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Anti-thymocyte serum delays clearance of poliovirus from the mouse central nervous system.

Antibody is of primary importance for protection from poliovirus-induced paralysis (poliomyelitis) and from other enterovirus infections. However, the components of the immune response involved in the clearance of an established enterovirus infection of the central nervous system (CNS) are not known. To assess the effect of thymus-dependent immune functions on a CNS poliovirus infection, adult BALB/c mice inoculated intracerebrally with the W-2 strain of human poliovirus type 2 (PV2) were treated with anti-thymocyte serum (ATS) and analyzed for clinical disease, virus persistence, antibody res…

The African Polio Laboratory Network: Advancing Regional Poliovirus Detection, Genomic Surveillance, and Eradication.

BACKGROUND: Sustaining progress toward polio eradication requires not only effective vaccination but also a resilient laboratory network capable of timely poliovirus detection, confirmation, and genetic characterization. In the WHO African region, the African polio laboratory network provides essential virological support for eradication efforts; however, persistent circulating Vaccine-derived Polioviruses (cVDPVs) outbreaks and increasing demands of genomic surveillance continue to challenge laboratory capacity. Despite its critical role, evidence describing the operational performance, adapt…

Recurring Outbreaks of Circulating Vaccine-derived Polioviruses: Implications for Global Poliovirus Immunization Strategy.

The incidence of polio has decreased by more than 99.9% and currently, only two countries are endemic for wild poliovirus. However, increasing outbreaks of circulating vaccine-derived poliovirus globally in the last few years, with the latest ones in high-income, exclusive inactivated polio virus vaccine (IPV)-using countries have brought out a new dimension to the end game of polio eradication. The inability of the current IPV to induce efficient mucosal immunity in the intestine is likely to be one of the key reasons behind the silent transmission of the polio virus in these countries. New c…

Conserved Antigenic Structure of Contemporary Wild Poliovirus Type 1 Strains Endemic in Pakistan.

BACKGROUND: Elimination of poliovirus in Pakistan and Afghanistan is challenged by notions against the role of oral poliovirus vaccine (OPV) in eradicating contemporary wild poliovirus (WPV) strains. METHODS: A total of 1055 WPV type 1 (WPV1) strains isolated between 2013 and 2018 were categorized into 68 antigenic groups and tested for neutralization by OPV-derived antibodies. Molecular docking was conducted to determine neutralization efficiency of antibodies against WPV. The clinical significance of WPV1 variants was assessed to ascertain their role in patient outcomes. RESULTS: We found …

Estimating population immunity to poliovirus in Lebanon: Results from a seroprevalence survey, 2016.

INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Prog…

Assessment of poliovirus antibody seroprevalence in polio high risk areas of West Africa.

We conducted a serological survey of anti-polio antibodies in polio high-risk areas of Mali, Guinea and Cote d'Ivoire to assess risk of future poliovirus outbreaks. Random community sampling of children 6-11 and 36-48 months-old was conducted; neutralizing antibodies against poliovirus were detected using microneutralization assay. We analysed 1059/1064 (99.5%) of enrolled children. Seroprevalence to poliovirus type 1 (PV1) across all age groups and locations ranged between 92 and 100%, for PV2 it was 77-100%, and 89-95% for PV3. PV2 seroprevalence in the younger age group in Guinea and Cote d…

Modeling Undetected Live Poliovirus Circulation After Apparent Interruption of Transmission: Pakistan and Afghanistan.

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonst…

Boosting Immune Responses Following Fractional-Dose Inactivated Poliovirus Vaccine: A Randomized, Controlled Trial.

BACKGROUND: Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt. METHODS: We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28; serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion o…

Notes from the Field: Circulating Vaccine-Derived Poliovirus Outbreaks - Five Countries, 2014-2015.

In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin …

Contribution of Environmental Surveillance Toward Interruption of Poliovirus Transmission in Nigeria, 2012-2015.

BACKGROUND: Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. METHODS: The grap method was used to collect 1.75 L of raw flowing sewage every 2-4 weeks. Once collected, sa…

Spatial Dynamics and High Risk Transmission Pathways of Poliovirus in Nigeria 2001-2013.

