Temporal and spatial distribution trends of polio vaccine coverage in less than one-year old children in Brazil, 2011-2021.

BACKGROUND: Low polio vaccine coverage can result in the spread of Poliovirus to areas free from viral circulation. This study analyzed the temporal trends and spatial distribution of polio vaccine coverage in one year-old children in Brazil, between 2011 and 2021. METHODS: This was an ecological, time-series study (2011 to 2021) with annual vaccine coverages against poliomyelitis, extracted from the Information System of the National Immunization Program from the 26 States and the Distrito Federal (DF). The percentage reductions in vaccination coverage in Brazil and in the Regions were calculated. Prais-Winsten regression models were used to analyze time series for the Regions and States, and spatial analysis identified the distribution of clusters (high-high; low-low; high-low and low-high) of vaccination coverages across Brazilian municipalities, using a 5% significance level. RESULTS: From 2011 to 2021, the coverage of polio vaccines decreased by 29,9%. There was a progressive increase observed in clusters resulting in low vaccination coverages (140 low-low Brazilian municipalities in 2011 vs. 403 in 2021), mostly reported in the North and Northeast regions of the country. There was a downward trend in vaccination coverages in 24 of the 26 States and DF (p ≤ 0.05). CONCLUSIONS: The reduction in polio vaccine coverage, as observed in the North and Northeast regions of Brazil, may favor the spread of Poliovirus. Therefore, vaccination strategies should be prioritized for children residing in areas with sharp and recurrent declines in vaccination coverages, including travelers, migrants, and refugees.

Response to Vaccine-Derived Polioviruses Detected through Environmental Surveillance, Guatemala, 2019.

Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The Ministry of Health (MoH) response included event investigation through institutional and community retrospective case searches for acute flaccid paralysis (AFP) during 2018-2020 and a bivalent oral polio/measles, mumps, and rubella vaccination campaign in September 2019. This response was reviewed by an international expert team in July 2021. During the campaign, 93% of children 6 months <7 years of age received a polio-containing vaccine dose. No AFP cases were detected in the community search; institutional retrospective searches found 37% of unreported AFP cases in 2018‒2020. No additional VDPV was isolated from wastewater. No evidence of circulating VDPV was found; the 3 isolated VDPVs were classified as ambiguous VDPVs by the international team of experts. These detections highlight risk for poliomyelitis reemergence in countries with low polio vaccine coverage.

A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.

BACKGROUND: Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. OBJECTIVE: The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. METHODS: In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. RESULTS: The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. STUDY LIMITATION: Gene expression studies are absent that would have strengthened the findings of computational analysis. CONCLUSION: The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

Poliomyelitis is a current challenge: long-term sequelae and circulating vaccine-derived poliovirus.

For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First, around half of poliomyelitis elderly survivors suffer late poliomyelitis sequelae with a substantial impact on daily activities and quality of life, experiencing varying degrees of residual weakness as they age. The post-polio syndrome as well as accelerated aging may be involved. Second, after the worldwide Sabin oral poliovirus (OPV) vaccination, the recent reappearance of strains of vaccine-derived poliovirus (VDPV) circulating in the environment is worrisome and able to persistent person-to-person transmission. Such VDPV strains exhibit atypical genetic characteristics and reversed neurovirulence that can cause paralysis similarly to wild poliovirus, posing a significant obstacle to the elimination of polio. Immunization is essential for preventing paralysis in those who are exposed to the poliovirus. Stress the necessity of maintaining high vaccination rates because declining immunity increases the likelihood of reemergence. If mankind wants to eradicate polio in the near future, measures to raise immunization rates and living conditions in poorer nations are needed, along with strict observation. New oral polio vaccine candidates offer a promissory tool for this goal.

CD155 is a putative therapeutic target in medulloblastoma.

