Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.143
Filtrar
1.
Cell Host Microbe ; 29(1): 3-5, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33444554

RESUMO

Troubled by an unstable world beset by new and emerging viruses? Virus evolution is here to help. Through detailed studies of poliovirus vaccine reversion to virulence, Valesano and colleagues remind us that some things in life can, indeed, be counted on.


Assuntos
Poliomielite , Poliovirus , Humanos , Mutação , Poliomielite/prevenção & controle , Poliovirus/genética , Vacina Antipólio Oral , Vacinação
2.
Brasília, D.F.; OPAS; 2021-01-19. (OPAS-W/BRA/FPL/20-176).
Não convencional em Português | PAHO-IRIS | ID: phr2-53204

RESUMO

A Estratégia de Erradicação da Poliomielite 2019-2023 posicionou o atual período estratégico de cinco anos da GPEI em relação à dupla emergência enfrentada pelo esforço de erradicação da poliomielite: que o programa deve interromper o WPV1 e parar a transmissão do cVDPV. Em consideração às implicações potenciais de longo prazo para surtos de cVDPV, a Estratégia de Erradicação sinalizou a importância de um plano de contingência para mitigar o risco de cVDPVs por meio de intervenções de curto prazo, protocolos de emergência e mudanças de políticas. A Estratégia para a Resposta ao Poliovírus Derivado da Vacina Circulante Tipo 2 2020–2021 é oferecida como um adendo que atende a essa necessidade de um plano de contingência. Foi desenvolvida por um grupo de trabalho e em consulta com especialistas da parceria GPEI: a Organização Mundial da Saúde (OMS), o Fundo das Nações Unidas para a Infância (UNICEF), o Rotary International, os Centros para Controle e Prevenção de Doenças dos EUA (CDC), a Fundação Bill & Melinda Gates (FBMG) e a Gavi, a Aliança das Vacinas. O Anexo A fornece uma visão geral sobre a supervisão e gestão desse adendo para responder aos surtos de cVDPV2. A estratégia será regularmente revisada e atualizada conforme necessário para atender a necessidades contínuas. Essa estratégia de 18 meses (janeiro de 2020 a junho de 2021) apresenta uma série de medidas de mitigação de risco para interromper a propagação do cVDPV2. Ela prioriza o uso de ativos do programa e utiliza uma nova vacina para melhorar os resultados da resposta ao surto. Prevê-se que essa nova vacina, chamada de nova VOP2, forneça imunidade intestinal semelhante à da Sabin VOP2, embora seja substancialmente mais estável geneticamente e, portanto, resistente à reversão, reduzindo os riscos associados à resposta cVDPV2. Com duas candidatas na linha de pesquisa e desenvolvimento, a nova VOP2 deve estar disponível em meados de 2020 por meio da Lista de Uso de Emergência da OMS (LUE)3. Informações sobre o licenciamento e a produção da nova VOP2 são fornecidas no Anexo B.


Assuntos
Pandemias , Poliomielite , Imunização , Erradicação de Doenças , Poliovirus , Vacinas contra Poliovirus
3.
MMWR Morb Mortal Wkly Rep ; 69(5152): 1648-1652, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33382673

RESUMO

On January 30, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a Public Health Emergency of International Concern (1). On March 24, 2020, the Global Polio Eradication Initiative (GPEI) suspended all polio supplementary immunization activities and recommended the continuation of polio surveillance (2). In April 2020, GPEI shared revised polio surveillance guidelines in the context of the COVID-19 pandemic, which focused on reducing the risk for transmission of SARS-CoV-2, the virus that causes COVID-19, to health care workers and communities by modifying activities that required person-to-person contact, improving hand hygiene and personal protective equipment use practices, and overcoming challenges related to movement restrictions, while continuing essential polio surveillance functions (3). GPEI assessed the impact of the COVID-19 pandemic on polio surveillance by comparing data from January to September 2019 to the same period in 2020. Globally, the number of acute flaccid paralysis (AFP) cases reported declined 33% and the mean number of days between the second stool collected and receipt by the laboratory increased by 70%. Continued analysis of AFP case reporting and stool collection is critical to ensure timely detection and response to interruptions of polio surveillance.


