IPV introduction yield approximately $1 billion in incremental net benefits due to saved vaccination costs, although the logistics of implementation of OPV cessation remain uncertain and challenging.ConclusionsAll countries should maintain the highest possible levels of population immunity to transmission for each poliovirus serotype prior to the coordinated cessation of the OPV serotype to manage cVDPV risks. If OPV2 cessation gets delayed, then global health leaders should consider other OPV cessation timing options.

Vaccine-Derived Polioviruses

The attenuated oral poliovirus vaccine (OPV) has many properties favoring its use in polio eradication: ease of administration, efficient induction of intestinal immunity, induction of durable humoral immunity, and low cost. Despite these advantages, OPV has the disadvantage of genetic instability, resulting in rare and sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) and the emergence of genetically divergent vaccine-derived polioviruses (VDPVs). Whereas VAPP is an adverse event following exposure to OPV, VDPVs are polioviruses whose genetic properties indicate prolonged replication or transmission. Three categories of VDPVs are recognized: (1) circulating VDPVs (cVDPVs) from outbreaks in settings of low OPV coverage, (2) immunodeficiency-associated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVDPVs), which cannot be definitively assigned to either of the first 2 categories. Because most VDPVs are type 2, the World Health Organization's plans call for coordinated worldwide replacement of trivalent OPV with bivalent OPV containing poliovirus types 1 and 3.

Vaccine-associated paralytic poliomyelitis in Japan

Despite WHO's recommendation to switch the poliomyelitis vaccine from oral polio vaccine (OPV) to inactivated polio vaccine (IPV) in countries where polio elimination has been achieved, Japan has continued to use OPV. In Japan, OPV is given twice to children aged from 3 to 18 months.1 More than 10 years after the elimination of wild polio virus, tragic cases of vaccine-associated paralytic poliomyelitis (VAPP) continue to be reported every year—most recently in May, 2011. The Ministry of Health, Labour and Welfare claims that IPV is still being developed by Japanese vaccine companies and that it will not be available until the end of 2012 at the earliest. The growing tension between the Government, which persists with domestically produced OPV, and the parents, who request IPV to avoid VAPP, has evoked huge media attention.

History of polio vaccination

Poliomyelitis is an acute paralytic disease caused by three poliovirus (PV) serotypes. Less than 1% of PV infections result in acute flaccid paralysis. The disease was controlled using the formalin-inactivated Salk polio vaccine (IPV) and the Sabin oral polio vaccine (OPV). Global poliomyelitis eradication was proposed in 1988 by the World Health Organization to its member states. The strategic plan established the activities required for polio eradication, certification for regions, OPV cessation phase and post-OPV phase. OPV is the vaccine of choice for the poliomyelitis eradication program because it induces both a systemic and mucosal immune response. The major risks of OPV vaccination are the appearance of Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) and the emergence of Vaccine Derived Polioviruses strains. The supplementary immunization with monovalent strains of OPV type 1 or type 3 or with a new bivalent oral polio vaccine bOPV (containing type 1 and type 3 PV) has been introduced in those regions where the virus has been difficult to control. Most countries have switched the schedule of vaccination by using IPV instead of OPV because it poses no risk of vaccine-related disease. Until 2008, poliomyelitis was controlled in Romania, an Eastern European country, predominantly using OPV. The alternative vaccination schedule (IPV/OPV) was implemented starting in September 2008, while beginning in 2009, the vaccination was IPV only. The risk of VAPP will disappear worldwide with the cessation of use of OPV. The immunization for polio must be maintained for at least 5 to 10 years using IPV.

Impacto económico de la introducción de la vacuna inactivada inyectable contra la poliomielitis en Colombia

Evaluate the cost-effectiveness of introducing the injectable inactivated polio vaccine (IPV) in Colombia versus the current system based on the use of the oral vaccine (OPV). A Markov model was designed, based on a hypothetical cohort of newborns that would receive the IPV or the OPV vaccine, with a two-year follow-up and monthly estimates of the number of cases of vaccine-associated paralytic poliomyelitis (VAPP) that would emerge. The cost was analyzed from the perspective of the insurer (costs throughout life) and society (cases of VAPP and disability-adjusted life years [DALYs] prevented). From 1988 to 1998, some 22.5 million doses of OVP were administered in Colombia and nine cases of VAPP were detected, for a rate of 4.0 yen 10-7 dose. According to the model, 2 to 4 cases of VAPP could be anticipated in the following two years. The cost of treating the VAPP cases would total US$302,008, with the cost of vaccination with OPV coming to US$737,037 and with IPV, US$5,527,777. Vaccination with IPV would prevent 64 DALYs, at a cost of US$71,062 per DALY prevented; preventing one case of VAPP by substituting OPV with IPV would cost between US$1.8 and US$2.2 million. Substituting OPV with IPV is not a cost-effective measure in Colombia, even if the cellular vaccine against whooping cough currently in use were replaced with an acellular vaccine combined with an IPV.

Switching from OPV to IPV: are we behind the schedule in Latin America?

Oral polio vaccine (OPV) has been an effective strategy since it was initiated almost five decades ago. However, concern regarding its collateral effects has been increasing in recent years among the scientific and policymaker community, since it has proved to be of risk for immunocompetent and immunocompromised individuals by causing cases and even outbreaks of poliomyelitis disease in countries where the virus is not circulating. Enhanced-potency inactivated polio vaccine (IPV), a safer, effective and inexpensive vaccine, has been available for the past couple of decades. Different points of view have emerged regarding stopping the use of OPV to start routine general IPV but, despite the evidence of OPVs derived and associated with unnecessary poliomyelitis cases, Central and South America are still lacking a strategy in place to make the switch from OPV to IPV, and there are no leading efforts to start this strategy. This review gives some evidence-based elements to help raise criteria regarding the best vaccine to choose and highlights the current need for strategic planning in Latin America to avoid more vaccine-associated paralytic poliomyelitis cases.

Molecular characterization of poliovirus isolates from children who contracted vaccine-associated paralytic poliomyelitis (VAPP) following administration of monovalent type 3 oral poliovirus vaccine in the 1960s in Hungary

Hungarian children were immunized with monovalent oral poliovaccine (mOPV) delivered at 6-week intervals in the order Sabin 1, Sabin 3, Sabin 2, from 1959 until 1992. During that period, 90 cases of vaccine-associated paralytic poliomyelitis (VAPP) were reported, 52 of which were associated with Sabin 3-related virus (76% of VAPP cases with virologic data). Because of renewed interest in type 3 mOPV (mOPV3), molecular methods were used to reanalyze 18 of the Sabin 3-related isolates from 15 VAPP patients, confirming the original identification. All isolates had the U472C 5'-untranslated region (5'-UTR) substitution associated with reversion to neurovirulence, and from zero to seven nucleotide substitutions in the virus protein 1 (VP1) region. No evidence was found for prolonged mOPV3 replication in the VAPP patients or for spread of Sabin 3-related viruses beyond close vaccinee contacts. The VAPP diseases were prevented by a single dose of inactivated poliovirus vaccine from 1992 to 2006 in Hungary, as proved by continuous surveillance of acute flaccid paralysis.

Vaccine-associated paralytic poliomyelitis in an infant with perianal abscesses

We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19days after receiving the OPV and fell 4days later. Flaccid paralysis of the right leg appeared 26days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.

Three cases of paralytic poliomyelitis associated with type 3 vaccine poliovirus strains in Bulgaria

Oral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine-associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine-associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4-month-old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin-like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U-to-C back mutation at nt 472 of the 5' UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine-associated paralytic poliomyelitis in all the three patients.