关键词： 随机对照试验   灰质   脊髓   免疫原性   疫苗   口服   补锌   巴基斯坦  

摘要： 在巴基斯坦，根除脊髓灰质炎仍是一项挑战，消灭脊髓灰质炎失败的原因是复杂的。在巴基斯坦，营养不良和微量营养素缺乏，尤其是锌缺乏，是主要的公共健康问题，可能潜在影响肠道疫苗的免疫应答，包括口服脊髓灰质炎疫苗。

关键词： POLIOVIRUS   RNA polymerases   GENETIC recombination in viruses   RIBAVIRIN   DRUG resistance in microorganisms   THERAPEUTIC use  

摘要： RNA recombination is important in the formation of picornavirus species groups and the ongoing evolution of viruses within species groups. In this study, we examined the structure and function of poliovirus polymerase, 3D(pol), as it relates to RNA recombination. Recombination occurs when nascent RNA products exchange one viral RNA template for another during RNA replication. Because recombination is a natural aspect of picornavirus replication, we hypothesized that some features of 3D(pol) may exist, in part, to facilitate RNA recombination. Furthermore, we reasoned that alanine substitution mutations that disrupt 3D(pol)-RNA interactions within the polymerase elongation complex might increase and/or decrease the magnitudes of recombination. We found that an L420A mutation in 3D(pol) decreased the frequency of RNA recombination, whereas alanine substitutions at other sites in 3D(pol) increased the frequency of recombination. The 3D(pol) Leu420 side chain interacts with a ribose in the nascent RNA product 3 nucleotides from the active site of the polymerase. Notably, the L420A mutation that reduced recombination also rendered the virus more susceptible to inhibition by ribavirin, coincident with the accumulation of ribavirin-induced G -> A and C -> U mutations in viral RNA. We conclude that 3D(pol) Leu420 is critically important for RNA recombination and that RNA recombination contributes to ribavirin resistance. IMPORTANCE Recombination contributes to the formation of picornavirus species groups and the emergence of circulating vaccine-derived polioviruses (cVDPVs). The recombinant viruses that arise in nature are occasionally more fit than either parental strain, especially when the two partners in recombination are closely related, i.e., members of characteristic species groups, such as enterovirus species groups A to H or rhinovirus species groups A to C. Our study shows that RNA recombination requires conserved features of the viral polymerase. Furthermore, a p

关键词： poliomyelitis   polio   vaccination   poliovirus   vaccine-derived poliovirus   viruses   children   primary immunodeficiency   Iran  

摘要： Widespread use of oral poliovirus vaccine has led to an approximate to 99.9% decrease in global incidence of poliomyelitis (from approximate to 350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses.

关键词： Public health   polio   vaccination (immunization)   vaccine policy development  

摘要： In August 2013, a nationwide vaccination campaign with bivalent oral polio vaccine (bOPV) was initiated after isolation of wild-type poliovirus type 1 (WPV-1) in routine sewage surveillance in Israel. The campaign started in the Southern district and later extended to the entire country. This study examined the association between socioeconomic status (SES), and compliance with bOPV vaccine during the campaign. Nationwide data relating to SES by geographical cluster were correlated with vaccine coverage rates in the same areas. All analyses were conducted separately for Jews and Arabs. Coverage with the bOPV vaccination campaign in the Arab population (92.4%) was higher than in the Jewish population (59.2%). This difference was consistently present in all SES clusters. In the Jewish population there was an inverse correlation between SES and vaccination coverage rates (R = -0.93, P < 0.001). Lower vaccination coverage with supplemental vaccine activities in higher SES groups is a challenge that needs to be addressed in future public health events and emergencies in order to achieve satisfactory protection rates for the public.

关键词： poliovirus receptor   oncolytic viruses   malignant gliomas   poliovirus   virotherapy  

摘要： A humanized line of rat C6 glioma cells expressing human poliovirus receptor was obtained and tested for the sensitivity to oncolytic effects of vaccine strains of type 1, 2, and 3 polioviruses. Presentation of the poliovirus receptor on the surface of C6 glioma cells was shown to be a necessary condition for the interaction of cells with polioviruses, but insufficient for complete poliovirus oncolysis.

