Talk:Abnormal Development - Polio Virus

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Cite this page: Hill, M.A. (2021, September 22) Embryology Abnormal Development - Polio Virus. Retrieved from


Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame

PLoS Pathog. 2016 Jul 6;12(7):e1005728. doi: 10.1371/journal.ppat.1005728. eCollection 2016.

Pons-Salort M1, Burns CC2, Lyons H3, Blake IM1, Jafari H4, Oberste MS2, Kew OM2, Grassly NC1.

Abstract Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently "missed" groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004-2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55-0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the threshold permitting VDPV2 circulation. A failure to implement this risk-based approach could mean these SIAs actually increase the risk of VDPV2 emergence and spread.

PMID 27384947

Coordination as a best practice from the polio eradication initiative: Experiences from five member states in the African region of the World Health Organization

Vaccine. 2016 Jul 2. pii: S0264-410X(16)30392-9. doi: 10.1016/j.vaccine.2016.05.066.

Okeibunor J1, Nsubuga P2, Salla M3, Mihigo R3, Mkanda P3.


BACKGROUND: As part of the efforts to eradicate polioviruses in the African Region, structures were put in place to ensure coordinated mobilization and deployment of resources within the framework of the global polio eradication initiative (PEI). The successes of these structures made them not only attractive to other public health interventions, but also caused them to be deployed to the response efforts of other diseases interventions, without any systematic documentation. This article documents the contributions of PEI coordination units to other public health interventions in the African Region of World Health Organization METHODS: We reviewed the contributions of PEI coordination units to other public health interventions in five countries in the African Region. RESULTS: The analysis identified significant involvement of PEI coordination structures in the implementation of routine immunization programs in all the countries analyzed. Similarly, maternal and child health programs were planned, implemented, monitored and evaluation the Inter-Agency Coordination Committees of the PEI programs in the different countries. The hubs system used in PEI in Chad facilitated the efficient coordination of resources for immunization and other public health interventions in Chad. Similarly, in the Democratic Republic of Congo PEI led coordination activities benefited other public health programs like disease control and the national nutrition program, the national malaria control program, and the tuberculosis control program. In Nigeria, the polio Expert Review Committee effectively deployed the Emergency Operation Center for the implementation of prioritized strategies and activities of the National Polio Eradication Emergency Plan, and it was utilized in the response to Ebola Virus Disease outbreak in the country. CONCLUSIONS: The PEI-led coordination systems are thus recognized as having made significant contribution to the coordination and delivery of other public health interventions in the African Region. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved. KEYWORDS: Coordination; PEI; Public health interventions; Resources

PMID 27381643



Pediatrics. 2011 Oct;128(4):805-8. Epub 2011 Sep 26. Committee on Infectious Diseases.


Despite marked progress in global polio eradication, the threat of polio importation into the United States remains; therefore, all children should be protected against the disease. The standard schedule for poliovirus immunization remains 4 doses of inactivated poliovirus vaccine at 2, 4, and 6 through 18 months and 4 through 6 years of age. The minimum interval between doses 1 and 2 and between doses 2 and 3 is 4 weeks, and the minimum interval between doses 3 and 4 is 6 months. The minimum age for dose 1 is 6 weeks. Minimal age and intervals should be used when there is imminent threat of exposure, such as travel to an area in which polio is endemic or epidemic. The final dose in the inactivated poliovirus vaccine series should be administered at 4 through 6 years of age, regardless of the previous number of doses administered before the fourth birthday, and at least 6 months since the last dose was received.

PMID 21949143

A statistical model of the international spread of wild poliovirus in Africa used to predict and prevent outbreaks

PLoS Med. 2011 Oct;8(10):e1001109. Epub 2011 Oct 18.

O'Reilly KM, Chauvin C, Aylward RB, Maher C, Okiror S, Wolff C, Nshmirimana D, Donnelly CA, Grassly NC.Source Medical Research Council Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom.


BACKGROUND: Outbreaks of poliomyelitis in African countries that were previously free of wild-type poliovirus cost the Global PolioEradication Initiative US$850 million during 2003-2009, and have limited the ability of the program to focus on endemic countries. A quantitative understanding of the factors that predict the distribution and timing of outbreaks will enable their prevention and facilitate the completion of global eradication.