BACKGROUND: Medulloblastoma is the most common pediatric malignant brain tumor, consisting of four molecular subgroups (WNT, SHH, Group 3, Group 4) and 12 subtypes. Expression of the cell surface poliovirus receptor (PVR), CD155, is necessary for entry of the viral immunotherapeutic agent, PVSRIPO, a polio:rhinovirus chimera. CD155, physiologically expressed in the mononuclear phagocytic system, is widely expressed ectopically in solid tumors. The objective of this study is to elucidate CD155 expression as both a receptor for PVSRIPO and a therapeutic target in medulloblastoma. METHODS: PVR mRNA expression was determined in several patient cohorts and human medulloblastoma cell lines. Patient samples were also analyzed for CD155 expression using immunohistochemistry and cell lines were analyzed using Western Blots. CD155 was blocked using a monoclonal antibody and cell viability, invasion, and migration were assessed. RESULTS AND DISCUSSION: PVR mRNA expression was highest in the WNT subgroup and lowest in Group 4. PVR expression in the subgroups of medulloblastoma were similar to other pediatric brain and non-brain tumors. PVR expression was largely not associated with subgroup or subtype. Neither PVR protein expression intensity nor frequency were associated with overall survival. PVR expression was elevated in Group 3 patients with metastases but there was no difference in paired primary and metastatic medulloblastoma. Blocking PVR resulted in dose-dependent cell death, decreased invasion in vitro, and modestly inhibited cell migration. CONCLUSIONS: CD155 is expressed across medulloblastoma subgroups and subtypes. Blocking CD155 results in cell death and decreased cellular invasion. This study provides rationale for CD155-targeting agents including PVSRIPO and antibody-mediated blockade of CD155.

A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

The role of a genetically stable, novel oral type 2 poliovirus vaccine in the poliomyelitis endgame / Utilidad de una nueva vacuna antipoliomielítica oral del serotipo 2 genéticamente estable contra el poliovirus de tipo 2 en la erradicación de la poliomielitis / O papel de uma nova vacina oral contra o poliovírus tipo 2, geneticamente estável, no estágio final da eliminação da poliomielite

ABSTRACT Poliovirus infection causes paralysis in up to 1 in 200 infected persons. The use of safe and effective inactivated poliovirus vaccines and live attenuated oral poliovirus vaccines (OPVs) means that only two pockets of wild-type poliovirus type 1 remain, in Afghanistan and Pakistan. However, OPVs can revert to virulence, causing outbreaks of circulating vaccine-derived poliovirus (cVDPV). During 2020-2022, cVDPV type 2 (cVDPV2) was responsible for 97-99% of poliomyelitis cases, mainly in Africa. Between January and August 2022, cVDPV2 was detected in sewage samples in Israel, the United Kingdom and the United States of America, where a case of acute flaccid paralysis caused by cVDPV2 also occurred. The Pan American Health Organization has warned that Brazil, the Dominican Republic, Haiti and Peru are at very high risk for the reintroduction of poliovirus and an additional eight countries in Latin America are at high risk, following dropping vaccination rates (average 80% coverage in 2022). Sabin type 2 monovalent OPV has been used to control VDPV2 outbreaks, but its use could also lead to outbreaks. To address this issue, a more genetically stable, novel OPV2 (nOPV2) was developed against cVDPV2 and in 2020 was granted World Health Organization Emergency Use Listing. Rolling out a novel vaccine under the Emergency Use Listing in mass settings to contain outbreaks requires unique local regulatory and operational preparedness.

RESUMEN La infección por poliovirus ocasiona parálisis en hasta 1 de cada 200 personas infectadas. La utilización de vacunas con poliovirus inactivados y de vacunas antipoliomielíticas orales con poliovirus vivos atenuados (OPV) seguras y eficaces ha logrado que solo queden dos focos de poliovirus salvaje de tipo 1, en Afganistán y Pakistán. Sin embargo, las vacunas con OPV pueden revertir a la virulencia y producir brotes de poliovirus circulantes de origen vacunal (cVDPV). Durante el período 2020-2022, el cVDPV de tipo 2 (cVDPV2) fue la causa del 97-99% de los casos de poliomielitis, sobre todo en África. Entre enero y agosto del 2022, se encontró el cVDPV2 en muestras de aguas residuales en Estados Unidos de América, donde se produjo un caso de parálisis flácida aguda por el cVDPV2, Israel y Reino Unido y. La Organización Panamericana de la Salud ha advertido que, tras la caída de las tasas de vacunación (con una cobertura promedio del 80% en el 2022), Brasil, Haití, Perú y República Dominicana corren un riesgo muy alto de reintroducción del poliovirus, en tanto que otros ocho países de América Latina se encuentran en una situación de alto riesgo. La OPV monovalente de tipo 2 de Sabin se ha utilizado para controlar los brotes de VDPV2, pero su empleo también podría ocasionar brotes. Para hacer frente a este problema, se creó una nueva OPV2 (nOPV2) contra el cVDPV2, genéticamente más estable, que en el 2020 se incluyó en la lista de uso en emergencias de la Organización Mundial de la Salud. El despliegue a gran escala de una nueva vacuna incluida en la lista de uso en emergencias con el fin de contener los brotes exige una extraordinaria preparación regulatoria y operativa local.

