Cobertura das vacinas pneumocócica, contra poliomielite e rotavírus no Brasil: estudo descritivo, 2017 a 2020 / Coverage of pneumococcal, polio and rotavirus vaccines in Brazil: descriptive study, 2017 to 2020 / Cobertura de las vacunas antineumocócica, antipoliomielítica y rotavirus en Brasil: estudio descriptivo, 2017 a 2020

Introdução: Os últimos anos têm sido marcados por queda nas coberturas vacinais, gerando risco para surtos e epidemias de doenças imunopreveníveis. Objetivo: Descrever a cobertura das vacinas pneumocócica, contra poliomielite e rotavírus, de 2017 a 2020, nas regiões e unidades da federação (UFs) do Brasil. Métodos: Estudo descritivo com dados do Sistema de Informação do Programa Nacional de Imunizações (SI-PNI). Obtiveram-se as coberturas vacinais para cada imunobiológico nas 27 UFs, bem como para as diferentes regiões e para o Brasil no período de 2017 a 2020. Além disso, calcularam-se as diferenças absolutas das coberturas de cada vacina entre os anos de 2019 e 2020. Resultados: Em 2017 e 2020, a vacina pneumocócica registrou índices de 92,2 e 81,0%, respectivamente, enquanto a contra poliomielite teve cobertura de 84,7 e 75,8%, e a contra rotavírus apresentou cobertura de 85,1 e 77,0%. A diferença absoluta das coberturas dos imunobiológicos foi de aproximadamente 8 pontos percentuais entre 2019 e 2020. Nenhuma UF atingiu cobertura adequada para poliomielite e rotavírus. Conclusão: Houve redução na cobertura vacinal durante o período entre 2019 e 2020, com as coberturas mais afetadas sendo as da vacina contra poliomielite, seguida pela vacina contra rotavírus e, por fim, da vacina pneumocócica. Essa diminuição pode estar relacionada à pandemia da doença do novo coronavírus (COVID-19).

Introduction: Recent years have been marked by a drop in vaccine coverage, creating a risk of outbreaks and epidemics of vaccine-preventable diseases. Objective: To describe the coverage of pneumococcal, polio and rotavirus vaccines from 2017 to 2020, in the regions and federative units (FUs). Methods: Descriptive study, with data from the Information System of the National Immunization Program. The vaccination coverage of each immunobiological agent was obtained according to the twenty-seven FUs, regions and whole Brazil, and the absolute differences in the coverage of each vaccine, from 2019 compared to 2020, were calculated. Results: In 2017 and 2020, respective coverage rates for pneumococcal vaccine were 92.2 and 81.0%, for polio vaccine 84.7 and 75.8% and for rotavirus vaccine 85.1 and 77.0%. The coverage of immunologicals showed an absolute difference of approximately 8 percentage points in the period between 2019 and 2020. No FU achieved adequate coverage for poliomyelitis and rotavirus. Conclusion: There was a drop in vaccination coverage between 2019 and 2020, with lower coverage for poliomyelitis, followed by rotavirus and pneumococcal disease, which may be related to the COVID-19 pandemic.

Introducción: Los últimos años se han caracterizado por una caída en la cobertura de vacunas, creando un riesgo de brotes y epidemias de enfermedades prevenibles por vacunación. Objetivo: Describir la cobertura de las vacunas antineumocócica, antipoliomielítica y rotavirus, de 2017 a 2020, en las regiones y unidades de la federación (UFs). Métodos: Estudio descriptivo, con datos del Sistema de Información del Programa Nacional de Inmunizaciones. Se obtuvo la cobertura de vacunación de cada agente inmunobiológico según las veintisiete UF, regiones y Brasil, y se calcularon las diferencias absolutas en la cobertura de cada vacuna, de 2019 con respecto a 2020. Resultados: En 2017 y 2020, la enfermedad neumocócica aumentó del 92,2 al 81,0%, poliomielitis del 84,7 al 75,8%, rotavirus del 85,1 al 77,0%. La cobertura de inmunológicos mostró una diferencia absoluta de aproximadamente 8 puntos porcentuales en el período comprendido entre 2019 y 2020. Ninguna UF logró una cobertura adecuada para poliomielitis y rotavirus. Conclusión: hubo una caída en la cobertura de vacunación entre 2019 y 2020, con menor cobertura de poliomielitis, seguida de rotavirus y enfermedad neumocócica, que pueden estar relacionados con la pandemia COVID-19.

