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Sample records for poliovirus vaccine ipv

  1. Decay of Sabin inactivated poliovirus vaccine (IPV)-boosted poliovirus antibodies

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    Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W.

    2015-01-01

    Introduction: We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21–22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. Methods: In 2012, 60 healthy adult males aged 19–23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvant...

  2. Decay of Sabin inactivated poliovirus vaccine (IPV)-boosted poliovirus antibodies.

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    Resik, Sonia; Tejeda, Alina; Fonseca, Magile; Sein, Carolyn; Hung, Lai Heng; Martinez, Yenisleidys; Diaz, Manuel; Okayasu, Hiromasa; Sutter, Roland W

    We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21-22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. In 2012, 60 healthy adult males aged 19-23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21-22 months after vaccination, and tested for neutralizing antibodies to Sabin poliovirus types 1, 2 and 3. We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all poliovirus types, 21-22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21-22 months, there was a reduction of ⩾87.4% in median antibody levels for all poliovirus types in all study groups, with no significant differences between the study groups. The decay of poliovirus antibodies over a 21-22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.

  3. Decay of Sabin inactivated poliovirus vaccine (IPV-boosted poliovirus antibodies

    Directory of Open Access Journals (Sweden)

    Sonia Resik

    2015-01-01

    Conclusion: The decay of poliovirus antibodies over a 21–22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.

  4. [Poliovirus vaccine].

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    Shimizu, Hiroyuki

    2012-06-01

    To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world.

  5. Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

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    Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang

    2018-03-30

    Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

  6. Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.

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    Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody

    2017-06-03

    Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.

  7. First-in-human safety and immunogenicity investigations of three adjuvanted reduced dose inactivated poliovirus vaccines (IPV-Al SSI) compared to full dose IPV Vaccine SSI when given as a booster vaccination to adolescents with a history of IPV vaccination at 3, 5, 12months and 5years of age.

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    Lindgren, Line M; Tingskov, Pernille N; Justesen, Annette H; Nedergaard, Bettina S; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Sørensen, Charlotte; Dietrich, Jes; Thierry-Carstensen, Birgit

    2017-01-23

    There is a demand of affordable IPV in the World. Statens Serum Institut (SSI) has developed three reduced dose IPV formulations adsorbed to aluminium hydroxide; 1/3 IPV-Al, 1/5 IPV-Al and 1/10 IPV-Al SSI, and now report the results of the first investigations in humans. 240 Danish adolescents, aged 10-15years, and childhood vaccinated with IPV were booster vaccinated with 1/3 IPV-Al, 1/5 IPV-Al, 1/10 IPV-Al or IPV Vaccine SSI. The booster effects (GMTRs) of the three IPV-Al SSI were compared to IPV Vaccine SSI, and evaluated for non-inferiority. The pre-vaccination GMTs were similar across the groups; 926 (type 1), 969 (type 2) and 846 (type 3) in the total trial population. The GMTRs by poliovirus type and IPV formulation were: Type 1: 17.0 (1/3 IPV-Al), 13.0 (1/5 IPV-Al), 7.1 (1/10 IPV-Al) and 42.2 (IPV Vaccine SSI). Type 2: 12.5 (1/3 IPV-Al), 13.1 (1/5 IPV-Al), 7.6 (1/10 IPV-Al) and 47.8 (IPV Vaccine SSI). Type 3: 14.5 (1/3 IPV-Al), 16.2 (1/5 IPV-Al), 8.9 (1/10 IPV-Al) and 62.4 (IPV Vaccine SSI) Thus, the three IPV-Al formulations were highly immunogenic, but inferior to IPV Vaccine SSI, in this booster vaccination trial. No SAE and no AE of severe intensity occurred. 59.2% of the subjects reported at least one AE. Injection site pain was the most frequent AE in all groups; from 24.6% to 43.3%. Injection site redness and swelling frequencies were<5% in most and<10% in all groups. The most frequent systemic AEs were fatigue (from 8.2% to 15.0%) and headache (from 15.0% to 28.3%). Most AEs were of mild intensity. In conclusion, the three IPV-Al SSI were safe in adolescents and the booster effects were satisfactory. ClinicalTrials.gov registration number: NCT02280447. Copyright © 2016. Published by Elsevier Ltd.

  8. Vial usage, device dead space, vaccine wastage, and dose accuracy of intradermal delivery devices for inactivated poliovirus vaccine (IPV).

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    Jarrahian, Courtney; Rein-Weston, Annie; Saxon, Gene; Creelman, Ben; Kachmarik, Greg; Anand, Abhijeet; Zehrung, Darin

    2017-03-27

    Intradermal delivery of a fractional dose of inactivated poliovirus vaccine (IPV) offers potential benefits compared to intramuscular (IM) delivery, including possible cost reductions and easing of IPV supply shortages. Objectives of this study were to assess intradermal delivery devices for dead space, wastage generated by the filling process, dose accuracy, and total number of doses that can be delivered per vial. Devices tested included syringes with staked (fixed) needles (autodisable syringes and syringes used with intradermal adapters), a luer-slip needle and syringe, a mini-needle syringe, a hollow microneedle device, and disposable-syringe jet injectors with their associated filling adapters. Each device was used to withdraw 0.1-mL fractional doses from single-dose IM glass vials which were then ejected into a beaker. Both vial and device were weighed before and after filling and again after expulsion of liquid to record change in volume at each stage of the process. Data were used to calculate the number of doses that could potentially be obtained from multidose vials. Results show wide variability in dead space, dose accuracy, overall wastage, and total number of doses that can be obtained per vial among intradermal delivery devices. Syringes with staked needles had relatively low dead space and low overall wastage, and could achieve a greater number of doses per vial compared to syringes with a detachable luer-slip needle. Of the disposable-syringe jet injectors tested, one was comparable to syringes with staked needles. If intradermal delivery of IPV is introduced, selection of an intradermal delivery device can have a substantial impact on vaccine wasted during administration, and thus on the required quantity of vaccine that needs to be purchased. An ideal intradermal delivery device should be not only safe, reliable, accurate, and acceptable to users and vaccine recipients, but should also have low dead space, high dose accuracy, and low overall

  9. Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats.

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    Ma, Lei; Cai, Wei; Sun, Mingbo; Cun, Yina; Zhou, Jian; Liu, Jing; Hu, Wenzhu; Zhang, Xinwen; Song, Shaohui; Jiang, Shude; Liao, Guoyang

    2016-12-01

    The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 th days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions

  10. Inactivated polio vaccine development for technology transfer using attenuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV.

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    Bakker, Wilfried A M; Thomassen, Yvonne E; van't Oever, Aart G; Westdijk, Janny; van Oijen, Monique G C T; Sundermann, Lars C; van't Veld, Peter; Sleeman, Eelco; van Nimwegen, Fred W; Hamidi, Ahd; Kersten, Gideon F A; van den Heuvel, Nico; Hendriks, Jan T; van der Pol, Leo A

    2011-09-22

    Industrial-scale inactivated polio vaccine (IPV) production dates back to the 1960s when at the Rijks Instituut voor de Volksgezondheid (RIV) in Bilthoven a process was developed based on micro-carrier technology and primary monkey kidney cells. This technology was freely shared with several pharmaceutical companies and institutes worldwide. In this contribution, the history of one of the first cell-culture based large-scale biological production processes is summarized. Also, recent developments and the anticipated upcoming shift from regular IPV to Sabin-IPV are presented. Responding to a call by the World Health Organization (WHO) for new polio vaccines, the development of Sabin-IPV was continued, after demonstrating proof of principle in the 1990s, at the Netherlands Vaccine Institute (NVI). Development of Sabin-IPV plays an important role in the WHO polio eradication strategy as biocontainment will be critical in the post-OPV cessation period. The use of attenuated Sabin strains instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel to clinical trial material production, process development, optimization and formulation research is being carried out to further optimize the process and reduce cost per dose. Also, results will be shown from large-scale (to prepare for future technology transfer) generation of Master- and Working virus seedlots, and clinical trial material (for phase I studies) production. Finally, the planned technology transfer to vaccine manufacturers in low and middle-income countries is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Immunity to poliovirus after infection and vaccination

    NARCIS (Netherlands)

    Herremans, Martina Maria Petronella Theresia

    1999-01-01

    The aim of this thesis was defined as the study of the contribution of IPV vaccination to the induction of a) protection against poliovirus infection and b) mucosal immunity.We have described the development of new immunological tools for the rapid detection of poliovirus-specific antibodies and

  12. Innovative IPV from attenuated Sabin poliovirus or newly designed alternative seed strains.

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    Hamidi, Ahd; Bakker, Wilfried A M

    2012-11-01

    This article gives an overview of the patent literature related to innovative inactivated polio vaccine (i-IPV) based on using Sabin poliovirus strains and newly developed alternative recombinant poliovirus strains. This innovative approach for IPV manufacturing is considered to attribute to the requirement for affordable IPV in the post-polio-eradication era, which is on the horizon. Although IPV is a well-established vaccine, the number of patent applications in this field was seen to have significantly increased in the past decade. Currently, regular IPV appears to be too expensive for universal use. Future affordability may be achieved by using alternative cell lines, alternative virus seed strains, improved and optimized processes, dose sparing, or the use of adjuvants. A relatively short-term option to achieve cost-price reduction is to work on regular IPV, using wild-type poliovirus strains, or on Sabin-IPV, based on using attenuated poliovirus strains. This price reduction can be achieved by introducing efficiency in processing. There are also multiple opportunities to work on dose sparing, for example, by using adjuvants or fractional doses. Renewed interest in this field was clearly reflected in the number and diversity of patent applications. In a later stage, several innovative approaches may become even more attractive, for example the use of recombinant virus strains or even a totally synthetic vaccine. Currently, such work is mainly carried out by research institutes and universities and therefore clinical data are not available.

  13. [Inactivated poliovirus vaccines: an inevitable choice for eliminating poliomyelitis].

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    Vidor, J D; Jean-Denis, Shu

    2016-12-06

    The inactivated poliovirus vaccine (IPV) is a very old tool in the fight against poliomyelitis. Though supplanted by oral poliovirus vaccine (OPV) in the 1960s and 1970s, the IPV has now become an inevitable choice because of the increasingly recognized risks associated with continuous use of OPVs. Following the pioneering work of Jonas Salk, who established key principles for the IPV, considerable experience has accumulated over the years. This work has led to modern Salk IPV-containing vaccines, based on the use of inactivated wildtype polioviruses, which have been deployed for routine use in many countries. Very good protection against paralysis is achieved with IPV through the presence of circulating antibodies able to neutralize virus infectivity toward motor neurons. In addition, with IPV, a variable degree of protection against mucosal infection (and therefore transmission) through mucosal antibodies and immune cells is achieved, depending on previous exposure of subjects to wildtype or vaccine polioviruses. The use of an IPV-followed-by-OPV sequential immunization schedule has the potential advantage of eliminating the vaccine-associated paralytic poliomyelitis (VAPP) risk, while limiting the risks of vaccine-derived poliovirus (VDPVs). Sabin strain-derived IPVs are new tools, only recently beginning to be deployed, and data are being generated to document their performance. IPVs will play an irreplaceable role in global eradication of polio.

  14. Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

    OpenAIRE

    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2014-01-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...

  15. Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

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    Sun, Mingbo; Li, Changgui; Xu, Wenbo; Liao, Guoyang; Li, Rongcheng; Zhou, Jian; Li, Yanping; Cai, Wei; Yan, Dongmei; Che, Yanchun; Ying, Zhifang; Wang, Jianfeng; Yang, Huijuan; Ma, Yan; Ma, Lei; Ji, Guang; Shi, Li; Jiang, Shude; Li, Qihan

    2017-05-15

    A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine. Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types. All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera. Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions. NCT01056705. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Antibody titers against vaccine and contemporary wild poliovirus type 1 in children immunized with IPV+OPV and young adults immunized with OPV.

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    Lukashev, Alexander N; Yarmolskaya, Maria S; Shumilina, Elena Yu; Sychev, Daniil A; Kozlovskaya, Liubov I

    2016-02-02

    In 2010, a type 1 poliovirus outbreak in Congo with 445 lethal cases was caused by a virus that was neutralized by sera of German adults vaccinated with inactivated polio vaccine with a reduced efficiency. This seroprevalence study was done in two cohorts immunized with other vaccination schedules. Russian children aged 3-6 years immunized with a combination of inactivated and live polio vaccines were reasonably well protected against any wild type poliovirus 1, including the Congolese isolate. Adults aged 20-29 years immunized only with live vaccine were apparently protected against the vaccine strain (92% seropositive), but only 50% had detectable antibodies against the Congo-2010 isolate. Both waning immunity and serological divergence of the Congolese virus could contribute to this result. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. [Immunogenicity of sabin inactivated poliovirus vaccine induced by diphtheria-tetanus-acellular pertussis and Sabin inactivated poliovirus combined vaccine].

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    Ma, Yan; Qin, Min; Hu, Hui-Qiong; Ji, Guang; Feng, Ling; Gao, Na; Gu, Jie; Xie, Bing-Feng; He, Ji-Hong; Sun, Ming-Bo

    2011-06-01

    In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine (DTaP-sIPV), the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. Two batches of DTaP-sLPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostrix-polio, GSK, Belgium) as control group, the DTaP-sIPV were administrated on three-dose schedule at 0, 1, 2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. Two batches of prepared DTaP-sIPV and control sLPV were according to the requirement of Chinese Pharmacopoeia (Volume III, 2005 edition) and showed good stability. The seropositivity rates were 100% for sabin inactivated poliovirus antigen in all groups. The GMTs (Geometric mean titers) of neutralizing antibodies against three types poliovirus increased. The prepared DTaP-sIPV was safe, stable and effective and could induced high level neutralizing antibody against poliovirus on rats.

  18. Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

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    Anand, Abhijeet; Molodecky, Natalie A; Pallansch, Mark A; Sutter, Roland W

    2017-05-19

    The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, pvaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries. Copyright © 2017. Published by Elsevier Ltd.

  19. ERADIKASI POLIO DAN IPV (INACTIVATED POLIO VACCINE

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    Gendrowahyuhono Gendrowahyuhono

    2012-09-01

    that 100% of children of the study already have antibody against three types of polioviruses. From the result of the study conclude that the study can be continued untill the data can answer the question whether IPV is the only vaccine which can be use after OPV cessation   Key words: eradikasi, polio

  20. Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

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    Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

    2015-05-01

    Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Methods for the Quality Control of Inactivated Poliovirus Vaccines.

    Science.gov (United States)

    Wilton, Thomas

    2016-01-01

    Inactivated poliovirus vaccine (IPV) plays an instrumental role in the Global Poliovirus Eradication Initiative (GPEI). The quality of IPV is controlled by assessment of the potency of vaccine batches. The potency of IPV can be assessed by both in vivo and in vitro methods. In vitro potency assessment is based upon the assessment of the quantity of the D-Antigen (D-Ag) units in an IPV. The D-Ag unit is used as a measure of potency as it is largely expressed on native infectious virions and is the protective immunogen. The most commonly used in vitro test is the indirect ELISA which is used to ensure consistency throughout production.A range of in vivo assays have been developed in monkeys, chicks, guinea pigs, mice, and rats to assess the potency of IPV. All are based on assessment of the neutralizing antibody titer within the sera of the respective animal model. The rat potency test has become the favored in vivo potency test as it shows minimal variation between laboratories and the antibody patterns of rats and humans are similar. With the development of transgenic mice expressing the human poliovirus receptor, immunization-challenge tests have been developed to assess the potency of IPVs. This chapter describes in detail the methodology of these three laboratory tests to assess the quality of IPVs.

  2. Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine.

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    Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y

    2013-05-01

    Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans. Copyright © 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  3. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  4. Reactogenicity and immunogenicity of inactivated poliovirus vaccine produced from Sabin strains: a phase I Trial in healthy adults in Cuba.

    Science.gov (United States)

    Resik, Sonia; Tejeda, Alina; Fonseca, Magilé; Alemañi, Nilda; Diaz, Manuel; Martinez, Yenisleidys; Garcia, Gloria; Okayasu, Hiromasa; Burton, Anthony; Bakker, Wilfried A M; Verdijk, Pauline; Sutter, Roland W

    2014-09-22

    To ensure that developing countries have the option to produce inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV). This trial assessed the reactogenicity and immunogenicity of Sabin IPV and adjuvanted Sabin IPV in healthy adults in Cuba. This is a randomized, controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human volunteers, aged 19-23 years to receive one dose of either Sabin IPV (20:32:64 DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV (40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring of adverse events. The secondary endpoint measured boosting immune responses (i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by neutralization assays. Sixty subjects fulfilled the study requirements. No serious adverse events reported were attributed to trial interventions during the 6-month follow-up period. Twenty-eight days after vaccination, boosting immune responses against poliovirus types 1-3 were between 90% and 100% in all vaccination groups. There was a more than 6-fold increase in median antibody titers between pre- and post-vaccination titers in all vaccination groups. Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and immunogenic against all poliovirus serotypes. This result suggests that the aluminum adjuvant may allow a 50% (or higher) dose reduction. Copyright © 2014. Published by Elsevier Ltd.

  5. Development and introduction of inactivated poliovirus vaccines derived from Sabin strains in Japan.

    Science.gov (United States)

    Shimizu, Hiroyuki

    2016-04-07

    During the endgame of global polio eradication, the universal introduction of inactivated poliovirus vaccines is urgently required to reduce the risk of vaccine-associated paralytic poliomyelitis and polio outbreaks due to wild and vaccine-derived polioviruses. In particular, the development of inactivated poliovirus vaccines (IPVs) derived from the attenuated Sabin strains is considered to be a highly favorable option for the production of novel IPV that reduce the risk of facility-acquired transmission of poliovirus to the communities. In Japan, Sabin-derived IPVs (sIPVs) have been developed and introduced for routine immunization in November 2012. They are the first licensed sIPVs in the world. Consequently, trivalent oral poliovirus vaccine was used for polio control in Japan for more than half a century but has now been removed from the list of vaccines licensed for routine immunization. This paper reviews the development, introduction, characterization, and global status of IPV derived from attenuated Sabin strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

    Science.gov (United States)

    Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

    2011-05-01

    Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

  7. IPV v2.0 : upgrading the established inactivated polio vaccine production process

    NARCIS (Netherlands)

    Thomassen, Y.E.

    2014-01-01

    The first vaccine against poliovirus (PV), the causative agent of poliomyelitis, was developed in the 1950s by Jonas Salk. The vaccine (IPV) consists of an injected dose of purified and inactivated wild-type PVs (all three serotypes). Soon after this discovery, at the Rijks Instituut voor de

  8. Switch from oral to inactivated poliovirus vaccine in Yogyakarta Province, Indonesia: summary of coverage, immunity, and environmental surveillance.

    Science.gov (United States)

    Wahjuhono, Gendro; Revolusiana; Widhiastuti, Dyah; Sundoro, Julitasari; Mardani, Tri; Ratih, Woro Umi; Sutomo, Retno; Safitri, Ida; Sampurno, Ondri Dwi; Rana, Bardan; Roivainen, Merja; Kahn, Anna-Lea; Mach, Ondrej; Pallansch, Mark A; Sutter, Roland W

    2014-11-01

    Inactivated poliovirus vaccine (IPV) is rarely used in tropical developing countries. To generate additional scientific information, especially on the possible emergence of vaccine-derived polioviruses (VDPVs) in an IPV-only environment, we initiated an IPV introduction project in Yogyakarta, an Indonesian province. In this report, we present the coverage, immunity, and VDPV surveillance results. In Yogyakarta, we established environmental surveillance starting in 2004; and conducted routine immunization coverage and seroprevalence surveys before and after a September 2007 switch from oral poliovirus vaccine (OPV) to IPV, using standard coverage and serosurvey methods. Rates and types of polioviruses found in sewage samples were analyzed, and all poliovirus isolates after the switch were sequenced. Vaccination coverage (>95%) and immunity (approximately 100%) did not change substantially before and after the IPV switch. No VDPVs were detected. Before the switch, 58% of environmental samples contained Sabin poliovirus; starting 6 weeks after the switch, Sabin polioviruses were rarely isolated, and if they were, genetic sequencing suggested recent introductions. This project demonstrated that under almost ideal conditions (good hygiene, maintenance of universally high IPV coverage, and corresponding high immunity against polioviruses), no emergence and circulation of VDPV could be detected in a tropical developing country setting. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-03

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children Vietnamese children aged <2 years.

  10. Development of inactivated poliovirus vaccine from Sabin strains: A progress report.

    Science.gov (United States)

    Okayasu, Hiromasa; Sein, Carolyn; Hamidi, Ahd; Bakker, Wilfried A M; Sutter, Roland W

    2016-11-01

    The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in

  11. Estimated Effect of Inactivated Poliovirus Vaccine Campaigns, Nigeria and Pakistan, January 2014-April 2016.

    Science.gov (United States)

    Shirreff, George; Wadood, Mufti Zubair; Vaz, Rui Gama; Sutter, Roland W; Grassly, Nicholas C

    2017-02-01

    In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014-April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine-derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04-0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02-1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18-1.97; PR 0.45, 95% CI 0.21-0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved.

  12. Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

    Science.gov (United States)

    Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

    2016-02-25

    Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

  13. Immunogenicity and Reactogenicity of DTPa-IPV/Hib Vaccine Co-administered With Hepatitis B Vaccine for Primary and Booster Vaccination of Taiwanese Infants

    Directory of Open Access Journals (Sweden)

    Pei-Lan Shao

    2011-06-01

    Full Text Available Immunogenicity and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (Hib conjugate vaccine (DTPa-IPV/Hib, Infanrix™-IPV + Hib was assessed when co-administered with hepatitis B (HBV vaccine. Seventy healthy infants received DTPa-IPV/Hib at 1.5, 3.5, 6 and 15–18 months, and HBV at birth, 1.5, 6 and 15–18 months of age. Serological responses were assessed. Diphtheria, tetanus, Hib and pertussis seroprotection/seropositivity rates were 100% after primary vaccination. Post-primary immune responses to poliovirus could not be evaluated for technical reasons. However, after the booster dose, seroprotection/seropositivity rates, including poliovirus, were 100%. Over 95% were seroprotected against HBV. Post-booster geometric mean antibody concentrations/titers (GMC/GMTs rose from 14-fold to 45-fold, indicating effective priming against all antigens, including polioviruses. DTPa-IPV/Hib was well tolerated alone or co-administered with HBV. No serious adverse events were considered related to vaccination. Primary and booster vaccination with combined DTPa-IPV/Hib and HBV was immunogenic and well tolerated. Combination vaccines enable vaccine providers to conveniently provide routine pediatric immunizations, with minimal discomfort.

  14. Fractional-Dose Inactivated Poliovirus Vaccine Campaign - Sindh Province, Pakistan, 2016.

    Science.gov (United States)

    Pervaiz, Aslam; Mbaeyi, Chukwuma; Baig, Mirza Amir; Burman, Ashley; Ahmed, Jamal A; Akter, Sharifa; Jatoi, Fayaz A; Mahamud, Abdirahman; Asghar, Rana Jawad; Azam, Naila; Shah, Muhammad Nadeem; Laghari, Mumtaz Ali; Soomro, Kamaluddin; Wadood, Mufti Zubair; Ehrhardt, Derek; Safdar, Rana M; Farag, Noha

    2017-12-01

    Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities.

  15. Estimated Effect of Inactivated Poliovirus Vaccine Campaigns, Nigeria and Pakistan, January 2014–April 2016

    Science.gov (United States)

    Shirreff, George; Wadood, Mufti Zubair; Vaz, Rui Gama; Sutter, Roland W.

    2017-01-01

    In 2014, inactivated poliovirus vaccine (IPV) campaigns were implemented in Nigeria and Pakistan after clinical trials showed that IPV boosts intestinal immunity in children previously given oral poliovirus vaccine (OPV). We estimated the effect of these campaigns by using surveillance data collected during January 2014–April 2016. In Nigeria, campaigns with IPV and trivalent OPV (tOPV) substantially reduced the incidence of poliomyelitis caused by circulating serotype-2 vaccine–derived poliovirus (incidence rate ratio [IRR] 0.17 for 90 days after vs. 90 days before campaigns, 95% CI 0.04–0.78) and the prevalence of virus in environmental samples (prevalence ratio [PR] 0.16, 95% CI 0.02–1.33). Campaigns with tOPV alone resulted in similar reductions (IRR 0.59, 95% CI 0.18–1.97; PR 0.45, 95% CI 0.21–0.95). In Pakistan, the effect of IPV+tOPV campaigns on wild-type poliovirus was not significant. Results suggest that administration of IPV alongside OPV can decrease poliovirus transmission if high vaccine coverage is achieved. PMID:27861118

  16. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    Science.gov (United States)

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  17. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  18. CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus.

    Science.gov (United States)

    Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin

    2009-11-05

    Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.

  19. A novel multiplex poliovirus binding inhibition assay applicable for large serosurveillance and vaccine studies, without the use of live poliovirus.

    Science.gov (United States)

    Schepp, Rutger M; Berbers, Guy A M; Ferreira, José A; Reimerink, Johan H; van der Klis, Fiona R

    2017-03-01

    Large-scale serosurveillance or vaccine studies for poliovirus using the "gold standard" WHO neutralisation test (NT) are very laborious and time consuming. With the polio eradication at hand and with the removal of live attenuated Sabin strains from the oral poliovirus vaccine (OPV), starting with type 2 (as of April 2016), laboratories will need to conform to much more stringent laboratory biosafety regulations when handling live poliovirus strains. In this study, a poliovirus binding inhibition multiplex immunoassay (polio MIA) using inactivated poliovirus vaccine (IPV-Salk) was developed for simultaneous quantification of serum antibodies directed to all three poliovirus types. Our assay shows a good correlation with the NT and an excellent correlation with the ELISA-based binding inhibition assay (POBI). The assay is highly type-specific and reproducible. Additionally, serum sample throughput increases about fivefold relative to NT and POBI and the amount of serum needed is reduced by more than 90%. In conclusion, the polio MIA can be used as a safe and high throughput application, especially for large-scale surveillance and vaccine studies, reducing laboratory time and serum amounts needed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

    Science.gov (United States)

    O'Ryan, Miguel; Bandyopadhyay, Ananda S; Villena, Rodolfo; Espinoza, Mónica; Novoa, José; Weldon, William C; Oberste, M Steven; Self, Steve; Borate, Bhavesh R; Asturias, Edwin J; Clemens, Ralf; Orenstein, Walter; Jimeno, José; Rüttimann, Ricardo; Costa Clemens, Sue Ann

    2015-11-01

    Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups

  1. [The role of Sabin inactivated poliovirus vaccine in the final phase of global polio eradication].

    Science.gov (United States)

    Dong, S Z; Zhu, W B

    2016-12-06

    Global polio eradication has entered its final phase, but still faces enormous challenges. The Polio Eradication and Endgame Strategic Plan (2013-2018) set the target for making the world polio-free by 2018. Meanwhile, the World Heath Organization Global Action Plan (GAP Ⅲ) recommended that polioviruses be stored under strict conditions after eradication of the wild poliovirus. At least one dose of inactivated poliovirus vaccine (IPV) would be required for each newborn baby in the world to ensure successful completion of the final strategy and GAP Ⅲ. The Sabin IPV has a high production safety and low production cost, compared with the wild-virus IPV and, therefore, can play an important role in the final stage of global polio eradication.

  2. [The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

    Science.gov (United States)

    Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo

    2013-04-01

    To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

  3. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

    Science.gov (United States)

    Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-03-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  4. Wild and vaccine-derived poliovirus circulation, and implications for polio eradication.

    Science.gov (United States)

    Lopalco, P L

    2017-02-01

    Polio cases due to wild virus are reported by only three countries in the world. Poliovirus type 2 has been globally eradicated and the last detection of poliovirus type 3 dates to November 2012. Poliovirus type 1 remains the only circulating wild strain; between January and September 2016 it caused 26 cases (nine in Afghanistan, 14 in Pakistan, three in Nigeria). The use of oral polio vaccine (OPV) has been the key to success in the eradication effort. However, paradoxically, moving towards global polio eradication, the burden caused by vaccine-derived polioviruses (VDPVs) becomes increasingly important. In this paper circulation of both wild virus and VDPVs is reviewed and implications for the polio eradication endgame are discussed. Between April and May 2016 OPV2 cessation has been implemented globally, in a coordinated switch from trivalent OPV to bivalent OPV. In order to decrease the risk for cVDPV2 re-emergence inactivated polio vaccine (IPV) has been introduced in the routine vaccine schedule of all countries. The likelihood of re-emergence of cVDPVs should markedly decrease with time after OPV cessation, but silent circulation of polioviruses cannot be ruled out even a long time after cessation. For this reason, immunity levels against polioviruses should be kept as high as possible in the population by the use of IPV, and both clinical and environmental surveillance should be maintained at a high level.

  5. PER.C6(®) cells as a serum-free suspension cell platform for the production of high titer poliovirus: a potential low cost of goods option for world supply of inactivated poliovirus vaccine

    NARCIS (Netherlands)

    Sanders, Barbara P.; Edo-Matas, Diana; Custers, Jerome H. H. V.; Koldijk, Martin H.; Klaren, Vincent; Turk, Marije; Luitjens, Alfred; Bakker, Wilfried A. M.; Uytdehaag, Fons; Goudsmit, Jaap; Lewis, John A.; Schuitemaker, Hanneke

    2013-01-01

    There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to

  6. Comparison of serum and salivary antibodies in children vaccinated with oral live or parenteral inactivated poliovirus vaccines of different antigen concentrations.

    Science.gov (United States)

    Zaman, S; Carlsson, B; Jalil, F; Mellander, L; Van Wezel, A L; Böttiger, M; Hanson, L A

    1991-12-01

    A new antigen-rich inactivated poliovirus vaccine (IPV) in ordinary (IPV1), double (IPV2) and quadruple (IPV4) antigen concentrations was given in 2 doses to 6 and 18 week old Pakistani infants. The immune responses to poliovirus types 1 and 3 were compared to those in infants given three doses of oral poliovirus vaccine (OPV) at 6, 12 and 18 weeks of age. Enzyme-linked immunosorbent assay, ELISA, was used to estimate IgG and IgA in serum and secretory IgA (SIgA) in saliva. Two to three years later, a follow-up of the serum antibody response was carried out in the same infants using a microneutralization test. Serum IgG antibody responses to poliovirus type 1 antigen after two doses of IPV1, IPV2 and IPV4 were not significantly higher than the response after three doses of OPV at 21 weeks of age (p greater than 0.05). The serum IgG responses to poliovirus type 3 were similar to those against type 1 in all the groups. Mean neutralizing antibody titres to poliovirus type 1 was significantly higher in the IPV2 group than the rest of the groups (p less than 0.01). For type 3, these titres were highest but not significantly, in the IPV4 group (p greater than 0.05). This study shows that two doses of a new antigen-rich IPV can give similar immediate serum antibody responses as OPV but higher late responses. SIgA antibodies in saliva were more efficiently induced by OPV after three doses than after 2 doses of IPV (p less than 0.05).

  7. Phase 3 Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

    Science.gov (United States)

    Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Jiang, Shude; Li, Yanping; Mo, Zhaojun; Xia, Jielai; Xie, Zhongping; Che, Yanchun; Yang, Jingsi; Yin, Zhifang; Wang, Jianfeng; Chu, Jiayou; Cai, Wei; Zhou, Jian; Wang, Junzhi; Li, Qihan

    2016-12-01

     The development of a Sabin strain-based inactivated poliovirus vaccine (Sabin-IPV) is imperative to protecting against vaccine-associated paralytic poliomyelitis in developing countries.  In this double-blinded, parallel-group, noninferiority trial, eligible infants aged 60-90 days were randomly assigned in a ratio of 1:1 to receive either 3 doses of Sabin-IPV or Salk strain-based IPV (Salk-IPV) at 30-day intervals and a booster at the age of 18 months. Immunogenicity and safety were assessed on the basis of a protocol.  Of 1438 infants, 1200 eligible infants were recruited and received either Sabin-IPV or Salk-IPV. From the Sabin-IPV and Salk-IPV groups, 570 and 564 infants, respectively, completed the primary immunization and formed the per-protocol population. The seroconversion rates of the participants who received Sabin-IPV were 100%, 94.9%, and 99.0% (types I, II, and III, respectively), and those of the participants who received Salk-IPV were 94.7%, 91.3%, and 97.9% 1 month after the completion of primary immunization. An anamnestic response for poliovirus types I, II, and III was elicited by a booster in both groups. Except in the case of fever, other adverse events were similar between the 2 groups.  The immune response induced by Sabin-IPV was not inferior to that established with Salk-IPV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

    Science.gov (United States)

    Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

    2007-10-10

    A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

  9. Isolation of sabin-like polioviruses from wastewater in a country using inactivated polio vaccine.

    Science.gov (United States)

    Zurbriggen, Sebastian; Tobler, Kurt; Abril, Carlos; Diedrich, Sabine; Ackermann, Mathias; Pallansch, Mark A; Metzler, Alfred

    2008-09-01

    From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.

  10. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, Henrik; Samb, Badara

    2003-01-01

    Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...

  11. The Duration of Intestinal Immunity After an Inactivated Poliovirus Vaccine Booster Dose in Children Immunized With Oral Vaccine: A Randomized Controlled Trial.

    Science.gov (United States)

    John, Jacob; Giri, Sidhartha; Karthikeyan, Arun S; Lata, Dipti; Jeyapaul, Shalini; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Mani, Mohanraj; Hanusha, Janardhanan; Raman, Uma; Moses, Prabhakar D; Abraham, Asha; Bahl, Sunil; Bandyopadhyay, Ananda S; Ahmad, Mohammad; Grassly, Nicholas C; Kang, Gagandeep

    2017-02-15

    In 2014, 2 studies showed that inactivated poliovirus vaccine (IPV) boosts intestinal immunity in children previously immunized with oral poliovirus vaccine (OPV). As a result, IPV was introduced in mass campaigns to help achieve polio eradication. We conducted an open-label, randomized, controlled trial to assess the duration of the boost in intestinal immunity following a dose of IPV given to OPV-immunized children. Nine hundred healthy children in Vellore, India, aged 1-4 years were randomized (1:1:1) to receive IPV at 5 months (arm A), at enrollment (arm B), or no vaccine (arm C). The primary outcome was poliovirus shedding in stool 7 days after bivalent OPV challenge at 11 months. For children in arms A, B, and C, 284 (94.7%), 297 (99.0%), and 296 (98.7%), respectively, were eligible for primary per-protocol analysis. Poliovirus shedding 7 days after challenge was less prevalent in arms A and B compared with C (24.6%, 25.6%, and 36.4%, respectively; risk ratio 0.68 [95% confidence interval: 0.53-0.87] for A versus C, and 0.70 [0.55-0.90] for B versus C). Protection against poliovirus remained elevated 6 and 11 months after an IPV boost, although at a lower level than reported at 1 month. CTRI/2014/09/004979. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Safety and immunogenicity of inactivated poliovirus vaccine based on Sabin strains with and without aluminum hydroxide: a phase I trial in healthy adults.

    Science.gov (United States)

    Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Oberste, M Steven; Boog, Claire J; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

    2013-11-12

    An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle income countries in the context of the Global Polio Eradication Initiative. Safety and immunogenicity of the Sabin-IPV was evaluated in a double-blind, randomized, controlled, phase I 'proof-of-concept' trial. Healthy male adults received a single intramuscular injection with Sabin-IPV, Sabin-IPV adjuvanted with aluminum hydroxide or conventional IPV. Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after vaccination. No vaccine-related serious adverse events were observed, and all local and systemic reactions were mild or moderate and transient. In all subjects, an increase in antibody titer for all types of poliovirus (both Sabin and wild strains) was observed 28 days after vaccination. Sabin-IPV and Sabin-IPV adjuvanted with aluminum hydroxide administered as a booster dose were equally immunogenic and safe as conventional IPV. EudraCTnr: 2010-024581-22, NCT01708720. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

    Science.gov (United States)

    Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

    2012-10-05

    To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Stanley A. Plotkin

    2012-01-01

    Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

  15. Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.

    Science.gov (United States)

    Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai

    2017-06-03

    The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without

  16. Production of high titer attenuated poliovirus strains on the serum-free PER.C6(®) cell culture platform for the generation of safe and affordable next generation IPV.

    Science.gov (United States)

    Sanders, Barbara P; Oakes, Isabel de los Rios; van Hoek, Vladimir; Liu, Ying; Marissen, Wilfred; Minor, Philip D; Wimmer, Eckard; Schuitemaker, Hanneke; Custers, Jerome H H V; Macadam, Andrew; Cello, Jeronimo; Edo-Matas, Diana

    2015-11-27

    As poliovirus eradication draws closer, alternative Inactivated Poliovirus Vaccines (IPV) are needed to overcome the risks associated with continued use of the Oral Poliovirus Vaccine and of neurovirulent strains used during manufacture of conventional (c) IPV. We have previously demonstrated the susceptibility of the PER.C6(®) cell line to cIPV strains; here we investigated the suspension cell culture platform for growth of attenuated poliovirus strains. We examined attenuated Sabin strain productivity on the PER.C6(®) cell platform compared to the conventional Vero cell platform. The suitability of the suspension cell platform for propagation of rationally-attenuated poliovirus strains (stabilized Sabin type 3 S19 derivatives and genetically attenuated and stabilized MonoCre(X) strains), was also assessed. Yields were quantified by infectious titer determination and D-antigen ELISA using either serotype-specific polyclonal rabbit sera for Sabin strains or monoclonal cIPV-strain-specific antibodies for cIPV, S19 and MonoCre(X) strains. PER.C6(®) cells supported the replication of Sabin strains to yields of infectious titers that were in the range of cIPV strains at 32.5°C. Sabin strains achieved 30-fold higher yields (pSabin strain productivity on the PER.C6(®) cell platform was maintained at 10l scale. Yields of infectious titers of S19 and MonoCre(X) strains were 0.5-1 log10 lower than seen for cIPV strains, whereas D-antigen yield and productivities in doses/ml using rationally-attenuated strains were in line with yields reported for cIPV strains. Sabin and rationally-attenuated polioviruses can be grown to high infectious titers and D-antigen yields. Sabin strain infection shows increased productivity on the PER.C6(®) cell platform as compared to the conventional Vero cell platform. Novel cell platforms with the potential for higher yields could contribute to increased affordability of a next generation of IPV vaccines needed for achieving and

  17. The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Thompson, Kimberly M

    2016-12-01

    To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

  18. Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: a phase II, randomized, positive-controlled trial.

    Science.gov (United States)

    Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Li, Yanping; Chu, Jiayou; Jiang, Shude; Li, Qihan

    2012-01-15

    The production of Sabin inactivated poliovirus vaccine (IPV) can reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine (OPV) era. We conducted a phase II, randomized, positive-controlled trial to assess the safety and immunogenicity of Sabin IPV. The test groups (A, B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV), respectively, on the same schedule as that of groups A, B, and C. Serum samples were collected before and 30 days after the administration of the third dose. In total, 500 infants were randomly assigned to 5 groups, and 449 infants completed the vaccine series. No serious adverse events were associated with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D, and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1 poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and 98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. Sabin IPV has good safety characteristics. The seroconversion rates for type 1 poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU), and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control groups. NCT01056705.

  19. Introduction of Inactivated Poliovirus Vaccine and Impact on Vaccine-Associated Paralytic Poliomyelitis - Beijing, China, 2014-2016.

    Science.gov (United States)

    Zhao, Dan; Ma, Rui; Zhou, Tao; Yang, Fan; Wu, Jin; Sun, Hao; Liu, Fang; Lu, Li; Li, Xiaomei; Zuo, Shuyan; Yao, Wei; Yin, Jian

    2017-12-15

    When included in a sequential polio vaccination schedule, inactivated polio vaccine (IPV) reduces the risk for vaccine-associated paralytic poliomyelitis (VAPP), a rare adverse event associated with receipt of oral poliovirus vaccine (OPV). During January 2014, the World Health Organization (WHO) recommended introduction of at least 1 IPV dose into routine immunization schedules in OPV-using countries (1). The Polio Eradication and Endgame Strategic Plan 2013-2018 recommended completion of IPV introduction in 2015 and globally synchronized withdrawal of OPV type 2 in 2016 (2). Introduction of 1 dose of IPV into Beijing's Expanded Program on Immunization (EPI) on December 5, 2014 represented China's first province-wide IPV introduction. Coverage with the first dose of polio vaccine was maintained from 96.2% to 96.9%, similar to coverage with the first dose of diphtheria and tetanus toxoids and pertussis vaccine (DTP) (96.5%-97.2%); the polio vaccine dropout rate (the percentage of children who received the first dose of polio vaccine but failed to complete the series) was 1.0% in 2015 and 0.4% in 2016. The use of 3 doses of private-sector IPV per child decreased from 18.1% in 2014, to 17.4% in 2015, and to 14.8% in 2016. No cases of VAPP were identified during 2014-2016. Successful introduction of IPV into the public sector EPI program was attributed to comprehensive planning, preparation, implementation, robust surveillance for adverse events after immunization (AEFI), and monitoring of vaccination coverage. This evaluation provided information that helped contribute to the expansion of IPV use in China and in other OPV-using countries.

  20. Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba.

    Science.gov (United States)

    Resik, Sonia; Tejeda, Alina; Mach, Ondrej; Fonseca, Magile; Diaz, Manuel; Alemany, Nilda; Garcia, Gloria; Hung, Lai Heng; Martinez, Yenisleydis; Sutter, Roland

    2015-01-03

    The World Health Organization recommends that, as part of the new polio endgame, a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5th of full dose) IPV (fIPV) intradermally may reduce costs, but its administration is cumbersome with BCG needle and syringe. We evaluated performance of two newly developed intradermal-only jet injectors and compared the immune response induced by fIPV with that induced by full-dose IPV. Children between 12 and 20 months of age, who had previously received two doses of OPV, were enrolled in Camaguey, Cuba. Subjects received a single dose of IPV (either full-dose IPV intramuscularly with needle and syringe or fIPV intradermally administered with one of two new injectors or with BCG needle or a conventional needle-free injector). Serum was tested for presence of poliovirus neutralizing antibodies on day 0 (pre-IPV) and on days 3, 7 and 21 (post-vaccination). Complete data were available from 74.2% (728/981) subjects. Baseline median antibody titers were 713, 284, and 113 for poliovirus types 1, 2, and 3, respectively. Seroprevalence at study end were similar across the intervention groups (≥ 94.8%). The immune response induced with one new injector was similar to BCG needle and to the conventional injector; and superior to the other new injector. fIPV induced significantly lower boosting response compared to full-dose IPV. No safety concerns were identified. One of the two new injectors demonstrated its ability to streamline intradermal fIPV administration, however, further investigations are needed to assess the potential contribution of fIPV in the polio endgame plan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Feasibility of conducting intradermal vaccination campaign with inactivated poliovirus vaccine using Tropis intradermal needle free injection system, Karachi, Pakistan.

    Science.gov (United States)

    Yousafzai, Mohammad Tahir; Saleem, Ali Faisal; Mach, Ondrej; Baig, Attaullah; Sutter, Roland W; Zaidi, Anita K M

    2017-08-01

    Administration of intradermal fractional dose of inactivated poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its intradermal application using needle and syringe is technically difficult and requires trained personnel. We assessed feasibility of conducting an intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis needle-free injector. During the one-day fIPV campaign, we measured average "application time" to administer fIPV with Tropis, collected ergonomic information and measured vaccine wastage. Eleven vaccinator teams, after two-day training, immunized 582 children between 4 months and 5 years of age. Average "application time" ranged from 35-75 seconds; the "application time" decreased with the number of children vaccinated from 68 to 38 seconds between 1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11 (9%) assessed that it was not easy to remove air bubbles when filling the device. There was 0% vaccine loss reported. No adverse events following immunizations were reported. We demonstrated that it is feasible, safe and efficient to use Tropis for the administration of fIPV in a campaign setting.

  2. Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes.

    Science.gov (United States)

    Chan, Hui-Ting; Xiao, Yuhong; Weldon, William C; Oberste, Steven M; Chumakov, Konstantin; Daniell, Henry

    2016-11-01

    The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low-cost cold chain-free plant-made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50-fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant-derived adjuvants after single priming with IPV significantly increased VP1-IgG1 and VP1-IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (~3.17-10.17 log 2 titre) and seropositivity (70-90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant-cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA-approved antigens and adjuvants are discussed. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  3. Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

    Science.gov (United States)

    Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

    2013-07-15

    Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

  4. Comparison of IPV to tOPV week 39 boost of primary OPV vaccination in Indian infants: an open labelled randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Suman Kanungo

    2017-01-01

    Conclusions: This study indicates that an IPV boost at week 39 is equivalent to tOPV in intestinal immunity, and provides higher seroconversion compared to tOPV. The major limitation of the study was the additional OPV doses receive by infants during pulse polio immunization resulted in additional mucosal boosting, diminishing the impact of IPV or tOPV boost at week 39. However, IPV for OPV boost should prove to be a step forward in the global polio eradication initiative to reduce the problem of circulating vaccine-derived poliovirus (cVDPV.

  5. Update on vaccine-derived polioviruses - worldwide, July 2012-December 2013.

    Science.gov (United States)

    Diop, Ousmane M; Burns, Cara C; Wassilak, Steven G; Kew, Olen M

    2014-03-21

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population

  6. Immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine in infants: a comparative, observer-blind, randomised, controlled trial.

    Science.gov (United States)

    Sáez-Llorens, Xavier; Clemens, Ralf; Leroux-Roels, Geert; Jimeno, José; Clemens, Sue Ann Costa; Weldon, William C; Oberste, M Steven; Molina, Natanael; Bandyopadhyay, Ananda S

    2016-03-01

    Following the proposed worldwide switch from trivalent oral poliovirus vaccine (tOPV) to bivalent types 1 and 3 OPV (bOPV) in 2016, inactivated poliovirus vaccine (IPV) will be the only source of protection against poliovirus type 2. With most countries opting for one dose of IPV in routine immunisation schedules during this transition because of cost and manufacturing constraints, optimisation of protection against all poliovirus types will be a priority of the global eradication programme. We assessed the immunogenicity and safety of a novel monovalent high-dose inactivated poliovirus type 2 vaccine (mIPV2HD) in infants. This observer-blind, comparative, randomised controlled trial was done in a single centre in Panama. We enrolled healthy infants who had not received any previous vaccination against poliovirus. Infants were randomly assigned (1:1) by computer-generated randomisation sequence to receive a single dose of either mIPV2HD or standard trivalent IPV given concurrently with a third dose of bOPV at 14 weeks of age. At 18 weeks, all infants were challenged with one dose of monovalent type 2 OPV (mOPV2). Primary endpoints were seroconversion and median antibody titres to type 2 poliovirus 4 weeks after vaccination with mIPV2HD or IPV; and safety (as determined by the proportion and nature of serious adverse events and important medical events for 8 weeks after vaccination). The primary immunogenicity analyses included all participants for whom a post-vaccination blood sample was available. All randomised participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02111135. Between April 14 and May 9, 2014, 233 children were enrolled and randomly assigned to receive mIPV2HD (117 infants) or IPV (116 infants). 4 weeks after vaccination with mIPV2HD or IPV, seroconversion to poliovirus type 2 was recorded in 107 (93·0%, 95% CI 86·8-96·9) of 115 infants in the mIPV2HD group compared with 86 (74·8%, 65·8

  7. Rare adverse events associated with oral poliovirus vaccine in Brazil

    Directory of Open Access Journals (Sweden)

    Friedrich F.

    1997-01-01

    Full Text Available Oral poliovirus vaccine (OPV developed by A. Sabin has been effectively used to control poliomyelitis in Brazil, and the last case with the isolation of a wild poliovirus strain occurred in March 1989. Although the vaccine controlled the circulation of wild strains and poliomyelitis cases associated with these strains were not detected during the last eight years, rare cases classified as vaccine-associated paralytic poliomyelitis (VAPP have been detected. Molecular characterization studies of poliovirus strains isolated from VAPP cases and from healthy contacts have confirmed that the isolates are derived from the Sabin vaccine strains and also detected genomic modifications known or suspected to increase neurovirulence such as mutations and recombination. The molecular characterization of polioviruses isolated during the last eight years from paralysis cases classified as Guillain-Barré (GBS syndrome and transverse myelitits (TM, and from facial paralysis (FP cases also confirmed the vaccine origin of the strains and demonstrated mutations known to increase neurovirulence. Analysis of the epidemiologic data of these GBS, TM and FP cases demonstrated that in most of them the last OPV dose was given months or years before the onset of the disease and the isolation of the polioviruses. The temporal association between the isolation of these strains and the GBS, TM and FP suggested that the Sabin vaccine-derived poliovirus strains could also rarely trigger the diseases.

  8. Detection of Emerging Vaccine-Related Polioviruses by Deep Sequencing.

    Science.gov (United States)

    Sahoo, Malaya K; Holubar, Marisa; Huang, ChunHong; Mohamed-Hadley, Alisha; Liu, Yuanyuan; Waggoner, Jesse J; Troy, Stephanie B; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia; Maldonado, Yvonne; Pinsky, Benjamin A

    2017-07-01

    Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication. Copyright © 2017 Sahoo et al.

  9. Introduction of inactivated poliovirus vaccine leading into the polio eradication endgame strategic plan; Hangzhou, China, 2010-2014.

    Science.gov (United States)

    Liu, Yan; Wang, Jun; Liu, Shijun; Du, Jian; Wang, Liang; Gu, Wenwen; Xu, Yuyang; Zuo, Shuyan; Xu, Erping; An, Zhijie

    2017-03-01

    China's Expanded Program on Immunization (EPI) has provided 4 doses of oral poliovirus vaccine (OPV) since the 1970s. Inactivated poliovirus vaccine (IPV) became available in 2010 in Hangzhou as a private-sector, parent-chosen alternative to OPV. In 2015, WHO recommended that countries with all-OPV vaccination schedules introduce at least one dose of IPV, to mitigate risk associated with the withdrawal of type 2 OPV. We analyzed polio vaccine coverage and utilization in Hangzhou to determine patterns of IPV use and the occurrence of vaccine-associated paralytic polio (VAPP) in the various patterns identified. Children born between 2010 and 2014 and registered in Hangzhou's Immunization Information System (HZIIS) were included. VAPP cases were detected through the acute flaccid paralysis surveillance system. We used descriptive epidemiological methods to determine IPV and OPV usage patterns and VAPP occurrence. HZIIS data from 566,894 children were analyzed. Coverage levels of polio vaccine were greater than 92% for each birth cohort. Percentages of children using OPV-only, IPV-only, and IPV/OPV sequential schedules were 70.57%, 27.01% and 2.41%, respectively. IPV-only schedule utilization increased by birth cohort regardless of geographical area or whether the child was locally-born. The highest use of an all-IPV schedule (79.85%) was among urban, locally-born children in the 2014 birth cohort. Five VAPP cases were identified during the study years; all cases occurred following the first polio vaccine dose, which was always OPV for the cases. Type 2 vaccine virus was isolated from 2 VAPP cases, and type 2 and type 3 vaccine virus was isolated from one VAPP case. The incidence of VAPP in the 2010-2014 birth cohorts was 3.76 per 1million doses of OPV. Children in Hangzhou had high polio vaccination coverage. IPV-only schedule use increased by year, and was highest in urban areas among locally-born children. All cases of VAPP were associated with the first dose of OPV

  10. Combined use of inactivated and oral poliovirus vaccines in refugee camps and surrounding communities - Kenya, December 2013.