RESUMO A infecção pelo poliovírus causa paralisia em 1 de cada 200 pessoas infectadas. O uso de vacinas seguras e eficazes, tanto vacinas inativadas contra o poliovírus quanto vacinas orais contendo poliovírus atenuado (VOP), significa que restam apenas dois bolsões de poliovírus selvagem tipo 1, um no Afeganistão e outro no Paquistão. No entanto, a VOP pode reverter à virulência, causando surtos de poliovírus circulante derivado de vacina (cPVDV). No período 2020-2022, o cPVDV tipo 2 (cPVDV2) foi responsável por 97% a 99% dos casos de poliomielite, principalmente na África. Entre janeiro e agosto de 2022, o cPVDV2 foi detectado em amostras de esgoto em Israel, no Reino Unido e nos Estados Unidos da América, onde também houve um caso de paralisia flácida aguda causada pelo cPVDV2. A Organização Pan-Americana da Saúde alertou que, devido à queda nas taxas de vacinação (cobertura média de 80% em 2022), o Brasil, o Haiti, o Peru e a República Dominicana correm um risco muito alto de reintrodução do poliovírus e outros oito países da América Latina correm um risco alto. A VOP monovalente Sabin tipo 2 tem sido usada para controlar surtos de PVDV2, mas seu uso também pode levar a surtos. Para resolver esse problema, foi desenvolvida uma nova VOP2 (nVOP2), mais estável geneticamente, para combater o cPVDV2. Em 2020, a nVOP2 entrou na Lista de Uso Emergencial da Organização Mundial da Saúde. A distribuição de uma nova vacina incluída na Lista de Uso Emergencial em contextos de massa para conter surtos requer medidas originais de preparação operacional e regulatória em âmbito local.

Temporal and spatial distribution of polio vaccine coverage in Brazil between 1997 and 2021 / Distribuição temporal e espacial da cobertura vacinal contra poliomielite no Brasil entre 1997 e 2021

ABSTRACT Objective: To analyze the temporal and spatial distribution of polio vaccine coverage in Brazilian states. Methods: An ecological time series study was conducted using data from the National Immunization Program Information System. The analyzed period was from 1997 to 2021. Joinpoint software was used to calculate the annual percentage change and average annual percentage change through regressions. QGIS 3.10.7 software was used to construct thematic maps. GeoDa 1.20.0.10 software was used to estimate spatial autocorrelation using the Global Moran's Index and Local Moran's Index. Results: National vaccine coverage in 1997 was 89.27%, decreasing to 61.32% in 2021. The trend analysis indicated an average annual decrease of 1.5% in polio vaccine coverage in Brazil. Across the country, 17 states showed a statistically significant reduction in the average annual percentage change rate. The highest average reduction rates in vaccine coverage among Brazilian states were observed in Amapá (−3.7%; 95%CI −6.0; −1.4) and Pernambuco (−3.3%; 95%CI −4.0; −2.5). In the spatial analysis, in Moran Global, a positive autocorrelation was identified in the years 2012 to 2021 (p<0.02), with an index value of 0.361, which means that geographically close areas tended to have similar levels of vaccination coverage. Conclusion: There was significant heterogeneity in coverage among states and a strong decrease trend in vaccination rates, which could facilitate the circulation of the poliovirus and pose a threat to the susceptible population.

RESUMO Objetivo: Analisar a distribuição temporal e espacial da cobertura da vacina contra poliomielite nos estados brasileiros. Métodos: Estudo ecológico de séries temporais, cuja fonte de dados foi o Sistema de Informação do Programa Nacional de Imunizações. O período analisado foi de 1997 a 2021. Utilizou-se o software Joinpoint para calcular a variação percentual anual e variação percentual anual média por meio de regressões. Para construção de mapas temáticos foi utilizado o software QGis 3.10.7. Para estimar a autocorrelação espacial com o Índice de Moran Global e Índice de Moran Local foi utilizado o software GeoDa 1.20.0.10. Resultados: A cobertura vacinal nacional em 1997 foi de 89,27%, passando para 61,32% em 2021. A análise de tendência apontou o decréscimo médio de 1,5% ao ano na cobertura da vacina contra poliomielite no Brasil. Em todo o país, 17 estados apresentaram redução estatisticamente significativa na taxa de variação percentual anual média. As maiores taxas médias de redução da cobertura vacinal entre os estados brasileiros foram observadas no Amapá (−3,7%; IC95% −6,0; −1,4) e em Pernambuco (−3,3%; IC95% −4,0; −2,5). Na análise espacial, no Moran Global, foi identificada autocorrelação positiva nos anos de 2012 a 2021 (p<0,02), com valor de índice de 0,361, o que significa que as áreas geograficamente próximas tenderam a ter níveis semelhantes de cobertura vacinal. Conclusão: Evidenciou-se expressiva heterogeneidade na cobertura entre os estados e forte tendência de queda dos índices, o que pode propiciar a circulação do poliovírus e colocar sob ameaça a população susceptível.