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.

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.

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.

Development and verification of double antibody sandwich ELISA method for determination of D antigen content in s IPV vaccine / 中国生物制品学杂志

@#Objective To develop and verify a sandwich ELISA method with bovine polyclonal antibody against rabbit polyclonal antibody for the determination of D antigen content of Sabin strain inactivated poliovirus vaccine(sIPV).Methods The rabbit polyclonal antibodies were prepared with sIPV vaccine bulks of type Ⅰ,Ⅱ and Ⅲ as antigens and detected for the titer and specificity by indirect ELISA.A double antibody sandwich ELISA with bovine polyclonal antibody as coating antibody and rabbit polyclonal antibody as detection antibody was developed to determine D antigen content,and the accuracy,precision and specificity to D antigen of the method were verified.sIPV vaccine samples from five domestic enterprises were detected by the developed method.Results The rabbit polyclonal antibodies for type Ⅰ,Ⅱ and Ⅲ sIPV with good specificity and high titer were prepared,and the double antibody sandwich ELISA method was successfully developed.Using four-parameter fitting,all three standard curves showed good linear relationship,and R~2 values were more than 0.99.The spike recoveries of type Ⅰ,Ⅱ and Ⅲ D antigens were all within 80%～120%,with average values of98.11%,97.41% and 98.66%,respectively.The CVs of repeatability and intermediate precision were all below 10%.The method also distinguished D antigens from C antigens.The developed method determined the D antigen contents of sIPV vaccines from five enterprises.Conclusion A sandwich ELISA method for determination of D antigen content in sIPV vaccine was successfully developed with satisfying accuracy,precision and certain D antigen specificity,which can be used to detect vaccines produced by different manufacturers.

Immune persistence following intradermal vaccination with fractional dose of diphtheria-tetanus-acellular component pertussis and Sabin-derived inactivated poliovirus vaccine / 中国生物制品学杂志