    Science.gov (United States)

    Sheikh, Mohamed A; Makokha, Frederick; Hussein, Abdullahi M; Mohamed, Gedi; Mach, Ondrej; Humayun, Kabir; Okiror, Samuel; Abrar, Leila; Nasibov, Orkhan; Burton, John; Unshur, Ahmed; Wannemuehler, Kathleen; Estivariz, Concepcion F

    2014-03-21

    Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus (WPV) has continued without interruption in only three countries: Afghanistan, Nigeria, and Pakistan. During April-December 2013, a polio outbreak caused by WPV type 1 (WPV1) of Nigerian origin resulted in 217 cases in or near the Horn of Africa, including 194 cases in Somalia, 14 cases in Kenya, and nine cases in Ethiopia (all cases were reported as of March 10, 2014). During December 14-18, 2013, Kenya conducted the first-ever campaign providing inactivated poliovirus vaccine (IPV) together with oral poliovirus vaccine (OPV) as part of its outbreak response. The campaign targeted 126,000 children aged ≤59 months who resided in Somali refugee camps and surrounding communities near the Kenya-Somalia border, where most WPV1 cases had been reported, with the aim of increasing population immunity levels to ensure interruption of any residual WPV transmission and prevent spread from potential new importations. A campaign evaluation and vaccination coverage survey demonstrated that combined administration of IPV and OPV in a mass campaign is feasible and can achieve coverage >90%, although combined IPV and OPV campaigns come at a higher cost than OPV-only campaigns and require particular attention to vaccinator training and supervision. Future operational studies could assess the impact on population immunity and the cost-effectiveness of combined IPV and OPV campaigns to accelerate interruption of poliovirus transmission during polio outbreaks and in certain areas in which WPV circulation is endemic.

  11. A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-, 5- and 11- to 12-month Schedule.

    Science.gov (United States)

    Vesikari, Timo; Silfverdal, Sven-Arne; Jordanov, Emilia; Feroldi, Emmanuel

    2017-01-01

    To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age. Phase III, randomized, active-controlled, observer-blind, multicenter study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRP~T: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP~T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP~T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated. These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

  12. Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

    Science.gov (United States)

    Okayasu, Hiromasa; Sein, Carolyn; Chang Blanc, Diana; Gonzalez, Alejandro Ramirez; Zehrung, Darin; Jarrahian, Courtney; Macklin, Grace; Sutter, Roland W

    2017-07-01

    A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  13. Environmental Isolation of Circulating Vaccine-Derived Poliovirus After Interruption of Wild Poliovirus Transmission - Nigeria, 2016.

    Science.gov (United States)

    Etsano, Andrew; Damisa, Eunice; Shuaib, Faisal; Nganda, Gatei Wa; Enemaku, Ogu; Usman, Samuel; Adeniji, Adekunle; Jorba, Jaume; Iber, Jane; Ohuabunwo, Chima; Nnadi, Chimeremma; Wiesen, Eric

    2016-08-05

    In September 2015, more than 1 year after reporting its last wild poliovirus (WPV) case in July 2014 (1), Nigeria was removed from the list of countries with endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only remaining countries with endemic WPV. However, on April 29, 2016, a laboratory-confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was reported from an environmental sample collected in March from a sewage effluent site in Maiduguri Municipal Council, Borno State, a security-compromised area in northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the potential to cause paralysis and can circulate in areas with low population immunity. The Nigeria National Polio Emergency Operations Center initiated emergency response activities, including administration of at least 2 doses of oral poliovirus vaccine (OPV) to all children aged <5 years through mass campaigns; retroactive searches for missed cases of acute flaccid paralysis (AFP), and enhanced environmental surveillance. Approximately 1 million children were vaccinated in the first OPV round. Thirteen previously unreported AFP cases were identified. Enhanced environmental surveillance has not resulted in detection of additional VDPV isolates. The detection of persistent circulation of VDPV2 in Borno State highlights the low population immunity, surveillance limitations, and risk for international spread of cVDPVs associated with insurgency-related insecurity. Increasing vaccination coverage with additional targeted supplemental immunization activities and reestablishment of effective routine immunization activities in newly secured and difficult-to-reach areas in Borno is urgently needed.

  14. A novel multiplex poliovirus binding inhibition assay applicable for large serosurveillance and vaccine studies, without the use of live poliovirus.

    NARCIS (Netherlands)

    Schepp, Rutger M; Berbers, Guy A M; Ferreira, José A; Reimerink, Johan H; van der Klis, Fiona R

    2017-01-01

    Large-scale serosurveillance or vaccine studies for poliovirus using the "gold standard" WHO neutralisation test (NT) are very laborious and time consuming. With the polio eradication at hand and with the removal of live attenuated Sabin strains from the oral poliovirus vaccine (OPV), starting with

  15. Immunogenicity of type 2 monovalent oral and inactivated poliovirus vaccines for type 2 poliovirus outbreak response: an open-label, randomised controlled trial.

    Science.gov (United States)

    Zaman, Khalequ; Estívariz, Concepción F; Morales, Michelle; Yunus, Mohammad; Snider, Cynthia J; Gary, Howard E; Weldon, William C; Oberste, M Steven; Wassilak, Steven G; Pallansch, Mark A; Anand, Abhijeet

    2018-03-20

    Monovalent type 2 oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV) are used to respond to type 2 poliovirus outbreaks. We aimed to assess the effect of two mOPV2 doses on the type 2 immune response by varying the time interval between mOPV2 doses and IPV co-administration with mOPV2. We did a randomised, controlled, parallel, open-label, non-inferiority, inequality trial at two study clinics in Dhaka, Bangladesh. Healthy infants aged 6 weeks (42-48 days) at enrolment were randomly assigned (1:1:1:1) to receive two mOPV2 doses (each dose consisting of two drops [0·1 mL in total] of about 10 5 50% cell culture infectious dose of type 2 Sabin strain) at intervals of 1 week, 2 weeks, 4 weeks (standard or control group), or 4 weeks with IPV (0·5 mL of type 1 [Mahoney, 40 D-antigen units], type 2 [MEF-1, 8 D-antigen units], and type 3 [Saukett, 32 D-antigen units]) administered intramuscularly with the first mOPV2 dose. We used block randomisation, randomly selecting blocks of sizes four, eight, 12, or 16 stratified by study sites. We concealed randomisation assignment from staff managing participants in opaque, sequentially numbered, sealed envelopes. Parents and clinic staff were unmasked to assignment after the randomisation envelope was opened. Laboratory staff analysing sera were masked to assignment, but investigators analysing data and assessing outcomes were not. The primary outcome was type 2 immune response measured 4 weeks after mOPV2 administration. The primary modified intention-to-treat analysis included participants with testable serum samples before and after vaccination. A non-inferiority margin of 10% and p=0·05 (one-tailed) was used. This trial is registered at ClinicalTrials.gov, number NCT02643368, and is closed to accrual. Between Dec 7, 2015, and Jan 5, 2016, we randomly assigned 760 infants to receive two mOPV2 doses at intervals of 1 week (n=191), 2 weeks (n=191), 4 weeks (n=188), or 4 weeks plus IPV (n=190). Immune

  16. Modeling the dynamics of oral poliovirus vaccine cessation.

    Science.gov (United States)

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2014-11-01

    Oral poliovirus vaccine (OPV) results in an ongoing burden of poliomyelitis due to vaccine-associated paralytic poliomyelitis and circulating vaccine-derived polioviruses (cVDPVs). This motivates globally coordinated OPV cessation after wild poliovirus eradication. We modeled poliovirus transmission and OPV evolution to characterize the interaction between population immunity, OPV-related virus prevalence, and the emergence of cVDPVs after OPV cessation. We explored strategies to prevent and manage cVDPVs for countries that currently use OPV for immunization and characterized cVDPV emergence risks and OPV use for outbreak response. Continued intense supplemental immunization activities until OPV cessation represent the best strategy to prevent cVDPV emergence after OPV cessation in areas with insufficient routine immunization coverage. Policy makers must actively manage population immunity before OPV cessation to prevent cVDPVs and aggressively respond if prevention fails. Sufficiently aggressive response with OPV to interrupt transmission of the cVDPV outbreak virus will lead to die-out of OPV-related viruses used for response in the outbreak population. Further analyses should consider the risk of exportation to other populations of the outbreak virus and any OPV used for outbreak response. OPV cessation can successfully eliminate all circulating live polioviruses in a population. The polio end game requires active risk management. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.

    Science.gov (United States)

    Clarke, Ed; Saidu, Yauba; Adetifa, Jane U; Adigweme, Ikechukwu; Hydara, Mariama Badjie; Bashorun, Adedapo O; Moneke-Anyanwoke, Ngozi; Umesi, Ama; Roberts, Elishia; Cham, Pa Modou; Okoye, Michael E; Brown, Kevin E; Niedrig, Matthias; Chowdhury, Panchali Roy; Clemens, Ralf; Bandyopadhyay, Ananda S; Mueller, Jenny; Jeffries, David J; Kampmann, Beate

    2016-08-01

    The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7

  18. Comprehensive screening for immunodeficiency-associated vaccine-derived poliovirus: an essential oral poliovirus vaccine cessation risk management strategy.

    Science.gov (United States)

    Duintjer Tebbens, R J; Thompson, K M

    2017-01-01

    If the world can successfully control all outbreaks of circulating vaccine-derived poliovirus that may occur soon after global oral poliovirus vaccine (OPV) cessation, then immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) from rare and mostly asymptomatic long-term excretors (defined as ⩾6 months of excretion) will become the main source of potential poliovirus outbreaks for as long as iVDPV excretion continues. Using existing models of global iVDPV prevalence and global long-term poliovirus risk management, we explore the implications of uncertainties related to iVDPV risks, including the ability to identify asymptomatic iVDPV excretors to treat with polio antiviral drugs (PAVDs) and the transmissibility of iVDPVs. The expected benefits of expanded screening to identify and treat long-term iVDPV excretors with PAVDs range from US$0.7 to 1.5 billion with the identification of 25-90% of asymptomatic long-term iVDPV excretors, respectively. However, these estimates depend strongly on assumptions about the transmissibility of iVDPVs and model inputs affecting the global iVDPV prevalence. For example, the expected benefits may decrease to as low as US$260 million with the identification of 90% of asymptomatic iVDPV excretors if iVDPVs behave and transmit like partially reverted viruses instead of fully reverted viruses. Comprehensive screening for iVDPVs will reduce uncertainties and maximize the expected benefits of PAVD use.

  19. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication.

    Science.gov (United States)

    Minor, Philip D

    2016-01-01

    Poliomyelitis is caused by poliovirus, which is a positive strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confined to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organisation. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.

  20. A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

    Science.gov (United States)

    López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

    2017-11-01

    Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

  1. Update on Vaccine-Derived Polioviruses - Worldwide, January 2014-March 2015.

    Science.gov (United States)

    Diop, Ousmane M; Burns, Cara C; Sutter, Roland W; Wassilak, Steven G; Kew, Olen M

    2015-06-19

    six countries were found to excrete iVDPVs, and a patient in the United Kingdom was still excreting iVDPV2 in 2014 after more than 28 years. Ambiguous VDPVs were found among immunocompetent persons and environmental samples in 16 countries. Because the large majority of VDPV case-isolates are type 2, WHO has developed a plan for coordinated worldwide withdrawal of trivalent (types 1, 2, and 3) OPV (tOPV) and replacement with bivalent (types 1 and 3) OPV (bOPV) in April 2016, preceded by introduction of at least 1 dose of injectable inactivated poliovirus vaccine (IPV) into routine immunization schedules worldwide to maintain immunity to type 2 viruses.

  2. Poliovirus-specific memory immunity in seronegative elderly people does not protect against virus excretion.

    NARCIS (Netherlands)

    Abbink, Frithjofna; Buisman, Anne M; Doornbos, Gerda; Woldman, Jan; Kimman, Tjeerd G; Conyn- van Spaendonck, Marina A E

    2005-01-01

    BACKGROUND: Dutch people born between 1925 and 1945 were ineligible for vaccination with the inactivated poliovirus vaccine (IPV) introduced in 1957 and may have escaped natural infection because of reduced poliovirus circulation. We examined whether people with low or undetectable antibody levels

  3. Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine.

    OpenAIRE

    Bouchard, M J; Lam, D H; Racaniello, V R

    1995-01-01

    To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of the genome that conferred reduced neurovirulence. Exchange of smaller restriction fragments and sit...

  4. Immunogenicity and safety of three aluminium hydroxide adjuvanted vaccines with reduced doses of inactivated polio vaccine (IPV-Al) compared with standard IPV in young infants in the Dominican Republic: a phase 2, non-inferiority, observer-blinded, randomised, and controlled dose investigation trial.

    Science.gov (United States)

    Rivera, Luis; Pedersen, Rasmus S; Peña, Lourdes; Olsen, Klaus J; Andreasen, Lars V; Kromann, Ingrid; Nielsen, Pernille I; Sørensen, Charlotte; Dietrich, Jes; Bandyopadhyay, Ananda S; Thierry-Carstensen, Birgit

    2017-07-01

    Cost and supply constraints are key challenges in the use of inactivated polio vaccine (IPV). Dose reduction through adsorption to aluminium hydroxide (Al) is a promising option, and establishing its effectiveness in the target population is a crucial milestone in developing IPV-Al. The aim of this clinical trial was to show the non-inferiority of three IPV-Al vaccines to standard IPV. In this phase 2, non-inferiority, observer-blinded, randomised, controlled, single-centre trial in the Dominican Republic, healthy infants aged 6 weeks, not previously polio vaccinated, were allocated after computer-generated randomisation by block-size of four, to receive one of four IPV formulations (three-times reduced dose [1/3 IPV-Al], five-times reduced dose [1/5 IPV-Al], ten-times reduced dose [1/10 IPV-Al], or IPV) intramuscularly in the thigh at 6, 10, and 14 weeks of age. The primary outcome was seroconversion for poliovirus types 1, 2, and 3 with titres more than or equal to four-fold higher than the estimated maternal antibody titre and more than or equal to 8 after three vaccinations. Non-inferiority was concluded if the lower two-sided 90% CI of the seroconversion rate difference between IPV-Al and IPV was greater than -10%. The safety analyses were based on the safety analysis set (randomly assigned participants who received at least one trial vaccination) and the immunogenicity analyses were based on the per-protocol population. This study is registered with ClinicalTrials.gov registration, number NCT02347423. Between Feb 2, 2015, and Sept 26, 2015, we recruited 824 infants. The per-protocol population included 820 infants; 205 were randomly assigned to receive 1/3 IPV-Al, 205 to receive 1/5 IPV-Al, 204 to receive 1/10 IPV-Al, and 206 to receive IPV. The proportion of individuals meeting the primary endpoint of seroconversion for poliovirus types 1, 2, and 3 was already high for the three IPV-Al vaccines after two vaccinations, but was higher after three vaccinations

  5. Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.

    Science.gov (United States)

    Wright, Peter F; Connor, Ruth I; Wieland-Alter, Wendy F; Hoen, Anne G; Boesch, Austin W; Ackerman, Margaret E; Oberste, M Steven; Gast, Chris; Brickley, Elizabeth B; Asturias, Edwin J; Rüttimann, Ricardo; Bandyopadhyay, Ananda S

    2016-12-01

    Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools. In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants. 210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV-IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2

  6. High resolution identity testing of inactivated poliovirus vaccines.

    Science.gov (United States)

    Mee, Edward T; Minor, Philip D; Martin, Javier

    2015-07-09

    Definitive identification of poliovirus strains in vaccines is essential for quality control, particularly where multiple wild-type and Sabin strains are produced in the same facility. Sequence-based identification provides the ultimate in identity testing and would offer several advantages over serological methods. We employed random RT-PCR and high throughput sequencing to recover full-length genome sequences from monovalent and trivalent poliovirus vaccine products at various stages of the manufacturing process. All expected strains were detected in previously characterised products and the method permitted identification of strains comprising as little as 0.1% of sequence reads. Highly similar Mahoney and Sabin 1 strains were readily discriminated on the basis of specific variant positions. Analysis of a product known to contain incorrect strains demonstrated that the method correctly identified the contaminants. Random RT-PCR and shotgun sequencing provided high resolution identification of vaccine components. In addition to the recovery of full-length genome sequences, the method could also be easily adapted to the characterisation of minor variant frequencies and distinction of closely related products on the basis of distinguishing consensus and low frequency polymorphisms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico

    Science.gov (United States)

    Ferreyra-Reyes, Leticia; Cruz-Hervert, Luis Pablo; Troy, Stephanie B.; Huang, ChunHong; Sarnquist, Clea; Delgado-Sánchez, Guadalupe; Canizales-Quintero, Sergio; Holubar, Marisa; Ferreira-Guerrero, Elizabeth; Montero-Campos, Rogelio; Rodríguez-Álvarez, Mauricio; Mongua-Rodriguez, Norma; Maldonado, Yvonne

    2017-01-01

    Background Mexico introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV) twice a year during national health weeks (NHW) through 2015. Objectives To evaluate individual variables associated with poliovirus (PV) shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts. Materials and methods We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV) and 144 household contacts (both genders, 2 per household, children and adults) between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment). We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR) assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR. Analysis We estimated adjusted hazard ratios (HR) and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection. Results 216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142); PV1 in 1.2% (n = 29), PV2 in 4.1% (n = 103), and PV3 in 1.9% (n = 48). Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42), PV2 in 21.09% (n = 54), and PV3 in 23.05% (n = 59). Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with

  8. Assessing the individual risk of fecal poliovirus shedding among vaccinated and non-vaccinated subjects following national health weeks in Mexico.

    Directory of Open Access Journals (Sweden)

    Leticia Ferreyra-Reyes

    Full Text Available Mexico introduced inactivated polio vaccine (IPV into its routine immunization (RI schedule in 2007 but continued to give trivalent oral polio vaccine (tOPV twice a year during national health weeks (NHW through 2015.To evaluate individual variables associated with poliovirus (PV shedding among children with IPV-induced immunity after vaccination with tOPV and their household contacts.We recruited 72 children (both genders, ≤30 months, vaccinated with at least two doses of IPV and 144 household contacts (both genders, 2 per household, children and adults between 08/2010 and 09/2010 in Orizaba, Veracruz. Three NHW took place (one before and two after enrollment. We collected fecal samples monthly for 12 months, and tested 2500 samples for polioviruses types 1, 2 and 3 with three serotype-specific singleplex real-time RT-PCR (rRT-PCR assays. In order to increase the specificity for OPV virus, all positive and 112 negative samples were also processed with a two-step, OPV serotype-specific multiplex rRT-PCR.We estimated adjusted hazard ratios (HR and 95% CI using Cox proportional hazards regression for recurrent events models accounting for individual clustering to assess the association of individual variables with the shedding of any poliovirus for all participants and stratifying according to whether the participant had received tOPV in the month of sample collection.216 participants were included. Of the 2500 collected samples, using the singleplex rRT-PCR assay, PV was detected in 5.7% (n = 142; PV1 in 1.2% (n = 29, PV2 in 4.1% (n = 103, and PV3 in 1.9% (n = 48. Of the 256 samples processed by multiplex rRT-PCR, PV was detected in 106 (PV1 in 16.41% (n = 42, PV2 in 21.09% (n = 54, and PV3 in 23.05% (n = 59. Both using singleplex and multiplex assays, shedding of OPV among non-vaccinated children and subjects older than 5 years of age living in the same household was associated with shedding of PV2 by a household contact. All models were

  9. Virologic Monitoring of Poliovirus Type 2 after Oral Poliovirus Vaccine Type 2 Withdrawal in April 2016 - Worldwide, 2016-2017.

    Science.gov (United States)

    Diop, Ousmane M; Asghar, Humayun; Gavrilin, Evgeniy; Moeletsi, Nicksy Gumede; Benito, Gloria Rey; Paladin, Fem; Pattamadilok, Sirima; Zhang, Yan; Goel, Ajay; Quddus, Arshad

    2017-05-26

    The Global Polio Eradication Initiative (GPEI) has made substantial progress since its launch in 1988; only 37 wild poliovirus type 1 (WPV1) cases were detected in 2016, the lowest annual count ever. Wild poliovirus type 3 has not been detected since November 2012, and wild poliovirus type 2 was officially declared eradicated in September 2015. This success is attributable to the wide use of live oral poliovirus vaccines (OPVs). Since 2001, numerous outbreaks were caused by the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (1). In 2015, circulating VDPV type 2 (cVDPV2) outbreaks were detected in five countries worldwide (Nigeria, Pakistan, Guinea, Burma, and South Sudan), and VDPV2 single events were reported in 22 countries. These events prompted the GPEI to withdraw the type 2 component (Sabin2) of trivalent OPV (tOPV) in a globally coordinated, synchronized manner in April 2016 (2,3), at which time all OPV-using countries switched to using bivalent OPV (bOPV), containing Sabin types 1 and 3. This report details for the first time the virologic tracking of elimination of a live vaccine that has been withdrawn from routine and mass immunization systems worldwide (3). To secure elimination, further monitoring is warranted to detect any use of tOPV or monovalent OPV type 2 (mOPV2).

  10. The differential impact of oral poliovirus vaccine formulation choices on serotype-specific population immunity to poliovirus transmission.

    Science.gov (United States)

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2015-09-17

    Prior analyses demonstrated the need for some countries and the Global Polio Eradication Initiative (GPEI) to conduct additional supplemental immunization activities (SIAs) with trivalent oral poliovirus vaccine (tOPV) prior to globally-coordinated cessation of all serotype 2-containing OPV (OPV2 cessation) to prevent the creation of serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreaks after OPV2 cessation. The GPEI continues to focus on achieving and ensuring interruption of wild poliovirus serotype 1 (WPV1) and making vaccine choices that prioritize bivalent OPV (bOPV) for SIAs, nominally to increase population immunity to serotype 1, despite an aggressive timeline for OPV2 cessation. We use an existing dynamic poliovirus transmission model of northwest Nigeria and an integrated global model for long-term poliovirus risk management to explore the impact of tOPV vs. bOPV vaccine choices on population immunity and cVDPV2 risks. Using tOPV instead of bOPV for SIAs leads to a minimal decrease in population immunity to transmission of serotypes 1 and 3 polioviruses, but a significantly higher population immunity to transmission of serotype 2 polioviruses. Failure to use tOPV in enough SIAs results in cVDPV2 emergence after OPV2 cessation in both the northwest Nigeria model and the global model. Despite perceptions to the contrary, prioritizing the use of bOPV over tOPV prior to OPV2 cessation does not significantly improve serotype 1 population immunity to transmission. Immunization leaders need to focus on all three poliovirus serotypes to appropriately manage the risks of OPV cessation in the polio endgame. Focusing on population immunity to transmission to interrupt WPV1 transmission and manage pre-OPV cessation risks of cVDPVs, all countries performing poliovirus SIAs should use tOPV up until the time of OPV2 cessation, after which time they should continue to use the OPV vaccine formulation with all remaining serotypes until coordinated global

  11. Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

    Science.gov (United States)

    Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L

    2014-08-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing.

  12. Implementation of coordinated global serotype 2 oral poliovirus vaccine cessation: risks of inadvertent trivalent oral poliovirus vaccine use.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Hampton, Lee M; Thompson, Kimberly M

    2016-06-01

    The endgame for polio eradication includes coordinated global cessation of oral poliovirus vaccine (OPV), starting with the cessation of vaccine containing OPV serotype 2 (OPV2) by switching all trivalent OPV (tOPV) to bivalent OPV (bOPV). The logistics associated with this global switch represent a significant undertaking, with some possibility of inadvertent tOPV use after the switch. We used a previously developed poliovirus transmission and OPV evolution model to explore the relationships between the extent of inadvertent tOPV use, the time after the switch of the inadvertent tOPV use and corresponding population immunity to serotype 2 poliovirus transmission, and the ability of the inadvertently introduced viruses to cause a serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreak in a hypothetical population. We then estimated the minimum time until inadvertent tOPV use in a supplemental immunization activity (SIA) or in routine immunization (RI) can lead to a cVDPV2 outbreak in realistic populations with properties like those of northern India, northern Pakistan and Afghanistan, northern Nigeria, and Ukraine. At low levels of inadvertent tOPV use, the minimum time after the switch for the inadvertent use to cause a cVDPV2 outbreak decreases sharply with increasing proportions of children inadvertently receiving tOPV. The minimum times until inadvertent tOPV use in an SIA or in RI can lead to a cVDPV2 outbreak varies widely among populations, with higher basic reproduction numbers, lower tOPV-induced population immunity to serotype 2 poliovirus transmission prior to the switch, and a lower proportion of transmission occurring via the oropharyngeal route all resulting in shorter times. In populations with the lowest expected immunity to serotype 2 poliovirus transmission after the switch, inadvertent tOPV use in an SIA leads to a cVDPV2 outbreak if it occurs as soon as 9 months after the switch with 0.5 % of children aged 0-4 years inadvertently

  13. Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa

    Science.gov (United States)

    Vesikari, Timo; Rivera, Luis; Korhonen, Tiina; Ahonen, Anitta; Cheuvart, Brigitte; Hezareh, Marjan; Janssens, Winnie; Mesaros, Narcisa

    2017-01-01

    ABSTRACT Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12–15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1–3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued. PMID:28340322

  14. Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

    Science.gov (United States)

    Melo, Flor Irene Rodriguez; Morales, José Juan Renteria; De Los Santos, Abiel Homero Mascareñas; Rivas, Enrique; Vigne, Claire; Noriega, Fernando

    2017-06-01

    The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

  15. [Genetic recombination in vaccine poliovirus: comparative study in strains excreted in course of vaccination by oral poliovirus vaccine and circulating strains].

    Science.gov (United States)

    Haddad-Boubaker, S; Ould-Mohamed-Abdallah, M V; Ben-Yahia, A; Triki, H

    2010-12-01

    Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility. This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing. Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose. These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  16. Modeling options to manage type 1 wild poliovirus imported into Israel in 2013.

    Science.gov (United States)

    Kalkowska, Dominika A; Duintjer Tebbens, Radboud J; Grotto, Itamar; Shulman, Lester M; Anis, Emilia; Wassilak, Steven G F; Pallansch, Mark A; Thompson, Kimberly M

    2015-06-01

    After 25 years without poliomyelitis cases caused by circulating wild poliovirus (WPV) in Israel, sewage sampling detected WPV type 1 (WPV1) in April 2013, despite high vaccination coverage with only inactivated poliovirus vaccine (IPV) since 2005. We used a differential equation-based model to simulate the dynamics of poliovirus transmission and population immunity in Israel due to past exposure to WPV and use of oral poliovirus vaccine (OPV) in addition to IPV. We explored the influences of various immunization options to stop imported WPV1 circulation in Israel. We successfully modeled the potential for WPVs to circulate without detected cases in Israel. Maintaining a sequential IPV/OPV schedule instead of switching to an IPV-only schedule in 2005 would have kept population immunity high enough in Israel to prevent WPV1 circulation. The Israeli response to WPV1 detection prevented paralytic cases; a more rapid response might have interrupted transmission more quickly. IPV-based protection alone might not provide sufficient population immunity to prevent poliovirus transmission after an importation. As countries transition to IPV in immunization schedules, they may need to actively manage population immunity and consider continued use of OPV, to avoid the potential circulation of imported live polioviruses before globally coordinated cessation of OPV use. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.

    Science.gov (United States)

    Sun, Yuelian; Christensen, Jakob; Hviid, Anders; Li, Jiong; Vedsted, Peter; Olsen, Jørn; Vestergaard, Mogens

    2012-02-22

    Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. A population-based cohort study of 378,834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort. Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study. A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000 person-days), 32 children after the second (1.3 per 100,000 person-days), and 201 children after the third (8.5 per 100,000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100,000 person-days), 12

  18. Genetic analysis and characterization of wild poliovirus type 1 during sustained transmission in a population with >95% vaccine coverage, Israel 2013.

    Science.gov (United States)

    Shulman, Lester M; Martin, Javier; Sofer, Danit; Burns, Cara C; Manor, Yossi; Hindiyeh, Musa; Gavrilin, Eugene; Wilton, Thomas; Moran-Gilad, Jacob; Gamzo, Ronni; Mendelson, Ella; Grotto, Itamar

    2015-04-01

    Israel has >95% polio vaccine coverage with the last 9 birth cohorts immunized exclusively with inactivated polio vaccine (IPV). Using acute flaccid paralysis and routine, monthly countrywide environmental surveillance, no wild poliovirus circulation was detected between 1989 and February 2013, after which wild type 1 polioviruses South Asia genotype (WPV1-SOAS) have persistently circulated in southern Israel and intermittently in other areas without any paralytic cases as determined by intensified surveillance of environmental and human samples. We aimed to characterize antigenic and neurovirulence properties of WPV1-SOAS silently circulating in a highly vaccinated population. WPV1-SOAS capsid genes from environmental and stool surveillance isolates were sequenced, their neurovirulence was determined using transgenic mouse expressing the human poliovirus receptor (Tg21-PVR) mice, and their antigenicity was characterized by in vitro neutralization using human sera, epitope-specific monoclonal murine anti-oral poliovirus vaccine (OPV) antibodies, and sera from IPV-immunized rats and mice. WPV1 amino acid sequences in neutralizing epitopes varied from Sabin 1 and Mahoney, with little variation among WPV1 isolates. Neutralization by monoclonal antibodies against 3 of 4 OPV epitopes was lost. Three-fold lower geometric mean titers (Z = -4.018; P < .001, Wilcoxon signed-rank test) against WPV1 than against Mahoney in human serum correlated with 4- to 6-fold lower neutralization titers in serum from IPV-immunized rats and mice. WPV1-SOAS isolates were neurovirulent (50% intramuscular paralytic dose in Tg21-PVR mice: log10(7.0)). IPV-immunized mice were protected against WPV1-induced paralysis. Phenotypic and antigenic profile changes of WPV1-SOAS may have contributed to the intense silent transmission, whereas the reduced neurovirulence may have contributed to the absence of paralytic cases in the background of high population immunity. © The Author 2014. Published by

  19. Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria

    OpenAIRE

    Famulare, Michael; Chang, Stewart; Iber, Jane; Zhao, Kun; Adeniji, Johnson A.; Bukbuk, David; Baba, Marycelin; Behrend, Matthew; Burns, Cara C.; Oberste, M. Steven

    2015-01-01

    To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 sub...

  20. Safety and immunogenicity of a primary series of Sabin-IPV with and without aluminum hydroxide in infants.

    Science.gov (United States)

    Verdijk, Pauline; Rots, Nynke Y; van Oijen, Monique G C T; Weldon, William C; Oberste, M Steven; Okayasu, Hiromasa; Sutter, Roland W; Bakker, Wilfried A M

    2014-09-03

    An inactivated poliovirus vaccine (IPV) based on attenuated poliovirus strains (Sabin-1, -2 and -3) was developed for technology transfer to manufacturers in low- and middle-income countries in the context of the global polio eradication initiative. Safety and immunogenicity of Sabin-IPV (sIPV) was evaluated in a double-blind, randomized, controlled, dose-escalation trial in the target population. Healthy infants (n=20/group) aged 56-63 days, received a primary series of three intramuscular injections with low-, middle- or high-dose sIPV with or without aluminum hydroxide or with the conventional IPV based on wild poliovirus strains (wIPV). Virus-neutralizing titers against both Sabin and wild poliovirus strains were determined before and 28 days after three vaccinations. The incidence of local and systemic reactions was comparable with the wIPV. Seroconversion rates after three vaccinations were 100% for type 2 and type 3 polioviruses (both Sabin and wild strains) and 95-100% for type 1 polioviruses. Median titers were high in all groups. Titers were well above the log2(titer) correlated with protection (=3) for all groups. Median titers for Sabin-2 were 9.3 (range 6.8-11.5) in the low-dose sIPV group, 9.2 (range 6.8-10.2) in the low-dose adjuvanted sIPV group and 9.8 (range 5.5-15.0) in the wIPV group, Median titers against MEF-1 (wild poliovirus type 2) were 8.2 (range 4.8-10.8) in the low-dose sIPV group, 7.3 (range 4.5-10.2) in the low-dose adjuvanted Sabin-IPV group and 10.3 (range 8.5-17.0) in the wIPV group. For all poliovirus types the median titers increased with increasing dose levels. sIPV and sIPV adjuvanted with aluminum hydroxide were immunogenic and safe at all dose levels, and comparable with the wIPV. EudraCTnr: 2011-003792-11, NCT01709071. Copyright © 2014. Published by Elsevier Ltd.

  1. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    Science.gov (United States)

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Cluster of Paralytic Poliomyelitis Cases Due to Transmission of Slightly Diverged Sabin 2 Vaccine Poliovirus.

    Science.gov (United States)

    Korotkova, Ekaterina A; Gmyl, Anatoly P; Yakovenko, Maria L; Ivanova, Olga E; Eremeeva, Tatyana P; Kozlovskaya, Liubov I; Shakaryan, Armen K; Lipskaya, Galina Y; Parshina, Irina L; Loginovskikh, Nataliya V; Morozova, Nadezhda S; Agol, Vadim I

    2016-07-01

    Four cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems. The oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly

  3. Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

    Directory of Open Access Journals (Sweden)

    Margarita Pons-Salort

    2016-07-01

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

  4. Community transmission of type 2 poliovirus after cessation of trivalent oral polio vaccine in Bangladesh: an open-label cluster-randomised trial and modelling study.

    Science.gov (United States)

    Taniuchi, Mami; Famulare, Michael; Zaman, Khalequ; Uddin, Md Jashim; Upfill-Brown, Alexander M; Ahmed, Tahmina; Saha, Parimalendu; Haque, Rashidul; Bandyopadhyay, Ananda S; Modlin, John F; Platts-Mills, James A; Houpt, Eric R; Yunus, Mohammed; Petri, William A

    2017-10-01

    Trivalent oral polio vaccine (tOPV) was replaced worldwide from April, 2016, by bivalent types 1 and 3 oral polio vaccine (bOPV) and one dose of inactivated polio vaccine (IPV) where available. The risk of transmission of type 2 poliovirus or Sabin 2 virus on re-introduction or resurgence of type 2 poliovirus after this switch is not understood completely. We aimed to assess the risk of Sabin 2 transmission after a polio vaccination campaign with a monovalent type 2 oral polio vaccine (mOPV2). We did an open-label cluster-randomised trial in villages in the Matlab region of Bangladesh. We randomly allocated villages (clusters) to either: tOPV at age 6 weeks, 10 weeks, and 14 weeks; or bOPV at age 6 weeks, 10 weeks, and 14 weeks and either one dose of IPV at age 14 weeks or two doses of IPV at age 14 weeks and 18 weeks. After completion of enrolment, we implemented an mOPV2 vaccination campaign that targeted 40% of children younger than 5 years, regardless of enrolment status. The primary outcome was Sabin 2 incidence in the 10 weeks after the campaign in per-protocol infants who did not receive mOPV2, as assessed by faecal shedding of Sabin 2 by reverse transcriptase quantitative PCR (RT-qPCR). The effect of previous immunity on incidence was also investigated with a dynamical model of poliovirus transmission to observe prevalence and incidence of Sabin 2 virus. This trial is registered at ClinicalTrials.gov, number NCT02477046. Between April 30, 2015, and Jan 14, 2016, individuals from 67 villages were enrolled to the study. 22 villages (300 infants) were randomly assigned tOPV, 23 villages (310 infants) were allocated bOPV and one dose of IPV, and 22 villages (329 infants) were assigned bOPV and two doses of IPV. Faecal shedding of Sabin 2 in infants who did not receive the mOPV2 challenge did not differ between children immunised with bOPV and one or two doses of IPV and those who received tOPV (15 of 252 [6%] vs six of 122 [4%]; odds ratio [OR] 1·29, 95% CI 0

  5. [Eradication of poliomyelitis and emergence of pathogenic vaccine-derived polioviruses: from Madagascar to Cameroon].

    Science.gov (United States)

    Delpeyroux, Francis; Colbère-Garapin, Florence; Razafindratsimandresy, Richter; Sadeuh-Mba, Serge; Joffret, Marie-Line; Rousset, Dominique; Blondel, Bruno

    2013-11-01

    The oral poliovaccine, a live vaccine made of attenuated poliovirus strains, is the main tool of the vaccination campaigns organised for eradicating poliomyelitis. these campaigns had led to the decline and, thereafter, to the disappearance of wild poliovirus strains of the three serotypes (1-3) in most parts of the world. However, when the poliovaccine coverage becomes too low, vaccine polioviruses can circulate in insufficiently immunized populations and become then pathogenic by mutations and genetic recombination with other enteroviruses of the same species, in particular some coxsackievirus A. These mutated and recombinant vaccine strains have been implicated in several epidemics of paralytic poliomyelitis. Two polio outbreaks associated with these pathogenic circulating vaccine-derived poliovirus (cVDPV) occurred in 2001-2002 and 2005 in the South of Madagascar where vaccine coverage was low. These cVDPV, of serotype 2 or 3, were isolated from paralyzed children and some of their healthy contacts. Other cVDPV were isolated in the same region from healthy children in 2011, indicating that these viruses were circulating again. Vaccination campaigns could stop the outbreaks in 2002 and 2005, and most probably prevent another one in 2011. Therefore, the genetic plasticity of poliovaccine strains that threatens the benefit of vaccination campaigns is the target of an accurate surveillance and an important theme of studies in the virology laboratories of the Institut Pasteur international network. © 2013 médecine/sciences – Inserm.

  6. Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.

    Science.gov (United States)

    Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Sutter, Roland W; Wassilak, Steven G; Burns, Cara C

    2016-08-05

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide (1). One of the main tools used in polio eradication efforts has been the live, attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but provides long-term protection against paralytic disease. Through effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought wild polioviruses to the threshold of eradication (1). However, OPV use, particularly in areas with low routine vaccination coverage, is associated with the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (3). VDPVs can emerge among immunologically normal vaccine recipients and their contacts as well as among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (4).

  7. Identification of a consistent pattern of mutations in neurovirulent variants derived from the sabin vaccine strain of poliovirus type 2.

    OpenAIRE

    Equestre, M; Genovese, D; Cavalieri, F; Fiore, L; Santoro, R; Perez Bercoff, R

    1991-01-01

    Complete nucleotide sequencing of the RNAs of two unrelated neurovirulent isolates of Sabin-related poliovirus type 2 revealed that two nucleotides and one amino acid (amino acid 143 in the major capsid protein VP1) consistently departed from the sequences of the nonneurovirulent poliovirus type 2 712 and Sabin vaccine strains. This pattern of mutation appeared to be a feature common to all neurovirulent variants of poliovirus type 2.

  8. Global Polio Eradication Initiative (GPEI): Future Perspectives and Need for a New Generation of Inactivated Poliovirus Vaccine

    OpenAIRE

    VASHISHTHA, Vipin; NAVEEN, Thacker

    2010-01-01

    More than two decade-old Global Polio Eradication Initiative (GPEI) has finally tasted success and wild poliovirus is now on the verge of eradication. The pre-eradication era was full of challenges and a great learning experience for all those involved with this tedious process. Many new phenomena emerged and new information about poliovirus learned during this campaign. Many new developments such as vaccine-derived polioviruses (VDPVs) were not anticipated and resulted in serious thinking re...

  9. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    -acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...

  10. Seroprevalence of poliovirus antibodies in the Kansas City metropolitan area, 2012-2013.

    Science.gov (United States)

    Wallace, Gregory S; Pahud, Barbara A; Weldon, William C; Curns, Aaron T; Oberste, M Steven; Harrison, Christopher J

    2017-04-03

    No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012-2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants poliovirus serotypes. Seroprevalence was evaluated by demographics as well as between polio serotypes. The overall seroprevalence to poliovirus was 90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, respectively. Seroprevalence was high (88.6%-96.2%) for all 3 types of poliovirus for the 6-10 y old age group that was likely to have received a complete schedule of IPV-only vaccination. Children 2-3 y of age, who have not yet completed their full IPV series, had lower seroprevalence compared with all older age groups for types 1 and 2 (p-value poliovirus in the population surveyed. Seroprevalence for subjects aged 2-3 y was lower than all other age groups for serotypes 1 and 2 highlighting the importance of completing the recommended poliovirus vaccine series with a booster dose at age 4-6 y.

  11. Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

    Science.gov (United States)

    Decina, Daniela; Fournier-Caruana, Jacqueline; Takane, Marina; Ostad Ali Dehaghi, Razieh; Sutter, Roland

    2017-07-01

    Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Development of novel inactivated poliovirus vaccines: Breaking away from convention

    NARCIS (Netherlands)

    Sanders, B.P.

    2015-01-01

    Infection with poliovirus (a small, non-enveloped Picornavirus) can result in poliomyelitis, hallmarked by symptoms of paralysis which is caused by viral destruction of motor neurons. Circulating humoral neutralizing antibodies can effectively protect against the disease, an immune response which

  13. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

    Science.gov (United States)

    Butel, J. S.

    2000-01-01

    From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

  14. Alternative inactivated poliovirus vaccines adjuvanted with Quillaja brasiliensis or Quil-a saponins are equally effective in inducing specific immune responses.

    Directory of Open Access Journals (Sweden)

    Fernanda de Costa

    Full Text Available Inactivated polio vaccines (IPV have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV. An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control, Quil-A (50 µg, AE (400 µg or QB-90 (50 µg. Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

  15. Molecular Evolution of a Type 1 Wild-Vaccine Poliovirus Recombinant during Widespread Circulation in China

    Science.gov (United States)

    Liu, Hong-Mei; Zheng, Du-Ping; Zhang, Li-Bi; Oberste, M. Steven; Pallansch, Mark A.; Kew, Olen M.

    2000-01-01

    Type 1 wild-vaccine recombinant polioviruses were isolated from poliomyelitis patients in China from 1991 to 1993. We compared the sequences of 34 recombinant isolates over the 1,353-nucleotide (nt) genomic interval (nt 2480 to 3832) encoding the major capsid protein, VP1, and the protease, 2A. All recombinants had a 367-nt block of sequence (nt 3271 to 3637) derived from the Sabin 1 oral poliovirus vaccine strain spanning the 3′-terminal sequences of VP1 (115 nt) and the 5′ half of 2A (252 nt). The remaining VP1 sequences were closely (up to 99.5%) related to those of a major genotype of wild type 1 poliovirus endemic to China up to 1994. In contrast, the non-vaccine-derived sequences at the 3′ half of 2A were more distantly related (polioviruses from China. The vaccine-derived sequences of the earliest (April 1991) isolates completely matched those of Sabin 1. Later isolates diverged from the early isolates primarily by accumulation of synonymous base substitutions (at a rate of ∼3.7 × 10−2 substitutions per synonymous site per year) over the entire VP1-2A interval. Distinct evolutionary lineages were found in different Chinese provinces. From the combined epidemiologic and evolutionary analyses, we propose that the recombinant virus arose during mixed infection of a single individual in northern China in early 1991 and that its progeny spread by multiple independent chains of transmission into some of the most populous areas of China within a year of the initiating infection. PMID:11070012

  16. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  17. Effect of buffer on the immune response to trivalent oral poliovirus vaccine in Bangladesh: a community based randomized controlled trial.

    Science.gov (United States)

    Chandir, Subhash; Ahamed, Kabir U; Baqui, Abdullah H; Sutter, Roland W; Okayasu, Hiromasa; Pallansch, Mark A; Oberste, Mark S; Moulton, Lawrence H; Halsey, Neal A

    2014-11-01

    Polio eradication efforts have been hampered by low responses to trivalent oral poliovirus vaccine (tOPV) in some developing countries. Since stomach acidity may neutralize vaccine viruses, we assessed whether administration of a buffer solution could improve the immunogenicity of tOPV. Healthy infants 4-6 weeks old in Sylhet, Bangladesh, were randomized to receive tOPV with or without a sodium bicarbonate and sodium citrate buffer at age 6, 10, and 14 weeks. Levels of serum neutralizing antibodies for poliovirus types 1, 2, and 3 were measured before and after vaccination, at 6 and 18 weeks of age, respectively. Serologic response rates following 3 doses of tOPV for buffer recipients and control infants were 95% and 88% (P=.065), respectively, for type 1 poliovirus; 95% and 97% (P=.543), respectively, for type 2 poliovirus; and 90% and 89% (P=.79), respectively, for type 3 poliovirus. Administration of a buffer solution prior to vaccination was not associated with statistically significant increases in the immune response to tOPV; however, a marginal 7% increase (P=.065) in serologic response to poliovirus type 1 was observed. NCT01579825. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals

    Science.gov (United States)

    Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥7/9 and 8.9~228.1) than in the placebo group (≤1/10 and 0.8~1.7, P Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI. PMID:25715318

  19. The compatibility of inactivated-Enterovirus 71 vaccination with Coxsackievirus A16 and Poliovirus immunizations in humans and animals.

    Science.gov (United States)

    Mao, Qunying; Wang, Yiping; Shao, Jie; Ying, Zhifang; Gao, Fan; Yao, Xin; Li, Changgui; Ye, Qiang; Xu, Miao; Li, Rongcheng; Zhu, Fengcai; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) is the key pathogen for Hand, Foot, and Mouth Disease (HFMD) and can result in severe neurological complications and death among young children. Three inactivated-EV71 vaccines have gone through phase III clinical trials and have demonstrated good safety and efficacy. These vaccines will benefit young children under the threat of severe HFMD. However, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to include the EV71 vaccine in Expanded Program on Immunization (EPI). Here, we measured the neutralizing antibodies (NTAbs) against EV71, Coxsackievirus A16 (CA16) and Poliovirus from infants enrolled in those EV71 vaccine clinical trials. The results indicated that the levels of NTAb GMTs for EV71 increased significantly in all 3 vaccine groups (high, middle and low dosages, respectively) post-vaccination. Seroconversion ratios and Geometric mean fold increase were significantly higher in the vaccine groups (≥ 7/9 and 8.9 ~ 228.1) than in the placebo group (≤ 1/10 and 0.8 ~ 1.7, P < 0.05). But no similar NTAb response trends were found in CA16 and 3 types of Poliovirus. The decrease of 3 types of Poliovirus NTAb GMTs and an increase of CA16 GMTs post-EV71-vaccination were found in vaccine and placebo groups. Further animal study on CA16 and poliovirus vaccine co-immunization or pre-immunization with EV71 vaccine in mice indicated that there was no NTAb cross-activity between EV71 and CA16/Poliovirus. Our research showed that inactivated-EV71 vaccine has good specific-neutralizing capacity and can be included in EPI.

  20. Circulating type 1 vaccine-derived poliovirus may evolve under the pressure of adenosine deaminases acting on RNA.

    Science.gov (United States)

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Xu, Ruixue; Wang, Shujing

    2015-01-01

    Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the Picornaviridae family. An effective live-attenuated poliovirus vaccine strain (Sabin 1) has been developed and has protected humans from polio. However, a few cases of vaccine virulence reversion have been documented in several countries. For instance, circulating type 1 vaccine-derived poliovirus is a highly pathogenic poliovirus that evolved from an avirulent strain, but the mechanism by which vaccine strains undergo reversion remains unclear. In this study, vaccine strains exhibited A to G/U to C and G to A/C to U hypermutations in the reversed evolution of Sabin 1. Furthermore, the mutation ratios of U to C and C to U were higher than those of other mutation types. Dinucleotide editing context was then analyzed. Results showed that A to G and U to C mutations exhibited preferences similar to adenosine deaminases acting on RNA (ADAR). Hence, ADARs may participate in poliovirus vaccine evolution.

  1. Vaccine-Derived Poliovirus Outbreaks and Events - Three Provinces, Democratic Republic of the Congo, 2017.

    Science.gov (United States)

    Alleman, Mary M; Chitale, Rohit; Burns, Cara C; Iber, Jane; Dybdahl-Sissoko, Naomi; Chen, Qi; Van Koko, Djo-Roy; Ewetola, Raimi; Riziki, Yogolelo; Kavunga-Membo, Hugo; Dah, Cheikh; Andriamihantanirina, Rija

    2018-03-16

    The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence. This process occurs during extensive person-to-person transmission in populations with low immunity or after extended replication in the intestines of immune-deficient persons following vaccination (1-6). During 2017 (as of March 8, 2018), 25 VDPV cases were reported in three provinces in DRC: in Tanganyika province, an emergence with one VDPV2 case (pending final classification) in Kabalo health zone and an emergence with one ambiguous VDPV type 1 (aVDPV1) case in Ankoro health zone; in Maniema province, an emergence with two cVDPV2 cases; and in Haut Lomami province, an emergence with 20 cVDPV2 cases that originated in Haut Lomami province and later spread to Tanganyika province (hereafter referred to as the Haut Lomami outbreak area) and an emergence with one aVDPV type 2 (aVDPV2) case in Lwamba health zone (Table 1) (Figure) (6). Outbreak response supplementary immunization activities (SIAs) were conducted during June-December 2017 (Table 2) (6). Because of limitations in surveillance and suboptimal SIA quality and geographic scope, cVDPV2 circulation is likely continuing in 2018, requiring additional SIAs. DRC health officials and Global Polio Eradication Initiative (GPEI) partners are increasing human and financial resources to improve all aspects of outbreak response.

  2. Next Generation Inactivated Polio Vaccine Manufacturing to Support Post Polio-Eradication Biosafety Goals

    NARCIS (Netherlands)

    Thomassen, Y.E.; Oever, van 't A.G.; Oijen, van M.G.C.T.; Wijffels, R.H.; Pol, van der L.A.; Bakker, W.A.M.

    2013-01-01

    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

  3. Mucosal immunity to poliovirus.

    Science.gov (United States)

    Ogra, Pearay L; Okayasu, Hiromasa; Czerkinsky, Cecil; Sutter, Roland W

    2011-10-01

    The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and Poliovirus Vaccines: Impact on Wild Poliovirus Infection, Transmission and Vaccine Failure conference was organized to obtain a better understanding of the current status of global control of poliomyelitis and identify approaches to improve the immune responsiveness and effectiveness of the orally administered poliovirus vaccines in order to accelerate the global eradication of paralytic poliomyelitis.

  4. [Investigation of a Patient with Pre-vaccine-derived Poliovirus in Shandong Province, China].

    Science.gov (United States)

    Lin, Xiaojuan; Liu, Yao; Wang, Suting; Zhang Xiao; Song, Lizhi; Tao, Zexin; Ji, Feng; Xiong, Ping; Xu, Aiqiang

    2015-09-01

    To analyze the genetic characteristics of a polio-I highly variant vaccine recombinant virus in Shandong Province (China) in 2011 and to identify isolates from healthy contacts, two stool specimens from one patient with acute flaccid paralysis (AFP) and 40 stool specimens from his contacts were collected for virus isolation. The complete genome of poliovirus and VP1 coding region of the non-polio enterovirus were sequenced. Homologous comparison and phylogenetic analyses based on VP1 sequences were undertaken among coxsackievirus (CV) B1, CV-B3 isolates, and those in GenBank. One poliovirus (P1/11186), CV-A4 and CV-A8 were isolated from the AFP patient; one CV-A2, Echovirus 3 (E-3), E-12 and E-14, ten CV-B1, and five CV-B3 strains were isolated from his contacts. These results led us to believe that there may be a human enterovirus epidemic in this area, and that surveillance must be enhanced. P1/11186 was a type-1 vaccine-related poliovirus; it combined with type-2 and type-3 polioviruses in 2A and 3A regions, respectively. There were 25 nucleotide mutations with 9 amino-acid alterations in the entire genome. There were 8 nucleotide mutations with 5 amino-acid alterations in the VP1 region compared with the corresponding Sabin strains. Homology analyses suggested that the ten CV-B1 isolates had 97.0%-100% nucleotide and 98.9%-100% amino-acid identities with each other, as well as 92.6%-100% nucleotide and 99.2%-100% amino-acid identities among the five CV-B3 isolates. Phylogenetic analyses on the complete sequences of VP1 among CV-B1 and CV-B3 isolates showed that Shandong strains, together with strains from other provinces in China, had a close relationship and belonged to the same group.

