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Title order Author order Journal order Date order
Category: Polio Immunisation

Title: A cross-sectional survey of healthcare workers on the knowledge and attitudes towards polio vaccination in Pakistan
Author: Khan MU (1), Ahmad A (1), Aqeel T (2), Akbar N (2), Salman S (3), Idress J (4)
Affiliation: (1) Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia; (2) Department of Pharmacy Practice, Faculty of Pharmacy, University of Baluchistan, Quetta, Pakistan; (3) Department of Pharmacy, University of Peshawar, Peshawar, Pakistan; (4) Department of Integrated Sciences, Post Graduate Nursing College, Peshawar, Pakistan.
Journal: Public Library of Science
Citation: PLoS One. 2015 Nov 11;10(11):e0142485. doi: 10.1371/journal.pone.0142485. eCollection 2015.
Publication Year and Month: 2015 11

Abstract: INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan.

METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results.

RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42±2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75±5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio.

Conclusions: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Applying the concept of peptide uniqueness to anti-polio vaccination
Author: Kanduc D (1), Fasano C (1), Capone G (1), Pesce Delfino A (2), Calabrò M (2), Polimeno L (2)
Affiliation: (1) Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy; (2) Department of Emergency and Organ Transplantation (DETO), University of Bari, 70124 Bari, Italy
Journal: Journal of Immunology Research
Citation: J Immunol Res. 2015;2015:541282. Epub 2015 Oct 19
Publication Year and Month: 2015 10

Abstract: BACKGROUND: Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide.

OBJECTIVE: To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate.

METHODS: Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains.

RESULTS: Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host.

Conclusions: Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial
Author: Mychaleckyj JC (1), Haque R (2), Carmolli M (3), Zhang D (4), Colgate ER (3), Nayak U (4), Taniuchi M (5), Dickson D (3), Weldon WC (6), Oberste MS (6), Zaman K (2), Houpt ER (5), Alam M (2), Kirkpatrick BD (7), Petri WA Jr (8)
Affiliation: (1) Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (2) Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh; (3) Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA; (4) Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (5) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; (6) Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; (7) Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA; (8) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908-1340, USA
Journal: Vaccine
Citation: Vaccine. 2015 Nov 28. pii: S0264-410X(15)01695-3. doi: 10.1016/j.vaccine.2015.11.046. [Epub ahead of print]
Publication Year and Month: 2015 11

Abstract: BACKGROUND: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.

METHODS: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.

FINDINGS: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.

Conclusions: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.

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Category: Polio Immunisation

Title: Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel
Author: Moran-Gilad J (1), Mendelson E (2), Burns CC (3), Bassal R (4), Gdalevich M (5), Sofer D (6), Oberste MS (3), Shulman LM (2), Kaliner E (7), Hindiyeh M, Mor O (6), Shahar L (5), Iber J (3), Yishay R (8), Manor J (6), Lev B (9), Gamzu R (10), Grotto I (11)
Affiliation: (1) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; (2) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; (3) Viruses Branch, Centers for Disease Control and Prevention, Atlanta, USA; (4) Israel Center for Disease Control, Ministry of Health, Tel-Hashomer, Israel; (5) Southern District Health Office, Ministry of Health, Beer-Sheva, Israel; (6) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; (7) Public Health Services, Ministry of Health, Jerusalem, Israel; (8) Department of Laboratories, Public Health Services, Ministry of Health, Jerusalem, Israel; (9) Directorate, Ministry of Health, Jerusalem, Israel; (10) School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; Directorate, Ministry of Health, Jerusalem, Israel; (11) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Journal: Journal of Clinical Virology
Citation: J Clin Virol. 2015 May;66:51-5. doi: 10.1016/j.jcv.2015.03.005. Epub 2015 Mar 10
Publication Year and Month: 2015 05

Abstract: BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases.

OBJECTIVES: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV.

STUDY DESIGN: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping.

RESULTS: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity.

Conclusions: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Outcome of Research:

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Comments (if any): Erratum in: J Clin Virol. 2015 Aug;251. Hindiye, Musa [corrected to Hindiyeh, Musa]

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Category: Polio Immunisation

Title: Immunogenicity of two different sequential schedules of inactivated polio vaccine followed by oral polio vaccine versus oral polio vaccine alone in healthy infants in China
Author: Li RC (1), Li CG (2), Wang HB (3), Luo HM (3), Li YP (1), Wang JF (2), Ying ZF (2), Yu WZ (3), Shu JD (4), Wen N (3), Vidor E (5)
Affiliation: (1) Guangxi Center for Disease Prevention and Control, Nanning, China; (2) National Institutes for Food and Drug Control (NIFDC), Beijing, China; (3) Chinese Center for Disease Control and Prevention, Beijing, China; (4) Sanofi Pasteur, Beijing, China; (5) Sanofi Pasteur, Lyon, France
Journal: Journal of the Pediatric Infectious Diseases Society
Citation: J Pediatric Infect Dis Soc. 2015 Apr 16. pii: piv017
Publication Year and Month: 2015 04

Abstract: BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule.

METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored.

RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar.

Conclusions: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539 - https://clinicaltrials.gov/ct2/show/study/NCT01475539).

Outcome of Research: Effective

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Category: Polio Immunisation

Title: New vaccine strategies to finish polio eradication
Author: Grassly NC
Affiliation: Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Hospital, London W2 1PG, UK; Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Journal: The Lancet Infectious Diseases
Citation: Lancet Infect Dis, Volume 15, Issue 8, 864-865
Publication Year and Month: 2015 06

Abstract: The Global Polio Eradication Initiative (GPEI) currently faces two specific challenges. First, all the cases in the past 9 months caused by ongoing wild-virus transmission were in Afghanistan and Pakistan—Africa has had a remarkable 9 months without detection of the disease. Second, circulating vaccine-derived polioviruses are continuing to cause poliomyelitis in a few countries, a rare outcome associated with continued use of the live-attenuated oral poliovirus vaccine (OPV). In The Lancet Infectious Diseases, the results of two clinical trials of OPV that address these challenges are reported by Fatima Mir and colleagues and Concepción Estívariz and colleagues.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals
Author: Thomassen YE (1), van 't Oever AG (1), van Oijen MG (1), Wijffels RH (2), van der Pol LA (1), Bakker WA (1)
Affiliation: (1) Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; (2) Bioprocess Engineering, Wageningen University, Wageningen, The Netherlands
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 12;8(12):e83374. doi: 10.1371/journal.pone.0083374
Publication Year and Month: 2013 12

Abstract: Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

Conclusions:

Outcome of Research: Effective

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Category: Polio Immunisation

Title: Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication
Author: Aghamohammadi A (1), Abolhassani H (1), Kutukculer N (2), Wassilak SG (3), Pallansch MA (4), Kluglein S (5), Quinn J (6), Sutter RW (7), Wang X (8), Sanal O (9), Latysheva T (10), Ikinciogullari A (11), Bernatowska E (12), Tuzankina IA (13), Costa-Carvalho BT (14), Franco JL (15), Somech R (16), Karakoc-Aydiner E (17), Singh S (18), Bezrodnik L (19), Espinosa-Rosales FJ (20), Shcherbina A (21), Lau Y (22,23), Nonoyama S (24), Modell F (6), Modell V (6), The JMF Centers Network Investigators and Study Collaborators, Barbouche M (25), and McKinlay MA (5)
Affiliation: (1) Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran; (2) Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey; (3) Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, United States; (4) Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States; (5) Center for Vaccine Equity, Task Force for Global Health, Atlanta, GA, United States; (6) Jeffrey Modell Foundation, New York, NY, United States; (7) Research and Product Development, World Health Organization, Geneva, Switzerland' (8) Department of Clinical Immunology, Children’s Hospital of Fudan University, Shanghai, China; (9) Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey; (10) Department of Allergology and Immunotherapy, Institute of Immunology, Moscow, Russia; (11) Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; (12) Department of Clinical Immunology, The Children’s Memorial Health Institute, Warsaw, Poland; (13) Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia; (14) Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil; (15) Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellín, Colombia; (16) Pediatric Department A and the Immunology Service, Sheba Medical Center, Tel Hashomer, Jeffrey Modell Foundation Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; (17) Division of Pediatric Allergy and Immunology, Marmara Medical Faculty, Istanbul, Turkey; (18) Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, India; (19) Dr. Ricardo Gutierrez Hospital de Niños, Buenos Aires, Argentina; (20) Clinical Immunology and Allergy Unit, Instituto Nacional de Pediatría, Ciudad de México, Mexico; (21) Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; (22) Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong; (23) Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Hong Kong University-Shenzhen Hospital, Shenzhen, China; (24) Department of Pediatrics, National Defense Medical College, Saitama, Japan; (25) Department of Immunology, Institut Pasteur de Tunis, University Tunis El-Manar, Tunis, Tunisia.
Journal: Frontiers in Immunology
Citation: Front. Immunol. 8:685. doi: 10.3389/fimmu.2017.00685
Publication Year and Month: 2017 06

Abstract: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Conclusions: This study provides an estimate of the global iVDPV prevalence among PID patients without paralytic disease and supports expanded screening for iVDPV excretion in these patients. Although most previous studies focused on the risk of long-term iVDPV infection in antibody deficient patients, the predominance of risk in patients with combined immunodeficiencies included in the current study highlights the importance of considering this group of PID patients in any surveillance program. Reinfection with poliovirus and NPEV excretion in PID patients described elsewhere demonstrates the need for prolonged follow-up (17).