关键词： Africa   Asia   Biology and life sciences   Enteroviruses   Geographical locations   Immunity   Immunology   Infectious diseases   Medical microbiology   Medicine and health sciences   Microbial pathogens   Microbiology   Mucosal immunity   Nigeria   Organisms   Pakistan   Pathogens   Pathology and laboratory medicine   People and places   Poliomyelitis   Poliovirus   Preventive medicine   Public and occupational health   Research Article   RNA viruses   Vaccination and immunization   Vaccines   Viral diseases   Viral pathogens   Viruses  

摘要： Background Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s). Methods and Findings In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model. Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008-2009 and 2012-2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%-100%] in Nigeria and 84% [95% uncertainty interval 77%-91%] in Pakistan) had >70% population immunity among chil

关键词： Acute flaccid paralysis   Surveillance   Immunization   Herd immunity   Zero-dose children  

摘要： Objectives: To demonstrate the immunity status of children with non-polio acute flaccid paralysis (NP AFP) reported through the AFP surveillance system in the South South region of Nigeria. Study design: A retrospective study was conducted using AFP surveillance data collected routinely between January 2011 and December 2014 by the Disease Surveillance Department of the regional health service and the World Health Organization (WHO)-accredited regional reference polio laboratory. All cases of AFP reported to the Disease Surveillance Network from all six zones during this period were included in the study. Methods: In total, 5111 cases of AFP in children aged <= 15 years were reported between 2011 and 2014. These cases were investigated and verified by WHO surveillance officers using a standard questionnaire, which captured the number of doses of oral polio vaccine (OPV) received by the child. Two stool samples were collected for each case, 24-48 h apart, within 14 days of the onset of paralysis, and transported to the national polio laboratory under reverse cold chain storage. Data retrieved were stored in an AFP database hosted by the WHO server. EPIINFO software was used to query the database and extract the information required for analysis in this study. Results: The percentage of children who had received at least three doses of OPV (which serves as a threshold to measure immunity status) decreased from 87% in 2011 to 82% in 2014. The percentage of children who had not received any doses of OPV decreased from 2% in 2011 to 1% in 2014. Forty-eight percent of the children who had not received any doses of OPV were aged <1 year. Conclusion: Given the decrease in OPV immunity status, the region risks re-introduction of poliovirus. Swift steps should be taken to improve the immunization coverage, which would boost immunity status in Nigeria. (C) 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

关键词： Poliomyelitis   Seroprevalence   Kano   Nigeria   Oral poliovirus vaccine  

摘要： Introduction: In September 2015, Nigeria was removed from the list of polio-endemic countries after more than 12 months had passed since the detection of last wild poliovirus case in the country on 24 July 2014. We are presenting here a report of two polio seroprevalence surveys conducted in September 2013 and October 2014, respectively, in the Kano state of northern Nigeria. Methods: Health facility based seroprevalence surveys were undertaken at Murtala Mohammad Specialist Hospital, Kano. Parents or guardians of children aged 6-9 months, 36-47 months, 5-9 years and 10-14 years in 2013 and 6-9 months and 19-22 months (corresponding to 6-9 months range at the time of 2013 survey) in 2014 presenting to the outpatient department, were approached for participation, screened for eligibility and asked to provide informed consent. A questionnaire was administered and a blood sample collected for polio neutralization assay. Results: Among subjects aged 6-9 months in the 2013 survey, seroprevalence was 58% (95% confidence interval [CI] 51-66%) to poliovirus type 1, 42% (95% CI 34-50%) to poliovirus type 2, and 52% (95% CI 44-60%) to poliovirus type 3. Among children 36-47 months and older, seroprevalence was 85% or higher for all three serotypes. In 2014, seroprevalence in 6-9 month infants was 72% (95% CI 65-79%) for type 1, 59% (95% CI 52-66%) for type 2, and 65% (95% CI 57-72%) for type 3 and in 19-22 months, 80% (95% CI 74-85%), 57% (49-63%) and 78% (71-83%) respectively. Seroprevalence was positively associated with history of increasing oral poliovirus vaccine doses. Conclusions: There was significant improvement in seroprevalence in 2014 over the 2013 levels indicating a positive impact of recent programmatic interventions. However the continued low seroprevalence in 6-9 month age is a concern and calls for improved immunization efforts to sustain the polio-free Nigeria. (C) 2016 The Authors. Published by Elsevier Ltd.