Objective@#To evaluate the immune persistence following intradermal(ID) vaccination with diphtheria-tetanusacellular component pertussis and Sabin-derived inactivated poliovirus vaccine(DTacP-sIPV).@*Methods@#40 wistar rats were randomly assigned into four groups.Two test groups were injected intradermally with fractional-doses(1/5 and 1/10dose) of DTacP-sIPV(1/5D ID and 1/10D ID group);The positive control group was intramuscularly injected with full dose of DTacP-sIPV(full-dose IM group);The negative control group was injected with PBS intradermally.Wistar rats were immunized 3 times at 0,1 and 2 months and the blood samples were collected via tail vein 12 months after the last immunization and the serum samples were isolated.The titer of neutralizing antibody against poliovirus was detected by micro-neutralization test,and the titers of IgG antibodies against diphtheria toxin(DT),tetanus toxin(TT),pertussis toxin(PT),filamentous hemagglutinin(FHA) and pertactin(PRN) in rat serum were detected by indirect ELISA.The geometric mean titer(GMT)and positive rate of antibody were calculated.The rats were challenged with aerosolized B.pertussis for 30 min 12 months after the last immunization and determined for the white blood cell(WBC) count and colony-forming unit(CFU) in lung,trachea and nose at day 2,5 and 14 after challenge.@*Results@#Compared with the full-dose IM group,there was no significant difference in the positive rates of poliovirus type Ⅰ,Ⅱ and Ⅲ neutralizing antibodies between 1/5D ID and 1/10D ID groups(each P> 0.05) and the positive rates of all types of antibodies in the control group were 0.The positive rates of IgG antibodies against DT,TT,PT,FHA and PRN in 1/5D ID,1/10D ID and full-dose IM groups were all 100%,and those in control group were all 0.Compared with 2 d after challenge,the WBC counts of rats in control group increased significantly 5 d after aerosol challenge with B.pertussis(F=3.48,P <0.05),and then began to decrease,while those in other groups remained stable with time(F=0.14～1.30,P> 0.05).After aerosol challenge,the CFU in lungs of rats in control group was significantly higher than that in the other three groups(F=19.00～206.00,P<0.05),and B.pertussis was still detected 14 d after challenge;Except for the control group,the bacterial load in lungs of rats in the other three groups reached the peak 5d after challenge,the B.pertussis was basically cleared on the 14d,and there was no significant difference among the groups at each time point(F=1.14～1.25,P> 0.05).The bacterial load of trachea and nose in the control group was slightly higher than that in other groups at each time point,but the difference was not significant(F=0.71～3.54,P> 0.05).Except for the control group,the bacterial load in the trachea and nose of the other three groups were similar,and no significant difference was observed(F=0.75～3.41,P>0.05).@*Conclusion@#ID immunization with1/5 dose of DTacP-sIPV induced persistent protective antibodies against various components of the vaccine in rats.This study provided an experimental basis for the formulation of immunization strategy of ID immunization with fractional dose of DTacP-sIPV.

An epidemiological investigation on vaccine-hypervariable poliovirus in a case with acute flaccid paralysis in Zhejiang Province / 预防医学

Abstract@#Vaccine-hypervariable poliovirus type Ⅲ was detected in an acute flaccid paralysis infant at age of 6 months in Zhejiang Province in June, 2021, and the isolated and incubated virus had six nucleotide variations in the VP1 region as compared to the poliovirus Sabin vaccine strain. The infant had a history of three-dose poliovirus vaccination, and grade 2 muscle strength of the left upper limb upon onset. He was clinically diagnosed with cellulitis of the left shoulder, and recovered to normal following treatment. No abnormality was detected in the nervous system, and the infant was cured and discharged from hospital. No vaccine-hypervariable poliovirus was detected in subsequent infant' clinical samples or in close contacts, and no similar cases were identified during the active case detection by county/district medical institutions and among community populations. Since the infant did not present poliomyelitis-related clinical symptoms caused by vaccine-hypervariable poliovirus, poliomyelitis was excluded. The vaccine-hypervariable poliovirus was not spread because of timely identification and effective responses, suggesting the urgent need to maintain the sensitivity of the acute flaccid paralysis surveillance system and improve the coverage of poliovirus vaccination, so as to inhibit the transmission of poliovirus.

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.

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.

Preparation and immunogenicity evaluation of recombinant poliomyelitis type 2 virus-like particles / 中华微生物学和免疫学杂志

Objective:To express virus-like particles of poliovirus type 2 (PV2-VLP) in insect cells using a recombinant baculovirus expressing P1 and 3CD and to preliminarily evaluate its immunogenicity.Methods:Based on the codon preference of High 5 cells, the sequences of P1 gene and 3CD gene of PV2 were optimized and inserted into pUC57-Amp to construct pUC57-PV2-P1 and pUC57-PV2-3CD. UC57-PV2-P1s mutant that carried P1 gene mutation affecting thermostability was then constructed. Recombinant baculovirus strains of rBac-PV2-P1s-3CD and rBac-PV2-P1-3CD (wild type) were constructed using homologous recombination. The expression of target proteins was detected by Western blot. PV2-VLP was purified by ion exchange chromatography. The structure of VLP was observed under transmission electron microscopy to evaluate the assembly efficiency. The immunogenicity of PV2-VLP was assessed in a rat model.Results:The recombinant baculovirus with stable expression of P1s and 3CD proteins was successfully constructed. Western blot results showed that the yield of VLP was higher after thermostability mutation than that of the wild type. A three-dimensional structure with a diameter of about 30 nm was observed under electron microscopy, indicating that the VLP was successfully assembled. Animal experiment showed that the recombinant PV2-VLP had immunogenicity and could effectively induce the production of neutralizing antibodies.Conclusions:Effective VLP vaccines could be successfully prepared using the insect cell-baculovirus expression system, which provided reference for the development of polio VLP vaccine.