The Global Polio Eradication Initiative plans to cease use of OPV worldwide once WPV has been certified as eradicated, which will end the generation of new iVDPVs. However, there is currently no means for addressing the threat posed by existing immunodeficient persons infected with iVDPVs, either to the infected individual’s risk of paralytic disease, or to the community of a continuing source of poliovirus transmission. Antivirals represent a potential means to manage the treatment of iVDPV excreters and the risk they present to the eradication effort (32, 34). Two safe virus-specific antivirals acting by differing mechanisms are now being developed and may be used as a combination (e.g., pocapavir and V-7404). This strategy may resolve the individual’s infection, stop iVDPV excretion, and serve to eliminate the risk of poliovirus transmission in the community. Currently, pocapavir is being considered for use in poliovirus excreting PID patients on a compassionate use basis.

The potential risk posed by iVDPV excreters to the polio eradication effort indicates the immediate need to develop and implement a global iVDPV surveillance strategy. Utilizing this approach, individuals at risk of prolonged poliovirus excretion can be identified and antiviral treatment can be initiated.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12
Author: Iqbal S (1), Shi J (1), Seib K (2), Lewis P (1), Moro PL (1), Woo EJ (3), Shimabukuro T (1), Orenstein WA (2)
Affiliation: (1) Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; (2) Emory University, School of Medicine, Division of Infectious Diseases, Atlanta, GA, USA; (3) Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA
Journal: The Lancet Infectious Diseases
Citation: DOI: http://dx.doi.org/10.1016/S1473-3099(15)00059-6
Publication Year and Month: 2015 08

Abstract: BACKGROUND: Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS).

METHODS: We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV).

FINDINGS: Of the 41 792 adverse event reports submitted, 39 568 (95%) were for children younger than 7 years. 38 381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34 880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013.

INTERPRETATION: Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Review of the health consequences of SV40 contamination of poliomyelitis vaccines, and in particular a possible association with cancers
Author: Cossart Y, A0
Affiliation: Bosch Professor of Infectious Diseases, University of Sydney, Australia
Journal: Therapeutic Goods Administration Alert/Advisory
Citation:
Publication Year and Month: 2004 12

Abstract: The published papers concerning the human health risk of vaccines contaminated with SV40 virus falls into three groups: those published in the 1960s when the virus was discovered, a second group dating from the period when the two related human viruses BK and JC were described and the third recent period when molecular techniques were applied to the problem.

GROUP 1: SV40 was discovered in 1960 and shown
~ To be a common infection in healthy rhesus monkeys
~ To belong to the polyoma virus family
~ To cause tumours (especially ependymomas, osteosarcomas, mesotheliomas and lymphomas) when injected into baby hamsters
~ To be incompletely killed by the heat and formalin treatment used to inactivate polioviruses during "Salk" vaccine manufacture
~ To be capable of infecting human recipients of contaminated vaccine
~ To be capable of transforming human cells into cancer cells in the laboratory

Immediate steps were taken to free the vaccine seed cultures of SV40 and to ensure that all future batches of vaccine (both the inactivated "Salk" and the then prototype attenuated "Sabin" types) were made in monkey kidney cultures free of SV40. This was accomplished in 1963.

Many millions of children and adults had already been inoculated with polio vaccine before these measures were fully effective. It is not known which of the early batches actually contained infectious doses of SV40, but tests of recipients showed that many produced SV40 antibodies. This could be the result of either SV40 infection or "immunisation" by the killed SV40 in the vaccine.

Concern focussed on the risk to very young children but no increased risk of cancer was found in follow up of over 1000 vaccinees. As the tumour types induced in hamsters are rare these studies were supplemented with much larger studies comparing cancer registry data for children born (and presumably mostly immunised) during the period between introduction of polio vaccine and eradication of SV40 from manufacture (ie 1957-63) and children born within the preceding or subsequent five year periods. These studies were reassuring, although it was recognised that the follow up was not sufficiently long term to detect a risk of the cancers such as mesothelioma which occur in middle age and beyond. There were also some discrepant reports but in retrospect these (including the single Australian study) have significant design limitations.

GROUP 2: The issue was revived in the 1970s when two new human polyomaviruses (BK and JC) were discovered. These cause tumours and degenerative neurological disease in humans. They also share antigens and DNA sequences with SV40 which may cause cross reactions leading to false positive results in diagnostic tests. Surveys showed that serological evidence of infection with the two new agents was common in healthy people and that disease emerged almost exclusively in immune deficient individuals. Attempts to isolate SV40 from human tumours, even by explanting the cells in culture, were generally unsuccessful, but one typical SV40 strain was obtained from a melanoma and two others from diseased brain tissue. Serological surveys showed that earlier findings that up to 5% of the population had low titre SV40 antibody were mostly, if not entirely, due to cross reactions with the much commoner human polyoma viruses.

It was thus concluded that while SV40 involvement in human tumours could not be absolutely denied it must be very rare indeed.

GROUP 3 : The most recent group of publications has reported the use of molecular techniques to detect SV40 DNA in tumours. The results have been conflicting, some studies showing no positives
others a high proportion. Most workers have focussed on detection of the viral oncogene (T antigen) and/or its expression. Persistence of these sequences integrated into the host cell genome would be expected from experimental studies of polyomavirus induced tumours of other species. Unfortunately the SV40 sequences of interest are widely used as tools in molecular laboratories creating a very substantial risk of cross contamination when testing tumour samples. This casts doubt on these studies which has not yet been resolved. Another new avenue of research has revealed that the SV40 oncogene (Tag) acts through complexing with p53 and affects the pRb pathway of cell cycle control. Genetic mutations of these control elements makes the cell exquisitely sensitive to SV40 transformation. These mutations occur naturally in the population, and confer cancer susceptibility on individuals who often develop tumours of similar type to those associated with SV40. This may need to be taken into account in future epidemiological studies.

Conclusions: The literature establishes a plausible mechanism for human carcinogenesis by SV40 virus. Studies of the prevalence of SV40 antibody in the community and the presence of SV40 in human tumours do not absolutely exclude the possibility of rare involvement of the virus in individual cases of cancer, but fail to provide evidence of statistically greater risk for people immunised during the period when SV40 was likely to have been present in polio vaccine. This conclusion has also been reached by several international review panels.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Rotary’s PolioPlus Program: Lessons Learned, Transition Planning, and Legacy
Author: John L. Sever Michael McGovern Robert Scott Carol Pandak Amy Edwards David Goodstone
Affiliation:
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: The Journal of Infectious Diseases, Volume 216, Issue suppl_1 S355–S361, https://doi.org/10.1093/infdis/jiw556
Publication Year and Month: 2017 06

Abstract: Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015–2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time.

Conclusions: Through Rotary’s polio eradication efforts, the organization has learned how to raise funds with coordinated campaigns, and raise awareness with innovative communications methods and celebrity engagement. In addition, Rotary members learned how to work with other organizations to implement large-scale projects that required advocacy, security planning, and coordination in the field. Finally, the launch of PolioPlus as Rotary’s flagship project has a legacy of uniting Rotary members around the world behind a common goal. Ending polio will be a major stepping stone for the United Nations’ sustainable development goals, particularly goal 3, to “ensure healthy lives and promote well-being for all at all ages” [33]. When polio is finally gone, we will have the blueprint for tackling other global issues, even those beyond public health.

Outcome of Research: Not applicable

Availability of Paper: The full text of this paper has been generously made available by the publisher.

Comments (if any):

Link to Paper (if available): Click here to view full text or to download


There are currently 11 papers in this category.

Category: Polio Immunisation

Title: Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication
Author: Aghamohammadi A (1), Abolhassani H (1), Kutukculer N (2), Wassilak SG (3), Pallansch MA (4), Kluglein S (5), Quinn J (6), Sutter RW (7), Wang X (8), Sanal O (9), Latysheva T (10), Ikinciogullari A (11), Bernatowska E (12), Tuzankina IA (13), Costa-Carvalho BT (14), Franco JL (15), Somech R (16), Karakoc-Aydiner E (17), Singh S (18), Bezrodnik L (19), Espinosa-Rosales FJ (20), Shcherbina A (21), Lau Y (22,23), Nonoyama S (24), Modell F (6), Modell V (6), The JMF Centers Network Investigators and Study Collaborators, Barbouche M (25), and McKinlay MA (5)
Affiliation: (1) Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran; (2) Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey; (3) Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, United States; (4) Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States; (5) Center for Vaccine Equity, Task Force for Global Health, Atlanta, GA, United States; (6) Jeffrey Modell Foundation, New York, NY, United States; (7) Research and Product Development, World Health Organization, Geneva, Switzerland' (8) Department of Clinical Immunology, Children’s Hospital of Fudan University, Shanghai, China; (9) Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey; (10) Department of Allergology and Immunotherapy, Institute of Immunology, Moscow, Russia; (11) Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; (12) Department of Clinical Immunology, The Children’s Memorial Health Institute, Warsaw, Poland; (13) Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia; (14) Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil; (15) Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellín, Colombia; (16) Pediatric Department A and the Immunology Service, Sheba Medical Center, Tel Hashomer, Jeffrey Modell Foundation Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; (17) Division of Pediatric Allergy and Immunology, Marmara Medical Faculty, Istanbul, Turkey; (18) Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, India; (19) Dr. Ricardo Gutierrez Hospital de Niños, Buenos Aires, Argentina; (20) Clinical Immunology and Allergy Unit, Instituto Nacional de Pediatría, Ciudad de México, Mexico; (21) Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; (22) Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong; (23) Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Hong Kong University-Shenzhen Hospital, Shenzhen, China; (24) Department of Pediatrics, National Defense Medical College, Saitama, Japan; (25) Department of Immunology, Institut Pasteur de Tunis, University Tunis El-Manar, Tunis, Tunisia.
Journal: Frontiers in Immunology
Citation: Front. Immunol. 8:685. doi: 10.3389/fimmu.2017.00685
Publication Year and Month: 2017 06