Assuntos
Saúde Global , Poliomielite/epidemiologia , Vigilância da População , Técnicas de Laboratório Clínico/estatística & dados numéricos , Erradicação de Doenças , Fezes/virologia , Humanos , Poliomielite/prevenção & controle , Poliovirus/isolamento & purificação , Vacinas contra Poliovirus/administração & dosagem
4.
MMWR Morb Mortal Wkly Rep ; 69(40): 1464-1468, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031360

RESUMO

Wild poliovirus type 1 (WPV1) transmission is ongoing only in Afghanistan and Pakistan (1). Following a decline in case numbers during 2013-2016, the number of cases in Afghanistan has increased each year during 2017-2020. This report describes polio eradication activities and progress toward polio eradication in Afghanistan during January 2019-July 2020 and updates previous reports (2,3). Since April 2018, insurgent groups have imposed bans on house-to-house vaccination. In September 2019, vaccination campaigns in areas under insurgency control were restarted only at health facilities. In addition, during March-June 2020, all campaigns were paused because of the coronavirus disease 2019 (COVID-19) pandemic. The number of WPV1 cases reported in Afghanistan increased from 21 in 2018 to 29 in 2019. During January-July 2020, 41 WPV1 cases were reported as of August 29, 2020 (compared with 15 during January-July 2019); in addition, 69 cases of circulating vaccine-derived poliovirus type 2 (cVDPV2), and one case of ambiguous vaccine-derived poliovirus type 2 (aVDPV2) (isolates with no evidence of person-to-person transmission or from persons with no known immunodeficiency) were detected. Dialogue with insurgency leaders through nongovernmental and international organizations is ongoing in an effort to recommence house-to-house campaigns, which are essential to stopping WPV1 transmission in Afghanistan. To increase community demand for polio vaccination, additional community health needs should be addressed, and polio vaccination should be integrated with humanitarian services.


Assuntos
Erradicação de Doenças , Poliomielite/prevenção & controle , Vigilância da População , Adolescente , Afeganistão/epidemiologia , Criança , Pré-Escolar , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Poliomielite/epidemiologia , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Vacinação/estatística & dados numéricos
5.
Nucleic Acids Res ; 48(18): 10441-10455, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941651

RESUMO

Comprehensive genome-wide analysis has revealed the presence of translational elements in the 3' untranslated regions (UTRs) of human transcripts. However, the mechanisms by which translation is initiated in 3' UTRs and the physiological function of their products remain unclear. This study showed that eIF4G drives the translation of various downstream open reading frames (dORFs) in 3' UTRs. The 3' UTR of GCH1, which encodes GTP cyclohydrolase 1, contains an internal ribosome entry site (IRES) that initiates the translation of dORFs. An in vitro reconstituted translation system showed that the IRES in the 3' UTR of GCH1 required eIF4G and conventional translation initiation factors, except eIF4E, for AUG-initiated translation of dORFs. The 3' UTR of GCH1-mediated translation was resistant to the mTOR inhibitor Torin 1, which inhibits cap-dependent initiation by increasing eIF4E-unbound eIF4G. eIF4G was also required for the activity of various elements, including polyU and poliovirus type 2, a short element thought to recruit ribosomes by base-pairing with 18S rRNA. These findings indicate that eIF4G mediates translation initiation of various ORFs in mammalian cells, suggesting that the 3' UTRs of mRNAs may encode various products.


Assuntos
Fator de Iniciação 4G em Eucariotos/genética , GTP Cicloidrolase/genética , Fases de Leitura Aberta/genética , Serina-Treonina Quinases TOR/genética , Regiões 3' não Traduzidas/genética , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Naftiridinas/farmacologia , Poliovirus/genética , Biossíntese de Proteínas/genética , Capuzes de RNA/genética , RNA Mensageiro/genética , RNA Ribossômico 18S/genética , Ribossomos/genética , Serina-Treonina Quinases TOR/antagonistas & inibidores
6.
BMC Infect Dis ; 20(1): 641, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32867698

RESUMO

BACKGROUND: Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines. METHODS: There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 1:8) and maternal antibody positive (≥1:8), and the second one included maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels. RESULTS: The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ≥1:32 were significantly lower than those in participants with maternal antibody titer < 1:8 and 1:8 ~ < 1:32. CONCLUSIONS: Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.


