Materiały źródłowe

• #1 Poliomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558944/

  Poliovirus, enterovirus subtype C, is a small, single positive-stranded ribonucleic acid virus that is acid-resistant, non-enveloped, and encapsulated. This causative agent of acute polio and postpolio syndrome belongs to the family Picornaviridae and reproduces only in humans and some great apes. Poliovirus is extremely contagious, with seroconversion occurring in more than 90% of household contacts. Wild poliovirus (WPV) has 3 distinct serotypes (1, 2, and 3), each with a slightly different capsid protein (WPV1, WPV2, and WPV3). Surviving an infection confers complete and lifelong immunity, but only to the specific infecting serotype. […] Vaccine-associated paralytic polio (VAPP) and circulating vaccine-derived polioviruses (cVDPVs) cause illness that is clinically indistinguishable from poliomyelitis caused by WPV. VAPP results from the proliferation and mutation of polioviruses in OPV recipients or their contacts. Replicating viruses in the intestine revert to neurovirulent variants demonstrating close genetic similarity to the vaccine strain. VAPP is an adverse event triggered by immunization and is reportable under the Vaccine Adverse Event Reporting System.

• #1 Polio Virus- An Overview

  https://microbenotes.com/polio-virus/

  The mouth is the portal of entry for the virus, transmitted by fecal oral route on ingestion of contaminated water. […] Virus initially multiply in the oropharynx and gastrointestinal mucosa. […] The virus is regularly present in the throat and in the stools before the onset of illness. […] Virions are resistant to acidity of stomach and to lytic activities of the protease and other enzymes of the intestinal tract and bile. […] On entering the body, the virus infects and multiplies in the tonsils and Peyers patch of ileum. […] The incubation period is 9-12 days. […] The virus then spreads to regional lymph nodes and enters the blood causing primary viremia. […] Antibodies to the virus appear early in the disease, usually before paralysis occurs. […] The antibodies are produced to prevent infection from spreading.

• #1

  https://www.atsu.edu/faculty/chamberlain/website/tritzid/polio.htm

  The virus is ingested with fecally contaminated food or water. The initial multiplication occurs in the lymphatic tissue of the oropharynx (tonsils) and intestine (appendix). Dissemination to the regional lymphatics is followed by viremia. […] The mechanism by which circulating viruses cross the blood-brain barrier is probably by transcapillary diffusion. […] The non-neural aspects of poliomyelitis, so critical to the pathogenesis of the disease, are reflected not only in the lymph nodes but also in the spleen, liver, kidneys and other viscera.

• #1 Poliovirus – Wikipedia

  https://en.wikipedia.org/wiki/Poliovirus

  The primary determinant of infection for any virus is its ability to enter a cell and produce additional infectious particles. The presence of CD155 is thought to define the animals and tissues that can be infected by poliovirus. CD155 is found (outside of laboratories) only on the cells of humans, higher primates, and Old World monkeys. Poliovirus is, however, strictly a human pathogen, and does not naturally infect any other species (although chimpanzees and Old World monkeys can be experimentally infected). […] Poliovirus is an enterovirus. Infection occurs via the fecaloral route, meaning that one ingests the virus and viral replication occurs in the gastrointestinal tract. Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of viremia (virus in the bloodstream) occurs, and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads and replicates in other sites such as brown fat, reticuloendothelial tissue, and muscle. The sustained viral replication causes secondary viremia and leads to the development of minor symptoms such as fever, headache, and sore throat.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/life-sciences/Polio-Virion-Infection.aspx

  Poliovirus infection occurs by the fecal-oral route, when the host ingests the virus, which replicates in the alimentary tract. The virus is then shed in the feces. Most polio infections are asymptomatic. In about 5 percent of cases, the virus replicates in other tissues. Paralytic poliomyelitis occurs in less than 1 percent of cases. […] Poliovirus infection begins with the virus binds to the receptor CD155 on the host cell surface. CD155 is an immunoglobulin-like receptor also known as poliovirus receptor. Upon binding, an irreversible conformational change occurs to the viral particle. The mechanism by which the virus enters the cell is believed to be receptor-mediated endocytosis, after which the viral RNA is released into the cellular cytoplasm. […] The polyprotein is processed co-translationally by viral proteases into the viral proteins. It then undergoes myristoylation, the addition of a myristoyl group, and the N terminus of the protein chain. Viral 2A protease then cleaves the polyprotein to release a precursor protein myristoyl-P1 from the N terminus. The P1 protein contains all capsid protein sequences.

• #1 Poliomyelitis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/poliomyelitis

  Poliovirus is shed in feces and saliva, and is transmitted via the fecal-oral or respiratory route. It then replicates in oropharyngeal and lower gastrointestinal tract mucosa and enters the cervical and mesenteric lymph nodes. A primary (minor) viremia follows with spread of virus to the reticuloendothelial system. Infection may be contained at this point, or the virus may further multiply and cause several days of secondary viremia, culminating in the development of symptoms and antibodies. […] In paralytic infections, poliovirus enters the central nervous system either via secondary viremia or retrograde migration through peripheral nerves. Significant damage occurs in the spinal cord and brainstem, particularly in the areas controlling motor and autonomic function. Inflammation compounds the damage produced by primary viral invasion. Factors predisposing to serious neurologic damage include increasing age, recent tonsillectomy or intramuscular injection, pregnancy, humoral immunodeficiency, and physical exertion concurrent with onset of the central nervous system phase. […] Most poliovirus infections do not involve the central nervous system or cause paralysis.