Abstract: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Conclusions: This study provides an estimate of the global iVDPV prevalence among PID patients without paralytic disease and supports expanded screening for iVDPV excretion in these patients. Although most previous studies focused on the risk of long-term iVDPV infection in antibody deficient patients, the predominance of risk in patients with combined immunodeficiencies included in the current study highlights the importance of considering this group of PID patients in any surveillance program. Reinfection with poliovirus and NPEV excretion in PID patients described elsewhere demonstrates the need for prolonged follow-up (17).

The Global Polio Eradication Initiative plans to cease use of OPV worldwide once WPV has been certified as eradicated, which will end the generation of new iVDPVs. However, there is currently no means for addressing the threat posed by existing immunodeficient persons infected with iVDPVs, either to the infected individual’s risk of paralytic disease, or to the community of a continuing source of poliovirus transmission. Antivirals represent a potential means to manage the treatment of iVDPV excreters and the risk they present to the eradication effort (32, 34). Two safe virus-specific antivirals acting by differing mechanisms are now being developed and may be used as a combination (e.g., pocapavir and V-7404). This strategy may resolve the individual’s infection, stop iVDPV excretion, and serve to eliminate the risk of poliovirus transmission in the community. Currently, pocapavir is being considered for use in poliovirus excreting PID patients on a compassionate use basis.

The potential risk posed by iVDPV excreters to the polio eradication effort indicates the immediate need to develop and implement a global iVDPV surveillance strategy. Utilizing this approach, individuals at risk of prolonged poliovirus excretion can be identified and antiviral treatment can be initiated.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Review of the health consequences of SV40 contamination of poliomyelitis vaccines, and in particular a possible association with cancers
Author: Cossart Y, A0
Affiliation: Bosch Professor of Infectious Diseases, University of Sydney, Australia
Journal: Therapeutic Goods Administration Alert/Advisory
Citation:
Publication Year and Month: 2004 12

Abstract: The published papers concerning the human health risk of vaccines contaminated with SV40 virus falls into three groups: those published in the 1960s when the virus was discovered, a second group dating from the period when the two related human viruses BK and JC were described and the third recent period when molecular techniques were applied to the problem.

GROUP 1: SV40 was discovered in 1960 and shown
~ To be a common infection in healthy rhesus monkeys
~ To belong to the polyoma virus family
~ To cause tumours (especially ependymomas, osteosarcomas, mesotheliomas and lymphomas) when injected into baby hamsters
~ To be incompletely killed by the heat and formalin treatment used to inactivate polioviruses during "Salk" vaccine manufacture
~ To be capable of infecting human recipients of contaminated vaccine
~ To be capable of transforming human cells into cancer cells in the laboratory

Immediate steps were taken to free the vaccine seed cultures of SV40 and to ensure that all future batches of vaccine (both the inactivated "Salk" and the then prototype attenuated "Sabin" types) were made in monkey kidney cultures free of SV40. This was accomplished in 1963.

Many millions of children and adults had already been inoculated with polio vaccine before these measures were fully effective. It is not known which of the early batches actually contained infectious doses of SV40, but tests of recipients showed that many produced SV40 antibodies. This could be the result of either SV40 infection or "immunisation" by the killed SV40 in the vaccine.

Concern focussed on the risk to very young children but no increased risk of cancer was found in follow up of over 1000 vaccinees. As the tumour types induced in hamsters are rare these studies were supplemented with much larger studies comparing cancer registry data for children born (and presumably mostly immunised) during the period between introduction of polio vaccine and eradication of SV40 from manufacture (ie 1957-63) and children born within the preceding or subsequent five year periods. These studies were reassuring, although it was recognised that the follow up was not sufficiently long term to detect a risk of the cancers such as mesothelioma which occur in middle age and beyond. There were also some discrepant reports but in retrospect these (including the single Australian study) have significant design limitations.

GROUP 2: The issue was revived in the 1970s when two new human polyomaviruses (BK and JC) were discovered. These cause tumours and degenerative neurological disease in humans. They also share antigens and DNA sequences with SV40 which may cause cross reactions leading to false positive results in diagnostic tests. Surveys showed that serological evidence of infection with the two new agents was common in healthy people and that disease emerged almost exclusively in immune deficient individuals. Attempts to isolate SV40 from human tumours, even by explanting the cells in culture, were generally unsuccessful, but one typical SV40 strain was obtained from a melanoma and two others from diseased brain tissue. Serological surveys showed that earlier findings that up to 5% of the population had low titre SV40 antibody were mostly, if not entirely, due to cross reactions with the much commoner human polyoma viruses.

It was thus concluded that while SV40 involvement in human tumours could not be absolutely denied it must be very rare indeed.

GROUP 3 : The most recent group of publications has reported the use of molecular techniques to detect SV40 DNA in tumours. The results have been conflicting, some studies showing no positives
others a high proportion. Most workers have focussed on detection of the viral oncogene (T antigen) and/or its expression. Persistence of these sequences integrated into the host cell genome would be expected from experimental studies of polyomavirus induced tumours of other species. Unfortunately the SV40 sequences of interest are widely used as tools in molecular laboratories creating a very substantial risk of cross contamination when testing tumour samples. This casts doubt on these studies which has not yet been resolved. Another new avenue of research has revealed that the SV40 oncogene (Tag) acts through complexing with p53 and affects the pRb pathway of cell cycle control. Genetic mutations of these control elements makes the cell exquisitely sensitive to SV40 transformation. These mutations occur naturally in the population, and confer cancer susceptibility on individuals who often develop tumours of similar type to those associated with SV40. This may need to be taken into account in future epidemiological studies.

Conclusions: The literature establishes a plausible mechanism for human carcinogenesis by SV40 virus. Studies of the prevalence of SV40 antibody in the community and the presence of SV40 in human tumours do not absolutely exclude the possibility of rare involvement of the virus in individual cases of cancer, but fail to provide evidence of statistically greater risk for people immunised during the period when SV40 was likely to have been present in polio vaccine. This conclusion has also been reached by several international review panels.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: New vaccine strategies to finish polio eradication
Author: Grassly NC
Affiliation: Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Hospital, London W2 1PG, UK; Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Journal: The Lancet Infectious Diseases
Citation: Lancet Infect Dis, Volume 15, Issue 8, 864-865
Publication Year and Month: 2015 06

Abstract: The Global Polio Eradication Initiative (GPEI) currently faces two specific challenges. First, all the cases in the past 9 months caused by ongoing wild-virus transmission were in Afghanistan and Pakistan—Africa has had a remarkable 9 months without detection of the disease. Second, circulating vaccine-derived polioviruses are continuing to cause poliomyelitis in a few countries, a rare outcome associated with continued use of the live-attenuated oral poliovirus vaccine (OPV). In The Lancet Infectious Diseases, the results of two clinical trials of OPV that address these challenges are reported by Fatima Mir and colleagues and Concepción Estívariz and colleagues.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12
Author: Iqbal S (1), Shi J (1), Seib K (2), Lewis P (1), Moro PL (1), Woo EJ (3), Shimabukuro T (1), Orenstein WA (2)
Affiliation: (1) Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; (2) Emory University, School of Medicine, Division of Infectious Diseases, Atlanta, GA, USA; (3) Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA
Journal: The Lancet Infectious Diseases
Citation: DOI: http://dx.doi.org/10.1016/S1473-3099(15)00059-6
Publication Year and Month: 2015 08

Abstract: BACKGROUND: Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS).

METHODS: We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV).

FINDINGS: Of the 41 792 adverse event reports submitted, 39 568 (95%) were for children younger than 7 years. 38 381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34 880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013.

INTERPRETATION: Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Rotary’s PolioPlus Program: Lessons Learned, Transition Planning, and Legacy
Author: John L. Sever Michael McGovern Robert Scott Carol Pandak Amy Edwards David Goodstone
Affiliation:
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: The Journal of Infectious Diseases, Volume 216, Issue suppl_1 S355–S361, https://doi.org/10.1093/infdis/jiw556
Publication Year and Month: 2017 06

Abstract: Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015–2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time.