  5. Phenotypic and genomic analysis of serotype 3 Sabin poliovirus vaccine produced in MRC-5 cell substrate.

    Science.gov (United States)

    Alirezaie, Behnam; Taqavian, Mohammad; Aghaiypour, Khosrow; Esna-Ashari, Fatemeh; Shafyi, Abbas

    2011-05-01

    The cell substrate has a pivotal role in live virus vaccines production. It is necessary to evaluate the effects of the cell substrate on the properties of the propagated viruses, especially in the case of viruses which are unstable genetically such as polioviruses, by monitoring the molecular and phenotypical characteristics of harvested viruses. To investigate the presence/absence of mutation(s), the near full-length genomic sequence of different harvests of the type 3 Sabin strain of poliovirus propagated in MRC-5 cells were determined. The sequences were compared with genomic sequences of different virus seeds, vaccines, and OPV-like isolates. Nearly complete genomic sequencing results, however, revealed no detectable mutations throughout the genome RNA-plaque purified (RSO)-derived monopool of type 3 OPVs manufactured in MRC-5. Thirty-six years of experience in OPV production, trend analysis, and vaccine surveillance also suggest that: (i) different monopools of serotype 3 OPV produced in MRC-5 retained their phenotypic characteristics (temperature sensitivity and neuroattenuation), (ii) MRC-5 cells support the production of acceptable virus yields, (iii) OPV replicated in the MRC-5 cell substrate is a highly efficient and safe vaccine. These results confirm previous reports that MRC-5 is a desirable cell substrate for the production of OPV. Copyright © 2011 Wiley-Liss, Inc.

  6. Dynamic profiles of neutralizing antibody responses elicited in rhesus monkeys immunized with a combined tetravalent DTaP-Sabin IPV candidate vaccine.

    Science.gov (United States)

    Sun, Mingbo; Ma, Yan; Xu, Yinhua; Yang, Huijuan; Shi, Li; Che, Yanchun; Liao, Guoyang; Jiang, Shude; Zhang, Shumin; Li, Qihan

    2014-02-19

    The World Health Organization has recommended that a Sabin inactivated polio vaccine (IPV) should gradually and synchronously replace oral polio vaccines for routine immunizations because its benefits in eliminating vaccine-associated paralytic poliomyelitis have been reported in different phases of clinical trials. It is also considered important to explore new tetravalent diphtheria, tetanus, and acellular pertussis-Sabin IPV (DTaP-sIPV) candidate vaccines for possible use in developing countries. In this study, the immunogenicity of a combined tetravalent DTaP-sIPV candidate vaccine was investigated in primates by evaluating the neutralizing antibody responses it induced. The dynamic profiles of the antibody responses to each of the separate antigenic components and serotypes of Sabin IPV were determined and their corresponding geometric mean titers were similar to those generated by the tetravalent diphtheria, tetanus, and acellular pertussis-conventional IPV (DTaP-cIPV), the tetravalent diphtheria, tetanus, and acellular pertussis (DTaP), and Sabin IPV vaccines in the control groups. This implies that protective immunogenic effects are conferred by this combined tetravalent formulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Update on Vaccine-Derived Polioviruses - Worldwide, January 2016-June 2017.

    Science.gov (United States)

    Jorba, Jaume; Diop, Ousmane M; Iber, Jane; Henderson, Elizabeth; Sutter, Roland W; Wassilak, Steven G F; Burns, Cara C

    2017-11-03

    In 1988, the World Health Assembly launched the Global Polio Eradication Initiative (GPEI) (1). Among the three wild poliovirus (WPV) serotypes, only type 1 (WPV1) has been detected since 2012. Since 2014, detection of WPV1 has been limited to three countries, with 37 cases in 2016 and 11 cases in 2017 as of September 27. The >99.99% decline worldwide in polio cases since the launch of the GPEI is attributable to the extensive use of the live, attenuated oral poliovirus vaccine (OPV) in mass vaccination campaigns and comprehensive national routine immunization programs. Despite its well-established safety record, OPV use can be associated with rare emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose genetic drift from the parental OPV strains indicates prolonged replication or circulation (2). VDPVs can also emerge among persons with primary immunodeficiencies (PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in some persons with PIDs. In addition, circulating vaccine-derived polioviruses (cVDPVs) can emerge very rarely among immunologically normal vaccine recipients and their contacts in areas with inadequate OPV coverage and can cause outbreaks of paralytic polio. This report updates previous summaries regarding VDPVs (3). During January 2016-June 2017, new cVDPV outbreaks were identified, including two in the Democratic Republic of the Congo (DRC) (eight cases), and another in Syria (35 cases), whereas the circulation of cVDPV type 2 (cVDPV2) in Nigeria resulted in cVDPV2 detection linked to a previous emergence. The last confirmed case from the 2015-2016 cVDPV type 1 (cVDPV1) outbreak in Laos occurred in January 2016. Fourteen newly identified persons in 10 countries were found to excrete iVDPVs, and three previously reported patients in the United Kingdom and Iran (3) were still excreting type 2 iVDPV (iVDPV2) during the reporting period. Ambiguous VDPVs (aVDPVs), isolates that cannot be classified

  8. Evolution of the Sabin vaccine into pathogenic derivatives without appreciable changes in antigenic properties: need for improvement of current poliovirus surveillance.

    Science.gov (United States)

    Yakovenko, Maria L; Korotkova, Ekaterina A; Ivanova, Olga E; Eremeeva, Tatyana P; Samoilovich, Elena; Uhova, Iryna; Gavrilin, Gene V; Agol, Vadim I

    2009-04-01

    The Sabin oral polio vaccine (OPV) may evolve into pathogenic viruses, causing sporadic cases and outbreaks of poliomyelitis. Such vaccine-derived polioviruses (VDPV) generally exhibit altered antigenicity. The current paradigm to distinguish VDPV from OPV and wild polioviruses is to characterize primarily those poliovirus isolates that demonstrate deviations from OPV in antigenic and genetic intratypic differentiation (ITD) tests. Here we report on two independent cases of poliomyelitis caused by VDPVs with "Sabin-like" properties in several ITD assays. The results suggest the existence of diverse pathways of OPV evolution and necessitate improvement of poliovirus surveillance, which currently potentially misses this class of VDPV.

  9. A Supply and Demand Management Perspective on the Accelerated Global Introductions of Inactivated Poliovirus Vaccine in a Constrained Supply Market.

    Science.gov (United States)

    Lewis, Ian; Ottosen, Ann; Rubin, Jennifer; Blanc, Diana Chang; Zipursky, Simona; Wootton, Emily

    2017-07-01

    A total of 105 countries have introduced IPV as of September 2016 of which 85 have procured the vaccine through UNICEF. The Global Eradication and Endgame Strategic Plan 2013-2018 called for the rapid introduction of at least one dose of IPV into routine immunization schedules in 126 all OPV-using countries by the end of 2015. At the time of initiating the procurement process, demand was estimated based on global modeling rather than individual country indications. In its capacity as procurement agency for the Global Polio Eradication Initiative and Gavi, the Vaccine Alliance, UNICEF set out to secure access to IPV supply for around 100 countries. Based on offers received, sufficient supply was awarded to two manufacturers to meet projected routine requirements. However, due to technical issues scaling up vaccine production and an unforecasted demand for IPV use in campaigns to interrupt wild polio virus and to control type 2 vaccine derived polio virus outbreaks, IPV supplies are severely constrained. Activities to stretch supplies and to suppress demand have been ongoing since 2014, including delaying IPV introduction in countries where risks of type 2 reintroduction are lower, implementing the multi-dose vial policy, and encouraging the use of fractional dose delivered intradermally. Despite these efforts, there is still insufficient IPV supply to meet demand. The impact of the supply situation on IPV introduction timelines in countries are the focus of this article, and based on lessons learned with the IPV introductions, it is recommended for future health programs with accelerated scale up of programs, to take a cautious approach on supply commitments, putting in place clear allocation criteria in case of shortages or delays and establishing a communication strategy vis a vis beneficiaries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  10. A Supply and Demand Management Perspective on the Accelerated Global Introductions of Inactivated Poliovirus Vaccine in a Constrained Supply Market

    Science.gov (United States)

    Ottosen, Ann; Rubin, Jennifer; Blanc, Diana Chang; Zipursky, Simona; Wootton, Emily

    2017-01-01

    Abstract A total of 105 countries have introduced IPV as of September 2016 of which 85 have procured the vaccine through UNICEF. The Global Eradication and Endgame Strategic Plan 2013-2018 called for the rapid introduction of at least one dose of IPV into routine immunization schedules in 126 all OPV-using countries by the end of 2015. At the time of initiating the procurement process, demand was estimated based on global modeling rather than individual country indications. In its capacity as procurement agency for the Global Polio Eradication Initiative and Gavi, the Vaccine Alliance, UNICEF set out to secure access to IPV supply for around 100 countries. Based on offers received, sufficient supply was awarded to two manufacturers to meet projected routine requirements. However, due to technical issues scaling up vaccine production and an unforecasted demand for IPV use in campaigns to interrupt wild polio virus and to control type 2 vaccine derived polio virus outbreaks, IPV supplies are severely constrained. Activities to stretch supplies and to suppress demand have been ongoing since 2014, including delaying IPV introduction in countries where risks of type 2 reintroduction are lower, implementing the multi-dose vial policy, and encouraging the use of fractional dose delivered intradermally. Despite these efforts, there is still insufficient IPV supply to meet demand. The impact of the supply situation on IPV introduction timelines in countries are the focus of this article, and based on lessons learned with the IPV introductions, it is recommended for future health programs with accelerated scale up of programs, to take a cautious approach on supply commitments, putting in place clear allocation criteria in case of shortages or delays and establishing a communication strategy vis a vis beneficiaries. PMID:28838159

  11. Modeling the spread of polio in an IPV-vaccinated population: lessons learned from the 2013 silent outbreak in southern Israel.

    Science.gov (United States)

    Yaari, Rami; Kaliner, Ehud; Grotto, Itamar; Katriel, Guy; Moran-Gilad, Jacob; Sofer, Danit; Mendelson, Ella; Miller, Elizabeth; Huppert, Amit; Anis, E; Kopel, E; Manor, Y; Mor, O; Shulman, L; Singer, R; Weil, M

    2016-06-23

    Polio eradication is an extraordinary globally coordinated health program in terms of its magnitude and reach, leading to the elimination of wild poliovirus (WPV) in most parts of the world. In 2013, a silent outbreak of WPV was detected in Israel, a country using an inactivated polio vaccine (IPV) exclusively since 2005. The outbreak was detected using environmental surveillance (ES) of sewage reservoirs. Stool surveys indicated the outbreak to be restricted mainly to children under the age of 10 in the Bedouin population of southern Israel. In order to curtail the outbreak, a nationwide vaccination campaign using oral polio vaccine (OPV) was conducted, targeting all children under 10. A transmission model, fitted to the results of the stool surveys, with additional conditions set by the ES measurements, was used to evaluate the prevalence of WPV in Bedouin children and the effectiveness of the vaccination campaign. Employing the parameter estimates of the model fitting, the model was used to investigate the effect of alternative timings, coverages and dosages of the OPV campaign on the outcome of the outbreak. The mean estimate for the mean reproductive number was 1.77 (95 % credible interval, 1.46-2.30). With seasonal variation, the reproductive number maximum range was between zero and six. The mean estimate for the mean infectious periods was 16.8 (8.6-24.9) days. The modeling indicates the OPV campaign was effective in curtailing the outbreak. The mean estimate for the attack rate in Bedouin children under 10 at the end of 2014 was 42 % (22-65 %), whereas without the campaign the mean projected attack rate was 57 % (35-74 %). The campaign also likely shortened the duration of the outbreak by a mean estimate of 309 (2-846) days. A faster initiation of the OPV campaign could have reduced the incidence of WPV even if a lower coverage was reached, at the risk of prolonging the outbreak. OPV campaigns are essential for interrupting WPV transmission, even in a

  12. Lessons From Globally Coordinated Cessation of Serotype 2 Oral Poliovirus Vaccine for the Remaining Serotypes.

    Science.gov (United States)

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2017-07-01

    Comparing model expectations with the experience of oral poliovirus vaccine (OPV) containing serotype 2 (OPV2) cessation can inform risk management for the expected cessation of OPV containing serotypes 1 and 3 (OPV13). We compare the expected post-OPV2-cessation OPV2-related viruses from models with the evidence available approximately 6 months after OPV2 cessation. We also model the trade-offs of use vs nonuse of monovalent OPV (mOPV) for outbreak response considering all 3 serotypes. Although too early to tell definitively, the observed die-out of OPV2-related viruses in populations that attained sufficiently intense trivalent OPV (tOPV) use prior to OPV2 cessation appears consistent with model expectations. As expected, populations that did not intensify tOPV use prior to OPV2 cessation show continued circulation of serotype 2 vaccine-derived polioviruses (VDPVs). Failure to aggressively use mOPV to respond to circulating VDPVs results in a high risk of uncontrolled outbreaks that would require restarting OPV. Ensuring a successful endgame requires more aggressive OPV cessation risk management than has occurred to date for OPV2 cessation. This includes maintaining high population immunity to transmission up until OPV13 cessation, meeting all prerequisites for OPV cessation, and ensuring sufficient vaccine supply to prevent and respond to outbreaks. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  13. Correlation of mutations and recombination with growth kinetics of poliovirus vaccine strains.

    Science.gov (United States)

    Pliaka, V; Kyriakopoulou, Z; Tsakogiannis, D; Ruether, I G A; Gartzonika, C; Levidiotou-Stefanou, S; Krikelis, A; Markoulatos, P

    2010-12-01

    Attenuated strains of Sabin poliovirus vaccine replicate in the human gut and, in rare cases, may cause vaccine-associated paralytic poliomyelitis (VAPP). The genetic instability of Sabin strains constitutes one of the main causes of VAPP, a disease that is most frequently associated with type 3 and type 2 Sabin strains, and more rarely with type 1 Sabin strains. In the present study, the growth phenotype of eight oral poliovirus vaccine (OPV) isolates (two non-recombinants and six recombinants), as well as of Sabin vaccine strains, was evaluated using two different assays, the reproductive capacity at different temperatures (Rct) test and the one-step growth curve test in Hep-2 cells at two different temperatures (37°C and 40°C). The growth phenotype of isolates was correlated with genomic modifications in order to identify the determinants and mechanisms of reversion towards neurovirulence. All of the recombinant OPV isolates showed a thermoresistant phenotype in the Rct test. Moreover, both recombinant Sabin-3 isolates showed significantly higher viral yield than Sabin 3 vaccine strain at 37°C and 40°C in the one-step growth curve test. All of the OPV isolates displayed mutations at specific sites of the viral genome, which are associated with the attenuated and temperature-sensitive phenotype of Sabin strains. The results showed that both mutations and recombination events could affect the phenotype traits of Sabin derivatives and may lead to the reversion of vaccinal strains to neurovirulent ones. The use of phenotypic markers along with the genomic analysis may shed additional light on the molecular determinants of the reversed neurovirulent phenotype of Sabin derivatives.

  14. Sabin Vaccine Reversion in the Field: a Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria.

    Science.gov (United States)

    Famulare, Michael; Chang, Stewart; Iber, Jane; Zhao, Kun; Adeniji, Johnson A; Bukbuk, David; Baba, Marycelin; Behrend, Matthew; Burns, Cara C; Oberste, M Steven

    2016-01-01

    To assess the dynamics of genetic reversion of live poliovirus vaccine in humans, we studied molecular evolution in Sabin-like poliovirus isolates from Nigerian acute flaccid paralysis cases obtained from routine surveillance. We employed a novel modeling approach to infer substitution and recombination rates from whole-genome sequences and information about poliovirus infection dynamics and the individual vaccination history. We confirmed observations from a recent vaccine trial that VP1 substitution rates are increased for Sabin-like isolates relative to the rate for the wild type due to increased nonsynonymous substitution rates. We also inferred substitution rates for attenuating nucleotides and confirmed that reversion can occur in days to weeks after vaccination. We combine our observations for Sabin-like virus evolution with the molecular clock for VP1 of circulating wild-type strains to infer that the mean time from the initiating vaccine dose to the earliest detection of circulating vaccine-derived poliovirus (cVDPV) is 300 days for Sabin-like virus type 1, 210 days for Sabin-like virus type 2, and 390 days for Sabin-like virus type 3. Phylogenetic relationships indicated transient local transmission of Sabin-like virus type 3 and, possibly, Sabin-like virus type 1 during periods of low wild polio incidence. Comparison of Sabin-like virus recombinants with known Nigerian vaccine-derived poliovirus recombinants shows that while recombination with non-Sabin enteroviruses is associated with cVDPV, the recombination rates are similar for Sabin isolate-Sabin isolate and Sabin isolate-non-Sabin enterovirus recombination after accounting for the time from dosing to the time of detection. Our study provides a comprehensive picture of the evolutionary dynamics of the oral polio vaccine in the field. The global polio eradication effort has completed its 26th year. Despite success in eliminating wild poliovirus from most of the world, polio persists in populations

  15. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

    Science.gov (United States)

    Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

    2017-01-11

    DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. Isolation and characterization of a highly evolved type 3 vaccine-derived poliovirus in China.

    Science.gov (United States)

    Zhang, Xiaowei; Qin, Chong; Li, Wei; Zheng, Zhenhua; Wang, Hanzhong; Cui, Zongqiang

    2017-06-15

    In this study, we report the identification and characterization of a highly evolved type 3 vaccine-derived poliovirus (VDPV) strain designated as WIV14, isolated in 2014 from a 4-year-old child suspected of having an enteroviral infection in China. Complete genome sequence of WIV14 revealed multiple nucleotide substitutions when compared with the attenuated poliovirus (PV) Sabin 3, including the reversion of three major attenuation sites to wild type. From the nucleotide divergence for the P1/capsid region, we estimated that the evolution time of WIV14 was more than 7 years, indicating the possible long time of replication. WIV14 strain seemed to have differences in biological characteristics compared with attenuated PV strains, such as being non-temperature-sensitive and producing large plaques. The current isolation of a highly divergent type 3 VDPV gives an idea of the risk of emergent VDPV strains, and emphasizes the importance of maintaining high vaccination coverage and herd immunity against PVs in China. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. [Circulating vaccine-derived poliovirus type 2 outbreak in Democratic Republic of Congo 2011-2012].

    Science.gov (United States)

    Bazira, L; Coulibaly, T; Mayenga, M; Ncharre, C; Yogolelo, R; Mbule, A; Moudzeo, H; Lwamba, P; Mulumba, A W; Cabore, J

    2015-10-01

    According to the WHO records of 2013, the incidence of poliomyelitis was reduced by more than 99%, the number of endemic countries decreased from 125 in 1988 to 3 in 2013 and over 10 million cases were prevented from poliomyelitis thanks to the intensive use of Oral polio vaccine (OPV). However, the emergence of circulating vaccine-derived poliovirus strains (cVDPV), causing serious epidemics like the wild poliovirus, is a major challenge on the final straight towards the goal of eradication and OPV cessation. This paper describes the cVDPVoutbreak that occurred in the Democratic Republic of Congo (DRC) from November 2011 to April 2012. All children under 15 years of age with acute flaccid paralysis (AFP) and confirmed presence of cVDPV in the stool samples were included. Thirty (30) children, all from the administrative territories of Bukama and Malemba Nkulu in the Katanga Province (south-east DRC), were reported. The virus responsible was the cVDPV type 2 (0.7% -3.5% divergent from the reference Sabin 2 strain) in 29 children (97%) and the ambiguous vaccine-derived poliovirus strain (0.7% divergent) was confirmed in one case (3%), a boy seventeen months old and already vaccinated four times with OPV. Twentyfive children (83%) were protected by any of the routine EPI vaccines and 3 children (10%) had never received any dose of OPV. In reaction, DRC has conducted five local campaigns over a period of 10 months (from January to October 2012) and the epidemic was stopped after the second round performed in March 2012. As elsewhere in similar conditions, low immunization coverage, poor sanitation conditions and the stop of the use of OPV2 have favoured the emergence of the third cVDPV epidemic in DRC. The implementation of the Strategic Plan for Polio eradication and endgame strategic plan 2013-2018 will prevent the emergence of cVDPV and set up the conditions for a coordinated OPV phase out.

  18. Genetically Thermo-Stabilised, Immunogenic Poliovirus Empty Capsids; a Strategy for Non-replicating Vaccines.

    Directory of Open Access Journals (Sweden)

    Helen Fox

    2017-01-01

    Full Text Available While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models.

  19. Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus.

    Science.gov (United States)

    Dey, Ayan; Molodecky, Natalie A; Verma, Harish; Sharma, Prashant; Yang, Jae Seung; Saletti, Giulietta; Ahmad, Mohammad; Bahl, Sunil K; Wierzba, Thomas F; Nandy, Ranjan K; Deshpande, Jagadish M; Sutter, Roland W; Czerkinsky, Cecil

    2016-01-01

    The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4β7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (ppoliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4β7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to

  20. Neurovirulent vaccine-derived polioviruses in sewage from highly immune populations.

    Directory of Open Access Journals (Sweden)

    Lester M Shulman

    Full Text Available BACKGROUND: Vaccine-derived polioviruses (VDPVs have caused poliomyelitis outbreaks in communities with sub-optimal vaccination. Israeli environmental surveillance of sewage from populations with high (>95% documented vaccine coverage of confirmed efficacy identified two separate evolutionary clusters of VDPVs: Group 1 (1998-2005, one system, population 1.6x10(6 and Group 2 (2006, 2 systems, populations 0.7x10(6 and 5x10(4. PRINCIPAL FINDINGS: Molecular analyses support evolution of nine Group 1 VDPVs along five different lineages, starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1 recombinant strain, and independent evolution of three Group 2 VDPVs along one lineage starting from a different recombinant strain. The primary evidence for two independent origins was based on comparison of unique recombination fingerprints, the number and distribution of identical substitutions, and evolutionary rates. Geometric mean titers of neutralizing antibodies against Group 1 VDPVs were significantly lower than against vaccine strains in all age-group cohorts tested. All individuals had neutralizing titers >1:8 against these VDPVs except 7% of the 20-50 year cohort. Group 1 VDPVs were highly neurovirulent in a transgenic mouse model. Intermediate levels of protective immunity against Group 2 VDPVs correlated with fewer (5.0+1.0 amino acid substitutions in neutralizing antigenic sites than in Group 1 VDPV's (12.1+/-1.5. SIGNIFICANCE: VDPVs that revert from live oral attenuated vaccines and reacquire characteristics of wild-type polioviruses not only threaten populations with poor immune coverage, but are also a potential source for re-introduction of poliomyelitis into highly immune populations through older individuals with waning immunity. The presence of two independently evolved groups of VDPVs in Israel and the growing number of reports of environmental VDPV elsewhere make it imperative to determine the global frequency of

  1. Seroprevalence of poliovirus antibodies in the Kansas City metropolitan area, 2012–2013

    Science.gov (United States)

    Wallace, Gregory S.; Pahud, Barbara A.; Weldon, William C.; Curns, Aaron T.; Oberste, M. Steven; Harrison, Christopher J.

    2017-01-01

    ABSTRACT No indigenous cases of poliomyelitis have occurred in the US since 1979; however the risk of importation persists until global eradication is achieved. The seropositivity rate for different age cohorts with exposures to different poliovirus vaccine types and wild virus in the US are not presently known. A convenience sample was conducted in the Kansas City metropolitan area during 2012–2103 with approximately 100 participants enrolled for each of 5 age cohorts categorized based on vaccine policy changes over time in the US. Immunization records for poliovirus vaccination were required for participants poliovirus serotypes. Seroprevalence was evaluated by demographics as well as between polio serotypes. The overall seroprevalence to poliovirus was 90.7%, 94.4%, and 83.3%, for types 1, 2, and 3, respectively. Seroprevalence was high (88.6%–96.2%) for all 3 types of poliovirus for the 6–10 y old age group that was likely to have received a complete schedule of IPV-only vaccination. Children 2–3 y of age, who have not yet completed their full IPV series, had lower seroprevalence compared with all older age groups for types 1 and 2 (p-value poliovirus in the population surveyed. Seroprevalence for subjects aged 2–3 y was lower than all other age groups for serotypes 1 and 2 highlighting the importance of completing the recommended poliovirus vaccine series with a booster dose at age 4–6 y. PMID:28059613

  2. Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants.

    NARCIS (Netherlands)

    R.D. Semba; M. Muhilal; N.E. Mohgaddam (Nasrin); Z. Munasir; A. Akib; D. Permaesih; M.S. Muherdiyantiningsih; A.D.M.E. Osterhaus (Albert)

    1999-01-01

    textabstractChildhood immunization programs may provide infrastructure for delivering vitamin A supplements to infants in developing countries. The effect of giving vitamin A, an immune enhancer, on antibody responses to trivalent oral poliovirus vaccine (TOPV) is unknown. A

  3. Viral Aetiology of Acute Flaccid Paralysis Surveillance Cases, before and after Vaccine Policy Change from Oral Polio Vaccine to Inactivated Polio Vaccine

    Directory of Open Access Journals (Sweden)

    T. S. Saraswathy Subramaniam

    2014-01-01

    Full Text Available Since 1992, surveillance for acute flaccid paralysis (AFP cases was introduced in Malaysia along with the establishment of the National Poliovirus Laboratory at the Institute for Medical Research. In 2008, the Ministry of Health, Malaysia, approved a vaccine policy change from oral polio vaccine to inactivated polio vaccine (IPV. Eight states started using IPV in the Expanded Immunization Programme, followed by the remaining states in January 2010. The objective of this study was to determine the viral aetiology of AFP cases below 15 years of age, before and after vaccine policy change from oral polio vaccine to inactivated polio vaccine. One hundred and seventy-nine enteroviruses were isolated from the 3394 stool specimens investigated between 1992 and December 2012. Fifty-six out of 107 virus isolates were polioviruses and the remaining were non-polio enteroviruses. Since 2009 after the sequential introduction of IPV in the childhood immunization programme, no Sabin polioviruses were isolated from AFP cases. In 2012, the laboratory AFP surveillance was supplemented with environmental surveillance with sewage sampling. Thirteen Sabin polioviruses were also isolated from sewage in the same year, but no vaccine-derived poliovirus was detected during this period.

  4. Vaccine-derived poliovirus surveillance in China during 2001-2013: the potential challenge for maintaining polio free status.

    Science.gov (United States)

    Wang, Hai-Bo; Luo, Hui-Ming; Li, Li; Fan, Chun-Xiang; Hao, Li-Xin; Ma, Chao; Su, Qi-Ru; Yang, Hong; Reilly, Kathleen H; Wang, Hua-Qing; Wen, Ning

    2017-12-02

    The goal of polio eradication is to complete elimination and containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived poliovirus (VDPV) surveillance in China from 2001-2013 is summarized in this report, which has important implications for the global polio eradication initiative. Acute flaccid paralysis (AFP) cases and their contacts with VDPVs isolated from fecal specimens were identified in our AFP surveillance system or by field investigation. Epidemiological and laboratory information for these children were analyzed and the reasons for the VDPV outbreak was explored. VDPVs were isolated from a total of 49 children in more than two-thirds of Chinese provinces from 2001-2013, including 15 VDPV cases, 15 non-polio AFP cases and 19 contacts of AFP cases or healthy subjects. A total of 3 circulating VDPVs (cVDPVs) outbreaks were reported in China, resulting in 6 cVDPVs cases who had not been vaccinated with oral attenuated poliomyelitis vaccine. Among the 4 immunodeficiency-associated VDPVs (iVDPVs) cases, the longest duration of virus excretion was about 20 months. In addition, one imported VDPV case from Myanmar was detected in Yunnan Province. Until all wild, vaccine-related and Sabin polioviruses are eradicated in the world, high quality routine immunization and sensitive AFP surveillance should be maintained, focusing efforts on underserved populations in high risk areas.

  5. Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

    Science.gov (United States)

    Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

    2015-09-11

    We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Next generation inactivated polio vaccine manufacturing to support post polio-eradication biosafety goals.

    Directory of Open Access Journals (Sweden)

    Yvonne E Thomassen

    Full Text Available 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.

  7. Quantifying low-frequency revertants in oral poliovirus vaccine using next generation sequencing.

    Science.gov (United States)

    Sarcey, Eric; Serres, Aurélie; Tindy, Fabrice; Chareyre, Audrey; Ng, Siemon; Nicolas, Marine; Vetter, Emmanuelle; Bonnevay, Thierry; Abachin, Eric; Mallet, Laurent

    2017-08-01

    Spontaneous reversion to neurovirulence of live attenuated oral poliovirus vaccine (OPV) serotype 3 (chiefly involving the n.472U>C mutation), must be monitored during production to ensure vaccine safety and consistency. Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) has long been endorsed by the World Health Organization as the preferred in vitro test for this purpose; however, it requires radiolabeling, which is no longer supported by many laboratories. We evaluated the performance and suitability of next generation sequencing (NGS) as an alternative to MAPREC. The linearity of NGS was demonstrated at revertant concentrations equivalent to the study range of 0.25%-1.5%. NGS repeatability and intermediate precision were comparable across all tested samples, and NGS was highly reproducible, irrespective of sequencing platform or analysis software used. NGS was performed on OPV serotype 3 working seed lots and monovalent bulks (n=21) that were previously tested using MAPREC, and which covered the representative range of vaccine production. Percentages of 472-C revertants identified by NGS and MAPREC were comparable and highly correlated (r≥0.80), with a Pearson correlation coefficient of 0.95585 (p<0.0001). NGS demonstrated statistically equivalent performance to that of MAPREC for quantifying low-frequency OPV serotype 3 revertants, and offers a valid alternative to MAPREC. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. A safe and reliable neutralization assay based on pseudovirus to measure neutralizing antibody titer against poliovirus.

    Science.gov (United States)

    Liu, Shaohua; Song, Dongmei; Bai, Han; Lu, Weiwei; Dai, Xinxian; Hao, Chunsheng; Zhang, Zhongyang; Guo, Huijie; Zhang, Yue; Li, Xiuling

    2017-12-01

    With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping. © 2017 Wiley Periodicals, Inc.

  9. Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases: a systematic review and implications for polio eradication.

    Science.gov (United States)

    Guo, Jean; Bolivar-Wagers, Sara; Srinivas, Nivedita; Holubar, Marisa; Maldonado, Yvonne

    2015-03-03

    Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide. We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization. We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries. Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases. Copyright © 2015

  10. Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

    OpenAIRE

    Friedrich, F.; Filippis, A. M. B.; Schatzmayr, H. G.

    1996-01-01

    Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS) in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal a...

  11. Comparison of culture, single and multiplex real-time PCR for detection of Sabin poliovirus shedding in recently vaccinated Indian children.

    Science.gov (United States)

    Giri, Sidhartha; Rajan, Anand K; Kumar, Nirmal; Dhanapal, Pavithra; Venkatesan, Jayalakshmi; Iturriza-Gomara, Miren; Taniuchi, Mami; John, Jacob; Abraham, Asha Mary; Kang, Gagandeep

    2017-08-01

    Although, culture is considered the gold standard for poliovirus detection from stool samples, real-time PCR has emerged as a faster and more sensitive alternative. Detection of poliovirus from the stool of recently vaccinated children by culture, single and multiplex real-time PCR was compared. Of the 80 samples tested, 55 (68.75%) were positive by culture compared to 61 (76.25%) and 60 (75%) samples by the single and one step multiplex real-time PCR assays respectively. Real-time PCR (singleplex and multiplex) is more sensitive than culture for poliovirus detection in stool, although the difference was not statistically significant. © 2017 Wiley Periodicals, Inc.

  12. Ausencia de circulación de poliovirus en departamentos colombianos con coberturas vacunales inferiores a 80% Absence of poliovirus circulation in Colombian departments with vaccination coverage below 80%

    Directory of Open Access Journals (Sweden)

    María Mercedes González

    2012-08-01

    Full Text Available El presente estudio se propuso explorar la posible circulación silente de poliovirus salvajes y derivados de la vacuna (VDPV, por sus siglas en inglés, en departamentos de Colombia con cobertura de vacunación para polio (OPV, por sus siglas en inglés menor de 80%. Se colectaron 52 muestras de aguas residuales que se concentraron mediante precipitación con polietilenglicol y cloruro de sodio. La detección viral se realizó mediante aislamiento y la identificación por neutralización del efecto citopático, así como mediante reacción en cadena de la polimerasa convencional y en tiempo real, posterior a la transcripción reversa (TR-RCP y rTR-RCP. Los poliovirus aislados se caracterizaron por secuenciación del gen VP1. En dos de las 52 muestras hubo presencia de poliovirus Sabin 2 con más de 99% de similitud de secuencia con la cepa OPV Sabin 2. Se detectó circulación de enterovirus no polio en 17,3% de las muestras. Los serotipos identificados correspondieron a coxsackievirus B1, echovirus 30 y echovirus 11. No se detectaron evidencias de circulación de VDPV ni poliovirus salvaje en los departamentos de Colombia con coberturas de OPV inferiores a 80%.This study aims to explore a possible silent circulation of wild and vaccine-derived polioviruses in departments of Colombia with polio vaccination coverage of below 80%. The study collected 52 samples of wastewater concentrated as a result of precipitation with polyethylene glycol and sodium chloride. The viral detection was carried out through isolation and the identification through neutralization of the cytopathic effect, as well as through a conventional polymerase chain reaction following reverse transcription. The isolated polioviruses were characterized by the VP1 gene sequence. In two of the 52 samples, there was a presence of the Sabin type 2 poliovirus with more than 99% sequence similarity with the Sabin type 2 strain polio. Circulation of the nonpolio enterovirus was

  13. The golden jubilee of vaccination against poliomyelitis.

    Science.gov (United States)

    John, T Jacob

    2004-01-01

    Inactivated poliovirus vaccine (IPV), developed in the USA by Jonas Salk in the early 1950s, was field tested in 1954, and found to be safe and effective. The year 2004 marks the golden jubilee of this breakthrough. From 1955 IPV was used extensively in the US and polio incidence declined by more than 95 per cent. However, in 1962, when oral poliovirus vaccine (OPV) became available, the national policy was shifted to its exclusive use, for reasons other than science and economics. The World Health Organisation (WHO) also adopted the policy of the exclusive use of OPV in developing countries. Thus IPV fell into disrepute in much of the world, while Northern European countries continued to use it. New research led to improving its potency, reducing its manufacturing costs and combining it with the diphtheria-tetanus-pertussis (DTP) vaccine to simplify its administration and reduce programmatic costs. All countries that chose to persist with IPV eliminated poliovirus circulation without OPV-induced polio or the risk of live vaccine viruses reverting to wild-like nature. IPV is highly immunogenic, confers mucosal immunity and exerts herd protective effect, all qualities of a good vaccine. It can be used in harmony with the extendend programme on immunization (EPI) schedule of infant immunisation with DTP, thus reducing programmatic costs. During the last ten years IPV has once again regained its popularity and some 25 industrialised countries use it exclusively. The demand is increasing from other countries and the supply has not caught up, leaving market forces to dictate the sale price of IPV. Anticipating such a turn of events India had launched its own IPV manufacturing programme in 1987, but the project was closed in 1992. Today it is not clear if we can complete the job of global polio eradication without IPV, on account of the genetic instability of OPV and the consequent tendency of vaccine viruses to revert to wild-like properties. The option to use IPV is

  14. Modeling the costs and benefits of temporary recommendations for poliovirus exporting countries to vaccinate international travelers.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Thompson, Kimberly M

    2017-07-05

    Recognizing that infectious agents readily cross international borders, the International Health Regulations Emergency Committee issues Temporary Recommendations (TRs) that include vaccination of travelers from countries affected by public health emergencies, including serotype 1 wild polioviruses (WPV1s). This analysis estimates the costs and benefits of TRs implemented by countries with reported WPV1 during 2014-2016 while accounting for numerous uncertainties. We estimate the TR costs based on programmatic data and prior economic analyses and TR benefits by simulating potential WPV1 outbreaks in the absence of the TRs using the rate and extent of WPV1 importation outbreaks per reported WPV1 case during 2004-2013 and the number of reported WPV1 cases that occurred in countries with active TRs. The benefits of TRs outweigh the costs in 77% of model iterations, resulting in expected incremental net economic benefits of $210 million. Inclusion of indirect costs increases the costs by 13%, the expected savings from prevented outbreaks by 4%, and the expected incremental net benefits by 3%. Despite the considerable costs of implementing TRs, this study provides health and economic justification for these investments in the context of managing a disease in advanced stages of its global eradication. Copyright © 2017 The Auhors. Published by Elsevier Ltd.. All rights reserved.

  15. Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis.

    Science.gov (United States)

    Foiadelli, Thomas; Savasta, Salvatore; Battistone, Andrea; Kota, Majlinda; Passera, Carolina; Fiore, Stefano; Bino, Silvia; Amato, Concetta; Lozza, Alessandro; Marseglia, Gian Luigi; Fiore, Lucia

    2016-06-10

    Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame. Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV. This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.

  16. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

    Science.gov (United States)

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

    2011-01-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

  17. Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

    Directory of Open Access Journals (Sweden)

    F. Friedrich

    1996-02-01

    Full Text Available Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal association between the isolation of the strains and the disease. Although the isolates from the GBS cases may not be the etiological agent of the disease, this study strongly indicates that infections caused by Sabin-related vaccine strains can trigger the GBS in certain cases.

  18. Public health response to the silent reintroduction of wild poliovirus to Israel, 2013-2014.

    Science.gov (United States)

    Moran-Gilad, J; Kaliner, E; Gdalevich, M; Grotto, I

    2016-12-01

    During 2013/14, Israel witnessed the silent reintroduction and sustained transmission of wild poliovirus type 1 (WPV1) detected through routine environmental surveillance performed on sewage samples. The public health response to silent poliovirus transmission in a population with high inactivated polio vaccine (IPV) coverage poses an emerging challenge towards the 'End Game' of global poliovirus eradication. This paper reviews the risk assessment, risk management and risk communication aspects of this poliovirus incident. Special emphasis is placed on the use of scientific data generated in the risk assessment phase to inform the public health response. Reintroducing a live vaccine in supplemental immunization activities in response to transmission of WPV or vaccine-derived poliovirus should be considered close to the 'End Game' of polio eradication, especially if targeting the population at risk is feasible. Such circumstances require a comprehensive contingency plan that will support the generation of important public health evidence at the risk assessment stage, thereby allowing to tailor the risk management approaches and underpin appropriate risk communication. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. [Genetic Characteristics of Type 2 Vaccine-derived Poliovirus in Shanxi Province (China) in 2014].

    Science.gov (United States)

    Yan, Dongrei; Li, Xiaolei; Zhang, Yong; Yang, Jianfang; Zhu, Shuangli; Wang, Dongyan; Zhang, Chuangye; Zhu, Hui; Xu, Wenbo

    2015-03-01

    The World Health Organization redefined the type 2 vaccine-derived poliovirus (VDPV) in 2010. To study the genetic characteristics and evolution of type 2 VDPV under this new definition, we conducted genome sequencing and analyses of type 2 VDPVs isolated from one patient with acute flaccid paralysis in Shanxi province (China) in 2014. Nucleotide sequencing revealed that the full-length of type 2 VDPV is 7439 bases encoding 2207 amino acids with no insertion or deletion of nucleotides compared with Sabin2. One nucleotide substitution identified as a key determinant of the attenuated phenotype of the Sabin 2 strain (A-G reversion at nucleotide nt 481 in the 5-end of the untranslated region) had reverted in the Shanxi type 2 VDPV. The other known key determinant of the attenuated phenotype of the Sabin 2 strain (U-->C reversion at nt2909 in the VP1 coding region that caused a Ile143Thr substitution in VP1) had not reverted in the Shanxi VDPV. The Shanxi type 2 VDPV was S2/S1 recombinant, the crossover site of which mapped to the 3-end of the 3D region (between nt 6247 and nt 6281). A phylogentic tree based on the VP1 coding region showed that evolution of the Shanxi type 2 VDPV was independent of other type 2 VDPVs detected worldwide. We estimated that the strain circulated for approximately = 11 months in the population according to the known evolution rate. The present study confirmed that the Chinese Polio Laboratory Network could discover the VDPV promptly and that it played an important part in maintenance of a polio-free China.

  20. Characteristics of an environmentally monitored prolonged type 2 vaccine derived poliovirus shedding episode that stopped without intervention.

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    Tapani Hovi

    Full Text Available Vaccine derived poliovirus (VDPV type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003-2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5'UTR, P1, P2, P3, and 3'UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV, including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1 individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2 genetic divergence of VDPV strains may remain extensive during years long replication in humans.

  1. Characteristics of an Environmentally Monitored Prolonged Type 2 Vaccine Derived Poliovirus Shedding Episode that Stopped without Intervention

    Science.gov (United States)

    Hovi, Tapani; Paananen, Anja; Blomqvist, Soile; Savolainen-Kopra, Carita; Al-Hello, Haider; Smura, Teemu; Shimizu, Hiroyuki; Nadova, Katarina; Sobotova, Zdenka; Gavrilin, Eugene; Roivainen, Merja

    2013-01-01

    Vaccine derived poliovirus (VDPV) type 2 strains strongly divergent from the corresponding vaccine strain, Sabin 2, were repeatedly isolated from sewage in Slovakia over a period of 22 months in 2003–2005. Cell cultures of stool specimens from known immune deficient patients and from an identified putative source population of 500 people failed to identify the potential excretor(s) of the virus. The occurrence of VDPV in sewage stopped without any intervention. No paralytic cases were reported in Slovakia during the episode. According to a GenBank search and similarity plotting-analysis, the closest known relative of the first isolate PV2/03/SVK/E783 through all main sections of the genome was the type 2 poliovirus Sabin strain, with nucleotide identities in 5′UTR, P1, P2, P3, and 3′UTR parts of the genome of 88.6, 85.9, 87.3, 88.5, and 94.0 percent, respectively. Phenotypic properties of selected Slovakian aVDPV strains resembled those of VDPV strains isolated from immune deficient individuals with prolonged PV infection (iVDPV), including antigenic changes and moderate neurovirulence in the transgenic mouse model. One hundred and two unique VP1 coding sequences were determined from VDPV strains isolated from 34 sewage specimens. Nucleotide differences from Sabin 2 in the VP1 coding region ranged from 12.5 to 15.6 percent, and reached a maximum of 9.6 percent between the VDPV strains under study. Most of the nucleotide substitutions were synonymous but as many as 93 amino acid positions out of 301 in VP1 showed substitutions. We conclude that (1) individuals with prolonged poliovirus infection are not as rare as suggested by the studies on immune deficient patients known to the health care systems and (2) genetic divergence of VDPV strains may remain extensive during years long replication in humans. PMID:23935826

  2. Sensitivity of C6 Glioma Cells Carrying the Human Poliovirus Receptor to Oncolytic Polioviruses.

    Science.gov (United States)

    Sosnovtseva, A O; Lipatova, A V; Grinenko, N F; Baklaushev, V P; Chumakov, P M; Chekhonin, V P

    2016-10-01

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

  3. Gender-specific mortality in DTP-IPV- and MMR±MenC-eligible age groups to determine possible sex-differential effects of vaccination: an observational study.

    Science.gov (United States)

    Schurink-van't Klooster, Tessa M; Knol, Mirjam J; de Melker, Hester E; van der Sande, Marianne A B

    2015-03-24

    Several studies suggested that vaccines could have non-specific effects on mortality depending on the type of vaccine. Non-specific effects seem to be different in boys and girls. In this study we want to investigate whether there are differences in gender-specific mortality among Dutch children according to the last vaccination received. We tested the hypothesis that the mortality rate ratio for girls versus boys is more favourable for girls following MMR±MenC vaccination (from 14 months of age) compared with the ratio following DTP-IPV vaccination (2-13 months of age). Secondarily, we investigated whether there were gender-specific changes in mortality following booster vaccination at 4 years of age. This observational study included all Dutch children aged 0-11 years from 2000 until 2011. Age groups were classified according to the last vaccination offered. The mortality rates for all natural causes of death were calculated by gender and age group. Incidence rate ratios (IRRs) were computed using a multivariable Poisson analysis to compare mortality in boys and girls across different age groups. The study population consisted of 6,261,472 children. During the study period, 14,038 children (0.22%) died, 91% of which were attributed to a known natural cause of death. The mortality rate for natural causes was higher among boys than girls in all age groups. Adjusted IRRs for girls compared with boys ranged between 0.81 (95% CI 0.74-0.89) and 0.91 (95% CI 0.77-1.07) over the age groups. The IRR did not significantly differ between all vaccine-related age groups (p=0.723), between children 2-13 months (following DTP-IPV vaccination) and 14 months-3 years (following MMR±MenC vaccination) (p=0.493) and between children 14 months-3 years and 4-8 years old (following DTP-IPV vaccination) (p=0.868). In the Netherlands, a high income country, no differences in gender-specific mortality related to the type of last vaccination received were observed in DTP-IPV- and MMR

  4. Implementation of coordinated global serotype 2 oral poliovirus vaccine cessation: risks of potential non-synchronous cessation.

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    Duintjer Tebbens, Radboud J; Hampton, Lee M; Thompson, Kimberly M

    2016-05-26

    The endgame for polio eradication involves coordinated global cessation of oral poliovirus vaccine (OPV) with cessation of serotype 2 OPV (OPV2 cessation) implemented in late April and early May 2016 and cessation of serotypes 1 and 3 OPV (OPV13 cessation) currently planned for after 2018. The logistics associated with globally switching all use of trivalent OPV (tOPV) to bivalent OPV (bOPV) represent a significant undertaking, which may cause some complications, including delays that lead to different timing of the switch across shared borders. Building on an integrated global model for long-term poliovirus risk management, we consider the expected vulnerability of different populations to transmission of OPV2-related polioviruses as a function of time following the switch. We explore the relationship between the net reproduction number (Rn) of OPV2 at the time of the switch and the time until OPV2-related viruses imported from countries still using OPV2 can establish transmission. We also analyze some specific situations modeled after populations at high potential risk of circulating serotype 2 vaccine-derived poliovirus (cVDPV2) outbreaks in the event of a non-synchronous switch. Well-implemented tOPV immunization activities prior to the tOPV to bOPV switch (i.e., tOPV intensification sufficient to prevent the creation of indigenous cVDPV2 outbreaks) lead to sufficient population immunity to transmission to cause die-out of any imported OPV2-related viruses for over 6 months after the switch in all populations in the global model. Higher Rn of OPV2 at the time of the switch reduces the time until imported OPV2-related viruses can establish transmission and increases the time during which indigenous OPV2-related viruses circulate. Modeling specific connected populations suggests a relatively low vulnerability to importations of OPV2-related viruses that could establish transmission in the context of a non-synchronous switch from tOPV to bOPV, unless the gap

  5. The challenge of changing the inactivated poliomyelitis vaccine in Latin America: declaration of the Latin American Society of Pediatric Infectious Diseases (SLIPE).

    Science.gov (United States)

    Falleiros-Arlant, Luiza Helena; Avila-Agüero, María Luisa; Brea del Castillo, José; Mariño, Cristina

    2014-10-01

    Even though we have already covered 99% of the path to eradicate poliomyelitis from the world, this disease is still causing paralysis in children. Its eradication means not only the end of wild poliovirus circulation, but vaccine-derived poliovirus circulation as well. Taking into account different factors such as: current epidemiological data, adverse events of the attenuated oral poliomyelitis vaccine (OPV), the availability of an injectable inactivated vaccine (IPV) without the potential of causing the severe adverse events of the oral vaccine (OPV), the efficacy and effectiveness of the IPV in several countries of the world where it has been used for several years, the rationale of changing the vaccination schedule in different Latin American countries; the Latin American Society of Pediatric Infectious Diseases (SLIPE) announces its recommendation of switching to IPV in Latin America, by this Declaration, with an Action Plan for 2014-2015 period as regards vaccination against polio policies in Latin America. 1. The optimal proposed schedule consists of four IPV doses (three doses in the primary schedule plus a booster dose), whether IPV is combined or not with other indicated vaccines in the immunization program of the country. During the OPV to IPV transition phase, an alternative schedule is acceptable; 2. Countries should set optimal strategies in order to maintain and improve vaccination coverage, and implement a nominal immunization registry; 3. Improving the Epidemiological Surveillance of Acute Flaccid Paralysis (AFP) and setting up an environmental surveillance program; 4. Setting up strategies for introducing IPV in National Immunization Programs, such as communicating properly with the population, among others; 5. Bringing scientific societies closer to decision makers; 6. Ensuring optimal supply and prices for IPV introduction; 7. Training vaccination teams; 8. Enhancing the distribution and storing logistics of vaccines. In addition to the

  6. Molecular and Phenotypic Characterization of a Highly Evolved Type 2 Vaccine-Derived Poliovirus Isolated from Seawater in Brazil, 2014.

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    Klécia Marília S de Melo Cassemiro

    Full Text Available A type 2 vaccine-derived poliovirus (VDPV, differing from the Sabin 2 strain at 8.6% (78/903 of VP1 nucleotide positions, was isolated from seawater collected from a seaport in São Paulo State, Brazil. The P1/capsid region is related to the Sabin 2 strain, but sequences within the 5'-untranslated region and downstream of the P1 region were derived from recombination with other members of Human Enterovirus Species C (HEV-C. The two known attenuating mutations had reverted to wild-type (A481G in the 5'-UTR and Ile143Thr in VP1. The VDPV isolate had lost the temperature sensitive phenotype and had accumulated amino acid substitutions in neutralizing antigenic (NAg sites 3a and 3b. The date of the initiating OPV dose, estimated from the number of synonymous substitutions in the capsid region, was approximately 8.5 years before seawater sampling, a finding consistent with a long time of virus replication and possible transmission among several individuals. Although no closely related type 2 VDPVs were detected in Brazil or elsewhere, this VDPV was found in an area with a mobile population, where conditions may favor both viral infection and spread. Environmental surveillance serves as an important tool for sensitive and early detection of circulating poliovirus in the final stages of global polio eradication.

  7. Persistence of hepatitis B immune memory until 9-10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP∼T vaccination at 2, 4 and 6 months.

    Science.gov (United States)

    Kosalaraksa, Pope; Chokephaibulkit, Kulkanya; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate; B'Chir, Siham; Da Costa, Xavier; Vidor, Emmanuel

    2018-01-15

    To evaluate the long-term persistence of anti-hepatitis B surface (HBs) antibodies and the response to a HB challenge re-vaccination in children who had received a primary series of DTaP-IPV-HB-PRP∼T (Hexaxim™) or DTaP-IPV-HB/PRP∼T (Infanrix hexa™). Two cohorts of participants who had previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T co-administered with PCV7 at 2, 4, 6 months of age in a randomized, Phase III, observer-blind study in Thailand, were followed up for anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP] rate [% of participants with a titer ≥10 mIU/mL]) at 12-18 months of age and 9-10 years of age. A monovalent HB challenge re-vaccination was administered at 9-10 years of age and the anamnestic response was evaluated. Anti-HBs GMCs and SP rates in the DTaP-IPV-HB-PRP∼T and DTaP-IPV-HB/PRP∼T groups were high and similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL and 99.5%, respectively) and declined to a similar extent in each group at 12-18 months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively). Antibody levels further declined at 9-10 years of age (13.3 mIU/mL and 49.3% and 8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group post-HB challenge re-vaccination (92.8% and 98.7%, respectively). The kinetics of long-term anti-HBs antibody persistence were similar following a primary series of DTaP-IPV-HB-PRP∼T or DTaP-IPV-HB/PRP∼T. The response to a subsequent HB challenge re-vaccination was strong and similar in each group, demonstrating persisting immune memory.

  8. Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern Nigeria.

    Science.gov (United States)

    Gofama, Mustapha Modu; Verma, Harish; Abdullahi, Hamisu; Molodecky, Natalie A; Craig, Kehinde T; Urua, Utibe-Abasi; Garba, Mohammed Ashir; Alhaji, Mohammed Arab; Weldon, William C; Oberste, M Steven; Braka, Fiona; Muhammad, Ado J G; Sutter, Roland W

    2017-01-01

    Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV) on antibody seroprevalence. We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child's health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%), 86% (79-91%), and 72% (65-79%) in Borno State, and 75% (67-81%), 74% (66-81%) and 69% (61-76%) in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%)]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and anti

  9. Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern Nigeria.

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    Mustapha Modu Gofama

    Full Text Available Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV on antibody seroprevalence.We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child's health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%, 86% (79-91%, and 72% (65-79% in Borno State, and 75% (67-81%, 74% (66-81% and 69% (61-76% in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and

  10. Evolution and circulation of type-2 vaccine-derived polioviruses in Nad Ali district of Southern Afghanistan during June 2009-February 2011.