METHODS AND FINDINGS: Children with poliomyelitis in Africa from 1 January 2003 to 31 December 2010 were identified through routine surveillance of cases of acute flaccid paralysis, and separate outbreaks associated with importation of wild-type poliovirus were defined using the genetic relatedness of these viruses in the VP1/2A region. Potential explanatory variables were examined for their association with the number, size, and duration of poliomyelitis outbreaks in 6-mo periods using multivariable regression analysis. The predictive ability of 6-mo-ahead forecasts of poliomyelitis outbreaks in each country based on the regression model was assessed. A total of 142 genetically distinct outbreaks of poliomyelitis were recorded in 25 African countries, resulting in 1-228 cases (median of two cases). The estimated number of people arriving from infected countries and <5-y childhood mortality were independently associated with the number of outbreaks. Immunisation coverage based on the reported vaccination history of children with non-polio acute flaccid paralysis was associated with the duration and size of each outbreak, as well as the number of outbreaks. Six-month-ahead forecasts of the number of outbreaks in a country or region changed over time and had a predictive ability of 82%.

CONCLUSIONS: Outbreaks of poliomyelitis resulted primarily from continued transmission in Nigeria and the poor immunisation status of populations in neighbouring countries. From 1 January 2010 to 30 June 2011, reduced transmission in Nigeria and increased incidence in reinfected countries in west and central Africa have changed the geographical risk of polio outbreaks, and will require careful immunisation planning to limit onward spread. Please see later in the article for the Editors' Summary.

PMID 22028632

Intestinal microbiota promote enteric virus replication and systemic pathogenesis

Science. 2011 Oct 14;334(6053):249-52.

Kuss SK, Best GT, Etheredge CA, Pruijssers AJ, Frierson JM, Hooper LV, Dermody TS, Pfeiffer JK.Source Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.


Intestinal bacteria aid host health and limit bacterial pathogen colonization. However, the influence of bacteria on enteric viruses is largely unknown. We depleted the intestinal microbiota of mice with antibiotics before inoculation with poliovirus, an enteric virus. Antibiotic-treated mice were less susceptible to poliovirus disease and supported minimal viral replication in the intestine. Exposure to bacteria or their N-acetylglucosamine-containing surface polysaccharides, including lipopolysaccharide and peptidoglycan, enhanced poliovirus infectivity. We found that poliovirus binds lipopolysaccharide, and exposure of poliovirus to bacteria enhanced host cell association and infection. The pathogenesis of reovirus, an unrelated enteric virus, also was more severe in the presence of intestinal microbes. These results suggest that antibiotic-mediated microbiota depletion diminishes enteric virus infection and that enteric viruses exploit intestinal microbes for replication and transmission. Comment in Science. 2011 Oct 14;334(6053):168.PMID 21998395

The TLR3/TICAM-1 Pathway Is Mandatory for Innate Immune Responses to Poliovirus Infection

J Immunol. 2011 Oct 12.

Oshiumi H, Okamoto M, Fujii K, Kawanishi T, Matsumoto M, Koike S, Seya T.Source Department of Microbiology and Immunology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.


Cytoplasmic and endosomal RNA sensors recognize RNA virus infection and signals to protect host cells by inducing type I IFN. The cytoplasmic RNA sensors, retinoic acid inducible gene I/melanoma differentiation-associated gene 5, actually play pivotal roles in sensingvirus replication. IFN-β promoter stimulator-1 (IPS-1) is their common adaptor for IFN-inducing signaling. Toll/IL-1R homology domain-containing adaptor molecule 1 (TICAM-1), also known as TRIF, is the adaptor for TLR3 that recognizes viral dsRNA in the early endosome in dendritic cells and macrophages. Poliovirus (PV) belongs to the Picornaviridae, and melanoma differentiation-associated gene 5 reportedly detects replication of picornaviruses, leading to the induction of type I IFN. In this study, we present evidence that the TLR3/TICAM-1 pathway governs IFN induction and host protection against PV infection. Using human PVR transgenic (PVRtg) mice, as well as IPS-1(-/-) and TICAM-1(-/-) mice, we found that TICAM-1 is essential for antiviral responses that suppress PV infection. TICAM-1(-/-) mice in the PVRtg background became markedly susceptible to PV, and their survival rates were decreased compared with wild-type or IPS-1(-/-) mice. Similarly, serum and organ IFN levels were markedly reduced in TICAM-1(-/-)/PVRtg mice, particularly in the spleen and spinal cord. The sources of type I IFN were CD8α(+)/CD11c(+) splenic dendritic cells and macrophages, where the TICAM-1 pathway was more crucial for PV-derived IFN induction than was the IPS-1 pathway in ex vivo and in vitro analyses. These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection.

PMID 21998457

MMWR Morb Mortal Wkly Rep. 2011 Aug 12;60(31):1053-7.

Progress toward poliomyelitis eradication --- Nigeria, January 2010-June 2011

Centers for Disease Control and Prevention (CDC).