Assuntos
Anticorpos Antivirais/imunologia , Imunidade Materno-Adquirida/imunologia , Imunogenicidade da Vacina , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/uso terapêutico , Poliovirus/imunologia , Vacinação/métodos , Anticorpos Neutralizantes/imunologia , China , Feminino , Humanos , Lactente , Masculino , Poliomielite/virologia , Vacina Antipólio de Vírus Inativado/efeitos adversos , Soroconversão
8.
Arch Virol ; 165(11): 2627-2632, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776175

RESUMO

Due to the risk of poliovirus importation from Ukraine in 2015, a combined surveillance program monitoring the circulation of enteroviruses (EVs) in healthy children from at-risk areas and in the environment was conducted in Romania. Virological testing of stool samples collected from 155 healthy children aged from two months to six years and of 186 sewage water samples collected from different areas was performed. A total of 58 (37.42%) stool samples and 50 (26.88%) sewage water samples were positive for non-polio EVs, but no poliovirus was detected. A high level of circulation of echovirus (E) types 6 and 7 and coxsackievirus (CV) type B5 was observed.


Assuntos
Enterovirus Humano B/isolamento & purificação , Enterovirus/isolamento & purificação , Fezes/virologia , Esgotos/virologia , Criança , Pré-Escolar , Enterovirus/classificação , Enterovirus/genética , Enterovirus Humano B/genética , Infecções por Enterovirus/virologia , Meio Ambiente , Monitoramento Ambiental/métodos , Voluntários Saudáveis , Humanos , Lactente , Limite de Detecção , Modelos Logísticos , Tipagem Molecular/métodos , Filogenia , Poliovirus/genética , Poliovirus/isolamento & purificação , Romênia , Águas Residuárias/virologia
9.
Am J Trop Med Hyg ; 103(4): 1367-1369, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32861265

RESUMO

Polio is a deadly viral disease that has been paralyzing many children in Afghanistan. Despite fundamental efforts, primarily vaccination, to reduce the number of cases in Afghanistan, there are still many children who are deprived of the vaccine every year. Afghanistan is one of the two remaining countries endemic for polio, and the country has undergone various challenges that have hampered the eradication of this disease. The underlying challenges include inaccessibility of unsecured areas, illiteracy, refusal, and, most recently, COVID-19. The country is in the midst of a battle against COVID-19, and polio has almost entirely been neglected. Sadly, polio cases are increasing in the country, particularly in polio-free provinces. After an initial lockdown, many businesses have been allowed to resume, but the mass polio vaccination campaign has not restarted. New cases of polio will surge if endemic regions remain unvaccinated or inaccessible. To curb the further spread of polio, Afghanistan needs to resume nationwide house-to-house vaccination as restrictions due to COVID-19 are loosened.


Assuntos
Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Programas de Imunização/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Vacinas contra Poliovirus/administração & dosagem , Vacinação/estatística & dados numéricos , Afeganistão/epidemiologia , Betacoronavirus/patogenicidade , Pré-Escolar , Coinfecção , Infecções por Coronavirus/economia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Doenças Endêmicas/economia , Feminino , Humanos , Incidência , Lactente , Alfabetização/estatística & dados numéricos , Masculino , Pandemias/economia , Pneumonia Viral/economia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Poliomielite/economia , Poliomielite/imunologia , Poliovirus/patogenicidade , Pobreza/estatística & dados numéricos , Saúde Pública/ética , Terrorismo/estatística & dados numéricos
10.
BMC Infect Dis ; 20(1): 611, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811467