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    Salmaan Sharif

    Full Text Available Oral polio vaccine has been used successfully as a powerful tool to control the spread of wild polioviruses throughout the world; however, during replication in under immunized children, some vaccine viruses revert and acquire the neurovirulent phenotypic properties. In this study, we describe the evolution and circulation of Vaccine-Derived Polioviruses (VDPVs in Helmand province of Afghanistan. We investigated 2646 AFP cases of Afghan children from June 2009-February 2011 and isolated 103 (04% vaccine viruses, 45(1.7% wild type polioviruses and six (0.22% type 2 circulating vaccine-derived polioviruses (cVDPVs. These cVDPVs showed 97.7%-98.2% nucleotide and 98%-98.7% amino acid homology in VP1 region on comparison with Sabin type 2 reference strain. All these cVDPVs had two signature mutations of neurovirulent phenotypes and 12 additional mutations in P1 capsid region that might also have contributed to increase neurovirulence and replication. Phylogenetic analysis revealed that all these viruses were closely related and originated from previously reported Sabin like 2 virus from Pakistan which did not conform to the standard definition of VDPVs at that time. It was also observed that initial OPV dose was administered approximately 9 months prior to the collection of first stool specimen of index case. Our findings support that suboptimal surveillance and low routine immunization coverage have contributed to the emergence and spread of these viruses in Afghanistan. We therefore recommend high quality immunization campaigns not only in affected district Nad Ali but also in the bordering areas between Pakistan and Afghanistan to prevent the spread of cVDPVs.

  11. Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.

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    Tapani Hovi

    Full Text Available Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2 were compared to those of type 1 and type 3 wild poliovirus (WPV lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv bias and strikingly lower Ts/Tv rate ratios at the 2(nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (cVDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

  12. The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001-11: a retrospective analysis.

    Science.gov (United States)

    O'Reilly, Kathleen M; Durry, Elias; ul Islam, Obaid; Quddus, Arshad; Abid, Ni'ma; Mir, Tahir P; Tangermann, Rudi H; Aylward, R Bruce; Grassly, Nicholas C

    2012-08-04

    Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010-11 led the Executive Board of WHO in January, 2012, to declare polio eradication a "programmatic emergency for global public health". We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. We did a matched case-control analysis based on a database of 46,977 children aged 0-14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0-2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6-18·8) compared with 34·5% (16·1-48·9) for monovalent OPV (p=0·007) and 23·4% (10·4-34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006-11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced population

  13. The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001–11: a retrospective analysis

    Science.gov (United States)

    O'Reilly, Kathleen M; Durry, Elias; ul Islam, Obaid; Quddus, Arshad; Abid, Ni'ma; Mir, Tahir P; Tangermann, Rudi H; Aylward, R Bruce; Grassly, Nicholas C

    2012-01-01

    Summary Background Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010–11 led the Executive Board of WHO in January, 2012, to declare polio eradication a “programmatic emergency for global public health”. We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. Methods We did a matched case-control analysis based on a database of 46 977 children aged 0–14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0–2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. Findings Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6–18·8) compared with 34·5% (16·1–48·9) for monovalent OPV (p=0·007) and 23·4% (10·4–34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006–11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in

  14. Possible global strategies for stopping polio vaccination and how they could be harmonized.

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    Cochi, S L; Sutter, R W; Aylward, R B

    2001-01-01

    One of the challenges of the polio eradication initiative over the next few years will be the formulation of an optimal strategy for stopping poliovirus vaccination after global certification of polio eradication has been accomplished. This strategy must maximize the benefits and minimize the risks. A number of strategies are currently under consideration, including: (i) synchronized global discontinuation of use of oral poliovirus vaccine (OPV); (ii) regional or subregional coordinated OPV discontinuation; and (iii) moving from trivalent to bivalent or monovalent OPV. Other options include moving from OPV to global use of IPV for an interim period before cessation of IPV use (to eliminate circulation of vaccine-derived poliovirus, if necessary) or development of new OPV strains that are not transmissible. Each of these strategies is associated with specific advantages (financial benefits for OPV discontinuation) and disadvantages (cost of switch to IPV) and inherent uncertainties (risk of continued poliovirus circulation in certain populations or prolonged virus replication in immunodeficient persons). An ambitious research agenda addresses the remaining questions and issues. Nevertheless, several generalities are already clear. Unprecedented collaboration between countries, regions, and indeed the entire world will be required to implement a global OPV discontinuation strategy Regulatory approval will be needed for an interim bivalent OPV or for monovalent OPV in many countries. Manufacturers will need sufficient lead time to produce sufficient quantities of IPV Finally, the financial implications for any of these strategies need to be considered. Whatever strategy is followed it will be necessary to stockpile supplies of a poliovirus-containing vaccine (most probably all three types of monovalent OPV), and to develop contingency plans to respond should an outbreak of polio occur after stopping vaccination.

  15. Implementasi Migrasi Ipv4 Ke Ipv6

    OpenAIRE

    Syafrizal, Melwin; Qamar, Syamsul; Aji, Damawan Bayu

    2013-01-01

    IPv4 yang digunakan di jaringan publik (internet) sudah habis, sehingga kebutuhan koneksi internet baru tidak dapat dilayani. Layanan baru, konten baru, domain name baru, server baru, router baru tidak dapat koneksi ke internet, kecuali menggunakan IPv6. Migrasi IPv4 ke IPv6 bukan hal yang mudah, pengetahuan baru tentang IPv6 perlu dipelajari, kondisi-kondisi yang akan dialami akibat Perubahan IP, mekanisme transisi, atau mekanisme routing perlu dipahami. Cara-cara konfigurasi IPv6 pada berba...

  16. Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.

    Science.gov (United States)

    van den Bergh, Menno R; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H; Sanders, Elisabeth A M

    2016-07-01

    Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered. We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster. Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups. Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.

  17. Natural type 3/type 2 intertypic vaccine-related poliovirus recombinants with the first crossover sites within the VP1 capsid coding region.

    Science.gov (United States)

    Zhang, Yong; Zhu, Shuangli; Yan, Dongmei; Liu, Guiyan; Bai, Ruyin; Wang, Dongyan; Chen, Li; Zhu, Hui; An, Hongqiu; Kew, Olen; Xu, Wenbo

    2010-12-21

    Ten uncommon natural type 3/type 2 intertypic poliovirus recombinants were isolated from stool specimens from nine acute flaccid paralysis case patients and one healthy vaccinee in China from 2001 to 2008. Complete genomic sequences revealed their vaccine-related genomic features and showed that their first crossover sites were randomly distributed in the 3' end of the VP1 coding region. The length of donor Sabin 2 sequences ranged from 55 to 136 nucleotides, which is the longest donor sequence reported in the literature for this type of poliovirus recombination. The recombination resulted in the introduction of Sabin 2 neutralizing antigenic site 3a (NAg3a) into a Sabin 3 genomic background in the VP1 coding region, which may have been altered by some of the type 3-specific antigenic properties, but had not acquired any type 2-specific characterizations. NAg3a of the Sabin 3 strain seems atypical; other wild-type poliovirus isolates that have circulated in recent years have sequences of NAg3a more like the Sabin 2 strain. 10 natural type 3/type 2 intertypic VP1 capsid-recombinant polioviruses, in which the first crossover sites were found to be in the VP1 coding region, were isolated and characterized. In spite of the complete replacement of NAg3a by type 2-specific amino acids, the serotypes of the recombinants were not altered, and they were totally neutralized by polyclonal type 3 antisera but not at all by type 2 antisera. It is possible that recent type 3 wild poliovirus isolates may be a recombinant having NAg3a sequences derived from another strain during between 1967 and 1980, and the type 3/type 2 recombination events in the 3' end of the VP1 coding region may result in a higher fitness.

  18. Natural type 3/type 2 intertypic vaccine-related poliovirus recombinants with the first crossover sites within the VP1 capsid coding region.

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    Full Text Available BACKGROUND: Ten uncommon natural type 3/type 2 intertypic poliovirus recombinants were isolated from stool specimens from nine acute flaccid paralysis case patients and one healthy vaccinee in China from 2001 to 2008. PRINCIPAL FINDINGS: Complete genomic sequences revealed their vaccine-related genomic features and showed that their first crossover sites were randomly distributed in the 3' end of the VP1 coding region. The length of donor Sabin 2 sequences ranged from 55 to 136 nucleotides, which is the longest donor sequence reported in the literature for this type of poliovirus recombination. The recombination resulted in the introduction of Sabin 2 neutralizing antigenic site 3a (NAg3a into a Sabin 3 genomic background in the VP1 coding region, which may have been altered by some of the type 3-specific antigenic properties, but had not acquired any type 2-specific characterizations. NAg3a of the Sabin 3 strain seems atypical; other wild-type poliovirus isolates that have circulated in recent years have sequences of NAg3a more like the Sabin 2 strain. CONCLUSIONS: 10 natural type 3/type 2 intertypic VP1 capsid-recombinant polioviruses, in which the first crossover sites were found to be in the VP1 coding region, were isolated and characterized. In spite of the complete replacement of NAg3a by type 2-specific amino acids, the serotypes of the recombinants were not altered, and they were totally neutralized by polyclonal type 3 antisera but not at all by type 2 antisera. It is possible that recent type 3 wild poliovirus isolates may be a recombinant having NAg3a sequences derived from another strain during between 1967 and 1980, and the type 3/type 2 recombination events in the 3' end of the VP1 coding region may result in a higher fitness.

  19. An outbreak of type π vaccine-derived poliovirus in Sichuan province, China: emergence and circulation in an under-immunized population.

    Directory of Open Access Journals (Sweden)

    Hai-Bo Wang

    Full Text Available BACKGROUND: During August 2011-February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs occurred in Sichuan Province, China. METHODS: A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. RESULTS: One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8-1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5-12 nucleotides (nt and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months reported in Ngawa Prefecture in 2011, 4 (57.1% cases (including 2 polio cases did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs were conducted in February-May, 2012, and the strain has not been isolated since. CONCLUSION: High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.

  20. Inactivated polio vaccine: time to introduce it in India's national immunization schedule.

    Science.gov (United States)

    Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj

    2012-07-01

    Polio is a communicable disease caused by poliovirus that may attack nerve cells of the brain and spinal cord. The victims develop neurological complications, likes stiffness of the neck, muscular weakness, or paralysis of one or more limbs. In severe cases, it may be fatal due to respiratory paralysis. The world has seen tremendous gains in polio eradication over the past year. India and Nigeria saw a reduction in cases of almost 95% from 2009 to 2010, and cases of wild poliovirus type 3 (WPV3) fell by 92% globally over the same period. In fact, no case has been reported in India since February 2011, such that India may be on the verge of eradicating polio. Nevertheless, polio control experts are particularly worried about Vaccine-Derived Poliovirus (VDPV). Global surveillance efforts picked up 430 cases of VDPV from several countries between July 2009 and March 2011. In India, 7 cases of VDPV were reported during the year 2011. As long as OPV is used, virologists say that the world is at risk of VDPV causing polio in unprotected children. Achieving a polio-free world will require the "cessation of all OPV" and with it the elimination of the risk of vaccine-associated paralytic polio (VAPP) or VDPV infections. To this effect, in 2011 the Global Polio Eradication Initiative (GPEI) will produce and develop a new roadmap for VDPV Elimination. Several countries have shifted from all OPV to sequential OPV-IPV schedules and all-IPV schedules with elimination of live poliovirus. IPV will be indispensable in the post-eradication era when use of OPV has to stop but "vaccination against polio" cannot stop. IPV offers complete individual protection and has been considered as an additional tool at present for those who can afford the vaccine, and since we are nearing the eradication of polio, it is time to shift from OPV to sequential OPV-IPV schedule in India. Such a strategy will avoid inevitable problems with VAPP.

  1. Standardized Methods for Detection of Poliovirus Antibodies.

    Science.gov (United States)

    Weldon, William C; Oberste, M Steven; Pallansch, Mark A

    2016-01-01

    Testing for neutralizing antibodies against polioviruses has been an established gold standard for assessing individual protection from disease, population immunity, vaccine efficacy studies, and other vaccine clinical trials. Detecting poliovirus specific IgM and IgA in sera and mucosal specimens has been proposed for evaluating the status of population mucosal immunity. More recently, there has been a renewed interest in using dried blood spot cards as a medium for sample collection to enhance surveillance of poliovirus immunity. Here, we describe the modified poliovirus microneutralization assay, poliovirus capture IgM and IgA ELISA assays, and dried blood spot polio serology procedures for the detection of antibodies against poliovirus serotypes 1, 2, and 3.

  2. Combinations of Quality and Frequency of Immunization Activities to Stop and Prevent Poliovirus Transmission in the High-Risk Area of Northwest Nigeria.

    Directory of Open Access Journals (Sweden)

    Radboud J Duintjer Tebbens

    Full Text Available Frequent supplemental immunization activities (SIAs with the oral poliovirus vaccine (OPV represent the primary strategy to interrupt poliovirus transmission in the last endemic areas.Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs after OPV cessation.More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality. Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation.National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency.

  3. Combinations of Quality and Frequency of Immunization Activities to Stop and Prevent Poliovirus Transmission in the High-Risk Area of Northwest Nigeria.

    Science.gov (United States)

    Duintjer Tebbens, Radboud J; Pallansch, Mark A; Wassilak, Steven G F; Cochi, Stephen L; Thompson, Kimberly M

    2015-01-01

    Frequent supplemental immunization activities (SIAs) with the oral poliovirus vaccine (OPV) represent the primary strategy to interrupt poliovirus transmission in the last endemic areas. Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI) and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs) after OPV cessation. More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV) could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality). Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation. National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency.

  4. Polio Endgame, Information Gaps Related to Vaccines and Immunity.

    Science.gov (United States)

    Ahmad, Mohammad; Bahl, Sunil; Kunwar, Abhishek

    2016-08-07

    Evidence generated through research studies has guided programmatic actions and fine-tuned strategies for the Global Polio Eradication Initiative (GPEI). However, many gaps still persist in the understanding of a risk-free implementation of the polio endgame. Immediate concerns relate to the introduction of inactivated polio vaccine (IPV) and switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) in routine immunization schedule. A comprehensive understanding of mucosal immunity in populations and best response options against circulating vaccine derived poliovirus (cVDPV) outbreaks in post tOPV-bOPV switch is essential to mitigate the risks of wild and vaccine-derived poliovirus importations and emergence of cVDPVs in polio-free countries. A clearer picture is also needed on few operational issues, interference between polio vaccines and other EPI vaccines and products related to polio endgame. It is also extremely important to develop mechanisms to identify and manage long-term poliovirus excretors who may pose a risk of reintroduction into the population after global eradication of poliovirus.

  5. Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

    Science.gov (United States)

    Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

    2016-06-01

    Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

  6. The Switch From Trivalent to Bivalent Oral Poliovirus Vaccine in the South-East Asia Region.

    Science.gov (United States)

    Bahl, Sunil; Hasman, Andreas; Eltayeb, Abu Obeida; James Noble, Douglas; Thapa, Arun

    2017-07-01

    This analysis describes an innovative and successful approach to risk identification and mitigation in relation to the switch from trivalent to bivalent oral polio vaccine (OPV) in the 11 countries of the World Health Organization's (WHO's) South-East Asia Region (SEAR) in April 2016.The strong commitment of governments and immunization professionals to polio eradication and an exemplary partnership between the WHO, United Nations Children's Fund (UNICEF), and other partners and stakeholders in the region and globally were significant contributors to the success of the OPV switch in the SEAR. Robust national switch plans were developed and country-specific innovations were planned and implemented by the country teams. Close monitoring and tracking of the activities and milestones through dashboards and review meetings were undertaken at the regional level to ensure that implementation time lines were met, barriers identified, and solutions for overcoming challenges were discussed and implemented.The SEAR was the first WHO Region globally to complete the switch and declare the successful withdrawal of trivalent OPV from all countries on 17 May 2016.A number of activities implemented during the switch process are likely to contribute positively to existing immunization practices and to similar initiatives in the future. These activities include better vaccine supply chain management, improved mechanisms for disposal of vaccination-related waste materials, and a closer collaboration with drug regulators, vaccine manufacturers, and the private sector for immunization-related initiatives. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. IPv4-protokollasta siirtyminen IPv6-protokollaan

    OpenAIRE

    Ylituomaala, Jaakko

    2011-01-01

    Tässä työssä tutkitaan IPv6-osoiteavaruutta, sekä IPv6-protokollan yhteensopivuutta IPv4-protokollan kanssa. Työssä käydään läpi myös yleisimmät IPv4-yhteensopivat IPv6-reititysmenetelmät. Tutkimuksessa tutustutaan pääpiirteittäin IPv4-osoiteluokkiin, itse osoitteisiin ja IPv4-headeriin. IPv4 osoiteryhmiä on viisi, jotka ovat A, B, C, D ja E. Lisäksi luodaan katsaus IPv4-headerin eri osioihin ja tutustutaan niiden käyttötarkoituksiin. Työssä käydään läpi myös osittain NAT-toiminto. Tu...

  8. Intranasal and sublingual delivery of inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  9. A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.

    Science.gov (United States)

    Marlow, Robin; Kuriyakose, Sherine; Mesaros, Narcisa; Han, Htay Htay; Tomlinson, Richard; Faust, Saul N; Snape, Matthew D; Pollard, Andrew J; Finn, Adam

    2018-04-19

    To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group. Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. NCT01245049 (ClinicalTrials.gov). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All

  10. IPv6 Essentials

    CERN Document Server

    Hagen, Silvia

    2006-01-01

    IPv6 Essentials, Second Edition provides a succinct, in-depth tour of all the new features and functions in IPv6. It guides you through everything you need to know to get started, including how to configure IPv6 on hosts and routers and which applications currently support IPv6. Aimed at system and network administrators, engineers, network designers, and IT managers, this book will help you understand, plan for, design, and integrate IPv6 into your current IPv4 infrastructure

  11. Transition from IPv4 to IPv6

    DEFF Research Database (Denmark)

    Henten, Anders; Tadayoni, Reza

    The paper examines the transition from IPv4 to IPv6. More specifically, the aim of the paper is to present information on the status of the transition process and on the drivers and barriers concerning this transition. This includes an update on the availability of IPv4 addresses and on how far t...... the adoption of IPv6 has come. It also includes a discussion on what but also who the drivers and barriers are, including an examination of the implications of implementing transfer markets for IPv4 addresses.......The paper examines the transition from IPv4 to IPv6. More specifically, the aim of the paper is to present information on the status of the transition process and on the drivers and barriers concerning this transition. This includes an update on the availability of IPv4 addresses and on how far...

  12. IPv6-protokolla

    OpenAIRE

    Hautanen, Jukka-Pekka

    2012-01-01

    Tämän työn tarkoituksena on tutkia IPv6-protokollaa ja IPv6-protokollan yhteensopivuutta IPv4-protokollan kanssa. Työn alussa tarkastellaan IPv6-protokollan historiaa ja tämän hetkistä levinneisyyttä. Työssä paneudutaan tarkemmin IPv6-protokollan pääpiirteisiin: IPv6-protokollan osoitetyypit ja niiden esitystavat, aliverkotus, IPv6-protokollan uudistetun otsikon rakenne ja uudet lisäotsikot. Edellä mainittuja pääpiirteitä verrataan tarvittaessa IPv4-protokollaan, jotta nähdään parannukset...

  13. Rare natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus isolated from a case of acute flaccid paralysis in Brazil, 2015.

    Science.gov (United States)

    Cassemiro, Klécia M S M; Burlandy, Fernanda M; da Silva, Edson E

    2016-07-01

    A natural type 3/type 2 intertypic capsid recombinant vaccine-related poliovirus was isolated from an acute flaccid paralytic case in Brazil. Genome sequencing revealed the uncommon location of the crossover site in the VP1 coding region (nucleotides 3251-3258 of Sabin 3 genome). The Sabin 2 donor sequence replaced the last 118 nt of VP1, resulting in the substitution of the complete antigenic site IIIa by PV2-specific amino acids. The low overall number of nucleotide substitutions in P1 region indicated that the predicted replication time of the isolate was about 8-9 weeks. Two of the principal determinants of attenuation in Sabin 3 genomes were mutated (U472C and C2493U), but the temperature-sensitive phenotype of the isolate was preserved. Our results support the theory that there exists a PV3/PV2 recombination hotspot site in the tail region of the VP1 capsid protein and that the recombination may occur soon after oral poliovirus vaccine administration.

  14. Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data.

    Science.gov (United States)

    Pons-Salort, Margarita; Molodecky, Natalie A; O'Reilly, Kathleen M; Wadood, Mufti Zubair; Safdar, Rana M; Etsano, Andrew; Vaz, Rui Gama; Jafari, Hamid; Grassly, Nicholas C; Blake, Isobel M

    2016-10-01

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

  15. Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial.

    Science.gov (United States)

    Mir, Fatima; Quadri, Farheen; Mach, Ondrej; Ahmed, Imran; Bhatti, Zaid; Khan, Asia; Rehman, Najeeb Ur; Durry, Elias; Salama, Maha; Oberste, Steven M; Weldon, William C; Sutter, Roland W; Zaidi, Anita K M

    2015-08-01

    Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per

  16. IPv4 to IPv6 Transformation Schemes

    Science.gov (United States)

    Miyakawa, Shin

    According to the recent observations of IPv4 (Internet Protocol version 4) address allocation status, it will be running out within few years. Consequently, to ensure the continuous extension of the Internet operation, introducing IPv6 (Internet Protocol version 6) protocol is surely needed. But at the same time, such transformation must be “smooth” for every Internet users and be compatible with today's IPv4 based practices. This paper describes several techniques and usage scenario which are discussed mainly in the IETF — Internet Engineering Task Force — and tried to be implemented as prototype products to transform today's Internet towards the IPv6 based one.

  17. IPv6 Testing

    National Research Council Canada - National Science Library

    Landis, Christopher B

    2006-01-01

    .... The DoD is also forming working relationships to conduct testing and share information. IPv6 was developed to resolve the issues of IPv4, mainly the limited amount of addresses and lack of security...

  18. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America.

    Science.gov (United States)

    Tregnaghi, Miguel W; Abate, Héctor J; Valencia, Alejandra; Lopez, Pio; Da Silveira, Themis Reverbel; Rivera, Luis; Rivera Medina, Doris Maribel; Saez-Llorens, Xavier; Gonzalez Ayala, Silvia Elena; De León, Tirza; Van Doorn, Leen-Jan; Pilar Rubio, Maria Del; Suryakiran, Pemmaraju Venkata; Casellas, Javier M; Ortega-Barria, Eduardo; Smolenov, Igor V; Han, Htay-Htay

    2011-06-01

    The efficacy of a rotavirus vaccine against severe rotavirus gastroenteritis when coadministered with routine Expanded Program on Immunization (EPI) vaccines including oral polio vaccine (OPV) was evaluated in this study. Double-blind, randomized (2:1), placebo-controlled study conducted across 6 Latin American countries. Healthy infants (N = 6568) 6 to 12 weeks of age received 2 doses of RIX4414 vaccine or placebo following a 0, 1- to 2-month schedule. Routine vaccines including OPV were coadministered according to local EPI schedule. Vaccine efficacy (VE) against severe rotavirus gastroenteritis caused by circulating wild-type rotavirus from 2 weeks post-Dose 2 until 1 year of age was calculated with 95% confidence interval [CI]. Safety was assessed during the entire study period. Immunogenicity of RIX4414 and OPV was also assessed. During the efficacy follow-up period (mean duration = 7.4 months), 7 and 19 cases of severe rotavirus gastroenteritis were reported in the vaccine and placebo groups, respectively, with a VE of 81.6% (95% CI: 54.4-93.5). VE against severe rotavirus gastroenteritis caused by G1 type was 100% (95% CI: rotavirus types, respectively. There was no difference (P = 0.514) in the incidence of serious adverse events reported in the 2 groups. Antirotavirus IgA seropositivity rate at 1 to 2 months post-Dose 2 was 61.4% (95% CI: 53.7-68.6) in the RIX4414 group; similar seroprotection rates (≥96.0%) against the 3 antipoliovirus types was observed 1 month post-Dose 3 of OPV in both groups. RIX4414 was highly efficacious against severe rotavirus gastroenteritis caused by the circulating wild-type rotavirus (G1 and non-G1) when coadministered with routine EPI vaccines including OPV.

  19. IPv6:n tietoturvaominaisuudet

    OpenAIRE

    Sorsa, Kari

    2013-01-01

    Opinnäytetyön tavoitteena on esitellä IPv6-protokolla ja selvittää sen tärkeimmät tietoturvaominaisuudet ja -riskit. Työtä tullaan käyttämään teoreettisena apuna Turun Ammattikorkeakoulun Lemminkäisenkadun toimipisteen laboratorioverkon siirtämisessä IPv6:een. Opinnäytetyö on jaettu kolmeen osaan. Ensimmäisessä esitellään lyhyesti IPv6:n historia ja kehitysvaiheet sekä uuden protokollan ominaisuudet. Toinen osa koostuu ominaisuus- ja tietoturvavertailusta IPv4:n ja IPv6:n välillä, jo...

  20. Planning for IPv6

    CERN Document Server

    Hagen, Silvia

    2011-01-01

    It's official: with IPv4 network addresses close to depletion, moving to IPv6 is now business critical. This concise book helps you plan for IPv6 integration by providing a high-level overview of the technical-and nontechnical-steps involved. Many of the challenges for your enterprise are on the organizational level, and solutions differ from company to company. IPv6 Essentials author Silvia Hagen, a protocol analysis and directory service expert who's worked with IPv6 international groups and forums for 10 years, supplies answers to the issues most frequently discussed by the clients she co

  1. IPv6 Security

    Science.gov (United States)

    Babik, M.; Chudoba, J.; Dewhurst, A.; Finnern, T.; Froy, T.; Grigoras, C.; Hafeez, K.; Hoeft, B.; Idiculla, T.; Kelsey, D. P.; López Muñoz, F.; Martelli, E.; Nandakumar, R.; Ohrenberg, K.; Prelz, F.; Rand, D.; Sciabà, A.; Tigerstedt, U.; Traynor, D.; Wartel, R.

    2017-10-01

    IPv4 network addresses are running out and the deployment of IPv6 networking in many places is now well underway. Following the work of the HEPiX IPv6 Working Group, a growing number of sites in the Worldwide Large Hadron Collider Computing Grid (WLCG) are deploying dual-stack IPv6/IPv4 services. The aim of this is to support the use of IPv6-only clients, i.e. worker nodes, virtual machines or containers. The IPv6 networking protocols while they do contain features aimed at improving security also bring new challenges for operational IT security. The lack of maturity of IPv6 implementations together with the increased complexity of some of the protocol standards raise many new issues for operational security teams. The HEPiX IPv6 Working Group is producing guidance on best practices in this area. This paper considers some of the security concerns for WLCG in an IPv6 world and presents the HEPiX IPv6 working group guidance for the system administrators who manage IT services on the WLCG distributed infrastructure, for their related site security and networking teams and for developers and software engineers working on WLCG applications.

  2. Sabin and wild type polioviruses from children who presented with acute flaccid paralysis in Nigeria.

    Science.gov (United States)

    Adedeji, A O; Okonko, I O; Adu, F D

    2012-09-01

    Sensitive poliovirus surveillance to detect vaccine-derived-polioviruses will continue to increase in importance. Isolating and identifying poliovirus strains from children of pediatrics age in Nigeria. A total of 120 fecal samples were randomly collected from children under the age of five who presented with acute flaccid paralysis. Samples were tested by tissue culture technique and further characterized by intratypic differentiation testing using ELISA and PCR methods. The study confirmed the presence of 22(18.3%) enteroviral isolates comprising 19(86.4%) polioviruses and 3(13.6%) non-polio enteroviruses. These 19 polioviruses include: Sabin-type poliovirus-1 (15.8%), poliovirus-2 (10.5%), poliovirus-3 (10.5%) and wild-type poliovirus-1 (63.2%) isolates. It showed that poliovirus infection was higher in children ages 6-11 months (18.9%), females (18.4%), northern states (91.0%) with no vaccination record (75.0%). Wild-type poliovirus-1 was isolated from the stool samples of 12(54.6%) children from northern states and in all age groups except 18-23 months. No significant differences (P >0.05) between poliovirus infection and age (18.9% vs. 17.7%; 81.9% vs. 18.2%) and sex (18.3% vs. 18.4%). There was significant differences (Pvaccination (75.0% vs. 0.0%). No wild-type poliovirus was found in those with complete vaccination. This study further confirms the presence of Sabin and wild-type poliovirus among children in Nigeria. The isolation of Sabin strain of poliovirus is advantageous to the polio eradication program as it is capable of inducing natural immunity in susceptible hosts. Transmission of wild-type poliovirus among children with incomplete vaccination poses a serious threat to polio eradication program in Nigeria. Environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria.

  3. Current status of poliovirus infections.

    Science.gov (United States)

    Melnick, J L

    1996-07-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the number of new cases is falling dramatically. It is hoped that by the year 2000, we will accomplish the goal of the World Health Organization of "a world without polio." Then, because there is no animal reservoir, we can seriously discuss when and how to eliminate the need for vaccination and ultimately destroy our stocks of poliovirus.

  4. Deployment IPv6 over IPv4 network infrastructure

    OpenAIRE

    Hoang, Tien Dung

    2015-01-01

    The purpose of this thesis is doing the research about IPv6, concentrate in how to deploy an IPv6 network based on IPv4 network without making any interruption to IPv4 network. This thesis is made for Financing and Promoting Technology Corporation (FPT) in Vietnam. This thesis is completed in two main parts. The theoretical part is making research about IPv4 and IPv6 to have the point of view about IPv4 and IPv6 basically, and from those one, seeing the advantages of IPv6 comparing wit...

  5. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults.

    Science.gov (United States)

    Troy, Stephanie B; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

    2015-06-15

    Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody titers. We randomly assigned 231 adults with well-controlled human immunodeficiency virus infection at a ratio of 2:2:2:1 to receive 40% of the standard dose of IPV intradermally, 20% of the standard dose intradermally, the full standard dose intramuscularly, or 40% of the standard dose intramuscularly. Intradermal vaccination was done using the NanoPass MicronJet600 microneedle device. Baseline immunity was 87%, 90%, and 66% against poliovirus serotypes 1, 2, and 3, respectively. After vaccination, antibody titers increased a median of 64-fold. Vaccine response to 40% of the standard dose administered intradermally was comparable to that of the standard dose of IPV administered intramuscularly and resulted in higher (although not significantly) antibody titers. Intradermal administration had higher a incidence of local side effects (redness and itching) but a similar incidence of systemic side effects and was preferred by study participants over intramuscular administration. A 60% reduction in the standard IPV dose without reduction in antibody titers is possible through intradermal administration. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Natural Type 3/Type 2 Intertypic Vaccine-Related Poliovirus Recombinants with the First Crossover Sites within the VP1 Capsid Coding Region

    DEFF Research Database (Denmark)

    Zhang, Yong; Zhu, Shuangli; Yan, Dongmei

    2010-01-01

    Ten uncommon natural type 3/type 2 intertypic poliovirus recombinants were isolated from stool specimens from nine acute flaccid paralysis case patients and one healthy vaccinee in China from 2001 to 2008.......Ten uncommon natural type 3/type 2 intertypic poliovirus recombinants were isolated from stool specimens from nine acute flaccid paralysis case patients and one healthy vaccinee in China from 2001 to 2008....

  7. Intimate partner violence (IPV)

    DEFF Research Database (Denmark)

    Rasch, Vibeke; Van, Toan Ngo; Nguyen, Hanh Thi Thuy

    2018-01-01

    BACKGROUND: Intimate partner violence (IPV) is a global problem that affects one-third of all women. The present study aims to develop and determine the validity of a screening instrument for the detection of IPV in pregnant women in Tanzania and Vietnam and to determine the minimum number...

  8. Antiviral activity of 3(2H- and 6-chloro-3(2H-isoflavenes against highly diverged, neurovirulent vaccine-derived, type2 poliovirus sewage isolates.

    Directory of Open Access Journals (Sweden)

    Lester M Shulman

    Full Text Available BACKGROUND: Substituted flavanoids interfere with uncoating of Enteroviruses including Sabin-2 polio vaccine strains. However flavanoid resistant and dependent, type-2 polio vaccine strains (minimally-diverged, emerged during in vitro infections. Between 1998-2009, highly-diverged (8 to >15% type-2, aVDPV(2s, from two unrelated persistent infections were periodically isolated from Israeli sewage. AIM: To determine whether highly evolved aVDPV(2s derived from persistent infections retained sensitivity to isoflavenes. METHODS: Sabin-2 and ten aVDPV(2 isolates from two independent Israeli sources were titered on HEp2C cells in the presence and absence of 3(2H- Isoflavene and 6-chloro-3(2H-Isoflavene. Neurovirulence of nine aVDPV(2s was measured in PVR-Tg-21 transgenic mice. Differences were related to unique amino acid substitutions within capsid proteins. PRINCIPAL FINDINGS: The presence of either flavanoid inhibited viral titers of Sabin-2 and nine of ten aVDPV(2s by one to two log(10. The tenth aVDPV(2, which had unique amino acid substitution distant from the isoflavene-binding pocket but clustered at the three- and five-fold axies of symmetry between capsomeres, was unaffected by both flavanoids. Genotypic neurovirulence attenuation sites in the 5'UTR and VP1 reverted in all aVDPV(2s and all reacquired a full neurovirulent phenotype except one with amino acid substitutions flanking the VP1 site. CONCLUSION: Both isoflavenes worked equally well against Sabin 2 and most of the highly-diverged, Israeli, aVDPV(2s isolates. Thus, functionality of the hydrophobic pocket may be unaffected by selective pressures exerted during persistent poliovirus infections. Amino acid substitutions at sites remote from the drug-binding pocket and adjacent to a neurovirulence attenuation site may influence flavanoid antiviral activity, and neurovirulence, respectively.

  9. Scientific consultation on the safety and containment of new poliovirus strains for vaccine production, clinical/regulatory testing and research. Report of a meeting held at NIBSC, Potters Bar, Hertfordshire, UK, 6/7th July 2016.

    Science.gov (United States)

    Minor, Philip D; Lane, Blanche; Mimms, South; Bar, Potters

    2017-07-01

    When poliomyelitis is totally eradicated from the natural world containment will be vital to prevent its re-emergence. The matter has become pressing as type 2 component of oral polio vaccine was completely withdrawn by May 2016 as wild ty[e 2 was declared eradicated. Work on polioviruses must be contained in accordance with GAPIII (the third version of the Global Action Plan of WHO). Some activities will be essential for years after eradication. Vaccine production and control, surveillance and supportive applied and academic research must all continue. Most laboratories do not currently comply with GAPIII and could not do so in the short term without disruption of essential activities including vaccine supply. The development and use of safer strains is raised in GAPIII and the meeting considered the strains available and the uses to which they could be put to facilitate compliance with the aims of GAPIII. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  10. Progress Toward Containment of Poliovirus Type 2 - Worldwide, 2017.

    Science.gov (United States)

    Previsani, Nicoletta; Singh, Harpal; St Pierre, Jeanette; Boualam, Liliane; Fournier-Caruana, Jacqueline; Sutter, Roland W; Zaffran, Michel

    2017-06-23

    The Global Polio Eradication Initiative (GPEI) continues to make progress toward the eradication target. Only one of the three serotypes, wild poliovirus (WPV) type 1 (WPV1), is still circulating, and the numbers of cases and countries with endemic transmission are at record lows. With the certification of wild poliovirus type 2 (WPV2) eradication in 2015 and the global replacement of trivalent oral poliovirus vaccine (tOPV) containing Sabin poliovirus types 1, 2, and 3 with bivalent OPV containing only Sabin poliovirus types 1 and 3 during April-May 2016, poliovirus type 2 (PV2) is now an eradicated pathogen. However, in eight countries (Cameroon, Chad, Democratic Republic of Congo, Mozambique, Niger, Nigeria, Pakistan, and Syria), monovalent type 2 OPV (mOPV2) was authorized for large-scale outbreak control after tOPV withdrawal (1). Poliovirus containment, an evolving area of work that affects every country, aims to ensure that all PV2 specimens are safely contained to minimize the risk for reintroducing the virus into communities. This report summarizes the current status of poliovirus containment and progress since the last report (2), and outlines remaining challenges. Within 30 countries, 86 facilities have been designated by the relevant national authorities (usually the Ministry of Health) to become poliovirus-essential facilities for the continued storage or handling of PV2 materials; each country is responsible for ensuring that these facilities meet all biorisk management requirements.

  11. Investigation of an outbreak of type 3 wild poliovirus in Cote d'Ivoire ...

    African Journals Online (AJOL)

    adedamla

    three doses of polio vaccine compared to non-polio cases, OR: 16.9 [95% CI: 2.3 – 125.0]. More than 27% ... with only the poliovirus vaccine against the circulating poliovirus, people live in precarious socio-economic conditions ...... Sabin and.

  12. IPv6 Network Administration

    CERN Document Server

    Murphy, Niall Richard

    2009-01-01

    This essential guide explains what works, what doesn't, and most of all, what's practical about IPv6--the next-generation Internet standard. A must-have for network administrators everywhere looking to fix their network's scalability and management problems. Also covers other IPv6 benefits, such as routing, integrated auto-configuration, quality-of-services (QoS), enhanced mobility, and end-to-end security.

  13. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    Science.gov (United States)

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination. Copyright © 2015, American Society for Microbiology

  14. A RT-PCR method for selective amplification and phenotypic characterization of all three serotypes of Sabin-related polioviruses from viral mixtures

    Directory of Open Access Journals (Sweden)

    Eliane Veiga da Costa

    2012-08-01

    Full Text Available Outbreaks caused by vaccine-derived polioviruses are challenging the final eradication of paralytic poliomyelitis. Therefore, the surveillance of the acute flaccid paralysis cases based on poliovirus isolation and characterization remains an essential activity. Due to the use of trivalent oral poliovirus vaccine (OPV, mixtures containing more than one serotype of Sabin-related polioviruses are frequently isolated from clinical samples. Because each poliovirus isolate needs to be individually analyzed, we designed polymerase chain reaction primers that can selectively distinguish and amplify a genomic segment of the three Sabin-related poliovirus serotypes present in mixtures, thus, optimizing the diagnosis and providing prompt information to support epidemiologic actions.

  15. Isolamento e identificação intratípica de cêpas de poliovirus associadas com a administração de vacina Sabin Isolation and intratypical identification on poliovirus strains following the administration of Sabin vaccine

    Directory of Open Access Journals (Sweden)

    José Alberto Neves Candeias

    1969-12-01

    Full Text Available Estudou-se a taxa de excreção de enterovírus em dois grupos de crianças de 1 a 4 anos de idade, que receberam várias doses de vacina Sabin. No primeiro grupo a colheita de fezes foi feita 60 dias após a administração da última dose de vacina e no segundo grupo, passados somente 15 dias. No primeiro grupo as porcentagens de isolamento de poliovírus e outros enterovírus foram, respectivamente, de 12,12% e 13,63%. já no segundo, estas porcentagens foram de 37,61% e 9,17%. Em ambos os grupos foram isolados os três tipos sorológicos de poliovírus. As taxas de isolamentos de poliovírus e outros enterovírus não se mostraram estatìsticamente diferentes, em ambos os grupos, quando relacionadas com o número de doses de vacina recebidas - duas ou menos doses e três ou mais doses. A identificação intratípica das cêpas de poliovirus isoladas foi feita pelos "marcadores" RCT40 e ds. Das 8 cêpas isoladas do primeiro grupo, 6 foram identificadas como intermediárias e 2 como cêpas naturais. Estas 2 cêpas foram isoladas das duas únicas crianças que não tinham sido vacinadas contra a poliomielite. Das 41 cêpas isoladas do segundo grupo, 8 foram caracterizadas como intermediárias e 33 como ceêpas tipicamente vacinais.The author studied the incidence of enterovirus excretion in 2 groups of children aged between 1 and 4 years, who had been given varying doses of Sabin polio vaccine. In the first group faeces were collected 60 days and in the second group 15 days after the last dose of vaccine had been given. In the first group 12,12% yielded poliovirus and 13,63% yielded "other enteroviruses"; in the second group the percentages were 37,61% and 9,17%. In both groups all three serological types of poliovirus were isolated. The previous vaccination status of the children in both groups, whether vaccinated with two or less or three or more doses, did not have a statistically significant effect on the subsequent virus isolations. The

  16. Exceptional Financial Support for Introduction of Inactivated Polio Vaccine in Middle-Income Countries.

    Science.gov (United States)

    Blankenhorn, Anne-Line; Cernuschi, Tania; Zaffran, Michel J

    2017-07-01

    In May 2012, the World Health Assembly declared the completion of poliovirus eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. The Polio Eradication and Endgame Strategic Plan 2013-2018 was developed in response to this call and demands that all countries using Oral Polio Vaccine (OPV) only introduce at least 1 dose of Inactivated Polio Vaccine (IPV) into routine immunization schedules by the end of 2015. In November 2013, the Board of Gavi (the Vaccine Alliance) approved the provision of support for IPV introduction in the 72 Gavi-eligible countries. Following analytical work and stakeholder consultations, the IPV Immunization Systems Management Group (IMG) presented a proposal to provide exceptional financial support for IPV introduction to additional OPV-only using countries not eligible for Gavi support and that would otherwise not be able to mobilize the necessary financial resources within the Polio Eradication and Endgame Strategic Plan timelines. In June 2014, the Polio Oversight Board (POB) agreed to make available a maximum envelope of US $45 million toward supporting countries not eligible for Gavi funding. This article describes the design of the funding mechanism that was developed, its implementation and the lessons learned through this process. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. IPv4 and IPv6 protocol compatibility options analysis

    Directory of Open Access Journals (Sweden)

    Regina Misevičienė

    2013-09-01

    Full Text Available The popularity of the internet has led to a very rapid growth of IPv4 (Internet Protocol v4 users. This caused a shortage of IP addresses, so it was created a new version – IPv6 (Internet Protocol v6. Currently, there are two versions of IP for IPv4 and IPv6. Due to the large differences in addressing the protocols IPv4 and IPv6 are incompatible. It is therefore necessary to find ways to move from IPv4 to IPv6. To facilitate the transition from one version to another are developed various mechanisms and strategies. Comparative analysis is done for dual stack, 6to4 tunnel and NAT64 mechanisms in this work. It has helped to reveal the shortcomings of these mechanisms and their application in selection of realization decisions.

  18. 100 years poliovirus: from discovery to eradication. A meeting report.

    Science.gov (United States)

    Skern, Tim

    2010-09-01

    Just over hundred years ago, Karl Landsteiner and Erwin Popper identified a virus, later termed poliovirus, as the causative agent of poliomyelitis. This groundbreaking discovery simultaneously provided the basis for the measures that today prevent the outbreaks of the terrible epidemics caused by poliovirus. In 1988, the WHO started its eradication program to eliminate the virus from the planet. The symposium celebrated the discovery of poliovirus and discussed our current state of knowledge of poliovirus biology. Prospects for the eradication program were evaluated, with particular emphasis being placed on why certain countries still have not succeeding in interrupting wild-type transmission of poliovirus. Discussion also centred on the role of inactivated poliovirus vaccines in the eradication program and the maintenance of a poliovirus-free world, whenever this goal should be achieved.

  19. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    Science.gov (United States)

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  20. Assessing the stability of polio eradication after the withdrawal of oral polio vaccine

    Science.gov (United States)

    Selinger, Christian; McCarthy, Kevin A.; Eckhoff, Philip A.; Chabot-Couture, Guillaume

    2018-01-01

    The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population

  1. Assessing the stability of polio eradication after the withdrawal of oral polio vaccine.

    Directory of Open Access Journals (Sweden)

    Michael Famulare

    2018-04-01

    Full Text Available The oral polio vaccine (OPV contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore

  2. IPv6-specific misconfigurations in the DNS

    NARCIS (Netherlands)

    Hendriks, Luuk; de Boer, Pieter-Tjerk; Pras, Aiko

    2017-01-01

    With the Internet transitioning from IPv4 to IPv6, the number of IPv6-specific DNS records (AAAA) increases. Misconfigurations in these records often go unnoticed, as most systems are provided with connectivity over both IPv4 and IPv6, and automatically fall back to IPv4 in case of connection

  3. Bioinformatics analysis and genetic diversity of the poliovirus.

    Science.gov (United States)

    Liu, Yanhan; Ma, Tengfei; Liu, Jianzhu; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Wang, Shujing; Xu, Ruixue

    2014-12-01

    Poliomyelitis, a disease which can manifest as muscle paralysis, is caused by the poliovirus, which is a human enterovirus and member of the family Picornaviridae that usually transmits by the faecal-oral route. The viruses of the OPV (oral poliovirus attenuated-live vaccine) strains can mutate in the human intestine during replication and some of these mutations can lead to the recovery of serious neurovirulence. Informatics research of the poliovirus genome can be used to explain further the characteristics of this virus. In this study, sequences from 100 poliovirus isolates were acquired from GenBank. To determine the evolutionary relationship between the strains, we compared and analysed the sequences of the complete poliovirus genome and the VP1 region. The reconstructed phylogenetic trees for the complete sequences and the VP1 sequences were both divided into two branches, indicating that the genetic relationships of the whole poliovirus genome and the VP1 sequences are very similar. This branching indicates that the virulence and pathogenicity of poliomyelitis may be associated with the VP1 region. Sequence alignment of the VP1 region revealed numerous mutation sites in which mutation rates of >30 % were detected. In a group of strains recorded in the USA, mutation sites and mutation types were the same and this may be associated with their distribution in the evolutionary tree and their genetic relationship. In conclusion, the genetic evolutionary relationships of poliovirus isolate sequences are determined to a great extent by the VP1 protein, and poliovirus strains located on the same branch of the phylogenetic tree contain the same mutation spots and mutation types. Hence, the genetic characteristics of the VP1 region in the poliovirus genome should be analysed to identify the transmission route of poliovirus and provide the basis of viral immunity development. © 2014 The Authors.

  4. IPv6 in ESnet

    International Nuclear Information System (INIS)

    Matthews, W.; Fink, B.; Hicks, S.; Grigaliunas, V.

    2001-01-01

    The importance of the Internet to modern High Energy Physics collaborators is clearly immense, and understanding how new developments in network technology impact networks is critical to the future design of experiments. The next generation Internet Protocol (IPv6) is being deployed on testbeds and production networks throughout the world. The protocol has been designed to solve todays internet problems, and many of the features will be core Internet services in the future. In this talk the features of the protocol will be described. Details will be given on the deployment at sites important to High Energy Physics Research and the network services operating at these sites. In particular IPv6 deployment on the U.S. Energy Sciences Network (ESnet) will be reviewed. The connectivity and performance between High Energy Physics Laboratories, Universities and Institutes will be discussed

  5. PERFORMANCE ANALYSIS OF IPv4 AND IPv6 INTERNET TRAFFIC

    Directory of Open Access Journals (Sweden)

    Rupesh Jaiswal

    2015-12-01

    Full Text Available The gigantic growth of the internet communication technology has illustrated its value and benefits to private businesses, government organizations, worldwide professionals, academic institutes and individuals over the past few years. The size and range of computing devices connected to the internet, substantially increased because of IPv6 and offers the potential to establish a much more powerful internet compared to the IPv4. IPV6 developed by the IETF to deal with a shortage of IP addresses under IPv4. New features of IPv6 enhance packet processing speeds over routers, switches and end systems. These improved features will have different traffic characteristics than IPv4. The internet traffic which was earlier assumed as Poisson is now shown to have fractal characteristics as; heavy tailedness, self-similarity and long range dependency. Internet traffic showing above characteristics are found to have burstiness at multiple timescales. This behavior impacts network performance and degrades it substantially. It also increases complexity for network design and create difficulties to maintain desired QoS. IPv4 traffic has been well established as self-similar traffic. Nowadays, IPv6 forming a larger share of the internet traffic and it is pivotal to asses IPv6 with regards to fractal behavior. This will enable network designers to do necessary changes in the existing network to reconcile with IPv6. In this paper we compared IPv4 and IPv6 with respect to fractal behavioral characteristics. It is found that IPv6 shows higher degree of heavy tailedness, higher values of Hurst parameter values, higher fractal dimension values i.e. it is more self-similar, greater autocorrelation achieved even at larger lag and thus showing more burstiness.

  6. IPv6 Network Security using Snort

    OpenAIRE

    Kaur, Ravreet; Kumar, Sumit

    2013-01-01

    IPv6 is new routing protocol. IPv6 is introduced by IETF mainly due IPv4 address exhaustion but it is also an enhanced version of IPv4. There are many changes in IPv6 header, some fields from IPv6 header has been deprecated from IPv6 and some are newly added. There is also common misconception among people that IPv6 is more secure than IPv4, which is not true. Now a day's intruders are targeting IPv6 networks as it is widely being accepted by many organization for their network. An intruder c...

  7. Comparison Between IPv4 to IPv6 Transition Techniques

    OpenAIRE

    Cordeiro, Edwin; Carnier, Rodrigo; Zucchi, Wagner L

    2016-01-01

    The IPv4 addresses exhaustion demands a protocol transition from IPv4 to IPv6. The original transition technique, the dual stack, is not widely deployed yet and it demanded the creation of new transition techniques to extend the transition period. This work makes an experimental comparison of techniques that use dual stack with a limited IPv4 address. This limited address might be a RFC 1918 address with a NAT at the Internet Service Provider (ISP) gateway, also known as Carrier Grade NAT (CG...

  8. Poliovirus Laboratory Based Surveillance: An Overview.

    Science.gov (United States)

    Zaidi, Syed Sohail Zahoor; Asghar, Humayun; Sharif, Salmaan; Alam, Muhammad Masroor

    2016-01-01

    World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program.

  9. IPv6 sobre AT

    Directory of Open Access Journals (Sweden)

    Octavio José Salcedo

    2011-12-01

    Full Text Available Providing Quality of Service (QoS from communication networks in a global environment, is now one of the main fields of research, mainly due to the increasing importance of applications such as VoIP, video conferencing, stream video and audio, distance education, among others. This article is presented as a technology for providing uality service, the integration of IPv6 and ATM. The main objective is to present and discuss the main considerations and solutions that exist in the integration of IP trafÞ c in ATM technology.

  10. Migrating Applications to IPv6

    CERN Document Server

    York, Dan

    2011-01-01

    If IPv6 is to be adopted on a large scale, the applications running on desktop systems, laptops, and even mobile devices need to work just as well with this protocol as they do with IPv4. This concise book takes you beyond the network layer and helps you explore the issues you need to address if you are to successfully migrate your apps to IPv6. It's ideal for application developers, system/network architects, product managers, and others involved in moving your network to IPv6. Explore changes you need to make in your application's user interfaceMake sure your application is retrieving corre

  11. IPv6 deployment and management

    CERN Document Server

    Dooley, Michael

    2013-01-01

    A guide for understanding, deploying, and managing Internet Protocol version 6 The growth of the Internet has created a need for more addresses than are available with Internet Protocol version 4 (IPv4)-the protocol currently used to direct almost all Internet traffic. Internet Protocol version 6 (IPv6)-the new IP version intended to ultimately succeed IPv4-will expand the addressing capacity of the Internet to support the explosive growth of users and devices on the Internet as well as add flexibility to allocating addresses and efficiency for routing traffic. IPv6 Deploy

  12. A review of IPv6 security concerns

    CSIR Research Space (South Africa)

    Van Heerden, RP

    2012-08-01

    Full Text Available This study focuses on the security concerns of IPv6. We make a broad introduction to IPv6 then briefly look at the differences between the IPv6 and IPv4 protocols, their known vulnerabilities and identify some security concerns when implementing IPv...