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 invest…

Poliovirus immunity in newly resettled adult refugees in Idaho, United States of America.

BACKGROUND: In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern. METHODS: A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive. RESULTS: This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 …

Assessing the risks for poliovirus outbreaks in polio-free countries--Africa, 2012-2013.

In 2012, the World Health Assembly of the World Health Organization (WHO) declared the completion of polio eradication a programmatic emergency. Indigenous wild poliovirus (WPV) transmission remains uninterrupted in Nigeria (in the WHO African Region [AFR]) and in Afghanistan and Pakistan (in the WHO Eastern Mediterranean Region [EMR]). In the WHO AFR, multiple WPV outbreaks have occurred since 2003 after importation of indigenous West African WPV into 21 previously polio-free countries in a "WPV importation belt"* that extends across the continent. The Global Polio Eradication Initiative (GPE…

Evaluation of poliovirus antibody titers in orally vaccinated semi-captive chimpanzees in Uganda.

BACKGROUND: To understand immunological responses in chimpanzees vaccinated with live-attenuated vaccine (oral polio vaccine; OPV), serum neutralizing antibodies against poliovirus types 1, 2, and 3 were investigated over time. METHODS: The neutralizing antibody titers against poliovirus types 1, 2, and 3 were determined by microneutralization test using 100 ID(50) of poliovirus types 1, 2, and 3 (Sabin strains). RESULTS: Neutralizing antibodies against poliovirus types 1, 2, and 3 were detected in 85.7%, 71.4%, and 65% of the serum from 42 chimpanzees tested 9 years post-vaccination. The ne…

Поток кальция между эндоплазмическим ретикулумом и митохондрионом способствует апоптозу, вызванному полиомиелитвирусом.

Мы показываем, что полиомиелитвирусная инфекция (PV) вызывает увеличение концентрации цитосолического кальция (Ca(2+)) в нейробластомных клетках IMR5, по крайней мере частично через Ca(2+) высвобождение из эндоплазмического ретикулума люмена через каналы иноситола 1,4,5-трифосфатного рецептора (IP(3)R) и рианодина рецептора (RyR). Это приводит к аккумулированию Ca(2+) в митохондрии через митохондриальный канал Ca(2+) и анионный канал, зависящий от напряжения (VDAC). Это увеличение концентрации митохондриала Ca(2+) в PV-зараженных клетках ведет к митохондриальной дисфункции и апоптозу.

Совпадение в аннотации оригинала
We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca(2+)) concentration in neuroblastoma IMR5 cells, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP(3)R) and ryanodine receptor (RyR) channels. This leads to Ca(2+) accumulation in mitochondria through t…

Poliovirus induces Bax-dependent cell death mediated by c-Jun NH2-terminal kinase.

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member o…

Risks of paralytic disease due to wild or vaccine-derived poliovirus after eradication.

After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, con…

Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection.

Activation of NF-kappaB during viral infection is one of the critical elements in innate immune response. Several virus-specific factors, such as double-stranded RNA, can trigger host defense mechanisms by inducing NF-kappaB-mediated expression of cytokines and interferons. Early stages of poliovirus infection are also associated with degradation of IkappaB alpha and translocation of NF-kappaB into the nucleus. However, at later stages of poliovirus replication the p65-RelA component of the NF-kappaB complex undergoes a specific cleavage that coincides with the onset of intensive poliovirus pr…

Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man.

BACKGROUND: Individuals who chronically excrete neurovirulent poliovirus of vaccine-origin are of considerable concern to the Global Polio Eradication programme. Chronic infection with such polioviruses is a recognised complication of hypogammaglobulinaemia. METHODS: We did a series of in-vitro and in-vivo therapeutic studies, with a view to clearing persistent neurovirulent poliovirus infection in an individual with common variable immunodeficiency, using oral immunoglobulin, breast milk (as a source of secretory IgA), ribavirin, and the anti-picornaviral agent pleconaril. We undertook viral…