RESUMO

BACKGROUND: The poliovirus has been targeted for eradication since 1988. Kenya reported its last case of indigenous Wild Poliovirus (WPV) in 1984 but suffered from an outbreak of circulating Vaccine-derived Poliovirus type 2 (cVDPV2) in 2018. We aimed to describe Kenya's polio surveillance performance 2016-2018 using WHO recommended polio surveillance standards. METHODS: Retrospective secondary data analysis was conducted using Kenyan AFP surveillance case-based database from 2016 to 2018. Analyses were carried out using Epi-Info statistical software (version 7) and mapping was done using Quantum Geographic Information System (GIS) (version 3.4.1). RESULTS: Kenya reported 1706 cases of AFP from 2016 to 2018. None of the cases were confirmed as poliomyelitis. However, 23 (1.35%) were classified as polio compatible. Children under 5 years accounted for 1085 (63.6%) cases, 937 (55.0%) cases were boys, and 1503 (88.1%) cases had received three or more doses of Oral Polio Vaccine (OPV). AFP detection rate substantially increased over the years; however, the prolonged health workers strike in 2017 negatively affected key surveillance activities. The mean Non-Polio (NP-AFP) rate during the study period was 2.87/ 100,000 children under 15 years, and two adequate specimens were collected for 1512 (88.6%) AFP cases. Cumulatively, 31 (66.0%) counties surpassed target for both WHO recommended AFP quality indicators. CONCLUSIONS: The performance of Kenya's AFP surveillance system surpassed the minimum WHO recommended targets for both non-polio AFP rate and stool adequacy during the period studied. In order to strengthen the country's polio free status, health worker's awareness on AFP surveillance and active case search should be strengthened in least performing counties to improve case detection. Similar analyses should be done at the sub-county level to uncover underperformance that might have been hidden by county level analysis.


Assuntos
Surtos de Doenças/prevenção & controle , Monitoramento Epidemiológico , Paralisia/epidemiologia , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliovirus/imunologia , Adolescente , Criança , Pré-Escolar , Fezes/virologia , Feminino , Sistemas de Informação Geográfica , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Paralisia/virologia , Vacina Antipólio Oral/efeitos adversos , Vigilância da População , Estudos Retrospectivos , Software
11.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(7): 779-783, 2020 Jul 06.
Artigo em Chinês | MEDLINE | ID: mdl-32842302

RESUMO

Objective: To analyze the changing trend of polio vaccine immunization effectiveness and vaccine titer in Beijing in 2012, 2014, 2016 and 2018 before and after the adjustment of polio vaccine immunization program strategy. Methods: According to the convenient sampling method,the vaccination clinics of Chaoyang and Yanqing Districts in 2012, Fengtai and Daxing Districts in 2014, Tongzhou and Pinggu Districts in 2016, Dongcheng and Shunyi Districts in 2018 were selected as monitoring points. A total of 292 children were selected 4-8 weeks after the completion of 3 doses polio vaccine basic immunization which were 3 doses of trivalent oral poliovirus vaccine(tOPV)schedule before the strategy adjustment in 2012-2014 and 1 dose of inactivated poliovirus vaccine (IPV) following 2 doses of bivalent oral poliovirus vaccine (bOPV) sequential schedule after the adjustment in 2016-2018. About 1.0 ml blood samples were collected to detect type Ⅰ and Ⅲ neutralizing poliovirus antibody. A total of 9 oral poliovirus vaccines (8 vaccines in 2012) were selected from different sources of vaccine storage every year to test the vaccine titer using random number method. Results: The [M(P25,P75)] age of 292 children was 5 (5, 6) months, and the ratio of male to female was 1.04 (149/143). In 2012, 2014, 2016 and 2018, 66,72,68 and 86 children were investigated respectively. After basic immunization, antibody positive rates for type Ⅰ and Ⅲ poliovirus were 100%, except 98.61% (71) for type Ⅰ poliovirus in 2014. The neutralizing antibody titer of type Ⅰ and Ⅲ poliovirus was higher in 2016 and 2018 than that in 2012 and 2014 (P<0.001). The average titer of tOPV were (6.05±0.15) and (6.16±0.12) lgCCID50 per dose in 2012 and 2014. The average titer of bOPV were (6.88±0.21) and (6.26±0.14) lgCCID50 per 100 µl in 2016 and 2018 (P<0.001). Conclusion: Before and after the adjustment of polio vaccine immunization strategy in Beijing, the basic immunization success rate of the IPV-bOPV sequential immunization schedule was good as well as full tOPV schedule. The level of polio antibody produced by the IPV-bOPV sequential immunization schedule was higher. After adjustment, bOPV titer in 2016 was significantly higher than those before adjustment, while bOPV titer decreased significantly in 2018.