Conclusions: Through Rotary’s polio eradication efforts, the organization has learned how to raise funds with coordinated campaigns, and raise awareness with innovative communications methods and celebrity engagement. In addition, Rotary members learned how to work with other organizations to implement large-scale projects that required advocacy, security planning, and coordination in the field. Finally, the launch of PolioPlus as Rotary’s flagship project has a legacy of uniting Rotary members around the world behind a common goal. Ending polio will be a major stepping stone for the United Nations’ sustainable development goals, particularly goal 3, to “ensure healthy lives and promote well-being for all at all ages” [33]. When polio is finally gone, we will have the blueprint for tackling other global issues, even those beyond public health.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Applying the concept of peptide uniqueness to anti-polio vaccination
Author: Kanduc D (1), Fasano C (1), Capone G (1), Pesce Delfino A (2), Calabrò M (2), Polimeno L (2)
Affiliation: (1) Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy; (2) Department of Emergency and Organ Transplantation (DETO), University of Bari, 70124 Bari, Italy
Journal: Journal of Immunology Research
Citation: J Immunol Res. 2015;2015:541282. Epub 2015 Oct 19
Publication Year and Month: 2015 10

Abstract: BACKGROUND: Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide.

OBJECTIVE: To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate.

METHODS: Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains.

RESULTS: Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host.

Conclusions: Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: A cross-sectional survey of healthcare workers on the knowledge and attitudes towards polio vaccination in Pakistan
Author: Khan MU (1), Ahmad A (1), Aqeel T (2), Akbar N (2), Salman S (3), Idress J (4)
Affiliation: (1) Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia; (2) Department of Pharmacy Practice, Faculty of Pharmacy, University of Baluchistan, Quetta, Pakistan; (3) Department of Pharmacy, University of Peshawar, Peshawar, Pakistan; (4) Department of Integrated Sciences, Post Graduate Nursing College, Peshawar, Pakistan.
Journal: Public Library of Science
Citation: PLoS One. 2015 Nov 11;10(11):e0142485. doi: 10.1371/journal.pone.0142485. eCollection 2015.
Publication Year and Month: 2015 11

Abstract: INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan.

METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results.

RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42±2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75±5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio.

Conclusions: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Immunogenicity of two different sequential schedules of inactivated polio vaccine followed by oral polio vaccine versus oral polio vaccine alone in healthy infants in China
Author: Li RC (1), Li CG (2), Wang HB (3), Luo HM (3), Li YP (1), Wang JF (2), Ying ZF (2), Yu WZ (3), Shu JD (4), Wen N (3), Vidor E (5)
Affiliation: (1) Guangxi Center for Disease Prevention and Control, Nanning, China; (2) National Institutes for Food and Drug Control (NIFDC), Beijing, China; (3) Chinese Center for Disease Control and Prevention, Beijing, China; (4) Sanofi Pasteur, Beijing, China; (5) Sanofi Pasteur, Lyon, France
Journal: Journal of the Pediatric Infectious Diseases Society
Citation: J Pediatric Infect Dis Soc. 2015 Apr 16. pii: piv017
Publication Year and Month: 2015 04

Abstract: BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule.

METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored.

RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar.

Conclusions: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539 - https://clinicaltrials.gov/ct2/show/study/NCT01475539).

Outcome of Research: Effective

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Category: Polio Immunisation

Title: Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel
Author: Moran-Gilad J (1), Mendelson E (2), Burns CC (3), Bassal R (4), Gdalevich M (5), Sofer D (6), Oberste MS (3), Shulman LM (2), Kaliner E (7), Hindiyeh M, Mor O (6), Shahar L (5), Iber J (3), Yishay R (8), Manor J (6), Lev B (9), Gamzu R (10), Grotto I (11)
Affiliation: (1) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; (2) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; (3) Viruses Branch, Centers for Disease Control and Prevention, Atlanta, USA; (4) Israel Center for Disease Control, Ministry of Health, Tel-Hashomer, Israel; (5) Southern District Health Office, Ministry of Health, Beer-Sheva, Israel; (6) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; (7) Public Health Services, Ministry of Health, Jerusalem, Israel; (8) Department of Laboratories, Public Health Services, Ministry of Health, Jerusalem, Israel; (9) Directorate, Ministry of Health, Jerusalem, Israel; (10) School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; Directorate, Ministry of Health, Jerusalem, Israel; (11) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Journal: Journal of Clinical Virology
Citation: J Clin Virol. 2015 May;66:51-5. doi: 10.1016/j.jcv.2015.03.005. Epub 2015 Mar 10
Publication Year and Month: 2015 05

Abstract: BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases.

OBJECTIVES: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV.

STUDY DESIGN: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping.

RESULTS: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity.

Conclusions: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Outcome of Research:

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Comments (if any): Erratum in: J Clin Virol. 2015 Aug;251. Hindiye, Musa [corrected to Hindiyeh, Musa]

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Category: Polio Immunisation

Title: Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial
Author: Mychaleckyj JC (1), Haque R (2), Carmolli M (3), Zhang D (4), Colgate ER (3), Nayak U (4), Taniuchi M (5), Dickson D (3), Weldon WC (6), Oberste MS (6), Zaman K (2), Houpt ER (5), Alam M (2), Kirkpatrick BD (7), Petri WA Jr (8)
Affiliation: (1) Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (2) Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh; (3) Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA; (4) Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (5) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; (6) Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; (7) Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA; (8) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908-1340, USA
Journal: Vaccine
Citation: Vaccine. 2015 Nov 28. pii: S0264-410X(15)01695-3. doi: 10.1016/j.vaccine.2015.11.046. [Epub ahead of print]
Publication Year and Month: 2015 11

Abstract: BACKGROUND: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.

METHODS: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.

FINDINGS: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.

Conclusions: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.

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Category: Polio Immunisation

Title: Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals
Author: Thomassen YE (1), van 't Oever AG (1), van Oijen MG (1), Wijffels RH (2), van der Pol LA (1), Bakker WA (1)
Affiliation: (1) Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; (2) Bioprocess Engineering, Wageningen University, Wageningen, The Netherlands
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 12;8(12):e83374. doi: 10.1371/journal.pone.0083374
Publication Year and Month: 2013 12

Abstract: Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

Conclusions:

Outcome of Research: Effective

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There are currently 11 papers in this category.

Category: Polio Immunisation

Title: Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication
Author: Aghamohammadi A (1), Abolhassani H (1), Kutukculer N (2), Wassilak SG (3), Pallansch MA (4), Kluglein S (5), Quinn J (6), Sutter RW (7), Wang X (8), Sanal O (9), Latysheva T (10), Ikinciogullari A (11), Bernatowska E (12), Tuzankina IA (13), Costa-Carvalho BT (14), Franco JL (15), Somech R (16), Karakoc-Aydiner E (17), Singh S (18), Bezrodnik L (19), Espinosa-Rosales FJ (20), Shcherbina A (21), Lau Y (22,23), Nonoyama S (24), Modell F (6), Modell V (6), The JMF Centers Network Investigators and Study Collaborators, Barbouche M (25), and McKinlay MA (5)
Affiliation: (1) Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran; (2) Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey; (3) Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, United States; (4) Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States; (5) Center for Vaccine Equity, Task Force for Global Health, Atlanta, GA, United States; (6) Jeffrey Modell Foundation, New York, NY, United States; (7) Research and Product Development, World Health Organization, Geneva, Switzerland' (8) Department of Clinical Immunology, Children’s Hospital of Fudan University, Shanghai, China; (9) Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey; (10) Department of Allergology and Immunotherapy, Institute of Immunology, Moscow, Russia; (11) Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; (12) Department of Clinical Immunology, The Children’s Memorial Health Institute, Warsaw, Poland; (13) Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia; (14) Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil; (15) Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellín, Colombia; (16) Pediatric Department A and the Immunology Service, Sheba Medical Center, Tel Hashomer, Jeffrey Modell Foundation Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; (17) Division of Pediatric Allergy and Immunology, Marmara Medical Faculty, Istanbul, Turkey; (18) Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, India; (19) Dr. Ricardo Gutierrez Hospital de Niños, Buenos Aires, Argentina; (20) Clinical Immunology and Allergy Unit, Instituto Nacional de Pediatría, Ciudad de México, Mexico; (21) Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; (22) Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong; (23) Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Hong Kong University-Shenzhen Hospital, Shenzhen, China; (24) Department of Pediatrics, National Defense Medical College, Saitama, Japan; (25) Department of Immunology, Institut Pasteur de Tunis, University Tunis El-Manar, Tunis, Tunisia.
Journal: Frontiers in Immunology
Citation: Front. Immunol. 8:685. doi: 10.3389/fimmu.2017.00685
Publication Year and Month: 2017 06

Abstract: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Conclusions: This study provides an estimate of the global iVDPV prevalence among PID patients without paralytic disease and supports expanded screening for iVDPV excretion in these patients. Although most previous studies focused on the risk of long-term iVDPV infection in antibody deficient patients, the predominance of risk in patients with combined immunodeficiencies included in the current study highlights the importance of considering this group of PID patients in any surveillance program. Reinfection with poliovirus and NPEV excretion in PID patients described elsewhere demonstrates the need for prolonged follow-up (17).