  13. Problems of the internet transition from protocol IPv4 to IPv6

    OpenAIRE

    Potrebuješ , Nejc

    2013-01-01

    Internet currently coexist of older IPv4 networks, new IPv6 network and networks that supports both IPv6 and IPv4 stack. IPv4 and IPv6 networks are unfortunately incompatible. To enable communication between these two networks several mechanisms were developed. These mechanisms are so called »IPv4/v6 transition mechanisms«. In this thesis first there are IPv4 and IPv6 protocols presented, disadvantages of an IPv4 protocol and advantages of an IPv6 protocol. Further there are some transitio...

  14. Effective case/infection ratio of poliomyelitis in vaccinated populations.

    Science.gov (United States)

    Bencskó, G; Ferenci, T

    2016-07-01

    Recent polio outbreaks in Syria and Ukraine, and isolation of poliovirus from asymptomatic carriers in Israel have raised concerns that polio might endanger Europe. We devised a model to calculate the time needed to detect the first case should the disease be imported into Europe, taking the effect of vaccine coverage - both from inactivated and oral polio vaccines, also considering their differences - on the length of silent transmission into account by deriving an 'effective' case/infection ratio that is applicable for vaccinated populations. Using vaccine coverage data and the newly developed model, the relationship between this ratio and vaccine coverage is derived theoretically and is also numerically determined for European countries. This shows that unnoticed transmission is longer for countries with higher vaccine coverage and a higher proportion of IPV-vaccinated individuals among those vaccinated. Assuming borderline transmission (R = 1·1), the expected time to detect the first case is between 326 days and 512 days in different countries, with the number of infected individuals between 235 and 1439. Imperfect surveillance further increases these numbers, especially the number of infected until detection. While longer silent transmission does not increase the number of clinical diseases, it can make the application of traditional outbreak response methods more complicated, among others.

  15. Estimating the risk of re-emergence after stopping polio vaccination

    Directory of Open Access Journals (Sweden)

    Akira eSasaki

    2012-05-01

    Full Text Available Live vaccination against polio has effectively prevented outbreaks in most developed countries for more than 40 years, and there remain only a few countries where outbreaks of poliomyelitis by the wild strain still threaten the community. It is expected that worldwide eradication will be eventually achieved through careful surveillance and a well-managed immunization program. The present paper argues, however, that based on a simple stochastic model the risk of outbreak by a vaccine-derived strain after the cessation of vaccination is quite high, even if many years have passed since the last confirmed case. As vaccinated hosts are natural reservoirs for virulent poliovirus, the source of the risk is the vaccination itself, employed to prevent the outbreaks. The crisis after stopping vaccination will emerge when the following two conditions are met: the susceptible host density exceeds the threshold for epidemics and the vaccinated host density remains large enough to ensure the occurrence of virulent mutants in the population. Our estimates for transmission, recovery, and mutation rates, show that the probability of an outbreak of vaccine-derived virulent viruses easily exceeds 90%. Moreover, if a small fraction of hosts have a longer infectious period, as observed in individuals with innate immunodeficiency, the risk of an outbreak rises significantly. Under such conditions, successful global eradication of polio is restricted to a certain range of parameters even if inactive polio vaccine (IPV is extensively used after the termination of live vaccination.

  16. Current Status of IPv6 Management

    OpenAIRE

    Astic , Isabelle; Festor , Olivier

    2002-01-01

    Nowadays, we are at an important time of the development of the IPv6 (Internet Protocol version 6) network. Until now, this protocol was used only between IPv6 «islands». These islands were connected by IPv4 (Internet Protocol version 4) networks. So the transport of IPv6 packets was made through IPv4 ones, or into MPLS (MultiProtocol Label Switching) tunnels. Now, that real IPv6 native equipment appears, it is possible to create real native IPv6 networks.Because in these networks, IPv4 does ...

  17. Esimerkkiyrityksen IPv6-lähiverkko

    OpenAIRE

    Palkki, Ville

    2013-01-01

    Insinöörityön tavoitteena oli suunnitella ja toteuttaa esimerkkiyrityksen IPv6-lähiverkko. Toisena tavoitteena oli suunnitella esimerkkiyrityksen siirtyminen IPv4-protokollasta IPv6-protokollaan. Työssä käsiteltiin IPv6-protokollaa ensin teoreettisesti ja tämän jälkeen suunniteltiin sekä rakennettiin toimiva IPv6-lähiverkko. Aluksi työssä käytiin läpi IPv6-protokollan etuja verrattuna vanhaan IPv4-protokollaan. Teoriaosuudessa selvitettiin myös IPv6-protokollan rakennetta ja lähetysformaa...

  18. Modelling Risk to US Military Populations from Stopping Blanket Mandatory Polio Vaccination.

    Science.gov (United States)

    Burgess, Colleen; Burgess, Andrew; McMullen, Kellie

    2017-01-01

    Transmission of polio poses a threat to military forces when deploying to regions where such viruses are endemic. US-born soldiers generally enter service with immunity resulting from childhood immunization against polio; moreover, new recruits are routinely vaccinated with inactivated poliovirus vaccine (IPV), supplemented based upon deployment circumstances. Given residual protection from childhood vaccination, risk-based vaccination may sufficiently protect troops from polio transmission. This analysis employed a mathematical system for polio transmission within military populations interacting with locals in a polio-endemic region to evaluate changes in vaccination policy. Removal of blanket immunization had no effect on simulated polio incidence among deployed military populations when risk-based immunization was employed; however, when these individuals reintegrated with their base populations, risk of transmission to nondeployed personnel increased by 19%. In the absence of both blanket- and risk-based immunization, transmission to nondeployed populations increased by 25%. The overall number of new infections among nondeployed populations was negligible for both scenarios due to high childhood immunization rates, partial protection against transmission conferred by IPV, and low global disease incidence levels. Risk-based immunization driven by deployment to polio-endemic regions is sufficient to prevent transmission among both deployed and nondeployed US military populations.

  19. Packet traffic features of IPv6 and IPv4 protocol traffic

    OpenAIRE

    ÇİFLİKLİ, Cebrail; GEZER, Ali; ÖZŞAHİN, Abdullah Tuncay

    2012-01-01

    Nowadays, the IPv6 protocol is in a transition phase in operational networks. The ratio of its traffic volume is increasing day by day. The many provided facilities for IPv6 connection increasethe total IPv6 traffic load. IPv6-over-IPv4 tunnels, pilot programsto provide IPv6 connections, IPv6/IPv4 dual stack operating systems,and free IPv6 tunnel brokers cause the IPv6 protocol to expand quickly. For efficient resource utilization, the characteristics of network traffic should be determ...

  20. Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine S

    2016-01-01

    and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

  1. Health facility-based survey of poliovirus antibody prevalence ...

    African Journals Online (AJOL)

    Background: High level of Poliovirus protective antibodies, must at all times be sustained in a community if poliomyelitis eradication is to be achieved. For some time now children have been vaccinated against poliomyelitis through various means in Northern Nigeria without authorities taking steps to evaluate the ...

  2. Communications, Immunization, and Polio Vaccines: Lessons From a Global Perspective on Generating Political Will, Informing Decision-Making and Planning, and Engaging Local Support.

    Science.gov (United States)

    Menning, Lisa; Garg, Gaurav; Pokharel, Deepa; Thrush, Elizabeth; Farrell, Margaret; Kodio, Frederic Kunjbe; Veira, Chantal Laroche; Wanyoike, Sarah; Malik, Suleman; Patel, Manish; Rosenbauer, Oliver

    2017-07-01

    The requirements under objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018-to introduce at least 1 dose of inactivated poliomyelitis vaccine (IPV); withdraw oral poliomyelitis vaccine (OPV), starting with the type 2 component; and strengthen routine immunization programs-set an ambitious series of targets for countries. Effective implementation of IPV introduction and the switch from trivalent OPV (containing types 1, 2, and 3 poliovirus) to bivalent OPV (containing types 1 and 3 poliovirus) called for intense global communications and coordination on an unprecedented scale from 2014 to 2016, involving global public health technical agencies and donors, vaccine manufacturers, World Health Organization and United Nations Children's Fund regional offices, and national governments. At the outset, the new program requirements were perceived as challenging to communicate, difficult to understand, unrealistic in terms of timelines, and potentially infeasible for logistical implementation. In this context, a number of core areas of work for communications were established: (1) generating awareness and political commitment via global communications and advocacy; (2) informing national decision-making, planning, and implementation; and (3) in-country program communications and capacity building, to ensure acceptance of IPV and continued uptake of OPV. Central to the communications function in driving progress for objective 2 was its ability to generate a meaningful policy dialogue about polio vaccines and routine immunization at multiple levels. This included efforts to facilitate stakeholder engagement and ownership, strengthen coordination at all levels, and ensure an iterative process of feedback and learning. This article provides an overview of the global efforts and challenges in successfully implementing the communications activities to support objective 2. Lessons from the achievements by countries and partners will likely be drawn upon when

  3. Sabin and wild polioviruses from apparently healthy primary school children in northeastern Nigeria.

    Science.gov (United States)

    Baba, M M; Oderinde, B S; Patrick, P Z; Jarmai, M M

    2012-02-01

    Despite significant success of the Global Polio Eradication Initiative (GPEI) in Nigeria, Afghanistan, India, Pakistan, wild poliovirus still occurs due to persistently high proportions of under and unimmunized children. The study aimed at determining the type of poliovirus often excreted into the environment. Four hundred nine fecal samples collected from apparently healthy school children aged 5-16 years in Borno and Adamawa States, northeastern Nigeria, were tested for poliovirus by tissue culture technique. The isolates were characterized further by intratypic differentiation testing and genetic sequencing. Three wild poliovirus type, 11 Sabin type, combination of Sabin-types 1 + 2 and 2 + 3 poliovirus, and 22 non-polio enteroviruses were obtained. The continued excretion of wild-type poliovirus among children above 5 years old vaccinated with oral polio vaccine contributes to the persistent circulation of these viruses in the environment and may limit the population immunity. However, the excreted Sabin poliovirus is capable of immunizing the unvaccinated children and promotes herd immunity. Similarly, the excretion of combination of two polio serotypes indicates the child susceptibility to the missing serotype (s) and therefore indicates an immunity gap. The common unhygienic practices in the environment could aid the spread of these viruses through oral-fecal route. Asymptomatic transmission of wild poliovirus among older oral polio vaccine-vaccinated children poses a serious threat to polio eradication program in Nigeria and therefore, environmental and serological surveillance with larger sample size are important for monitoring poliovirus circulation in Nigeria. Copyright © 2011 Wiley Periodicals, Inc.

  4. IPv6 geolokace a vizualizace

    OpenAIRE

    Suchomel, Tomáš

    2011-01-01

    Tato diplomová práce se zabývá problematikou geolokace IPv6 adres a vizualizace jejich lokalit. Má za úkol prozkoumat oblast IPv6, dále porovnává současné přístupy ke geolokaci. Jejím hlavním cílem je vybudovat systém, který dokáže vytvořit geolokační databázi s pravidelnou aktualizací a který bude schopen zobrazit geografickou lokalitu IPv6 adresy na světové mapě. Geolokační systém nejprve získá geografické adresy pro jednotlivé prefixy IPv6 z veřejně přístupného systému Whois. Tyto adresy t...

  5. A review of IPv6 security concerns

    CSIR Research Space (South Africa)

    Van Heerden, RP

    2012-11-01

    Full Text Available This study focuses on the security concerns of IPv6. A broad introduction to IPv6 is made then briefly the differences between the IPv6 and IPv4 protocols are looked at, their known vulnerabilities and this identifies some security concerns when...

  6. DNS and BIND on IPv6

    CERN Document Server

    Liu, Cricket

    2011-01-01

    If you're preparing to roll out IPv6 on your network, this concise book provides the essentials you need to support this protocol with DNS. You'll learn how DNS was extended to accommodate IPv6 addresses, and how you can configure a BIND name server to run on the network. This book also features methods for troubleshooting problems with IPv6 forward- and reverse-mapping, and techniques for helping islands of IPv6 clients communicate with IPv4 resources. Topics include: DNS and IPv6-Learn the structure and representation of IPv6 addresses, and the syntaxes of AAAA and PTR records in the ip6.a

  7. Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.

    Science.gov (United States)

    Mohanty, Madhu Chhanda; Madkaikar, Manisha Rajan; Desai, Mukesh; Taur, Prasad; Nalavade, Uma Prajwal; Sharma, Deepa Kailash; Gupta, Maya; Dalvi, Aparna; Shabrish, Snehal; Kulkarni, Manasi; Aluri, Jahnavi; Deshpande, Jagadish Mohanrao

    2017-10-01

    Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). We isolated 8 enteroviruses (3 polioviruses and 5 nonpolio enteroviruses) in cell culture of 105 fecal samples collected from 42 patients. Only 1 patient with severe combined immunodeficiency was identified as a long-term VDPV3 excreter (for 2 years after identification of infection). Our results show that the risk of enterovirus excretion among children in India with PID is low; however, systematic screening is necessary to identify long-term poliovirus excreters until the use of oral polio vaccine is stopped.

  8. Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

    Directory of Open Access Journals (Sweden)

    Asghar Aghamohammadi

    2017-06-01

    Full Text Available 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.

  9. Use of Dedicated Mobile Teams and Polio Volunteer Community Mobilizers to Increase Access to Zero-Dose Oral Poliovirus Vaccine and Routine Childhood Immunizations in Settlements at High Risk for Polio Transmission in Northern Nigeria.

    Science.gov (United States)

    Ongwae, Kennedy M; Bawa, Samuel B; Shuaib, Faisal; Braka, Fiona; Corkum, Melissa; Isa, Hammanyero K

    2017-07-01

    The Polio Eradication Initiative in Nigeria, which started >20 years ago, faced many challenges, including initial denial, resistance from communities, and prolonged regional safety concerns. These challenges led into the structuring of the response including the development of the National Emergency Action Plan, improved partner coordination and government engagement, and the establishment of a Polio Emergency Operations Centre. Although monthly supplementary immunization activities (SIAs) continued, the targeting of settlements at high risk for polio transmission with routine immunization (RI) and other selected primary healthcare (PHC) services using dedicated mobile teams and volunteer community mobilizers (VCMs) became a key strategy for interrupting polio transmission in the high-risk areas. These efforts could have contributed to the wild poliovirus-free 2-year period between 24 July 2014 and 11 August 2016, when 2 cases of the virus were reported from Borno State, Northern Nigeria. A narrative analysis of polio-related program and other official documents was conducted to identify the relevant human resources and their role in the Polio Eradication Initiative and in RI. The data used in the article was obtained from United Nations Children's Fund (UNICEF) and World Health Organization project reports and a draft evaluation report of the dedicated mobile teams approach in Northern Nigeria. The data from 6 of the states that commenced the provision of polio, RI, and other selected PHC services using the dedicated mobile teams approach in 2014 showed an overall increase in the percentage of children aged 12-23 months in the settlements at high risk for polio transmission with a RI card seen, from 23% to 56%, and an overall increase in fully immunized children aged 12-23 months, from 19% to 55%. The number of newborns given the first dose of oral poliovirus vaccine (OPV) according to the RI schedule and the number of children given zero-dose OPV with the

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

    Science.gov (United States)

    Roscoe, Clay; Gilles, Ryan; Reed, Alex J; Messerschmidt, Matt; Kinney, Rebecca

    2015-06-12

    In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern. A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive. This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 and 3 combined, and 60% for serotypes 1 and 3 only. This study demonstrated a WPV immunity rate of poliovirus immunity in all newly arrived adult refugees, either by expanding pre-departure immunization or by screening for immunity at resettlement and vaccinating when indicated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Evaluating IPv6 Adoption in the Internet

    Science.gov (United States)

    Colitti, Lorenzo; Gunderson, Steinar H.; Kline, Erik; Refice, Tiziana

    As IPv4 address space approaches exhaustion, large networks are deploying IPv6 or preparing for deployment. However, there is little data available about the quantity and quality of IPv6 connectivity. We describe a methodology to measure IPv6 adoption from the perspective of a Web site operator and to evaluate the impact that adding IPv6 to a Web site will have on its users. We apply our methodology to the Google Web site and present results collected over the last year. Our data show that IPv6 adoption, while growing significantly, is still low, varies considerably by country, and is heavily influenced by a small number of large deployments. We find that native IPv6 latency is comparable to IPv4 and provide statistics on IPv6 transition mechanisms used.

  12. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

    Science.gov (United States)

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

  13. Interrupting poliovirus transmission -- new solutions to an old problem.

    Science.gov (United States)

    Aylward, R Bruce; Maher, Chris

    2006-06-01

    Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, knowledge as to the nature of circulating polioviruses and the challenges to their interruption has increased tremendously, particularly during the period 2000-2005. By January 2006, however, the systematic application of the standard polio eradication strategies, combined with recent refinements, had reduced the number of countries with ongoing transmission of indigenous wild polioviruses to just four (Nigeria, India, Pakistan, and Afghanistan), the lowest ever in history. In addition, only 8 of the 22 areas that had been re-infected by wild poliovirus in 2003-2005 still required large-scale 'mop-up' activities and circulating vaccine-derived poliovirus (cVDPV) outbreaks were being readily addressed. This progress, despite new challenges late in the GPEI, was greatly facilitated by a range of solutions that included two new monovalent oral polio vaccines (mOPVs), new and robust international standards for polio outbreak response, and renewed political commitment across the remaining infected countries.

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

    Science.gov (United States)

    Johnson Muluh, Ticha; Hamisu, Abdullahi Walla; Craig, Kehinde; Mkanda, Pascal; Andrew, Etsano; Adeniji, Johnson; Akande, Adefunke; Musa, Audu; Ayodeji, Isiaka; Nicksy, Gumede; Banda, Richard; Tegegne, Sisay G; Nsubuga, Peter; Oyetunji, Ajiboye; Diop, Ousmane; Vaz, Rui G; Muhammad, Ado J G

    2016-05-01

    Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015. The grap method was used to collect 1.75 L of raw flowing sewage every 2-4 weeks. Once collected, samples were shipped at 4 °C to a polio laboratory for concentration. ES data were then used to guide program implementation. From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged poliovirus transmission in Nigeria. © 2016 World Health Organization; licensee Oxford Journals.

  15. Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan.

    Science.gov (United States)

    Angez, Mehar; Shaukat, Shahzad; Alam, Muhammad M; Sharif, Salmaan; Khurshid, Adnan; Zaidi, Syed Sohail Zahoor

    2012-02-22

    Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP) patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Our results emphasize that there was a persistent transmission of wild type 1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas, associated with high risk population groups which include migrants

  16. Perancangan dan Analisis Perbandingan Implementasi OSPF pada Jaringan IPv4 dan IPv6

    Directory of Open Access Journals (Sweden)

    PAULINE RAHMIATI

    2016-02-01

    Full Text Available Abstrak OSPF (Open Shortest Path First adalah suatu routing protokol bersifat terbuka dan didukung oleh berbagai perangkat network. IPv4 telah mencapai batas maksimum dalam jumlah alamat sehingga IPv6 merupakan solusi dalam hal tersebut. Seperti IPv4, IPv6 juga sudah mulai diimplementasikan untuk routing protokol OSPF, oleh karena itu pada penelitian ini akan dirancang suatu routing protokol OSPF IPv6 dan sebagai bahan perbandingan akan dibandingkan dengan OSPF IPv4. Software Cisco Packet Tracer 5.3 digunakan untuk mensimulasikan perancangan jaringan yang dibuat. Pada penelitian ini akan dibandingkan 2 buah jaringan berbasis routing protokol OSPF, yaitu OSPF untuk IPv4 dan IPv6. Skenario pertama dilakukan 100 kali dalam 5 kasus untuk mengetahui nilai delay OSPF IPv4 dan OSPF IPv6. Skenario kedua dilakukan pemutusan link dilakukan sebanyak 30 kali, hal yang dilihat dari pengujian ini adalah hasil trace route dari cost yang ada. Skenario ketiga dilakukan dengan mengamati waktu konvergensi dari OSPF IPv4 dan IPv6. Secara keseluruhan nilai delay OSPF IPv6 lebih kecil dibandingkan dengan OSPF IPv4 sebesar 3-6%, Trace route dan nilai cost pada OSPF IPv6 dan OSPF IPv4 sama tetapi nilai delay OSPF IPv6 lebih kecil sebesar 3-6% dan waktu konvergensi OSPF IPv4 bernilai sama dengan OSPF IPv6 yaitu 10 detik. Kata kunci: OSPF, IPv4, Ipv6, delay, konvergensi Abstract OSPF (Open Shortest Path First is a routing protocol that opened and supported by a wide range of network devices. IPv4 has reached the maximum limit on the number of addresses that IPv6 are a solution in this case. Same as IPv4, IPv6 also has begun to be implemented for the OSPF routing protocol, therefore this study wiould design an IPv6 OSPF routing protocol and as a comparison will be compared to IPv4 OSPF. Cisco Packet Tracer 5.3 software was used to simulate the made network design. This research would compare two pieces of network-based routing protocol OSPF, OSPF for IPv4 and IPv6. The

  17. Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series.

    Science.gov (United States)

    Li, Li; Ivanova, Olga; Driss, Nadia; Tiongco-Recto, Marysia; da Silva, Rajiva; Shahmahmoodi, Shohreh; Sazzad, Hossain M S; Mach, Ondrej; Kahn, Anna-Lea; Sutter, Roland W

    2014-11-01

    Persons with primary immune deficiency disorders (PID), especially those disorders affecting the B-cell system, are at substantially increased risk of paralytic poliomyelitis and can excrete poliovirus chronically. However, the risk of prolonged or chronic excretion is not well characterized in developing countries. We present a summary of a country study series on poliovirus excretion among PID cases. Cases with PID from participating institutions were enrolled during the first year and after obtaining informed consent were tested for polioviruses in stool samples. Those cases excreting poliovirus were followed on a monthly basis during the second year until 2 negative stool samples were obtained. A total of 562 cases were enrolled in Bangladesh, China, Iran, Philippines, Russia, Sri Lanka, and Tunisia during 2008-2013. Of these, 17 (3%) shed poliovirus, including 2 cases with immunodeficient vaccine-derived poliovirus. Poliovirus was detected in a single sample from 5/17 (29%) cases. One case excreted for more than 6 months. None of the cases developed paralysis during the study period. Chronic polioviruses excretion remains a rare event even among individuals with PID. Nevertheless, because these individuals were not paralyzed they would have been missed by current surveillance; therefore, surveillance for polioviruses among PID should be established. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Caracterización de IPv6

    Directory of Open Access Journals (Sweden)

    Carlos A. Castillo Medina

    2013-05-01

    Full Text Available The present paper attempts to survey the current state of the network protocol called IPv6; starting from the evolution of IPv4 (which motivated the design of new features to the details that are comprised in the new version of the Internet Protocol. The main sections explain the drawbacks of IPv4 that can be overcome by implementing IPv6, highlighting aspects such as security, mobility, and Quality of Service (QoS.

  19. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick

  20. Managing the Planned Cessation of a Global Supply Market: Lessons Learned From the Global Cessation of the Trivalent Oral Poliovirus Vaccine Market.

    Science.gov (United States)

    Rubin, Jennifer; Ottosen, Ann; Ghazieh, Andisheh; Fournier-Caruana, Jacqueline; Ntow, Abraham Kofi; Gonzalez, Alejandro Ramirez

    2017-07-01

    The Polio Eradication and Endgame Strategic Plan 2013-2018 calls for the phased withdrawal of OPV, beginning with the globally synchronized cessation of tOPV by mid 2016. From a global vaccine supply management perspective, the strategy provided two key challenges; (1) the planned cessation of a high volume vaccine market; and (2) the uncertainty of demand leading and timeline as total vaccine requirements were contingent on epidemiology. The withdrawal of trivalent OPV provided a number of useful lessons that could be applied for the final OPV cessation. If carefully planned for and based on a close collaboration between programme partners and manufacturers, the cessation of a supply market can be undertaken with a successful outcome for both parties. As financial risks to manufacturers increase even further with OPV cessation, early engagement from the cessation planning phase and consideration of production lead times will be critical to ensure sufficient supply throughout to achieve programmatic objectives. As the GPEI will need to rely on residual stocks including with manufacturers through to the last campaign to achieve its objectives, the GPEI should consider to decide on and communicate a suitable mechanism for co-sharing of financial risks or other financial arrangement for the outer years. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  1. CORPORATE MIGRATION FROM IPv4 TO IPv6 USING DIFFERENT TRANSITION MECHANISMS

    OpenAIRE

    Nellore Karthikeyan*, K.Chandra Mouli

    2016-01-01

    Currently, the Internet world is confronting the huge issue that is exhaustion of IP addresses with the IPv4 protocol. This paper contains the imperative hypothetical ideas of new era Internet Protocol IPv6 which tackles the issue of IP tending to furthermore concentrate on IPv6 address design, directing and three mechanisms of migration from IPv4 to IPv6 system: Dual Stack, Translation and Tunneling utilizing Network Simulator as Packet tracer. This paper more accentuation on network migrati...

  2. IPv6 Geolocation Using Latency Constraints

    Science.gov (United States)

    2014-03-01

    ground truth datasets. In doing so, we investigate the following: • What is the accuracy of CBG when geolocating IPv6 hosts? • What are the accuracy...the overall PL is shorter for IPv6 than IPv4 which is consistent to what was found in recent work discussed in Section 3.5. Note that the average PL...growth of IPv6 addresses has increased significantly since 2010.The rate of increase of IPv6 usage is expected to continue; thus the need to determine

  3. World Health Organization Guidelines for Containment of Poliovirus Following Type-Specific Polio Eradication - Worldwide, 2015.

    Science.gov (United States)

    Previsani, Nicoletta; Tangermann, Rudolph H; Tallis, Graham; Jafari, Hamid S

    2015-08-28

    In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Among the three wild poliovirus (WPV) types (type 1, type 2, and type 3), WPV type 2 (WPV2) has been eliminated in the wild since 1999, and WPV type 3 (WPV3) has not been reported since 2012. In 2015, only Afghanistan and Pakistan have reported WPV transmission. On May 25, 2015, all WHO Member States endorsed World Health Assembly resolution 68.3 on full implementation of the Polio Eradication and Endgame Strategic Plan 2013-2018 (the Endgame Plan), and with it, the third Global Action Plan to minimize poliovirus facility-associated risk (GAPIII). All WHO Member States have committed to implementing appropriate containment of WPV2 in essential laboratory and vaccine production facilities* by the end of 2015 and of type 2 oral poliovirus vaccine (OPV2) within 3 months of global withdrawal of OPV2, which is planned for April 2016. This report summarizes critical steps for essential laboratory and vaccine production facilities that intend to retain materials confirmed to contain or potentially containing type-specific WPV, vaccine-derived poliovirus (VDPV), or OPV/Sabin viruses, and steps for nonessential facilities† that process specimens that contain or might contain polioviruses. National authorities will need to certify that the essential facilities they host meet the containment requirements described in GAPIII. After certification of WPV eradication, the use of all OPV will cease; final containment of all polioviruses after polio eradication and OPV cessation will minimize the risk for reintroduction of poliovirus into a polio-free world.

  4. Characterization of Vaccination Policies for Attendance and Employment at Day/Summer Camps in New York State.

    Science.gov (United States)

    Prescott, William A; Violanti, Kelsey C; Fusco, Nicholas M

    2018-01-01

    New York state requires day/summer camps to keep immunization records for all enrolled campers and strongly recommends requiring vaccination for all campers and staff. The objective of this study was to characterize immunization requirements/recommendations for children/adolescents enrolled in and staff employed at day/summer camps in New York state. An electronic hyperlink to a 9-question survey instrument was distributed via e-mail to 178 day/summer camps located in New York state cities with a population size greater than 100 000 people. A follow-up telephone survey was offered to nonresponders. The survey instrument included questions pertaining to vaccination documentation policies for campers/staff and the specific vaccines that the camp required/recommended. Fisher's exact and Chi-square tests were used to analyze categorical data. Sixty-five day/summer camps responded to the survey (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a policy/procedure for documenting vaccinations for campers and staff, respectively. Camps that had a policy/procedure for campers were more likely to have a policy/procedure for staff ( P = .0007). Age-appropriate vaccinations that were required/recommended for campers by at least 80% of camps included: measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B, inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and varicella. Age-appropriate vaccinations that were required/recommended for staff by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR, meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap). Vaccination policies at day/summer camps in New York state appear to be suboptimal. Educational outreach may encourage camps to strengthen their immunization policies, which may reduce the transmission of vaccine-preventable diseases.

  5. Antibodies to poliovirus detected by immunoradiometric assay with a monoclonal antibody

    International Nuclear Information System (INIS)

    Spitz, M.; Fossati, C.A.; Schild, G.C.; Spitz, L.; Brasher, M.

    1982-01-01

    An immunoradiometric assay (IRMA) for the assay of antibodies to poliovirus antigens is described. Dilutions of the test sera or whole (finger prick) blood samples were incubated with the poliovirus antigen bound to a solid phase and the specific antibody was detected by the addition of a mouse anti-human IgG monoclonal antibody (McAb), which was itself revealed by iodinated sheep IgG antimouse F(ab). The authors have shown that this technique is suitable for the estimation of IgG anti-poliovirus antibodies induced in children following polio vaccine. The present study shows that SPRIA provides a simple and inexpensive method for serological studies with poliovirus particularly for use in large-scale surveys. (Auth.)

  6. Antibodies to poliovirus detected by immunoradiometric assay with a monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Spitz, M.; Fossati, C.A.; Schild, G.C.; Spitz, L.; Brasher, M. (National Inst. for Biological Standards and Control, London (UK))

    1982-10-01

    An immunoradiometric assay (IRMA) for the assay of antibodies to poliovirus antigens is described. Dilutions of the test sera or whole (finger prick) blood samples were incubated with the poliovirus antigen bound to a solid phase and the specific antibody was detected by the addition of a mouse anti-human IgG monoclonal antibody (McAb), which was itself revealed by iodinated sheep IgG antimouse F(ab). The authors have shown that this technique is suitable for the estimation of IgG anti-poliovirus antibodies induced in children following polio vaccine. The present study shows that SPRIA provides a simple and inexpensive method for serological studies with poliovirus particularly for use in large-scale surveys.

  7. Reclaiming unused IPv4 addresses

    CERN Multimedia

    IT Department

    2016-01-01

    As many people might know, the number of IPv4 addresses is limited and almost all have been allocated (see here and here for more information).   Although CERN has been allocated some 340,000 addresses, the way these are allocated across the site is not as efficient as we would like. As we face an increasing demand for IPv4 addresses with the growth in virtual machines, the IT Department’s Communication Systems Group will be reorganising address allocation during 2016 to make more efficient use of the IPv4 address ranges that have been allocated to CERN. We aim, wherever possible, to avoid giving out fixed IP addresses, and have all devices connected to the campus network obtain an address dynamically each time they connect. As a first stage, starting in February, IP addresses that have not been used for more than 9 months will be reclaimed. No information about the devices concerned will be deleted from LANDB, but a new IP address will have to be requested if they are ever reconnected to t...

  8. Poliomyelitis in the United States: A Historical Perspective and Current Vaccination Policy.

    Science.gov (United States)

    Farizo, Karen M.; And Others

    1990-01-01

    Examines poliomyelitis in the United States by reviewing clinical manifestations and outcomes, history, recent epidemiologic characteristics, characteristics of currently available vaccines, controversies surrounding vaccination policy, current poliovirus vaccination recommendations, and prospects for worldwide eradication. Poliomyelitis remains…

  9. MicroRNA-134 regulates poliovirus replication by IRES targeting

    OpenAIRE

    Bakre, Abhijeet A.; Shim, Byoung-Shik; Tripp, Ralph A.

    2017-01-01

    Global poliovirus eradication efforts include high vaccination coverage with live oral polio vaccine (OPV), surveillance for acute flaccid paralysis, and OPV “mop-up” campaigns. An important objective involves host-directed strategies to reduce PV replication to diminish viral shedding in OPV recipients. In this study, we show that microRNA-134-5p (miR-134) can regulate Sabin-1 replication but not Sabin-2 or Sabin-3 via direct interaction with the PV 5′UTR. Hypochromicity data showed miR-134 ...

  10. Poliovirus seroprevalence before and after interruption of poliovirus transmission in Kano State, Nigeria.

    Science.gov (United States)

    Iliyasu, Zubairu; Verma, Harish; Craig, Kehinde T; Nwaze, Eric; Ahmad-Shehu, Amina; Jibir, Binta Wudil; Gwarzo, Garba Dayyabu; Gajida, Auwalu U; Weldon, William C; Steven Oberste, M; Takane, Marina; Mkanda, Pascal; Muhammad, Ado J G; Sutter, Roland W

    2016-09-30

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

  11. Molecular Properties of Poliovirus Isolates: Nucleotide Sequence Analysis, Typing by PCR and Real-Time RT-PCR.

    Science.gov (United States)

    Burns, Cara C; Kilpatrick, David R; Iber, Jane C; Chen, Qi; Kew, Olen M

    2016-01-01

    Virologic surveillance is essential to the success of the World Health Organization initiative to eradicate poliomyelitis. Molecular methods have been used to detect polioviruses in tissue culture isolates derived from stool samples obtained through surveillance for acute flaccid paralysis. This chapter describes the use of realtime PCR assays to identify and serotype polioviruses. In particular, a degenerate, inosine-containing, panpoliovirus (panPV) PCR primer set is used to distinguish polioviruses from NPEVs. The high degree of nucleotide sequence diversity among polioviruses presents a challenge to the systematic design of nucleic acid-based reagents. To accommodate the wide variability and rapid evolution of poliovirus genomes, degenerate codon positions on the template were matched to mixed-base or deoxyinosine residues on both the primers and the TaqMan™ probes. Additional assays distinguish between Sabin vaccine strains and non-Sabin strains. This chapter also describes the use of generic poliovirus specific primers, along with degenerate and inosine-containing primers, for routine VP1 sequencing of poliovirus isolates. These primers, along with nondegenerate serotype-specific Sabin primers, can also be used to sequence individual polioviruses in mixtures.

  12. An Unusual Case of Vaccine-Associated Paralytic Poliomyelitis

    Directory of Open Access Journals (Sweden)

    S Desai

    2014-01-01

    Full Text Available The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine.

  13. Siirtyminen IPv6-protokollaan yrityksen verkkolaitteistossa

    OpenAIRE

    Lindén, Kalle

    2012-01-01

    Tämän opinnäytetyön tarkoituksena on selvittää, mitä muutoksia Päijät-Hämeen koulutuskonsernin (PHKK) tietoverkon runkolaitteissa tarvitsee tehdä, jotta voidaan ottaa IPv6-protokolla käyttöön. Siirtyminen IPv6-protokollaan tulee olemaan välttämätön toimenpide, koska IPv4-protokollasta loppuvat uudet yksilölliset osoitteet. IPv4- ja IPv6-protokollien suurimmat erot ovat osoitekentän koon kasvaminen 32 bitistä 128 bittiin. Aluksi IPv4-osoitteistuksessa oli käytössä luokallinen osoitejärjest...

  14. Dynamics of Abusive IPv6 Networks

    Science.gov (United States)

    2014-09-01

    39 List of References 43 Initial Distribution List 47 vii THIS PAGE INTENTIONALLY LEFT BLANK viii List of Figures Figure 1.1 Google User IPv6 Adoption...2 Figure 1.1: Google User IPv6 Adoption Statistics, from June 2014 [3] For example, as a result of expanding use of IPv6, it is hypothesized that a...excessive annoyance of poorly crafted advertising emails, they can sometimes contain attachments or links to scam offers, phishing attempts, or malicious

  15. Home networking architecture for IPv6

    OpenAIRE

    Arkko, Jari; Weil, Jason; Troan, Ole; Brandt, Anders

    2012-01-01

    This text describes evolving networking technology within increasingly large residential home networks. The goal of this document is to define an architecture for IPv6-based home networking while describing the associated principles, considerations and requirements. The text briefly highlights the specific implications of the introduction of IPv6 for home networking, discusses the elements of the architecture, and suggests how standard IPv6 mechanisms and addressing can be employed in home ne...

  16. High-Throughput Next-Generation Sequencing of Polioviruses

    Science.gov (United States)

    Montmayeur, Anna M.; Schmidt, Alexander; Zhao, Kun; Magaña, Laura; Iber, Jane; Castro, Christina J.; Chen, Qi; Henderson, Elizabeth; Ramos, Edward; Shaw, Jing; Tatusov, Roman L.; Dybdahl-Sissoko, Naomi; Endegue-Zanga, Marie Claire; Adeniji, Johnson A.; Oberste, M. Steven; Burns, Cara C.

    2016-01-01

    ABSTRACT The poliovirus (PV) is currently targeted for worldwide eradication and containment. Sanger-based sequencing of the viral protein 1 (VP1) capsid region is currently the standard method for PV surveillance. However, the whole-genome sequence is sometimes needed for higher resolution global surveillance. In this study, we optimized whole-genome sequencing protocols for poliovirus isolates and FTA cards using next-generation sequencing (NGS), aiming for high sequence coverage, efficiency, and throughput. We found that DNase treatment of poliovirus RNA followed by random reverse transcription (RT), amplification, and the use of the Nextera XT DNA library preparation kit produced significantly better results than other preparations. The average viral reads per total reads, a measurement of efficiency, was as high as 84.2% ± 15.6%. PV genomes covering >99 to 100% of the reference length were obtained and validated with Sanger sequencing. A total of 52 PV genomes were generated, multiplexing as many as 64 samples in a single Illumina MiSeq run. This high-throughput, sequence-independent NGS approach facilitated the detection of a diverse range of PVs, especially for those in vaccine-derived polioviruses (VDPV), circulating VDPV, or immunodeficiency-related VDPV. In contrast to results from previous studies on other viruses, our results showed that filtration and nuclease treatment did not discernibly increase the sequencing efficiency of PV isolates. However, DNase treatment after nucleic acid extraction to remove host DNA significantly improved the sequencing results. This NGS method has been successfully implemented to generate PV genomes for molecular epidemiology of the most recent PV isolates. Additionally, the ability to obtain full PV genomes from FTA cards will aid in facilitating global poliovirus surveillance. PMID:27927929

  17. A comparison of two IPv4/IPv6 transition mechanisms - OpenVPN and IVI

    Science.gov (United States)

    Vu, Cong Tuan; Tran, Quang Anh; Jiang, Frank

    2012-09-01

    This document presents a comparison of two IPv4/IPv6 transition mechanisms. They are OpenVPN and IVI. Meanwhile OpenVPN is based on tunneling technology, IVI is a stateless IPv4/IPv6 translation technique which is developed by China Education and Research Network (CERNET). This research focus on the quantitative and qualitative comparison of these two main mechanisms; how they are applied in practical situation by the Internet Service Providers, as well as their advantages and drawbacks.

  18. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults

    OpenAIRE

    Troy, Stephanie B.; Kouiavskaia, Diana; Siik, Julia; Kochba, Efrat; Beydoun, Hind; Mirochnitchenko, Olga; Levin, Yotam; Khardori, Nancy; Chumakov, Konstantin; Maldonado, Yvonne

    2015-01-01

    Background. Inactivated polio vaccine (IPV) is necessary for global polio eradication because oral polio vaccine can rarely cause poliomyelitis as it mutates and may fail to provide adequate immunity in immunocompromised populations. However, IPV is unaffordable for many developing countries. Intradermal IPV shows promise as a means to decrease the effective dose and cost of IPV, but prior studies, all using 20% of the standard dose used in intramuscular IPV, resulted in inferior antibody tit...

  19. Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry

    Directory of Open Access Journals (Sweden)

    Grace Macklin

    2017-09-01

    Full Text Available Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93% prolonged excretors and 7/101 (7% chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72% cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4 and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.

  20. Polio vaccine - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC Polio Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ipv.html CDC review information for the Polio VIS: Page last reviewed: July 20, 2016 Page ...

  1. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

    Science.gov (United States)

    van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

    2016-02-15

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

  2. Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

    NARCIS (Netherlands)

    Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

    2016-01-01

    Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and

  3. Laboratory analysis of environmental samples taken following the reported release of live poliovirus

    NARCIS (Netherlands)

    Duizer E; REV; I&V

    2015-01-01

    Analyse poliomonsters na lozingsincident

    Op 2 september 2014 heeft het bedrijf GlaxoSmithKline (GSK), dat vaccins produceert, in België door een menselijke fout 45 liter geconcentreerd poliovirus op het riool geloosd. Via de nabijgelegen rioolwaterzuivering is dit water onder andere in de

  4. IPv6 Monitoring in Nederland : De Nulmeting

    NARCIS (Netherlands)

    Boen-Leo, M.; Holtzer, A.; Tijmes, M.R.; Smets, R.

    2010-01-01

    In dit document wordt de mate van uitrol van IPv6 in Nederland per april 2010 beschreven. De 'nulmeting' is uitgevoerd in opdracht van het Ministerie van Ecnomische Zaken en is de eerste van twee metingen die in 2010 worden uitgevoerd. Allereerst wordt een korte uitleg gegeven over IPv6 en het

  5. IPv6: The Next Generation Internet Protocol

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 3. IPv6: The Next Generation Internet Protocol - IPv4 and its Shortcomings. Harsha Srinath. General Article Volume 8 Issue 3 March 2003 pp 33-41. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. IPv6: The Next Generation Internet Protocol

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 4. IPv6: The Next Generation Internet Protocol - New Features in IPv6. Harsha Srinath. General Article Volume 8 Issue 4 April 2003 pp 8-16. Fulltext. Click here to view fulltext PDF. Permanent link:

  7. Implementation of IPv6 at the PřF JU

    OpenAIRE

    JOUDAL, Jakub

    2011-01-01

    Aspects of IPv6 implementation. Is the current network structure capable of deploying IPv6 JU? What would this change mean? What will be the financial costs of transition? The advantages of IPv6 in terms of high schools.

  8. Real-time reverse transcription-polymerase chain reaction assays for identification of wild poliovirus 1 & 3.

    Science.gov (United States)

    Sharma, Deepa K; Nalavade, Uma P; Deshpande, Jagadish M

    2015-10-01

    The poliovirus serotype identification and intratypic differentiation by real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay is suitable for serotype mixtures but not for intratypic mixtures of wild and vaccine poliovirus strains. This study was undertaken to develop wild poliovirus 1 and 3 (WPV1 and WPV3) specific rRT-PCR assays for use. Specific primers and probes for rRT-PCR were designed based on VP1 sequences of WPV1 and WPV3 isolated in India since 2000. The specificity of the rRT-PCR assays was evaluated using WPV1 and WPV3 of different genetic lineages, non-polio enteroviruses (NPEVs) and mixtures of wild/wild and wild/Sabin vaccine strains. The sensitivity of the assays was determined by testing serial 10-fold dilutions of wild poliovirus 1 and 3 stock suspensions of known titre. No cross-reactivity with Sabin strains, intertypic wild poliovirus isolates or 27 types of NPEVs across all the four Enterovirus species was found for both the wild poliovirus 1 and 3 rRT-PCR assays. All WPV1 and WPV3 strains isolated since 2000 were successfully amplified. The rRT-PCR assays detected 10 4.40 CCID 50 /ml of WPV1 and 10 4.00 CCID 50 /ml of WPV3, respectively either as single isolate or mixture with Sabin vaccine strains or intertypic wild poliovirus. rRT-PCR assays for WPV1 and WPV3 have been validated to detect all the genetic variations of the WPV1 and WPV3 isolated in India for the last decade. When used in combination with the current rRT-PCR assay testing was complete for confirmation of the presence of wild poliovirus in intratypic mixtures.

  9. Immunogenicity and reactogenicity of Infanrix™ when co-administered with meningococcal MenACWY-TT conjugate vaccine in toddlers primed with MenHibrix™ and Pediarix™.

    Science.gov (United States)

    Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Baccarini, Carmen; Miller, Jacqueline M

    2015-02-11

    Co-administration of an investigational quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) with the fourth dose of diphtheria-tetanus-acellular pertussis vaccine (DTaP) at age 15-18 months was investigated in 3-dose Haemophilus influenzae type b-meningococcal serogroups C/Y conjugate vaccine (HibMenCY-TT)-primed toddlers. Infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and DTaP-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine, or Hib-TT and DTaP-HBV-IPV (Control). HibMenCY-TT+ DTaP-HBV-IPV vaccinees were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months (MenACWY-TT group); MenACWY-TT co-administered with DTaP at 15-18 months (Coad group); or HibMenCY-TT at 12-15 months and DTaP at 15-18 months (HibMenCY-TT group). Controls received DTaP at 15-18 months. Only children in the HibMenCY-TT group received a fourth dose of Hib conjugate vaccine due to Hib conjugate vaccine shortage at the time of the study. DTaP immunogenicity and reactogenicity were assessed one month post-vaccination. Pre-defined statistical non-inferiority criteria between Coad and Control groups were met for diphtheria, tetanus and filamentous haemagglutinin but not pertussis toxoid and pertactin. Following vaccination ≥99% of children had anti-diphtheria/anti-tetanus concentrations ≥1.0 IU/ml. Pertussis GMCs were lower in all investigational groups versus Control. In post hoc analyses, pertussis antibody concentrations were above those in infants following 3-dose DTaP primary vaccination in whom efficacy against pertussis was demonstrated (Schmitt, von König, et al., 1996; Schmitt, Schuind, et al., 1996). The reactogenicity profile of the Coad group was similar to DTaP administered alone. Routine booster DTaP was immunogenic with an acceptable safety profile when co-administered with MenACWY-TT vaccine in HibMenCY-TT-primed toddlers. These data support the

  10. Seroprevalence of poliovirus antibodies amongst children in Zaria, Northern Nigeria.

    Science.gov (United States)

    Giwa, F J; Olayinka, A T; Ogunshola, F T

    2012-11-06

    Poliomyelitis is endemic in Northern Nigeria where there is continuous transmission of wild poliovirus 1 and 3 (WPV1 and 3) and circulating vaccine derived poliovirus 2 (cVDPV2) resulting in a high number of cases of children with acute flaccid paralysis. The seroprevalence of antibodies to polio serotypes which can be used to assess the immune status of children and the effectiveness of the vaccine against poliomyelitis is unknown, despite its endemicity in this part of the world. This study aimed to determine the seroprevalence of poliovirus antibodies in children aged 1-10 years in Zaria, Northern Nigeria. A descriptive, cross sectional, community based study was undertaken in Zaria, North Western Nigeria between 2008 and 2009. Two hundred and sixty-four (264) children aged 1-10 years were enrolled from two local government in Zaria by multistage random sampling method. Demographic data and polio immunisation history were retrieved from parents and caregivers by an interviewer administered questionnaire. Neutralising antibody titres to polioserotypes 1, 2 and 3 were assayed according to the WHO Manual for the virological investigation of polio. Antibody titres ≥ 1:8 were considered positive. The mean age of the 264 children studied was 6.25 years. Fifty-five percent of the children were protected against the three polioserotypes, while 86.4%, 76.1% and 77.3% of children had neutralising antibodies to P1, P2 and P3 polioserotypes respectively. 5 (1.9%) of the children had no antibodies to all the three polioserotypes. Polio antibody seropositivity was significantly associated with higher socioeconomic status and immunisation was the single most important determinant of seropositivity to poliovirus serotypes. Seroprevalence to poliovirus serotypes, though higher than values found in previous studies done in Nigeria, was lower compared to findings in the developed world. The use of more immunogenic vaccines and the balanced use of OPV formulations in SIAs, with

  11. Studies towards the potential of poliovirus as a vector for the expression of HPV 16 virus-like-particles.

    Science.gov (United States)

    van Kuppeveld, Frank J M; de Jong, Arjan; Dijkman, Henri B P M; Andino, Raul; Melchers, Willem J G

    2002-11-15

    Development of human cervical carcinomas is associated with infection by certain human papillomavirus (HPV) types. Thus, protection against HPV infection through vaccination may prevent development of cervical cancer. The purpose of this study was to investigate the possibility of using a poliovirus recombinant vector to induce immunity against HPV. A poliovirus recombinant was constructed which contained the complete coding sequence of the HPV 16 major capsid protein L1, between the P1 and P2 region of the poliovirus polyprotein. A replication-competent virus was obtained after transfection of the recombinant RNA into tissue culture cells. Electron microscopically examination of cells infected with the poliovirus-HPV L1 recombinant indicated that HPV 16 L1 self-assembles into virus-like particles. To investigate the immunological response in vivo, susceptible transgenic mice carrying the poliovirus receptor were infected with the recombinant poliovirus. In all mice a modest but consistent immune response against HPV 16 was observed. Based on these results, the potential for picornavirus-derived vectors in vaccine development against HPV infection is discussed.

  12. Mobile video with mobile IPv6

    CERN Document Server

    Minoli, Daniel

    2012-01-01

    Increased reliance on mobile devices and streaming of video content are two of the most recent changes that have led those in the video distribution industry to be concerned about the shifting or erosion of traditional advertising revenues. Infrastructure providers also need to position themselves to take advantage of these trends. Mobile Video with Mobile IPv6provides an overview of the current mobile landscape, then delves specifically into the capabilities and operational details of IPv6. The book also addresses 3G and 4G services, the application of Mobile IPv6 to streaming and other mobil

  13. Polio

    Science.gov (United States)

    ... despite a worldwide effort to wipe out polio, poliovirus continues to affect children and adults in parts ... occurring should receive a booster dose of inactivated poliovirus vaccine (IPV). Immunity after a booster lasts a ...

  14. Genetic relationships and epidemiological links between wild type 1 poliovirus isolates in Pakistan and Afghanistan

    Directory of Open Access Journals (Sweden)

    Angez Mehar

    2012-02-01

    Full Text Available Abstract Background/Aim Efforts have been made to eliminate wild poliovirus transmission since 1988 when the World Health Organization began its global eradication campaign. Since then, the incidence of polio has decreased significantly. However, serotype 1 and serotype 3 still circulate endemically in Pakistan and Afghanistan. Both countries constitute a single epidemiologic block representing one of the three remaining major global reservoirs of poliovirus transmission. In this study we used genetic sequence data to investigate transmission links among viruses from diverse locations during 2005-2007. Methods In order to find the origins and routes of wild type 1 poliovirus circulation, polioviruses were isolated from faecal samples of Acute Flaccid Paralysis (AFP patients. We used viral cultures, two intratypic differentiation methods PCR, ELISA to characterize as vaccine or wild type 1 and nucleic acid sequencing of entire VP1 region of poliovirus genome to determine the genetic relatedness. Results One hundred eleven wild type 1 poliovirus isolates were subjected to nucleotide sequencing for genetic variation study. Considering the 15% divergence of the sequences from Sabin 1, Phylogenetic analysis by MEGA software revealed that active inter and intra country transmission of many genetically distinct strains of wild poliovirus type 1 belonged to genotype SOAS which is indigenous in this region. By grouping wild type 1 polioviruses according to nucleotide sequence homology, three distinct clusters A, B and C were obtained with multiple chains of transmission together with some silent circulations represented by orphan lineages. Conclusion Our results emphasize that there was a persistent transmission of wild type1 polioviruses in Pakistan and Afghanistan during 2005-2007. The epidemiologic information provided by the sequence data can contribute to the formulation of better strategies for poliomyelitis control to those critical areas

  15. Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis.

    Science.gov (United States)

    Shen, Ling; Chen, Crystal Y; Huang, Dan; Wang, Richard; Zhang, Meihong; Qian, Lixia; Zhu, Yanfen; Zhang, Alvin Zhuoran; Yang, Enzhuo; Qaqish, Arwa; Chumakov, Konstantin; Kouiavskaia, Diana; Vignuzzi, Marco; Nathanson, Neal; Macadam, Andrew J; Andino, Raul; Kew, Olen; Xu, Junfa; Chen, Zheng W

    2017-07-15

    Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 7 to 10 9 50% tissue culture infective doses (TCID 50 ) consistently infected all the animals, and many monkeys receiving 10 8 or 10 9 TCID 50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with

  16. IPv4 to IPv6 Transition: Optimal Routing Protocol within Dual Stack and Tunneling

    OpenAIRE

    Aparna Sivaprakash; S. Kayalvizhi

    2016-01-01

    The number of global internet users has been growing exponentially, necessitating a much larger number of unique IP addresses for all the connected networking devices. The prevalent IP version 4 is not able to meet the current requirement for IP addresses. To meet the future IP address requirement, a new version IPv6 has been introduced since 1999. However IPv6 is not backward compatible with IPv4.since it is not possible to migrate all the networking devices to ...

  17. DICOM image secure communications with Internet protocols IPv6 and IPv4.

    Science.gov (United States)

    Zhang, Jianguo; Yu, Fenghai; Sun, Jianyong; Yang, Yuanyuan; Liang, Chenwen

    2007-01-01

    Image-data transmission from one site to another through public network is usually characterized in term of privacy, authenticity, and integrity. In this paper, we first describe a general scenario about how image is delivered from one site to another through a wide-area network (WAN) with security features of data privacy, integrity, and authenticity. Second, we give the common implementation method of the digital imaging and communication in medicine (DICOM) image communication software library with IPv6/IPv4 for high-speed broadband Internet by using open-source software. Third, we discuss two major security-transmission methods, the IP security (IPSec) and the secure-socket layer (SSL) or transport-layer security (TLS), being used currently in medical-image-data communication with privacy support. Fourth, we describe a test schema of multiple-modality DICOM-image communications through TCP/IPv4 and TCP/IPv6 with different security methods, different security algorithms, and operating systems, and evaluate the test results. We found that there are tradeoff factors between choosing the IPsec and the SSL/TLS-based security implementation of IPv6/IPv4 protocols. If the WAN networks only use IPv6 such as in high-speed broadband Internet, the choice is IPsec-based security. If the networks are IPv4 or the combination of IPv6 and IPv4, it is better to use SSL/TLS security. The Linux platform has more security algorithms implemented than the Windows (XP) platform, and can achieve better performance in most experiments of IPv6 and IPv4-based DICOM-image communications. In teleradiology or enterprise-PACS applications, the Linux operating system may be the better choice as peer security gateways for both the IPsec and the SSL/TLS-based secure DICOM communications cross public networks.

  18. Transformation and Tumorigenicity Testing of Simian Cell Lines and Evaluation of Poliovirus Replication.

    Directory of Open Access Journals (Sweden)

    Silvia Dotti

    Full Text Available The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field.

  19. Happy World IPv6 Day!

    CERN Multimedia

    Adrian Giordani (iSGTW)

    2011-01-01

    Almost 20 years after Tim Berners-Lee posted a summary of his World Wide Web project on the newsgroup, there are more than two billion users worldwide, and billions more web pages. It has transformed the way we socialize, conduct business, and even changed the way we do science. But unfortunately, the number of available Internet addresses has not grown at the same place to accommodate these changes.   The number of Internet addresses is fixed because of the way the Internet operates: data is routed through the Internet in packets that use numeric addresses to encode its origin and its destination. The layer of communication at this level is called Internet Protocol (IP), originally developed by Vint Cerf, a program manager at the US Department of Defense Advanced Research Projects Agency and now Vice President and Chief Internet Evangelist of Google, USA, and member of numerous boards including as Commissioner for the Broadband Commission for Digital Development in 2010. IPv4 addresses, w...

  20. Tcam от IPv4 к IPv6

    OpenAIRE

    Багинян, А.; Долбилов, А.

    2013-01-01

    Статья посвящена проблемам современной маршрутизации сети Интернет. Рассматриваются проблемы выборки маршрутов сетей, использования политик безопасности и качества обслуживания передаваемой информации. Отдельный раздел посвящен примерам использования свойств маски сетей для сокращения размеров таблиц маршрутизации. Рассмотрены различные возможные варианты компоновки адресной памяти, проведено сравнение между маршрутизацией по протоколу Ipv4 и Ipv6, а так же рассмотрены варианты программных и ...

  1. Linear and non-linear video and TV applications using IPv6 and IPv6 multicast

    CERN Document Server

    Minoli, Daniel

    2012-01-01

    Provides options for implementing IPv6 and IPv6 multicast in service provider networks New technologies, viewing paradigms, and content distribution approaches are taking the TV/video services industry by storm. Linear and Nonlinear Video and TV Applications: Using IPv6 and IPv6 Multicast identifies five emerging trends in next-generation delivery of entertainment-quality video. These trends are observable and can be capitalized upon by progressive service providers, telcos, cable operators, and ISPs. This comprehensive guide explores these evolving directions in the TV/v

  2. Design and implementation of scalable IPv4-IPv6 internetworking gateway

    Science.gov (United States)

    Zhu, Guo-sheng; Yu, Shao-hua; Dai, Jin-you

    2008-11-01

    This paper proposed a scalable architecture of IPv4-IPv6 internetworking gateway based on EZchip 10Gbps network processor NP-1c. The Application Layer Gateway(ALG) of control plane can be upgraded without needing to modify the data forwarding plane.A SIP ALG of 3GPP IMS(IP Multimedia Subsystem)was implemented and tested under real China Next Generation Internet(CNGI) network environment.IPv4 SIP UEs can communicate with IPv6 SIP UEs through the gateway.

  3. Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

    Science.gov (United States)

    Dunn, Glynis; Klapsa, Dimitra; Wilton, Thomas; Stone, Lindsay; Minor, Philip D; Martin, Javier

    2015-08-01

    There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

  4. Vaccination Coverage Among Children Aged 2 Years - U.S. Affiliated Pacific Islands, April-October, 2016.

    Science.gov (United States)

    Tippins, Ashley; Murthy, Neil; Meghani, Mehreen; Solsman, Amy; Apaisam, Carter; Basilius, Merlyn; Eckert, Maribeth; Judicpa, Peter; Masunu, Yolanda; Pistotnik, Kelsey; Pedro, Daisy; Sasamoto, Jeremy; Underwood, J Michael

    2018-05-25

    Vaccine-preventable diseases (VPDs) cause substantial morbidity and mortality in the United States Affiliated Pacific Islands (USAPI).* CDC collaborates with USAPI immunization programs to monitor vaccination coverage. In 2016, † USAPI immunization programs and CDC piloted a method for estimating up-to-date status among children aged 2 years using medical record abstraction to ascertain regional vaccination coverage. This was the first concurrent assessment of childhood vaccination coverage across five USAPI jurisdictions (American Samoa; Chuuk State, Federated States of Micronesia [FSM]; Commonwealth of the Northern Mariana Islands [CNMI]; Republic of the Marshall Islands [RMI]; and Republic of Palau). § Differences in vaccination coverage between main and outer islands ¶ were assessed for two jurisdictions where data were adequate.** Series coverage in this report includes the following doses of vaccines: ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP); ≥3 doses of inactivated poliovirus vaccine (IPV); ≥1 dose of measles, mumps, and rubella vaccine (MMR); ≥3 doses of Haemophilus influenzae type B (Hib) vaccine; ≥3 doses of hepatitis B (HepB) vaccine; and ≥4 doses of pneumococcal conjugate vaccine (PCV); i.e., 4:3:1:3:3:4. Coverage with ≥3 doses of rotavirus vaccine was also assessed. Completion of the recommended series of each of these vaccines †† was <90% in all jurisdictions except Palau. Coverage with the full recommended six-vaccine series (4:3:1:3:3:4) ranged from 19.5% (Chuuk) to 69.1% (Palau). In RMI and Chuuk, coverage was lower in the outer islands than in the main islands for most vaccines, with differences ranging from 0.9 to 66.8 percentage points. Medical record abstraction enabled rapid vaccination coverage assessment and timely dissemination of results to guide programmatic decision-making. Effectively monitoring vaccination coverage, coupled with implementation of data-driven interventions

  5. Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.

    Science.gov (United States)

    Sazzad, Hossain M S; Rainey, Jeanette J; Kahn, Anna-Lea; Mach, Ondrej; Liyanage, Jayantha B L; Alam, Ahmed Nawsher; Kawser, Choudhury A; Hossain, Asgar; Sutter, Roland; Luby, Stephen P

    2014-11-01

    Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion. Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD. From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative. The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. A Literature Survey on Handoff for Mobile IPv6

    OpenAIRE

    Zongpu Jia; Gaolei Wang; Ran Zhao

    2011-01-01

    With the development of network technology, IPv6 will be widely used in the next generation Internet, IPv6 will be used in the next generation Internet, IPv6 could combine mobile networks and fixed wireless networks closely, which brings great convenience to people’s live. The handoff delay of Mobile IPv6 seriously affected the real-time communication service quality, therefore various improvement methods based on the basic Mobile IPv6 protocol are proposed. The working principle of Mob...

  7. WLCG and IPv6 - the HEPiX IPv6 working group

    Science.gov (United States)

    Campana, S.; Chadwick, K.; Chen, G.; Chudoba, J.; Clarke, P.; Eliáš, M.; Elwell, A.; Fayer, S.; Finnern, T.; Goossens, L.; Grigoras, C.; Hoeft, B.; Kelsey, D. P.; Kouba, T.; López Muñoz, F.; Martelli, E.; Mitchell, M.; Nairz, A.; Ohrenberg, K.; Pfeiffer, A.; Prelz, F.; Qi, F.; Rand, D.; Reale, M.; Rozsa, S.; Sciaba, A.; Voicu, R.; Walker, C. J.; Wildish, T.

    2014-06-01

    The HEPiX (http://www.hepix.org) IPv6 Working Group has been investigating the many issues which feed into the decision on the timetable for the use of IPv6 (http://www.ietf.org/rfc/rfc2460.txt) networking protocols in High Energy Physics (HEP) Computing, in particular in the Worldwide Large Hadron Collider (LHC) Computing Grid (WLCG). RIPE NCC, the European Regional Internet Registry (RIR), ran out ofIPv4 addresses in September 2012. The North and South America RIRs are expected to run out soon. In recent months it has become more clear that some WLCG sites, including CERN, are running short of IPv4 address space, now without the possibility of applying for more. This has increased the urgency for the switch-on of dual-stack IPv4/IPv6 on all outward facing WLCG services to allow for the eventual support of IPv6-only clients. The activities of the group include the analysis and testing of the readiness for IPv6 and the performance of many required components, including the applications, middleware, management and monitoring tools essential for HEP computing. Many WLCG Tier 1/2 sites are participants in the group's distributed IPv6 testbed and the major LHC experiment collaborations are engaged in the testing. We are constructing a group web/wiki which will contain useful information on the IPv6 readiness of the various software components and a knowledge base (http://hepix-ipv6.web.cern.ch/knowledge-base). This paper describes the work done by the working group and its future plans.

  8. WLCG and IPv6 – the HEPiX IPv6 working group

    International Nuclear Information System (INIS)

    Campana, S; Elwell, A; Goossens, L; Grigoras, C; Martelli, E; Nairz, A; Pfeiffer, A; Chadwick, K; Chen, G; Chudoba, J; Eliáš, M; Kouba, T; Clarke, P; Fayer, S; Finnern, T; Ohrenberg, K; Hoeft, B; Kelsey, D P; Muñoz, F López; Mitchell, M

    2014-01-01

    The HEPiX (http://www.hepix.org) IPv6 Working Group has been investigating the many issues which feed into the decision on the timetable for the use of IPv6 (http://www.ietf.org/rfc/rfc2460.txt) networking protocols in High Energy Physics (HEP) Computing, in particular in the Worldwide Large Hadron Collider (LHC) Computing Grid (WLCG). RIPE NCC, the European Regional Internet Registry (RIR), ran out ofIPv4 addresses in September 2012. The North and South America RIRs are expected to run out soon. In recent months it has become more clear that some WLCG sites, including CERN, are running short of IPv4 address space, now without the possibility of applying for more. This has increased the urgency for the switch-on of dual-stack IPv4/IPv6 on all outward facing WLCG services to allow for the eventual support of IPv6-only clients. The activities of the group include the analysis and testing of the readiness for IPv6 and the performance of many required components, including the applications, middleware, management and monitoring tools essential for HEP computing. Many WLCG Tier 1/2 sites are participants in the group's distributed IPv6 testbed and the major LHC experiment collaborations are engaged in the testing. We are constructing a group web/wiki which will contain useful information on the IPv6 readiness of the various software components and a knowledge base (http://hepix-ipv6.web.cern.ch/knowledge-base). This paper describes the work done by the working group and its future plans.

  9. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  10. The Deployment of IPv6 in an IPv4 World and Transition Strategies.

    Science.gov (United States)

    Bouras, C.; Ganos, P.; Karaliotas, A.

    2003-01-01

    The current version of the IP protocol, IPv4, is the most widely used protocol in computer networks. This article describes mechanisms that can be used to facilitate the transition to the new version of the IP protocol, IPv6, and examines usability, usefulness and manageability. Describes how some of these mechanisms were applied to the Greek…

  11. PROPUESTA DE CONEXIÓN DE ENTORNOS IPv6 MEDIANTE UN BACKBONE MPLS/IPv4

    Directory of Open Access Journals (Sweden)

    Nancy Yaneth Gelvez García

    2013-09-01

    Full Text Available Las redes actuales MPLS/IPv4 presentan las ventajas de poder implementar ingeniería de tráfico, así como realizar diferenciación de flujos mediante clases de servicio (CoS frente a las redes con enrutamiento IP tradicional. En aras de aprovechar cualidades estratégicas durante la etapa de coexistencia entre IPv4 e IPv6 existen 4 métodos para proveer conectividad a islas IPv6 [1] remotas a través de una infraestructura de core MPLS con IPv4 nativo [2], sin embargo una de las formas que permite un rápida y fácil provisión de la misma dados los mínimos requisitos de configuración y de equipos es la de disponer túneles IPv6 en los enrutadores de acceso (CE de la red. No obstante, sus cuatro variantes (manual, GRE, 6to4 e IPv6 compatible IPv4 [3] resultan adecuadas o no según las características inherentes de la red a interconectar; por tanto este artículo presenta las ventajas y desventajas propias de la utilización de cada técnica de entunelamiento como resultado de la interconexión con los cuatro tipos de túneles de una red emulada mediante GNS3+Dynamips.

  12. Strain differentiation of polioviruses with monoclonal antibodies.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; A.J.H. Stegmann; J.A.A.M. van Asten (Jack)

    1984-01-01

    textabstractPanels of monoclonal antibodies raised against different poliovirus type 1, 2 and 3 strains, were tested in a micro-neutralization test and in a micro-enzyme linked immunosorbent assay against a large number of poliovirus strains. The results were compared with those obtained with the

  13. An acute flaccid paralysis surveillance-based serosurvey of poliovirus antibodies in Western Uttar Pradesh, India.

    Science.gov (United States)

    Bahl, Sunil; Gary, Howard E; Jafari, Hamid; Sarkar, Bidyut K; Pathyarch, Surendra K; Sethi, Raman; Deshpande, Jagadish

    2014-11-01

    Despite intensified use of monovalent oral poliovirus type 1 vaccine and improved coverage of immunization campaigns, wild poliovirus type 1 persisted in Indian states of Uttar Pradesh and Bihar during 2006 to 2009. A serosurvey was conducted among cases of acute flaccid paralysis in the 25 high-polio-incidence districts of western Uttar Pradesh. Children were recruited by age group (6-11 months, 12-24 months, and 25-69 months) from among cases reported through the acute flaccid paralysis surveillance system between November 2008 and August 2009. Seroprevalence for type 1 wild poliovirus was >96.4% for each age group. The seroprevalence of wild poliovirus types 2 and 3 increased with age, from 36.7% to 73.4% for type 2 and from 39.0% to 74.1% for type 3. In addition to the number of type-specific vaccine doses, father's level of education, being from a Muslim family, height for age, and female sex were the socioeconomic risk factors associated with seronegativity to poliovirus. The seroprevalence and risk factors identified in this study were consistent with the epidemiology of polio, and the findings were instrumental in optimizing vaccination strategy in western Uttar Pradesh with respect to the choice of OPV types, the frequency of supplementary immunization campaigns, and the urgency to improve routine immunization services. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Current status of poliovirus infections.

    OpenAIRE

    Melnick, J L

    1996-01-01

    Two scientists who played leading roles in the conquest of poliomyelitis died recently. In 1954, Jonas Salk provided the first licensed polio vaccine, the formalin (and heat)-inactivated virus. Albert Sabin gave us the attenuated live virus vaccine, which was licensed in 1962. This paper takes the reader through the history of the disease, including its pathogenesis, epidemiology, vaccines, and future directions. The emphasis is on vaccines, for it seems that with proper vaccination the numbe...

  15. Inhibition of poliovirus RNA synthesis by brefeldin A.

    OpenAIRE

    Maynell, L A; Kirkegaard, K; Klymkowsky, M W

    1992-01-01

    Brefeldin A (BFA), a fungal metabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was found to inhibit poliovirus replication 10(5)- to 10(6)-fold. BFA does not inhibit entry of poliovirus into the cell or translation of viral RNA. Poliovirus RNA synthesis, however, is completely inhibited by BFA. A specific class of membranous vesicles, with which the poliovirus replication complex is physically associated, is known to proliferate in poliovirus-infect...

  16. Relationship between synthesis and cleavage of poliovirus-specific proteins.

    OpenAIRE

    Thomas, A A; Voorma, H O; Boeye, A

    1983-01-01

    Poliovirus proteinase was studied in vitro in lysates from poliovirus-infected HeLa cells. Preincubation of these lysates caused (i) a reduction in poliovirus proteinase activity and (ii) a partial dependence on exogenous mRNA for optimal translation. Proteins translated from endogenous poliovirus RNA in preincubated extracts from virus-infected HeLa cells are poorly cleaved. This cleavage deficiency is alleviated by adding fresh poliovirus RNA to the translation system, thus, allowing re-ini...

  17. Application of IPv6 in GIS

    Science.gov (United States)

    Wang, Zhen-feng; Wang, Liang

    2008-10-01

    The inherent flaws in current network, especially the inadequate IP address space, make the born of NGN (Next Generation Network). The NGN aims to enable the information sharing and inter-operation of heterogeneous networks. As the core of NGN, IPv6 (Internet Protocol version 6), which is designed as the successor of IPv4 running now, brings us many new features. It provides larger address space, supports mobile devices, and has built-in security policy, and so on. Although it brings us so many advantages and the backbone of NGN also has been constructed in many countries, we have difficulties moving to NGN. One of the main reasons is there are few killer applications for it. So what features can be employed by GIS, and how to use them is the main content of this paper. The IPv6 certainly offers new entry to solve some problems in GIS.

  18. Cross-sectional serologic assessment of immunity to poliovirus infection in high-risk areas of northern India.

    Science.gov (United States)

    Bahl, Sunil; Estívariz, Concepción F; Sutter, Roland W; Sarkar, Bidyut K; Verma, Harish; Jain, Vibhor; Agrawal, Ashutosh; Rathee, Mandeep; Shukla, Hemant; Pathyarch, Surendra K; Sethi, Raman; Wannemuehler, Kathleen A; Jafari, Hamid; Deshpande, Jagadish M

    2014-11-01

    The objectives of this survey were to assess the seroprevalence of antibodies to poliovirus types 1 and 3 and the impact of bivalent (types 1 and 3) oral poliovirus vaccine (bOPV) use in immunization campaigns in northern India. In August 2010, a 2-stage stratified cluster sampling method identified infants aged 6-7 months in high-risk blocks for wild poliovirus infection. Vaccination history, weight and length, and serum were collected to test for neutralizing antibodies to poliovirus types 1, 2, and 3. Seroprevalences of antibodies to poliovirus types 1, 2, and 3 were 98% (95% confidence interval [CI], 97%-99%), 66% (95% CI, 62%-69%), and 77% (95% CI, 75%-79%), respectively, among 664 infants from Bihar and 616 infants from Uttar Pradesh. Infants had received a median of 3 bOPV doses and 2 monovalent type 1 OPV (mOPV1) doses through campaigns and 3 trivalent OPV (tOPV) doses through routine immunization. Among subjects with 0 tOPV doses, the seroprevalences of antibodies to type 3 were 50%, 77%, and 82% after 2, 3, and 4 bOPV doses, respectively. In multivariable analysis, malnutrition was associated with a lower seroprevalence of type 3 antibodies. This study confirmed that replacing mOPV1 with bOPV in campaigns was successful in maintaining very high population immunity to type 1 poliovirus and substantially decreasing the immunity gap to type 3 poliovirus. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  19. Initial results from an IPv6 Darknet

    OpenAIRE

    Ronan, John; Ford, Matthew; Stevens, Jonathan

    2006-01-01

    A darknet is an advertised and routed portion of Internet address space that contains no advertised services. Any traffic observed on a darknet is therefore illegitimate and darknets are useful tools for observing the level of background ‘noise’ on a larger network. Darknets have been used in existing IPv4 networks to help to identify malicious traffic, malware trends, or the consequences of misconfiguration. We have created what may be the world’s first IPv6 darknet to help us observe the ‘n...

  20. IPv6 for Future Wireless Networks

    DEFF Research Database (Denmark)

    Nielsen, Thomas Toftegaard

    2001-01-01

    The functionalities of the next generation Internet protocol, IPv6, havebecome increasingly interesting due to the current merging of the traditionalcellular mobile communications and the traditional data-communications intothe future wireless systems, as e.g., UMTS. IPv6 provides several...... enhancedfunctionalities requested for the future mobile systems. In this article thelargest advantages in relation to mobile systems are presented. Variousaspects of introducing IP throughout the entire mobile network (core, accessand termainals) are also presented along with an illustration of the abilitiesof the future...

  1. Investigating the Performance of the MPT Multipath Communication Library in IPv4 and IPv6

    Directory of Open Access Journals (Sweden)

    Béla Almási

    2016-01-01

    Full Text Available The currently used mobile devices (laptops, tablets, mobile phones contain many built-in network cards for communication (e.g. Wi-Fi, 3G, Bluetooth, etc.. A natural request could be combining the resources of the different network connection possibilities in order to increase the throughput of the communication. Unfortunately the standard IP communication technology does not support it: the communication is restricted to one IP address (i.e. to one interface. The Multipath TCP (MPTCP specification (appeared in January 2013 offers a Transport layer solution of using more than one interface in a TCP communication session. In this paper we investigate a Network layer solution. The MPT multipath communication library opens the multipath communication possibility in the Network layer. Using the MPT library, applications built on the UDP protocol are also able to perform multipath communication. The MPT library was developed by using a full dual-stack technology, which means the MPT based multipath environment can be used both in IPv4 and IPv6. Protocol version change is also possible: an IPv6 based application is able to run in an IPv4 multipath environment, and an IPv4 application can be used in an IPv6 multipath environment. In this paper we give a short overview on the MPT communication library’s working mechanism and detailed numerical examples will be shown to present how the MPT library aggregates the paths’ throughput in IPv4 and IPv6 environments. The main contribution of the paper is to demonstrate the effective throughput aggregation property of the MPT library in IPv6 and in mixed (i.e. protocol version change environments.

  2. TRANSPORTE DE VOZ (VoIP SOBRE REDES IPv4 e IPv6

    Directory of Open Access Journals (Sweden)

    Fausto Alexander Gamboa

    2012-05-01

    Full Text Available El presente artículo tiene como finalidad evaluar el comportamiento de la VoIP en redes IPv6 y compararlo con IPv4, de igual manera presentar las arquitecturas que la soportan. Con el fin de que los resultados sean los más cercanos a la realidad, el artículo no solo se soporta en simulaciones si no en implementaciones reales. Dentro de las conclusiones más sobresalientes se encontró que la VoIP6 presenta mejor rendimiento ante el Jitter y el retardo que VoIPv4.

  3. Introduction of Sequential Inactivated Polio Vaccine–Oral Polio Vaccine Schedule for Routine Infant Immunization in Brazil’s National Immunization Program

    Science.gov (United States)

    Domingues, Carla Magda Allan S.; de Fátima Pereira, Sirlene; Marreiros, Ana Carolina Cunha; Menezes, Nair; Flannery, Brendan

    2015-01-01

    In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule. PMID:25316829

  4. Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

    Science.gov (United States)

    Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

    2015-09-08

    The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Cross-sectional Serologic Assessment of Immunity to Poliovirus in Differential Risk Areas of India: India Seroprevalence Survey - 2014.

    Science.gov (United States)

    Ahmad, Mohammad; Bahl, Sunil; Kunwar, Abhishek

    2016-08-07

    To assess the seroprevalence against all three poliovirus serotypes in traditional high risk areas in Bihar, lowest routine immunization coverage areas in Madhya Pradesh and migrant population living in Mumbai urban slums. Cross-sectional Survey. Subjects selected by house to house visit (community based) and transported to government health facilities for further study procedures. 1137 randomly selected healthy infants 6-11 months of age residing in the selected high-risk areas. Serum samples from the study site were shipped to Enterovirus Research Centre (ERC), Mumbai to determine the neutralizing antibodies against all three poliovirus serotypes. Children with a reciprocal antibody titer ≥1:8 were considered seropositive to the specific poliovirus. Overall, seroprevalence in all the three study areas was 98%, 98% and 91% against poliovirus type-1, type-2 and type-3, respectively. Bihar had a seroprevalence of 99%, 99% and 92% against type-1, type-2 and type-3 respectively. Corresponding figures for Madhya Pradesh and Mumbai were 98%, 99% and 88% and 98%, 97% and 94%, respectively. The study found high seroprevalence against all three poliovirus types not only in the traditional high-risk areas for polio in India, but even in the areas known to have low routine immunization coverage and among the migratory clusters living in Mumbai urban slums. Type-2 seroprevalence was found to be high. These findings are reassuring against the threat of emergence of circulating vaccine derived polioviruses (cVDPVs) in the country subsequent to switch from trivalent oral polio vaccine to bivalent oral polio vaccine in the routine immunization schedule from April 2016.

  6. The production deployment of IPv6 on WLCG

    Science.gov (United States)

    Bernier, J.; Campana, S.; Chadwick, K.; Chudoba, J.; Dewhurst, A.; Eliáš, M.; Fayer, S.; Finnern, T.; Grigoras, C.; Hartmann, T.; Hoeft, B.; Idiculla, T.; Kelsey, D. P.; López Muñoz, F.; Macmahon, E.; Martelli, E.; Millar, A. P.; Nandakumar, R.; Ohrenberg, K.; Prelz, F.; Rand, D.; Sciabà, A.; Tigerstedt, U.; Voicu, R.; Walker, C. J.; Wildish, T.

    2015-12-01

    The world is rapidly running out of IPv4 addresses; the number of IPv6 end systems connected to the internet is increasing; WLCG and the LHC experiments may soon have access to worker nodes and/or virtual machines (VMs) possessing only an IPv6 routable address. The HEPiX IPv6 Working Group has been investigating, testing and planning for dual-stack services on WLCG for several years. Following feedback from our working group, many of the storage technologies in use on WLCG have recently been made IPv6-capable. This paper presents the IPv6 requirements, tests and plans of the LHC experiments together with the tests performed on the group's IPv6 test-bed. This is primarily aimed at IPv6-only worker nodes or VMs accessing several different implementations of a global dual-stack federated storage service. Finally the plans for deployment of production dual-stack WLCG services are presented.

  7. RIPng- A next Generation Routing Protocal (IPv6) | Falaye | Journal ...

    African Journals Online (AJOL)

    ... Information Protocol Next Generation (RIPng) owing to the current depletion rate of IPv4. ... that support the Internet Protocol Version 6 (IPv6).addressing scheme. ... A brief history is given; its various versions are discussed, and detailed ...

  8. Role of Global Alliance for Vaccines and Immunization (GAVI) in Accelerating Inactivated Polio Vaccine Introduction.

    Science.gov (United States)

    Thacker, Naveen; Thacker, Deep; Pathak, Ashish

    2016-08-07

    Global Alliance for Vaccines and Immunization (GAVI, the Vaccine Alliance) is an international organization built through public-private partnership. GAVI has supported more than 200 vaccine introductions in the last 5 years by financing major proportion of costs of vaccine to 73 low-income countries using a co-financing model. GAVI has worked in close co-ordination with Global Polio Eradication Initiative (GPEI) since 2013, to strengthen health systems in countries so as to accelerate introduction of inactivated polio vaccine (IPV). GAVI is involved in many IPV related issues like demand generation, supply, market shaping, communications, country readiness etc. Most of the 73 GAVI eligible countries are also high priority countries for GPEI. GAVI support has helped India to accelerate introduction of IPV in all its states. However, GAVI faces challenges in IPV supply-related issues in the near future. It also needs to play a key role in global polio legacy planning and implementation.

  9. IPV Screening and Readiness to Respond to IPV in Ob-Gyn Settings: A Patient-Physician Study

    Directory of Open Access Journals (Sweden)

    Katherine M. Jones

    2018-01-01

    Full Text Available Purpose. Intimate partner violence (IPV is a serious, preventable public health concern that largely affects women of reproductive age. Obstetrician-gynecologists (ob-gyns have a unique opportunity to identify and support women experiencing IPV to improve women’s health. Considering recent efforts to increase IPV awareness and intervention, the present study aimed to provide a current evaluation of nationally representative samples to assess ob-gyn readiness to respond to IPV as well as patient IPV-related experiences. Methods. 400 ob-gyns were randomly selected from American College of Obstetricians and Gynecologists’ (ACOG Collaborative Ambulatory Research Network. Each physician was mailed one physician survey and 25 patient surveys. Results. IPV training/education and IPV screening practices were associated with most measures of ob-gyn readiness to respond to IPV. Among respondents, 36.8% endorsed screening all patients at annual exams; however, 36.8% felt they did not have sufficient training to assist individuals in addressing IPV. Workplace encouragement of IPV response was associated with training, screening, detection, preparation/knowledge, response practices, and resources. Thirty-one percent of patients indicated their ob-gyn had asked about possible IPV experiences during their medical visit. Conclusion. Findings highlight specific gaps in ob-gyns’ IPV knowledge and response practices to be further addressed by IPV training.

  10. Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells.

    Science.gov (United States)

    Mohanty, Madhu C; Deshpande, Jagadish M

    2013-01-01

    Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains) do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV) and Sabin attenuated type 1 poliovirus (Sabin PV) in cultured human neuronal cells. By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs) and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH) infected with Sabin PV and wild PV. Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5) m-RNA in neuronal cells at the beginning of infection (up to 4 h) as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

  11. Differential induction of Toll-like receptors & type 1 interferons by Sabin attenuated & wild type 1 polioviruses in human neuronal cells

    Directory of Open Access Journals (Sweden)

    Madhu C Mohanty

    2013-01-01

    Full Text Available Background & objectives: Polioviruses are the causative agent of paralytic poliomyelitis. Attenuated polioviruses (Sabin oral poliovirus vaccine strains do not replicate efficiently in neurons as compared to the wild type polioviruses and therefore do not cause disease. This study was aimed to investigate the differential host immune response to wild type 1 poliovirus (wild PV and Sabin attenuated type 1 poliovirus (Sabin PV in cultured human neuronal cells. Methods: By using flow cytometry and real time PCR methods we examined host innate immune responses and compared the role of toll like receptors (TLRs and cytoplasmic RNA helicases in cultured human neuronal cells (SK-N-SH infected with Sabin PV and wild PV. Results: Human neuronal cells expressed very low levels of TLRs constitutively. Sabin PV infection induced significantly higher expression of TLR3, TLR7 and melanoma differentiation-associated protein-5 (MDA-5 m-RNA in neuronal cells at the beginning of infection (up to 4 h as compared to wild PV. Further, Sabin PV also induced the expression of interferon α/β at early time point of infection. The induced expression of IFN α/β gene by Sabin PV in neuronal cells could be suppressed by inhibiting TLR7. Interpretation & conclusions: Neuronal cell innate immune response to Sabin and wild polioviruses differ significantly for TLR3, TLR7, MDA5 and type 1 interferons. Effects of TLR7 activation and interferon production and Sabin virus replication in neuronal cells need to be actively investigated in future studies.

  12. Systematization of the Introduction of IPV and Switch from tOPV to bOPV in the Americas.

    Science.gov (United States)

    Pedreira, Cristina; Thrush, Elizabeth; Jauregui, Barbara

    2017-07-01

    The synchronized introduction of the inactivated polio vaccine (IPV) and the switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio vaccine (bOPV) has constituted an effort without precedents, and with astonishing results. Within the established time frame, all countries in our region managed to carry out the decision, planning, and introduction of this vaccine and subsequent switch to their national immunization schedules.The purpose of this article is to systematize the process of IPV introduction and switch in Latin America and the Caribbean, which constitutes an important piece in the documentation of the polio legacy in the Americas. Regional level as well as country perspectives and viewpoints are described. Analyzing and summarizing the lessons learned from the introduction of IPV and the switch from tOPV to bOPV can be useful for the introduction of new vaccines in the Pan American Health Organization (PAHO) region and in other regions of the world, and to help our own region successfully carry out another synchronized vaccine introduction in the future, if necessary. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  13. In vitro replication of poliovirus

    International Nuclear Information System (INIS)

    Lubinski, J.M.

    1986-01-01

    Poliovirus is a member of the Picornaviridae whose genome is a single stranded RNA molecule of positive polarity surrounded by a proteinaceous capsid. Replication of poliovirus occurs via negative strand intermediates in infected cells using a virally encoded RNA-dependent RNA polymerase and host cell proteins. The authors have exploited the fact that complete cDNA copies of the viral genome when transfected onto susceptible cells generate virus. Utilizing the bacteriophage SP6 DNA dependent RNA polymerase system to synthesize negative strands in vitro and using these in an in vitro reaction the authors have generated full length infectious plus strands. Mutagenesis of the 5' and 3' ends of the negative and positive strands demonstrated that replication could occur either de novo or be extensions of the templates from their 3' ends or from nicks occurring during replication. The appearance of dimeric RNA molecules generated in these reactions was not dependent upon the same protein required for de novo initiation. Full length dimeric RNA molecules using a 5' 32 P end-labelled oligo uridylic acid primer and positive strand template were demonstrated in vitro containing only the 35,000 Mr host protein and the viral RNA-dependent RNA polymerase. A model for generating positive strands without protein priming by cleavage of dimeric RNA molecules was proposed

  14. IPv6: The Next Generation Internet Protocol

    Indian Academy of Sciences (India)

    addressing, new generation internet. 2. ... required the creation of the next generation of Internet ... IPv6 standards have defined the following Extension headers ..... addresses are represented as x:x:x:x:x:x:x:x, where each x is the hexadecimal ...

  15. Discovery of IPV6 Router Interface Addresses via Heuristic Methods

    Science.gov (United States)

    2015-09-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS DISCOVERY OF IPV6 ROUTER INTERFACE ADDRESSES VIA HEURISTIC METHODS by Matthew D. Gray September...AND SUBTITLE DISCOVERY OF IPV6 ROUTER INTERFACE ADDRESSES VIA HEURISTIC METHODS 5. FUNDING NUMBERS CNS-1111445 6. AUTHOR(S) Matthew D. Gray 7...Internet Assigned Numbers Authority, there is continued pressure for widespread IPv6 adoption. Because the IPv6 address space is orders of magnitude

  16. IPV6 Deployment - Mauritius to benefit from Opportunities and World ...

    African Journals Online (AJOL)

    user1

    gaming, and many other new applications cost even higher to be deployed on IPv4 ... mitigate the effects of the imminent depletion of the IPv4 address space and .... The government of Korea plans to achieve complete IPv6 transition in the.

  17. IPV6 Deployment - Mauritius to benefit from Opportunities and World ...

    African Journals Online (AJOL)

    The current standard protocol, IPV4, has reached its limit in terms of addressing possibilities, being limited by the 32-bits addressing scheme. Its successor, IPV6, had been devised since the mid 1990's. In addition to handling the address limitations, IPV6 also includes a number of improved features, making it superior to ...

  18. Measuring and Comparing the Stability of Internet Paths over IPv4 & IPv6

    OpenAIRE

    Golkar, Forough

    2014-01-01

    Enormous Internet growth is an obvious trend nowadays while Internet protocol version 4 address space exhaustion led into the invention of Internet protocol version 6 and subsequently raised the transitioning challenges from one protocol to the other one. As the Internet protocol version 6 have not been around for a long time, thus there is a limitation knowledge in topology, routing change and performance of IPv6. Several studies are going on in order to getting the information about IPv6 wh...

  19. Interworking between IP security and NAT-PT under IPv4/IPv6 co-existent environments

    Science.gov (United States)

    Ye, Run-Guo; Yu, Shu-Yao; Yang, Hong-Wei; Song, Chuck

    2005-02-01

    Similar to conventional NAT gateways, NAT-PT gateways break traditional TCP/IP"s end-to-end argument property; hence, any IP-based applications protected by IPSec protocol cannot traverse NAT-PT gateways properly. The interworking issues between IPSec and NAT-PT gateways under IPv4/IPv6 co-existent environments were studied: this paper first pointed out the deficiency of current NAT-Traversal scheme when interworking with NAT-PT gateways and proposed an enhanced scheme, which enabled interworking between IPSec and NAT-PT gateways and served the following three scenarios: 1) secure communication between IPv6 hosts and IPv4 hosts; 2) secure communication between IPv6 subnets and IPv4 subnets; 3) secure communication between remote IPv6 hosts and legacy IPv4 subnets.

  20. Modelo para la integración de redes IPv4 – IPv6 basado en túneles

    Directory of Open Access Journals (Sweden)

    Danilo López

    2010-12-01

    Full Text Available The intention of this paper is to set up a general model in order to interconnect heterogeneous nets IPv4-IPv6, guarantying the integrity of the data, making use of transition techniques.

  1. From IPv4 to eternity - the HEPiX IPv6 working group

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The much-heralded exhaustion of the IPv4 networking address space has finally started. While many of the research and education networks have been ready and poised for years to carry IPv6 traffic, there is a well-known lack of academic institutes using the new protocols. One reason for this is an obvious absence of pressure due to the extensive use of NAT or that most currently still have sufficient IPv4 addresses. More importantly though, the fact is that moving your distributed applications to IPv6 involves much more than the routing, naming and addressing solutions provided by your campus and national networks. Application communities need to perform a full analysis of their applications, middleware and tools to confirm how much development work is required to use IPv6 and to plan a smooth transition. A new working group of HEPiX (http://www.hepix.org) was formed in Spring 2011 to address exactly these issues for the High Energy Physics community. The HEPiX IPv6 Working Group has been investigating the ma...

  2. [VACCINES].

    Science.gov (United States)

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  3. Hematopoietic Cancer Cell Lines Can Support Replication of Sabin Poliovirus Type 1

    Science.gov (United States)

    van Eikenhorst, Gerco; de Gruijl, Tanja D.; van der Pol, Leo A.; Bakker, Wilfried A. M.

    2015-01-01

    Viral vaccines can be produced in adherent or in suspension cells. The objective of this work was to screen human suspension cell lines for the capacity to support viral replication. As the first step, it was investigated whether poliovirus can replicate in such cell lines. Sabin poliovirus type 1 was serially passaged on five human cell lines, HL60, K562, KG1, THP-1, and U937. Sabin type 1 was capable of efficiently replicating in three cell lines (K562, KG1, and U937), yielding high viral titers after replication. Expression of CD155, the poliovirus receptor, did not explain susceptibility to replication, since all cell lines expressed CD155. Furthermore, we showed that passaged virus replicated more efficiently than parental virus in KG1 cells, yielding higher virus titers in the supernatant early after infection. Infection of cell lines at an MOI of 0.01 resulted in high viral titers in the supernatant at day 4. Infection of K562 with passaged Sabin type 1 in a bioreactor system yielded high viral titers in the supernatant. Altogether, these data suggest that K562, KG1, and U937 cell lines are useful for propagation of poliovirus. PMID:25815312

  4. Response to a wild poliovirus type 2 (WPV2)-shedding event following accidental exposure to WPV2, the Netherlands, April 2017.

    Science.gov (United States)

    Duizer, Erwin; Ruijs, Wilhelmina Lm; van der Weijden, Charlie P; Timen, Aura

    2017-05-25

    On 3 April 2017, a wild poliovirus type 2 (WPV2) spill occurred in a Dutch vaccine manufacturing plant. Two fully vaccinated operators with risk of exposure were advised on stringent personal hygiene and were monitored for virus shedding. Poliovirus (WPV2-MEF1) was detected in the stool of one, 4 days after exposure, later also in sewage samples. The operator was isolated at home and followed up until shedding stopped 29 days after exposure. No further transmission was detected. This article is copyright of The Authors, 2017.

  5. An IPv6 Multihomed Host for Outbound Traffic

    Science.gov (United States)

    Chen, Chin-Ling; Cao, Sheng-Lung

    Though the technology of IPv6 network has become mature in recent years, it still takes long to dispose IPv6 in an all-round way in the internet. In this research, we have designed an IPv6 multihomed host architecture to connect both IPv6 network and 6to4 network. This paper describes a load balance mechanism that allows applications on multihomed devices to utilize the individual networks efficiently to transmit streams that could be part of a session. We experiment the relevant parameters in the IPv6 testbed environment to demonstrate its effectiveness.

  6. Acute flaccid paralysis surveillance in bosnia and herzegovina: Recent isolation of two sabin like type 2 poliovirus.

    Science.gov (United States)

    Fontana, Stefano; Buttinelli, Gabriele; Fiore, Stefano; Mulaomerovic, Mirsada; Aćimović, Jela; Amato, Concetta; Delogu, Roberto; Rezza, Giovanni; Stefanelli, Paola

    2017-09-01

    The WHO Regional Commission for the Certification of Poliomyelitis Eradication has recently indicated Bosnia and Herzegovina (B&H) as a high risk country for transmission, following importation, of wild poliovirus (WPV) or circulating vaccine-derived poliovirus (cVDPV). We analyzed data on Acute Flaccid Paralysis (AFP) surveillance between 2007 to 2016, and the trend of polio immunization coverage in B&H. The majority of AFP cases was recorded in 2016 suggesting an enhancement of the AFP surveillance activities. However, the decline in the immunization coverage, around 74%, and the isolation of two Sabin-like poliovirus type 2 strains, one of them close to a VDPV, require a particular attention in the area. Although B&H has successfully maintained its polio-free status since 2002 several challenges need to be addressed. © 2017 Wiley Periodicals, Inc.

  7. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21

    International Nuclear Information System (INIS)

    Nagata, Noriyo; Iwasaki, Takuya; Ami, Yasushi; Sato, Yuko; Hatano, Ikuyoshi; Harashima, Ayako; Suzaki, Yuriko; Yoshii, Takao; Hashikawa, Tsutomu; Sata, Tetsutaro; Horiuchi, Yoshinobu; Koike, Satoshi; Kurata, Takeshi; Nomoto, Akio

    2004-01-01

    Transgenic mice bearing the human poliovirus receptor (TgPVR) are less susceptible to oral inoculation, although they are susceptible to parenteral inoculation. We investigated the susceptibility of TgPVR 21 line [Arch. Virol. 130 (1994) 351] to poliovirus through various mucosal routes. Intranasal inoculation of a neurovirulent Mahoney strain (OM1) caused flaccid paralysis with viral replication in the central nervous system at a dose of 10 6 cell culture infectious dose (CCID 50 ), in contrast, no paralysis following oral or intragastric inoculation of the same dose. Intranasal inoculation of a vaccine strain, Sabin 1, at 10 6 CCID 50 , resulted in no paralysis. Initial replication of poliovirus in the nasal cavity was confirmed by virus isolation and detection of negative-stranded replicative intermediates by RT-PCR and viral antigens using a high-sensitive immunohistochemistry and genome/transcripts by in situ hybridization. Poliovirus-specific IgG antibodies were elevated in the sera of surviving TgPVR21. This model can be used as a mucosal infection model and for differentiation of neurovirulent and attenuated poliovirus strains

  8. Characterization and standardization of Sabin based inactivated polio vaccine: proposal for a new antigen unit for inactivated polio vaccines.

    Science.gov (United States)

    Westdijk, Janny; Brugmans, Debbie; Martin, Javier; van't Oever, Aart; Bakker, Wilfried A M; Levels, Lonneke; Kersten, Gideon

    2011-04-18

    GMP-batches of Sabin-IPV were characterized for their antigenic and immunogenic properties. Antigenic fingerprints of Sabin-IPV reveal that the D-antigen unit is not a fixed amount of antigen but depends on antibody and assay type. Instead of the D-antigen unit we propose standardization of IPV based on a combination of protein amount for dose and D-antigenicity for quality of the vaccine. Although Sabin-IPV type 2 is less immunogenic than regular wild type IPV type 2, the immunogenicity (virus neutralizing titers) per microgram antigen for Sabin-IPV type 2 is in the same order as for wild type serotypes 1 and 3. The latter observations are in line with data from human trials. This suggests that a higher dose of Sabin-IPV type 2 to compensate for the lower rat immunogenicity may not be necessary. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Poliovirus Studies during the Endgame of the Polio Eradication Program.

    Science.gov (United States)

    Arita, Minetaro

    2017-01-24

    Since the beginning of Global Polio Eradication Initiative in 1988, poliomyelitis cases caused by wild poliovirus (PV) have been drastically reduced, with only 74 cases reported in 2 endemic countries in 2015. The current limited PV transmission suggests that we are in the endgame of the polio eradication program. However, specific challenges have emerged in the endgame, including tight budget, switching of the vaccines, and changes in biorisk management of PV. To overcome these challenges, several PV studies have been implemented in the eradication program. Some of the responses to the emerging challenges in the polio endgame might be valuable in other infectious diseases eradication programs. Here, I will review challenges that confront the polio eradication program and current research to address these challenges.

  10. IPV6 Network Infrastructure and Stability Inference

    Science.gov (United States)

    2014-09-01

    the Too Big Trick ( TBT ) to induce the remote targets to return fragmented responses. By evaluating the responses, the uptime for approximately 35% of...Internet. Approximately 50,000 IPv6 addresses were probed continuously from March to June 2014, using the Too Big Trick ( TBT ) to induce the remote targets...SNMP Simple Network Management Protocol TSval Timestamp Value TCP Transmission Control Protocol TBT Too Big Trick USG U.S. government xiv

  11. IPv6 races across the Atlantic

    CERN Multimedia

    2003-01-01

    "...Scientists at the California Institute of Technology and the European Organization for Nuclear Research (CERN) have set a new Internet2 land speed record using IPv6, the next-generation Internet protocol. The team sustained a single stream transmission control protocol (TCP) rate of 983 Mbits/s for more than an hour between CERN's facility in Geneva and Chicago, spanning more than 7000 km" (1/2 page).

  12. HIV Positive Diagnosis During Pregnancy Increases Risk of IPV Postpartum Among Women with No History of IPV in Their Relationship.

    Science.gov (United States)

    Groves, Allison K; Reyes, H Luz McNaughton; Moodley, Dhayendre; Maman, Suzanne

    2017-07-24

    There has been limited study of whether and for whom physical intimate partner violence (IPV) is a consequence of an HIV-positive diagnosis. Per the diathesis stress model, the consequences of HIV infection may be worse for women with a history of IPV. We hypothesize that the positive association between HIV diagnosis in pregnancy and postpartum IPV will be exacerbated for women with a history of IPV. Data come from a prospective cohort study with 1015 participants who completed a baseline antenatal and 9-month postpartum visit. Using logistic regression analyses, we found a statistically significant interaction between HIV diagnosis, history of IPV and postpartum IPV (AOR: 0.40, 95% CI 0.17-0.96). The findings were in the opposite direction as expected: HIV-diagnosis was not associated with IPV for women with a history of IPV (AOR: 2.17, 95% CI 1.06, 4.42). However, HIV-positive women without a history of IPV faced more than two times the risk of incident postpartum IPV than HIV-negative women (AOR: 2.17, 95% CI 1.06, 4.42). Interventions to reduce incident and ongoing IPV during the perinatal period are needed.

  13. IPv6 Addressing Proxy: Mapping Native Addressing from Legacy Technologies and Devices to the Internet of Things (IPv6

    Directory of Open Access Journals (Sweden)

    Peter Kirstein

    2013-05-01

    Full Text Available Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT. IPv6 provides addressing space to reach this ubiquitous set of sensors, but legacy technologies, such as X10, European Installation Bus (EIB, Controller Area Network (CAN and radio frequency ID (RFID from the industrial, home automation and logistic application areas, do not support the IPv6 protocol. For that reason, a technique must be devised to map the sensor and identification technologies to IPv6, thus allowing homogeneous access via IPv6 features in the context of the IoT. This paper proposes a mapping between the native addressing of each technology and an IPv6 address following a set of rules that are discussed and proposed in this work. Specifically, the paper presents a technology-dependent IPv6 addressing proxy, which maps each device to the different subnetworks built under the IPv6 prefix addresses provided by the internet service provider for each home, building or user. The IPv6 addressing proxy offers a common addressing environment based on IPv6 for all the devices, regardless of the device technology. Thereby, this offers a scalable and homogeneous solution to interact with devices that do not support IPv6 addressing. The IPv6 addressing proxy has been implemented in a multi-protocol Sensors 2013, 13 6688 card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6.

  14. IPv6 Addressing Proxy: Mapping Native Addressing from Legacy Technologies and Devices to the Internet of Things (IPv6)

    Science.gov (United States)

    Jara, Antonio J.; Moreno-Sanchez, Pedro; Skarmeta, Antonio F.; Varakliotis, Socrates; Kirstein, Peter

    2013-01-01

    Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT). IPv6 provides addressing space to reach this ubiquitous set of sensors, but legacy technologies, such as X10, European Installation Bus (EIB), Controller Area Network (CAN) and radio frequency ID (RFID) from the industrial, home automation and logistic application areas, do not support the IPv6 protocol. For that reason, a technique must be devised to map the sensor and identification technologies to IPv6, thus allowing homogeneous access via IPv6 features in the context of the IoT. This paper proposes a mapping between the native addressing of each technology and an IPv6 address following a set of rules that are discussed and proposed in this work. Specifically, the paper presents a technology-dependent IPv6 addressing proxy, which maps each device to the different subnetworks built under the IPv6 prefix addresses provided by the internet service provider for each home, building or user. The IPv6 addressing proxy offers a common addressing environment based on IPv6 for all the devices, regardless of the device technology. Thereby, this offers a scalable and homogeneous solution to interact with devices that do not support IPv6 addressing. The IPv6 addressing proxy has been implemented in a multi-protocol card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6. PMID:23686145

  15. IPv6 addressing proxy: mapping native addressing from legacy technologies and devices to the Internet of Things (IPv6).

    Science.gov (United States)

    Jara, Antonio J; Moreno-Sanchez, Pedro; Skarmeta, Antonio F; Varakliotis, Socrates; Kirstein, Peter

    2013-05-17

    Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT). IPv6 provides addressing space to reach this ubiquitous set of sensors, but legacy technologies, such as X10, European Installation Bus (EIB), Controller Area Network (CAN) and radio frequency ID (RFID) from the industrial, home automation and logistic application areas, do not support the IPv6 protocol. For that reason, a technique must be devised to map the sensor and identification technologies to IPv6, thus allowing homogeneous access via IPv6 features in the context of the IoT. This paper proposes a mapping between the native addressing of each technology and an IPv6 address following a set of rules that are discussed and proposed in this work. Specifically, the paper presents a technology-dependent IPv6 addressing proxy, which maps each device to the different subnetworks built under the IPv6 prefix addresses provided by the internet service provider for each home, building or user. The IPv6 addressing proxy offers a common addressing environment based on IPv6 for all the devices, regardless of the device technology. Thereby, this offers a scalable and homogeneous solution to interact with devices that do not support IPv6 addressing. The IPv6 addressing proxy has been implemented in a multi-protocol Sensors 2013, 13 6688 card and evaluated successfully its performance, scalability and interoperability through a protocol built over IPv6.

  16. The Department of Defense's Transition of Program of Record (POR) Systems from Internet Protocol Version Four (IPv4) to Internet Protocol Version Six (IPv6)

    National Research Council Canada - National Science Library

    Perkins, Kyle L; Scott, Michael A

    2006-01-01

    .... The research outlines the initial intended useful life and limitations of IPv4 and IPv6. The financial aspects of transitioning to IPv6 are examined from a programs perspective, relative to the Program Objective Memorandum (POM...

  17. Sabin and wild type polioviruses from children who presented with ...

    African Journals Online (AJOL)

    Conclusion: This study further confirms the presence of Sabin and wild-type poliovirus among children in Nigeria. The isolation of Sabin strain of poliovirus is advantageous to the polio eradication program as it is capable of inducing natural immunity in susceptible hosts. Transmission of wild-type poliovirus among children ...

  18. 21 CFR 866.3405 - Poliovirus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Poliovirus serological reagents. 866.3405 Section... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3405 Poliovirus serological reagents. (a) Identification. Poliovirus serological reagents are devices that consist of antigens...

  19. The postpolio syndrome: no evidence for poliovirus persistence

    NARCIS (Netherlands)

    Melchers, W.; de Visser, M.; Jongen, P.; van Loon, A.; Nibbeling, R.; Oostvogel, P.; Willemse, D.; Galama, J.

    1992-01-01

    To investigate the possibility of poliovirus persistence in patients with the postpolio syndrome, we examined skeletal muscle biopsy specimens, cerebrospinal fluid specimens, and sera for the presence of poliovirus RNA by the polymerase chain reaction, and for IgM antibodies by a poliovirus

  20. Five of Five VHHs Neutralizing Poliovirus Bind the Receptor-Binding Site.

    Science.gov (United States)

    Strauss, Mike; Schotte, Lise; Thys, Bert; Filman, David J; Hogle, James M

    2016-01-13

    Nanobodies, or VHHs, that recognize poliovirus type 1 have previously been selected and characterized as candidates for antiviral agents or reagents for standardization of vaccine quality control. In this study, we present high-resolution cryo-electron microscopy reconstructions of poliovirus with five neutralizing VHHs. All VHHs bind the capsid in the canyon at sites that extensively overlap the poliovirus receptor-binding site. In contrast, the interaction involves a unique (and surprisingly extensive) surface for each of the five VHHs. Five regions of the capsid were found to participate in binding with all five VHHs. Four of these five regions are known to alter during the expansion of the capsid associated with viral entry. Interestingly, binding of one of the VHHs, PVSS21E, resulted in significant changes of the capsid structure and thus seems to trap the virus in an early stage of expansion. We describe the cryo-electron microscopy structures of complexes of five neutralizing VHHs with the Mahoney strain of type 1 poliovirus at resolutions ranging from 3.8 to 6.3Å. All five VHHs bind deep in the virus canyon at similar sites that overlap extensively with the binding site for the receptor (CD155). The binding surfaces on the VHHs are surprisingly extensive, but despite the use of similar binding surfaces on the virus, the binding surface on the VHHs is unique for each VHH. In four of the five complexes, the virus remains essentially unchanged, but for the fifth there are significant changes reminiscent of but smaller in magnitude than the changes associated with cell entry, suggesting that this VHH traps the virus in a previously undescribed early intermediate state. The neutralizing mechanisms of the VHHs and their potential use as quality control agents for the end game of poliovirus eradication are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. The global introduction of inactivated polio vaccine can circumvent the oral polio vaccine paradox

    NARCIS (Netherlands)

    Heinsbroek, E.; Ruitenberg, E.J.

    2010-01-01

    This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become

  2. Mandatory vaccinations in European countries, undocumented information, false news and the impact on vaccination uptake: the position of the Italian pediatric society.

    Science.gov (United States)

    Bozzola, Elena; Spina, Giulia; Russo, Rocco; Bozzola, Mauro; Corsello, Giovanni; Villani, Alberto

    2018-06-14

    High rates of vaccination coverage are important in preventing infectious diseases. Enforcing mandatory vaccinations is one of the strategies that some Countries adopted to protect the community when vaccination coverage is not satisfactory. In Italy, in 2017 vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella became compulsory in childhood. In order to contrast vaccination policies, anti-vaccination campaigns contribute to the spread of fake news. Among them, there is the false information that Italy is the only one country with mandatory vaccination policy. Aim of our study is confronting vaccination policies in children under 18 months against among different European countries for the following vaccines: diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella. Information on policies of mandatory or recommended vaccinations of the European Countries were gathered by ECDC and compared to the Italian one. European Countries recommend or contemplate compulsory vaccines. Among them, eleven Countries (35.4%) have mandatory vaccinations for at least one out of diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella vaccine. Not only in Italy, vaccination against diphtheria, tetanus, pertussis, hepatitis B, poliovirus, Haemophilus influenzae type b, measles, mumps, rubella and varicella is mandatory in children under 18 months. Other European countries adopted compulsory policies in order to prevent the spread of infectious diseases and to protect the community.

  3. The association between child exposure to intimate partner violence (IPV) and perpetration of IPV in adulthood-A systematic review.

    Science.gov (United States)

    Kimber, Melissa; Adham, Sami; Gill, Sana; McTavish, Jill; MacMillan, Harriet L

    2018-02-01

    Increasingly recognized as a distinct form of childhood maltreatment, children's exposure to intimate partner violence (IPV) has been shown to be associated with an array of negative psychosocial outcomes, including elevated risk for additional violence over the life course. Although studies have identified child exposure to IPV as a predictor of IPV perpetration in adulthood, no review has critically evaluated the methodology of this quantitative work. The present study examines the association between childhood exposure to IPV and the perpetration of IPV in adulthood based on a systematic review of the literature from inception to January 4, 2016. Databases searched included Medline, Embase, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, Sociological Abstracts and ERIC. Database searches were complemented with backward and forward citation chaining. Studies were critically appraised using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of 5601 articles identified by the search, 19 studies were included for data extraction. Sixteen of these studies found that child exposure to IPV was significantly and positively associated with adult IPV perpetration; three studies reported null findings. The methodological quality of the studies was low. Work thus far has tended to focus on child exposure to physical IPV and the perpetration of physical IPV within heterosexual contexts. In addition, measures of child exposure to IPV vary in their classification of what exposure entails. We critically discuss the strengths and limitations of the existing evidence and the theoretical frameworks informing this work. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats.

    Science.gov (United States)

    Sedita, Jeff; Perrella, Stefanie; Morio, Matt; Berbari, Michael; Hsu, Jui-Shan; Saxon, Eugene; Jarrahian, Courtney; Rein-Weston, Annie; Zehrung, Darin

    2018-03-14

    Despite limitations of glass packaging for vaccines, the industry has been slow to implement alternative formats. Polymer containers may address many of these limitations, such as breakage and delamination. However, the ability of polymer containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD) competitive with that of glass containers is unclear, especially for cost-sensitive low- and lower-middle-income countries. COGS and TCOD models for oral and parenteral vaccine packaging formats were developed based on information from subject matter experts, published literature, and Kenya's comprehensive multiyear plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were used as representative examples of oral and parenteral vaccines, respectively. Packaging technologies evaluated included glass vials, blow-fill-seal (BFS) containers, preformed polymer containers, and compact prefilled auto-disable (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS multi-monodose (MMD) ampoules were the least expensive format, with a COGS of $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40. BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60 per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine formats at $1.56 per dose delivered. Of the polymer containers for parenteral vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered, whereas preformed CPAD devices remained the most expensive format, at $2.25 per dose delivered. Given their potential to address the limitations of glass and reduce COGS and TCOD, polymer containers deserve further consideration as alternative

  5. Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

    Science.gov (United States)

    Clark, Sarah J; Cowan, Anne E; Freed, Gary L

    2011-04-01

    Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

  6. Quadrivalent meningococcal (MenACWY-TT) conjugate vaccine or a fourth dose of H. influenzae-N. meningitidis C/Y conjugate vaccine (HibMenCY-TT) is immunogenic in toddlers who previously received three doses of HibMenCY-TT in infancy.

    Science.gov (United States)

    Leonardi, Michael; Latiolais, Thomas; Sarpong, Kwabena; Simon, Michael; Twiggs, Jerry; Lei, Paul; Rinderknecht, Stephen; Blatter, Mark; Bianco, Veronique; Baine, Yaela; Friedland, Leonard R; Miller, Jacqueline M

    2015-02-11

    Immunogenicity and safety of a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT were evaluated in the second year of life in HibMenCY-TT-primed toddlers. Healthy infants were randomized (5:1) and primed at 2, 4 and 6 months of age with HibMenCY-TT and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTaP-HBV-IPV) vaccine; or Hib-TT and DTaP-HBV-IPV (control). Recipients of HibMenCY-TT+DTaP-HBV-IPV were re-randomized (2:2:1) to receive MenACWY-TT at 12-15 months and DTaP at 15-18 months; MenACWY-TT co-administered with DTaP at 15-18 months; or HibMenCY-TT at 12-15 months and DTaP at 15-18 months. Controls received DTaP only at 15-18 months due to Hib conjugate vaccine shortage. Serum bactericidal activity using human complement (hSBA) and safety were assessed one month after meningococcal vaccination. After vaccination with MenACWY-TT at 12-15 months or MenACWY-TT+DTaP at 15-18 months, all subjects previously primed for serogroups C/Y had hSBA ≥1:8 for these serogroups. At least 96.1% also had hSBA ≥1:8 for serogroups A/W. All subjects in the HibMenCY-TT group had hSBA ≥1:8 for serogroups C/Y. All pre-defined statistical criteria for meningococcal immunogenicity were satisfied. All vaccination regimens had acceptable safety profiles. Children primed with three doses of HibMenCY-TT who then received a single dose of MenACWY-TT or a fourth dose of HibMenCY-TT had robust increases in hSBA titers for serogroups C/Y. These data provide support that MenACWY-TT, given with or without the fourth scheduled dose of DTaP could be administered as an alternative to a fourth dose of HibMenCY-TT in the second year of life. This study (110870/110871) is registered at www.clinicaltrials.gov NCT00614614. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Deployment of IPv6-only CPU resources at WLCG sites

    Science.gov (United States)

    Babik, M.; Chudoba, J.; Dewhurst, A.; Finnern, T.; Froy, T.; Grigoras, C.; Hafeez, K.; Hoeft, B.; Idiculla, T.; Kelsey, D. P.; López Muñoz, F.; Martelli, E.; Nandakumar, R.; Ohrenberg, K.; Prelz, F.; Rand, D.; Sciabà, A.; Tigerstedt, U.; Traynor, D.

    2017-10-01

    The fraction of Internet traffic carried over IPv6 continues to grow rapidly. IPv6 support from network hardware vendors and carriers is pervasive and becoming mature. A network infrastructure upgrade often offers sites an excellent window of opportunity to configure and enable IPv6. There is a significant overhead when setting up and maintaining dual-stack machines, so where possible sites would like to upgrade their services directly to IPv6 only. In doing so, they are also expediting the transition process towards its desired completion. While the LHC experiments accept there is a need to move to IPv6, it is currently not directly affecting their work. Sites are unwilling to upgrade if they will be unable to run LHC experiment workflows. This has resulted in a very slow uptake of IPv6 from WLCG sites. For several years the HEPiX IPv6 Working Group has been testing a range of WLCG services to ensure they are IPv6 compliant. Several sites are now running many of their services as dual-stack. The working group, driven by the requirements of the LHC VOs to be able to use IPv6-only opportunistic resources, continues to encourage wider deployment of dual-stack services to make the use of such IPv6-only clients viable. This paper presents the working group’s plan and progress so far to allow sites to deploy IPv6-only CPU resources. This includes making experiment central services dual-stack as well as a number of storage services. The monitoring, accounting and information services that are used by jobs also need to be upgraded. Finally the VO testing that has taken place on hosts connected via IPv6-only is reported.

  8. The design of IPv6's transitional scheme in university

    Science.gov (United States)

    Li, Biqing; Li, Zhao

    2017-05-01

    According to the current network environment of campus, the specific scheme of network transition is proposed, which has conducted detailed analyses for the basic concepts, the types of address, the necessary technology for transition and the agreement and principle of transition. According to the tunneling technology of IPv6, the IPv4 network and IPv6 network can communicate with each other, and the network of whole campus can operate well.

  9. A Brief History of MPLS Usage in IPv6

    OpenAIRE

    Vanaubel, Yves; Mérindol, Pascal; Pansiot, Jean-Jacques; Donnet, Benoît

    2016-01-01

    Recent researches have stated the fast deployment of IPv6. It has been demonstrated that IPv6 grows much faster, being so more and more adopted by both Internet service providers but also by servers and end-hosts. In parallel, researches have been conducted to discover and assess the usage of MPLS tunnels. Indeed, recent developments in the ICMP protocol make certain categories of MPLS tunnels transparent to traceroute probing. However, these studies focus only on IPv4, where MPLS is st...

  10. Molecular characterization and phylogenetic relationship of wild type 1 poliovirus strains circulating across Pakistan and Afghanistan bordering areas during 2010-2012.

    Directory of Open Access Journals (Sweden)

    Shahzad Shaukat

    Full Text Available Pakistan and Afghanistan share a long uncontrolled border with extensive population movement on both sides. Wild poliovirus transmission has never been interrupted in this block due to war against terrorism, poor public health infrastructure, misconceptions about polio vaccines and inadequate immunization activities. All these issues complicate the eradication operations and reinforce the complexity of wiping out poliomyelitis from this region. This study illustrates the origins and routes of cross-border wild poliovirus type 1 (WPV1 transmission during 2010-2012 between Pakistan and Afghanistan. Sequence analyses were conducted based on complete VP1 capsid protein sequences for WPV1 study strains to determine the origin of poliovirus genetic lineages and their evolutionary relationships. Phylogenetic tree was constructed from VP1 gene sequences applying Maximum Likelihood method using Kimura 2- parameter model in MEGA program v 5.0. A total of 72 (14.3% out of 502 wild-type 1 polioviruses were found circulating in border areas of both countries during 2010-2012. Molecular phylogenetic analysis classified these strains in to two sub-genotypes with four clusters and 18 lineages. Genetic data confirmed that the most of WPV1 lineages (12; 66.6% were transmitted from Pakistan to Afghanistan. However, the genetic diversity was significantly reduced during 2012 as most of the lineages were completely eliminated. In conclusion, Pakistan-Afghanistan block has emerged as a single poliovirus reservoir sharing the multiple poliovirus lineages due to uncontrolled movement of people across the borders between two countries. If it is neglected, it can jeopardize the extensive global efforts done so-far to eradicate the poliovirus infection. Our data will be helpful to devise the preventive strategies for effective control of wild poliovirus transmission in this region.

  11. Assessing Inactivated Polio Vaccine Introduction and Utilization in Kano State, Nigeria, April-November 2015.

    Science.gov (United States)

    Osadebe, Lynda U; MacNeil, Adam; Elmousaad, Hashim; Davis, Lora; Idris, Jibrin M; Haladu, Suleiman A; Adeoye, Olorunsogo B; Nguku, Patrick; Aliu-Mamudu, Uneratu; Hassan, Elizabeth; Vertefeuille, John; Bloland, Peter

    2017-07-01

    Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Evaluation of IPV6 and MOFI IOT

    OpenAIRE

    Waleed Shahjehan; Dr. Mohammad Haseeb Zafar

    2017-01-01

    One of the internet’s new revolution is Internet of Things (IOT) due to this objects themselves can recognize one another, get intelligence, transfer information to each other about their own and their ability to access the information that has been combined by other things.. The basic design of the IPV6 was that only end devices are the one with high intelligence and network is used for delivery of packets simply. In present Internet it is observed that inefficiency is created in Internet Pr...

  13. Evaluation of IPV6 and MOFI IOT

    OpenAIRE

    Shahjehan , Waleed; Zafar , Mohammad ,; Hussain , Irshad; Farooq , Muhammad

    2017-01-01

    International audience; One of the internet’s new revolution is Internet of Things (IOT) due to this objects themselves can recognize one another, get intelligence, transfer information to each other about their own and their ability to access the information that has been combined by other things.. The basic design of the IPV6 was that only end devices are the one with high intelligence and network is used for delivery of packets simply. In present Internet it is observed that inefficiency i...

  14. [Immunoreactivity of chimeric proteins carrying poliovirus epitopes on the VP6 of rotavirus as a vector].

    Science.gov (United States)

    Pan, X-X; Zhao, B-X; Teng, Y-M; Xia, W-Y; Wang, J; Li, X-F; Liao, G-Y; Yang, С; Chen, Y-D

    2016-01-01

    Rotavirus and poliovirus continue to present significant risks and burden of disease to children in developing countries. Developing a combined vaccine may effectively prevent both illnesses and may be advantageous in terms of maximizing compliance and vaccine coverage at the same visit. Recently, we sought to generate a vaccine vector by incorporating multiple epitopes into the rotavirus group antigenic protein, VP6. In the present study, a foreign epitope presenting a system using VP6 as a vector was created with six sites on the outer surface of the vector that could be used for insertion of foreign epitopes, and three VP6-based PV1 epitope chimeric proteins were constructed. The chimeric proteins were confirmed by immunoblot, immunofluorescence assay, and injected into guinea pigs to analyze the epitope-specific humoral response. Results showed that these chimeric proteins reacted with anti-VP6F and -PV1 antibodies, and elicited antibodies against both proteins in guinea pigs. Antibodies against the chimeric proteins carrying PV1 epitopes neutralized rotavirus Wa and PV1 infection in vitro. Our study contributes to a better understanding of the use of VP6-based vectors as multiple-epitope delivery vehicles and the epitopes displayed in this form could be considered for development of epitope-based vaccines against rotavirus and poliovirus.

  15. Nivel de desempeño en redes IPv4 con respecto a redes IPv6 con MPLS y RSVP

    Directory of Open Access Journals (Sweden)

    Alexis Guevara Peña

    2011-06-01

    Full Text Available This paper contains relevant information of the state of art of traffic engineering, MPLS (Multiprotocol Lable Switching and RSVP (Resource Reservation Protocol, as a case study and the techniques used under the new version of IPV6, against IPV4 version. The paper is intended to serve as a framework for the study of Engineering Traffic Based on the new version of IPV6, specifically MPLS and RSVP, takinginto account relevant considerations necessary when making decisions regarding the stability of the Backbone remains the key to Internet service providers that have recently stabilized its IPv4 infrastructure.

  16. Poliovirus Polymerase Leu420 Facilitates RNA Recombination and Ribavirin Resistance

    Science.gov (United States)

    Kempf, Brian J.; Peersen, Olve B.

    2016-01-01

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

  17. Introduction of sequential inactivated polio vaccine-oral polio vaccine schedule for routine infant immunization in Brazil's National Immunization Program.

    Science.gov (United States)

    Domingues, Carla Magda Allan S; de Fátima Pereira, Sirlene; Cunha Marreiros, Ana Carolina; Menezes, Nair; Flannery, Brendan

    2014-11-01

    In August 2012, the Brazilian Ministry of Health introduced inactivated polio vaccine (IPV) as part of sequential polio vaccination schedule for all infants beginning their primary vaccination series. The revised childhood immunization schedule included 2 doses of IPV at 2 and 4 months of age followed by 2 doses of oral polio vaccine (OPV) at 6 and 15 months of age. One annual national polio immunization day was maintained to provide OPV to all children aged 6 to 59 months. The decision to introduce IPV was based on preventing rare cases of vaccine-associated paralytic polio, financially sustaining IPV introduction, ensuring equitable access to IPV, and preparing for future OPV cessation following global eradication. Introducing IPV during a national multivaccination campaign led to rapid uptake, despite challenges with local vaccine supply due to high wastage rates. Continuous monitoring is required to achieve high coverage with the sequential polio vaccine schedule. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. Environmental Surveillance of Polioviruses in Rio de Janeiro, Brazil, in Support to the Activities of Global Polio Eradication Initiative.

    Science.gov (United States)

    de Oliveira Pereira, Joseane Simone; da Silva, Lidiane Rodrigues; de Meireles Nunes, Amanda; de Souza Oliveira, Silas; da Costa, Eliane Veiga; da Silva, Edson Elias

    2016-03-01

    Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio-free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine-derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period.

  19. Heat-accelerated radioinactivation of attenuated poliovirus

    International Nuclear Information System (INIS)

    Dugan, V.L.; Trujillo, R.

    1975-01-01

    Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment. (orig.) [de

  20. Inkubasi Implementasi Ipv6 di Lingkungan PT Telekomunikasi Indonesia Tbk

    Directory of Open Access Journals (Sweden)

    Lunel Candra

    2013-12-01

    ABSTRACT As a network and information service provider in Indonesia, PT Telekomunikasi Indonesia (Telkom is facing a number of problems of exhausted IP addresses, which is also being faced by global telecommunications world. IP addresses widely used todays, i.e. IPv4, have a limitation in terms of number and will be out soon. However, there are some solutions that can be done by telecom operators including implementation of NAT (Network Address Translation 444, dual stack IPv4 and IPv6, tunneling, and native IPv6. Each of the solutions mentioned above have advantages and disadvantages, but the target native IPv6 as main target seems to be the only feasible solution to be addressed by IT industry players, including Telkom. Telkom RDC as the unit mainly focusing in the research of IT technology has been reviewing and testing a lab-scale IPv6 implementation. This also focused on the capabilities incubation for enabling IPv6 on existing telecommunications equipment and interoperability test between the devices. This study provides the result of function, multi-layer integration and interoperability test of IPv6 conducted in Telkom RDC OASIS v6 lab, which also can be considered as references for decision makers within the company to adopt IP technology to be implemented in the future.

  1. The Impact of IPv6 on Penetration Testing

    NARCIS (Netherlands)

    Ottow, Christiaan; van Vliet, Frank; de Boer, Pieter-Tjerk; Pras, Aiko

    In this paper we discuss the impact the use of IPv6 has on remote penetration testing of servers and web applications. Several modifications to the penetration testing process are proposed to accommodate IPv6. Among these modifications are ways of performing fragmentation attacks, host discovery and

  2. Analisis Performa File Transport Protocol pada Perbandingan Metode IPv4 Murni, IPv6 Murni dan Tunneling 6to4 Berbasis Router Mikrotik

    Directory of Open Access Journals (Sweden)

    Siswo Wardoyo

    2014-09-01

    Full Text Available The use of IPv4 which has more than 30 years led to the capacity of available addresses is running out availability. Currently emerging new generation IP (IPnext generation is IPv6. Many methods for the implementation of IPv6, one with tunneling. 6to4 is a tunneling method that can be directly implemented on an IPv4 network. This study compared the performance level of a pure IPv4 network, IPv6 6to4 tunneling with pure and searching FTP throughput performance. Throughput results obtained pure IPv6 is smaller than the value of 42.9% pure IPv4 throughput, 6to4 tunneling is smaller than 39.4% pure IPv4 and IPv6 pure value 53.626% greater throughput than 6to4 tunneling configuration.

  3. Firewall for Dynamic IP Address in Mobile IPv6

    Science.gov (United States)

    Qiu, Ying; Bao, Feng; Zhou, Jianying

    Mobile communication is becoming the mainstream with the rapid growth of mobile devices penetrating our daily life. More and more mobile devices such as mobile phones, personal digital assistants, notebooks etc, are capable of Internet access. Mobile devices frequently change their communication IP addresses in mobile IPv6 network following its current attached domain. This raises a big challenge for building firewall for mobile devices. The conventional firewalls are primarily based on IPv4 networks where the security criteria are specified only to the fixed IP addresses or subnets, which apparently do not apply to mobile IPv6. In this paper we propose three solutions for mobile IPv6 firewall. Our approaches make the firewall adaptive to dynamic IP addresses in mobile IPv6 network. They have different expense and weight corresponding to different degree of universality. The paper focuses the study more from practical aspect.

  4. A Brief History of Vaccines Against Polio.

    Science.gov (United States)

    Vashishtha, Vipin M; Kamath, Sachidanand

    2016-08-07

    Poliomyelitis, a dreaded disease of the last century that had already crippled millions of people across the globe, is now on the verge of eradication thanks mainly to two polio vaccines, inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Ever since their development in late 1950s and early 1960s, the journey of their early development process, clinical trials, licensure and ultimately widespread clinical use in different countries provide a fascinating tale of events. Oral polio vaccine has been the mainstay of global polio eradication initiative (GPEI) in most of the countries. With the advent of 'polio endgame', the focus has now shifted back to IPV. However, there are certain issues associated with global cessation of OPV use and universal implementation of IPV in routine immunization schedules across the globe that need to be dealt with some urgency, before proclaiming the global victory over polio.

  5. Maternal vaccination to prevent pertussis in infants

    African Journals Online (AJOL)

    2016-09-09

    Sep 9, 2016 ... that maternal immunisation with the Tdap (tetanus, diphtheria and acellular pertussis) vaccine is safe. Indeed, maternal vaccination is now recommended to prevent pertussis infection in vulnerable young infants. In the USA and UK, the immunisation of pregnant women with a Tdap or dTaP/IPV (diphtheria, ...

  6. IPv6 Test Bed for Testing Aeronautical Applications

    Science.gov (United States)

    Wilkins, Ryan; Zernic, Michael; Dhas, Chris

    2004-01-01

    Aviation industries in United States and in Europe are undergoing a major paradigm shift in the introduction of new network technologies. In the US, NASA is also actively investigating the feasibility of IPv6 based networks for the aviation needs of the United States. In Europe, the Eurocontrol lead, Internet Protocol for Aviation Exchange (iPAX) Working Group is actively investigating the various ways of migrating the aviation authorities backbone infrastructure from X.25 based networks to an IPv6 based network. For the last 15 years, the global aviation community has pursued the development and implementation of an industry-specific set of communications standards known as the Aeronautical Telecommunications Network (ATN). These standards are now beginning to affect the emerging military Global Air Traffic Management (GATM) community as well as the commercial air transport community. Efforts are continuing to gain a full understanding of the differences and similarities between ATN and Internet architectures as related to Communications, Navigation, and Surveillance (CNS) infrastructure choices. This research paper describes the implementation of the IPv6 test bed at NASA GRC, and Computer Networks & Software, Inc. and these two test beds are interface to Eurocontrol over the IPv4 Internet. This research work looks into the possibility of providing QoS performance for Aviation application in an IPv6 network as is provided in an ATN based network. The test bed consists of three autonomous systems. The autonomous system represents CNS domain, NASA domain and a EUROCONTROL domain. The primary mode of connection between CNS IPv6 testbed and NASA and EUROCONTROL IPv6 testbed is initially a set of IPv6 over IPv4 tunnels. The aviation application under test (CPDLC) consists of two processes running on different IPv6 enabled machines.

  7. Studies on the potency of oral polio vaccine using RD cell line and ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... Oral polio vaccine (OPV) proved to be superior in administration eliminating the need of sterile syringes and making the vaccine more suitable for mass vaccination campaigns. Poliovirus is heat sensitive in nature, and thus OPV is stored at low temperature (frozen). The growth medium containing.

  8. Molecular Mechanisms of Attenuation of the Sabin Strain of Poliovirus Type 3

    OpenAIRE

    Guest, Stephen; Pilipenko, Evgeny; Sharma, Kamal; Chumakov, Konstantin; Roos, Raymond P.

    2004-01-01

    Mutations critical for the central nervous system (CNS) attenuation of the Sabin vaccine strains of poliovirus (PV) are located within the viral internal ribosome entry site (IRES). We examined the interaction of the IRESs of PV type 3 (PV3) and Sabin type 3 (Sabin3) with polypyrimidine tract-binding protein (PTB) and a neural cell-specific homologue, nPTB. PTB and nPTB were found to bind to a site directly adjacent to the attenuating mutation, and binding at this site was less efficient on t...

  9. Cell-Free, De Nova Synthesis of Poliovirus

    Science.gov (United States)

    Molla, Akhteruzzaman; Paul, Aniko V.; Wimmer, Eckard

    1991-12-01

    Cell-free translation of poliovirus RNA in an extract of uninfected human (HeLa) cells yielded viral proteins through proteolysis of the polyprotein. In the extract, newly synthesized proteins catalyzed poliovirus-specific RNA synthesis, and formed infectious poliovirus de novo. Newly formed virions were neutralized by type-specific antiserum, and infection of human cells with them was prevented by poliovirus receptor-specific antibodies. Poliovirus synthesis was increased nearly 70-fold when nucleoside triphosphates were added, but it was abolished in the presence of inhibitors of translation or viral genome replication. The ability to conduct cell-free synthesis of poliovirus will aid in the study of picornavirus proliferation and in the search for the control of picornaviral disease.

  10. Immunogenicity study to investigate the interchangeability among three different types of polio vaccine: A cohort study in Japan.

    Science.gov (United States)

    Ohfuji, Satoko; Ito, Kazuya; Ishibashi, Motoki; Shindo, Shizuo; Takasaki, Yoshio; Yokoyama, Takashi; Yokoyama, Takato; Yamashita, Yuji; Shibao, Keigo; Nakano, Takashi; Tsuru, Tomomi; Irie, Shin; Hirota, Yoshio

    2017-06-01

    In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naïve infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

  11. Japanese Women’s Perceptions of Intimate Partner Violence (IPV)

    Science.gov (United States)

    Nagae, Miyoko; Dancy, Barbara L.

    2013-01-01

    Intimate partner violence (IPV) is a serious problem in Japan. The purpose of this study was to describe IPV as perceived by Japanese adult females who were in a heterosexual marriage and lived with their spouses at the time of IPV. Using a cross-sectional retroactive qualitative description research design with individual face-to-face in-depth interviews, a purposive sample of 11 Japanese adult females from three urban areas in Japan was interviewed. All women reported that they and their husbands were born in Japan. At the time of the interview, the women had a mean age of 38 years whereas at the time of the IPV, their mean age was 28 years. Data was analyzed using the directed qualitative content analysis method. The results revealed that IPV occurred at the women’s homes primarily at night. All the women reported that they experienced physical and emotional abuse and 82% reported experiencing sexual abuse. Additionally, 64% reported that their parents-in-law emotionally abused them. Communication between these women and their husbands were characterized as unilateral with the husbands initiating and dominating the conversations with orders, lectures, and reprimands. The women identified that the cultural influences of the Japanese patriarchal system that reinforces male superiority and dominance and women inferiority were directly related to IPV. The implication is that health professionals need to actively advocate for effective legislation and policies to address IPV in Japan. PMID:19465572

  12. Intimate partner violence: IPV in the LGBT community.

    Science.gov (United States)

    Chen, Ping-Hsin; Jacobs, Abbie; Rovi, Susan L D

    2013-09-01

    Nationally, the rates of intimate partner violence (IPV) among lesbian, gay, bisexual, or transgender (LGBT) individuals are similar to or greater than rates for heterosexuals. Many have experienced psychological and physical abuse as sexual minorities, making it difficult for them to seek help for IPV. Physician behavior, such as not assuming that all patients are heterosexual, being nonjudgmental, and using inclusive language, can empower LGBT patients to disclose IPV. Also, physicians should ascertain the degree to which the patient is out. The threat of being outed can be an aspect of the power and control exerted by an abusive partner and a significant barrier to seeking help. Physicians should screen for IPV and intervene in a similar manner with LGBT and non-LGBT patients, but they should be aware of potential limitations in resources for LGBT patients, such as shelters. As sexual minorities experiencing IPV, LGBT individuals are at greater risk of depression and substance abuse than are non-LGBT individuals. Minority stress, resulting from stigmatization and discrimination, can be exacerbated by IPV. Physicians should learn about legal issues for LGBT individuals and the availability of community or advocacy programs for LGBT perpetrators or victims of IPV. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  13. Research on IPv6 intrusion detection system Snort-based

    Science.gov (United States)

    Shen, Zihao; Wang, Hui

    2010-07-01

    This paper introduces the common intrusion detection technologies, discusses the work flow of Snort intrusion detection system, and analyzes IPv6 data packet encapsulation and protocol decoding technology. We propose the expanding Snort architecture to support IPv6 intrusion detection in accordance with CIDF standard combined with protocol analysis technology and pattern matching technology, and present its composition. The research indicates that the expanding Snort system can effectively detect various intrusion attacks; it is high in detection efficiency and detection accuracy and reduces false alarm and omission report, which effectively solves the problem of IPv6 intrusion detection.

  14. Factors determining anti-poliovirus type 3 antibodies among orally immunised Indian infants.

    Science.gov (United States)

    Kaliappan, Saravanakumar Puthupalayam; Venugopal, Srinivasan; Giri, Sidhartha; Praharaj, Ira; Karthikeyan, Arun S; Babji, Sudhir; John, Jacob; Muliyil, Jayaprakash; Grassly, Nicholas; Kang, Gagandeep

    2016-09-22

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

  15. Pricing strategies for combination pediatric vaccines based on the lowest overall cost formulary.

    Science.gov (United States)

    Behzad, Banafsheh; Jacobson, Sheldon H; Sewell, Edward C

    2012-10-01

    This paper analyzes pricing strategies for US pediatric combination vaccines by comparing the lowest overall cost formularies (i.e., formularies that have the lowest overall cost). Three pharmaceutical companies compete pairwise over the sale of monovalent and combination vaccines. Particular emphasis is placed on examining the price of Sanofi Pasteur's DTaP-IPV/HIb under different conditions. The main contribution of the paper is to provide the lowest overall cost formularies for different prices of DTaP-IPV/HIb and other Sanofi Pasteur vaccines. The resulting analysis shows that DTaP-IPV/HIb could have been more competitively priced compared with the combination vaccine DTaP-HepB-IPV, for federal contract prices in 2009, 2010 and 2011. This study also proposes the lowest overall cost formularies when shortages of monovalent vaccines occur.

  16. IPv6 Addressing Proxy: Mapping Native Addressing from Legacy Technologies and Devices to the Internet of Things (IPv6)

    OpenAIRE

    Jara, Antonio J.; Moreno-Sanchez, Pedro; Skarmeta, Antonio F.; Varakliotis, Socrates; Kirstein, Peter

    2013-01-01

    Sensors utilize a large number of heterogeneous technologies for a varied set of application environments. The sheer number of devices involved requires that this Internet be the Future Internet, with a core network based on IPv6 and a higher scalability in order to be able to address all the devices, sensors and things located around us. This capability to connect through IPv6 devices, sensors and things is what is defining the so-called Internet of Things (IoT). IPv6 provides addressing spa...

  17. Vaccine preventable viral diseases and risks associated with waterborne transmission

    Directory of Open Access Journals (Sweden)

    Franco Maria Ruggeri

    2012-12-01

    Full Text Available Rotavirus and poliovirus are paradigmatic viruses for causing major diseases affecting the human population. The impact of poliovirus is remarkably diminished because of vaccination during the last half century. Poliomyelitis due to wild polio currently affects a limited number of countries, and since 2000 sporadic outbreaks have been associated to neurovirulent vaccine-derived polioviruses. Conversely, rotavirus is presently very diffuse, accounting for the largest fraction of severe gastroenteritis among children <5 years-old. Vaccination towards rotavirus is still in its dawn, and zoonotic strains contribute to the emergence and evolution of novel strains pathogenic to man. The environment, particularly surface water, is a possible vehicle for large transmission of both viruses, but environmental surveillance of circulating strains can help promptly monitor entry of new virulent strains into a country, their shedding and spread.

  18. Implementation of a Network Address Translation Mechanism Over IPv6

    National Research Council Canada - National Science Library

    Baumgartner, Trevor

    2004-01-01

    ...; however, NAT provides several other benefits. NAT can be used to mask the internal IP addresses of an Intranet - IPv6, the emerging standard for Internet addressing, provides three times the number of bits for IP addressing...

  19. Mobile Multicast in Hierarchical Proxy Mobile IPV6

    Science.gov (United States)

    Hafizah Mohd Aman, Azana; Hashim, Aisha Hassan A.; Mustafa, Amin; Abdullah, Khaizuran

    2013-12-01

    Mobile Internet Protocol Version 6 (MIPv6) environments have been developing very rapidly. Many challenges arise with the fast progress of MIPv6 technologies and its environment. Therefore the importance of improving the existing architecture and operations increases. One of the many challenges which need to be addressed is the need for performance improvement to support mobile multicast. Numerous approaches have been proposed to improve mobile multicast performance. This includes Context Transfer Protocol (CXTP), Hierarchical Mobile IPv6 (HMIPv6), Fast Mobile IPv6 (FMIPv6) and Proxy Mobile IPv6 (PMIPv6). This document describes multicast context transfer in hierarchical proxy mobile IPv6 (H-PMIPv6) to provide better multicasting performance in PMIPv6 domain.

  20. A Comparison of Internet Protocol (IPv6 Security Guidelines

    Directory of Open Access Journals (Sweden)

    Steffen Hermann

    2014-01-01

    Full Text Available The next generation of the Internet Protocol (IPv6 is currently about to be introduced in many organizations. However, its security features are still a very novel area of expertise for many practitioners. This study evaluates guidelines for secure deployment of IPv6, published by the U.S. NIST and the German federal agency BSI, for topicality, completeness and depth. The later two are scores defined in this paper and are based on the Requests for Comments relevant for IPv6 that were categorized, weighted and ranked for importance using an expert survey. Both guides turn out to be of practical value, but have a specific focus and are directed towards different audiences. Moreover, recommendations for possible improvements are presented. Our results could also support strategic management decisions on security priorities as well as for the choice of security guidelines for IPv6 roll-outs.

  1. Evaluation de la mise en ceuvre des services du protocole IPV6 ...

    African Journals Online (AJOL)

    At present, the configurations of networks are based on the protocol ipv4. The addresses ipv4 begin to run out. Groups of search work on the new version of the protocol IPV6 (in France, in United States, in Japan). Certain networks run under ipv6. However the great majority of the existing networks always use the ...

  2. So you've got IPv6 address space. Can you defend it?

    OpenAIRE

    Sande, Mikal

    2014-01-01

    Internet Protocol version 6 (IPv6) is the successor of Internet Protocol version 4 (IPv4). IPv6 will become the next standard networking protocol on the Internet. It brings with it a great increase in address space, changes to network operations, and new network security concerns. In this thesis we examine IPv6 from a security perspective. The security of IPv6 is important to all protocols that use IPv6 on the Internet. The goal of this thesis is to introduce the reader to existing IPv6 secur...

  3. Kondisi Migrasi Internet Protocol version 6 (IPv6 di Indonesia

    Directory of Open Access Journals (Sweden)

    Fahrizal Lukman Budiono

    2011-06-01

    Full Text Available    Sejalan dengan pertumbuhan industri Internet di Indonesia tersebut, maka kebutuhan akan alamat Internet Protocol (IP juga pasti meningkat. Operator Internet akan membutuhkan alamat IP untuk mengembangkan layanannya hingga ke seluruh pelosok negeri. Saat ini, jaringan Internet di Indonesia berikut perangkat-perangkat pendukungnya hingga di tingkat end user masih menggunakan Internet Protocol version 4 (IPv4. Kenyataan yang dihadapi dunia sekarang adalah menipisnya persediaan alamat IPv4 yang dialokasikan. Hal ini dikarenakan jumlah alamat yang dapat didukung oleh IPv4 adalah 232 bits, sedangkan data terakhir didapatkan bahwa alokasi IPv4 telah habis dialokasikan pada akhir April 2011 di tingkat Internet Assigned Numbers Authority (IANA, organisasi yang mengelola sumberdaya protokol Internet dunia. Untuk mempercepat migrasi, stakeholder internet di Indonesia yaitu Kementerian Komunikasi dan Informatika dan Industri Penyelenggara Internet membentuk ID-IPv6TF. Dalam studi ini, ditemukan bahwa implementasi IPv6 di Indonesia termasuk dalam kategori baik dibandingkan dengan negara lain di dunia. Namun, terlihat bahwa perkembangan ini masih sporadis dengan kurangnya peran koordinator, serta sosialiasi ke masyarakat yang tidak ada.

  4. Konsep Tingkat Kematangan penerapan Internet Protokol versi 6 (Capability Maturity Model for IPv6 Implementation

    Directory of Open Access Journals (Sweden)

    Riza Azmi

    2015-03-01

    Full Text Available Internet Protocol atau IP merupakan standar penomoran internet di dunia yang jumlahnya terbatas. Di dunia, alokasi IP diatur oleh Internet Assignd Number Authority (IANA dan didelegasikan ke melalui otoritas masing-masing benua. IP sendiri terdiri dari 2 jenis versi yaitu IPv4 dan IPv6 dimana alokasi IPv4 dinyatakan habis di tingkat IANA pada bulan April 2011. Oleh karena itu, penggunaan IP diarahkan kepada penggunaan IPv6. Untuk melihat bagaimana kematangan suatu organisasi terhadap implementasi IPv6, penelitian ini mencoba membuat sebuah model tingkat kematangan penerapan IPv6. Konsep dasar dari model ini mengambil konsep Capability Maturity Model Integrated (CMMI, dengan beberapa tambahan yaitu roadmap migrasi IPv6 di Indonesia, Request for Comment (RFC yang terkait dengan IPv6 serta beberapa best-practice implementasi dari IPv6. Dengan konsep tersebut, penelitian ini menghasilkan konsep Capability Maturity for IPv6 Implementation.

  5. Environmental Surveillance System To Track Wild Poliovirus Transmission

    Science.gov (United States)

    Deshpande, Jagadish M.; Shetty, Sushmitha J.; Siddiqui, Zaeem A.

    2003-01-01

    Eradication of poliomyelitis from large metropolis cities in India has been difficult due to high population density and the presence of large urban slums. Three paralytic poliomyelitis cases were reported in Mumbai, India, in 1999 and 2000 in spite of high immunization coverage and good-quality supplementary immunization activities. We therefore established a systematic environmental surveillance study by weekly screening of sewage samples from three high-risk slum areas to detect the silent transmission of wild poliovirus. In 2001, from among the 137 sewage samples tested, wild poliovirus type 1 was isolated from 35 and wild poliovirus type 3 was isolated from 1. Acute flaccid paralysis (AFP) surveillance indicated one case of paralytic poliomyelitis from the city. Phylogenetic analysis with complete VP1 sequences revealed that the isolates from environmental samples belonged to four lineages of wild polioviruses recently isolated from poliomyelitis cases in Uttar Pradesh and not to those previously isolated from AFP cases in Mumbai. Wild poliovirus thus introduced caused one case of paralytic poliomyelitis. The virus was detected in environmental samples 3 months before. It was found that wild polioviruses introduced several times during the year circulated in Mumbai for a limited period before being eliminated. Environmental surveillance was found to be sensitive for the detection of wild poliovirus silent transmission. Nucleotide sequence analysis helped identify wild poliovirus reservoir areas. PMID:12732567

  6. Evaluation of immunity against poliovirus serotypes among children ...

    African Journals Online (AJOL)

    Eight (4%) of the children had no detectable antibody, 178 (89%), 180 (90%) and 181 (90.5%) were positive for antibodies to poliovirus types 1, 2 and 3, respectively. Overall, 162 (81%) of the children had antibodies to the three poliovirus serotypes at a titre of at least 1:8. The study shows the need for proper monitoring of ...

  7. Glutathione is a highly efficient thermostabilizer of poliovirus Sabin strains.

    Science.gov (United States)

    Abdelnabi, Rana; Delang, Leen; Neyts, Johan

    2017-03-07

    Glutathione (GSH) is the most abundant thiol peptide in animal cells and has a critical role in antioxidation. GSH was reported to be essential for stabilization of some enteroviruses, including poliovirus (PV), during viral morphogenesis. Here, we explored the potential use of GSH as a thermostabilizer of oral poliomyelitis vaccine (OPV) formulations. GSH significantly protected the three types of PV from heat-inactivation in a concentration-dependent manner. At a GSH concentration of 20mM, nearly complete protection was observed against heating temperatures up to 53°C for 2min.GSH also markedly protected PV1 from heat-inactivation and this up to 6 h at temperatures of 44°C and 46°C and 3 h at 48°C. The fact that GSH is naturally present at high concentration in the human body makes it an efficient candidate stabilizer for OPV formulations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. [Role of the National Poliovirus Laboratory for the Program of eradication and poliomyelitis surveillance].

    Science.gov (United States)

    Trallero, Gloria; Cabrerizo, María; Avellón, Ana

    2013-01-01

    The Spanish acute flaccid paralysis surveillance network is coordinated by the National Poliovirus Laboratory (NPL), which, since 1998, carries out polioviruses (PV) and other enteroviruses detected characterization by cell culture and molecular techniques. A total of 110,725 (70046+40679) samples were studied between 1998-2012 and enteroviruses were detected in 8% of these. Among these enteroviruses 241 PV were characterized as PV Sabin-like, except samples belong to an imported poliomyelitis case, all of which were characterised as vaccine derived PV type 2. The NPL has carried out the serotyping and the intratypic differentiation of all the isolated PV in Spain of any syndrome. It is shown that wild PV has not circulated in our country during the 15 years studied and that has led to the signing of the Act of the "eradication of poliomyelitis in Spain" by WHO in 2001, and the /"certification of the eradication of wild PV free for European countries" on 21 June 2002. Currently only 3 countries have endemic transmission of wild PV (Pakistan, Afghanistan and Nigeria). Until a complete worldwide eradication, was achieved, Spain will actively continue to participate in the maintenance of the poliomyelitis eradication infrastructure by monitoring and vaccination as well as the wild PV containment plan to avoid the spread of wild PV.

  9. Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications.

    Science.gov (United States)

    Korotkova, Ekaterina; Laassri, Majid; Zagorodnyaya, Tatiana; Petrovskaya, Svetlana; Rodionova, Elvira; Cherkasova, Elena; Gmyl, Anatoly; Ivanova, Olga E; Eremeeva, Tatyana P; Lipskaya, Galina Y; Agol, Vadim I; Chumakov, Konstantin

    2017-11-22

    Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These "weak" segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

  10. Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications

    Directory of Open Access Journals (Sweden)

    Ekaterina Korotkova

    2017-11-01

    Full Text Available Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These “weak” segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination.

  11. Risk assessment, risk management and risk-based monitoring following a reported accidental release of poliovirus in Belgium, September to November 2014.

    Science.gov (United States)

    Duizer, Erwin; Rutjes, Saskia; de Roda Husman, Ana Maria; Schijven, Jack

    2016-01-01

    On 6 September 2014, the accidental release of 10(13) infectious wild poliovirus type 3 (WPV3) particles by a vaccine production plant in Belgium was reported. WPV3 was released into the sewage system and discharged directly to a wastewater treatment plant (WWTP) and subsequently into rivers that flowed to the Western Scheldt and the North Sea. No poliovirus was detected in samples from the WWTP, surface waters, mussels or sewage from the Netherlands. Quantitative microbial risk assessment (QMRA) showed that the infection risks resulting from swimming in Belgium waters were above 50% for several days and that the infection risk by consuming shellfish harvested in the eastern part of the Western Scheldt warranted a shellfish cooking advice. We conclude that the reported release of WPV3 has neither resulted in detectable levels of poliovirus in any of the samples nor in poliovirus circulation in the Netherlands. This QMRA showed that relevant data on water flows were not readily available and that prior assumptions on dilution factors were overestimated. A QMRA should have been performed by all vaccine production facilities before starting up large-scale culture of WPV to be able to implement effective interventions when an accident happens.

  12. New approaches to poliovirus diagnosis using laboratory techniques: memorandum from a WHO meeting.

    OpenAIRE

    1992-01-01

    Laboratory diagnosis of poliomyelitis is an important part of the WHO initiative for global eradication of poliomyelitis. During the last year, new methods have been developed for the detection of poliovirus in clinical specimens, for intratypic differentiation, for the analysis of poliovirus neurovirulence, and for the detection of poliovirus antibodies. Progress in laboratory techniques for detection of poliovirus antibodies and for characterization of poliovirus isolates has suggested seve...

  13. Applying the Concept of Peptide Uniqueness to Anti-Polio Vaccination

    Directory of Open Access Journals (Sweden)

    Darja Kanduc

    2015-01-01

    Full Text Available 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. Conclusion. 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.

  14. Applying the Concept of Peptide Uniqueness to Anti-Polio Vaccination.

    Science.gov (United States)

    Kanduc, Darja; Fasano, Candida; Capone, Giovanni; Pesce Delfino, Antonella; Calabrò, Michele; Polimeno, Lorenzo

    2015-01-01

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

  15. Simulasi Penggunaan Ipv6 Pada PD. Pumas Jaya Menggunakan Metode Manual Tunneling

    Directory of Open Access Journals (Sweden)

    Elidjen Elidjen

    2010-12-01

    Full Text Available Internet usage trends with IPv4 addresses that only have 32-bit addresses could no longer cope with the large allocation of the required addresses. Internet Engineering Task Force (IETF has issued a new standard of Internet protocol called IPv6 to anticipate this problem. PD. Pumas Jaya, which started in 1996 in the field of marine products in particular marinated seafood, such as salted fish, rebon shrimp, cuttlefish, anchovies and other marine products to anticipate the need for this in its network. However, IPv6 can not simply be used to replace IPv4 as the existing network infrastructure with IPv4. This research discussed IPv6 simulation tunneling with manual methods so that an IPv6 site can communicate with other IPv6 site even if separated by an infrastructure that supports only IPv4. 

  16. Analisis Kesiapan Penyelenggara Jaringan Internet di Indonesia dalam Migrasi ke IPv6

    Directory of Open Access Journals (Sweden)

    Riza Azmi

    2012-06-01

    Full Text Available Internet Protocol merupakan sumberdaya pengalamatan jaringan yang sifatnya terbatas. Sejak dikembangkankan konsep TCP/IP, sumberdaya pengalamatan jaringan dan internet berbasiskan pada Internet Protokol versi 4 (IPv4 yang memiliki 4 miliar alamat unik. Data dari potaroo.net pada 18 maret 2011, diperkirakan alokasi IPv4 berakhir pada bulan May 2011. Dalam menghadapi keterbatasan IPv4 tersebut, dibuatlah konsep pengalamatan baru IPv6 yang memiliki jumlah alamat 6,5 x 1038 alamat unik. Di Indonesia sendiri dalam rangka mengantisipasi habisnya penggunaan IPv4 tersebut, stakeholder internet di Indonesia yang dikomandoi oleh Kementerian Komunikasi dan Informatika cq. Ditjen Postel membentuk Indonesia IPv6 Task Force (ID-IPv6TF. ID-IPv6TF merumuskan peta jalan / roadmap migrasi ke IPv6 versi 2 yang berakhir pada 2012. Studi ini melakukan evaluasi formatif sejauhmana kesiapan migrasi dari IPv4 ke IPv6 di Indonesia pada tingkat Penyelenggara Jaringan Internet  dengan melihat dari dimensi kesiapan aplikasi, strategi migrasi dan kesiapan infrastruktur. Kesiapan migrasi tersebut dikategorkan menjadi 5 level yaitu IPv6 Agnostic, IPv6 Aware,. Hasil studi menunjukkan bahwa Indonesia berada pada level IPv6 Savvy dengan distribusi level yang beragam.

  17. A Case Study of IPv6 Network Performance: Packet Delay, Loss, and Reordering

    Directory of Open Access Journals (Sweden)

    Fuliang Li

    2017-01-01

    Full Text Available Internet Protocol (IP is used to identify and locate computers on the Internet. Currently, IPv4 still routes most Internet traffic. However, with the exhausting of IPv4 addresses, the transition to IPv6 is imminent, because, as the successor of IPv4, IPv6 can provide a larger available address space. Existing studies have addressed the notion that IPv6-centric next generation networks are widely deployed and applied. In order to gain a deep understanding of IPv6, this paper revisits several critical IPv6 performance metrics. Our extensive measurement shows that packet delay and loss rate of IPv6 are similar to IPv4 when the AS-level paths are roughly the same. Specifically, when the link utilization exceeds a threshold, for example, 0.83 in our study, variation of packet delay presents a similar pattern with the variation of link utilization. If packet delay of a path is large, packet-loss rate of that path is more likely to fluctuate. In addition, we conduct a first-ever analysis of packet reordering in IPv6 world. Few IPv6 probe packets are out-of-order and the reordering rate is 2.3⁎10-6, which is much lower than that of 0.79% in IPv4 world. Our analysis consolidates an experimental basis for operators and researchers of IPv6 networks.

  18. Enabling IPv6 at FZU - WLCG Tier2 in Prague

    International Nuclear Information System (INIS)

    Kouba, Tomáš; Chudoba, Jiří; Eliáš, Marek

    2014-01-01

    The usage of the new IPv6 protocol in production is becoming reality in the HEP community and the Computing Centre of the Institute of Physics in Prague participates in many IPv6 related activities. Our contribution presents experience with monitoring in HEPiX distributed IPv6 testbed which includes 11 remote sites. We use Nagios to check availability of services and Smokeping for monitoring the network latency. Since it is not always trivial to setup DNS in a dual stack environment properly, we developed a Nagios plugin for checking whether a domain name is resolvable when using only IP protocol version 6 and only version 4. We will also present local area network monitoring and tuning related to IPv6 performance. One of the most important software for a grid site is a batch system for a job execution. We will present our experience with configuring and running Torque batch system in a dual stack environment. We also discuss the steps needed to run VO specific jobs in our IPv6 testbed.

  19. Enabling IPv6 at FZU - WLCG Tier2 in Prague

    Science.gov (United States)

    Kouba, Tomáš; Chudoba, Jiří; Eliáš, Marek

    2014-06-01

    The usage of the new IPv6 protocol in production is becoming reality in the HEP community and the Computing Centre of the Institute of Physics in Prague participates in many IPv6 related activities. Our contribution presents experience with monitoring in HEPiX distributed IPv6 testbed which includes 11 remote sites. We use Nagios to check availability of services and Smokeping for monitoring the network latency. Since it is not always trivial to setup DNS in a dual stack environment properly, we developed a Nagios plugin for checking whether a domain name is resolvable when using only IP protocol version 6 and only version 4. We will also present local area network monitoring and tuning related to IPv6 performance. One of the most important software for a grid site is a batch system for a job execution. We will present our experience with configuring and running Torque batch system in a dual stack environment. We also discuss the steps needed to run VO specific jobs in our IPv6 testbed.

  20. Modeling the IPv6 internet AS-level topology

    Science.gov (United States)

    Xiao, Bo; Liu, Lian-dong; Guo, Xiao-chen; Xu, Ke

    2009-02-01

    To measure the IPv6 internet AS-level topology, a network topology discovery system, called Dolphin, was developed. By comparing the measurement result of Dolphin with that of CAIDA’s Scamper, it was found that the IPv6 Internet at AS level, similar to other complex networks, is also scale-free but the exponent of its degree distribution is 1.2, which is much smaller than that of the IPv4 Internet and most other scale-free networks. In order to explain this feature of IPv6 Internet we argue that the degree exponent is a measure of uniformity of the degree distribution. Then, for the purpose of modeling the networks, we propose a new model based on the two major factors affecting the exponent of the EBA model. It breaks the lower bound of degree exponent which is 2 for most models. To verify the validity of this model, both theoretical and experimental analyses have been carried out. Finally, we demonstrate how this model can be successfully used to reproduce the topology of the IPv6 Internet.

  1. A Discussion on Internet Security Based on the IPv6 agreement%基于IPv6协议的网络安全问题探讨

    Institute of Scientific and Technical Information of China (English)

    张贵军

    2011-01-01

    With the increase of the Internet application of next generation, our government、net service providers and consumers paid more attention to the safety of IPv6. This essay introduced the IPv6 agreement first, then analyzed some security issues. We hope these problems can be solved in the deploy process of IPv6 agreement.%随着下一代互联网应用的不断增加,国家、网络运营商和用户对于IPv6的安全问题日益重视。本文在对IPv6协议简单介绍的基础上,分析了IPv6网络目前存在的一些安全问题,希望在部署IPv6协议的过程中能够不断地解决这些问题。

  2. Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections

    DEFF Research Database (Denmark)

    Sørup, Signe; Benn, Christine Stabell; Poulsen, Anja

    2014-01-01

    ). Nationwide Danish registers provided data on vaccinations and hospital admissions. The recommended vaccination schedule was inactivated vaccine against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) administered at ages 3, 5, and 12 months and MMR at age 15 months...

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

    Science.gov (United States)

    2013-09-20

    In 2012, the World Health Assembly of the World Health Organization (WHO) declared the completion of polio eradication a programmatic emergency. Indigenous wild poliovirus (WPV) transmission remains uninterrupted in Nigeria (in the WHO African Region [AFR]) and in Afghanistan and Pakistan (in the WHO Eastern Mediterranean Region [EMR]). In the WHO AFR, multiple WPV outbreaks have occurred since 2003 after importation of indigenous West African WPV into 21 previously polio-free countries in a "WPV importation belt"* that extends across the continent. The Global Polio Eradication Initiative (GPEI) and WHO regional offices have used indicators of population immunity, surveillance quality, and other factors (e.g., high-risk subpopulations and proximity to WPV-affected countries) to assess the risk for outbreaks in polio-free countries and guide the implementation of risk mitigation measures to limit poliovirus transmission after WPV importation and prevent the emergence of circulating vaccine-derived poliovirus (cVDPV). Despite risk mitigation efforts, a polio outbreak, first confirmed in May 2013, is ongoing; as of September 10, a total of 178 WPV type 1 (WPV1) cases have been reported in Somalia† (163 cases), Kenya (14 cases) and Ethiopia (1 case), after importation of WPV1 of West African origin. This report summarizes steps taken by the GPEI to assess and mitigate the risks for outbreaks after WPV importation or the emergence of cVDPV in polio-free countries within the WHO AFR's "WPV importation belt." All countries will continue to have some level of risk for WPV outbreaks as long as endemic circulation continues in Afghanistan, Nigeria, and Pakistan.

  4. Integrated Environment for Ubiquitous Healthcare and Mobile IPv6 Networks

    Science.gov (United States)

    Cagalaban, Giovanni; Kim, Seoksoo

    The development of Internet technologies based on the IPv6 protocol will allow real-time monitoring of people with health deficiencies and improve the independence of elderly people. This paper proposed a ubiquitous healthcare system for the personalized healthcare services with the support of mobile IPv6 networks. Specifically, this paper discusses the integration of ubiquitous healthcare and wireless networks and its functional requirements. This allow an integrated environment where heterogeneous devices such a mobile devices and body sensors can continuously monitor patient status and communicate remotely with healthcare servers, physicians, and family members to effectively deliver healthcare services.

  5. Methods for Intelligent Mapping of the IPV6 Address Space

    Science.gov (United States)

    2015-03-01

    the " Internet of Things " ( IoT ). (2013, Jan. 7). Forbes. [Online]. Available: http://www.forbes.com/sites/quora/2013/01/07/ how-many- things -are...currently-connected-to-the- internet -of- things - iot / 57 [13] G. Huston, “IPv4 address report,” Mar 2015. [Online]. Available: http://www.potaroo.net/tools/ipv4...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Due to the rapid growth of the Internet , the available pool of unique

  6. The Cutter incident and the development of a Swedish polio vaccine, 1952-1957

    OpenAIRE

    Axelsson, Per

    2012-01-01

    The creation of two different vaccines to eradicate polio stands out as one of modern science most important accomplishments. The current article examines Swedish polio vaccine research, the vaccination campaign and especially how the Cutter incident came to affect Swedish Science, scientists and society in the 1950s. Sweden is one of the few countries that came to produce its own inactivated polio vaccine (IPV) in the 1950s, a type of vaccine they never abandoned. This article highlights the...

  7. Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

    Science.gov (United States)

    Viktorova, Ekaterina G.; Nchoutmboube, Jules; Ford-Siltz, Lauren A.

    2015-01-01

    ABSTRACT It is hypothesized that targeting stable cellular factors involved in viral replication instead of virus-specific proteins may raise the barrier for development of resistant mutants, which is especially important for highly adaptable small (+)RNA viruses. However, contrary to this assumption, the accumulated evidence shows that these viruses easily generate mutants resistant to the inhibitors of cellular proteins at least in some systems. We investigated here the development of poliovirus resistance to brefeldin A (BFA), an inhibitor of the cellular protein GBF1, a guanine nucleotide exchange factor for the small cellular GTPase Arf1. We found that while resistant viruses can be easily selected in HeLa cells, they do not emerge in Vero cells, in spite that in the absence of the drug both cultures support robust virus replication. Our data show that the viral replication is much more resilient to BFA than functioning of the cellular secretory pathway, suggesting that the role of GBF1 in the viral replication is independent of its Arf activating function. We demonstrate that the level of recruitment of GBF1 to the replication complexes limits the establishment and expression of a BFA resistance phenotype in both HeLa and Vero cells. Moreover, the BFA resistance phenotype of poliovirus mutants is also cell type dependent in different cells of human origin and results in a fitness loss in the form of reduced efficiency of RNA replication in the absence of the drug. Thus, a rational approach to the development of host-targeting antivirals may overcome the superior adaptability of (+)RNA viruses. IMPORTANCE Compared to the number of viral diseases, the number of available vaccines is miniscule. For some viruses vaccine development has not been successful after multiple attempts, and for many others vaccination is not a viable option. Antiviral drugs are needed for clinical practice and public health emergencies. However, viruses are highly adaptable and can

  8. Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

    International Nuclear Information System (INIS)

    Labadie, Karine; Pelletier, Isabelle; Saulnier, Aure; Martin, Javier; Colbere-Garapin, Florence

    2004-01-01

    Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

  9. Characterization of human monoclonal antibodies that neutralize multiple poliovirus serotypes.

    Science.gov (United States)

    Puligedda, Rama Devudu; Kouiavskaia, Diana; Al-Saleem, Fetweh H; Kattala, Chandana Devi; Nabi, Usman; Yaqoob, Hamid; Bhagavathula, V Sandeep; Sharma, Rashmi; Chumakov, Konstantin; Dessain, Scott K

    2017-10-04

    Following the eradication of wild poliovirus (PV), achieving and maintaining a polio-free status will require eliminating potentially pathogenic PV strains derived from the oral attenuated vaccine. For this purpose, a combination of non-cross-resistant drugs, such as small molecules and neutralizing monoclonal antibodies (mAbs), may be ideal. We previously isolated chimpanzee and human mAbs capable of neutralizing multiple PV types (cross-neutralization). Here, we describe three additional human mAbs that neutralize types 1 and 2 PV and one mAb that neutralizes all three types. Most bind conformational epitopes and have unusually long heavy chain complementarity determining 3 domains (HC CDR3). We assessed the ability of the mAbs to neutralize A12 escape mutant PV strains, and found that the neutralizing activities of the mAbs were disrupted by different amino acid substitutions. Competitive binding studies further suggested that the specific mAb:PV interactions that enable cross-neutralization differ among mAbs and serotypes. All of the cloned mAbs bind PV in the vicinity of the "canyon", a circular depression around the 5-fold axis of symmetry through which PV recognizes its cellular receptor. We were unable to generate escape mutants to two of the mAbs, suggesting that their epitopes are important for the PV life cycle. These data indicate that PV cross-neutralization involves binding to highly conserved structures within the canyon that binds to the cellular receptor. These may be facilitated by the long HC CDR3 domains, which may adopt alternative binding configurations. We propose that the human and chimpanzee mAbs described here could have potential as anti-PV therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Construction and characterization of poliovirus subgenomic replicons.

    Science.gov (United States)

    Kaplan, G; Racaniello, V R

    1988-05-01

    Poliovirus RNAs containing in-frame deletions within the capsid-coding region were produced by in vitro transcription of altered poliovirus type 1 cDNA by using bacteriophage T7 RNA polymerase. Three RNAs were transcribed that contained deletions of 2,317 nucleotides (bases 747 to 3064), 1,781 nucleotides (bases 1,175 to 2,956), and 1,295 nucleotides (bases 1,175 to 2,470). All three subgenomic RNAs replicated after transfection into HeLa cells, demonstrating that sequences encoding the capsid polypeptides are not essential for viral RNA replication in vivo. Viral RNA containing the largest deletion (R1) replicated approximately three times better than full-length RNA produced in vitro. Northern blot (RNA blot) hybridization analysis of total cellular RNA from HeLa cells at different times after transfection with R1 demonstrated the presence of increasing amounts of the expected 5.1-kilobase subgenomic RNA. Analysis by immunoprecipitation of viral proteins induced after transfection of R1 RNA into HeLa cells revealed the presence of proteins 2Apro, 2C, and 3Dpol and its precursors, suggesting that the polyprotein cleavages are similar to those occurring in virus-infected cells. Replication of P2/Lansing virion RNA was inhibited by cotransfection with the R1 replicon, as demonstrated by hybridization analysis with a serotype-specific oligonucleotide probe. A higher level of inhibition of RNA replication was observed when P2/Lansing RNA was cotransfected into HeLa cells with truncated R1 transcripts (R1-PvuII) that were missing 395 3' nucleotides and a poly(A) tail. These internally and terminally deleted RNAs inhibited the replication of subgenomic replicons R1, R2, and R3 and caused a reduction in plaque size when cotransfected with P1/Mahoney or P2/Lansing viral RNA, suggesting that individual cells had received both RNAs. No inhibition of plaque size was observed when replicon RNAs were used that were missing 1,384 or 1,839 3' nucleotides or contained plasmid

  11. Análise de campo do desempenho de acessos Web em IPv6.

    OpenAIRE

    Pirani, Deivis Fernandes

    2014-01-01

    Este trabalho apresenta um estudo de campo, comparativo, sobre a utilização dos protocolos IPv4 e IPv6 no acesso a páginas web. Foi considerada a perspectiva de um usuário real deste tipo de serviço, no atual período de transição do IPv4 para o IPv6. Para que tal estudo pudesse ser realizado, foi desenvolvido um arranjo no qual três configurações de endereçamento do Protocolo de Internet, IPv4, IPv6 e Pilha Dupla (IPv4+IPv6), foram utilizadas nos acessos às 100 páginas web, com suporte ao I v...

  12. Manfacturers, service providers gear up for the next Big Thing IPV6

    CERN Multimedia

    2003-01-01

    "IPv6 apparently is the heir apparent to the current communication standard, IPv4, and communications equipment manufacturers are taking this into consideration as they design their next-generation gear" (1/2 page).

  13. Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis▿‡

    Science.gov (United States)

    Chen, Zhaochun; Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Makiya, Michelle; Neverov, Alexander; Rezapkin, Gennady; Sebrell, Andrew; Purcell, Robert

    2011-01-01

    Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 μg/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case. PMID:21345966

  14. Environmental surveillance for polioviruses in the Global Polio Eradication Initiative.

    Science.gov (United States)

    Asghar, Humayun; Diop, Ousmane M; Weldegebriel, Goitom; Malik, Farzana; Shetty, Sushmitha; El Bassioni, Laila; Akande, Adefunke O; Al Maamoun, Eman; Zaidi, Sohail; Adeniji, Adekunle J; Burns, Cara C; Deshpande, Jagadish; Oberste, M Steve; Lowther, Sara A

    2014-11-01

    This article summarizes the status of environmental surveillance (ES) used by the Global Polio Eradication Initiative, provides the rationale for ES, gives examples of ES methods and findings, and summarizes how these data are used to achieve poliovirus eradication. ES complements clinical acute flaccid paralysis (AFP) surveillance for possible polio cases. ES detects poliovirus circulation in environmental sewage and is used to monitor transmission in communities. If detected, the genetic sequences of polioviruses isolated from ES are compared with those of isolates from clinical cases to evaluate the relationships among viruses. To evaluate poliovirus transmission, ES programs must be developed in a manner that is sensitive, with sufficiently frequent sampling, appropriate isolation methods, and specifically targeted sampling sites in locations at highest risk for poliovirus transmission. After poliovirus ceased to be detected in human cases, ES documented the absence of endemic WPV transmission and detected imported WPV. ES provides valuable information, particularly in high-density populations where AFP surveillance is of poor quality, persistent virus circulation is suspected, or frequent virus reintroduction is perceived. Given the benefits of ES, GPEI plans to continue and expand ES as part of its strategic plan and as a supplement to AFP surveillance. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. IPv6 testing and deployment at Prague Tier 2

    Science.gov (United States)

    Kouba, Tomáŝ; Chudoba, Jiří; Eliáŝ, Marek; Fiala, Lukáŝ

    2012-12-01

    Computing Center of the Institute of Physics in Prague provides computing and storage resources for various HEP experiments (D0, Atlas, Alice, Auger) and currently operates more than 300 worker nodes with more than 2500 cores and provides more than 2PB of disk space. Our site is limited to one C-sized block of IPv4 addresses, and hence we had to move most of our worker nodes behind the NAT. However this solution demands more difficult routing setup. We see the IPv6 deployment as a solution that provides less routing, more switching and therefore promises higher network throughput. The administrators of the Computing Center strive to configure and install all provided services automatically. For installation tasks we use PXE and kickstart, for network configuration we use DHCP and for software configuration we use CFEngine. Many hardware boxes are configured via specific web pages or telnet/ssh protocol provided by the box itself. All our services are monitored with several tools e.g. Nagios, Munin, Ganglia. We rely heavily on the SNMP protocol for hardware health monitoring. All these installation, configuration and monitoring tools must be tested before we can switch completely to IPv6 network stack. In this contribution we present the tests we have made, limitations we have faced and configuration decisions that we have made during IPv6 testing. We also present testbed built on virtual machines that was used for all the testing and evaluation.

  16. IPv6 testing and deployment at Prague Tier 2

    International Nuclear Information System (INIS)

    Kouba, Tomáŝ; Chudoba, Jiří; Eliáŝ, Marek; Fiala, Lukáŝ

    2012-01-01

    Computing Center of the Institute of Physics in Prague provides computing and storage resources for various HEP experiments (D0, Atlas, Alice, Auger) and currently operates more than 300 worker nodes with more than 2500 cores and provides more than 2PB of disk space. Our site is limited to one C-sized block of IPv4 addresses, and hence we had to move most of our worker nodes behind the NAT. However this solution demands more difficult routing setup. We see the IPv6 deployment as a solution that provides less routing, more switching and therefore promises higher network throughput. The administrators of the Computing Center strive to configure and install all provided services automatically. For installation tasks we use PXE and kickstart, for network configuration we use DHCP and for software configuration we use CFEngine. Many hardware boxes are configured via specific web pages or telnet/ssh protocol provided by the box itself. All our services are monitored with several tools e.g. Nagios, Munin, Ganglia. We rely heavily on the SNMP protocol for hardware health monitoring. All these installation, configuration and monitoring tools must be tested before we can switch completely to IPv6 network stack. In this contribution we present the tests we have made, limitations we have faced and configuration decisions that we have made during IPv6 testing. We also present testbed built on virtual machines that was used for all the testing and evaluation.

  17. Cost-optimization of the IPv4 zeroconf protocol

    NARCIS (Netherlands)

    Bohnenkamp, H.C.; van der Stok, Peter; Hermanns, H.; Vaandrager, Frits

    2003-01-01

    This paper investigates the tradeoff between reliability and effectiveness for the IPv4 Zeroconf protocol, proposed by Cheshire/Adoba/Guttman in 2002, dedicated to the selfconfiguration of IP network interfaces. We develop a simple stochastic cost model of the protocol, where reliability is measured

  18. Threats and surprises behind IPv6 extension headers

    NARCIS (Netherlands)

    Hendriks, Luuk; Velan, Petr; de Oliveira Schmidt, Ricardo; De Boer, Pieter Tjerk; Pras, Aiko

    2017-01-01

    The concept of Extension Headers, newly introduced with IPv6, is elusive and enables new types of threats in the Internet. Simply dropping all traffic containing any Extension Header - a current practice by operators-seemingly is an effective solution, but at the cost of possibly dropping legitimate

  19. High-frequency mapping of the IPv6 Internet using Yarrp

    OpenAIRE

    Gaston, Eric W.

    2017-01-01

    Approved for public release; distribution is unlimited Both the number of hosts using Internet Protocol version 6 (IPv6), and the volume of IPv6 traffic, has increased exponentially since 2012.With this adoption, the IPv6 routed infrastructure becomes an increasingly important component of global critical infrastructure and network policy. Unfortunately, the tools and techniques used to perform active network topology discovery were designed for Internet Protocol version 4 (IPv4), leading ...

  20. Exploring the fitness landscape of poliovirus

    Science.gov (United States)

    Bianco, Simone; Acevedo, Ashely; Andino, Raul; Tang, Chao

    2012-02-01

    RNA viruses are known to display extraordinary adaptation capabilities to different environments, due to high mutation rates. Their very dynamical evolution is captured by the quasispecies concept, according to which the viral population forms a swarm of genetic variants linked through mutation, which cooperatively interact at a functional level and collectively contribute to the characteristics of the population. The description of the viral fitness landscape becomes paramount towards a more thorough understanding of the virus evolution and spread. The high mutation rate, together with the cooperative nature of the quasispecies, makes it particularly challenging to explore its fitness landscape. I will present an investigation of the dynamical properties of poliovirus fitness landscape, through both the adoption of new experimental techniques and theoretical models.

  1. Construction and characterization of poliovirus subgenomic replicons

    International Nuclear Information System (INIS)

    Kaplan, G.; Racaniello, V.R.

    1988-01-01

    Poliovirus RNAs containing in-frame deletions within the capsid-coding region were produced by in vitro transcription of altered poliovirus type 1 cDNA by using bacteriophage T7 RNA polymerase. Three RNAs were transcribed that contained deletions of 2,317 nucleotides (bases 747 to 3,064), 1,781 nucleotides (bases 1,175 to 2,956), and 1,295 nucleotides (bases 1,175 to 2,470). All three subgenomic RNAs replicated after transfection into HeLa cells, demonstrating that sequences encoding the capsid polypeptides are not essential for viral RNA replication in vivo. Viral RNA containing the largest deletion (R1) replicated approximately three times better than full-length RNA produced in vitro. Northern blot (RNA blot) hybridization analysis of total cellular RNA from HeLa cells at different times after transfection with R1 demonstrated the presence of increasing amounts of the expected 5.1-kilobase subgenomic RNA. Analysis by immunoprecipitation of [ 35 S-labeled] viral proteins induced after transfection of R1 RNA into HeLa cells revealed the presence of proteins 2A pro , 2C, and 3D pol and its precursors, suggesting that the polyprotein cleavages are similar to those occurring in virus-infected cells. These internally and terminally deleted RNAs inhibited the replication of subgenomic replicons R1, R2, and R3 and caused a reduction in plaque size when cotransfected with P1/Mahoney or P2/Lansing viral RNA, suggesting that individual cells had received both RNAs

  2. IPV among Adolescent Reproductive Health Patients: The Role of Relationship Communication

    Science.gov (United States)

    Messinger, Adam M.; Davidson, Leslie L.; Rickert, Vaughn I.

    2011-01-01

    Population-specific data on factors that affect intimate partner violence (IPV) are needed on female adolescents and young adults, a cohort at greatest risk of IPV in the United States (Rennison, 2001). Studies have frequently overlooked the role of relationship communication as a gatekeeper to IPV (Ridley & Feldman, 2003). To address this…

  3. Flow-based detection of IPv6-specific network layer attacks

    NARCIS (Netherlands)

    Hendriks, Luuk; Velan, Petr; de O. Schmidt, Ricardo; de Boer, Pieter-Tjerk; Pras, Aiko; Tuncer, Daphne; Koch, Robert; Badonne, Rémi; Stiller, Burkhard

    2017-01-01

    With a vastly different header format, IPv6 introduces new vulnerabilities not possible in IPv4, potentially requiring new detection algorithms. While many attacks specific to IPv6 have proven to be possible and are described in the literature, no detection solutions for these attacks have been

  4. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses.

    Science.gov (United States)

    Holmblat, Barbara; Jégouic, Sophie; Muslin, Claire; Blondel, Bruno; Joffret, Marie-Line; Delpeyroux, Francis

    2014-08-05

    Most of the circulating vaccine-derived polioviruses (cVDPVs) implicated in poliomyelitis outbreaks in Madagascar have been shown to be recombinants between the type 2 poliovirus (PV) strain of the oral polio vaccine (Sabin 2) and another species C human enterovirus (HEV-C), such as type 17 coxsackie A virus (CA17) in particular. We studied intertypic genetic exchanges between PV and non-PV HEV-C by developing a recombination model, making it possible to rescue defective type 2 PV RNA genomes with a short deletion at the 3' end by the cotransfection of cells with defective or infectious CA17 RNAs. We isolated over 200 different PV/CA17 recombinants, using murine cells expressing the human PV receptor (PVR) and selecting viruses with PV capsids. We found some homologous (H) recombinants and, mostly, nonhomologous (NH) recombinants presenting duplications of parental sequences preferentially located in the regions encoding proteins 2A, 2B, and 3A. Short duplications appeared to be stable, whereas longer duplications were excised during passaging in cultured cells or after multiplication in PVR-transgenic mice, generating H recombinants with diverse sites of recombination. This suggests that NH recombination events may be a transient, intermediate step in the generation and selection of the fittest H recombinants. In addition to the classical copy-choice mechanism of recombination thought to generate mostly H recombinants, there may also be a modular mechanism of recombination, involving NH recombinant precursors, shaping the genomes of recombinant enteroviruses and other picornaviruses. Importance: The multiplication of circulating vaccine-derived polioviruses (cVDPVs) in poorly immunized human populations can render these viruses pathogenic, causing poliomyelitis outbreaks. Most cVDPVs are intertypic recombinants between a poliovirus (PV) strain and another human enterovirus, such as type 17 coxsackie A viruses (CA17). For further studies of the genetic exchanges

  5. Empirical analysis of the effects and the mitigation of IPv4 address exhaustion

    OpenAIRE

    Richter, Philipp

    2017-01-01

    IP addresses are essential resources for communication over the Internet. In IP version 4, an address is represented by 32 bits in the IPv4 header; hence there is a finite pool of roughly 4B addresses available. The Internet now faces a fundamental resource scarcity problem: The exhaustion of the available IPv4 address space. In 2011, the Internet Assigned Numbers Authority (IANA) depleted its pool of available IPv4 addresses. IPv4 scarcity is now reality. In the subsequent years, IPv4 a...

  6. The Rise of IPv6: Benefits and Costs of Transforming Military Cyberspace

    Science.gov (United States)

    2015-04-01

    people, the structure of the Internet is changing for the first time in its history with the ex- haustion of the IP version four ( IPv4 ) protocol and the...have.4 The need to transition from IPv4 to IPv6 is not hy- pothetical since the global supply of IP addresses in IPv4 is quickly be- ing exhausted...Registry (RIR) IPv4 Address Run-Down Model Year RI R Ad dr es s Po ol (/ 8s ) 2013 2014 2015 2016 2017 2018 2019 2020 4.5 4 3.5 3 2.5 2 1.5 1 0.5

  7. Performance evaluation of secured DICOM image communication with next generation internet protocol IPv6

    Science.gov (United States)

    Yu, Fenghai; Zhang, Jianguo; Chen, Xiaomeng; Huang, H. K.

    2005-04-01

    Next Generation Internet (NGI) technology with new communication protocol IPv6 emerges as a potential solution for low-cost and high-speed networks for image data transmission. IPv6 is designed to solve many of the problems of the current version of IP (known as IPv4) with regard to address depletion, security, autoconfiguration, extensibility, and more. We choose CTN (Central Test Node) DICOM software developed by The Mallinckrodt Institute of Radiology to implement IPv6/IPv4 enabled DICOM communication software on different operating systems (Windows/Linux), and used this DICOM software to evaluate the performance of the IPv6/IPv4 enabled DICOM image communication with different security setting and environments. We compared the security communications of IPsec with SSL/TLS on different TCP/IP protocols (IPv6/IPv4), and find that there are some trade-offs to choose security solution between IPsec and SSL/TLS in the security implementation of IPv6/IPv4 communication networks.

  8. Analisis Kematangan Implementasi Internet Protocol versi 6 (IPv6 di Indonesia dengan Interim Maturity Level (IML

    Directory of Open Access Journals (Sweden)

    Riza Azmi

    2012-12-01

    Full Text Available Cepat atau lambat, IPv6 akan menggantikan IPv4 dalam penomoran internet. Hal ini dikarenakan IANA telah mengalokasikan blok IPv4 terakhirnya pada Januari 2011 lalu. Pesatnya permintaan terhadap IP ini dikarenakan boomingnya .com sejak tahun 2000. Dengan habisnya IPv4, terdapat beberapa metode untuk melakukan migrasi ke peenomoran baru IPv6. Terkait dengan hal tersebut, penelitian ini mencoba mengukur tingkat kematangan beberapa penyelenggara jasa internet di Indonesia dalam hal implementasi IPv6 dengan menggunakan konsep Capability Maturity Model for IPv6 Implementation. Metode assesmen yang dilakukan dengan Interim Maturity Level, yaitu dengan memberikan seperangkat pertanyaan yang diisi sendiri oleh penyelenggara jasa internet. Hasil yang didapat adalah, sebagian besar penyelenggara internet masih berada pada Level 2 – Savvy.

  9. Spatial data efficient transmission in WebGIS based on IPv6

    Science.gov (United States)

    Wang, Zhen-feng; Liu, Ji-ping; Wang, Liang; Tao, Kun-wang

    2008-12-01

    Large-size of spatial data and limited bandwidth of network make it restricted to transmit spatial data in WebGIS. This paper employs IPv6 (Internet Protocol version 6), the successor of IPv4 running now, to transmit spatial data efficiently. As the core of NGN (Next Generation Network), IPv6 brings us many advantages to resolve performance problems in current IPv4 network applications. Multicast, which is mandatory in IPv6 routers, can make one server serve many clients simultaneously efficiently, thus to improve capacity of network applications. The new type of anycast address in IPv6 will make network client applications possible to find the nearest server. This makes data transmission between client and server fastest. The paper introduces how to apply IPv6 multicast and anycast in WebGIS to transmit data efficiently.

  10. MULTI-LINK SUPPORT FOR IPV6 NETWORKS

    Directory of Open Access Journals (Sweden)

    Cüneyt Akınlar

    2016-03-01

    Full Text Available IPv6 ağ konfigürasyonu için genel pratik ağ üzerindeki her fiziksel bağ için ayrı bir altağ öneki atamaktır. Bu uygulama hem birden fazla ağ öneki gereksimine sebep olur, hem de elle yönetim ve konfigürasyon gerektirir. Buna alternatif konfigürasyon yöntemi bütün bağları IPv6 seviyesinde bir köprü ile bağlamak ve bu sayede bütün ağ için tek bir ağ öneki ataması yapmaktır. Bu metoda çoklu-bağ öneki ismi verilir. Bu makalede IPv6 ağları için çoklu-bağ öneki oto-konfigürasyonu konusu ele alınmıştır. Öncelikle tek yönlendiricili ağlar için coklu-bağ desteğinin nasıl gerçekleneceği tarif edilmiş, daha sonra bu yöntemin çok yönlendiricili ağlara nasıl uygulanacağı anlatılmıştır. Önerilen oto-konfigürasyon yöntemleri standart alıcı otokonfigürasyon protokollerini tamamlamakta ve IPv6 ağlarının yaygın kurulum ve kullanımları için gerekli tak-çalıştır metodolojine olanak sağlamaktadır

  11. The Unexplored Impact of IPv6 on Intrusion Detection Systems

    Science.gov (United States)

    2012-03-01

    Protocol Version 4 IPv4 Internet Protocol Version 6 IRC Internet Relay Chat LAN Local Area Network xv MiTM Man in the Middle MLD Multicast Listener...section. 1. Sniffing 2. Application Layer Attacks 3. Rogue Devices 4. Man In the Middle ( MITM ) 5. Flooding 6. Reconnaissance 7. Unauthorized access 8...the method by which worms find hosts may have to change. Man In The Middle ( MITM ) The general theory of the Man in the Middle ( MITM ) threat does not

  12. IPv6 testing and deployment at Prague Tier 2

    Czech Academy of Sciences Publication Activity Database

    Kouba, Tomáš; Chudoba, Jiří; Eliáš, Marek; Fiala, Lukáš

    2012-01-01

    Roč. 396, č. 4 (2012), s. 1-6 ISSN 1742-6588. [International Conference on Computing in High Energy and Nuclear Physics 2012 (CHEP2012). New York, 21.05.2012-25.05.2012] Institutional research plan: CEZ:AV0Z10100502 Keywords : IPv6 grid computing HEP Subject RIV: BF - Elementary Particles and High Energy Physics http://iopscience.iop.org/1742-6596/396/4/042034

  13. Advanced mobility handover for mobile IPv6 based wireless networks.

    Science.gov (United States)

    Safa Sadiq, Ali; Fisal, Norsheila Binti; Ghafoor, Kayhan Zrar; Lloret, Jaime

    2014-01-01

    We propose an Advanced Mobility Handover scheme (AMH) in this paper for seamless mobility in MIPv6-based wireless networks. In the proposed scheme, the mobile node utilizes a unique home IPv6 address developed to maintain communication with other corresponding nodes without a care-of-address during the roaming process. The IPv6 address for each MN during the first round of AMH process is uniquely identified by HA using the developed MN-ID field as a global permanent, which is identifying uniquely the IPv6 address of MN. Moreover, a temporary MN-ID is generated by access point each time an MN is associated with a particular AP and temporarily saved in a developed table inside the AP. When employing the AMH scheme, the handover process in the network layer is performed prior to its default time. That is, the mobility handover process in the network layer is tackled by a trigger developed AMH message to the next access point. Thus, a mobile node keeps communicating with the current access point while the network layer handover is executed by the next access point. The mathematical analyses and simulation results show that the proposed scheme performs better as compared with the existing approaches.

  14. Duplicate Address Detection Table in IPv6 Mobile Networks

    Science.gov (United States)

    Alisherov, Farkhod; Kim, Taihoon

    In IP networks, each computer or communication equipment needs an IP address. To supply enough IP addresses, the new Internet protocol IPv6 is used in next generatoion mobile communication. Although IPv6 improves the existing IPv4 Internet protocol, Duplicate Address Detection (DAD) mechanism may consume resources and suffer from long delay. DAD is used to ensure whether the IP address is unique or not. When a mobile node performs an inter-domain handoff, it will first generate a new IP and perform a DAD procedure. The DAD procedure not only wastes time but also increases the signaling load on Internet. In this paper, the author proposes a new DAD mechanism to speed up the DAD procedure. A DAD table is created in access or mobility routers in IP networks and record all IP addresses of the area. When a new IP address needs to perform DAD, it can just search in the DAD table to confirm the uniqueness of the address.

  15. Advanced Mobility Handover for Mobile IPv6 Based Wireless Networks

    Science.gov (United States)

    Safa Sadiq, Ali; Fisal, Norsheila Binti; Ghafoor, Kayhan Zrar; Lloret, Jaime

    2014-01-01

    We propose an Advanced Mobility Handover scheme (AMH) in this paper for seamless mobility in MIPv6-based wireless networks. In the proposed scheme, the mobile node utilizes a unique home IPv6 address developed to maintain communication with other corresponding nodes without a care-of-address during the roaming process. The IPv6 address for each MN during the first round of AMH process is uniquely identified by HA using the developed MN-ID field as a global permanent, which is identifying uniquely the IPv6 address of MN. Moreover, a temporary MN-ID is generated by access point each time an MN is associated with a particular AP and temporarily saved in a developed table inside the AP. When employing the AMH scheme, the handover process in the network layer is performed prior to its default time. That is, the mobility handover process in the network layer is tackled by a trigger developed AMH message to the next access point. Thus, a mobile node keeps communicating with the current access point while the network layer handover is executed by the next access point. The mathematical analyses and simulation results show that the proposed scheme performs better as compared with the existing approaches. PMID:25614890

  16. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  17. A national reference for inactivated polio vaccine derived from Sabin strains in Japan.

    Science.gov (United States)

    Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji

    2014-09-08

    As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Optimization in Mobile IPv6 with Dynamic DNS

    OpenAIRE

    塩津, 達郎

    2005-01-01

    機器の高性能化により、モバイル端末においてもインターネットを利用した様々なアプリケーションを利用する要求が増え、無線通信環境の充実により、モバイル端末への通信を継続する仕組みが求められるようになった。 移動中の継続的な通信を可能とする技術の一つとして Mobile IPv6 がある。Mobile IPv6 にり、端末が移動しても通信を継続できる移動透過性が提供される。この移動透過性を実現するために、Mobile IPv6 では移動する端末とその端末と通信をしている端末の仲介役となる Home Agent が必要になる。ところが、仲介役となる必要のない場合でも Home Agent が仲介役として動き、無駄なパケットがインターネット上に流れてしまう。 本論文では、Mobile IPv6 という技術に加えて、Dynamic DNS という技術を用いて、Mobile IPv6 ネットワークの最適化を行う手法を提案し、性能評価を行った。...

  19. [Effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine and its safety].

    Science.gov (United States)

    Bian, Chuan-xiu; Jiang, Shu-de; Yang, Jian-yong; Sun, Ming-bo; Xie, Ming-xue; Zhang, Xin-wen; Liao, Guo-yang; Li, Wei-dong

    2007-03-01

    To investigate the effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine (IPV). Sabin IPV samples containing 5 mg or 7 mg 2-phenoxyethanol each dosage respectively were placed separately at 4 degrees C, 37 degrees C for 2 days and 7 days. D-antigen contents were tested with ELISA method. Then neutralizing antibodies in mice and guinea pigs were detected. The safety experiment was performed according to unusual toxicity test of China requirement for biological product. After addition of 2-phenoxyethanol, the I, II, and III D-antigen contents of Sabin IPV did not change. The antibody levels in mice and guinea pigs were not different between experimental group and control group. Animals were safe during observation period. 2-Phenoxyethanol had no effect on potency and safety of Sabin IPV. It can be used as antiseptic for Sabin IPV.

  20. АНАЛІЗ МЕТОДІВ ВИРІШЕННЯ ПРОБЛЕМ ЩОДО ВПРОВАДЖЕННЯ ПРОТОКОЛУ IPV6

    OpenAIRE

    Созонник, Галина Дмитрівна; Гамза, Дмитро Євгенійович

    2017-01-01

    IPv6 implementation problems research IPv6 implementation problems research, analysis of the IPv6 advantages and its’ compatibility with IPv4; methods of transition from IPv6 to IPv4, transitional technologies

  1. Polio endgame: the global introduction of inactivated polio vaccine.

    Science.gov (United States)

    Patel, Manish; Zipursky, Simona; Orenstein, Walt; Garon, Julie; Zaffran, Michel

    2015-05-01

    In 2013, the World Health Assembly endorsed a plan that calls for the ultimate withdrawal of oral polio vaccines (OPV) from all immunization programs globally. The withdrawal would begin in a phased manner with removal of the type 2 component of OPV in 2016 through a global switch from trivalent OPV to bivalent OPV (containing only types 1 and 3). To mitigate risks associated with immunity gaps after OPV type 2 withdrawal, the WHO Strategic Advisory Group of Experts has recommended that all 126 OPV-only using countries introduce at least one dose of inactivated polio vaccine into routine immunization programs by end-2015, before the trivalent OPV-bivalent OPV switch. The introduction of inactivated polio vaccine would reduce risks of reintroduction of type 2 poliovirus by providing some level of seroprotection, facilitating interruption of transmission if outbreaks occur, and accelerating eradication by boosting immunity to types 1 and 3 polioviruses.

  2. Implantación de IPv6 : red, mecanismos de transición IPv4-IPv6, servicios de aplicación y migración de aplicaciones

    OpenAIRE

    Rodríguez Hervella, Juan Francisco

    2003-01-01

    El presente proyecto fin de carrera trata los aspectos más importantes de la gestión y migración de las redes IP hacia el nuevo protocolo de red IPv6 y pone gran énfasis en experiencias de implantación de los mismos. A lo largo de este proyecto se profundiza sobre los distintos mecanismos de transición IPv4/IPv6 existentes, concretamente se describen y se prueban (en entornos Linux y FreeBSD) los siguientes: .Túneles 6t04, automáticos, configurados. .Mecanismo DSTM, TRT, ISATAP, NAT-PT. Tambi...

  3. Antigen sparing with adjuvanted inactivated polio vaccine based on Sabin strains.

    Science.gov (United States)

    Westdijk, Janny; Koedam, Patrick; Barro, Mario; Steil, Benjamin P; Collin, Nicolas; Vedvick, Thomas S; Bakker, Wilfried A M; van der Ley, Peter; Kersten, Gideon

    2013-02-18

    Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7-20-27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. RENEW: a real-time and effective network emulator of windows for IPv6

    Science.gov (United States)

    Zhao, Bing; Jin, Zhigang; Shu, Yantai; Li, Yu; Cen, Dan

    2007-09-01

    Although IPv4 is still working, IPv6 is considered as the backbone and characteristic of the NGI. With the development of Internet, new protocols and network equipments are required to develop. It is necessary to test the new protocols and network equipments extensively before deployment. This paper proposes the design and implementation of RENEW, a useable and accurate network emulator which supports both IPv4 and IPv6 protocols. Besides, it also works on Windows platform. In our IPv6 testbed, we use RENEW to emulate various network characteristics and conditions including bandwidth, delay packet loss and jitter. Compared with the expected values, results are acceptable. Through implementation and experimentation study, we have shown that RENEW does provide the real-time control and change on the parameters of IPv6 network conditions effectively and expediently on Windows. It also gives enough accuracy and more satisfactory convenience to the development and test work for the new protocols.

  5. Deployment of 464XLAT (RFC6877) alongside IPv6-only CPU resources at WLCG sites

    Science.gov (United States)

    Froy, T. S.; Traynor, D. P.; Walker, C. J.

    2017-10-01

    IPv4 is now officially deprecated by the IETF. A significant amount of effort has already been expended by the HEPiX IPv6 Working Group on testing dual-stacked hosts and IPv6-only CPU resources. Dual-stack adds complexity and administrative overhead to sites that may already be starved of resource. This has resulted in a very slow uptake of IPv6 from WLCG sites. 464XLAT (RFC6877) is intended for IPv6 single-stack environments that require the ability to communicate with IPv4-only endpoints. This paper will present a deployment strategy for 464XLAT, operational experiences of using 464XLAT in production at a WLCG site and important information to consider prior to deploying 464XLAT.

  6. Evolution of IPv6 Internet topology with unusual sudden changes

    Science.gov (United States)

    Ai, Jun; Zhao, Hai; Kathleen, M. Carley; Su, Zhan; Li, Hui

    2013-07-01

    The evolution of Internet topology is not always smooth but sometimes with unusual sudden changes. Consequently, identifying patterns of unusual topology evolution is critical for Internet topology modeling and simulation. We analyze IPv6 Internet topology evolution in IP-level graph to demonstrate how it changes in uncommon ways to restructure the Internet. After evaluating the changes of average degree, average path length, and some other metrics over time, we find that in the case of a large-scale growing the Internet becomes more robust; whereas in a top—bottom connection enhancement the Internet maintains its efficiency with links largely decreased.

  7. Evolution of IPv6 Internet topology with unusual sudden changes

    International Nuclear Information System (INIS)

    Ai Jun; Su Zhan; Li Hui; Zhao Hai; Carley, Kathleen M.

    2013-01-01

    The evolution of Internet topology is not always smooth but sometimes with unusual sudden changes. Consequently, identifying patterns of unusual topology evolution is critical for Internet topology modeling and simulation. We analyze IPv6 Internet topology evolution in IP-level graph to demonstrate how it changes in uncommon ways to restructure the Internet. After evaluating the changes of average degree, average path length, and some other metrics over time, we find that in the case of a large-scale growing the Internet becomes more robust; whereas in a top—bottom connection enhancement the Internet maintains its efficiency with links largely decreased

  8. Antigenic variation and resistance to neutralization in poliovirus type 1.

    NARCIS (Netherlands)

    D.C. Diamond; B.A. Jameson; J. Bonin; M. Kohara; S. Abe; H. Itoh; T. Komatsu; M. Arita; S. Kuge; A. Nomoto; A.D.M.E. Osterhaus (Albert); R. Crainic; E. Wimmer

    1985-01-01

    textabstractMutations have been identified in variants of poliovirus, type 1 (Mahoney) on the basis of their resistance to neutralization by individual monoclonal antibodies. The phenotypes of these variants were defined in terms of antibody binding; the pattern of epitopes expressed or able to be

  9. Isolation and Characterization of Poliovirus in Cell Culture Systems.

    Science.gov (United States)

    Thorley, Bruce R; Roberts, Jason A

    2016-01-01

    The isolation and characterization of enteroviruses by cell culture was accepted as the "gold standard" by clinical virology laboratories. Methods for the direct detection of all enteroviruses by reverse transcription polymerase chain reaction, targeting a conserved region of the genome, have largely supplanted cell culture as the principal diagnostic procedure. However, the World Health Organization's Global Polio Eradication Initiative continues to rely upon cell culture to isolate poliovirus due to the lack of a reliable sensitive genetic test for direct typing of enteroviruses from clinical specimens. Poliovirus is able to infect a wide range of mammalian cell lines, with CD155 identified as the primary human receptor for all three seroytpes, and virus replication leads to an observable cytopathic effect. Inoculation of cell lines with extracts of clinical specimens and subsequent passaging of the cells leads to an increased virus titre. Cultured isolates of poliovirus are suitable for testing by a variety of methods and remain viable for years when stored at low temperature.This chapter describes general procedures for establishing a cell bank and routine passaging of cell lines. While the sections on specimen preparation and virus isolation focus on poliovirus, the protocols are suitable for other enteroviruses.

  10. Protocolo IPv6 com pilha dupla em um campus universitário

    Directory of Open Access Journals (Sweden)

    Fernando Barreto

    2015-11-01

    Full Text Available Com o esgotamento do endereçamento IPv4 sendo uma realidade, a adoção do IPv6 se torna cada vez mais necessária. Os protocolos IPv4 e IPv6 são incompatíveis e têm questões de operação diferentes, o que torna a implementação do IPv6 relativamente difícil para administradores de rede IPv4. Com o objetivo de reduzir essa dificuldade, este artigo apresenta uma comparação entre IPv4 e IPv6 com foco no dia a dia de administração de rede de campus. Esse artigo também apresenta as soluções, experiências e lições adquiridas de uma implementação de sucesso do IPv6, utilizando a técnica de Pilha Dupla em um pequeno campus universitário.

  11. RAZVOJ MODELA IN SIMULACIJA IZČRPANJA IPv4 NASLOVNEGA PROSTORA

    OpenAIRE

    Ciber, Peter

    2014-01-01

    Magistrsko delo obravnava razvoj modela in simulacijo izčrpanja IPv4 naslovnega prostora. Za dodeljevanje IPv4 naslovnega prostora skrbi organizacija IANA, ki je po petih celinah sveta dodelila velike kose IPv4 naslovnega prostora. V Evropi tako za nadaljnjo razdelitev skrbi organizacija RIPE NCC, v Afriki AFRINIC, v azijsko-pacifiški regiji APNIC, v Ameriki ARIN v Latinski Ameriki in Karibih pa LACNIC. Zanimalo nas je koliko in kako je IANA razdelila IPv4 naslove po celinah in kako so region...

  12. Detection of poliovirus infection in children with acute gastroenteritis in Chiang Mai, Thailand.

    Science.gov (United States)

    Kumthip, Kattareeya; Khamrin, Pattara; Maneekarn, Niwat

    2017-05-01

    Poliovirus (PV) is typically transmitted by the fecal-oral route, which means that the risk of infection and virus distribution could be achieved by exposure to the virus contaminated in food and water. The aim of this study was to determine the occurrence of PV strains by detecting the virus in pediatric patients who admitted to the hospitals with diarrhea in Chiang Mai, Thailand during 2010-2015. By applying a reverse transcription-polymerase chain reaction and nucleotide sequencing analysis of 1,300 stool specimens collected from pediatric patients, PVs were detected at 0.61% (8 out of 1,300 specimens). Among eight PV positive samples, mixed infection with norovirus or human bocavirus was detected in one each out of eight cases. All PV strains detected in this study were characterized further by phylogenetic analysis of 343 bp of the 5' UTR and 315 bp of the partial VP1 sequences. The results revealed that eight PV strains detected in the present study two of each were PV1 and PV2, and four were PV3 serotypes of the Sabin vaccine strains. The data demonstrated the presence of PV1, PV2, and PV3 Sabin vaccine strains in children with acute gastroenteritis in Chiang Mai, Thailand. J. Med. Virol. 89:775-781, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark

    DEFF Research Database (Denmark)

    Sørup, Signe; Stensballe, Lone G; Krause, Tyra Grove

    2016-01-01

    Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children with inactiv......Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children...... with inactivated diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods.  A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses...... of DTaP-IPV-Hib, were observed from 24 months (first OPV dose) to 36 months of age. Results.  Oral polio vaccine was associated with a lower rate of admissions with any type of non-polio infection compared with DTaP-IPV-Hib as most recent vaccine (adjusted incidence rate ratio [IRR], 0.85; 95% confidence...

  14. Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010.

    Science.gov (United States)

    Drexler, Jan Felix; Grard, Gilda; Lukashev, Alexander N; Kozlovskaya, Liubov I; Böttcher, Sindy; Uslu, Gökhan; Reimerink, Johan; Gmyl, Anatoly P; Taty-Taty, Raphaël; Lekana-Douki, Sonia Etenna; Nkoghe, Dieudonné; Eis-Hübinger, Anna M; Diedrich, Sabine; Koopmans, Marion; Leroy, Eric M; Drosten, Christian

    2014-09-02

    In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL → 221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15-29% were unprotected according to their neutralization titers (poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.

  15. New Approaches to Attenuated Hepatitis a Vaccine Development: Cloning and Sequencing of Cell-Culture Adapted Viral cDNA.

    Science.gov (United States)

    1987-10-13

    after multiple passages in vivo and in vitro. J. Gen. Virol. 67, 1741- 1744. Sabin , A.B. (1985). Oral poliovirus vaccine : history of its development...IN (N NEW APPROACHES TO ATTENUATED HEPATITIS A VACCINE DEVELOPMENT: Q) CLONING AND SEQUENCING OF CELL-CULTURE ADAPTED VIRAL cDNA I ANNUAL REPORT...6ll02Bsl0 A 055 11. TITLE (Include Security Classification) New Approaches to Attenuated Hepatitis A Vaccine Development: Cloning and Sequencing of Cell

  16. CONFIGURACIÓN DE UNA RED DE NUEVA GENERACIÓN PARA CONECTIVIDAD CON INTERNET RESPALDADO POR UN SERVICIO DNS CON SOPORTE PARA IPV4 E IPV6.

    Directory of Open Access Journals (Sweden)

    Carlos Andrés Martínez

    2012-05-01

    Full Text Available Se presentan las características mas representativas de la implementación de la isla ipv6 del centro de computación de alto desempeño CECAD, realizando pruebas de conexión y desempeño en el tráfico interno con las subredes de la Universidad Distrital y posteriormente con su conexión a Internet a través del protocolo NAT-PT secundado por un servidor de nombres de domino recursivo como base de conectividad y soporte sobre estructuras Ipv4 e Ipv6 nativas.

  17. Comparison of ELISA and dual stage real time RT-PCR to differentiate Sabin like and non-Sabin like poliovirus isolates.

    Science.gov (United States)

    Kaundal, Nirmal; Sarkate, Purva; Prakash, Charu; Rishi, Narayan

    2017-06-01

    Environmental surveillance of polioviruses has been used as an important tool in monitoring circulation of wild polioviruses and/or Vaccine derived polioviruses in sewage samples. It is important to distinguish Sabin like isolates from non-Sabin like; ELISA & dual stage real time RT-PCR have been used for the same. Current study was carried out on sewage isolates to compare ELISA & RT-PCR with sequencing to distinguish Sabin like from non-Sabin like. Out of 468 sewage specimens, 91 (19.44%) were non-polio enteroviruses positive and 377 (80.56%) were polio positive by virus isolation method. A total of 488 polio virus isolates were detected by L20B and RD route which were further subjected to ELISA and RT-PCR. The results were compared with sequencing. On comparison, the specificity of ELISA was only 66.67% in spite of very low sensitivity (3.43%). The sensitivity of RT-PCR was 97.71% which makes it a good primary screening test for detection of non-Sabin like viruses. However, the specificity was only 33.33%. RT-PCR appears to be a sensitive tool for detecting non-Sabin like viruses however; the isolates which are non-Sabin like by RT-PCR may not necessarily be mutated viruses. ELISA cannot be used for differentiation of Sabin likes from non-Sabin likes due to low sensitivity.