• #1 Poliomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558944/

  VDPVs result from the naturally selective proliferation of OPV viruses in populations with low herd immunity (cVDPVs) or prolonged carriage in immunocompromised individuals (iVDVPs). Recombination with other enteroviruses or reversion of OPV strains allows the resulting cVDPVs to regain the neurovirulence and transmissibility of WPV. Genetic divergence of cVDPVs from the attenuated OPV virus indicates prolonged replication and circulation. cVDPVs derived from OPV type 2 (cVDPV2) are the most common, although cVDVP types 1 and 3 also occur. […] Following exposure, poliovirus replicates in oropharynx and gastrointestinal tract tissues. Maternal antibodies or those acquired during a previous infection or oral vaccination often confine the virus to these tissues. In the absence of antibodies, a typically transient and asymptomatic viremia occurs. However, in a small minority of viremic cases, the virus enters the central nervous system (CNS) by crossing the blood-brain barrier or via peripheral nerve retrograde axonal transport. Depending on the virus type and location of invasion, CNS invasion causes non-paralytic aseptic meningitis in up to 5% of symptomatic infections. CNS invasion can also result in infection and destruction of alpha motor neurons in the anterior horns of the spinal cord, the cranial nerve nuclei of the medulla oblongata, and the pons and midbrain. Inflammatory infiltration of these motor neurons causes cell destruction and eventual glial cell scarring.

• #1 Epidemics to eradication: the modern history of poliomyelitis | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-4-70

  As the infection progresses, the virus will spread further to other sites of the reticuloendothelial system. […] Consequently, the great majority of PV infections, nearly 95%, including almost all infections in which a minor viremia develops, are 'innaparent’ or asymptomatic. […] In turn, a minute segment of infected individuals that experience major viremia will progress to develop signs and symptoms indicating PV invasion of the CNS, as characterized by non-paralytic aseptic meningitis or paralytic poliomyelitis. […] The precise mechanism(s) of PV invasion of the CNS is not well understood. […] Three hypotheses for mechanisms utilized by the virus to gain entry into the CNS have been proposed: (1) the virus invades the CNS by retrograde axonal transport; (2) the virus crosses the blood-brain barrier (BBB), presumably independent of the presence of the cellular receptor for PV, CD155; and (3) the virus is imported into the CNS by infected macrophages the Trojan horse mechanism.

• #1 Poliovirus – Wikipedia

  https://en.wikipedia.org/wiki/Poliovirus

  Paralytic poliomyelitis occurs in less than 1% of poliovirus infections. Paralytic disease occurs when the virus enters the central nervous system (CNS) and replicates in motor neurons within the spinal cord, brain stem, or motor cortex, resulting in the selective destruction of motor neurons leading to temporary or permanent paralysis. This is a very rare event in babies, who still have anti-poliovirus antibodies acquired from their mothers. […] The mechanisms by which poliovirus enters the CNS are poorly understood. Three nonmutually exclusive hypotheses have been suggested to explain its entry. All theories require primary viremia. The first hypothesis predicts that virions pass directly from the blood into the central nervous system by crossing the bloodbrain barrier independent of CD155. A second hypothesis suggests that the virions are transported from peripheral tissues that have been bathed in the viremic blood, for example muscle tissue, to the spinal cord through nerve pathways via retrograde axonal transport. A third hypothesis is that the virus is imported into the CNS via infected monocytes or macrophages.

• #1 Molecular aspects of poliovirus pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3859295/

  The development of a mouse model for poliomyelitis makes it considerably simpler to investigate the efficiency of poliovirus dissemination in an entire organism. […] The rates of accumulation of the virus in the brain is more than 100 times higher than that of albumin, which is not thought to permeate the BBB via a specific transport system, and is similar to that of cationized rat serum albumin, which is known to efficiently permeate the BBB. […] Thus, some host cell molecules other than hPVR must be involved in the BBB permeation of poliovirus. […] A pathway of the neural dissemination caused by poliovirus has been reported for humans, monkeys, and transgenic mice. […] These findings afford renewed interest in studying the neural pathway of poliovirus. […] The involvement of hPVR in poliovirus pathogenesis via the neural pathway suggested that poliovirus-related materials in the sciatic nerve are conformationally altered poliovirus (135S and 80S particles) and not 160S virion particles.

• #1 Polio pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polio_pathophysiology

  Although the mechanism of viral spread to the CNS is not fully understood, two main hypotheses have been proposed: Poliovirus diffuses directly through the blood brain barrier from the bloodstream to the CNS, regardless of cellular receptors. Poliovirus is transported from the peripheral muscles to the brain and spinal cord, through retrograde axonal transport. This hypothesis has been experimentally proven in mice, after CD155 transformation. […] The main explanation for increased susceptibility to retrograde axonal transport of poliovirus in areas of injured muscle has been explained. In a neuronal synapse, the rate of endocytosis is related to the level of neuron activity. Correspondingly, for a motor neuron, the level of neuron activity and rate of endocytosis at the neuromuscular junction is related to the extent of muscle contraction. This explains the connection between extreme exercise or muscle injury and development of poliomyelitis in patients with viremia.

• #1 Acute Poliomyelitis: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/306440-overview

  The poliovirus enters the nervous system by either crossing the blood-brain barrier or by axonal transportation from a peripheral nerve. It can cause nervous system infection by involving the precentral gyrus, thalamus, hypothalamus, motor nuclei of the brainstem and surrounding reticular formation, vestibular and cerebellar nuclei, and neurons of the anterior and intermediate columns of the spinal cord. The nerve cells undergo central chromatolysis along with an inflammatory reaction while multiplication of the virus precedes onset of paralysis. As the chromatolysis process goes on further, muscle paralysis or even atrophy appears when fewer than 10% of neurons survive in the corresponding cord segments. Gliosis develops when the inflammatory infiltrate has subsided, but most surviving neurons show full recovery.