Achieving high immunogenicity against poliovirus with fractional doses of inactivated poliovirus vaccine in Ecuador-results from a cross-sectional serological survey.

Background: In January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; and bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titres of polio antibodies achieved by the past and the current immunization schedules. Methods: This was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay. Findings: We obtained 321 analysable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50·0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 - 3·5 vs. 4·8, CI95%= 4·5 - 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients. Interpretation: Ecuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and potentially a cost-effective option in polio immunization. Funding: WHO obtained funds for the study from Rotary International.

Vigilancia ambiental de la circulación de poliovirus en tres municipios considerados como punto transitorio de migrantes en Colombia 2017-2019 / Environmental surveillance of the circulation of poliovirus in municipalities considered as transitory point of migrants in Colombia 2017-2019

Resumen Objetivo: Determinar la circulación de poliovirus en tres municipios considerados como punto transitorio de migrantes en Colombia. Material y método: Se colectaron muestras de aguas residuales (n=36) de municipios fronterizos, seleccionados por mayor tránsito de migrantes regulares como irregulares, en el periodo comprendido entre el 2017-2019. Las muestras fueron concentradas y cultivadas siguiendo el algoritmo de vigilancia ambiental para la circulación de poliovirus de la Organización Mundial de la Salud (OMS). La identificación molecular se realizo mediante reacción en cadena de la polimerasa empleando cebadores específicos de grupo, de serotipo y de cepa vacunal sabin. Resultados y Discusión: Se detectó la presencia de Enterovirus no polio (EVNP) en las muestras ambientales obtenidas y no se hallo circulación de poliovirus deriva dos de la vacuna ni de poliovirus salvaje en los tres municipos evaluados; sin embargo en dos estudios previos publicados por Gonzalez y col con una metodologia similar en el año 2005 y 2015 evaluando las aguas residuales de la ciudad de Armenia-Quindio; se logró identificar la presencia de virus derivado de vacuna, con resultados negativos para la identificación de poliovirus salvaje. Conclusiones: Los hallazgos indican que el sistema de monitoreo de aguas residuales con el fin de determinar la presencia de virus es una herramienta util para realizar vigilancia ambiental.

Abstract Objective: To determine the circulation of poliovirus in three municipalities considered as transitory points for migrants in Colombia. Material and Method: Wastewater samples (n = 36) were collected from border municipalities, selected for greater transit of regular and irregular migrants, in the period between 2017-2019. The samples were concentrated and cultured following the World Health Organization (WHO) environmental surveillance algorithm for poliovirus circulation. Molecular identification was performed by polymerase chain reaction using group-specific, serotype and sabin vaccine strain primers. Results: The presence of non-polio Enterovirus (NPV) was detected in the environmental samples obtained and no circulation of poliovirus derived from the vaccine or wild poliovirus was found in the three evaluated municipalities; However, in two previous studies published by Gonzales et al with a similar methodology in 2005 and 2015 evaluating the wastewater of the city of Armenia-Quindío; It was possible to identify the presence of virus derived from vaccine, with negative results for the identification of wild poliovirus. Conclusions: The findings indicate that the wastewater monitoring system in order to determine the presence of viruses is a useful tool to carry out environmental surveillance.

Economic assessment of incorporating the hexavalent vaccine as part of the National Immunization Program of Peru.

BACKGROUND: This study aimed to estimate the economic impact of replacing the current Peruvian primary immunization scheme for infants under 1 year old with an alternative scheme with similar efficacy, based on a hexavalent vaccine. METHODS: A cost-minimization analysis compared the costs associated with vaccine administration, adverse reactions medical treatment, logistical activities, and indirect social costs associated with time spent by parents in both schemes. A budgetary impact analysis assessed the financial impact of the alternative scheme on healthcare budget. RESULTS: Incorporating the hexavalent vaccine would result in a 15.5% net increase in healthcare budget expenditure ($48,281,706 vs $55,744,653). Vaccination costs would increase by 54.1%, whereas logistical and adverse reaction costs would be reduced by 59.8% and 33.1%, respectively. When including indirect social costs in the analysis, the budgetary impact was reduced to 8.7%. Furthermore, the alternative scheme would enable the liberation of 17.5% of national vaccines storage capacity. CONCLUSIONS: Despite of the significant reduction of logistical and adverse reaction costs, including the hexavalent vaccine into the National Immunization Program of Peru in place of the current vaccination scheme for infants under 1 year of age would increase the public financial budget of the government as it would represent larger vaccine acquisition costs. Incorporating the indirect costs would reduce the budgetary impact demonstrating the social value of the alternative scheme. This merits consideration by government bodies, and future studies investigating such benefits would be informative.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception.

Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8-6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7-6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Environmental Surveillance for Risk Assessment in the Context of a Phase 2 Clinical Trial of Type 2 Novel Oral Polio Vaccine in Panama.

Environmental surveillance was recommended for risk mitigation in a novel oral polio vaccine-2 (nOPV2) clinical trial (M5-ABMG) to monitor excretion, potential circulation, and loss of attenuation of the two nOPV2 candidates. The nOPV2 candidates were developed to address the risk of poliovirus (PV) type 2 circulating vaccine-derived poliovirus (cVDPV) as part of the global eradication strategy. Between November 2018 and January 2020, an environmental surveillance study for the clinical trial was conducted in parallel to the M5-ABMG clinical trial at five locations in Panama. The collection sites were located upstream from local treatment plant inlets, to capture the excreta from trial participants and their community. Laboratory analyses of 49 environmental samples were conducted using the two-phase separation method. Novel OPV2 strains were not detected in sewage samples collected during the study period. However, six samples were positive for Sabin-like type 3 PV, two samples were positive for Sabin-like type 1 PV, and non-polio enteroviruses NPEVs were detected in 27 samples. One of the nOPV2 candidates has been granted Emergency Use Listing by the World Health Organization and initial use started in March 2021. This environmental surveillance study provided valuable risk mitigation information to support the Emergency Use Listing application.

Environmental Surveillance for Polioviruses in Haïti (2017-2019): The Dynamic Process for the Establishment and Monitoring of Sampling Sites.

Haïti is at risk for wild poliovirus (WPV) importation and circulation, as well as vaccine-derived poliovirus (VDPV) emergence. Environmental surveillance (ES) for polioviruses was established in Port au Prince and Gonaïves in 2016. During 2017-2019, initial ES sites were re-evaluated, and ES was expanded into Cap Haïtien and Saint Marc. Wastewater samples and data on weather, hour of collection, and sample temperature and pH were collected every 4 weeks during March 2017-December 2019 (272 sampling events) from 21 sites in Cap Haïtien, Gonaïves, Port au Prince, and Saint Marc. Samples were processed for the detection of polio and non-polio enteroviruses using the two-phase and "Concentration and Filter Elution" methodologies. Polioviruses were serotyped and underwent intra-typic characterization. No WPV or VDPVs were isolated. Sabin-like polioviruses (oral vaccine strain) of serotypes 1 and 3 were sporadically detected. Five of six (83%), one of six (17%), five of six (83%), and two of three (67%) sites evaluated in Cap Haïtien, Gonaïves, Port au Prince, and Saint Marc, respectively, had enterovirus isolation from >50% of sampling events; these results and considerations, such as watershed population size and overlap, influence of sea water, and excessive particulates in samples, were factors in site retention or termination. The evaluation of 21 ES sampling sites in four Haïtian cities led to the termination of 11 sites. Every-four-weekly sampling continues at the remaining 10 sites across the four cities as a core Global Polio Eradication Initiative activity.

Environmental Surveillance through Next-Generation Sequencing to Unveil the Diversity of Human Enteroviruses beyond the Reported Clinical Cases.

The knowledge about circulation of Human Enteroviruses (EVs) obtained through medical diagnosis in Argentina is scarce. Wastewater samples monthly collected in Córdoba, Argentina during 2011-2012, and then in 2017-2018 were retrospectively studied to assess the diversity of EVs in the community. Partial VP1 gene was amplified by PCR from wastewater concentrates, and amplicons were subject of next-generation sequencing and genetic analyses. There were 41 EVs detected, from which ~50% had not been previously reported in Argentina. Most of the characterized EVs (60%) were detected at both sampling periods, with similar values of intratype nucleotide diversity. Exceptions were enterovirus A71, coxsackievirus B4, echovirus 14, and echovirus 30, which diversified in 2017-2018. There was a predominance of types from EV-C in 2017-2018, evidencing a common circulation of these types throughout the year in the community. Interestingly, high genetic similarity was evidenced among environmental strains of echovirus 30 circulating in 2011-2012 and co-temporal isolates obtained from patients suffering aseptic meningitis in different locations of Argentina. This study provides an updated insight about EVs circulating in an important region of South America, and suggests a valuable role of wastewater-based epidemiology in predicting outbreaks before the onset of cases in the community.