Relationship between poliovirus receptor and prognosis of gastric cancer patients / 国际生物医学工程杂志

Objective:To explore the prognostic value of poliovirus receptor(PVR) in patients with gastric cancer.Methods:Bioinformatics methods were used to analyze the expression of PVR mRNA in gastric cancer tissues and adjacent normal tissues and its relationship with prognosis. The clinicopathological data of 73 gastric cancer patients who underwent surgical treatment were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of PVR in gastric cancer tissue and adjacent normal tissue, and its relationship with the clinicopathological characteristics of gastric cancer patients was analyzed.Results:The expression level of PVR mRNA in gastric cancer tissues was higher than that in adjacent normal tissues ( P<0.05). The expression of PVR is related to the clinical prognosis of gastric cancer patients, and the higher the expression of PVR, the lower the overall survival rate ( P=0.011) and the disease-free survival rate ( P=0.032) of gastric cancer patients. The results of immunohistochemical staining showed that PVR was highly expressed in gastric cancer tissue, mainly in the cytoplasm, while it was not expressed or lowly expressed in normal gastric tissue. High expression of PVR was associated with tumor size ( P=0.001) and recurrence 3-years after surgery ( P=0.013). Conclusions:PVR is overexpressed in gastric cancer tissue, and gastric cancer patients with high expression of PVR have a worse prognosis. The level of PVR has great value for the prognosis evaluation of gastric cancer patients.

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.

Padronização de teste para quantificar anticorpos anti-poliovírus utilizando vírus vacinal / Standardization of a test for quantifying the antibodies against poliovirus using the vaccine virus

A poliomielite é uma doença endêmica no Afeganistão e no Paquistão, apesar dos esforços para ser erradicada, representando uma ameaça para outros países principalmente devido às viagens internacionais. A Organização Mundial da Saúde (OMS) tem como objetivo erradicar a poliomielite causada pelo poliovírus selvagem no mundo. O requisito essencial para a erradicação da poliomielite é a eliminação da cepa do poliovírus selvagem, que é empregada no teste padrão-ouro. Com o intuito de auxiliar na erradicação do poliovírus selvagem, o objetivo deste estudo foi modificar o teste padrão-ouro usando o poliovírus derivado da vacina oral atenuada. Foram testados 63 soros pelo ensaio de neutralização utilizando-se antígenos vacinais. A concordância do sorotipo 1 (k=0,74) foi considerada substancial, enquanto o sorotipo 2 (k=1,00) e sorotipo 3 (k= 0,95) foram consideradas quase perfeitas. A sensibilidade dos testes de soroneutralização utilizando os sorotipos 1, 2 e 3 foi de 94,83%, 100,00% e 100,00%, respectivamente. Em conclusão, o ensaio com antígenos vacinais pode ser usado como procedimento laboratorial seguro, especialmente em estudos de vigilância em larga escala. (AU)