• #1 Polio pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polio_pathophysiology

  Once at the cell body of the neuron, the change from axoplasm to cytoplasm is thought to interfere with the stability of the viral coat, leading to the exposure of the viral RNA. Viral replication interferes with neuron stability, killing the motor neuron. Death of a motor neuron paralyzes the respective muscle fiber.

• #1 Polio – Wikipedia

  https://en.wikipedia.org/wiki/Polio

  The destruction of neuronal cells produces lesions within the spinal ganglia; these may also occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar nuclei. Inflammation associated with nerve cell destruction often alters the color and appearance of the gray matter in the spinal column, causing it to appear reddish and swollen. Other destructive changes associated with paralytic disease occur in the forebrain region, specifically the hypothalamus and thalamus.

• #1 Molecular aspects of poliovirus pathogenesis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3859295/

  It is not known, to date, why hPVR-mediated conformational change does not occur for poliovirus-related particles in the sciatic nerve. […] The difference in efficiency in the 2 dissemination routes (BBB permeation and retrograde axonal transport) was not observed between the virulent and attenuated poliovirus strains. […] Thus, strain-specific neurovirulence levels appear to depend primarily on the replication ability of the virus in the CNS. […] These results suggest that the neurovirulence levels of individual poliovirus strains reflect their IRES activities; that is, the capability of translation initiation activity in the CNS. […] The cumulative evidences offered by the data obtained thus far led us to the notion of IRES-dependent virus tropism. […] This phenomenon is specific for neural cells but has not been observed in other cells such as HeLa cells. […] Much research remains to be done to gain insights into the mechanisms of poliovirus neurovirulence.

• #1 Poliovirus – Wikipedia

  https://en.wikipedia.org/wiki/Poliovirus

  Poliomyelitis is a disease of the central nervous system. However, CD155 is believed to be present on the surface of most or all human cells. Therefore, receptor expression does not explain why poliovirus preferentially infects certain tissues. This suggests that tissue tropism is determined after cellular infection. Recent work has suggested that the type I interferon response (specifically that of interferon alpha and beta) is an important factor that defines which types of cells support poliovirus replication.

• #1 Poliovirus, pathogenesis of poliomyelitis, and apoptosis – Research – Institut Pasteur

  https://research.pasteur.fr/en/publication/poliovirus-pathogenesis-of-poliomyelitis-and-apoptosis/

  Poliovirus (PV) is the causal agent of paralytic poliomyelitis, an acute disease of the central nervous system (CNS) resulting in flaccid paralysis. […] In particular, it has been shown that PV-induced apoptosis is an important component of the tissue injury in the CNS of infected mice, which leads to paralysis. […] In this review the molecular biology of PV and the pathogenesis of poliomyelitis are briefly described, and then several models of PV-induced apoptosis are considered; the role of the cellular receptor of PV, CD155, in the modulation of apoptosis is also addressed.

• #1 Immune-System Related Disease: Polio

  https://www.bio.davidson.edu/courses/immunology/students/spring2003/holmberg/polio.htm

  It has also been proposed that when CD155 binds in the viral canyon, it disrupts a hydrocarbon binding pocket, decreasing sphigosine affinity to the pocket. […] Data has indicated that a physical association between CD44 and CD155 exists and that CD44 may able to transduce an apoptotic signal to the host cell on which it is located, contributing to lysis and cell damage. […] The problem with IPV is that the dead virus is incapable of replication or synthesis of viral proteins in the cytoplasm of infected cells. […] This means that no proteins will be present that can be displayed by MHCI and illicit a CD8 T-cell response. […] The problem with OPV is the risk of developing vaccine-associated paralytic poliomyelitis (VAPP). […] Strains of OPV mutate quickly in humans, occurring as a result of selective pressure from neutralizing antibodies and temperature constraints. […] If mutation randomly occurs at very precise sites, the live attenuated virus can revert back to the wild-type virus.

• #1

  https://www.cdc.gov/mmwr/preview/mmwrhtml/00046568.htm

  The overall risk for VAPP is approximately one case in 2.4 million doses distributed. However, among immunocompetent persons, 82% of cases among vaccine recipients and 65% of cases among contacts occur following administration of the first dose. […] Genetic sequencing studies suggest that reversion of Sabin poliovirus strains to potentially more neurovirulent phenotypes occurs commonly after OPV administration. […] Findings from a third more systematic study designed to examine the issue of reversion suggest that, although administration of a dose of IPV before two or more doses of OPV may reduce shedding of type 3 virus (the most common cause of VAPP), the practice will not influence the shedding of types 1 or 2 or the extent of reversion. […] The recommended sequential IPV-OPV vaccination schedule may also reduce the occurrence of such cases. […] Only the exclusive use of IPV or the discontinuation of all poliovirus vaccination efforts after achievement of global poliomyelitis eradication will completely eliminate VAPP.

• #1 Poliomyelitis and post-polio syndrome – UpToDate

  https://www.uptodate.com/contents/polio-and-other-infectious-causes-of-acute-flaccid-paralysis

  Polioviruses are neurotropic enteroviruses that target motor neurons in the spinal cord and brainstem causing poliomyelitis (often referred to as „polio”). As a result of eradication efforts, polio no longer poses the public health threat that it once did; however, limited areas of endemic wild-type poliovirus transmission remain, and rare cases of oral polio vaccine-associated poliomyelitis continue to occur. […] Post-polio syndrome (PPS) is a condition characterized by new or progressive muscle weakness that develops in the decades following a poliomyelitis infection. PPS occurs in up to one-half of patients with prior poliomyelitis infection. […] Virology and forms of illness — Human enteroviruses contain a single positive-strand ribonucleic acid (RNA) genome and are subdivided into four species by genetic homology: human enterovirus types A, B, C, and D. Polioviruses belong to the human enterovirus C species. There are three poliovirus serotypes, each of which can cause motor neuron disease. Most paralytic disease in the prevaccination era was caused by wild-type poliovirus serotype 1 (WPV1).