Poliomielitis, una historia de inicio triste y final feliz / Poliomyelitis, a story with a sad beginning and a happy ending

Se desarrollan los principales elementos históricos en el estudio y la lucha contra la poliomielitis, su aislamiento por Karl Landsteiner en 1909, la primera vacuna con virus muerto (Jonas Salk, 1955), la segunda vacuna con virus vivo atenuado (Albert Sabin, 1961) y la reducción paulatina de la polio en todo el mundo, hasta llegar a menos de 200 casos al año (virus salvaje)(AU)

The main historical events in the study and fight against polio are shown, its isolation by Karl Landsteiner in 1909, the development of the first vaccine with dead virus (Jonas Salk, 1955), the second vaccine with live attenuated virus (Albert Sabin, 1961) and the gradual reduction of polio worldwide, reaching less than 200 cases a year (wild virus)(AU)

Attitude and perception towards vaccination against poliomyelitis in Peshawar, Pakistan

ABSTRACT OBJECTIVE: This research aimed to quantitatively assess the general public's awareness, attitude and perception of polio and its vaccination in Peshawar KPK, Pakistan. METHODS: We conducted a survey-based study to understand the surge in polio cases from 2015 to 2019 in the Peshawar city of the Khyber Pakhtunkhwa (KPK), Pakistan. A pre-tested questionnaire-based study was conducted in 2019 to assess the attitude and general perception of residents of Peshawar KPK towards polio vaccination. RESULTS: Out of 241 country-wide polio cases, 63 (26.1%) polio cases were reported in Peshawar city from 2015-2019. The questionnaire revealed that individuals between 18-30 years of age had sufficient knowledge (65.1%) about polio. Male and female participants had equal awareness (~ 43%). Participants with higher education (45.9%), those with better financial status (49.5%), individuals with children < 5 years of age (46.4%), and those who had experience of a polio patient (63.1%) had better knowledge. Participants inhabiting the central city were better aware (50.5%) of polio than individuals living in the outskirts. CONCLUSION: The data indicated that poor knowledge and negative attitudes of people towards polio vaccination are the main causes of the polio eradication program's failure. Moreover, religious beliefs, unchecked migration between the Pak-Afghan border, and lack of knowledge about polio vaccination are identified as critical barriers to polio eradication.

Current polio status in the world / Estado atual de poliomielite no mundo

ABSTRACT Poliomyelitis is still an endemic disease in Afghanistan, Nigeria, and Pakistan despite the efforts to eradicate the disease. Therefore, there is a potential risk of international spread. Since the start of the polio eradication program by the Global Polio Eradication Initiative in 1988, the incidence of polio has been reduced by 99%. In the last decade, wild poliovirus type 2 (WPV2) was eliminated and declared eradicated in 2015. Wild poliovirus type 3 (WPV3) was last reported in November 2012. These changes have allowed the removal of Sabin poliovirus type 2 from the oral poliovirus vaccine (OPV) in April 2016 and countries either introduced bivalent OPV (bOPV) containing Sabin types 1 + 3 poliovirus or added at least one dose of inactivated poliovirus vaccine (IPV) into their routine immunization schedule. Many efforts are needed to eradicate polio, and new strategies should be implemented such as the development and approval of new genetically stable OPV, and vaccines that do not require infectious processes for virus growth, such as virus-like particles (VLPs), or packing-cell technology. IPV will increasingly be produced from Sabin strains, and further attenuated or genetically modified strains. Furthermore, there is also a need for the development of antiviral drugs to treat immunodeficient patients who are long-term excretors infected with poliovirus, thus avoiding contamination of individuals susceptible to polioviruses, due to reversal of pathogenicity. If all these measures are successfully implemented, the world will be close to the global