The Global Polio Eradication Initiative plans to cease use of OPV worldwide once WPV has been certified as eradicated, which will end the generation of new iVDPVs. However, there is currently no means for addressing the threat posed by existing immunodeficient persons infected with iVDPVs, either to the infected individual’s risk of paralytic disease, or to the community of a continuing source of poliovirus transmission. Antivirals represent a potential means to manage the treatment of iVDPV excreters and the risk they present to the eradication effort (32, 34). Two safe virus-specific antivirals acting by differing mechanisms are now being developed and may be used as a combination (e.g., pocapavir and V-7404). This strategy may resolve the individual’s infection, stop iVDPV excretion, and serve to eliminate the risk of poliovirus transmission in the community. Currently, pocapavir is being considered for use in poliovirus excreting PID patients on a compassionate use basis.

The potential risk posed by iVDPV excreters to the polio eradication effort indicates the immediate need to develop and implement a global iVDPV surveillance strategy. Utilizing this approach, individuals at risk of prolonged poliovirus excretion can be identified and antiviral treatment can be initiated.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel
Author: Moran-Gilad J (1), Mendelson E (2), Burns CC (3), Bassal R (4), Gdalevich M (5), Sofer D (6), Oberste MS (3), Shulman LM (2), Kaliner E (7), Hindiyeh M, Mor O (6), Shahar L (5), Iber J (3), Yishay R (8), Manor J (6), Lev B (9), Gamzu R (10), Grotto I (11)
Affiliation: (1) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; (2) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; (3) Viruses Branch, Centers for Disease Control and Prevention, Atlanta, USA; (4) Israel Center for Disease Control, Ministry of Health, Tel-Hashomer, Israel; (5) Southern District Health Office, Ministry of Health, Beer-Sheva, Israel; (6) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; (7) Public Health Services, Ministry of Health, Jerusalem, Israel; (8) Department of Laboratories, Public Health Services, Ministry of Health, Jerusalem, Israel; (9) Directorate, Ministry of Health, Jerusalem, Israel; (10) School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; Directorate, Ministry of Health, Jerusalem, Israel; (11) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Journal: Journal of Clinical Virology
Citation: J Clin Virol. 2015 May;66:51-5. doi: 10.1016/j.jcv.2015.03.005. Epub 2015 Mar 10
Publication Year and Month: 2015 05

Abstract: BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases.

OBJECTIVES: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV.

STUDY DESIGN: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping.

RESULTS: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity.

Conclusions: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Outcome of Research:

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Comments (if any): Erratum in: J Clin Virol. 2015 Aug;251. Hindiye, Musa [corrected to Hindiyeh, Musa]

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Category: Polio Immunisation

Title: Applying the concept of peptide uniqueness to anti-polio vaccination
Author: Kanduc D (1), Fasano C (1), Capone G (1), Pesce Delfino A (2), Calabrò M (2), Polimeno L (2)
Affiliation: (1) Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy; (2) Department of Emergency and Organ Transplantation (DETO), University of Bari, 70124 Bari, Italy
Journal: Journal of Immunology Research
Citation: J Immunol Res. 2015;2015:541282. Epub 2015 Oct 19
Publication Year and Month: 2015 10

Abstract: BACKGROUND: Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide.

OBJECTIVE: To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate.

METHODS: Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains.

RESULTS: Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host.

Conclusions: Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Immunogenicity of two different sequential schedules of inactivated polio vaccine followed by oral polio vaccine versus oral polio vaccine alone in healthy infants in China
Author: Li RC (1), Li CG (2), Wang HB (3), Luo HM (3), Li YP (1), Wang JF (2), Ying ZF (2), Yu WZ (3), Shu JD (4), Wen N (3), Vidor E (5)
Affiliation: (1) Guangxi Center for Disease Prevention and Control, Nanning, China; (2) National Institutes for Food and Drug Control (NIFDC), Beijing, China; (3) Chinese Center for Disease Control and Prevention, Beijing, China; (4) Sanofi Pasteur, Beijing, China; (5) Sanofi Pasteur, Lyon, France
Journal: Journal of the Pediatric Infectious Diseases Society
Citation: J Pediatric Infect Dis Soc. 2015 Apr 16. pii: piv017
Publication Year and Month: 2015 04

Abstract: BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule.

METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored.

RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar.

Conclusions: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539 - https://clinicaltrials.gov/ct2/show/study/NCT01475539).

Outcome of Research: Effective

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Category: Polio Immunisation

Title: Rotary’s PolioPlus Program: Lessons Learned, Transition Planning, and Legacy
Author: John L. Sever Michael McGovern Robert Scott Carol Pandak Amy Edwards David Goodstone
Affiliation:
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: The Journal of Infectious Diseases, Volume 216, Issue suppl_1 S355–S361, https://doi.org/10.1093/infdis/jiw556
Publication Year and Month: 2017 06

Abstract: Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015–2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time.

Conclusions: Through Rotary’s polio eradication efforts, the organization has learned how to raise funds with coordinated campaigns, and raise awareness with innovative communications methods and celebrity engagement. In addition, Rotary members learned how to work with other organizations to implement large-scale projects that required advocacy, security planning, and coordination in the field. Finally, the launch of PolioPlus as Rotary’s flagship project has a legacy of uniting Rotary members around the world behind a common goal. Ending polio will be a major stepping stone for the United Nations’ sustainable development goals, particularly goal 3, to “ensure healthy lives and promote well-being for all at all ages” [33]. When polio is finally gone, we will have the blueprint for tackling other global issues, even those beyond public health.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals
Author: Thomassen YE (1), van 't Oever AG (1), van Oijen MG (1), Wijffels RH (2), van der Pol LA (1), Bakker WA (1)
Affiliation: (1) Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; (2) Bioprocess Engineering, Wageningen University, Wageningen, The Netherlands
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 12;8(12):e83374. doi: 10.1371/journal.pone.0083374
Publication Year and Month: 2013 12

Abstract: Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

Conclusions:

Outcome of Research: Effective

Availability of Paper: The full text of this paper has been generously made available by the publisher.

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Category: Polio Immunisation

Title: A cross-sectional survey of healthcare workers on the knowledge and attitudes towards polio vaccination in Pakistan
Author: Khan MU (1), Ahmad A (1), Aqeel T (2), Akbar N (2), Salman S (3), Idress J (4)
Affiliation: (1) Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia; (2) Department of Pharmacy Practice, Faculty of Pharmacy, University of Baluchistan, Quetta, Pakistan; (3) Department of Pharmacy, University of Peshawar, Peshawar, Pakistan; (4) Department of Integrated Sciences, Post Graduate Nursing College, Peshawar, Pakistan.
Journal: Public Library of Science
Citation: PLoS One. 2015 Nov 11;10(11):e0142485. doi: 10.1371/journal.pone.0142485. eCollection 2015.
Publication Year and Month: 2015 11

Abstract: INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan.

METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results.

RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42±2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75±5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio.

Conclusions: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12
Author: Iqbal S (1), Shi J (1), Seib K (2), Lewis P (1), Moro PL (1), Woo EJ (3), Shimabukuro T (1), Orenstein WA (2)
Affiliation: (1) Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; (2) Emory University, School of Medicine, Division of Infectious Diseases, Atlanta, GA, USA; (3) Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA
Journal: The Lancet Infectious Diseases
Citation: DOI: http://dx.doi.org/10.1016/S1473-3099(15)00059-6
Publication Year and Month: 2015 08

Abstract: BACKGROUND: Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS).

METHODS: We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV).

FINDINGS: Of the 41 792 adverse event reports submitted, 39 568 (95%) were for children younger than 7 years. 38 381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34 880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013.

INTERPRETATION: Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: New vaccine strategies to finish polio eradication
Author: Grassly NC
Affiliation: Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Hospital, London W2 1PG, UK; Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Journal: The Lancet Infectious Diseases
Citation: Lancet Infect Dis, Volume 15, Issue 8, 864-865
Publication Year and Month: 2015 06

Abstract: The Global Polio Eradication Initiative (GPEI) currently faces two specific challenges. First, all the cases in the past 9 months caused by ongoing wild-virus transmission were in Afghanistan and Pakistan—Africa has had a remarkable 9 months without detection of the disease. Second, circulating vaccine-derived polioviruses are continuing to cause poliomyelitis in a few countries, a rare outcome associated with continued use of the live-attenuated oral poliovirus vaccine (OPV). In The Lancet Infectious Diseases, the results of two clinical trials of OPV that address these challenges are reported by Fatima Mir and colleagues and Concepción Estívariz and colleagues.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Review of the health consequences of SV40 contamination of poliomyelitis vaccines, and in particular a possible association with cancers
Author: Cossart Y, A0
Affiliation: Bosch Professor of Infectious Diseases, University of Sydney, Australia
Journal: Therapeutic Goods Administration Alert/Advisory
Citation:
Publication Year and Month: 2004 12

Abstract: The published papers concerning the human health risk of vaccines contaminated with SV40 virus falls into three groups: those published in the 1960s when the virus was discovered, a second group dating from the period when the two related human viruses BK and JC were described and the third recent period when molecular techniques were applied to the problem.

GROUP 1: SV40 was discovered in 1960 and shown
~ To be a common infection in healthy rhesus monkeys
~ To belong to the polyoma virus family
~ To cause tumours (especially ependymomas, osteosarcomas, mesotheliomas and lymphomas) when injected into baby hamsters
~ To be incompletely killed by the heat and formalin treatment used to inactivate polioviruses during "Salk" vaccine manufacture
~ To be capable of infecting human recipients of contaminated vaccine
~ To be capable of transforming human cells into cancer cells in the laboratory

Immediate steps were taken to free the vaccine seed cultures of SV40 and to ensure that all future batches of vaccine (both the inactivated "Salk" and the then prototype attenuated "Sabin" types) were made in monkey kidney cultures free of SV40. This was accomplished in 1963.