• #1 Poliomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558944/

  The pathogenic mechanisms resulting in PPS are incompletely understood. The most common theory involves degeneration of the enlarged motor units formed following the initial infection. Longitudinal research results demonstrate a parallel between a decreasing size and number of active motor units and a gradual strength decline in PPS. The precise etiology of this decline is unclear; it likely results from the overuse of remaining motor units, stress-induced aging of motor units, deteriorating neuromuscular junctions, weight gain, deconditioning, and other factors. Although some authors suggest subgroups of patients may have a predominantly neuroinflammatory pathogenesis of their PPS, recent evidence does not support the role of humoral or cellular pro-inflammatory processes. Normal age-related sarcopenia contributes significantly and independently to decreasing muscle mass and strength; however, PPS may accelerate the decline in some patients, with an annual loss of up to 8% of muscle strength.

• #1 What is Post-Polio Syndrome? – Post Polio

  https://post-polio.org/education/what-is-post-polio-syndrome/

  What causes post-polio syndrome? In the early years, there was some speculation that the cause might be a „recurrence” of polio or reactivation of the poliovirus, which is not the case. The generally accepted theory is best demonstrated by the following diagrams. […] […] Degeneration of Nerve cells (Neurons) during Acute Polio […] Destruction of the infected nerve cells results a lack of nerve supply to the muscles. […] If this process occurs on a large enough scale, it can result in loss of muscular function, and can cause weakness or paralysis. […] […] Mechanism of Post-Polio Syndrome […] Wiechers and Hubbell proposed that these new sprouts are not indefinitely stable… […] but rather degenerate over time due to an „overexertion” phenomenon resulting once again in muscle fibers that no longer contract, which a survivor recognizes as new weakness and loss of function.

• #1 Inactivated poliovirus vaccine – GPEI

  https://polioeradication.org/about-polio/the-vaccines/ipv/

  Inactivated polio vaccine (IPV) was developed in 1955 by Dr Jonas Salk. Also called the Salk vaccine IPV consists of inactivated (killed) poliovirus strains of all three poliovirus types. IPV is given by intramuscular or intradermal injection and needs to be administered by a trained health worker. IVP produces antibodies in the blood to all three types of poliovirus. In the event of infection, these antibodies prevent the spread of the virus to the central nervous system and protect against paralysis. […] IPV induces very low levels of immunity in the intestine. As a result, when a person immunized with IPV is infected with wild poliovirus, the virus can still multiply inside the intestines and be shed in the faeces, risking continued circulation. […] IPV is highly effective in preventing paralytic disease caused by all three types of poliovirus.

• #1 Inactivated poliovirus vaccine – GPEI

  https://polioeradication.org/about-polio/the-vaccines/ipv/

  However, as IPV does not stop transmission of the virus, OPV is used wherever a polio outbreak needs to be contained, even in countries which rely exclusively on IPV for their routine immunization programme. Once polio has been eradicated, use of all OPV will need to be stopped to prevent re-establishment of transmission due to VDPVs.

• #1 Polio: The Disease & Vaccines | Children’s Hospital of Philadelphia

  https://www.chop.edu/vaccine-education-center/vaccine-details/polio-vaccine

  Polio is caused by a virus and is highly contagious. It affects people differently some don’t feel sick at all, others complain of anything from a sore throat to fever, stomach pain or vomiting, stiff neck or headache. The virus does its damage by first replicating, or reproducing, itself in the intestines, then traveling through the bloodstream where it can infect the brain and spinal cord. Paralysis caused by polio occurs when the virus replicates in and attacks the nervous system. […] IPV, unlike OPV, cannot reproduce itself (or replicate) and, therefore, cannot possibly revert back to natural polio. To make IPV, poliovirus is purified and killed with a chemical (formaldehyde). IPV elicits antibodies in the bloodstream, not the intestines. It prevents the virus from traveling through the blood to the brain or spinal cord, thereby preventing paralysis. In a sense, because the vaccine induces antibodies in the bloodstream, and not the intestines, IPV induces a „second line” of defense against infection. […] The inactivated polio vaccine, which we use in this country and have only used since the year 2000, is very good at preventing poliovirus from entering the bloodstream and traveling to the brain or spinal cord and causing harm.

• #1 “Breaking the back of polio” < Yale School of Medicine

  https://medicine.yale.edu/news/yale-medicine-magazine/article/breaking-the-back-of-polio/

  The drive to combat polio was led by the National Foundation for Infantile Paralysis, now known as the March of Dimes. […] Three major problems had to be solved. First, researchers would have to determine how many different types of poliovirus there were. Second, they would have to develop a safe and steady supply of each virus type for use in a vaccine. Third, they would have to discover the true pathogenesis of polioits route to the central nervous systemin order to fix the exact time and place for the vaccine to do its work. […] Horstmann had determined the time (early in the infection) and the place (the bloodstream) for the battle against polio to be waged. Her findings meant that an immunizing vaccine, packing low levels of antibody, could destroy the virus before it entered the central nervous system.