Poliomyelitis is an endemic disease in Afghanistan and Pakistan in despite of the efforts to eradicate it, and it represents a threat to other countries mainly due to the international trips. The World Health Organization (WHO) aims at eradicating the polio disease worldwide. An essential requirement for eradicating the poliomyelitis is the elimination of the wild poliovirus strain, which is employed in the gold standard test. As a support for the eradication of wild poliovirus, the present study aimed at modifying the gold standard test by using poliovirus derived from the oral attenuated vaccine. Sixty-three sera samples were tested by neutralization assay using vaccine antigens. The degree of agreement of the serotype 1 (k=0.74) was considered substantial, while the serotype 2 (k=1.00) and 3 (k= 0.95) showed almost perfect agreement. The sensitivity of serotypes 1, 2 and 3 was 94.83%, 100.00% and 100.00%, respectively. In conclusion, the assay with the vaccine antigens can be used as a safe application, especially for large-scale surveillance studies. (AU)

Padronização de teste para quantificar anticorpos anti-poliovírus utilizando vírus vacinal / Standardization of a test for quantifying the antibodies against poliovirus using the vaccine virus

A poliomielite é uma doença endêmica no Afeganistão e no Paquistão, apesar dos esforços para ser erradicada, representando uma ameaça para outros países principalmente devido às viagens internacionais. A Organização Mundial da Saúde (OMS) tem como objetivo erradicar a poliomielite causada pelo poliovírus selvagem no mundo. O requisito essencial para a erradicação da poliomielite é a eliminação da cepa do poliovírus selvagem, que é empregada no teste padrão-ouro. Com o intuito de auxiliar na erradicação do poliovírus selvagem, o objetivo deste estudo foi modificar o teste padrão-ouro usando o poliovírus derivado da vacina oral atenuada. Foram testados 63 soros pelo ensaio de neutralização utilizando-se antígenos vacinais. A concordância do sorotipo 1 (k=0,74) foi considerada substancial, enquanto o sorotipo 2 (k=1,00) e sorotipo 3 (k= 0,95) foram consideradas quase perfeitas. A sensibilidade dos testes de soroneutralização utilizando os sorotipos 1, 2 e 3 foi de 94,83%, 100,00% e 100,00%, respectivamente. Em conclusão, o ensaio com antígenos vacinais pode ser usado como procedimento laboratorial seguro, especialmente em estudos de vigilância em larga escala.

Poliomyelitis is an endemic disease in Afghanistan and Pakistan in despite of the efforts to eradicate it, and it represents a threat to other countries mainly due to the international trips. The World Health Organization (WHO) aims at eradicating the polio disease worldwide. An essential requirement for eradicating the poliomyelitis is the elimination of the wild poliovirus strain, which is employed in the gold standard test. As a support for the eradication of wild poliovirus, the present study aimed at modifying the gold standard test by using poliovirus derived from the oral attenuated vaccine. Sixty-three sera samples were tested by neutralization assay using vaccine antigens. The degree of agreement of the serotype 1 (k=0.74) was considered substantial, while the serotype 2 (k=1.00) and 3 (k= 0.95) showed almost perfect agreement. The sensitivity of serotypes 1, 2 and 3 was 94.83%, 100.00% and 100.00%, respectively. In conclusion, the assay with the vaccine antigens can be used as a safe application, especially for large-scale surveillance studies.

Availability of AFP Specimen Collection Kits and Data Tools in Health Facilities in Selected States in Nigeria

Background: Acute flaccid paralysis (AFP) surveillance was adopted globally as a key strategy for monitoring the progress of the polio eradication initiative. The main objective of AFP surveillance is to detect the presence of circulating wild-type poliovirus and other subtypes of polioviruses. Stool specimen collection kits for AFP surveillance and data tools, regrettably are not always available in health facilities, and thus cause gaps in specimen collection and proper documentation which could ultimately lead to under-reporting of cases. Methods: This survey was undertaken to determine the availability of stool collection kits and data capturing tools in health facilities in some randomly selected states in Nigeria. The main aim was to relate the findings with the quality of the surveillance system in the areas visited and an overall indication of the functionality of the process in the country. Results: The outcome of the study found only 32,598 (74.7%) health facilities out of the 43,644 health facilities who visited and had stool specimen collection kits, while of the 43,582 health facilities visited, only 38,029 (87.3%) health facilities had data tools. Conclusions: Gaps were noticed in the supply of key AFP surveillance components to the health facilities visited, which by extension could apply to those not visited. Countries that are still polio-endemic will have to regularly survey their facilities for the availability of these very important materials. The methodology can be adapted to other diseases to evaluate the strength of the surveillance system.