Many millions of children and adults had already been inoculated with polio vaccine before these measures were fully effective. It is not known which of the early batches actually contained infectious doses of SV40, but tests of recipients showed that many produced SV40 antibodies. This could be the result of either SV40 infection or "immunisation" by the killed SV40 in the vaccine.

Concern focussed on the risk to very young children but no increased risk of cancer was found in follow up of over 1000 vaccinees. As the tumour types induced in hamsters are rare these studies were supplemented with much larger studies comparing cancer registry data for children born (and presumably mostly immunised) during the period between introduction of polio vaccine and eradication of SV40 from manufacture (ie 1957-63) and children born within the preceding or subsequent five year periods. These studies were reassuring, although it was recognised that the follow up was not sufficiently long term to detect a risk of the cancers such as mesothelioma which occur in middle age and beyond. There were also some discrepant reports but in retrospect these (including the single Australian study) have significant design limitations.

GROUP 2: The issue was revived in the 1970s when two new human polyomaviruses (BK and JC) were discovered. These cause tumours and degenerative neurological disease in humans. They also share antigens and DNA sequences with SV40 which may cause cross reactions leading to false positive results in diagnostic tests. Surveys showed that serological evidence of infection with the two new agents was common in healthy people and that disease emerged almost exclusively in immune deficient individuals. Attempts to isolate SV40 from human tumours, even by explanting the cells in culture, were generally unsuccessful, but one typical SV40 strain was obtained from a melanoma and two others from diseased brain tissue. Serological surveys showed that earlier findings that up to 5% of the population had low titre SV40 antibody were mostly, if not entirely, due to cross reactions with the much commoner human polyoma viruses.

It was thus concluded that while SV40 involvement in human tumours could not be absolutely denied it must be very rare indeed.

GROUP 3 : The most recent group of publications has reported the use of molecular techniques to detect SV40 DNA in tumours. The results have been conflicting, some studies showing no positives
others a high proportion. Most workers have focussed on detection of the viral oncogene (T antigen) and/or its expression. Persistence of these sequences integrated into the host cell genome would be expected from experimental studies of polyomavirus induced tumours of other species. Unfortunately the SV40 sequences of interest are widely used as tools in molecular laboratories creating a very substantial risk of cross contamination when testing tumour samples. This casts doubt on these studies which has not yet been resolved. Another new avenue of research has revealed that the SV40 oncogene (Tag) acts through complexing with p53 and affects the pRb pathway of cell cycle control. Genetic mutations of these control elements makes the cell exquisitely sensitive to SV40 transformation. These mutations occur naturally in the population, and confer cancer susceptibility on individuals who often develop tumours of similar type to those associated with SV40. This may need to be taken into account in future epidemiological studies.

Conclusions: The literature establishes a plausible mechanism for human carcinogenesis by SV40 virus. Studies of the prevalence of SV40 antibody in the community and the presence of SV40 in human tumours do not absolutely exclude the possibility of rare involvement of the virus in individual cases of cancer, but fail to provide evidence of statistically greater risk for people immunised during the period when SV40 was likely to have been present in polio vaccine. This conclusion has also been reached by several international review panels.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial
Author: Mychaleckyj JC (1), Haque R (2), Carmolli M (3), Zhang D (4), Colgate ER (3), Nayak U (4), Taniuchi M (5), Dickson D (3), Weldon WC (6), Oberste MS (6), Zaman K (2), Houpt ER (5), Alam M (2), Kirkpatrick BD (7), Petri WA Jr (8)
Affiliation: (1) Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (2) Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh; (3) Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA; (4) Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (5) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; (6) Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; (7) Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA; (8) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908-1340, USA
Journal: Vaccine
Citation: Vaccine. 2015 Nov 28. pii: S0264-410X(15)01695-3. doi: 10.1016/j.vaccine.2015.11.046. [Epub ahead of print]
Publication Year and Month: 2015 11

Abstract: BACKGROUND: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.

METHODS: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.

FINDINGS: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.

Conclusions: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.

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There are currently 11 papers in this category.

Category: Polio Immunisation

Title: Rotary’s PolioPlus Program: Lessons Learned, Transition Planning, and Legacy
Author: John L. Sever Michael McGovern Robert Scott Carol Pandak Amy Edwards David Goodstone
Affiliation:
Journal: NEW - PUT DETAILS IN CITATION FIELD
Citation: The Journal of Infectious Diseases, Volume 216, Issue suppl_1 S355–S361, https://doi.org/10.1093/infdis/jiw556
Publication Year and Month: 2017 06

Abstract: Hundreds of thousands of Rotary volunteers have provided support for polio eradication activities and continue to this day by making financial contributions to the Rotary PolioPlus program, participating in national immunization days, assisting with surveillance, working on local, national, and international advocacy programs for polio eradication, assisting at immunization posts and clinics, and mobilizing their communities for immunization activities (including poliovirus and other vaccines) and other health benefits. Rotary has contributed more than $1.61 billion for the global eradication of polio and has committed to provide an additional $35 million each year until 2018 (all dollar amounts represent US dollars). Its unwavering commitment to eradicate polio has been vital to the success of the program. Rotary is providing additional support for routine immunization and healthcare. When polio is finally gone, we will have the knowledge from the lessons learned with PolioPlus, such as the value of direct involvement by local Rotarians, the program for emergency funding, innovative tactics, and additional approaches for tackling other global issues, even those beyond public health. Rotary has already transitioned its grants program to include 6 areas of focus: disease prevention and treatment, water and sanitation, maternal and child health, basic education and literacy, economic and community development, and peace and conflict prevention/resolution. Funding for these grants in 2015–2016 was $71 million. The legacy of the polio program will be the complete eradication of poliovirus and the elimination of polio for all time.

Conclusions: Through Rotary’s polio eradication efforts, the organization has learned how to raise funds with coordinated campaigns, and raise awareness with innovative communications methods and celebrity engagement. In addition, Rotary members learned how to work with other organizations to implement large-scale projects that required advocacy, security planning, and coordination in the field. Finally, the launch of PolioPlus as Rotary’s flagship project has a legacy of uniting Rotary members around the world behind a common goal. Ending polio will be a major stepping stone for the United Nations’ sustainable development goals, particularly goal 3, to “ensure healthy lives and promote well-being for all at all ages” [33]. When polio is finally gone, we will have the blueprint for tackling other global issues, even those beyond public health.

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication
Author: Aghamohammadi A (1), Abolhassani H (1), Kutukculer N (2), Wassilak SG (3), Pallansch MA (4), Kluglein S (5), Quinn J (6), Sutter RW (7), Wang X (8), Sanal O (9), Latysheva T (10), Ikinciogullari A (11), Bernatowska E (12), Tuzankina IA (13), Costa-Carvalho BT (14), Franco JL (15), Somech R (16), Karakoc-Aydiner E (17), Singh S (18), Bezrodnik L (19), Espinosa-Rosales FJ (20), Shcherbina A (21), Lau Y (22,23), Nonoyama S (24), Modell F (6), Modell V (6), The JMF Centers Network Investigators and Study Collaborators, Barbouche M (25), and McKinlay MA (5)
Affiliation: (1) Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Science, Tehran, Iran; (2) Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey; (3) Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, United States; (4) Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States; (5) Center for Vaccine Equity, Task Force for Global Health, Atlanta, GA, United States; (6) Jeffrey Modell Foundation, New York, NY, United States; (7) Research and Product Development, World Health Organization, Geneva, Switzerland' (8) Department of Clinical Immunology, Children’s Hospital of Fudan University, Shanghai, China; (9) Division of Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey; (10) Department of Allergology and Immunotherapy, Institute of Immunology, Moscow, Russia; (11) Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; (12) Department of Clinical Immunology, The Children’s Memorial Health Institute, Warsaw, Poland; (13) Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, Russia; (14) Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil; (15) Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad de Antioquia, Medellín, Colombia; (16) Pediatric Department A and the Immunology Service, Sheba Medical Center, Tel Hashomer, Jeffrey Modell Foundation Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; (17) Division of Pediatric Allergy and Immunology, Marmara Medical Faculty, Istanbul, Turkey; (18) Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, India; (19) Dr. Ricardo Gutierrez Hospital de Niños, Buenos Aires, Argentina; (20) Clinical Immunology and Allergy Unit, Instituto Nacional de Pediatría, Ciudad de México, Mexico; (21) Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; (22) Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong; (23) Shenzhen Primary Immunodeficiency Diagnostic and Therapeutic Laboratory, Hong Kong University-Shenzhen Hospital, Shenzhen, China; (24) Department of Pediatrics, National Defense Medical College, Saitama, Japan; (25) Department of Immunology, Institut Pasteur de Tunis, University Tunis El-Manar, Tunis, Tunisia.
Journal: Frontiers in Immunology
Citation: Front. Immunol. 8:685. doi: 10.3389/fimmu.2017.00685
Publication Year and Month: 2017 06

Abstract: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Conclusions: This study provides an estimate of the global iVDPV prevalence among PID patients without paralytic disease and supports expanded screening for iVDPV excretion in these patients. Although most previous studies focused on the risk of long-term iVDPV infection in antibody deficient patients, the predominance of risk in patients with combined immunodeficiencies included in the current study highlights the importance of considering this group of PID patients in any surveillance program. Reinfection with poliovirus and NPEV excretion in PID patients described elsewhere demonstrates the need for prolonged follow-up (17).