Assuntos
Poliomielite/prevenção & controle , Poliovirus , Pequim , Criança , Feminino , Humanos , Programas de Imunização , Esquemas de Imunização , Lactente , Masculino , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral , Vacinação
12.
Medicine (Baltimore) ; 99(31): e21298, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756110

RESUMO

Serums were collected from people to assess whether polio immunity level was high enough to satisfy the polio vaccine immunization switch in Chongqing.People in 7 age groups (<1 year, 1-2 years, 3-4 years, 5-6 years, 7-14 years, 15-19 years, ≧20 years) were randomly selected in 3 areas by different geographical features in 2015. Peripheral venous blood samples were obtained and assays to detect poliovirus (PV) -neutralizing antibodies were performed. Acute flaccid paralysis (AFP) data was collected from 2012 to 2016 in Chongqing to evaluate the performance of AFP surveillance system by indicator analysis.A total of 636 people were tested for PV neutralization antibodies (NA). Overall NA seroprevalence for PV1, PV2 and PV3 were 93.40%, 96.38% and 91.82%, and geometric mean titers (GMTs) were 61.14, 66.78 and 21.47, respectively. GMTs and NA seroprevalence for PV1, PV2 and PV3 in older people were lower than young people. There were significant differences in seroprevalences of PV1 and PV3 among geographic areas (P < .05) in Chongqing.High seroprevalence for PV1, PV2, and PV3 and qualified capability for monitoring AFP cases showed that the polio eradication program has made positive achievements in Chongqing and established a stable base for a polio vaccine immunization switch. Nevertheless, GMTs were negatively associated with age in the geographic districts with poor economical features, which will increase the risk of emergence of vaccine-derived PV after polio vaccine switch. More than 1 dose of inactivated polio vaccine should be introduced into the polio vaccine schedule, and the supplementary immunization of polio should still be annually carried out after polio vaccine switch, especially among elder children and the adults.


Assuntos
Anticorpos Antivirais/sangue , Paralisia/epidemiologia , Poliovirus/imunologia , Adolescente , Anticorpos Neutralizantes/sangue , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Hipotonia Muscular , Paralisia/sangue , Paralisia/etiologia , Estudos Soroepidemiológicos , Adulto Jovem
13.
MMWR Morb Mortal Wkly Rep ; 69(28): 913-917, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32673297

RESUMO

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.


Assuntos
Saúde Global/estatística & dados numéricos , Síndromes de Imunodeficiência/complicações , Poliomielite/epidemiologia , Vacina Antipólio Oral/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Poliomielite/prevenção & controle , Poliovirus/genética , Poliovirus/isolamento & purificação , Vacina Antipólio Oral/administração & dosagem , Sorogrupo
16.
Nucleic Acids Res ; 48(14): 8006-8021, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32556302

RESUMO

The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds to stem-loop IV of the IRES. When PCBP2 is cleaved in its linker region by viral proteinase 3CD, translation initiation ceases allowing the next stage of replication to commence. Here, we investigate the interaction of PCBP2 with the apical region of stem-loop IV (SLIVm) of poliovirus RNA in its full-length and truncated form. CryoEM structure reconstruction of the full-length PCBP2 in complex with SLIVm solved to 6.1 Å resolution reveals a compact globular complex of PCBP2 interacting with the cruciform RNA via KH domains and featuring a prominent GNRA tetraloop. SEC-SAXS, SHAPE and hydroxyl-radical cleavage establish that PCBP2 stabilizes the SLIVm structure, but upon cleavage in the linker domain the complex becomes more flexible and base accessible. Limited proteolysis and REMSA demonstrate the accessibility of the linker region in the PCBP2/SLIVm complex and consequent loss of affinity of PCBP2 for the SLIVm upon cleavage. Together this study sheds light on the structural features of the PCBP2/SLIV complex vital for ribosomal docking, and the way in which this key functional interaction is regulated following translation of the poliovirus genome.