RESUMEN La poliomielitis sigue siendo una enfermedad endémica en Afganistán, Nigeria y Pakistán a pesar de los esfuerzos por erradicar la enfermedad. Por lo tanto, existe un riesgo de propagación mundial. Desde el inicio del programa de erradicación de la poliomielitis por la Iniciativa de Erradicación Mundial de la Poliomielitis [Global Polio Eradication Initiative (GPEI)] en 1988, la incidencia de la poliomielitis se ha reducido en un 99%. En la última década, el poliovirus salvaje tipo 2 (WPV2) fue eliminado y declarado erradicado en 2015. El poliovirus salvaje tipo 3 (WPV3) se informó por última vez en noviembre de 2012. Estos cambios han permitido la eliminación del poliovirus Sabin tipo 2 de la vacuna antipoliomielítica oral (VPO) en abril de 2016, y los países introdujeron la VPO de tipo bivalente (bVPO), que contiene poliovirus Sabin tipos 1 y 3, o agregaron al menos una dosis de vacuna antipoliomielítica inactivada (VPI) al programa de inmunización de rutina. Se necesitan muchos esfuerzos para erradicar la poliomielitis y se deben implementar nuevas estrategias, como el desarrollo y aprobación de nuevas VPO genéticamente estables y vacunas que no requieren procesos infecciosos para el crecimiento del virus, como partículas pseudovirales (VLP) o tecnología de células empaquetadas (packing-cell). La VIP se producirá cada vez más a partir de cepas Sabin y otras cepas más atenuadas o modificadas genéticamente. Además, también es necesario desarrollar fármacos antivirales para tratar a pacientes inmunodeficientes que son excretores a largo plazo, evitando así la contaminación de individuos susceptibles a poliovirus, debido a la reversión de la patogenicidad. Si todas estas medidas se implementan con éxito, el mundo estará cerca de la interrupción global de la transmisión del WPV y la erradicación de la poliomielitis.

RESUMO A poliomielite ainda é uma doença endêmica no Afeganistão, na Nigéria e no Paquistão, apesar dos esforços para erradicá-la. Portanto, há risco de propagação mundial. Desde o início do programa de erradicação da poliomielite pela Iniciativa de Erradicação Global da Pólio [Global Polio Eradication Initiative (GPEI)], em 1988, a incidência da doença foi reduzida em 99%. Na última década, o poliovírus selvagem do tipo 2 (WPV2) foi eliminado e declarado erradicado em 2015. O poliovírus selvagem do tipo 3 (WPV3) foi reportado pela última vez em novembro de 2012. Essas mudanças promoveram a remoção do poliovírus Sabin tipo 2 da vacina oral antipólio (VOP) em abril de 2016, e os países introduziram a vacina oral bivalente (VOPb), que contém os poliovírus Sabin tipos 1 + 3, ou adicionaram pelo menos uma dose da vacina inativada contra o poliovírus (VIP) no calendário de imunização. É necessário muito empenho para erradicar a poliomielite. Novas estratégias devem ser implementadas, como o desenvolvimento e a aprovação de novas VOPs geneticamente estáveis e vacinas que não requerem processos infecciosos para o crescimento do vírus, como partículas pseudovirais (VLP), ou tecnologia de células de empacotamento (packing-cell). A VIP será cada vez mais produzida a partir de cepas Sabin, de outras cepas atenuadas ou geneticamente modificadas. Além disso, é imprescindível o desenvolvimento de medicamentos antivirais para tratar os pacientes imunodeficientes que são excretores de longo prazo, evitando assim a contaminação de indivíduos suscetíveis aos poliovírus, devido à reversão da patogenicidade. Se todas essas medidas forem implementadas com sucesso, o mundo estará próximo da interrupção global de transmissão do WPV e da erradicação da poliomielite.

Estado actual de la poliomielitis en Latinoamérica

Resumen La vacuna oral contra el poliovirus (OPV) ha sido fundamental en controlar la epidemia de poliomielitis, y destaca por su seguridad, eficacia, facilidad de administración oral y bajo costo. Sin embargo, a pesar de estas ventajas, al tratarse de una vacuna con virus vivos atenuados, existe la posibilidad de mutaciones que confieran neurovirulencia. Por ende, es importante la vigilancia de parálisis flácida aguda (PFA), ya sea asociada a las vacunas atenuadas (VAPP) o a los virus derivados de vacunas (VDPV). En esta revisión presentamos datos importantes de Latinoamérica en los últimos años, donde se revisan los datos de VDPV de transmisión comunitaria, de origen ambiguo y asociadas con inmunodeficiencias. Debido a la presencia de VDPV, es importante fortalecer el sistema de vigilancia epidemiológica por PFA, con datos muy inferiores a los recomendados en estos últimos años en las Américas. Adicionalmente, es fundamental mejorar las coberturas vacunales para reducir la cantidad de lactantes en riesgo de adquirir poliomielitis. En consecuencia, presentamos las tasas de cobertura vacunal con la vacuna inactivada contra el poliovirus (IPV) en la región y analizamos los programas de vacunación contra la poliomielitis en concordancia con las recomendaciones de la Sociedad Latinoamericana de Infectología Pediátrica (SLIPE; mínimo 3 dosis de IPV) y del Grupo de Expertos en Asesoramiento Estratégico (SAGE) sobre Inmunización de la OMS (mínimo 2 dosis de IPV). El estudio concluye con recomendaciones de los autores para el cambio de OPV a uso exclusivo de IPV, para aumentar las coberturas vacunales y para reforzar la vigilancia por PFA en la región.