The Global Polio Eradication Initiative plans to cease use of OPV worldwide once WPV has been certified as eradicated, which will end the generation of new iVDPVs. However, there is currently no means for addressing the threat posed by existing immunodeficient persons infected with iVDPVs, either to the infected individual’s risk of paralytic disease, or to the community of a continuing source of poliovirus transmission. Antivirals represent a potential means to manage the treatment of iVDPV excreters and the risk they present to the eradication effort (32, 34). Two safe virus-specific antivirals acting by differing mechanisms are now being developed and may be used as a combination (e.g., pocapavir and V-7404). This strategy may resolve the individual’s infection, stop iVDPV excretion, and serve to eliminate the risk of poliovirus transmission in the community. Currently, pocapavir is being considered for use in poliovirus excreting PID patients on a compassionate use basis.

The potential risk posed by iVDPV excreters to the polio eradication effort indicates the immediate need to develop and implement a global iVDPV surveillance strategy. Utilizing this approach, individuals at risk of prolonged poliovirus excretion can be identified and antiviral treatment can be initiated.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: A cross-sectional survey of healthcare workers on the knowledge and attitudes towards polio vaccination in Pakistan
Author: Khan MU (1), Ahmad A (1), Aqeel T (2), Akbar N (2), Salman S (3), Idress J (4)
Affiliation: (1) Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia; (2) Department of Pharmacy Practice, Faculty of Pharmacy, University of Baluchistan, Quetta, Pakistan; (3) Department of Pharmacy, University of Peshawar, Peshawar, Pakistan; (4) Department of Integrated Sciences, Post Graduate Nursing College, Peshawar, Pakistan.
Journal: Public Library of Science
Citation: PLoS One. 2015 Nov 11;10(11):e0142485. doi: 10.1371/journal.pone.0142485. eCollection 2015.
Publication Year and Month: 2015 11

Abstract: INTRODUCTION: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan.

METHODS: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results.

RESULTS: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42±2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75±5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio.

Conclusions: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

Outcome of Research: Not applicable

Availability of Paper: The full text of this paper has been generously made available by the publisher.

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Category: Polio Immunisation

Title: Effect of substituting IPV for tOPV on immunity to poliovirus in Bangladeshi infants: An open-label randomized controlled trial
Author: Mychaleckyj JC (1), Haque R (2), Carmolli M (3), Zhang D (4), Colgate ER (3), Nayak U (4), Taniuchi M (5), Dickson D (3), Weldon WC (6), Oberste MS (6), Zaman K (2), Houpt ER (5), Alam M (2), Kirkpatrick BD (7), Petri WA Jr (8)
Affiliation: (1) Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (2) Center for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Mohakhali 1212, Dhaka, Bangladesh; (3) Vaccine Testing Center, University of Vermont College of Medicine, Burlington, VT 05405, USA; (4) Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; (5) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; (6) Centers for Disease Control and Prevention, Atlanta, GA 30333, USA; (7) Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA; (8) Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, VA 22908-1340, USA
Journal: Vaccine
Citation: Vaccine. 2015 Nov 28. pii: S0264-410X(15)01695-3. doi: 10.1016/j.vaccine.2015.11.046. [Epub ahead of print]
Publication Year and Month: 2015 11

Abstract: BACKGROUND: The Polio Endgame strategy includes phased withdrawal of oral poliovirus vaccines (OPV) coordinated with introduction of inactivated poliovirus vaccine (IPV) to ensure population immunity. The impact of IPV introduction into a primary OPV series of immunizations in a developing country is uncertain.

METHODS: Between May 2011 and November 2012, we enrolled 700 Bangladeshi infant-mother dyads from Dhaka slums into an open-label randomized controlled trial to test whether substituting an injected IPV dose for the standard Expanded Program on Immunization (EPI) fourth tOPV dose at infant age 39 weeks would reduce fecal shedding and enhance systemic immunity. The primary endpoint was mucosal immunity to poliovirus at age one year, measured by fecal excretion of any Sabin virus at five time points up to 25 days post-52 week tOPV challenge, analyzed by the intention to treat principle.

FINDINGS: We randomized 350 families to the tOPV and IPV vaccination arms. Neither study arm resulted in superior intestinal protection at 52 weeks measured by the prevalence of infants shedding any of three poliovirus serotypes, but the IPV dose induced significantly higher seroprevalence and seroconversion rates. This result was identical for poliovirus detection by cell culture or RT-qPCR. The non-significant estimated culture-based shedding risk difference was -3% favoring IPV, and the two vaccination schedules were inferred to be equivalent within a 95% confidence margin of -10% to +4%. Results for shedding analyses stratified by poliovirus type were similar.

Conclusions: Neither of the vaccination regimens is superior to the other in enhancing intestinal immunity as measured by poliovirus shedding at 52 weeks of age and the IPV regimen provides similar intestinal immunity to the four tOPV series, although the IPV regimen strongly enhances humoral immunity. The IPV-modified regimen may be considered for vaccination programs without loss of intestinal protection.

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Category: Polio Immunisation

Title: Applying the concept of peptide uniqueness to anti-polio vaccination
Author: Kanduc D (1), Fasano C (1), Capone G (1), Pesce Delfino A (2), Calabrò M (2), Polimeno L (2)
Affiliation: (1) Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70126 Bari, Italy; (2) Department of Emergency and Organ Transplantation (DETO), University of Bari, 70124 Bari, Italy
Journal: Journal of Immunology Research
Citation: J Immunol Res. 2015;2015:541282. Epub 2015 Oct 19
Publication Year and Month: 2015 10

Abstract: BACKGROUND: Although rare, adverse events may associate with anti-poliovirus vaccination thus possibly hampering global polio eradication worldwide.

OBJECTIVE: To design peptide-based anti-polio vaccines exempt from potential cross-reactivity risks and possibly able to reduce rare potential adverse events such as the postvaccine paralytic poliomyelitis due to the tendency of the poliovirus genome to mutate.

METHODS: Proteins from poliovirus type 1, strain Mahoney, were analyzed for amino acid sequence identity to the human proteome at the pentapeptide level, searching for sequences that (1) have zero percent of identity to human proteins, (2) are potentially endowed with an immunologic potential, and (3) are highly conserved among poliovirus strains.

RESULTS: Sequence analyses produced a set of consensus epitopic peptides potentially able to generate specific anti-polio immune responses exempt from cross-reactivity with the human host.

Conclusions: Peptide sequences unique to poliovirus proteins and conserved among polio strains might help formulate a specific and universal anti-polio vaccine able to react with multiple viral strains and exempt from the burden of possible cross-reactions with human proteins. As an additional advantage, using a peptide-based vaccine instead of current anti-polio DNA vaccines would eliminate the rare post-polio poliomyelitis cases and other disabling symptoms that may appear following vaccination.

Outcome of Research: More research required

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Category: Polio Immunisation

Title: Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000–12
Author: Iqbal S (1), Shi J (1), Seib K (2), Lewis P (1), Moro PL (1), Woo EJ (3), Shimabukuro T (1), Orenstein WA (2)
Affiliation: (1) Immunization Safety Office, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA; (2) Emory University, School of Medicine, Division of Infectious Diseases, Atlanta, GA, USA; (3) Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA
Journal: The Lancet Infectious Diseases
Citation: DOI: http://dx.doi.org/10.1016/S1473-3099(15)00059-6
Publication Year and Month: 2015 08

Abstract: BACKGROUND: Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS).

METHODS: We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV).

FINDINGS: Of the 41 792 adverse event reports submitted, 39 568 (95%) were for children younger than 7 years. 38 381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34 880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013.

INTERPRETATION: Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: New vaccine strategies to finish polio eradication
Author: Grassly NC
Affiliation: Department of Infectious Disease Epidemiology, Imperial College London, St Mary's Hospital, London W2 1PG, UK; Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, Tamil Nadu, India
Journal: The Lancet Infectious Diseases
Citation: Lancet Infect Dis, Volume 15, Issue 8, 864-865
Publication Year and Month: 2015 06

Abstract: The Global Polio Eradication Initiative (GPEI) currently faces two specific challenges. First, all the cases in the past 9 months caused by ongoing wild-virus transmission were in Afghanistan and Pakistan—Africa has had a remarkable 9 months without detection of the disease. Second, circulating vaccine-derived polioviruses are continuing to cause poliomyelitis in a few countries, a rare outcome associated with continued use of the live-attenuated oral poliovirus vaccine (OPV). In The Lancet Infectious Diseases, the results of two clinical trials of OPV that address these challenges are reported by Fatima Mir and colleagues and Concepción Estívariz and colleagues.