Analysis of poliovirus receptor, CD155 expression in different human colorectal cancer cell lines: Implications for poliovirus virotherapy

Context: Poliovirus (PV) receptor (CD155) is expressed on several kinds of cells and exerts diverse functions. Various investigations have confirmed that changes in CD155 expression in cancer cell lines affect metastasis, proliferation, and migration. Aims: The purpose of the present study was to investigate the CD155 transcript and protein expression in human colon adenocarcinoma cell lines in comparison to normal fetal human colon (FHC) cells. Materials and Methods: The CD155 expression level in four human adenocarcinoma cell lines and normal colon cell line were assessed using the SYBR green quantitative real-time polymerase chain reaction (PCR) and flowcytometry. Results: The results of real-time PCR indicated that CD155 was significantly overexpressed in all human adenocarcinoma cell lines (P = 0.000). The highest and the lowest expression level of CD155 messenger RNA was observed in SW480 and HT29 cell lines by 491.14, and 12.04 fold changes, respectively, in comparison with the human normal cell line (FHC). Results of flowcytometry indicate that protein was strongly expressed in cancer cell lines. SW480 cells showed the highest CD155 protein expression level of 98.1%, whereas this protein expression was 1.3% in human normal colon cell line (FHC). Totally, these data indicate that CD155 expression is significantly elevated in cancer cell lines. Conclusions: The preferential expression of CD155 on cancer cell lines rather than on normal cell line suggests that CD155 could be targeted for future PV virotherapy

Observation on safety of sequential vaccination schedule of different strain inactivated poliovirus vaccines / 中华流行病学杂志

Objective@#To evaluate the safety of population based sequential vaccination schedule of inactivated poliovirus vaccines prepared with different strains.@*Methods@#This randomized, parallel-group controlled trial was conducted from March, 2017 to May, 2018, in Shanghai. Adverse reaction data of Sabin strain inactivated polio vaccine (sIPV), wild strains inactivated polio vaccines (wIPV) and bivalent types Ⅰ and Ⅲ oral poliomyelitis vaccine (bOPV) were systematically collected through active observation in 1 917 infants in Shanghai after the vaccination at 2, 3, 4 months old. The eligible infants aged 2 months were divided into 4 groups: ①sIPV+sIPV+bOPV group; ②sIPV+wIPV+bOPV group; ③wIPV+sIPV+bOPV group; ④wIPV+wIPV+bOPV group.@*Results@#The incidence of adverse reaction 30 days later after 3 basic dose vaccinations was 16.79% (946/5 633). No serious adverse reaction was reported. Local and systemic reactions were mainly mild. Common local reactions were pain, erythema, cutaneous nodule, etc.; and common systemic reactions were abnormal crying, drowsiness, diarrhea and appetite lost, etc.. The incidence of local reactions 30 days later after 3 basic dose vaccinations was 1.65% (93/5 633), and the incidence rates of grade 1-3 reactions were1.26% (71/5 633), 0.21% (12/5 633) and 0.20% (11/5 633) respectively. The incidence rate of systemic reactions 30 days later after 3 basic vaccinations was 15.14% (853/5 633), and the incidence rates of grade 1-3 reactions were 11.33% (638/5 633), 3.18% (179/5 633) and 0.64% (36/5 633) respectively. There were no significant differences in the rate of grade 3 reaction among different groups (χ2=4.17, P=0.24).@*Conclusions@#No severe adverse reactions related to sequential vaccination of different strain inactivated polio vaccines were observed, most of reactions were mild and all of them were cured. It is safe to use sIPV and wIPV simultaneously or alternately for childhood sequential vaccination.