• #1 Epidemics to eradication: the modern history of poliomyelitis | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-4-70

  Poliomyelitis has afflicted humankind since antiquity, and for nearly a century now, we have known the causative agent, poliovirus. This pathogen is an enterovirus that in recent history has been the source of a great deal of human suffering. […] In the last 20 years the Global Polio Eradication Initiative has proven successful in greatly diminishing the number of cases worldwide but has encountered obstacles in its path which have made halting the transmission of wild polioviruses a practical impossibility. […] It is imperative that we critically evaluate what is known about the molecular biology of this pathogen and the intricacies of its interaction with its host so that in future attempts we may better equipped to more effectively combat this important human pathogen. […] Since initial descriptions of poliomyelitis were first documented to the present time, innumerable milestones have been reached in understanding the molecular biology of PV and the pathogenesis of poliomyelitis. Such advances have certainly led to the more effective management of poliomyelitis. Nonetheless, many questions remain unanswered. One such question pertains to the determinants of neuropathogenesis, specifically regions of the virus genome important for aspects of virus replication in the cells which it targets.

• #1 An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication | SpringerLink

  https://link.springer.com/protocol/10.1007/978-1-4939-3292-4_1

  Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). […] Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. […] the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. […] However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. […] Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.

• #1 The world needs to prepare now to prevent polio resurgence post eradication – World | ReliefWeb

  https://reliefweb.int/report/world/world-needs-prepare-now-prevent-polio-resurgence-post-eradication

  The authors have since deliberated on a possible mechanism to motivate polio vaccine decision makers as well as suppliers to make these investments to secure vaccine supply for the future. […] The mechanism proposed by the authors is a risk-sharing advance guarantee that will incentivise investment in inactivated polio vaccine (IPV) production and mitigate the risk of mid-term to long-term shortages of IPV stand-alone and IPV-containing hexavalent vaccines. […] The financial guarantee mechanism would provide national and global health policy makers with the confidence to adopt IPV and IPV-containing hexavalent vaccines and prevent recurrence of polio, secure in the knowledge that manufacturers would scale up production for surge in demand in the future.

• #2 Polio – Wikipedia

  https://en.wikipedia.org/wiki/Polio

  Poliomyelitis does not affect any species other than humans. The disease is caused by infection with a member of the genus Enterovirus known as poliovirus (PV). This group of RNA viruses colonize the gastrointestinal tract specifically the oropharynx and the intestine. Its structure is quite simple, composed of a single (+) sense RNA genome enclosed in a protein shell called a capsid. In addition to protecting the virus’ genetic material, the capsid proteins enable poliovirus to infect certain types of cells. Three serotypes of poliovirus have been identified wild poliovirus type 1 (WPV1), type 2 (WPV2), and type 3 (WPV3) each with a slightly different capsid protein. All three are extremely virulent and produce the same disease symptoms. WPV1 is the most commonly encountered form, and the one most closely associated with paralysis. WPV2 was certified as eradicated in 2015 and WPV3 certified as eradicated in 2019.

• #2 Poliomyelitis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/poliomyelitis

  Poliovirus is shed in feces and saliva, and is transmitted via the fecal-oral or respiratory route. It then replicates in oropharyngeal and lower gastrointestinal tract mucosa and enters the cervical and mesenteric lymph nodes. A primary (minor) viremia follows with spread of virus to the reticuloendothelial system. Infection may be contained at this point, or the virus may further multiply and cause several days of secondary viremia, culminating in the development of symptoms and antibodies. […] In paralytic infections, poliovirus enters the central nervous system either via secondary viremia or retrograde migration through peripheral nerves. Significant damage occurs in the spinal cord and brainstem, particularly in the areas controlling motor and autonomic function. Inflammation compounds the damage produced by primary viral invasion. Factors predisposing to serious neurologic damage include increasing age, recent tonsillectomy or intramuscular injection, pregnancy, humoral immunodeficiency, and physical exertion concurrent with onset of the central nervous system phase. […] Most poliovirus infections do not involve the central nervous system or cause paralysis.

• #2 Polio Virus- An Overview

  https://microbenotes.com/polio-virus/

  The mouth is the portal of entry for the virus, transmitted by fecal oral route on ingestion of contaminated water. […] Virus initially multiply in the oropharynx and gastrointestinal mucosa. […] The virus is regularly present in the throat and in the stools before the onset of illness. […] Virions are resistant to acidity of stomach and to lytic activities of the protease and other enzymes of the intestinal tract and bile. […] On entering the body, the virus infects and multiplies in the tonsils and Peyers patch of ileum. […] The incubation period is 9-12 days. […] The virus then spreads to regional lymph nodes and enters the blood causing primary viremia. […] Antibodies to the virus appear early in the disease, usually before paralysis occurs. […] The antibodies are produced to prevent infection from spreading.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/life-sciences/Polio-Virion-Infection.aspx

  Poliovirus infection occurs by the fecal-oral route, when the host ingests the virus, which replicates in the alimentary tract. The virus is then shed in the feces. Most polio infections are asymptomatic. In about 5 percent of cases, the virus replicates in other tissues. Paralytic poliomyelitis occurs in less than 1 percent of cases. […] Poliovirus infection begins with the virus binds to the receptor CD155 on the host cell surface. CD155 is an immunoglobulin-like receptor also known as poliovirus receptor. Upon binding, an irreversible conformational change occurs to the viral particle. The mechanism by which the virus enters the cell is believed to be receptor-mediated endocytosis, after which the viral RNA is released into the cellular cytoplasm. […] The polyprotein is processed co-translationally by viral proteases into the viral proteins. It then undergoes myristoylation, the addition of a myristoyl group, and the N terminus of the protein chain. Viral 2A protease then cleaves the polyprotein to release a precursor protein myristoyl-P1 from the N terminus. The P1 protein contains all capsid protein sequences.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/life-sciences/Poliovirus-Structure.aspx

  Poliovirus infection occurs by the fecal-oral route. The host ingests the virus, which replicates in the alimentary tract. The virus is then shed in the feces. Most polio infections are asymptomatic. In about 5 percent of cases, the virus replicates in other tissues. Paralytic poliomyelitis occurs in less than 1 percent of cases. […] Poliovirus infection begins with the virus binds to the receptor CD155 on the host cell surface. CD155 is an immunoglobulin-like receptor also known as poliovirus receptor (PVR). […] Upon binding, an irreversible conformational change occurs to the viral particle. The altered form of the viral particle is known as the A particle. […] Particle A is believed to be a necessary intermediate to entry of the poliovirus into cells. It is thought that the N terminus of VP1 forms an amphipathic helix that inserts itself into the cell membrane, creating a pore through which the viral RNA passes from the capsid into the cytosol. Another possible mechanism by which the virus enters the cell is believed to be receptor-mediated endocytosis, after which the viral RNA is released into the cellular cytoplasm.