Conclusions:

Outcome of Research: Not applicable

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Category: Polio Immunisation

Title: Field study of fecal excretion as a decision support tool in response to silent reintroduction of wild-type poliovirus 1 into Israel
Author: Moran-Gilad J (1), Mendelson E (2), Burns CC (3), Bassal R (4), Gdalevich M (5), Sofer D (6), Oberste MS (3), Shulman LM (2), Kaliner E (7), Hindiyeh M, Mor O (6), Shahar L (5), Iber J (3), Yishay R (8), Manor J (6), Lev B (9), Gamzu R (10), Grotto I (11)
Affiliation: (1) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; (2) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; (3) Viruses Branch, Centers for Disease Control and Prevention, Atlanta, USA; (4) Israel Center for Disease Control, Ministry of Health, Tel-Hashomer, Israel; (5) Southern District Health Office, Ministry of Health, Beer-Sheva, Israel; (6) Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel; (7) Public Health Services, Ministry of Health, Jerusalem, Israel; (8) Department of Laboratories, Public Health Services, Ministry of Health, Jerusalem, Israel; (9) Directorate, Ministry of Health, Jerusalem, Israel; (10) School of Public Health, Tel-Aviv University, Tel-Aviv, Israel; Directorate, Ministry of Health, Jerusalem, Israel; (11) Public Health Services, Ministry of Health, Jerusalem, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Journal: Journal of Clinical Virology
Citation: J Clin Virol. 2015 May;66:51-5. doi: 10.1016/j.jcv.2015.03.005. Epub 2015 Mar 10
Publication Year and Month: 2015 05

Abstract: BACKGROUND: Israel has used an inactivated polio vaccine (IPV)-only schedule since 2005 (95% coverage). Silent reintroduction of wild type poliovirus 1 (WPV1) into Israel in early 2013 was detected in Southern Israel via routine environmental surveillance without clinical cases.

OBJECTIVES: To estimate the rate of WPV1 excretion by age and residence and inform decision-making regarding supplemental immunization with OPV.

STUDY DESIGN: A convenience sample of Bedouin and Jewish residential areas in the epicenter of the incident, focusing on under 8 year-olds who not previously given OPV. Fecal samples were directly tested for WPV1 RNA using a novel qRT-PCR assay. Positive samples were confirmed by gold standard cell culture and subject to genotyping.

RESULTS: Overall, 2196 non-duplicate fecal samples were collected and analyzed. WPV1 was detected in 61 samples (2.8%), 55 of which (90.2%) were from Bedouins. WPV1 excretion rates were 5.4% among Bedouins and 0.6% among Jewish individuals. Respective age-specific rates among Bedouin and Jewish children were 4.9% and 0.2% for 0-2 years and 7.2% and 1.7% for 2-8 years. Molecular testing had 89.5% sensitivity (higher than culture) and 100% specificity.

Conclusions: The rapid performance of a field study to evaluate WPV1 excretion unequivocally demonstrated substantial WPV1 infection rates among children under 8 years in Southern Israel, thus informing the decision to vaccinate this age group with bOPV and risk communication to both healthcare personnel and the public. Rapid development and implementation of molecular screening can thus underpin risk assessment and management in complex epidemiological situations.

Outcome of Research:

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Comments (if any): Erratum in: J Clin Virol. 2015 Aug;251. Hindiye, Musa [corrected to Hindiyeh, Musa]

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Category: Polio Immunisation

Title: Immunogenicity of two different sequential schedules of inactivated polio vaccine followed by oral polio vaccine versus oral polio vaccine alone in healthy infants in China
Author: Li RC (1), Li CG (2), Wang HB (3), Luo HM (3), Li YP (1), Wang JF (2), Ying ZF (2), Yu WZ (3), Shu JD (4), Wen N (3), Vidor E (5)
Affiliation: (1) Guangxi Center for Disease Prevention and Control, Nanning, China; (2) National Institutes for Food and Drug Control (NIFDC), Beijing, China; (3) Chinese Center for Disease Control and Prevention, Beijing, China; (4) Sanofi Pasteur, Beijing, China; (5) Sanofi Pasteur, Lyon, France
Journal: Journal of the Pediatric Infectious Diseases Society
Citation: J Pediatric Infect Dis Soc. 2015 Apr 16. pii: piv017
Publication Year and Month: 2015 04

Abstract: BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule.

METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored.

RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar.

Conclusions: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539 - https://clinicaltrials.gov/ct2/show/study/NCT01475539).

Outcome of Research: Effective

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Category: Polio Immunisation

Title: Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals
Author: Thomassen YE (1), van 't Oever AG (1), van Oijen MG (1), Wijffels RH (2), van der Pol LA (1), Bakker WA (1)
Affiliation: (1) Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands; (2) Bioprocess Engineering, Wageningen University, Wageningen, The Netherlands
Journal: Public Library of Science
Citation: PLoS One. 2013 Dec 12;8(12):e83374. doi: 10.1371/journal.pone.0083374
Publication Year and Month: 2013 12

Abstract: Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

Conclusions:

Outcome of Research: Effective

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Category: Polio Immunisation

Title: Review of the health consequences of SV40 contamination of poliomyelitis vaccines, and in particular a possible association with cancers
Author: Cossart Y, A0
Affiliation: Bosch Professor of Infectious Diseases, University of Sydney, Australia
Journal: Therapeutic Goods Administration Alert/Advisory
Citation:
Publication Year and Month: 2004 12

Abstract: The published papers concerning the human health risk of vaccines contaminated with SV40 virus falls into three groups: those published in the 1960s when the virus was discovered, a second group dating from the period when the two related human viruses BK and JC were described and the third recent period when molecular techniques were applied to the problem.

GROUP 1: SV40 was discovered in 1960 and shown
~ To be a common infection in healthy rhesus monkeys
~ To belong to the polyoma virus family
~ To cause tumours (especially ependymomas, osteosarcomas, mesotheliomas and lymphomas) when injected into baby hamsters
~ To be incompletely killed by the heat and formalin treatment used to inactivate polioviruses during "Salk" vaccine manufacture
~ To be capable of infecting human recipients of contaminated vaccine
~ To be capable of transforming human cells into cancer cells in the laboratory

Immediate steps were taken to free the vaccine seed cultures of SV40 and to ensure that all future batches of vaccine (both the inactivated "Salk" and the then prototype attenuated "Sabin" types) were made in monkey kidney cultures free of SV40. This was accomplished in 1963.

Many millions of children and adults had already been inoculated with polio vaccine before these measures were fully effective. It is not known which of the early batches actually contained infectious doses of SV40, but tests of recipients showed that many produced SV40 antibodies. This could be the result of either SV40 infection or "immunisation" by the killed SV40 in the vaccine.

Concern focussed on the risk to very young children but no increased risk of cancer was found in follow up of over 1000 vaccinees. As the tumour types induced in hamsters are rare these studies were supplemented with much larger studies comparing cancer registry data for children born (and presumably mostly immunised) during the period between introduction of polio vaccine and eradication of SV40 from manufacture (ie 1957-63) and children born within the preceding or subsequent five year periods. These studies were reassuring, although it was recognised that the follow up was not sufficiently long term to detect a risk of the cancers such as mesothelioma which occur in middle age and beyond. There were also some discrepant reports but in retrospect these (including the single Australian study) have significant design limitations.

GROUP 2: The issue was revived in the 1970s when two new human polyomaviruses (BK and JC) were discovered. These cause tumours and degenerative neurological disease in humans. They also share antigens and DNA sequences with SV40 which may cause cross reactions leading to false positive results in diagnostic tests. Surveys showed that serological evidence of infection with the two new agents was common in healthy people and that disease emerged almost exclusively in immune deficient individuals. Attempts to isolate SV40 from human tumours, even by explanting the cells in culture, were generally unsuccessful, but one typical SV40 strain was obtained from a melanoma and two others from diseased brain tissue. Serological surveys showed that earlier findings that up to 5% of the population had low titre SV40 antibody were mostly, if not entirely, due to cross reactions with the much commoner human polyoma viruses.

It was thus concluded that while SV40 involvement in human tumours could not be absolutely denied it must be very rare indeed.

GROUP 3 : The most recent group of publications has reported the use of molecular techniques to detect SV40 DNA in tumours. The results have been conflicting, some studies showing no positives
others a high proportion. Most workers have focussed on detection of the viral oncogene (T antigen) and/or its expression. Persistence of these sequences integrated into the host cell genome would be expected from experimental studies of polyomavirus induced tumours of other species. Unfortunately the SV40 sequences of interest are widely used as tools in molecular laboratories creating a very substantial risk of cross contamination when testing tumour samples. This casts doubt on these studies which has not yet been resolved. Another new avenue of research has revealed that the SV40 oncogene (Tag) acts through complexing with p53 and affects the pRb pathway of cell cycle control. Genetic mutations of these control elements makes the cell exquisitely sensitive to SV40 transformation. These mutations occur naturally in the population, and confer cancer susceptibility on individuals who often develop tumours of similar type to those associated with SV40. This may need to be taken into account in future epidemiological studies.

Conclusions: The literature establishes a plausible mechanism for human carcinogenesis by SV40 virus. Studies of the prevalence of SV40 antibody in the community and the presence of SV40 in human tumours do not absolutely exclude the possibility of rare involvement of the virus in individual cases of cancer, but fail to provide evidence of statistically greater risk for people immunised during the period when SV40 was likely to have been present in polio vaccine. This conclusion has also been reached by several international review panels.

Outcome of Research: Not applicable

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