Abstract The Global Polio Eradication Initiative (GPEI) was launched by the World Health Assembly in 1988. By 2006, transmission of indigenous wildpoliovirus (WPV) was interrupted in all countries except Nigeria, Afghanistan, Pakistan, and India. Among the 36 states and Federal Capital Territory of Nigeria, WPV transmission has persisted in eight northern states considered at high risk; in addition, four other northern states have been considered at high risk for WPV transmission. In these 12 high-risk states, type 2 circulating vaccine-derived poliovirus (cVDPV2) transmission also was observed during 2005-2011. This report updates GPEI progress in Nigeria during January 2010--June 2011 and describes activities required to interrupt transmission. In Nigeria, confirmed WPV cases decreased 95%, from 388 in 2009 to 21 in 2010; cVDPV2 cases decreased 82%, from 154 in 2009 to 27 in 2010. However, as of July 26, 2011, Nigeria had reported 24 WPV cases (including one WPV/cVDPV2 coinfection) and 11 cVDPV2 cases during January-June 2011, compared with six WPV cases and 10 cVDPV2 cases during January-June 2010. Despite substantial progress, immunization activities and surveillance sensitivity will need to be enhanced further to interrupt WPV transmission in Nigeria by the end of 2011.

PMID 21832977

Putting together the pieces of polio: how Dorothy Horstmann helped solve the puzzle

Yale J Biol Med. 2011 Jun;84(2):83-9.

Carleton HA.


Yale School of Medicine, Boyer Center forMolecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.

Abstract Dr. Dorothy Horstmann, epidemiologist, virologist, clinician, and educator, was the first woman appointed as a professor at the Yale School of Medicine. Horstmann made significant contributions to the fields of public health and virology, her most notable being the demonstration thatpoliovirus reached the central nervous system via the bloodstream, upsetting conventional wisdom and paving the way for polio vaccines. In 1961, she was appointed a professor at Yale School of Medicine, and in 1969, she became the first woman at Yale to receive an endowed chair, which was named in honor of her mentor, Dr. John Rodman Paul. In this review, the major scientific contributions of Dr. Dorothy Horstmann will be highlighted from her more than 50-year tenure at Yale School of Medicine. PMID 21698038

Japanese vaccinations and practices, with particular attention to polio and pertussis

Travel Med Infect Dis. 2011 Jul;9(4):169-75. Epub 2010 Jun 3.

Nakano T.

Source Mie National Hospital, 357 Ozato-Kubota, Tsu, Mie 514-0125, Japan.


This article introduces Japanese vaccinations and practices, focusing on polio and pertussis. Japan is one of the few industrialized countries still using live attenuated oral poliovirus vaccine (OPV). Current status of vaccine-associated paralytic poliomyelitis in Japan is discussed. This review is intended to encourage early conversion of OPV to inactivated poliovirus vaccine (IPV) for the routine vaccination as soon as possible. The other topic pertains to the results of a study designed to evaluate the safety and immunogenicity of the Japanese DPT vaccine in adults when administered at the dose of 0.2ml (2/5th of the ordinary dose). In Japan, there is no system for providing advice to adults on vaccination once the childhood schedule is completed. The author, however, wishes to propose here that if the currently approved DPT vaccine can be better utilized as Tdap, we may improve the means for disease prophylaxis.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID 21995861

N Engl J Med. 2011 Oct 6;365(14):1355; author reply 1355.

Vaccine-derived poliomyelitis 12 years after infection

MacLennan CA, Huissoon AP, Kumararatne DS.Comment on

N Engl J Med. 2011 Jun 16;364(24):2316-23.

"DeVries et al. (June 16 issue)1 describe a patient with vaccine-derived poliomyelitis. We were unable to clear chronic, asymptomatic, neurovirulent poliovirus infection in a similarly antibody-deficient patient despite the use of antiviral therapy, breast milk, and oral immune globulin.2 In our patient, the mean IgG trough levels were 1000 mg per deciliter, and paralysis did not develop during an estimated 29 years of poliovirus infection. Neutralizing antibodies against his own poliovirus isolates were detected in his replacement immune globulin by the National Institute for Biological Standards and Control.3 In the patient described by DeVries et al., the IgG trough levels were 438 and 648 mg per deciliter before the onset of paralysis, and the immune globulin–replacement product had recently been changed. Since immunity to enteroviruses is primarily antibody-mediated,4 adequate immune globulin replacement is key for the prevention of paralysis in immunodeficient poliovirus carriers. Where possible, replacement immune globulin should be tested for antiviral activity against poliovirus isolates from such carriers until new antiviral agents that can cure this condition are available."

PMID 21991972

Expert Rev Vaccines. 2011 Oct;10(10):1389-92.Mucosal immunity to poliovirus.Ogra PL, Okayasu H, Czerkinsky C, Sutter RW.Source State University of New York, Women and Children's Hospital, 219 Bryant street, Buffalo, NY 14222, USA. Abstract The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis. PMID 21988303