• #2 Poliovirus – Wikipedia

  https://en.wikipedia.org/wiki/Poliovirus

  The primary determinant of infection for any virus is its ability to enter a cell and produce additional infectious particles. The presence of CD155 is thought to define the animals and tissues that can be infected by poliovirus. CD155 is found (outside of laboratories) only on the cells of humans, higher primates, and Old World monkeys. Poliovirus is, however, strictly a human pathogen, and does not naturally infect any other species (although chimpanzees and Old World monkeys can be experimentally infected). […] Poliovirus is an enterovirus. Infection occurs via the fecaloral route, meaning that one ingests the virus and viral replication occurs in the gastrointestinal tract. Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of viremia (virus in the bloodstream) occurs, and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads and replicates in other sites such as brown fat, reticuloendothelial tissue, and muscle. The sustained viral replication causes secondary viremia and leads to the development of minor symptoms such as fever, headache, and sore throat.

• #2

  https://www.bionity.com/en/encyclopedia/Poliovirus.html

  Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae. Poliovirus is composed of a RNA genome and a protein capsid. The genome is single-stranded positive-sense RNA genome that is about 7500 nucleotides long. […] Poliovirus is an enterovirus. Infection occurs via the fecal-oral route; meaning that one ingests the virus and it is within the alimentary tract that virus replication occurs. Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of the virus in the bloodstream occurs (called a viremia) and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads, and replicates in other sites such as brown fat, the reticuloendothelial tissues, and muscle. This sustained replication causes a secondary viremia, and leads to the development of minor symptoms such as fever, headache and sore throat. Paralytic poliomyletis occurs in less than 1% of poliovirus infections. Paralytic disease occurs when the virus enters the central nervous system (CNS) and replicates in motor neurons within the spinal cord, brain stem, or motor cortex, resulting in the selective destruction of motor neurons; leading to either temporary or permanent paralysis and, in rare cases, to respiratory arrest and death.

• #2 Polio pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polio_pathophysiology

  The specific cells of the gastrointestinal tract, where poliovirus replicates, are not known, however, the virus was successfully isolated from lymphatic cells of the GI tract, including: Tonsillar cells, Peyer’s patches of the ileum, Lymph nodes of the mesenterium. The virus enters the bloodstream and migrates to the reticuloendothelial cells across the body. Poliovirus is able to reach the central nervous system in a small fraction of the symptomatic patients. […] The pathological mechanism responsible for the clinical manifestations of CNS poliomyelitis is characterized by selective destruction of motor neurons. Depending of the involved site, motor neuron loss may lead to focal or generalized symptoms. Most commonly observed signs and symptoms include asymmetric limb paralysis in spinal polio and respiratory disturbance with cranial nerve defects in bulbar polio.

• #2 Poliovirus – Wikipedia

  https://en.wikipedia.org/wiki/Poliovirus

  Paralytic poliomyelitis occurs in less than 1% of poliovirus infections. Paralytic disease occurs when the virus enters the central nervous system (CNS) and replicates in motor neurons within the spinal cord, brain stem, or motor cortex, resulting in the selective destruction of motor neurons leading to temporary or permanent paralysis. This is a very rare event in babies, who still have anti-poliovirus antibodies acquired from their mothers. […] The mechanisms by which poliovirus enters the CNS are poorly understood. Three nonmutually exclusive hypotheses have been suggested to explain its entry. All theories require primary viremia. The first hypothesis predicts that virions pass directly from the blood into the central nervous system by crossing the bloodbrain barrier independent of CD155. A second hypothesis suggests that the virions are transported from peripheral tissues that have been bathed in the viremic blood, for example muscle tissue, to the spinal cord through nerve pathways via retrograde axonal transport. A third hypothesis is that the virus is imported into the CNS via infected monocytes or macrophages.

• #2

  https://www.bionity.com/en/encyclopedia/Poliovirus.html

  The mechanisms by which poliovirus enters the CNS are poorly understood. Three theories have been suggested to explain its entry, which are not mutually exclusive, and require that the virus be present in the blood (viremia). One theory is that virus passes directly from the blood into the central nervous system by crossing the blood brain barrier, independent of CD155. A second hypothesis suggests that the virus is transported from the muscle to the spinal cord through nerve pathways by retrograde axonal transport. A third hypothesis is that the virus is imported into the CNS by infected monocytes or macrophages. […] Poliomyelitis is a disease of the central nervous system. However, CD155 is believed to be present on the surface of most, if not all, human cells and does not explain why poliovirus preferentially infects certain tissues, suggesting that tissue tropism is determined after infection. Recent work has suggested that the type I interferon response (specifically that of interferon alpha and beta) is an important factor that defines which types of cells are infected by poliovirus.

• #2 Polio pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polio_pathophysiology

  Although the mechanism of viral spread to the CNS is not fully understood, two main hypotheses have been proposed: Poliovirus diffuses directly through the blood brain barrier from the bloodstream to the CNS, regardless of cellular receptors. Poliovirus is transported from the peripheral muscles to the brain and spinal cord, through retrograde axonal transport. This hypothesis has been experimentally proven in mice, after CD155 transformation. […] The main explanation for increased susceptibility to retrograde axonal transport of poliovirus in areas of injured muscle has been explained. In a neuronal synapse, the rate of endocytosis is related to the level of neuron activity. Correspondingly, for a motor neuron, the level of neuron activity and rate of endocytosis at the neuromuscular junction is related to the extent of muscle contraction. This explains the connection between extreme exercise or muscle injury and development of poliomyelitis in patients with viremia.

• #2 Epidemics to eradication: the modern history of poliomyelitis | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-4-70

  As the infection progresses, the virus will spread further to other sites of the reticuloendothelial system. […] Consequently, the great majority of PV infections, nearly 95%, including almost all infections in which a minor viremia develops, are 'innaparent’ or asymptomatic. […] In turn, a minute segment of infected individuals that experience major viremia will progress to develop signs and symptoms indicating PV invasion of the CNS, as characterized by non-paralytic aseptic meningitis or paralytic poliomyelitis. […] The precise mechanism(s) of PV invasion of the CNS is not well understood. […] Three hypotheses for mechanisms utilized by the virus to gain entry into the CNS have been proposed: (1) the virus invades the CNS by retrograde axonal transport; (2) the virus crosses the blood-brain barrier (BBB), presumably independent of the presence of the cellular receptor for PV, CD155; and (3) the virus is imported into the CNS by infected macrophages the Trojan horse mechanism.

• #2 Polio – Wikipedia

  https://en.wikipedia.org/wiki/Polio

  The destruction of neuronal cells produces lesions within the spinal ganglia; these may also occur in the reticular formation, vestibular nuclei, cerebellar vermis, and deep cerebellar nuclei. Inflammation associated with nerve cell destruction often alters the color and appearance of the gray matter in the spinal column, causing it to appear reddish and swollen. Other destructive changes associated with paralytic disease occur in the forebrain region, specifically the hypothalamus and thalamus.

• #2 Polio pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Polio_pathophysiology

  Once at the cell body of the neuron, the change from axoplasm to cytoplasm is thought to interfere with the stability of the viral coat, leading to the exposure of the viral RNA. Viral replication interferes with neuron stability, killing the motor neuron. Death of a motor neuron paralyzes the respective muscle fiber.

• #2 Poliomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558944/

  The pathogenic mechanisms resulting in PPS are incompletely understood. The most common theory involves degeneration of the enlarged motor units formed following the initial infection. Longitudinal research results demonstrate a parallel between a decreasing size and number of active motor units and a gradual strength decline in PPS. The precise etiology of this decline is unclear; it likely results from the overuse of remaining motor units, stress-induced aging of motor units, deteriorating neuromuscular junctions, weight gain, deconditioning, and other factors. Although some authors suggest subgroups of patients may have a predominantly neuroinflammatory pathogenesis of their PPS, recent evidence does not support the role of humoral or cellular pro-inflammatory processes. Normal age-related sarcopenia contributes significantly and independently to decreasing muscle mass and strength; however, PPS may accelerate the decline in some patients, with an annual loss of up to 8% of muscle strength.

• #2 What is Post-Polio Syndrome? – Post Polio

  https://post-polio.org/education/what-is-post-polio-syndrome/

  What causes post-polio syndrome? In the early years, there was some speculation that the cause might be a „recurrence” of polio or reactivation of the poliovirus, which is not the case. The generally accepted theory is best demonstrated by the following diagrams. […] […] Degeneration of Nerve cells (Neurons) during Acute Polio […] Destruction of the infected nerve cells results a lack of nerve supply to the muscles. […] If this process occurs on a large enough scale, it can result in loss of muscular function, and can cause weakness or paralysis. […] […] Mechanism of Post-Polio Syndrome […] Wiechers and Hubbell proposed that these new sprouts are not indefinitely stable… […] but rather degenerate over time due to an „overexertion” phenomenon resulting once again in muscle fibers that no longer contract, which a survivor recognizes as new weakness and loss of function.

• #2 Drug Summary

  https://www.pdr.net/drug-summary/Ipol-poliovirus-vaccine-inactivated-973

  Mechanism of Action: Poliovirus vaccine, inactivated, IPV stimulates the immune system to produce antibodies against poliovirus wild-types 1, 2, and 3. Following intramuscular or subcutaneous administration, the antigens (inactivated viruses) get presented to the antigen-presenting cells (e.g., B cells, macrophages). The antigen-presenting cells process and present the antigens and allow B-cells to proliferate, differentiate, and produce anti-poliovirus serum antibodies. The serum anti-poliovirus antibodies are capable of opsonization, neutralization, and complement activation. […] In natural infection, the polio viruses invade and replicate in mucosal tissues. The virus may invade the blood stream and produce disease at distant systemic sites. Parenteral immunization with non-replicating agents, such as the IPV may fail to induce specific mucosal responses. Vaccination with either IPV or the live attenuated oral poliovirus vaccine (OPV) usually induces secretory antibody (IgA) production in the pharynx and gut, but mucosal immunity induced by IPV is less than mucosal immunity induced by OPV. The development of serum anti-poliovirus antibodies caused by either OPV or IPV are effective in the prevention of systemic disease despite their different routes of administration. The IPV helps reduce pharyngeal acquisition of poliovirus and to a lesser extent, intestinal acquisition. Herd immunity is possible with IPV, including populations vaccinated only with IPV.

• #2 Poliomyelitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK558944/

  VDPVs result from the naturally selective proliferation of OPV viruses in populations with low herd immunity (cVDPVs) or prolonged carriage in immunocompromised individuals (iVDVPs). Recombination with other enteroviruses or reversion of OPV strains allows the resulting cVDPVs to regain the neurovirulence and transmissibility of WPV. Genetic divergence of cVDPVs from the attenuated OPV virus indicates prolonged replication and circulation. cVDPVs derived from OPV type 2 (cVDPV2) are the most common, although cVDVP types 1 and 3 also occur. […] Following exposure, poliovirus replicates in oropharynx and gastrointestinal tract tissues. Maternal antibodies or those acquired during a previous infection or oral vaccination often confine the virus to these tissues. In the absence of antibodies, a typically transient and asymptomatic viremia occurs. However, in a small minority of viremic cases, the virus enters the central nervous system (CNS) by crossing the blood-brain barrier or via peripheral nerve retrograde axonal transport. Depending on the virus type and location of invasion, CNS invasion causes non-paralytic aseptic meningitis in up to 5% of symptomatic infections. CNS invasion can also result in infection and destruction of alpha motor neurons in the anterior horns of the spinal cord, the cranial nerve nuclei of the medulla oblongata, and the pons and midbrain. Inflammatory infiltration of these motor neurons causes cell destruction and eventual glial cell scarring.

• #2 An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication | SpringerLink

  https://link.springer.com/protocol/10.1007/978-1-4939-3292-4_1

  Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). […] Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. […] the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. […] However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. […] Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.

• #3 Acute Poliomyelitis: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/306920-overview

  Acute poliomyelitis is a disease of the anterior horn motor neurons of the spinal cord and brain stem caused by poliovirus. Flaccid asymmetrical weakness and muscle atrophy are the hallmarks of its clinical manifestations, due to loss of motor neurons and denervation of their associated skeletal muscles. […] Acute poliomyelitis is caused by small ribonucleic acid (RNA) viruses of the enterovirus group of the picornavirus family. The single-stranded RNA core is surrounded by a protein capsid without a lipid envelope, which makes poliovirus resistant to lipid solvents and stable at low pH. Three antigenically distinct strains are known, with type I accounting for 85% of cases of paralytic illnesses. Infection with one type does not protect from the other types; however, immunity to each of the 3 strains is lifelong.

• #3

  https://www.atsu.edu/faculty/chamberlain/website/tritzid/polio.htm

  The virus is ingested with fecally contaminated food or water. The initial multiplication occurs in the lymphatic tissue of the oropharynx (tonsils) and intestine (appendix). Dissemination to the regional lymphatics is followed by viremia. […] The mechanism by which circulating viruses cross the blood-brain barrier is probably by transcapillary diffusion. […] The non-neural aspects of poliomyelitis, so critical to the pathogenesis of the disease, are reflected not only in the lymph nodes but also in the spleen, liver, kidneys and other viscera.

• #3 Immune-System Related Disease: Polio

  https://www.bio.davidson.edu/courses/immunology/students/spring2003/holmberg/polio.htm

  Poliovirus is a human enterovirus, placing it in a family of viruses that reproduce in the gastrointestinal tract at the start of their infection. […] The virus targets cells bearing CD155, the receptor for the poliovirus, a gene only present in humans and old-world primates. […] Poliovirus can infect follicular-associated epithelial cells as well as cells in the Peyers patches and tonsils that lie under the epithelial surface. […] However, damage to epithelial cells is virtually nonexistent, while significant damage is seen in the tonsils and Peyers patches, suggesting that most viral replication takes place here. […] Infection is aided by the fact that these epithelial cells have little IgA or mucus secretions, exempting the virus from one of the first lines of host defense. […] In the Peyers patches and tonsils, the virus replicates and infects cells expressing CD155 such as follicular dendritic cells and B-cells.

• #3 Immune-System Related Disease: Polio

  https://www.bio.davidson.edu/courses/immunology/students/spring2003/holmberg/polio.htm

  However, on rare occasions, the poliovirus can enter the bloodstream. […] From the circulation, the poliovirus will eventually end up in the central nervous system via transport across the blood-brain barrier or via retrograde axonal transport. […] Neuronal cells bear CD155, allowing the poliovirus to infect them and replicate within. […] As neuronal cells are destroyed, paralytic poliomyelitis can result. […] Poliovirus interacts with its receptor on human cells (PVR), also known as CD155, to gain entry into the cell. […] Following ligation, CD155 induces structural changes in the poliovirus, creating an altered virus commonly called the A particle or 135S state. […] After a VP3 plug is removed, RNA can leave the viral capsid and enter the cytoplasm of the host cell. […] Here the virus replicates and causes cell lysis, continuing the spread to other cells.

• #3 Acute Poliomyelitis: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/306440-overview

  Acute poliomyelitis is a disease of the anterior horn motor neurons of the spinal cord and brain stem caused by poliovirus. Flaccid asymmetrical weakness and muscle atrophy are the hallmarks of its clinical manifestations, due to loss of motor neurons and denervation of their associated skeletal muscles. […] Acute poliomyelitis is caused by small ribonucleic acid (RNA) viruses of the enterovirus group of the picornavirus family. The single-stranded RNA core is surrounded by a protein capsid without a lipid envelope, which makes poliovirus resistant to lipid solvents and stable at low pH. Three antigenically distinct strains are known, with type I accounting for 85% of cases of paralytic illnesses. […] The enteroviruses of poliomyelitis infect the human intestinal tract mainly through the fecal-oral route (hand to mouth). The viruses multiply in oropharyngeal and lower gastrointestinal tract mucosa during the first 1-3 weeks of the incubation period. Virus may be secreted in saliva and feces during this period, causing most host-to-host transmission. After the initial alimentary phase, the virus drains into the cervical and mesenteric lymph nodes and then into the blood stream. Only 5% of infected patients have selective nervous system involvement after viremia. It is believed that replication in extraneural sites maintains the viremia and increases the likelihood that the virus will enter the nervous system.

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