关键词： Africa   Biology and life sciences   Chemical properties   Chemistry   Enteroviruses   Geographical locations   Immunity   Immunology   Infectious diseases   Medical microbiology   Medicine and health sciences   Microbial pathogens   Microbiology   Nigeria   Organisms   Pathogens   Pathology and laboratory medicine   People and places   Physical chemistry   Physical sciences   Poliomyelitis   Poliovirus   Population biology   Population density   Population metrics   Population size   Preventive medicine   Public and occupational health   Research Article   RNA viruses   Specific gravity   Vaccination and immunization   Viral diseases   Viral pathogens   Viruses  

摘要： The polio eradication programme in Nigeria has been successful in reducing incidence to just six confirmed cases in 2014 and zero to date in 2015, but prediction and management of future outbreaks remains a concern. A Poisson mixed effects model was used to describe poliovirus spread between January 2001 and November 2013, incorporating the strength of connectivity between districts (local government areas, LGAs) as estimated by three models of human mobility: simple distance, gravity and radiation models. Potential explanatory variables associated with the case numbers in each LGA were investigated and the model fit was tested by simulation. Spatial connectivity, the number of non-immune children under five years old, and season were associated with the incidence of poliomyelitis in an LGA (all P < 0.001). The best-fitting spatial model was the radiation model, outperforming the simple distance and gravity models (likelihood ratio test P < 0.05), under which the number of people estimated to move from an infected LGA to an uninfected LGA was strongly associated with the incidence of poliomyelitis in that LGA. We inferred transmission networks between LGAs based on this model and found these to be highly local, largely restricted to neighbouring LGAs (e.g. 67.7% of secondary spread from Kano was expected to occur within 10 km). The remaining secondary spread occurred along routes of high population movement. Poliovirus transmission in Nigeria is predominantly localised, occurring between spatially contiguous areas. Outbreak response should be guided by knowledge of high-probability pathways to ensure vulnerable children are protected.

关键词： Poliovirus   Seroprevalence   OPV   Infants   Immunogenicity   India  

摘要： Background: Among the three poliovirus serotypes, the lowest responses after vaccination with trivalent oral polio vaccine (tOPV) are to serotype 3. Although improvements in routine immunisation and supplementary immunisation activities have greatly increased vaccine coverage, there are limited data on antibody prevalence in Indian infants. Methods: Children aged 5-11 months with a history of not having received inactivated polio vaccine were screened for serum antibodies to poliovirus serotype 3 (PV3) by a micro-neutralisation assay according to a modified World Health Organization (WHO) protocol. Limited demographic information was collected to assess risk-factors for a lack of protective antibodies. Student's t-test, logistic regression and multilevel logistic regression (MLR) model were used to estimate model parameters. Results: Of 8454 children screened at a mean age of 8.3 (standard deviation [SD]-1.8) months, 88.1% (95% confidence interval (Cl): 87.4-88.8) had protective antibodies to PV3. The number of tOPV doses received was the main determinant of seroprevalence;the maximum likelihood estimate yields a 37.7% (95% CI: 36.2-38.3) increase in seroprevalence per dose of tOPV. In multivariable logistic regression analysis increasing age, male sex, and urban residence were also independently associated with seropositivity (Odds Ratios (OR);1.17 (95% CI: 1.12-1.23) per month of age, 1.27 (1.11-1.46) and 1.24 (1.05-1.45) respectively). Conclusion: Seroprevalence of antibodies to PV3 is associated with age, gender and place of residence, in addition to the number of tOPV doses received. Ensuring high coverage and monitoring of response are essential as long as oral vaccines are used in polio eradication. (C) 2016 The Authors. Published by Elsevier Ltd.