Abstract Oral poliovirus vaccine (OPV) has been instrumental in controlling the polio epidemic, and stands out for its safety, efficacy, ease of oral administration, and low cost. However, despite these advantages, as it is a live attenuated virus vaccine, there is the possibility of mutations that confer neurovirulence. Therefore, surveillance for acute flaccid paralysis (AFP) is important, whether associated with live vaccines (VAPP) or vaccine-derived viruses (VDPV). In this review we present important data from Latin America in recent years, where data on VDPV of community transmission, of ambiguous origin and associated with immunodeficiencies are reviewed. Due to the presence of VDPV, it is important to strengthen the epidemiological surveillance system for AFP, with data much lower than those recommended in recent years in the Americas. Additionally, it is essential to improve vaccination coverage to reduce the number of infants at risk of acquiring poliomyelitis. Consequently, we present the vaccination coverage rates with the inactivated vaccine against poliovirus (IPV) in the region and analyze the vaccination programs against poliomyelitis in accordance with the recommendations of the Latin American Society of Pediatric Infectious Diseases (SLIPE; minimum 3 doses of IPV) and the WHO Strategic Advisory Expert Group (SAGE) on Immunization (minimum 2 doses of IPV). The study concludes with recommendations from the authors for the change from OPV to exclusive use of IPV, to increase vaccination coverage and to strengthen surveillance for AFP in the region.

Vacuna hexavalente en el Perú. Hacia la cobertura segura y sostenida de la vacunación en la infancia. Consenso de expertos / Hexavalent vaccine in Peru. Towards safe and sustained coverage of childhood immunization. Expert consensus

Objetivo. La inmunización es una de las intervenciones más importantes para prevenir la morbimortalidad en la población mundial. No obstante, aún persisten brechas para alcanzar coberturas ideales de vacunación. Además, las múltiples dosis y vacunas dificultan alcanzar las metas mínimas establecidas. Por ello, se desarrollan vacunas combinadas y fraccionadas para reducir el número de inyecciones, errores programáticos, reactogenicidad y mejorar la adherencia. En tres días distintos, durante 9 horas, se reunieron 6 médicos pediatras expertos en vacunas en el Perú siguiendo el método RAND/UCLA, con el objeto de elaborar un consenso de opinión y actualización de la vacuna combinada hexavalente [DTaP+Haemophilus influenzae tipo b (Hib)+Hepatitis B (HVB)+antipolio inactivada (IPV)] y su eventual uso en el Programa ampliado de inmunizaciones (PAI). Las recomendaciones del consenso son: reemplazar las vacunas, antipolio oral (OPV) por IPV, pertussis de células enteras por vacunas acelulares y DTP de los 4 años por dTap entre los 4 y 6 años; usar la vacuna hexavalente para la serie primaria (2, 4 y 6 meses); usar 4 dosis de vacuna contra Hib (2, 4, 6 y 18 meses); incorporar la vacuna hexavalente en el PAI; no usar la IPV fraccionada (fIPV) y administrar solo 4 dosis de IPV.

Objetive. Immunization is one of the most important interventions to prevent morbidity and mortality in the world population. However, gaps persist to achieve ideal vaccination coverage. In addition, the multiple vaccines and necessary doses make it difficult to reach the minimum established goals. On this scenario, combined and fractionated vaccines are being developed with the aim of reducing the injections number, programmatic errors, reactogenicity and improving adherence. On three different days, for 9 hours, 6 pediatricians experts in vaccines in Peru met following the RAND/UCLA method in order to develop a consensus opinion and update of the combined hexavalent vaccine [DTaP+Haemophilus influenzae type b (Hib)+Hepatitis B (HVB)+Inactivated Polio Vaccine (IPV)] and its eventual use in the Extended Immunization Program (EPI). The consensus recommendation are: replace the vaccines, Oral Polio Vaccine (OPV) by IPV, pertussis of whole cells by acellular vaccines and DTP of 4 years old by dTap between 4 and 6 years old; use the hexavalent vaccine for the primary series (2, 4 and 6 months); use 4 doses of Hib vaccine (2, 4, 6 and 18 months); incorporate the hexavalent vaccine in the EPI; do not use fractionated IPV (fIPV) and only administer 4 doses of IPV.