Assuntos
Iniciação Traducional da Cadeia Peptídica , Poliovirus/genética , RNA Viral/química , Proteínas de Ligação a RNA/química , Microscopia Crioeletrônica , Modelos Moleculares , Conformação de Ácido Nucleico , Conformação Proteica , RNA Viral/metabolismo , Proteínas de Ligação a RNA/metabolismo , Espalhamento a Baixo Ângulo , Difração de Raios X
17.
Appl Environ Microbiol ; 86(15)2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32444474

RESUMO

The Polio Endgame Strategy 2019-2023 has been developed. However, more effective and efficient surveillance activities should be conducted with the preparedness of emergence for vaccine-derived poliovirus (VDPV) or wild poliovirus (WPV). We reviewed the impact of the case-based acute flaccid paralysis (AFP) surveillance (1991 to 2018) and environmental surveillance (2011 to 2018) in polio eradication in Shandong province of China. Clinical characteristics of AFP cases and enterovirus (EV) investigation of research samples were assessed. During the period, 10,224 AFP cases were investigated, and 352 sewage samples were collected. The nonpolio AFP rate sustained at over 2.0/100,000 since 1997. Of 10,224 cases, males and young children experienced a higher risk of severe diseases, and 68.5% suffered lower limb paralysis. We collected 1,707 EVs from AFP cases, including 763 polioviruses and 944 nonpolio enteroviruses (NPEVs). No WPV was isolated since 1992. The AFP surveillance showed high sensitivity in detecting 143 vaccine-associated paralytic poliomyelitis (VAPP) cases and 6 VDPVs. For environmental surveillance, 217 (61.6%) samples were positive for poliovirus, and altogether, 838 polioviruses and 2,988 NPEVs were isolated. No WPV was isolated in environmental surveillance, although one VDPV2 was identified. Phylogenetic analysis revealed environmental surveillance had the capacity to detect a large scope of NPEVs. The case-based AFP surveillance will be indispensable for detecting VAPP cases and VDPV circulation in countries using oral polio vaccine. Environmental surveillance is advantageous in identifying EV circulation and responding to ongoing circulating VDPV outbreaks and should be expanded to complement the AFP surveillance.IMPORTANCE Interrupting wild poliovirus transmission and stopping circulating vaccine-derived poliovirus (cVDPV) outbreaks have been proposed as two global goals by the World Health Organization in the Global Polio Eradication Initiative (GPEI). This analysis, based on the 28-year acute flaccid paralysis (AFP) surveillance and 8-year environmental surveillance, provides continued high-quality surveillance performance in achieving the GPEI and detecting the circulation of enterovirus. Given the ongoing cVDPV outbreaks in the world, we present the surveillance capacity of environmental surveillance in capturing enterovirus circulation. The final poliovirus (especially VDPV) elimination has become increasingly complex, and the case-based AFP surveillance alone will lead to difficulties in early detecting dynamics of poliovirus transmission and monitoring the extent of environmental circulation. This study goes beyond previous work to provide a detailed comprehensive evaluation of the enterovirus surveillance and can be used to formulate a set of implementation plan and performance indicators for environmental surveillance.


Assuntos
Monitoramento Ambiental , Paralisia/diagnóstico , Poliomielite/prevenção & controle , Vigilância da População , China , Enterovirus/isolamento & purificação , Humanos , Poliomielite/complicações , Poliomielite/diagnóstico , Poliovirus/isolamento & purificação
18.
Epidemiol Infect ; 148: e157, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32398193

RESUMO

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055-0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191-0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.


Assuntos
Modelos Biológicos , Poliomielite/epidemiologia , Poliomielite/virologia , Poliovirus/isolamento & purificação , Vigilância da População/métodos , Emigrantes e Imigrantes , Inglaterra/epidemiologia , Humanos , Estudos Retrospectivos , País de Gales/epidemiologia
20.
Lancet Infect Dis ; 20(9): 1071-1079, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32442523

RESUMO

BACKGROUND: The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV. METHODS: This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560. RESULTS: Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups. INTERPRETATION: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen. FUNDING: Chinese Center for Disease Control and Prevention and China National Biotec Group Company.


Assuntos
Imunogenicidade da Vacina , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/imunologia , Poliovirus/imunologia , Idoso , China/epidemiologia , Feminino , Humanos , Esquemas de Imunização , Masculino , Poliovirus/classificação , Soroconversão , Sorogrupo , Vacinação/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA