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Tropis® – Information Dossier RATIONALE FOR fIPV WITH TROPIS® INTRADERMAL INJECTION SYSTEM

INTRODUCTION Polio Eradication and Endgame Strategic Plan (Polio Endgame Strategy) 2013–2018 was developed in response to the World Health Assembly declaration in 2012 that the disease constitutes a global public health emergency. The plan includes the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunisation schedules. The information below summarizes the key reasons for introduction of IPV, challenges surrounding the strategy and consideration of Tropis® Needle-Free Injection System to mitigate the same.1

INCLUSION OF IPV INTO ROUTINE IMMUNISATION SCHEDULES IPV was first developed in 1955 and is given by injection. It is available only in trivalent form containing all the 3 virus serotypes which are known to cause disease. Oral Polio Vaccine (OPV) was initially introduced in early sixties as a monovalent vaccine and soon converted into a trivalent version (tOPV).1 GLOBAL CHALLENGE: IPV SHORTAGE

The components of tOPV had to be relooked for the below reasons. There were no new cases of polio As part of the Polio Endgame Strategy and as recommended by the WHO, all 126 countries which at caused by serotype 2 for over 15 years. In contrast, there were several cases of serotype 2 vaccine the start of 2013 were only using OPV, were required to introduce at least 1 dose of IPV into routine associated paralytic polio. This led to the recommendation on the cessation of use of the serotype immunisation schedules. This would require an increase in the long-term supply of IPV provided by the 2 2 component of OPV and a switch from tOPV to bivalent OPV (bOPV), which contains types 1 and 3 vaccine manufacturers. viruses only. This bOPV has been licensed and used in some settings since December 2009. Following the planned global switch from tOPV to bOPV in April 2016, tOPV will no longer be available and will be Vaccine manufacturers had initially been confident that the scale-up of IPV production would ensure replaced by bOPV.1 sufficient capacity to meet the global demand for IPV. Unfortunately, the rapid scale-up of IPV production has encountered multiple challenges, leading to a global shortage in the available supply. In March 2016, WHO recommends the inclusion of at least one dose of IPV in the vaccination schedule for all countries the largest IPV supplier to the Global Polio Eradication Initiative (GPEI) announced an approximately 2 using OPV in the national immunisation programme. The primary purpose of this IPV dose is to induce 40% reduction in supply for 2016 and 2017, which are related to production scale up issues. an immunity base that could be rapidly boosted should there be an outbreak of polio due to poliovirus type 2 following the removal of serotype 2 virus from OPV. Additionally, depending on the timing of the The shortage in IPV supply is being managed globally, with prioritisation of IPV delivery to countries at administration of the dose or doses of IPV, the inclusion of IPV may reduce risks for the development of highest risk. Certain plans are put in place to mitigate risks should there be a delay in the receipt of IPV. vaccine-associated paralytic poliomyelitis and could boost immunity against poliovirus types 1 and 3 in One option is to provide an alternative to the intramuscular injection of a full IPV dose, wherein countries vaccine recipients.1 in any situation may choose the implementation of a two-dose fractional dose schedule (using 1/5 of a full dose), via the intradermal (ID) route.2 RATIONALE FOR fIPV WITH TROPIS® INTRADERMAL INJECTION SYSTEM

FRACTIONAL DOSE IPV (fIPV) AND ITS EFFICACY BENEFITS OF TROPIS® INTRADERMAL INJECTION SYSTEM FOR Intradermal IPV administration with fractional doses of IPV (0.1 mL or 1/5 of a full dose) offers potential fIPV ADMINISTRATION cost reduction and allows immunisation of a larger number of persons with a given vaccine supply. Ongoing research on fIPV from the 1990s up to the recent years has come to demonstrate that two Tropis® Intradermal Injection System uses jet injector technology that propels liquid at high pressure to fractional doses administered intradermally offer higher immunogenicity compared to one full 0.5 mL deliver vaccines through the skin without utilising needles. intramuscular (IM) dose of IPV. Collectively, the data generated supports the strong recommendation from the WHO Strategic Advisory Group of Experts on Immunization (SAGE) for a two-dose fIPV schedule. The advantages of using the system are as follows: The following table summarizes the studies conducted comparing two ID fIPV doses with one full IM IPV Superior Coverage: It has a potential for dose-sparing by virtue of the fact that delivery can be targeted dose.3 to the intradermal layer. Considering that the dose of fIPV is 0.1 mL and two doses are to be administered, the total vaccine required is just 0.2 mL, in comparison with 0.5 mL which would be required for IM route; thus ensuring a 60% savings in amount of vaccine used. Thus, more than double the number of Schedule Seroconversion (%) Publication children benefit from the same quantity of vaccine when given via IM route.4 Country (Year) 2 fractional 1 full dose 2 fractional 1 full dose doses doses Greater Safety: Being a needle-free injection system, there is no fear of needle-stick injuries to Resik S, et al the healthcare workers or caregivers. The device is manufactured in such a manner that there is no Cuba 6, 10 weeks 6 weeks 55 36 (2010) opportunity for accidental or intentional reuse of the disposable syringes.4 Mohammed AJ, et Oman 2, 4 months 2 months 72 32 al (2010) Ease-of-use: A recent study assessed the feasibility of using the Tropis® Needle-Free Injection System for an intradermal fIPV campaign. In this study, eleven vaccinator teams underwent a two-day training Resik S, et al. Cuba 4, 8 months 4 months 98 63 and immunized 582 children between 4 months and 5 years of age. Application time was defined as time (2013) period from charging of the device till disposal of the used syringe. The average application time was 48 Anand A, et al. seconds which decreased towards campaign completion. The time of application of the vaccine using Bangladesh 6, 14 weeks 6 weeks 81 39 (2015) Tropis® Needle-Free Injection System is likely to be considerably shorter than traditional intradermal injections, though a head-to-head comparison has not been done. The vaccinators reported that filling the device and administration of the injection was easy. There was also no vaccine loss during the entire The approach of using two fractional doses instead of one full dose increases the immunogenicity of study. The authors concluded that it is feasible, safe and efficient to use the Tropis® Needle-Free Injection IPV and can extend coverage if supplies are limited. This dose sparing method could ensure that more System for the administration of fIPV in a campaign setting.5 eligible infants receive IPV and results in better immunogenicity than a single full dose of IPV. 3

In order to ensure early protection, a schedule of fractional intradermal doses administered at 6 and CONCLUSION 14 weeks from birth may be considered, ascertaining that the two fractional doses are separated by a In order to achieve global aim to successfully implement Polio Endgame Strategy and resolve the issue minimum interval of 4 weeks.3 of polio vaccine shortage, the introduction of a safe and effective solution is necessary. Tropis® Needle- free Injection System not only provides a quick, effective and safe solution to the polio vaccination CHALLENGES WITH ADMINISTRATION OF fIPV schedule, but also helps to address the global shortage of IPV by the introduction of fIPV, which is fully aligned with the WHO SAGE recommendation on immunization. Thus allowing for better immunization Intradermal delivery of fIPV using needle and syringe can be performed using the Mantoux technique, as well as helping to resolve vaccine shortage issue in order to achieve the Polio Endgame Strategy. wherein the needle is inserted at a narrow angle from the skin surface and the vaccine deposited underneath the skin. Generally, the procedure is considered to be slow and technically challenging, especially when vaccinating an infant. Intradermal vaccine delivery systems with the use of needle-free injectors could potentially alleviate this concern.4 2016, 91, 145-168 No 12 Weekly epidemiological record Relevé épidémiologique hebdomadaire

25 MARCH 2016, 91th YEAR / 25 MARS 2016, 91e ANNÉE No 12, 2016, 91, 145–168 http://www.who.int/wer

Polio vaccines: WHO Note de synthèse de Contents position paper – March, l’OMS sur les vaccins 145 Polio vaccines: WHO position 2016 antipoliomyélitiques – paper – March, 2016 mars 2016

Sommaire Introduction Introduction In accordance with its mandate to provide Conformément à son mandat qui est de donner 145 Note de synthèse de l’OMS sur les vaccins antipoliomyéli- guidance to Member States on health aux États Membres des conseils sur les ques- tiques – mars 2016 policy matters, WHO issues a series of tions de politique de santé, l’OMS publie une regularly updated position papers on série de notes de synthèse régulièrement actua- vaccines and combinations of vaccines lisées sur les vaccins et les associations vacci- against diseases that have an international nales contre les maladies ayant un impact sur public health impact. These papers are la santé publique au niveau international. Ces concerned primarily with the use of notes portent essentiellement sur l’utilisation vaccines in large-scale immunization des vaccins dans le cadre des programmes de programmes. They summarize essential vaccination à grande échelle. Elles résument les background information on diseases and informations essentielles sur les maladies et les vaccines and conclude with the current vaccins et présentent en conclusion la position WHO position on the use of vaccines actuelle de l’OMS concernant l’utilisation des worldwide. vaccins dans le contexte mondial. The position papers are designed to be Ces notes de synthèse s’adressent avant tout used mainly by national public health offi- aux fonctionnaires de la santé publique au cials and managers of immunization niveau national et aux administrateurs des programmes. They may also be of interest programmes de vaccination, mais elles peuvent to international funding agencies, vaccine également présenter un intérêt pour les orga- advisory groups, vaccine manufacturers, nismes internationaux de financement, les Inclusion of IPV into Routine the medical community, the scientific groupes consultatifs sur les vaccins, les fabri- media, and the public. The papers have cants de vaccins, le corps médical, les milieux been reviewed by external experts and scientifiques et le grand public. Elles ont été Immunisation Schedules WHO staff, and are reviewed and endorsed examinées par des experts externes et des by the WHO Strategic Advisory Group of membres du personnel de l’Organisation, et Polio Eradication and Endgame Strategic Plan (Polio Endgame Strategy) 2013–2018 was Experts on Immunization (SAGE) (http:// sont analysées et approuvées par le Groupe www.who.int/immunization/sage/en). The stratégique consultatif d’experts (SAGE) sur la developed in response to the World Health Assembly declaration in 2012 that polio is a GRADE methodology is used to system- vaccination de l’OMS (http://www.who.int/ global public health emergency. atically assess the quality of available immunization/sage/fr). La méthodologie evidence. A description of the processes GRADE est utilisée pour évaluer de manière WHO recommends the inclusion of at least one dose of IPV in the vaccination schedule followed for the development of vaccine systématique la qualité des éléments dispo- for all countries using OPV in the national immunisation programme. The objective of this position papers is available at: http://www. nibles. Une description du processus suivi WORLD HEALTH who.int/immunization/position_papers/ pour l’élaboration de ces notes est disponible IPV dose is to induce an immunity base that could be rapidly boosted should there be an ORGANIZATION position_paper_process.pdf à l’adresse: http://www.who.int/immunization/ outbreak of polio due to poliovirus type 2 following the removal of serotype 2 virus from Geneva position_papers/position_paper_process.pdf. OPV. Additionally, depending on the timing of the administration of the dose or doses ORGANISATION MONDIALE In response to the World Health Assembly En réponse à la déclaration de l’Assemblée DE LA SANTÉ of IPV, the inclusion of IPV may reduce risks for the development of vaccine-associated Genève (WHA) declaration in 2012 that polio mondiale de la Santé (WHA) de 2012 faisant paralytic poliomyelitis and could boost immunity against poliovirus types 1 and 3 in eradication constitutes a global public de l’éradication de la poliomyélite une urgence health emergency, the Polio Eradication de santé publique mondiale, le Plan straté- vaccine recipients. Annual subscription / Abonnement annuel Sw. fr. / Fr. s. 346.– and Endgame Strategic Plan 2013–2018 gique pour l’éradication de la poliomyélite et was developed. This plan includes the la phase finale 2013-2018 a été mis au point. 03.2016 ISSN 0049-8114 introduction of at least one dose of inac- Ce Plan prévoit l’introduction d’au moins une Printed in Switzerland tivated polio vaccine (IPV) into routine dose de vaccine antipoliomyélitique inactivé 145 these settings, type 2 vaccine virus interferes with Dans de tels contextes, le virus vaccinal de type 2 interfère avec Duration of protection Durée de la protection immunological responses to vaccine virus types 1 and 3; les réponses immunologiques aux virus vaccinaux de types 1 There is no evidence that protective immunity against Il n’existe pas de preuve que l’immunité protectrice acquise consequently type 2 virus induces seroconversion pref- et 3; en conséquence, le type 2 induit préférentiellement une paralytic disease wanes over time. After induction of contre la poliomyélitique paralytique disparaisse au cours du erentially, and children require multiple doses of OPV séroconversion et les enfants doivent recevoir de multiples active immunity either by vaccination or exposure to temps. Après l’induction d’une immunité active par vaccination in order to respond to all 3 serotypes. A clinical trial doses de VPO pour répondre à l’ensemble des 3 sérotypes. Un poliovirus, usually measured by circulating antibody ou exposition à des poliovirus, habituellement mesurée par le evaluating the immunogenicity of different OPV formu- essai clinique évaluant l’immunogénicité de différentes formu- titre, protection is life-long. However, as antibody titres titre d’anticorps circulants, la protection conférée s’exerce la vie lations – mOPV1, mOPV3, and bOPV – compared to lations de VPO (VPOm1, VPOm2 et VPOb) par rapport à celle decline over time and may fall below detectable levels, durant. Néanmoins, comme ces titres diminuent avec le temps tOPV in an Indian population found that seroconver- du VPOt dans une population indienne a constaté que les taux seroprevalence may not reflect the true immune status et deviennent parfois indétectables, la séroprévalence peut ne sion rates to poliovirus types 1 and 3 following immu- de séroconversion contre les poliovirus de types 1 et 3 après la of a given population. While seroconversion is a reliable pas refléter le statut immunitaire vrai d’une population donnée. nization with bOPV were significantly higher than those vaccination par le VPOb étaient significativement plus élevés correlate of immunity against paralytic disease, there is Si la séroconversion est un corrélat fiable de l’immunité contre induced by tOPV.33 Cumulative 2-dose seroconversion que ceux induits par le VPOt.33 Après 2 doses cumulées, la séro- no evidence that loss of detectable antibody puts immu- la poliomyélite paralytique, il n’existe pas d’élément prouvant for poliovirus type 1 was 90% for mOPV1 and 86% for conversion contre le poliovirus de type 1 était de 90% avec le nocompetent individuals at risk for paralytic disease. que la disparition d’une concentration détectable d’anticorps bOPV compared with 63% for tOPV, and for type 3 it VPOm1 et de 86% avec le VPOb, à comparer au taux de 63% expose un individu immunocompétent à un risque de contrac- was 84% for mOPV3 and 74% for bOPV compared with obtenu avec le VPOt et contre le poliovirus de type 3, elle était ter cette maladie. 52% for tOPV.34 de 84% avec le VPOm3 et de 74% avec le VPOb, à comparer à la valeur de 52% obtenue avec le VPOt.34 In Sri Lanka, a cross-sectional community-based survey Au Sri Lanka, une enquête transversale en communauté a été was carried out in 3 districts (Colombo, Badulla, and réalisée dans 3 districts (Colombo, Badulla et Killinochi) en A dose of OPV administered at birth, or as soon as Une dose de VPO administrée à la naissance ou dès que possible Killinochi) in 2014. All 4 age groups tested (9–11 months, 2014. L’ensemble des 4 tranches d’âge testées (9-11 mois, 3-4 ans, possible after birth, can significantly improve the sero- après celle-ci, peut notablement améliorer les taux de sérocon- 3–4 years, 7–9 years, and 15 years) demonstrated high 7-9 ans et 15 ans) ont présenté des taux élevés de séropréva- conversion rates to the types of polioviruses contained version contre les types de poliovirus contenus dans le vaccin seroprevalence levels. In the 15-year age group, the sero- lence. Dans le groupe des enfants de 15 ans, les taux de séro- in the vaccine after subsequent doses in some settings, après administration des doses ultérieures dans certains positivity rates were 97%, 100% and 75% for type 1, 2 positivité étaient respectivement de 97%, 100% et 75% contre and induce mucosal protection before enteric pathogens contextes, et induire une protection mucosale avant que des and 3, respectively.40 In this study and others, les types 1,2 et 3.40 Dans le cadre de cette étude et d’autres, la can interfere with the immune response.35, 36 Theoreti- agents pathogènes entériques ne puissent interférer avec la type 3 seroprevalence declined with increasing age, séroprévalence du type 3 diminuait avec l’âge, car les titres cally, giving the first OPV dose at a time when the infant réponse immunitaire.35, 36 Théoriquement, administrer la première since type 3 antibody titres are lower and fall below d’anticorps contre le type 3 sont plus faibles et chutent is still protected by maternally-derived antibodies may dose de VPO lorsque le nourrisson est encore protégé par des detectable levels earlier than titres for types 1 and 2. au-dessous du seuil de détectabilité plus tôt que les titres d’an- also prevent VAPP. anticorps d’origine maternelle peut aussi prévenir la PPAV. ticorps contre les types 1 et 2. Although data on birth dose seroconversion to OPV Bien que les données sur la séroconversion en réponse à la dose In Gambia, following routine vaccination, slightly En Gambie, suite à la vaccination systématique, on a observé rates show great variability – from low rates in India de naissance de VPO puissent présenter une grande variabilité declining antibody concentrations against type 1 were une légère baisse des concentrations d’anticorps contre le type (around 10%–15%), median rates in Egypt (32%), to – avec des taux bas en Inde (environ 10-15%), des taux moyens found in children aged 8–9 years compared with chil- 1 chez les enfants de 8-9 ans par rapport aux enfants de 3-4 ans, high rates in South Africa (76%) – data from Brazil, en Égypte (32%) et des taux élevés en Afrique du Sud (76%) – les dren aged 3–4 years, but in these age groups the percent- mais, dans les 2 tranches d’âge, les pourcentages d’enfants avec China, Ghana, and India demonstrate that, in general, données émanant du Brésil, de la Chine, du Ghana et de l’Inde ages of children with detectable antibody were almost des anticorps détectables étaient pratiquement identiques (88 et the birth dose increases the levels of poliovirus neutral- montrent qu’en général la dose à la naissance accroît les concen- identical (88% and 89%, respectively). Fewer children 89%, respectivement). Les enfants de la tranche 8-9 ans étaient izing antibodies and seroconversion rates achieved after trations d’anticorps neutralisants dirigés contre les poliovirus et aged 8–9 years than those aged 3–4 years had antibod- moins nombreux que ceux de la tranche 3-4 ans à posséder des completion of the routine vaccination schedule.37, 38 A les taux de séroconversion obtenus après achèvement du calen- ies against type 3 (78% versus 89%, p<0.001). Among anticorps contre le type 3 (78% contre 89%, p <0,001). Parmi systematic review of reports published between 1959 drier de vaccination systématique.37, 38 Une revue systématique 67 children who had received only 2 doses of tOPV, les 67 enfants ayant reçu 2 doses de VPOt, >80% présentaient and 2011 on seroconversion rates in infants 4–8 weeks des rapports publiés entre 1959 et 2011 sur les taux de sérocon- >80% retained neutralizing antibodies when tested encore des anticorps neutralisants lorsqu’ils subissaient un after a single birth dose (given ≤7 days after birth) version chez les nourrissons de 4-8 semaines après une dose after 5 years.41, 42 Given the limited time since first use dosage au bout de 5 ans.41, 42 Le VPOb ayant été utilisé pour la found that: (i) for tOPV the proportion of infants who unique à la naissance (administrée 7 jours ou moins après la of bOPV in 2009, no long-term data on the persistence première fois en 2009, la période écoulée depuis est relativement seroconverted at 8 weeks was in the range 6%–42% naissance) a relevé que: 1) pour le VPOt, le pourcentage de of antibody conferred by this vaccine are available. The courte et on ne dispose pas de données à long terme sur la (median: 25%) for poliovirus type 1, 2%–63% (median: nouveau-nés séroconvertis à 8 semaines se situait dans la plage higher initial immunogenicity of bOPV compared to persistance des anticorps induits par ce vaccin. La plus forte 38%) for type 2, and 1%–35% (median: 15%) for type 3; 6-42% (valeur médiane: 25%) pour le poliovirus de type 1, dans tOPV for types 1 and 3 suggests that the persistence of immunogénicité initiale du VPOb par rapport au VPOt contre (ii) for mOPV1, the seroconversion range was 10%–76% la plage 2-63% (valeur médiane: 38%) pour le type 2, et dans la antibody following vaccination with bOPV should be les types 1 et 3 laisse à penser que les anticorps formés suite (median: 31%); (iii) for mOPV3, the range was 12%–58% plage 1-35% (valeur médiane: 15%) pour le type 3; 2) que pour non-inferior or superior to that following tOPV. à la vaccination par le VPOb devraient persister au moins (median: 35%); and (iv) for the only study on bOPV, the le VPOm1, ce pourcentage était compris dans la plage 10-76% autant, sinon plus, que ceux dont la production est induite par seroconversion rate was 20% for type 1 and 7% for (valeur médiane: 31%); 3) que pour le VPOm3, il se trouvait dans le VPOt. type 3.39 la plage 12-58% (valeur médiane: 35%); et 4) que pour l’unique étude sur le VPOb, le taux de séroconversion était de 20% pour Co-administration with other vaccines Coadministration avec d’autres vaccins 39 le type 1 et de 7% pour le type 3. OPV is usually administered concurrently with other Le VPO est actuellement administré en même temps que vaccines including Bacillus Calmette-Guérin (BCG), d’autres vaccins dont le bacille Calmette-Guérin (BCG), le vaccin

33 Sutter RW et al. Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a 33 Sutter RW et al. Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, diphtheria- pertussis- tetanus (DPT), hepatitis B, antidiphtérique, antitétanique, anticoquelucheux (DTC), les randomised, double-blind, controlled trial. Lancet. 2010; 376 (9753):1682–1688. double-blind, controlled trial. Lancet. 2010; 376 (9753):1682–1688. measles, Haemophilus influenzae type b (Hib), pneumo- vaccins contre l’hépatite B, la rougeole et Haemophilus influen- 34 John TJ. Immunisation against polioviruses in developing countries. Rev Med Virol. 34 John TJ. Immunisation against polioviruses in developing countries. Rev Med Virol. 1993; coccal conjugate and/or rotavirus vaccines. No interfer- zae type b (Hib), le vaccin antipneumococcique conjugué et/ 1993; 3:149–160. 3:149–160. ence with regard to effectiveness or increased incidence ou les vaccins antirotavirus. Aucune interférence en termes 35 Bhaskaram P et al. Systemic and mucosal immune response to polio vaccination 35 Bhaskaram P et al. Systemic and mucosal immune response to polio vaccination with additional with additional dose in newborn period. J Trop Paediatrics. 1997; 43(4): 232–234. dose in newborn period. J Trop Paediatrics. 1997; 43(4): 232–234. 36 Grading of scientific evidence – table II: Birth dose of OPV. Available at http://www. 36 Cotation des preuves scientifiques – tableau II. Birth dose of OPV. Disponible uniquement en who.int/immunization/polio_grad_opv_birth_dose.pdf, accessed February 2016. langue anglaise sur http://www.who.int/immunization/polio_grad_opv_birth_dose.pdf, consul- 40 Gamage D et al. Achieving high seroprevalence against polioviruses in Sri Lanka- 40 Gamage D et al. Achieving high seroprevalence against polioviruses in Sri Lanka-Results from a té en février 2016. Results from a serological survey, 2014. J Epidemiol Glob Health. 2015 Dec;5(4 serological survey, 2014. J Epidemiol Glob Health. 2015 Dec;5(4 Suppl 1):S67–71 37 De-Xiang D et al. Immunization of neonates with trivalent oral poliomyelitis vaccine 37 De-Xiang D et al. Immunization of neonates with trivalent oral poliomyelitis vaccine (Sabin). Suppl 1):S67–71 (Sabin). Bull World Health Organ. 1986; 64(6):853–860. Bull World Health Organ. 1986; 64(6):853–860. 41 Nishio O et al. The trend of acquired immunity with live poliovirus vaccine and the 41 Nishio O et al. The trend of acquired immunity with live poliovirus vaccine and the effect of 38 John TJ et al. Monovalent type 1 oral poliovirus vaccine among infants in India: 38 John TJ et al. Monovalent type 1 oral poliovirus vaccine among infants in India: report of two effect of revaccination: follow up of vaccinees for ten years. J Biol Standardization. revaccination: follow up of vaccinees for ten years. J Biol Standardization. 1984; 12(1):1–10. report of two randomized double-blind controlled clinical trials. Vaccine. 2011 Aug randomized double-blind controlled clinical trials. Vaccine. 2011 Aug 5;29(34):5793–5801 1984; 12(1):1–10. 5;29(34):5793–5801 42 Grading of scientific evidence – table III: Antibody persistence. Available at http:// 42 Cotation des preuves scientifiques – tableau III. Antibody persistence. Disponible uniquement 39 Mateen FJ et al. Oral and inactivated poliovirus vaccines in the newborn: a review. 39 Mateen FJ et al. Oral and inactivated poliovirus vaccines in the newborn: a review. Vaccine. www.who.int/entity/immunization/polio_grad_duration_protection.pdf, accessed en langue anglaise sur http://www.who.int/entity/immunization/polio_grad_duration_protec- Vaccine. 2013; 31(21):2517–2524. 2013; 31(21):2517–2524. February 2016. tion.pdf, consulté en février 2016. 154 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 155 immunization schedules as a strategy to mitigate the (VPI) dans les calendriers de vaccination systématique en tant from only 2 countries in 2015 compared to 9 countries régressé, les pays notifiant des cas d’infection par ce type de potential consequences should any re-emergence of que stratégie pour atténuer les conséquences potentielles d’une in 2014. virus n’étant plus que 2 en 2015, contre 9 en 2014. type 2 poliovirus occur following the planned with- éventuelle réémergence de poliovirus de type 2 après le retrait The last case of poliomyelitis caused by naturally circu- Le dernier cas de poliomyélite causé par un PVS de type 2 drawal of Sabin type 2 strains from oral polio vaccine prévu des souches Sabin de type 2 du vaccin antipoliomyéli- lating WPV type 2 (WPV2) was recorded in India in (PVS2) naturellement circulant est apparu en Inde en 1999. (OPV).1 tique oral (VPO).1 1999. Global eradication of WPV2 was certified in 2015. L’éradication à l’échelle mondiale des PVS2 a été certifiée en This position paper on polio vaccines replaces the 2014 Cette note de synthèse actualisée sur les vaccins antipoliomyé- No case due to WPV type 3 (WPV3) has been detected 2015. Aucun cas dû à un PVS de type 3 (PVS3) n’a été détecté WHO position paper, and summarizes recent develop- litiques remplace la note précédente de l’OMS publiée en 2014 globally since 10 November 2012 in Nigeria. depuis le 10 novembre 2012 au Nigéria. ments in the field. The recommendations from the 2014 et résume les faits récents dans le domaine. Les recommanda- In the absence of cases of polio caused by WPV2 for En l’absence de cas de poliomyélite causé par un PVS2 depuis WHO position paper on the use of polio vaccine, in tions de cette précédente note sur l’utilisation du vaccin anti- >16 years, type 2 vaccine viruses which are components >16 ans, les virus vaccinaux de type 2 entrant dans la compo- particular on the addition of at least one dose of IPV poliomyélitique, en particulier concernant l’addition d’au moins of the current live OPV have become a significant cause sition du VPO vivant actuel sont devenus une cause d’ampleur for countries using exclusively OPV, remain valid. This une dose de VPI pour les pays qui utilisent exclusivement le of paralytic polio. It is now important to eliminate this significative de poliomyélite paralytique. Il est maintenant position paper reflects the global switch from trivalent VPO, restent valides. La nouvelle note de synthèse traite du vaccine-related disease burden. important d’éliminer la charge de morbidité liée à la vaccina- to bivalent OPV scheduled to take place in April 2016. passage à l’échelle mondiale du VPO trivalent au VPO bivalent tion. Recommendations on the use of polio vaccines have prévu en avril 2016. Les recommandations relatives à l’utilisa- been discussed on multiple occasions by SAGE, most tion des vaccins antipoliomyélitiques ont été discutées en de Pathogen Agent pathogène recently in October 2015; evidence presented at these multiples occasions par le SAGE et en dernier lieu en octobre meetings can be accessed at: http://www.who.int/immu- 2015; les éléments présentés lors de ces réunions peuvent être Polioviruses are human enteroviruses of the Picorna- Les poliovirus sont des entérovirus humains de la famille des nization/sage/previous/en/index.html. consultés à l’adresse: http://www.who.int/immunization/sage/ viridae family. Polioviruses are non-enveloped viruses Picornaviridae. Il s’agit de virus non enveloppés, avec un previous/en/index.html. with a single-stranded RNA genome and a protein génome constitué d’ARN monocaténaire et une capside protéi- capsid. The 3 serotypes of polioviruses have different nique. Les protéines de capside des 3 sérotypes de poliovirus Background Contexte antigenic sites in the capsid proteins. présentent des sites antigéniques différents. Polioviruses share most of their biochemical and Les poliovirus ont en commun avec d’autres entérovirus la Epidemiology Épidémiologie biophysical properties with other enteroviruses. They plupart de leurs propriétés biochimiques et biophysiques. Ils Poliomyelitis is an acute communicable disease caused La poliomyélite est une maladie transmissible aiguë causée par are resistant to inactivation by many common deter- résistent à l’inactivation par de nombreux détergents et désin- by any of 3 poliovirus serotypes (types 1, 2 or 3). In the l’un des 3 sérotypes de poliovirus (1, 2 ou 3). Avant l’ère des gents and disinfectants, including soaps, but are rapidly fectants courants, y compris les savons, mais sont rapidement pre-vaccine era when poliovirus was the leading cause vaccins, lorsque les poliovirus représentaient la principale cause inactivated by exposure to ultraviolet light. Viral infec- inactivés par une exposition à la lumière ultraviolette. L’infec- of permanent disability in children, almost all children d’incapacité permanente chez les enfants, la quasi-totalité de la tivity is stable for months at +4 °C and for several days tiosité virale est stable pendant plusieurs mois à +4° C et became infected by polioviruses, with on average 1 in population infanto-juvénile était infectée par ces virus et, en at +30 °C.2 pendant plusieurs jours à +30° C.2 200 susceptible individuals developing paralytic polio- moyenne, 1 individu sensible sur 200 contractait une poliomyé- myelitis.2 Polioviruses are spread by faecal-to-oral and lite paralytique.2 Les poliovirus se propagent par transmission Disease Maladie oral-to-oral transmission. Where sanitation is poor, fécale-orale ou orale-orale. Lorsque l’assainissement est insuf- faecal-to-oral transmission predominates, whereas oral- fisant, la transmission fécale-orale est prédominante, tandis que The incubation period is commonly 7–10 days (range La période d’incubation est habituellement de 7 à 10 jours to-oral transmission may be more common where stan- le mode de transmission oral-oral peut être plus courant dans 4–35 days). Most people infected with poliovirus do not (plage de variation: 4-35 jours). La plupart des personnes infec- dards of sanitation are high. In most settings, mixed les zones où les normes d’assainissement sont strictes. Dans la have symptoms; viral replication in the pharynx and tées par un poliovirus ne présentent pas de symptôme, la répli- patterns of transmission are likely to occur. plupart des contextes, on rencontrera probablement un schéma gastrointestinal tract results in virus excretion in saliva cation virale dans le tractus gastro-intestinal ou le pharynx de transmission mixte. and faeces. Approximately 25% of those infected develop entraînant l’excrétion du virus dans la salive et les selles. Envi- transient minor symptoms, including fever, headache, ron 25% des individus infectés manifestent des symptômes In 1988, when the annual global burden of paralytic En 1988, alors que la charge annuelle mondiale de poliomyélite malaise, nausea, vomiting and sore throat. In some indi- mineurs et transitoires, qui peuvent être de la fièvre, des cépha- poliomyelitis was estimated to be >350 000 cases, with paralytique était estimée à plus de 350 000 cas, avec une trans- viduals (approximately 4%) with this minor illness, lées, une sensation de malaise, des nausées, des vomissements wild poliovirus (WPV) transmission reported in mission de poliovirus sauvages (PVS) signalée dans >125 pays,3 signs of meningeal irritation develop, with neck stiff- ou un mal de gorge. Chez certaines personnes présentant cette >125 countries,3 the WHA resolved to eradicate polio- l’Assemblée mondiale de la Santé a pris la résolution d’éradi- ness, severe headache, and pain in limbs, the back and forme mineure de la maladie (approximativement 4%), des myelitis by the year 2000 and the Global Polio Eradica- quer la poliomyélite d’ici 2000 et l’Initiative mondiale pour the neck, suggestive of aseptic meningitis (non-para- signes d’irritation méningée apparaissent, y compris une tion Initiative (GPEI) was established. Worldwide, l’éradication de la poliomyélite (IMEP) a été mise en place. À lytic polio). This form of polio lasts between 2 and raideur de la nuque, des céphalées sévères ou des douleurs dans sustained use of polio vaccines since 1988 has led to l’échelle de la planète, l’utilisation suivie des vaccins antipolio- 10 days and in almost all cases recovery is complete. les membres, le dos ou la nuque, orientant vers une méningite a precipitous drop in the global incidence of poliomy- myélitiques a conduit à une chute vertigineuse de l’incidence aseptique (poliomyélite non paralytique). Cette forme de polio- elitis by >99% and the number of countries with mondiale de la poliomyélite de >99% et le nombre de pays myélite dure entre 2 et 10 jours et aboutit à un rétablissement endemic polio from 125 to just 2 in 2015 (Afghanistan d’endémie pour cette maladie est passé de 125 à 2 seulement complet dans presque tous les cas. and Pakistan). Of the 359 reported cases of paralytic (Afghanistan et Pakistan). Sur les 359 cas notifiés de poliomyé- polio caused by wild polioviruses with onset in 2014, all lite paralytique provoquée par un poliovirus sauvage apparus Paralytic poliomyelitis is a rare outcome and occurs La poliomyélite paralytique est rare et se développe lorsque le were due to WPV type 1 (WVP1). In contrast, only en 2014, la totalité était due à un PVS de type 1 (PVS1). when poliovirus enters the central nervous system by poliovirus pénètre dans le système nerveux central par le flux 73 cases with onset in 2015, all due to WPV1, were À contrario, 73 cas seulement, tous dus à des PVS1, ont été peripheral or cranial nerve axonal flow and replicates axonal dans les nerfs périphériques ou crâniens et se réplique reported, the lowest number for any calendar year on notifiés comme apparus en 2015, soit le chiffre le plus faible in anterior horn cells (motor neurons) of the spinal dans les cellules de la corne antérieure de la moelle épinière record. The geographic distribution of WPV transmis- enregistré jusqu’à présent pour une année calendaire. Les zones cord. It is observed in <1% of poliovirus infections in (neurones moteurs). Elle est observée chez <1% des enfants de sion has been progressively reduced, with cases reported géographiques de transmission des PVS ont progressivement children <5 years of age, varying with serotype and age. <5 ans infectés par le poliovirus, avec des variations en fonction The ratio of paralytic cases to infections was estimated du sérotype et de l’âge. La proportion de cas paralytiques parmi per 100 infections at approximately 0.5 for serotype 1, les individus infectés par un poliovirus a été estimée, pour 0.05 for serotype 2, and 0.08 for serotype 3, based on 100 infections à approximativement 0,5 pour le sérotype 1, à data from 15 countries.2 Depending on the degree and 0,05 pour le sérotype 2 et à 0,08 pour le sérotype 3, d’après des 1 Polio Eradication and Endgame Strategic Plan 2013–2018. Available at http://www. 1 Plan stratégique pour l’éradication de la poliomyélite et la phase finale 2013-2018. Disponible 2 polioeradication.org/resourcelibrary/strategyandwork.aspx, accessed March 2016. à l’adresse: http://www.polioeradication.org/Resourcelibrary/Strategyandwork.aspx, consulté extent to which motor neurons are affected, temporary données émanant de 15 pays. Selon l’intensité et l’ampleur de en mars 2016. or permanent paralysis of the affected muscles may l’atteinte des neurones moteurs, il peut s’ensuivre une paralysie 2 Bernier R. Some observations on poliomyelitis lameness surveys. Rev Infect Dis. 2 Bernier R. Some observations on poliomyelitis lameness surveys. Rev Infect Dis. 1984; May- ensue. In rare cases, viral destruction of bulbar cells temporaire ou permanente des muscles touchés. Dans de rares 1984; May-Jun:6, Suppl 2:S371–375. Jun:6 Suppl 2:S371–375. 3 Sutter RW et al. Poliovirus vaccine-live. In: Plotkin SA, Orenstein WA, Offit PA. 3 Sutter RW et al. Poliovirus vaccine-live. In Plotkin SA, Orenstein WA, Offit PA. Vaccines, results in respiratory paralysis and death. cas, la destruction par le virus des cellules bulbaires entraîne Vaccines, 6th edition 2013. Philadelphia: Elsevier-Saunders, 598–645. 6th edition 2013. Philadelphia: Elsevier-Saunders, 598–645. une paralysie respiratoire et la mort. 146 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 147 The typical clinical manifestation of paralytic poliomy- La manifestation clinique typique de la poliomyélite paraly- other environmental samples for the presence of polio- compatibles avec une poliomyélite ou non poliomyélitiques. La elitis is acute flaccid paralysis (AFP) affecting the limbs, tique est la paralysie flasque aiguë (PFA) qui touche les virus. surveillance de la PFA est complétée par une surveillance envi- principally the legs, usually asymmetrically, while sensa- membres, principalement les jambes, habituellement de façon ronnementale, qui consiste notamment à analyser des échantil- tion remains intact. Persistent paralysis and resulting asymétrique, la sensibilité restant intacte. Une paralysie persis- lons d’eaux usées ou d’autres prélèvements environnementaux deformities are common sequelae. The case-fatality tante et les déformations qui en résultent font partie des pour rechercher la présence de poliovirus. rates among paralytic cases range from 5% to 10% in séquelles courantes. Le taux de létalité parmi les cas de para- children and from 15% to 30% in adolescents and lysie se situe entre 5 et 10% chez l’enfant et entre 15 et 30% Naturally-acquired immunity Immunité acquise de manière naturelle adults, predominantly associated with bulbar involve- chez l’adolescent et l’adulte, en association dans la majorité des Immunocompetent individuals infected by poliovirus Chez les sujets immunocompétents infectés par le poliovirus, ment. Post-polio syndrome, with symptoms appearing cas avec une atteinte bulbaire. Un syndrome postpoliomyéli- develop immunity through humoral (circulating anti- une immunité se développe par le biais des réponses immuni- 15–30 years after recovery from the original paralytic tique, dont les symptômes se manifestent 15 à 30 jours après body) and mucosal (secretory immunoglobulin A) taires humorale (anticorps circulants) et mucosale (immuno- attack, occurs in 25%–50% of cases, with symptoms la guérison de l’attaque paralytique initiale, apparaît dans 25 à immune responses. The presence in blood of neutral- globuline A sécrétoire). La présence dans le sang d’anticorps including acute or increased muscular weakness, pain 50% des cas; ces symptômes incluent une faiblesse musculaire izing antibody against polioviruses indicates protective neutralisants dirigés contre les poliovirus indique l’acquisition in the muscles, and fatigue. accrue ou aiguë, des douleurs musculaires et une grande fatigue. immunity; detectable antibody is an excellent correlate d’une immunité protectrice; cette présence à un niveau détec- of protection against paralytic disease.5 However, immu- table est extrêmement bien corrélée à l’existence d’une protec- Treatment Traitement nity is serotype-specific with no cross-protection tion contre la forme paralytique de la maladie.5 Cependant, No specific anti-viral drugs are available for poliomy- Aucun médicament antiviral spécifique n’est disponible contre between serotypes. Mucosal immunity decreases the l’immunité obtenue est spécifique d’un sérotype, sans protec- elitis, although some poliovirus antiviral compounds la poliomyélite, même si certains antiviraux visant les poliovi- replication and excretion (shedding) of the virus, and tion croisée entre sérotypes différents. L’immunité mucosale are currently being developed (see section on immuno- rus sont actuellement en cours de mise au point (voir le para- thus provides a potential barrier to its transmission. réduit la réplication et l’excrétion du virus et fait ainsi poten- compromised persons). Treatment consists of support- graphe consacré aux personnes immunodéprimées). Le traite- Individuals with B-cell related immunodeficiency disor- tiellement obstacle à sa transmission. Les individus souffrant ive, symptomatic care during the acute phase, including ment consiste en des soins symptomatiques et de soutien ders are at increased risk for paralytic manifestations d’un déficit immunitaire en lymphocytes B sont exposés à un respiratory support in cases with respiratory muscle pendant la phase aiguë, y compris une assistance respiratoire of poliomyelitis or prolonged excretion of virus. risque accru de manifestations paralytiques de la poliomyélite paralysis. Neuromuscular sequelae are mitigated by dans les cas de paralysie des muscles de la respiration. Les ou d’excrétion prolongée du virus. physiotherapy and orthopaedic treatment. séquelles neuromusculaires sont atténuées par la kinésithérapie et le traitement orthopédique. Vaccines Vaccins IPV, first developed and licensed in 1955, is given by Le VPI, mis au point en premier et homologué en 1955, est Diagnosis Diagnostic injection and is available only in trivalent form contain- administré par injection et n’est disponible que dans une The diagnosis of paralytic poliomyelitis is supported Le diagnostic de la poliomyélite paralytique s’appuie sur: ing the 3 virus serotypes PV1, PV2 and PV3. OPV was formulation trivalente, contenant les 3 poliovirus sérotypés PV1, by: (i) clinical course, (ii) virological testing, and i) l’évolution clinique, ii) les tests virologiques et iii) le déficit initially licensed in 1961 as a monovalent (mOPV) PV2 et PV3. Le VPO a été initialement homologué en 1961 en (iii) residual neurologic deficit 60 days after onset of neurologique résiduel 60 jours après l’apparition des symp- vaccine, followed by a trivalent version (tOPV) licensed tant que vaccin monovalent (VPOm), puis dans une version symptoms.1 tômes.1 in 1963. trivalente (VPOt) en 1963. Laboratory testing, such as the measurement of anti- Des analyses de laboratoire, comme le dosage des anticorps (en Bivalent OPV (bOPV containing types 1 and 3 Sabin Un VPO bivalent (VPOb contenant des virus Sabin de types 1 bodies (especially pre- and post-onset of paralysis), and particulier avant et après l’apparition de la paralysie), ainsi que viruses) has been licensed and used in some settings et 3) a été homologué. Il est utilisé dans certains contextes other studies, such as magnetic resonance imaging, elec- d’autres méthodes d’investigation comme l’imagerie par réson- since December 2009. Following the planned global depuis décembre 2009. Après le passage planifié du VPOt au tromyography, and/or nerve conduction tests, can help nance magnétique (IRM), l’électromyographie et/ou les tests de switch from tOPV to bOPV in April 2016, tOPV will no VPOb en avril 2016, le VPOt ne sera plus disponible et sera strengthen or exclude the diagnosis of poliomyelitis. conduction nerveuse, peuvent contribuer à renforcer ou exclure longer be available and will be replaced by bOPV. There- remplacé par le VPOb. Par la suite, le seul VPO renfermant le un diagnostic de poliomyélite. after, the only OPV containing serotype 2 will be type sérotype 2 sera le VPO monovalent type 2 (VPOm2), avec des 2 monovalent OPV (mOPV2) stockpiled for emergency stocks disponibles pour faire face aux situations d’urgence (voir WHO uses a sensitive screening case definition for the Dans le cadre du dépistage de la maladie, l’OMS utilise une use (see below). plus loin). identification of AFP cases and for investigation of any définition de cas sensible pour l’identification des cas dePFA case of AFP in a person younger than 15 years or in a et pour l’investigation de tout cas de PFA chez une personne 1. Oral poliovirus vaccine (OPV) 1. Vaccin antipoliomyélitique oral (VPO) person of any age in whom poliomyelitis is suspected. <15 ans ou chez une personne d’âge quelconque que l’on However, virological examination is essential for confir- suspecte d’être atteinte de poliomyélite. Néanmoins, l’examen Vaccine characteristics Caractéristiques du vaccin mation of the diagnosis of poliomyelitis; this involves virologique est essentiel pour confirmer le diagnostic de polio- OPV is composed of live attenuated polioviruses derived Le VPO contient des poliovirus atténués vivants, dérivés par detection of poliovirus from the stools of patients with myélite; il suppose la détection du poliovirus dans les selles des of their parent WPV strains by passage in nonhuman passage de leurs souches parentes (PVS) dans des cellules d’origine AFP and further characterization of the isolated polio- patients souffrant de PFA et la caractérisation plus poussée du cells to obtain the 3 vaccine strains (Sabin 1, 2, and 3). non humaines en vue d’obtenir les 3 souches vaccinales (Sabin 1, virus to determine whether it is vaccine-associated, poliovirus isolé pour déterminer s’il s’agit d’un virus associé Attenuation of the virus in cell culture greatly reduces 2 et 3). L’atténuation du virus par cultures successives réduit gran- 4 4 vaccine-derived or wild virus. Molecular diagnostics au vaccin, dérivé de celui-ci ou sauvage. Des méthodes de its neurovirulence and transmissibility.6 dement sa neurovirulence et sa capacité de transmission.6 such as polymerase chain reaction are used to differen- diagnostic moléculaires comme l’amplification génique (PCR) tiate WPV, VDPV, and Sabin-like poliovirus. In addition sont employées pour différencier les PVS, les PVDV et les polio- There have been several licensed formulations of OPV: (i) Plusieurs formulations de VPO ont été homologuées: i) une all discordant poliovirus isolates are partially sequenced virus analogues d’une souche Sabin. En outre, tous les isole- monovalent OPVs against type 1 (mOPV1), type 2 (mOPV2) forme monovalente contre le type 1 (PVOm1), contre le type 2 to determine their origin and relatedness to other ments de poliovirus pour lesquels les tentatives de catégorisa- or type 3 (mOPV3); (ii) bivalent OPV (bOPV) containing (PVOm2) ou le type 3 (VPOm3); ii) une forme bivalente (VPOb) isolates. According to the laboratory results and review tion donnent des résultats contradictoires sont partiellement types1 and 3; and (iii) trivalent (tOPV) containing types 1, contenant les types1 et 3; et iii) une forme trivalente (VPOt) 7 7 by national polio expert committees, cases are further séquencés pour déterminer leur origine et leur degré de parenté 2 and 3. renfermant les types 1, 2 et 3. classified as confirmed, polio-compatible, or polio-nega- avec d’autres isolements. En fonction des résultats de labora- tive. The AFP surveillance is supplemented by environ- toire et de l’examen par un comité national d’experts de la 5 Sutter RW et al. Defining surrogate serologic tests with respect to predicting pro- 5 Sutter RW et al. Defining surrogate serologic tests with respect to predicting protective vaccine tective vaccine efficacy: Poliovirus vaccination. Williams JC, Goldenthal KL, Burns D, efficacy: Poliovirus vaccination. Williams JC, Goldenthal KL, Burns D, Lewis BP (eds), in Combi- mental surveillance which involves testing sewage or poliomyélite, les cas sont ensuite classés comme confirmés, Lewis BP (eds), in Combined Vaccines and Simultaneous Administration: Current ned Vaccines and Simultaneous Administration: Current Issues and Perspectives. New York Aca- Issues and Perspectives. New York Academy Sciences, New York, 1995; 289–299. demy Sciences, New York, 1995; 289–299. 6 Sabin AB, et al. History of Sabin attenuated poliovirus oral live vaccine strains. J Biol 6 Sabin AB, et al. History of Sabin attenuated poliovirus oral live vaccine strains. J Biol Standardi- Standardization. 1973; 1:115–118. zation. 1973; 1:115–118. 7 Recommendations to assure the quality, safety and efficacy of live attenuated polio- 7 Recommendations to assure the quality, safety and efficacy of live attenuated poliomyelitis myelitis vaccine (oral). [Replacement of: WHO Technical Report Series (TSR) 904, vaccine (oral). [Replacement of: WHO Technical Report Series (TRS) 904, Annex 1 and Addendum Annex 1 and Addendum TRS 910, Annex 1]. Geneva, World Health Organiza- TRS 910, Annex1]. Genève: Organisation mondiale de la Santé; 2012. Disponible uniquement 4 WHO-IVB, Polio Laboratory Manual 2004. Available at http://whqlibdoc.who.int/ 4 WHO-IVB, Polio Laboratory Manual, 2004. Disponible sur http://whqlibdoc.who.int/hq/2004/ tion,2012. Available at http://www.who.int/biologicals/vaccines/BS2185_OPV_ en langue anglaise à l’adresse suivante: http://www.who.int/biologicals/vaccines/BS2185_ hq/2004/WHO_IVB_04.10.pdf, accessed February 2016. WHO_IVB_04.10.pdf, consulté en février 2016. Post_ECBS_DB_TZ_DBFinal12Feb2013.pdf, accessed February 2016. OPV_Post_ECBS_DB_TZ_DBFinal12Feb2013.pdf, consulté en février 2016. 148 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 149 The eradication of indigenous WPV2 in 1999, coupled L’éradication des PVS2 autochtones en 1999, ainsi que l’émer- India10 and Iran.11 The main factors contributing to this maladie en fonction de l’âge étant centrée sur la tranche d’âge with the continuing emergence of neurovirulent circu- gence en continu de poliovirus circulants dérivés d’une souche difference are believed to be lower immune responsive- 1-4 ans, comme le montrent des données provenant d’Inde10 et lating type 2 vaccine-derived polioviruses (cVDPV2s) as vaccinale de type 2 neurovirulants (PVDV2c) et de poliomyé- ness to OPV and higher prevalence of maternally- d’Iran.11 On pense que les principaux facteurs contribuant à well as vaccine-associated paralytic poliomyelitis lites paralytiques associées au vaccin (PPAV), ont amené l’OMS derived antibody in populations in low-income settings. cette différence sont la plus faible réactivité immunitaire au (VAPP), led to the recommendation that there should à recommander la cessation coordonnée à l’échelle mondiale The introduction of one dose of IPV prior to vaccina- VPO et la plus forte prévalence des anticorps d’origine mater- be coordinated global cessation of use of the type 2 de l’utilisation de la composante du VPO dirigée contre le tion with OPV led to the elimination of VAPP in nelle dans les populations des zones à faible revenu. L’introduc- component of OPV and a switch from tOPV to bOPV; type 2 et le passage du VPOt au VPOb, dont le SAGE a préconisé Hungary.12 tion d’une dose de VPI avant la vaccination par le VPO a abouti this was recommended by SAGE to take place in April qu’il s’effectue en avril 2016. Après cette transition, le VPOm2, à l’élimination de la PPAV en Hongrie.12 2016. After the switch, mOPV2, which is licensed for homologué pour répondre à une éventuelle flambée à l’aide outbreak response using an emergency stockpile, will d’un stock d’urgence, sera par la suite destiné uniquement à Vaccine-derived polioviruses (VDPVs) Poliovirus dérivés d’une souche vaccinale (PVDV) then be used solely for this purpose, e.g. following an cette fin, par exemple suite à l’émergence de PVDV2c ou de The attenuated viruses in live OPV vaccines (Sabin Les virus atténués présents dans les vaccins VPO vivants (virus emergence of cVDPV2 or WPV2. PVS2. viruses) may, through prolonged replication in an indi- Sabin) peuvent, à l’issue d’une réplication prolongée chez un OPV is administered as 2 drops (~0.1 mL), directly into Le VPO s’administre en introduisant 2 gouttes (~0,1 ml) direc- vidual or in a community, re-acquire the neurovirulence individu ou dans une collectivité, réacquérir les caractéristiques the mouth. It is highly heat-sensitive and must be kept tement dans la bouche. C’est un vaccin très sensible à la chaleur, and transmissibility characteristics of WPV. They may de neurovirulence et de transmissibilité des PVS. Ils peuvent then become cVDPVs that cause isolated cases or devenir des PVDVc, à l’origine de cas isolés ou de flambées de frozen for long-term storage or, after thawing, at qui doit être conservé à l’état congelé pour un stockage de 13, 14, 15 13, 14, 15 temperatures between +2 °C and +8 °C for a maximum longue durée ou après décongélation, à une température outbreaks of paralytic poliomyelitis. During 2011– poliomyélite paralytique. Au cours de la période 2011-2015, of 6 months. Vaccine vial monitors give a visual indica- comprise entre 2 °C et +8 °C pendant 6 mois au maximum. La 2015, almost 90% of reported cVDPV cases (204/230) près de 90% des cas de PVDVc notifiés (204/230) étaient associés tion of whether the vaccine has been kept at the correct pastille de contrôle placée sur les flacons de vaccin donne une were associated with the type 2 component of tOPV. à la composante de type 2 du VPOt. temperature conditions. indication visuelle du respect des conditions de température VDPVs are genetically divergent forms of the original Les PVDV sont des formes génétiquement divergentes du virus pendant la conservation. Sabin vaccine virus conventionally defined by >1% vaccinal Sabin original, définies par convention comme présen- genetic divergence (or >10 nucleotide [nt] changes) for tant un taux de divergence génétique >1% (ou >10 modifications Safety of OPV Innocuité du VPO PV1 and PV3 and >0.6% (or >6 nt changes) for PV2. nucléotidiques [nt]) pour le PV1 et le PV3 et >0,6% (ou >6 modi- The only serious adverse events associated with OPV Les seules manifestations indésirables graves associées au VPO These viruses are further subdivided into 3 categories: fications nt) pour le PV2. Ces virus se subdivisent ensuite en3 are rare cases of vaccine-associated paralytic poliomy- sont les cas rares de poliomyélite paralytique associés à la (1) cVDPVs, when evidence of person-to-person trans- catégories: 1) les PVDVc lorsqu’il existe des preuves d’une trans- elitis, which can occur in vaccinated individuals or their vaccination, qui peuvent apparaître chez des individus vaccinés mission in the community exists; (2) immunodeficiency- mission interhumaine dans la collectivité; 2) les PVDV associés contacts, and the emergence of vaccine-derived polio- ou leurs contacts, et l’émergence de poliovirus dérivés d’une associated VDPVs (iVDPVs), which are isolated from à une immunodéficience (PVDVi), qui sont isolés chez certaines viruses.2 All available evidence indicates that OPV is souche vaccinale.2 Tous les éléments disponibles indiquent que some people with primary B-cell or combined immu- personnes souffrant d’un déficit primaire en lymphocytes B ou non-teratogenic and safe to administer to pregnant le VPO n’est pas tératogène et peut être administré sans risque nodeficiency disorders (with defects in antibody d’immunodéficience combinée (chez lesquelles la production women and HIV-infected persons. Since bOPV contains aux femmes enceintes et aux personnes infectées par le VIH. production) who may have prolonged VDPV infections d’anticorps est déficiente) présentant des infections prolongées only 2 of the 3 components of tOPV, its safety profile is Le VPOb ne renfermant que 2 des 3 composantes du VPOt, on (in individual cases excretion has been reported to par des PVDV (dans certains cas, une excrétion persistant sur 10 assumed to be better than that of tOPV, because suppose que son profil d’innocuité est meilleur que celui du persist for 10 years or more16, 17); and (3) ambiguous ans ou plus a été rapportée16, 17) et 3) les PVDV ambigus (PVDVa), 26%–31% of VAPP cases are caused by Sabin type 2 VPOt, car 26 à 31% des cas de PPAV sont causés par des virus VDPVs (aVDPVs), which are either clinical isolates from que l’on trouve dans des isolements cliniques provenant d’indi- viruses.8 Sabin de type 2.8 persons with no known immunodeficiency, or sewage vidus sans déficit immunitaire connu ou dans des isolements isolates of unknown origin.14 effectués sur des eaux usées d’origine inconnue.14 Vaccine-associated paralytic poliomyelitis (VAPP) Poliomyélite paralytique associée à la vaccination (PPAV) The term ‘persistent cVDPV’ refers to cVDPVs that On désigne par le terme «PVDVc persistants» des PVDVc qui Cases of VAPP are clinically indistinguishable from Les cas de PPAV sont cliniquement impossibles à distinguer continue to circulate for >6 months following detection. continuent de circuler pendant >6 mois après leur détection. poliomyelitis caused by WPV. Given the complexities of d’une poliomyélite causée par un PVS. Compte tenu de la Persistent cVDPVs represent programmatic failures to Les PVDVc persistants représentent des échecs programma- 9 9 VAPP diagnosis and classification, additional follow-up complexité du diagnostic des PPAV et de leur classification, un contain the cVDPV outbreak within 6 months of detec- tiques pour endiguer la flambée de PVDVc dans les 6 mois and review by a national expert classification committee suivi et un examen complémentaires par un comité national tion. suivant sa détection. is necessary, and consequently there are limited data on d’experts de la classification sont nécessaires et on dispose donc VAPP incidence from developing countries. The inci- de peu de données sur l’incidence des PPAV en provenance des In July 2015, the GPEI revised the definition of cVDPV En juillet 2015, l’IMEP a révisé la définition d’un PVDVc en dence of VAPP has been estimated at 2–4 cases/million pays en développement. Cette incidence a été estimée à 2-4 cas/ to enhance its sensitivity.18 In the new guidelines renforçant sa sensibilité.18 Dans les nouvelles lignes directrices, birth cohort per year in countries using OPV.8 million d’individus d’une cohorte de naissance et par an dans les pays utilisant le VPO.8 10 Kohler KA et al. Vaccine-associated paralytic poliomyelitis in India during 1999: 10 Kohler KA et al. Vaccine-associated paralytic poliomyelitis in India during 1999: decreased risk Available data suggest differences in the epidemiology Les données disponibles suggèrent l’existence de différences decreased risk despite massive use of oral polio vaccine. Bull World Health Organ. despite massive use of oral polio vaccine. Bull World Health Organ. 2002; 80(3):210–216. 2002; 80(3):210–216. of VAPP in developing and industrialized countries. In dans l’épidémiologie des PPAV entre les pays en développement 11 Considerations for the timing of a single dose of IPV in the routine immunization 11 Considerations for the timing of a single dose of IPV in the routine immunization schedule the latter, VAPP occurs mainly in early infancy associ- et les pays industrialisés. Dans ces derniers, la PPAV apparaît schedule http://www.who.int/immunization/sage/meetings/2013/november/1_Sut- http://www.who.int/immunization/sage/meetings/2013/november/1_Sutter_IPV_age_tech_ ated with the first dose of OPV and decreases sharply principalement pendant la petite enfance, en association avec ter_IPV_age_tech_background_14_October_2013_final.pdf, accessed February background_14_October_2013_final.pdf , consulté en février 2016. 2016. (>10 fold) with subsequent OPV doses. In lower-income la première dose de VPO et diminue très fortement (d’un 12 Dömök I. Experiences associated with the use of live poliovirus vaccine in 12 Dömök I. Experiences associated with the use of live poliovirus vaccine in Hungary,1959–1982. countries, which experience relatively lower rates of facteur supérieur à 10) avec les doses de VPO suivantes. Dans Hungary,1959–1982. Rev Inf Dis. 1984; 6(Suppl. 2):S413–S418. Rev Inf Dis. 1984; 6(Suppl. 2):S413–S418. vaccine seroconversion, this decline is more gradual les pays disposant de moindres revenus, où les taux de séro- 13 Estívariz CF et al. A large vaccine-derived poliovirus outbreak on Madura Island– 13 Estívariz CF et al. A large vaccine-derived poliovirus outbreak on Madura Island–Indonesia. J Inf and VAPP may occur with second or subsequent doses conversion avec le vaccin sont relativement plus bas, cette dimi- Indonesia. J Inf Dis. 2005; 197:347–354. Dis. 2005; 197:347–354. 14 Jenkins HE et al. Implications of a circulating vaccine-derived poliovirus in Nigeria 14 Jenkins HE et al. Implications of a circulating vaccine-derived poliovirus in Nigeria for polio of OPV, with the age distribution concentrated among nution est plus progressive et une PPAV peut se déclarer avec for polio eradication. N Eng J Med. 2010; 362:2360–2369. eradication. N Eng J Med. 2010; 362:2360-2369. children aged 1–4 years, as demonstrated by data from la deuxième dose de VPO ou les suivantes, la distribution de la 15 Duintjer Tebbens RJ et al. Oral poliovirus vaccine evolution and insights relevant to 15 Duintjer Tebbens RJ et al. Oral poliovirus vaccine evolution and insights relevant to modeling modeling the risks of circulating vaccine-derived polioviruses (cVDPVs). Risk Anal the risks of circulating vaccine-derived polioviruses (cVDPVs). Risk Anal 2013;23(4):680-702. 2013;23(4):680–702. 16 See No. 42, 2006, pp. 398–404. 16 Voir No 42, 2006, pp. 398-404. 17 Duintjer Tebbens RJ et al. Modeling the prevalence of immunodeficiency-associated 17 Duintjer Tebbens RJ et al. Modeling the prevalence of immunodeficiency-associated long-term long-term vaccine-derived poliovirus excretors and the potential benefits of vaccine-derived poliovirus excretors and the potential benefits of antiviral drugs. BMC Infect Dis 8 Platt LR et al. Vaccine-associated paralytic poliomyelitis: a review of the epidemio- 8 Platt LR et al. Vaccine-associated paralytic poliomyelitis: a review of the epidemiology and esti- antiviral drugs. BMC Infect Dis 2015;15(379):doi:10.1186/s12879-015-1115-5. 2015;15(379):doi:10.1186/s12879-015-1115-5. logy and estimation of the global burden. J Infect Dis. 2014;210 suppl 1:S380–9. mation of the global burden. J Infect Dis. 2014;210 suppl 1:S380–9. 18 Global Polio Eradication Initiative (2015). Reporting and classification of vaccine- 18 Global Polio Eradication Initiative (2015). Reporting and classification of vaccine-derived polio- 9 Sutter RW et al. A new epidemiologic and laboratory classification system for para- 9 Sutter RW et al. A new epidemiologic and laboratory classification system for paralytic polio- derived polioviruses. Available at http://www.polioeradication.org/Portals/0/ viruses. Disponible sur http://www.polioeradication.org/Portals/0/Document/Resources/VDPV_ lytic poliomyelitis cases. Am Public Health. 1989; 79:495–498. myelitis cases. Am Public Health. 1989; 79:495–498. Document/Resources/VDPV_ReportingClassification.pdf, accessed February 2016. ReportingClassification.pdf, consulté en février 2016. 150 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 151 cVDPVs are defined as genetically linked VDPVs isolated les PVDVc sont définis comme: des PVDV génétiquement liés During the first 4–6 weeks following OPV vaccination, Pendant les 4 à 6 premières semaines suivant la vaccination, la from: (i) at least 2 individuals – not necessarily AFP isolés: 1) chez au moins 2 individus – non nécessairement des the vast majority of non-immune vaccine recipients grande majorité des personnes qui étaient non immunisées cases – who are not household contacts; (ii) one indi- cas de PFA – qui ne sont pas des contacts domestiques, 2) chez shed Sabin poliovirus in nasopharyngeal secretions and lorsqu’elles avaient reçu le vaccin excrètent le poliovirus Sabin vidual and one or more environmental surveillance (ES) un individu et dans un ou plusieurs échantillons fournis par la faeces. In unvaccinated populations, these vaccine dans leurs sécrétions nasopharyngées et leurs selles. Parmi les samples; or (iii) at least 2 ES samples if they were surveillance environnementale, ou 3) dans au moins 2 échan- viruses are easily transmitted within and to a lesser populations non vaccinées, ces virus vaccinaux se transmettent collected at more than one distinct ES collection site tillons environnementaux s’ils ont été recueillis dans plus d’un degree outside households, thereby vaccinating and facilement au sein des foyers et dans une moindre mesure à (no overlapping of catchment areas), or from one site site de collecte pour la surveillance environnementale distincts inducing immunity in persons not reached directly by l’extérieur, en provoquant une vaccination ou en induisant une if collection was more than 2 months apart, or a single (sans recouvrement des zones de captage), ou encore dans un immunization programmes. In addition, such transmis- immunité chez des personnes non touchées directement par les VDPV isolate with genetic features indicating prolonged seul site si les échantillons ont été recueillis à plus de 2 mois sion may boost intestinal immunity in some persons programmes de vaccination. En outre, une telle transmission circulation (i.e. a number of nt changes from parent d’intervalle, ou bien comme un isolement unique de PVDV, and help to increase community protection if virulent peut renforcer l’immunité intestinale chez certains individus et Sabin strains suggesting ≥1.5 years of circulation, or présentant des caractéristiques génétiques qui indiquent une viruses are introduced. contribuer à accroître la protection collective en cas d’intro- 15 nt changes). circulation prolongée (c’est-à-dire un nombre de modifications duction de virus virulents. nt par rapport aux souches Sabin parentes laissant supposer While non-immune vaccine recipients shed Sabin poliovi- Si les personnes non immunisées recevant le vaccin excrètent une circulation pendant ≥1,5 ans, ou 15 modifications nt). rus after initial OPV vaccination, shedding is significantly des poliovirus Sabin après une vaccination initiale avec le VPO, The epidemiological characteristics of cVDPVs are Les caractéristiques épidémiologiques des PVDVc sont analo- reduced when subsequent vaccine doses are administered cette excrétion diminue significativement lorsqu’ils reçoivent les similar or identical to those of WPVs; they cause simi- gues ou identiques à celles des PVS: ils causent une maladie to individuals who had previously received OPV.23 doses vaccinales ultérieures.23 lar paralytic disease and have capacity for sustained paralytique similaire et sont capables d’une transmission inte- In high-income countries, seroconversion rates in chil- Dans les pays à revenu élevé, les taux de séroconversion des enfants person-to-person transmission. They have lost the orig- rhumaine soutenue. Ils ont perdu leurs mutations d’atténuation dren following administration of 3 doses of tOPV après l’administration de 3 doses de VPOt approchent les 100% inal attenuating mutations, can replicate at 39.5 °C, and de départ, peuvent se répliquer à 39,5 °C et sont habituellement approach 100% for all 3 poliovirus types.24, 25 In large pour les 3 types de poliovirus.24, 25 Dans le cadre d’études contrôlées are usually recombinants with other species of entero- susceptibles de se recombiner avec d’autres espèces d’entérovi- case-controlled studies in Taiwan26 and Oman27 the de grande ampleur menées à Taïwan26 et Oman,27 l’efficacité sur le virus. cVDPVs were first recognized in 2000 during an rus. Les PVDVc ont été reconnus pour la première fois en 2000, field-effectiveness of the 3-dose tOPV schedule was esti- terrain du calendrier d’administration en 3 doses de VPOt a été outbreak in Hispaniola.19 Recent experience indicates lors d’une flambée survenue à Hispaniola.19 L’expérience récente mated to be >90%. However, in some developing coun- estimée comme >90%. Cependant, dans certains pays en dévelop- that low vaccination coverage is a major risk factor for indique qu’une faible couverture vaccinale représente un facteur tries, the same 3-dose course of tOPV in children was pement, on a constaté que le même déroulement en 3 doses de la cVDPV outbreaks, that cVDPVs have the ability to de risque majeur pour l’apparition de flambées de PVDVc, que found to induce detectable antibodies in only 73% vaccination par le VPOt n’induisait une réponse en anticorps détec- continue circulating for prolonged periods, as seen in les PVDVc ont la capacité de circuler sur des périodes prolon- (range, 36%–99%), 90% (range 77%–100%) and 70% table contre les poliovirus de types 1, 2 et 3 que chez 73% (plage Nigeria and Pakistan, and that cVDPVs can be imported gées, comme on l’a observé au Nigéria et au Pakistan, et qu’ils (range, 40%–99%) to poliovirus type 1, 2 and 3, respec- de variation: 36-99%), 90% (plage de variation: 77-100%) et 70% and spread in any under-vaccinated community in a peuvent être importés et propagés dans toute collectivité sous- tively.28 In lower-income settings, the response to OPV (plage de variation: 40-99%) respectivement des enfants.28 Dans les developed country, as occurred in the Amish commu- vaccinée d’un pays développé, comme cela s’est produit pour appears to vary, e.g. in Northern India seroconversion pays à faible revenu, la réponse au VPO semble variable: dans le nity, USA.20 la Communauté Amish aux États-Unis d’Amérique.20 rates were relatively low,29, 30 whereas in Thailand31 and nord de l’Inde, par exemple, les taux de séroconversion observés In 2014, a total of 56 cases of paralytic poliomyelitis En 2014, 56 cas au total de poliomyélite paralytique causée par Indonesia32 the rates were high. étaient relativement bas,29, 30 tandis qu’en Thaïlande31 et en Indo- caused by cVDPVs were reported from 5 countries; in un PVDVc ont été notifiés par 5 pays, dans 55 de ces cas, le nésie,32 ils étaient élevés. 55 of the cases the virus was serotype 2 and in one it virus appartenait au sérotype 2 et dans un autre, au sérotype 1. The reduced antibody response to OPV in children in La diminution de la réponse en anticorps des enfants au VPO was serotype 1. Nigeria reported the largest number of C’est au Nigéria que le plus grand nombre de cas (n=30) a été some low-income settings probably results from dans certains pays à faible revenu résulte probablement d’inte- cases (n=30).21 In 2015, as of 15 December, 7 countries signalé.21 Au 15 décembre 2015, 7 pays avaient notifié au total complex interactions between the host (e.g. levels of ractions complexes entre l’hôte (concentrations d’anticorps reported a total of 24 cases of paralytic poliomyelitis 24 cas de poliomyélite paralytique provoquée par un PVDVc, maternal antibody, poor intestinal immunity in maternels, immunité intestinale insuffisante chez les enfants caused by cVDPVs, most of which were serotype 1 appartenant dans la plupart des cas au sérotype (n=17). Ces cas malnourished children, diarrhoea at the time of vacci- mal nourris, diarrhée au moment de la vaccination ou exposi- (n=17). These cases occurred in Madagascar (n=10), Lao sont apparus à Madagascar (n=10), en République démocra- nation, and household exposure to other OPV recipi- tion au sein du foyer à d’autres personnes ayant reçu le VPO, People’s Democratic Republic (n=5), Guinea, Myanmar, tique populaire lao (n=5), en Guinée, au Myanmar, en Ukraine ents), the vaccine and its delivery, and the environment par exemple), le vaccin et sa délivrance, et l’environnement Ukraine and Pakistan (n=2 each) and Nigeria (n=1). et au Pakistan (n=2 chaque fois) ainsi qu’au Nigéria (n=1). (e.g. prevalence of other enteric infectious agents). In (prévalence d’autres agents entériques infectieux, par exemple). Immunogenicity and effectiveness Immunogénicité et efficacité The effectiveness of OPV in controlling poliomyelitis L’efficacité du VPO dans l’endiguement de la poliomyélite et 23 Hird TR et al. Systematic review of mucosal immunity induced by oral and inactiva- 23 Hird TR et al. Systematic review of mucosal immunity induced by oral and inactivated poliovirus ted poliovirus vaccines against virus shedding following oral poliovirus vaccine vaccines against virus shedding following oral poliovirus vaccine challenge. PLoS Pathogens. and eliminating the circulation of wild polioviruses is dans l’élimination des poliovirus sauvages circulants est ample- challenge. PLoS Pathogens. 2012; 8(4)e1002599. 2012; 8(4)e1002599. amply demonstrated by the sharp decline in the inci- ment démontrée par la baisse radicale de l’incidence de la 24 Bar-On ES et al. Combined DTP-HBV-HIB vaccine versus separately administered 24 Bar-On ES et al. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and dence of poliomyelitis following the introduction of poliomyélite suite à l’introduction de ce vaccin dans les pays DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophi- 22 22 hepatitis B and Haemophilus influenzae b (HIB). Cochrane Database Systematic lus influenzae b (HIB). Cochrane Database Systematic Review. 2012 (http://onlinelibrary.wiley. OPV in both industrialized and developing countries. industrialisés et en développement. Jusqu’à ce jour, le VPOt a Review. 2012 (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005530. com/doi/10.1002/14651858.CD005530.pub3/pdf/standard, consulté en février 2016). Until now tOPV has been the vaccine of choice for the représenté le vaccin de choix pour l’IMEP et son utilisation a pub3/pdf/standard, accessed February 2016). GPEI and its use was largely responsible for the prog- été responsable, pour une très grande part, des progrès réalisés 25 McBean AM et al. Serologic response to oral polio vaccine and enhanced potency 25 McBean AM et al. Serologic response to oral polio vaccine and enhanced potency inactivated ress towards eradication, including the eradication of vers l’éradication, y compris l’éradication des PVS2 à l’échelle inactivated polio vaccines. Am J Epidem. 1988; 128:615–628. polio vaccines. Am J Epidem. 1988; 128:615–628. 26 Kim–Farley RJ et al Outbreak of paralytic poliomyelitis, Taiwan. Lancet. 1984; 26 Kim–Farley RJ et al Outbreak of paralytic poliomyelitis, Taiwan. Lancet. 1984; 2:1322–1324. WPV2 globally in 1999. mondiale en 1999. 2:1322–1324. 27 Sutter RW et al. Outbreak of paralytic poliomyelitis in Oman: evidence for wides- 27 Sutter RW et al. Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmis- pread transmission among fully vaccinated children. Lancet. 1991; 338:715–720. sion among fully vaccinated children. Lancet. 1991; 338:715–720. 28 Patriarca PA. Factors affecting the immunogenicity of OPV in developing countries: 28 Patriarca PA. Factors affecting the immunogenicity of OPV in developing countries: a review. Rev a review. Rev Inf Dis. 1991; Sep-Oct; 13(5):926–939. Inf Dis. 1991; Sep-Oct; 13(5):926–939. 19 Kew OM et al. Outbreak of poliomyelitis in Hispaniola associated with circulating 19 Kew OM et al. Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 29 Estívariz CF et al. Immunogenicity of poliovirus vaccines administered at age 29 Estívariz CF et al. Immunogenicity of poliovirus vaccines administered at age 6-9 months in type 1 vaccine–derived poliovirus. Science. 2002; 296:356–359. vaccine–derived poliovirus. Science. 2002; 296:356–359. 6-9 months in Moradabad District, India: A randomized controlled phase 3 trial. Moradabad District, India: A randomized controlled phase 3 trial. Lancet Inf Dis. 2012; 12:128– 20 Alexander JP et al. Transmission of imported vaccine-derived poliovirus in an under- 20 Alexander JP et al. Transmission of imported vaccine-derived poliovirus in an under-vaccinated Lancet Inf Dis. 2012; 12:128–135. 135. vaccinated community: Minnesota , USA. J Inf Dis. 2009; 391–397. community: Minnesota , USA. J Inf Dis. 2009; 391–397. 30 Grassly NC et al. Protective efficacy of a monovalent oral type 1 poliovirus vaccine. 30 Grassly NC et al. Protective efficacy of a monovalent oral type 1 poliovirus vaccine. Lancet. 21 Circulating vaccine-derived poliovirus (cVDPV) 2000–2013. Available at http:// 21 Circulating vaccine-derived poliovirus (cVDPV) 2000–2013. Disponible sur http://www.polioe- Lancet. 2007; 369:1356–1362. 2007; 369:1356–1362. www.polioeradication.org/Dataandmonitoring/Poliothisweek/Circulatingvaccine- radication.org/Dataandmonitoring/Poliothisweek/Circulatingvaccinederivedpoliovirus.aspx, 31 WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines: Com- 31 WHO Collaborative Study Group on Oral and Inactivated Poliovirus Vaccines: Combined immu- derivedpoliovirus.aspx, accessed February 2016. consulté en février 2016. bined immunization of infants with oral and inactivated poliovirus vaccines: Results nization of infants with oral and inactivated poliovirus vaccines: Results of a randomized trial 22 Grading of scientific evidence – table I: Efficacy/effectiveness of OPV. Available at 22 Cotation des preuves scientifiques – tableau I. Efficacy/effectiveness of OPV. Disponible unique- of a randomized trial in the Gambia, Oman, and Thailand. Bull World Health Organ. in the Gambia, Oman, and Thailand. Bull World Health Organ. 1996; 74:253–268. http://www.who.int/immunization/polio_grad_opv_effectiveness.pdf, accessed ment en langue anglaise sur http://www.who.int/immunization/polio_grad_opv_effectiveness. 1996; 74:253–268. February 2016. pdf, consulté en février 2016. 32 See No. 5, 2008, pp. 45–48. 32 Voir No 5, 2008, pp. 45-48. 152 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 153 of adverse events have been observed when tOPV was d’efficacité ou d’augmentation de l’incidence des manifestations Poliovirus antivirals are currently being developed for Des antiviraux visant les poliovirus sont actuellement en cours administered with these vaccines.2, 43 Interference with secondaires n’a été observée lors de l’administration du VPOt treatment of immunodeficient individuals in order to de mise au point pour le traitement des individus immunodé- the immune response to rotavirus vaccine when avec ces vaccins.2, 43 Une interférence avec la réponse immuni- clear the infection in those who chronically shed polio- ficients en vue d’éliminer l’infection chez ceux qui excrètent co-administered with OPV has been noted after the first taire au vaccin antirotavirus coadministré avec le VPO a été virus. The most advanced antiviral agent, pocapavir chroniquement de tels virus. Il a été démontré que l’agent anti- dose but not after completion of the full primary series, notée après la première dose, mais pas à l’achèvement de la (V-073), a capsid inhibitor, has been shown to shorten viral dont le développement est le plus avancé, le pocapavir while the response to the poliovirus types was unaf- série primaire, tandis que la réponse aux différents types de poliovirus excretion following a challenge with OPV.52 (V-073), un inhibiteur de liaison à la capside, abrégeait l’excré- fected.44 No immunological interference with tOPV has poliovirus n’était pas affectée.44 Aucune interférence immuno- The development of additional antiviral candidates with tion de poliovirus après une épreuve de provocation avec le been observed when given together with supplementary logique n’a été observée avec le VPOt lorsque ce vaccin était differing mechanisms of action continues to be a prior- VPO.52 La mise au point d’autres antiviraux candidats avec des vitamin A.2 The limited available evidence supports the administré en même temps qu’une supplémentation en vita- ity (to prevent the emergence of resistance), with the mécanismes d’action différents continue d’être une priorité (en safety and immunogenicity of co-administration of OPV mine A.2 Les éléments limités disponibles sont en faveur de goal of having at least 2 antiviral agents available for vue de prévenir l’émergence d’une résistance), en se donnant and oral cholera vaccines.45 Although no data are avail- l’innocuité et de l’immunogénicité de la coadministration du use in combination therapy for iVDPV excretors. comme objectif de disposer de 2 agents antiviraux au moins able for bOPV, it is assumed that, as for tOPV, no inter- VPO et des vaccins anticholériques oraux.45 Bien que l’on ne pour les utiliser sous forme de traitement combiné chez les ference would occur between bOPV and the other dispose d’aucune donnée pour le VPOb, on suppose que, comme excréteurs de PVDVi. routinely administered vaccines. pour le VPOt, aucune interférence ne devrait intervenir entre le VPOb et les autres vaccins administrés de manière systéma- 2. Inactivated poliovirus vaccine (IPV) 2. Vaccin antipoliomyélitique inactivé (VPI) tique. Vaccine characteristics Caractéristiques du vaccin Immunocompromised persons as special risk groups Personnes immunodéprimées en tant que groupe à risque particulier IPV is made from selected WPV strains – Mahoney or Le VPI est préparé à partir de souches de PVS sélectionnées In a small proportion of individuals with a primary Chez un faible pourcentage des individus souffrant d’un déficit Brunhilde (type 1), MEF-1 (type2), and Saukett (type 3) – Mahoney ou Brunhilde (type 1), MEF-1 (type 2) et Saukett immunodeficiency disease, OPV immunization can lead immunitaire primaire, la vaccination avec le VPO peut entraîner – or from Sabin strains, and are now grown in Vero cell (type 3) – ou à partir de souches Sabin, toutes ces souches étant to persistent iVDPV infections, with chronic shedding des infections par des PVDVi persistantes, s’accompagnant de culture or in human diploid cells. An IPV based on the maintenant cultivées sur des cellules Vero ou sur des cellules of iVDPVs that show regained neurovirulence, as l’excrétion chronique de PVDVi ayant retrouvé une neuroviru- attenuated Sabin virus strains (sIPV) was developed diploïdes humaines. Un VPI préparé à partir d’une souche virale demonstrated by genetic sequencing.46 To date, approx- lence, comme le montre le séquençage génétique.46 À ce jour, and licensed in Japan in 2012. The advantages of sIPV Sabin atténuée (PVIs) a récemment été mis au point et homo- imately 100 persons with primary immunodeficiency approximativement 100 personnes dans le monde présentant are that biocontainment requirements are less stringent logué au Japon en 2012. Le PVIs a notamment comme avantages, diseases worldwide have been reported to be excreting un immunodéficit primaire ont été signalées comme excrétant than for wild viruses and the consequences of any par rapport aux poliovirus sauvages, des exigences moins iVDPVs.17, 47 However, the true incidence of chronic des PVDVi.17, 47 Cependant, l’incidence vraie des infections chro- release of Sabin strains into populations would be less strictes en matière de confinement biologique et une moindre 53 iVDPV infections remains uncertain,48 because only niques par des PVDVi reste incertaine,48 car seules certaines serious than with release of wild strains. gravité des conséquences d’une éventuelle diffusion des souches 53 some infections lead to AFP, the primary marker for infections débouchent sur une PFA, le principal marqueur de vaccinales parmi des populations. detection of poliomyelitis. To date, no iVDPV is known la poliomyélite. À ce jour, on ne connaît pas de situation où un All current IPV vaccines have substantially greater anti- Tous les vaccins VPI actuels présentent une antigénicité subs- to have generated secondary cases with paralysis. PVDVi aurait généré des cas secondaires avec paralysie. genicity than those produced in the 1950s, and are tantiellement plus forte que ceux produits dans les années 1950 Data suggest that acquired (secondary) immunodefi- Les données laissent à penser que les syndromes d’immunodé- sometimes termed ‘enhanced potency IPV’ (eIPV). IPV et sont parfois appelés VPI à activité améliorée. La fabrication ciency syndromes, such as that caused by HIV infection, ficience acquise (secondaire), tels que ceux provoqués par l’in- manufacturing relies on inactivation of cell culture- du VPI repose sur l’inactivation au formaldéhyde de poliovirus do not lead to prolonged poliovirus excretion after OPV fection à VIH, n’entraînent pas l’excrétion prolongée de polio- derived polioviruses with formaldehyde, in a final dérivés sur culture cellulaire pour obtenir une formulation vaccination.49 HIV infection does not appear to be a risk virus après une vaccination avec le VPO.49 L’infection par le VIH formulation containing sufficient antigen units for each finale contenant suffisamment d’unités antigéniques pour 54 54 factor for VAPP or paralytic poliomyelitis caused by ne parait pas être un facteur de risque pour l’apparition d’une serotype. IPV may contain formaldehyde, as well as chaque sérotype. Le VPI peut contenir du formaldéhyde, ainsi WPV.50 Although in many developing countries the PPAV ou d’une poliomyélite paralytique due à un PVS.50 Si, dans traces of streptomycin, neomycin or polymyxin B. Some que des traces de streptomycine, de néomycine ou de poly- immune status of infants is not known, the first doses de nombreux pays en développement, le statut immunitaire des formulations of IPV contain 2-phenoxyethanol (0.5%) myxine B. Certaines formulations de VPI renferment du of OPV are administered at an age when HIV infection nourrissons n’est pas connu, les premières doses de VPO sont as a preservative for multi-dose vials. IPV formulations 2-phénoxyéthanol (0,5%) en tant que conservateur pour les would not have caused immunodeficiency. The immune administrées à un âge où l’infection à VIH ne devrait pas avoir do not contain thiomersal, which is incompatible with flacons multidoses. Ces formulations ne font pas appel au thio- response to OPV in HIV-infected and non-infected provoqué de déficit immunologique. La réponse immunitaire à IPV antigenicity. The vaccine should be refrigerated to mersal, qui est incompatible avec l’antigénicité du VPI. Les infants at standard routine immunization age does not l’administration du VPO à l’âge prévu par le calendrier de preserve potency but not frozen as this could diminish vaccins devront être réfrigérés pour préserver leur activité, appear to differ.51 vaccination systématique ne semble pas différer entre les nour- potency. Current 10-dose and 5-dose IPV vials can be mais la congélation est à éviter car elle pourrait diminuer cette rissons infectés et non infectés par le VIH.51 used according to the WHO multi-dose vial policy and même activité. Les flacons de 10 ou 5 doses de VPI actuellement kept for up to 28 days after opening.55 disponibles peuvent être utilisés conformément à la politique de l’OMS relative aux flacons multidoses et conservés jusqu’à 43 WHO prequalified vaccines [online database]; available at http://www.who.int/ 43 WHO prequalified vaccines [online database]; Disponible sur http://www.who.int/immuniza- 28 jours après ouverture.55 immunization_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html, ac- tion_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html, consulté en février 2016. cessed February 2016. IPV is available either as a stand-alone product or in Le VPI est disponible sous forme indépendante ou en association 44 Patel M et al. Influence of oral polio vaccines on performance of the monovalent 44 Patel M et al. Influence of oral polio vaccines on performance of the monovalent and penta- and pentavalent rotavirus vaccines. Vaccine. 2012; 30, Suppl 1, A30–A35. valent rotavirus vaccines. Vaccine. 2012; 30, Suppl 1, A30–A35. combination with one or more other vaccine antigens avec un ou plusieurs autres antigènes vaccinaux, dont ceux du 45 Kollaritsch H et al. Safety and Immunogenicity of Live Oral Cholera and Typhoid 45 Kollaritsch H et al. Safety and Immunogenicity of Live Oral Cholera and Typhoid Vaccines Admi- including DTP, hepatitis B, or Hib. DTP, du vaccin contre l’hépatite B ou du vaccin contre le Hib. Vaccines Administered Alone or in Combination with Antimalarial Drugs, Oral Polio nistered Alone or in Combination with Antimalarial Drugs, Oral Polio Vaccine, or Yellow Fever Vaccine, or Yellow Fever Vaccine. The Journal of Infectious Diseases 1997;175:871– Vaccine. The Journal of Infectious Diseases 1997;175:871–875. 875. 46 Yang C et al. Intratypic recombination among lineages of type 1 vaccine-derived 46 Yang C et al. Intratypic recombination among lineages of type 1 vaccine-derived poliovirus 52 52 poliovirus emerging during chronic Infection of an immunodeficient patient, J Virol. emerging during chronic Infection of an immunodeficient patient, J Virol. 2005; 79(20): 12623– McKinlay MA et al. Progress in the development of poliovirus antiviral agents and McKinlay MA et al. Progress in the development of poliovirus antiviral agents and their essential 2005; 79(20): 12623–12634. 12634. their essential role in reducing risks that threaten eradication. J Infect Dis. (2014) role in reducing risks that threaten eradication. J Infect Dis. (2014) 210 (suppl 1): S447-S453. 210 (suppl 1): S447–S453. 47 See No.25, 2015, 309–320. 47 Voir No 25, 2015, 309-320. 53 53 48 48 Bakker WAM et al. Inactivated polio vaccine development for technology transfer Bakker WAM et al. Inactivated polio vaccine development for technology transfer using atte- Duintjer Tebbens RJ et al. Risks of paralytic disease due to wild or vaccine-derived Duintjer Tebbens RJ et al. Risks of paralytic disease due to wild or vaccine-derived poliovirus using attenuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV. Vac- nuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV. Vaccine. 2011;29(41):7188– poliovirus after eradication. Risk Analysis. 2006; 26(6):1471–1505. after eradication. Risk Analysis. 2006; 26(6):1471–1505. cine. 2011;29(41):7188–7196. 7196. 49 49 Hennessey KA et al. Poliovirus vaccine shedding among persons with HIV in Abi- Hennessey KA et al. Poliovirus vaccine shedding among persons with HIV in Abidjan, Côte 54 Recommendations to assure the quality, safety and efficacy of poliomyelitis vac- 54 Recommendations to assure the quality, safety and efficacy of poliomyelitis vaccines (inactiva- djan, Côte d’Ivoire. J Inf Dis. 2005; 192:2124–2128. d’Ivoire. J Inf Dis. 2005; 192:2124–2128. cines (inactivated). WHO Technical Report Series 993, 2014. Geneva, World Health ted). WHO Technical Report Series 993, 2014. Genève, Organisation mondiale de la Santé. Dis- 50 Vernon A et al. Paralytic poliomyelitis and HIV infection in Kinshasa, Zaire. In: Pro- 50 Vernon A et al. Paralytic poliomyelitis and HIV infection in Kinshasa, Zaire. In: Proceedings of Organization. Available at http://who.int/biologicals/vaccines/Annex3_IPV_Recom- ponible uniquement en langue anglaise à l’adresse suivante: http://who.int/biologicals/ ceedings of the Sixth International Conference on AIDS . San Francisco, CA; June the Sixth International Conference on AIDS . San Francisco, CA; June 20–24 1990. mendations_eng.pdf?ua=1, accessed February 2016. vaccines/Annex3_IPV_Recommendations_eng.pdf?ua=1, consulté en février 2016. 20–24,1990. 55 Application of WHO Multi-Dose Vial Policy for Inactivated Polio Vaccine. Available 55 Application of WHO Multi-Dose Vial Policy for Inactivated Polio Vaccine. Disponible sur http:// 51 Clements CJ et al. How about HIV infection and routine childhood immunization: a 51 Clements CJ et al. How about HIV infection and routine childhood immunization: a review. Bull at http://www.who.int/immunization/diseases/poliomyelitis/inactivated_polio_ www.who.int/immunization/diseases/poliomyelitis/inactivated_polio_vaccine/MDVP_ review. Bull World Health Organ. 1987; 65(6):905–911. World Health Organ. 1987; 65(6):905–911. vaccine/MDVP_Nov2014.pdf, accessed February 2016. Nov2014.pdf, consulté en février 2016. 156 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 157 According to manufacturer specifications, IPV can be Conformément aux spécifications du fabricant, le VPI peut être IPV is less effective than OPV in inducing intestinal Le VPI offre une moindre efficacité que le VPO dans l’induction administered by subcutaneous or intramuscular injec- administré par injection sous cutanée ou intramusculaire. mucosal immunity in previously unvaccinated indi- d’une immunité mucosale intestinale chez les individus aupa- tion. When combined with an adjuvanted vaccine the Lorsqu’il est associé à un vaccin adjuvanté, l’injection doit être viduals. Children given IPV then challenged with OPV ravant non vaccinés. Des enfants ayant reçu le VPI et subissant injection must be intramuscular. A fractional dose of intramusculaire. Une dose fractionnée de VPI en formulation become infected and shed OPV in their faeces. None- par la suite une épreuve de provocation par le VPO ont été stand-alone IPV can also be administered via the intra- indépendante peut aussi être administrée par voie intrader- theless, IPV can reduce the quantity and duration of infectés et ont excrété le VPO dans leurs selles. Néanmoins, le dermal route (see below). mique (vois plus loin). virus shedding in faeces, which may contribute to a VPI est susceptible de diminuer l’ampleur et la durée de l’excré- reduction in transmission. It has been suggested that tion virale dans les selles, ce qui peut contribuer à réduire la Safety of IPV Innocuité du VPI IPV may have a greater impact on oropharyngeal transmission. Il a été suggéré que le VPI pouvait avoir un IPV is considered very safe, whether given alone or in Le VPI est considéré comme très sûr, qu’il soit administré seul shedding, although there is limited evidence to support impact plus important sur l’excrétion oropharyngée, même si combination with other vaccines. There is no proven ou en combinaison avec d’autres vaccins. Il n’existe pas de rela- this observation.66 However, two studies have shown les preuves à l’appui de cette observation sont limitées.66 Toute- causal relationship with any adverse events other than tion de causalité prouvée avec une manifestation indésirable that IPV is more effective than an additional dose of fois, deux études ont montré que le VPI était plus efficace transient minor local erythema (0.5%–1%), induration autre qu’un érythème local transitoire mineur (0,5-1%), une OPV in reducing shedding in previously OPV-vacci- qu’une dose supplémentaire de VPO pour réduire l’excrétion (3%–11%) and tenderness (14%–29%).56, 57 induration (3-11%) ou une douleur à la palpation (14-29%).56, 57 nated children.67, 68 chez des enfants antérieurement vaccinés avec le VPO.67, 68 Differences in reduction of shedding by OPV and IPV Les différences entre les réductions de l’excrétion obtenues avec Immunogenicity, efficacy and effectiveness Immunogénicité, efficacité et efficience may be illustrated by the persistent circulation of WPV le VPO et le VPI ont été illustrées notamment par la circulation IPV has been shown to be highly effective in eliciting Le VPI s’est révélé hautement efficace dans la génération de in Israel in 2013,69 suggesting that WPV transmission persistante de PVS en Israël en 2013,69 ce qui amène à penser humoral antibody responses to poliovirus in both high- réponses en anticorps humorales aux poliovirus dans les pays à can be sustained for months if undetected in areas with que la transmission de tels virus peut rester soutenue pendant 58, 59 58, 59 income and low-income settings. In Sweden, IPV was revenu élevé, comme dans ceux disposant de revenus plus faibles. high IPV coverage where local factors facilitate trans- plusieurs mois si elle n’est pas détectée dans des zones de forte 60, 61 60, 61 used to eliminate poliovirus. In the USA a 2-dose En Suède, le VPI a été utilisé pour éliminer les poliovirus. Aux mission (e.g. poor hygiene and living conditions).70 couverture par le VPI, où des facteurs locaux facilitent la trans- schedule at 2 and 4 months of age achieved seroconver- États-Unis, un calendrier comprenant 2 doses administrées à 2 et mission (conditions d’hygiène et de de vie médiocres, par 62 sion in 95% of vaccine recipients for all 3 serotypes. 4 mois a permis d’obtenir un taux de séroconversion de 95% chez exemple).70 In Cuba, where WPVs stopped circulating decades ago les bénéficiaires de la vaccination pour l’ensemble des 3 séro- and OPV is delivered only in 2 supplemental campaigns types.62 À Cuba, où les PVS ont cessé de circuler il y a plusieurs A systematic review of seroconversion rates after a Une étude systématique des taux de séroconversion après l’ad- each year, 2 doses of IPV given at 4 and 8 months décennies et où le VPO n’est délivré que dans le cadre de single dose of IPV given at or shortly after birth ministration d’une dose unique de VPI à la naissance ou peu induced antibodies to type 1, 2 and 3 polioviruses in 2 campagnes supplémentaires par an, 2 doses de VPI administrées (<7 days after birth) found a seroconversion rate of de temps après (<7 jours après celle-ci) a relevé un taux de 100%, 100%, and 99.4% of vaccinees, respectively, and a à 4 et 8 mois induisaient la formation d’anticorps contre les polio- 8%–100% for type 1, 15%–100% for type 2, and 15%–94% séroconversion de 8-100% contre le type 1, de 15-100% contre 35 3-dose schedule given at 6, 10, and 14 weeks induced virus de types 1, 2 et 3 chez respectivement 100, 100 et 99,4% des for type 3, measured at 4–6 weeks of age. The wide le type 2, et de 15-94% contre le type 3, lors d’un dosage à 35 antibodies to type 1, 2, and 3 polioviruses in 94%, 83% personnes vaccinées et un calendrier en 3 doses, administrées à range of seroconversion rates is probably due to differ- 4-6 semaines. La plage de variation étendue des taux de séro- and 100% of vaccine recipients, respectively.63, 11, 64 6, 10 et 14 semaines générait une réponse en anticorps contre les ing levels of interference by maternal antibodies. Sero- conversion est probablement imputable à la diversité des poliovirus de types 1, 2 et 3, respectivement chez 94%, 83% et 100% conversion was strongly dependent on the age at vacci- niveaux d’interférence des anticorps maternels. La séroconver- des personnes vaccinées.63, 11, 64 nation. Even in the absence of seroconversion, IPV may sion était fortement dépendante de l’âge lors de la vaccination. prime individuals for a subsequent booster dose. In a Même en l’absence de séroconversion, le VPI pourrait réaliser The immunogenicity of IPV schedules depends on the L’immunogénicité des calendriers vaccinaux incluant le VPI large randomized controlled trial in Cuba, among un amorçage de la réponse immunitaire des individus en atten- age at administration and number of doses, due to dépend de l’âge d’administration et du nombre de doses en infants aged 4 months, 63% seroconverted to type 2 dant une dose de rappel ultérieure. Dans le cadre d’un essai interference by maternal antibodies. A study of immu- raison de l’interférence avec les anticorps maternels. Une étude following a single full dose of IPV administered intra- contrôlé et randomisé de grande ampleur, mené chez des nogenicity of a 3-dose schedule in Puerto Rico found examinant l’immunogénicité d’un calendrier en 3 doses à Porto muscularly, and 98% of infants who did not seroconvert enfants cubains de 4 mois, 63% des sujets ont subi une séro- seroconversion rates of 85.8%, 86.2% and 96.9% for Rico a relevé des taux de séroconversion de 85,8%, 86,2% et 96,9% were successfully primed (i.e. developed detectable anti- conversion contre le type 2 après l’administration d’une dose serotypes 1, 2 and 3 respectively on a 6, 10, 14 week pour les sérotypes 1, 2 et 3 respectivement avec un calendrier de body within 7 days of receiving a second dose, which unique complète de VPI par voie intramusculaire, et 98% des schedule, compared with 99.6%, 100% and 99.1% on a vaccination à 6, 10 et 14 semaines, contre des taux de 99,6%, 100% would not be expected in a naïve population).64, 71, 72 nourrissons non séroconvertis ont bénéficié d’un amorçage 65 65 2, 4, 6 month schedule. et 99,1% avec un calendrier de vaccination à 2, 4 et 6 mois. Thus, either seroconversion or priming resulted from a réussi de la réponse immunitaire (c’est-à-dire qu’ils ont produit full dose of IPV in 99% of study infants; the extent to une réponse en anticorps détectable dans les 7 jours suivant la which priming alone would provide protection from réception d’une seconde dose, pourcentage qu’on ne s’attend paralysis upon reinfection remains unknown. In pas à observer dans une population naïve).64, 71, 72 Ainsi, l’admi-

56 Vidor E et al. Poliovirus vaccine-inactivated. In Plotkin SA, Orenstein WA, Offit PA. 56 Vidor E et al. Poliovirus vaccine-inactivated. In O. W. Plotkin SA, Orenstein WA, Offit PA. Vac- Hungary VAPP disappeared following the introduction nistration d’une dose complète de VPI a entraîné une sérocon- Vaccines, 2013, 6th edition 2013. Philadelphia: Elsevier-Saunders, pp. 573–597. cines, 2013, 6th edition 2013. Philadelphia: Elsevier-Saunders, pp. 573–597. of a sequential schedule using 1 dose of IPV before OPV. version ou un amorçage de la réponse immunitaire chez 99% 57 Iqbal S et al. Preparation for global introduction of inactivated poliovirus vaccine: 57 Iqbal S et al. 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New Eng Med J. 2007; 356:1536–1544. 71 Priming is defined as the absence of seroconversion after the first IPV dose along 71 Priming is defined as the absence of seroconversion after the first IPV dose along with an anti- 64 Resik S et al. Priming after a fractional dose of inactivated poliovirus vaccine. New 64 Resik S et al. Priming after a fractional dose of inactivated poliovirus vaccine. New Eng J Med. with an antibody titre at 8 months, 7 days, 4 times greater than the titre at body titre at 8 months, 7 days, 4 times greater than the titre at 8 months; or an undetectable Eng J Med. 2013; 368:416–424. 2013; 368:416–424. 8 months; or an undetectable reciprocal titre at 8 months and a detectable recipro- reciprocal titre at 8 months and a detectable reciprocal titre at 8 months, 7 days. 65 Dayan GH et al. Serologic response to inactivated polio vaccine: a randomized cli- 65 Dayan GH et al. 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En Hongrie, la PPAV a disparu a booster dose either at 6 or 10 years of age.60, 77 250 jeunes adultes suédois (18 ans) ayant reçu 3 doses de VPI for the serotype after 1 and 2 doses. Other trials have suite à l’introduction d’un calendrier séquentiel prévoyant 1 dans leur petite enfance, avec une dose de rappel à l’âge de demonstrated that earlier administration of 1 dose of dose de VPI avant l’administration du VPO. Néanmoins, l’in- 6 ou 10 ans. 60, 77 IPV (e.g. at 6–8 weeks) gave much lower type 2 sero- vestigation d’une flambée de poliomyélite due à un PVS a Although antibody may decline over time in some indi- Même si les titres d’anticorps diminuent avec le temps chez conversion rates of 32%–39%.23, 73 mis en évidence une efficacité pour 1 dose et 2 doses de VPI viduals, and may fall below detectable levels, there is certains individus et peuvent passer au-dessous du seuil de de 36 et 89% respectivement, cohérente avec les taux de séro- no evidence that this leads to increased susceptibility détectabilité, il n’existe aucune preuve que ce phénomène conversion pour le sérotype considéré après 1 et 2 doses. to poliomyelitis (paralytic disease).38 Almost all high- conduise à une augmentation de la sensibilité à la poliomyélite D’autres essais ont montré que l’administration plus précoce income countries use 3 or more doses of IPV. The long- (forme paralytique).38 Presque tous les pays à revenu élevé d’une dose de VPI (par exemple à 6-8 semaines) donnait des term protection afforded by a single dose of IPV is utilisent 3 doses de VPI ou plus. La protection à long terme taux de séroconversion contre le type 2 bien plus bas de 32 under investigation. apportée par une dose unique de VPI est en cours d’étude. à 39%.23, 73 Intradermal IPV administration with fractional doses L’administration intradermique de doses fractionnées de VPI Co-administration with other vaccines Coadministration avec d’autres vaccins of IPV (0.1mL or 1/5 of a full dose) offers potential cost (0,1 ml ou 1/5 de la dose complète) offre la possibilité de réduire No clinically relevant interference has been reported Aucune interférence d’importance clinique n’a été rapportée reduction and allows immunization of a larger number les coûts et de vacciner un plus grand nombre de personnes avec when IPV is used in association with licensed diphthe- lorsque le VPI était administré en association avec des vaccins of persons with a given vaccine supply.74 Studies have un stock de vaccin donné.74 Des études montrent qu’en général ria-tetanus-whole cell pertussis (DTwP)/ diphtheria– homologués antidiphtériques-antitétaniques à composante generally demonstrated that a single fractional dose of une seule dose fractionnée de VPI (1/5 de la dose complète) tetanus–acellular pertussis (DTaP), Hib, hepatitis B, coquelucheuse acellulaire ou à cellules entières, contre le Hib, IPV (1/5 of the full dose) gives lower seroconversion donne des taux de séroconversion plus faibles qu’une dose pneumococcal polysaccharide conjugate, rotavirus l’hépatite B ou les rotavirus, avec le vaccin antipneumococcique rates than a full dose but after 2 doses the rates are complète, mais qu’après l’administration de 2 doses fractionnées, vaccines39 /or measles-containing vaccines.78 polyosidique conjugué39 ou encore avec des vaccins renfermant similar to those after 2 full doses. In all cases the median les taux sont similaires à ceux obtenus après 2 doses complètes. une composante rougeole.78 antibody titres induced by the 2 fractional doses, Dans tous les cas, les valeurs médianes des titres d’anticorps although high, were lower than with the 2 full doses. In induits par les doses fractionnées, bien qu’élevées, sont plus Immunocompromised and special risk groups Individus immunodéprimés et groupes à risque particuliers studies in Cuba64 and in Bangladesh,74 2 doses of frac- faibles que pour les doses complètes. Dans le cadre d’études In some countries that routinely use OPV, IPV is given Certains pays utilisant systématiquement le VPO administrent tional-dose IPV induced seroconversion rates of 98% to menées à Cuba64 et au Bangladesh,74 2 doses fractionnées de VPI instead of OPV to special risk groups, including HIV- le VPI au lieu du VPO à des groupes à risque particuliers, dont type 2 poliovirus in Cuba (when given at age 4 and 8 ont induit des taux de séroconversion de 98% contre les polio- infected infants. One study showed that 80% of HIV- les nourrissons infectés par le VIH. Une étude a mis en évidence months) and 81% to type 2 poliovirus in Bangladesh virus de type 2 à Cuba (lorsqu’elles étaient administrées à l’âge infected children, with a presumed intact immune que 80% des enfants infectés par le VIH, avec un système immu- (when given at 6 and 14 weeks). The results indicate de 4 et 8 mois) et de 81% contre les poliovirus de type 2 au system, seroconverted after 2 doses of IPV.79 Haemo- nitaire présumé intact, avaient manifesté une séroconversion that 2 fractional doses of IPV provide higher serocon- Bangladesh (lorsqu’elles étaient administrées à l’âge de 6 et philiac adults responded to IPV but HIV infection in après 2 doses de VPI.79 Des adultes hémophiles ont répondu au version rates than a single full dose, as shown in Cuba 14 semaines). Ces résultats indiquent que 2 doses fractionnées this group had a negative effect on the overall titre VPI, mais, dans ce groupe, l’infection par le VIH a eu un effet (63% when given at age 4 months) and in Bangladesh de VPI conduisent à des taux de séroconversion plus élevés levels.80 Patients with chronic renal failure81 and négatif sur le niveau global des titres.80 Des patients atteints (39% when given at age 6 weeks). This approach, using qu’une dose unique complète, comme cela a été montré à Cuba re-immunized patients after bone-marrow transplanta- d’une insuffisance rénale chronique81 et d’autres revaccinés 2 fractional doses instead of 1 full dose, increases the (63% avec une administration à 4 mois) et au Bangladesh (39% tion82 responded well, although at least 2 doses of IPV après une greffe de moelle osseuse82 ont bien répondu, mais immunogenicity of IPV and can extend coverage if avec une administration à 6 semaines). Cette approche consistant were needed. 2 doses au moins de VPI ont été nécessaires supplies are limited. à utiliser 2 doses fractionnées au lieu d’une dose unique accroît l’immunogénicité du PVI et peut permettre d’étendre davantage Co-administration of OPV and IPV Coadministration du VPO et du VPI la couverture vaccinale lorsque les approvisionnements sont In developing country settings the concurrent adminis- Dans des pays en développement, l’utilisation simultanée du limités. tration of tOPV and IPV has induced uniformly high VPO et du VPI a induit des réponses en anticorps uniformément antibody responses to all 3 poliovirus types, consistent fortes contre les 3 types de poliovirus, cohérentes avec l’emploi Duration of protection Durée de la protection with responses induced by multiple doses of polio plusieurs de vaccins antipoliomyélitiques en doses multiples. Information on the duration of IPV-induced protection Les informations relatives à la durée de la protection induite vaccines. A study conducted in 3 countries – Gambia, Une étude menée dans 3 pays – la Gambie, l’État d’Oman et la from high-income countries indicates that circulating par le VPI émanant de pays à revenu élevé indiquent que la Oman and Thailand – comparing an OPV birth dose Thaïlande – et comparant, après l’injection d’une dose de VPO antibody persists for decades and possibly for life. présence d’anticorps circulants persiste sur des décennies (et plus either OPV at 6, 10 and 14 weeks or OPV and IPV à la naissance, l’administration d’une dose de VPO à 6, 10, et However, as antibody titres decrease over time, some potentiellement, sur le vie entière). Néanmoins, comme les titres simultaneously at 6, 10 and 14 weeks, found that in 14 semaines à l’administration simultanée du VPO et du VPI à adults may lack detectable antibody. Persisting neutral- d’anticorps diminuent avec le temps, ils ne sont parfois plus Gambia and Oman, infants who received IPV and OPV 6, 10 et 14 semaines, a constaté qu’à Gambie, Oman et en, les izing antibodies against polioviruses are usually found détectables chez certains adultes. On observe habituellement la simultaneously had the highest seroconversion rates. In nourrissons qui avaient reçu simultanément le VPO et le VPI in all vaccine recipients 5 years after the primary immu- persistance d’anticorps neutralisants contre les poliovirus chez Thailand, the seroconversion rates were similar in both présentaient les taux de séroconversion les plus élevés. En Thaï- 75, 76 nization series of 3–4 doses. Neutralizing antibodies toute les personnes vaccinées 5 ans après l’administration de groups.29 In Pakistan comparison of the serological lande, les taux de séroconversion étaient similaires dans les 75, 76 were found in all of 250 young adults (18 years) in la série vaccinale primaire de 3-4 doses. On a retrouvé des responses to various OPV or IPV schedules, or combined 2 groupes.29 Au Pakistan, la comparaison des réponses sérolo-

77 Von Magnus H et al. Vaccination with inactivated poliovirus vaccine and oral polio- 77 Von Magnus H et al. Vaccination with inactivated poliovirus vaccine and oral poliovirus vaccine virus vaccine in Denmark. Rev Inf Dis. 1984; 6(Suppl.):S471–S474. in Denmark. Rev Inf Dis. 1984; 6(Suppl.):S471–S474. 78 Klein NP et al. An open-label, randomized, multi-center study of the immunogeni- 78 Klein NP et al. An open-label, randomized, multi-center study of the immunogenicity and safety city and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in 73 Simasathien S et al. Comparison of enhanced potency inactivated poliovirus vaccine 73 Simasathien S et al. Comparison of enhanced potency inactivated poliovirus vaccine (EIPV) without varicella vaccine in healthy pre-school age children. Vaccine. 2012 Jan healthy pre-school age children. Vaccine. 2012 Jan 11;30(3):668–674. (EIPV) versus standard oral poliovirus vaccine (OPV) in Thai infants. Scand J Inf Dis. versus standard oral poliovirus vaccine (OPV) in Thai infants. Scand J Inf Dis. 1994; 26:731–738. 11;30(3):668–674. 1994; 26:731–738. 79 Barbi M et al. Antibody response to inactivated polio vaccine (E-IPV) in children 79 Barbi M et al. Antibody response to inactivated polio vaccine (E-IPV) in children born to HIV 74 Anand A et al Early priming with inactivated poliovirus vaccine (IPV) and intrader- 74 Anand A et al Early priming with inactivated poliovirus vaccine (IPV) and intradermal fractional born to HIV positive mothers. Euro J Epidem. 1992; 8:211–216. positive mothers. Euro J Epidem. 1992; 8:211–216. mal fractional dose IPV administered by a microneedle device: A randomized dose IPV administered by a microneedle device: A randomized controlled trial. Vaccine, 2015 controlled trial. Vaccine, 2015 Nov 27;33(48):6816–6822. Nov 27;33(48):6816–6822. 80 Varon D et al. Response of hemophilic patients to poliovirus vaccination: correlation 80 Varon D et al. Response of hemophilic patients to poliovirus vaccination: correlation with HIV with HIV serology and with immunological parameters. J Med Virol. 1993; 40:91– serology and with immunological parameters. J Med Virol. 1993; 40:91–95. 75 Carlsson RM et al. Antibody persistence in five-year-old children who received a 75 Carlsson RM et al. Antibody persistence in five-year-old children who received a pentavalent 95. pentavalent combination vaccine in infancy. Ped Inf Dis J. 2002; 21(6):535–541. combination vaccine in infancy. Ped Inf Dis J. 2002; 21(6):535–541. 81 Sipila R et al. Good seroresponse to enhanced-potency inactivated poliovirus vac- 81 Sipila R et al. Good seroresponse to enhanced-potency inactivated poliovirus vaccine in patients 76 Langue J et al. Persistence of antibodies at 5-6 years of age for children who had 76 Langue J et al. Persistence of antibodies at 5-6 years of age for children who had received a cine in patients on chronic dialysis. Nephrol Dialysis Transplant. 1990; 5:352–355. on chronic dialysis. Nephrol Dialysis Transplant. 1990; 5:352–355. received a primary series vaccination with a pentavalent whole-cell pertussis vac- primary series vaccination with a pentavalent whole-cell pertussis vaccine and a first booster cine and a first booster with a pentavalent acellular pertussis vaccine. Vaccine, with a pentavalent acellular pertussis vaccine. Vaccine, 2004; 22(11-12):1406–1414. 82 Engelhard D et al. Immune response to polio vaccination in bone marrow transplant 82 Engelhard D et al. Immune response to polio vaccination in bone marrow transplant recipients. 2004; 22(11-12):1406–1414. recipients. Bone Marrow Transplant. 1991; 8:295–300. Bone Marrow Transplant. 1991; 8:295–300. 160 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 161 schedules, confirmed the favourable immunological giques à divers calendriers de vaccination utilisant le VPO ou OPV challenge, compared to no polio vaccination.88, 89 de 38 à 76% la prévalence de l’excrétion de poliovirus (selon la response to combined IPV+OPV vaccination.83 Combined le VPI, ou encore à des calendriers combinés, a confirmé que These studies also indicated that IPV is more effective tranche d’âge) après une épreuve de provocation avec le VPO, IPV+OPV schedules appear to correct for the lower le résultat le plus favorable était obtenu avec la vaccination in boosting intestinal mucosal immunity than OPV par comparaison avec l’absence de vaccination contre la polio- immunogenicity of OPV in developing countries. combinée VPI +VPO.83 L’administration de calendriers combi- among OPV-immunized individuals.67 myélite.88, 89 Ces études ont également indiqué une plus grande nés VPI + VPO semble corriger la plus faible immunogénicité efficacité du VPI par rapport au VPO dans le renforcement de du VPO dans les pays en développement. l’immunité mucosale intestinale chez les individus vaccinés par le VPO.67 The clinical impact of combined IPV+OPV vaccination L’impact clinique de la vaccination combinée VPI + VPO a été was demonstrated in the Gaza Strip, where the inci- démontré dans la Bande de Gaza, où l’incidence de la polio- There are few data specifically showing benefits of a dose On dispose de peu de données attestant spécifiquement des dence of paralytic poliomyelitis had remained high myélite paralytique était restée forte (≥10 cas/100 000 habitants), of OPV in IPV-vaccinated individuals. Limited results bénéfices d’une dose de VPO chez les individus vaccinés avec (≥10 cases/100 000 inhabitants) despite 90% coverage malgré un taux de couverture de 90% par le VPO. Suite au from a clinical trial in Gambia showed no significant le VPI. Les résultats limités d’un essai clinique réalisé en Gambie with OPV. Following the change from OPV alone to joint passage du VPO seul à la vaccination simultanée par le VPI et differences in seroconversion in infants who had either n’ont fait apparaître aucune différence significative dans la IPV+OPV vaccination in 1978, (i.e. tOPV at 1 month, le VPO en 1978 (c’est-à-dire l’administration du VPOt à 1 mois, an OPV or IPV primary series followed by an OPV séroconversion des nourrissons ayant reçu soit une série followed by IPV+tOPV given at 2.5 months and suivie de celle de la combinaison VPI+VPOt à 2,5 mois et à booster at 1 year (OPV–OPV versus IPV–OPV).86, 90 primaire de doses de VPO, soit une série primaire de doses de 4 months, then tOPV at 5.5 months and 12 months), the 4 mois, puis dc celle du VPOt à 5,5 mois et à 12 mois), l’inci- VPI, suivie d’une dose de rappel de VPO à 1 an (VPO-VPO annual incidence of paralytic poliomyelitis fell from 10 dence annuelle de la poliomyélite paralytique a chuté de 10 à contre VPI-VPO).86, 90 to 2.2/100 000 inhabitants during the first 3 years and 2,2 cas pour 100 000 habitants pendant les 3 premières années, A recent study in India assessed a schedule with bOPV Une étude récemment réalisée en Inde a évalué un calendrier during the following 5 years (1981–1985) to 0.16/100 000 puis à 0,16 cas/100 000 habitants au cours des 5 années suivantes followed by the simultaneous administration of prévoyant l’administration de VPOb suivie de l’injection simul- inhabitants.84 (1981-1985).84 bOPV+IPV; bOPV was administered at birth, 6 and tanée des vaccins VPOb + VPI; le VPOb a été administré à la 10 weeks, and bOPV+IPV at 14 weeks. This schedule, naissance et à 6 et 10 semaines, tandis que la combinaison VPOb Sequential use of IPV and OPV Utilisation séquentielle du VPI et du VPO 4 doses of bOPV and 1 dose of IPV, resulted in excellent + VPI était délivrée à 14 semaines. Ce calendrier comprenant 4 Sequential administration of IPV followed by OPV L’administration séquentielle du VPI suivie de celle du VPO seroconversion rates (>99% to poliovirus type 1, doses de VPOb et 1 dose de VPI a donné des taux de sérocon- appears to reduce or prevent VAPP while maintaining semble réduire ou prévenir la PPAV, tout en maintenant les 69%–78% to type 2, and >98% to type 3).91 version excellents (>99% contre le poliovirus de type 1, 69-78% the high levels of intestinal mucosal immunity conferred niveaux élevés d’immunité mucosale intestinale conférés par le contre le type 2 et >98% contre le type 3).91 by OPV. Sequential schedules of IPV followed by 2 or VPO. Des calendriers séquentiels prévoyant l’administration du more doses of OPV have been used or studied in several VPI, puis celle de 2 doses ou plus de VPO ont été mis en œuvre A recent study in Chile assessed a sequential schedule, Une étude récente au Chili a évalué un calendrier séquentiel countries including Israel, Oman, Pakistan, UK and USA. ou étudiés dans plusieurs pays, dont Israël, Oman, le Pakistan, using IPV at 2 months followed by 2 doses of bOPV at prévoyant l’administration d’une dose de VPI à 2 mois, suivie Such schedules reduce the number of doses of IPV and le Royaume-Uni et les États-Unis d’Amérique. Ces calendriers 4 and 6 months. The resulting seroconversion rates were de 2 doses de VPO à 4 et 6 mois. Les taux de séroconversion may theoretically optimize both the humoral and muco- permettent de réduire le nombre de doses de VPI et théorique- >98% to poliovirus type 1, >80% to type 2, and >98% résultants étaient >98% contre le poliovirus de type 1, > 80% sal immunogenicity of polio vaccines. This approach ment d’optimiser à la fois l’immunogénicité humorale et l’im- to type 3, respectively, indicating high immunogenicity contre le type 2, et >98% contre le type 3 respectivement, ce effectively prevented poliomyelitis caused by VAPP in munogénicité mucosale des vaccins antipoliomyélitiques. Cette with this schedule.92 qui indique une forte immunogénicité de ce calendrier.92 Denmark64 using a schedule of 3 doses of IPV followed approche a prévenu avec efficacité la poliomyélite sous forme by 3 doses of OPV, in Hungary11 using a schedule of de PPAV au Danemark,64 où l’on a utilisé un calendrier compre- Cost-effectiveness of eradication Rapport coût/efficacité de l’éradication 1 dose of IPV followed by 3 doses of OPV, and in the nant 3 doses de VPI suivies de 3 doses de VPO, en Hongrie,11 An economic analysis of polio eradication as a strategy Une analyse économique de l’éradication de la poliomyélite en USA85 which recommended 2 doses of IPV prior to où le calendrier de vaccination prévoyait 1 dose de VPI suivie reflected the status of the programme as of February tant que stratégie a reflété la situation programmatique en 2 doses of OPV during the period of transition from de 3 doses de VPO, et aux États-Unis d’Amérique,85 où il était 2010, including full consideration of post-eradication février 2010, en prenant pleinement en considération les poli- use of an OPV-only schedule to an IPV-only schedule. recommandé d’administrer 2 doses de VPI avant 2 doses de policies. For cost-effectiveness analysis of the eradica- tiques postéradication. Pour l’analyse du rapport coût/efficacité VPO pendant la période de transition entre l’utilisation d’un tion interventions, current pre-eradication experiences des interventions d’éradication, on a pris en compte les expé- calendrier comprenant seulement des doses de VPO et celle and two distinct potential future post-eradication vacci- riences prééradication actuelles et deux politiques futures d’un calendrier à base de VPI uniquement. nation policies were considered. Routine vaccination for potentielles distinctes pour la vaccination postéradication. On polio without specific eradication activities was used as a utilisé comme référence des comparaisons la vaccination Previous studies also suggest that a single dose of IPV Des études antérieures amènent également à penser qu’une dose a comparator. Poliomyelitis incidence was estimated systématique contre la poliomyélite sans les activités spéci- will effectively close immunity gaps to poliovirus type unique de VPI comblera efficacement les lacunes immunitaires using a dynamic infection transmission model and fiques à l’éradication. On a estimé l’incidence de la poliomyélite 2 (and types 1 and 3) in previously tOPV-vaccinated à l’égard du poliovirus de type 2 (et de ceux des types 1 et 3) costs based on numbers of vaccinated children. The à l’aide d’un modèle dynamique de la transmission de l’infec- children.86, 87 In addition, 2 recent studies in India found chez les enfants antérieurement vaccinés avec le VPOt.86, 87 En polio eradication strategy using tOPV followed by OPV tion et les coûts à partir des nombres d’enfants vaccinés. En se that in infants and children with a history of multiple outre, 2 études récemment menées en Inde ont constaté que cessation after successful WPV eradication was found fondant sur des critères standards, la stratégie d’éradication de doses of OPV, a single dose of IPV boosted intestinal chez des nourrissons et des enfants ayant reçu par le passé to be highly cost-effective based on standard criteria. la poliomyélite faisant appel au VPOt, puis cessant d’employer mucosal immunity and reduced by 38%–76% the preva- plusieurs doses de VPO, l’administration d’une dose unique de lence of excretion (depending on age group) after an VPI renforçait l’immunité mucosale intestinale et réduisait

88 Scientific evidence in support of: Note for the Record: 5th Meeting of the SAGE 88 Scientific evidence in support of: Note for the Record: 5th Meeting of the SAGE Working Group, Working Group, World Health Organization, Geneva, September 3-4, 2012 (http:// World Health Organization, Geneva, September 3-4, 2012 (http://www.who.int/immunization/ www.who.int/immunization/sage/meetings/2012/november/3__SAGE_WG_Scien- sage/meetings/2012/november/3__SAGE_WG_Scientific_Evidence22Oct2012.pdf, consulté en tific_Evidence22Oct2012.pdf, accessed February 2016). février 2016.). 89 Scientific evidence in support of: Note for the Record: 5th Meeting of the SAGE 89 Scientific evidence in support of: Note for the Record: 5th Meeting of the SAGE Working Group, 83 83 du Chatelet IP et al. Serological response and poliovirus excretion following dif- du Chatelet IP et al. Serological response and poliovirus excretion following different combined Working Group, World Health Organization, Geneva, September 3–4, 2012 (http:// World Health Organization, Geneva, September 3-4, 2012 (http://www.who.int/immunization/ ferent combined oral and inactivated poliovirus vaccines immunization schedules. oral and inactivated poliovirus vaccines immunization schedules. Vaccine. 2003; 21:1710–1718. www.who.int/immunization/sage/meetings/2012/november/3__SAGE_WG_Scien- sage/meetings/2012/november/3__SAGE_WG_Scientific_Evidence22Oct2012.pdf, consulté en Vaccine. 2003; 21:1710–1718. tific_Evidence22Oct2012.pdf, accessed February 2016). février 2016.). 84 84 Goldblum N et al. Poliomyelitis control in Israel, the West Bank and Gaza Strip: Goldblum N et al. Poliomyelitis control in Israel, the West Bank and Gaza Strip: changing stra- 90 Grading of scientific evidence – table V: Sequential administration IPV–OPV. Avai- 90 Cotation des preuves scientifiques – tableau V. Sequential administration IPV–OPV. Disponible changing strategies with the goal of eradication in an endemic area. Bull World tegies with the goal of eradication in an endemic area. Bull World Health Organ.1994; lable at http://www.who.int/immunization/polio_sequential_administration_IPV_ uniquement en langue anglaise sur http://www.who.int/immunization/polio_sequential_admi- Health Organ.1994; 72(5):783–796. 72(5):783–796. OPV.pdf, accessed February 2016. nistration_IPV_OPV.pdf, consulté en février 2016. 85 85 Alexander LN et al. Vaccine policy changes and epidemiology of poliomyelitis in the Alexander LN et al. Vaccine policy changes and epidemiology of poliomyelitis in the United 91 Sutter RW et al. Immunogenicity of a new routine vaccination schedule for global 91 Sutter RW et al. Immunogenicity of a new routine vaccination schedule for global poliomyelitis United States. JAMA. 2004; 292(14):1696–1701. States. JAMA. 2004; 292(14):1696–1701. poliomyelitis prevention: an open-label, randomised controlled trial. Lancet 2015. prevention: an open-label, randomised controlled trial. Lancet 2015. 18 September 2015 (http:// 86 Hanlon P et al. Serological comparisons of approaches to polio vaccination in the 86 Hanlon P et al. Serological comparisons of approaches to polio vaccination in the Gambia. 18 September 2015 (http://dx.doi.org/10.1016/S0140-6736(15)00237-8). dx.doi.org/10.1016/S0140-6736(15)00237-8). Gambia. Lancet.1987; 1(8536):800–801. Lancet.1987; 1(8536):800–801. 92 O’Ryan M et al. Inactivated poliovirus vaccine given alone or in a sequential sche- 92 O’Ryan M et al. Inactivated poliovirus vaccine given alone or in a sequential schedule with biva- 87 Moriniere BJ et al. Immunogenicity of a supplemental dose of oral versus inactiva- 87 Moriniere BJ et al. Immunogenicity of a supplemental dose of oral versus inactivated poliovirus dule with bivalent oral poliovirus vaccine in Chilean infants: a randomized, control- lent oral poliovirus vaccine in Chilean infants: a randomized, controlled, open-label, phase 4, ted poliovirus vaccine. Lancet. 1993; Jun 19; 341(8860):1545–1550. vaccine. Lancet. 1993; Jun 19; 341(8860):1545–1550. led, open-label, phase 4, non-inferiority study. Lancet Infect Dis 2015;15:1273–1282. non-inferiority study. Lancet Infect Dis 2015;15:1273–1282. 162 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 163 Sensitivity analysis suggested that the finding of posi- les VPO après l’éradication réussie des PVS a été trouvée d’un Vaccination with OPV plus IPV Vaccination avec le VPO plus le VPI tive net benefits of the GPEI remained robust over a très bon rapport coût/efficacité. L’analyse de sensibilité laisse à For all countries using OPV in the national immuniza- Pour l’ensemble des pays utilisant le VPO dans leur programme wide range of assumptions, providing a strong economic penser que le résultat attribuant des bénéfices nets positifs à tion programme, WHO continues to recommend the national de vaccination, l’OMS continue de recommander l’in- justification for polio eradication despite rising costs. l’IMEP reste solide si l’on fait varier très largement les hypo- inclusion of at least one dose of IPV in the vaccination clusion d’au moins une dose de VPI dans le calendrier vaccinal. Incremental net benefits of polio eradication between thèses de départ, d’où une forte justification économique pour schedule. The primary purpose of this IPV dose is to La finalité première de la dose de VPI est d’induire une base 1988 and 2035 were estimated at US$ 40–50 billion l’éradication de la poliomyélite malgré la hausse des coûts. Les induce an immunity base that could be rapidly boosted immunitaire qui pourrait rapidement être renforcée en cas de (2008 US$; 1988 net present values), with the lower value bénéfices incrémentaux nets de l’éradication de la poliomyélite should there be an outbreak of polio due to poliovirus flambée de poliomyélite due à un poliovirus de type 2 après le corresponding to increased adoption of IPV. Despite the entre 1988 et 2035 ont été estimés à US$ 40-50 milliards (US$ type 2 after the removal of type 2 virus from OPV. Addi- retrait du VPO du sérotype 2. En outre, selon le moment ou high costs of achieving eradication in low-income coun- de 2008; valeurs actuelles nettes en 1988), la valeur basse corres- tionally, depending on the timing of the administration intervient l’administration de la dose ou des doses de VPI, tries, they account for approximately 85% of the total pondant à une adoption plus large du VPI. Si les coûts pour of the dose or doses of IPV, the inclusion of IPV may l’introduction du VPI peut réduire les risques de PPAV et pour- net benefits generated by the GPEI in the base case obtenir l’éradication de la poliomyélite dans les pays à faible reduce risks for the development of VAPP and could rait renforcer l’immunité tant humorale que mucosale contre analysis.93 revenu sont élevés, ces pays recueillent aussi environ 85% des boost both humoral and mucosal immunity against les poliovirus de types 1 et 3 chez les personnes vaccinées. bénéfices totaux nets générés par l’IMEP dans l’analyse du cas poliovirus types 1 and 3 in vaccine recipients. de base.93 In polio-endemic countries and in countries at high risk Dans les pays d’endémie de la poliomyélite et dans ceux très Country-specific analyses of the incremental cost-effec- Des analyses par pays de l’évolution du rapport coût/efficacité for importation and subsequent spread of poliovirus,97 exposés au risque d’importation et de propagation ultérieure tiveness of switching from tOPV to IPV (in Australia, résultant du passage du VPOt au VPI (en Afrique du Sud, en WHO recommends a bOPV birth dose (zero dose) de poliovirus,97 l’OMS préconise une dose de VPO à la naissance South Africa and the USA) primarily for VAPP preven- Australie et aux États-Unis) principalement pour prévenir la followed by a primary series of 3 bOPV doses and at (dose zéro), suivie d’une série primaire de 3 doses de VPO et tion, concluded that changing from tOPV to IPV was PPAV, ont conclu que cette transition n’offrait pas un bon least 1 IPV dose. d’au moins 1 dose de VPI. not cost effective.79, 94, 95 Despite the additional cost, those rapport coût/efficacité.79, 94, 95 En dépit du coût supplémentaire, countries nevertheless switched to IPV to avoid the risk ces pays sont néanmoins passés au VPI pour tenter d’éliminer The zero dose of bOPV should be administered at birth, La dose zéro de VPO devra être administrée à la naissance ou of VAPP. The costs of IPV are expected to decrease as le risque de PPAV. On s’attend à ce que les coûts du VPI baissent or as soon as possible after birth, to maximize serocon- dès que possible après celle-ci pour maximiser les taux de séro- global demand increases. A recent analysis of the avec l’accroissement de la demande mondiale. Une analyse version rates following subsequent doses and to induce conversion avec les doses ultérieures et induire une protection economics of poliovirus eradication and risk manage- récente des aspects économiques de l’éradication des poliovirus mucosal protection before enteric pathogens may inter- mucosale avant que des agents pathogènes entériques ne ment for 2013–2052 reported approximately US$16 billion et de la gestion des risques pour la période 2013-2052 a prévu fere with the immune response. Also, a first dose of puissent interférer avec la réponse immunitaire. De même, in global net benefits (2013 US$) associated with the des bénéfices nets mondiaux à hauteur d’approximativement bOPV given while infants are still protected by mater- l’administration de la première dose de VPO pendant que les expected investments of the current strategic plan, US$ 16 milliards (US$ de 2013) comme conséquence des inves- nally-derived antibodies may, at least theoretically, nourrissons sont encore protégés par des anticorps d’origine coordinated OPV cessation (i.e. OPV2 cessation in 2016, tissements attendus du plan stratégique actuel, de l’arrêt coor- prevent VAPP. Even in cases of perinatal HIV infection, maternelle peut, tout au moins théoriquement, prévenir la PPAV. bOPV cessation in 2019), and the polio endgame through donné du VPO (c’est-à-dire de l’arrêt du PVO2 en 2016 et de early bOPV vaccination seems to be well tolerated, and Même dans les cas d’infection périnatale par le VIH, la vacci- 2052.93 celui du VPOb en 2019) et de la phase finale de l’éradication de no additional risk of VAPP has been documented in nation précoce avec le VPO semble bien tolérée et aucun risque la poliomyélite devant se dérouler jusqu’en 2052.93 such children. supplémentaire n’a été relevé pour ces enfants. The primary series consisting of 3 bOPV doses plus L’administration de la série primaire, composée de 3 doses de WHO position Position de l’OMS 1 IPV dose can be initiated from the age of 6 weeks VPO plus 1 dose de VPI, peut débuter à l’âge de 6 semaines, All children worldwide should be fully vaccinated Tous les enfants dans le monde devraient être intégralement with a minimum interval of 4 weeks between the bOPV avec un intervalle minimum de 4 semaines entre les doses de against polio, and every country should seek to achieve vaccinés contre la poliomyélite, et chaque pays devrait s’efforcer doses. If 1 dose of IPV is used, it should be given at VPOb. Si l’on utilise une seule dose de VPI, elle devra être admi- and maintain high levels of coverage with polio vaccine d’obtenir et de maintenir des niveaux élevés de couverture par 14 weeks of age or later (when maternal antibodies have nistrée à partir de l’âge de 14 semaines (lorsque les anticorps in support of the global commitment to eradicate polio. la vaccination antipoliomyélitique à l’appui de l’engagement diminished and immunogenicity is significantly higher) maternels auront baissé et que l’immunogénicité sera notable- mondial à éradiquer cette maladie. and can be co-administered with a bOPV dose. ment plus forte) et elle pourra éventuellement être injectée en Programmes may consider alternative schedules based même temps que celle de VPOb. Les programmes pourraient Indigenous wild poliovirus type 2 has not been detected Il n’a pas été détecté de poliovirus sauvage autochtone de type on local epidemiology, including the documented risk envisager d’autres calendriers en fonction de l’épidémiologie since 1999. Immunity gaps resulting from insufficient 2 depuis 1999. Les lacunes immunitaires résultant de l’utilisation of VAPP prior to 4 months of age. locale et notamment du risque observé de PPAV avant l’âge de use of tOPV with low vaccination coverage have led to insuffisante du VPOt, s’accompagnant d’une faible couverture 4 mois. increasing emergence of cVDPVs, with 26%–31% of vaccinale, ont entraîné un accroissement de l’émergence de cases of VAPP associated with the type 2 component in PVDVc, avec 26 à 31% des cas de PPAV associés à la composante The primary series can be administered according to La série primaire peut être administrée selon les calendriers tOPV. It is therefore essential to switch from tOPV de type 2 du VPOt. Il est donc essentiel de passer du VPOt (conte- the regular schedules of national immunization habituels des programmes nationaux de vaccination, par (containing type 1, 2 and 3 serotypes) to bOPV (contain- nant les sérotypes 1, 2 et 3) au VPOb (ne renfermant que les programmes, e.g. at 6, 10, and 14 weeks (bOPV, bOPV, exemple à 6, 10 et 14 semaines (VPOb, VPOb, VPOb +VPI) ou ing only type 1 and 3 serotypes) in national immuniza- sérotypes 1 et 3) dans les programmes de vaccination nationaux bOPV+IPV), or at 2, 4, and 6 months (bOPV, bOPV+IPV, à 2, 4 et 6 mois (VPOb, VPOb +VPI, VPOb ou VPOb, VPOb, tion programmes and to coordinate the switch globally. et de coordonner cette transition à l’échelle mondiale. En 2015, bOPV or bOPV, bOPV, bOPV+IPV). Both OPV and IPV VPOb+VPI). Le VPO, comme le VPI, peuvent être coadministrés In 2015 the World Health Assembly agreed that all l’Assemblée mondiale de la Santé est convenue que tous les États may be co-administered with other infant vaccines. avec d’autres vaccinations infantiles. Member States which currently use OPV should prepare Membres qui utilisent actuellement le vaccin antipoliomyélitique For infants starting the routine immunization schedule Pour les nourrissons débutant tardivement le calendrier de for the global withdrawal of the type 2 component of oral devront se préparer au retrait mondial, en avril 2016, de la late (age >3 months) the IPV dose should be adminis- vaccination systématique (à >3 mois), la dose de VPI devra OPV in April 2016.96 All stocks of tOPV should then be composante de type 2 du vaccin antipoliomyélitique oral.96 Tous tered at the first immunization contact along with bOPV être administrée lors du premier contact vaccinal, en même removed and destroyed from service delivery points les stocks de VPOt devront être retirés des points de délivrance and the other routinely recommended vaccines. temps que le VPOb et les autres vaccins systématiquement and their removal confirmed to WHO. et détruits et leur élimination devra être confirmée à l’OMS. recommandés.

93 Duintjer Tebbens RJ et al. Economic analysis of the global polio eradication initia- 93 Duintjer Tebbens RJ et al. Economic analysis of the global polio eradication initiative. Vaccine. As an alternative to the intramuscular injection of a full En tant qu’alternative à l’injection intramusculaire d’une dose tive. Vaccine. 2010; 29(2), 334–343. 2010; 29(2), 334–343. dose of IPV, countries may consider using fractional complète de VPI, les pays peuvent envisager l’administration 94 Griffiths UK et al. The cost-effectiveness of alternate polio immunization policies in 94 Griffiths UK et al. The cost-effectiveness of alternate polio immunization policies in South Africa. doses (1/5 of the full IPV dose) via the intradermal de doses fractionnées (1/5 de la dose complète de VPI) par South Africa. Vaccine. 2006; 24:5670–5678. Vaccine. 2006; 24:5670–5678. route, but the programmatic cost and logistic implica- voie intradermique, mais le coût programmatique et les impli- 95 Tucker AW et al. Cost-effectiveness analysis of changing from live oral poliovirus 95 Tucker AW et al. Cost-effectiveness analysis of changing from live oral poliovirus vaccine to vaccine to inactivated poliovirus vaccine in Australia. Aust N Z J Public Health. 2001; inactivated poliovirus vaccine in Australia. Aust N Z J Public Health. 2001; 25(5):411–416. tions of this option should be considered. In the context cations logistiques de cette option devront aussi être exami- 25(5):411–416. 96 68th World Health Assembly, 2015, agenda item 15.2. Poliomyelitis. Available at 96 68e Assemblée mondiale de la Santé, 2015, point 15.2 de l’ordre du jour. Poliomyélite. Dispo- http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_R3-en.pdf, accessed February nible sur http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_R3-fr.pdf, consulté en février 97 The risk of importation and subsequent spread is determined mainly by the level of 97 Le risque d’importation et de propagation ultérieure est déterminé principalement par le niveau 2016. 2016. immunization coverage, sanitation, and overall socioeconomic status. de couverture vaccinale et d’assainissement et par la situation socioéconomique globale.

164 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 165 of an IPV shortage, countries could consider instituting nés. Dans le contexte d’une pénurie de VPI, les pays devront 14-week schedule) then a booster dose should be given injecter une dose de rappel à l’issue d’un intervalle de ≥6 mois a 2-dose fractional dose schedule which could ensure envisage de mettre en place un calendrier comprenant 2 doses after an interval of ≥6 months (for a 4-dose schedule). (pour un calendrier en 4 doses). that all eligible infants receive IPV, is dose-sparing and fractionnées, qui permettrait de garantir que tous les nour- results in better immunogenicity than a single full dose rissons répondant aux critères pour recevoir le VPI bénéficient Switching to sequential schedules or exclusive Passage à un calendrier séquentiel ou tout VPI of IPV. To ensure early protection a schedule of frac- de ce vaccin, de réaliser des économies de doses et d’obtenir use of IPV tional intradermal doses administered at 6 and 14 weeks une meilleure immunogénicité qu’une dose unique complète To mitigate the risk of undetected transmission, WHO Pour diminuer le risque de transmission non détectée, l’OMS may be considered. The 2 fractional doses should be de VPI. Pour assurer une protection précoce, on peut envisa- recommends that endemic countries and countries with recommande aux pays d’endémie ou exposés à un risque consé- separated by a minimum interval of 4 weeks. One frac- ger l’administration d’un calendrier composé de doses frac- a high risk of WPV importation99 should not switch to quent d’importation de PVS99 de ne pas passer à un calendrier tional-dose IPV may be particularly appropriate for tionnées à 6 et 14 semaines. Les deux doses fractionnées an IPV-only or a sequential IPV–bOPV schedule at this «tout VPI» ou séquentiel VPI-VPOb pour l’instant. Ils devront outbreak response if supplies are limited. devront être séparées d’un intervalle minimum de 4 semaines. time. The 3 bOPV+1 IPV schedule as currently recom- adopter le calendrier 3 VPOb + VPI actuellement recommandé Le VPI sous forme de dose fractionnée intradermique unique mended should be adopted and SIAs should continue et poursuivre les AVS en vue d’appuyer les efforts intensifs pour peut être tout particulièrement adapté à la réponse à une to support intensive efforts to eliminate poliovirus éliminer la transmission des poliovirus. Un calendrier séquen- flambée si les approvisionnements sont limités. transmission. A sequential IPV–bOPV schedule or IPV- tiel VPI-VPOb ou «tout VPI» peut être envisagé pour minimiser In the event that vaccination with IPV cannot be done Dans les cas où la vaccination avec le VPI ne peut être effec- only schedule can be considered in order to minimize le risque de PPAV, mais seulement après un examen approfondi before the switch from tOPV to bOPV because of supply tuée avant le passage du VPOT au VPOb en raison d’une pénu- the risk of VAPP, but only after a thorough review of de l’épidémiologie locale. shortages, catch-up vaccination should be carried out rie de vaccins, des vaccinations de rattrapage devront être local epidemiology. when sufficient supplies become available. Stocks of pratiquées lorsque des approvisionnements suffisants seront mOPV2 and IPV are available for outbreak response if disponibles. Des stocks de VPOm2 et de VPI sont à disposition Special populations, contraindications Populations particulières, contre-indications a VDPV2 is detected in any country after the withdrawal pour répondre aux flambées en cas de détection d’un PVDV2 and precautions et précautions of tOPV.98 dans un pays quelconque après le retrait du VPOt.98 Polio vaccine (IPV or bOPV) may be administered safely Le vaccin antipoliomyélitique (VPI ou VPO) peut être adminis- to asymptomatic HIV-infected infants. HIV testing is tré sans risque à des nourrissons infectés par le VIH asympto- The implementation of the new infant schedule (3 bOPV La mise en œuvre d’un nouveau calendrier infantile (3 doses not a prerequisite for vaccination. matiques. Le dépistage du VIH n’est pas un prérequis pour la doses + 1 IPV dose) does not replace the need for de VPOb + 1 dose de VPI) n’élimine pas la nécessité d’activités vaccination. supplementary immunization activities (SIAs). Those de vaccination supplémentaires (AVS). Les pays dont la couver- countries with insufficient routine vaccination coverage ture par la vaccination systématique est insuffisante et qui bOPV is contraindicated in severely immunocompro- Le VPOb est contre-indiqué chez les patients sévèrement immu- and which rely on SIAs to increase population immunity s’appuient sur des AVS pour accroître l’immunité de leur popu- mised patients with known underlying conditions such nodéprimés présentant des pathologies sous-jacentes connues should continue the SIAs using bOPV until routine lation devront poursuivre ces AVS avec le VPOb jusqu’à ce que as primary immunodeficiencies, disorders of the telles que déficit immunitaire primaire, troubles thymiques, coverage improves or until the globally-coordinated la couverture par la vaccination systématique s’améliore ou thymus, symptomatic HIV infection or low CD4 T-cell infection à VIH symptomatique ou faible numération des withdrawal of bOPV. jusqu’au retrait coordonné à l’échelle mondiale du VPOb. values,100 malignant neoplasm treated with chemother- lymphocytes T CD4,100 néoplasme malin traité par chimiothé- apy, recent haematopoietic stem cell transplantation, rapie, greffe récente de cellules-souches hématopoïétiques, prise Sequential IPV–OPV schedule Calendrier séquentiel VPI-VPO drugs with known immunosuppressive or immuno- de médicaments ayant des propriétés immunosuppressives ou In countries with high vaccination coverage (e.g. Dans les pays bénéficiant d’une forte couverture vaccinale modulatory properties (e.g. high dose systemic cortico- immunomodulatoires connues (corticoïdes à haute dose par 90%–95%) and low importation risk (neighbouring (90-95%, par exemple) et où le risque d’importation est faible steroids, alkylating drugs, antimetabolites, TNF-α inhib- voie systémique, agents alkylants, antimétabolites, inhibiteurs countries and major population movement all having (avec des pays limitrophes et des populations déplacées impor- itors, IL-1 blocking agent, or other monoclonal antibod- du TNF-α, agent bloquant l’IL-1 ou autres anticorps monoclo- similarly high coverage) an IPV–bOPV sequential tantes présentant également des taux de couverture élevés), un ies targeting immune cells), and current or recent naux ciblant les cellules immunitaires), ou encore radiothérapie schedule can be used when VAPP is a significant calendrier séquentiel VPI-VPOb peut être appliqué si les PPAV radiation therapies targeting immune cells. These popu- en cours ou récente visant des cellules immunitaires. Ces popu- concern. Where a sequential IPV–bOPV schedule is représentent une préoccupation importante. Lorsqu’on utilise lations can safely receive IPV. lations peuvent recevoir sans risque le VPI. used, the initial administration of 1 or 2 doses of IPV un tel calendrier, l’administration initiale de 1 ou 2 doses de should be followed by ≥2 doses of bOPV to ensure both VPI doit être suivie de celle de ≥2 doses de VPOb pour garan- Co-administration with other vaccines Coadministration avec d’autres vaccins sufficient levels of protection in the intestinal mucosa tir un niveau suffisant de protection de la muqueuse intestinale IPV and bOPV may be administered concurrently and Le VPI et le VPOb peuvent être injectés simultanément et l’un and a decrease in the burden of VAPP. For sequential et une diminution acceptable de la charge de PPAV. Pour les both can be given together with other vaccines. comme l’autre peuvent être administrés en association avec les IPV–bOPV schedules, WHO recommends that IPV be calendriers séquentiels VPI-VPOb, l’OMS préconise d’adminis- autres vaccins. given at 2 months of age (e.g. a 3-dose IPV–bOPV–bOPV trer le VPI à l’âge de 2 mois (calendrier en 3 doses VPI-VPOb- schedule), or at 2 months and 3–4 months of age (e.g. VPOb, par exemple) ou à 2 mois et à 3-4 mois (calendrier en Vaccination of travellers Vaccination des voyageurs a 4-dose IPV–IPV–OPV–OPV schedule) followed by at 4 doses VPI-VPI-VPO-VPO, par exemple), puis au moins 2 doses Before travelling abroad, persons residing in countries Avant de se rendre à l’étranger, les personnes résidant dans des least 2 doses of bOPV. Each of the doses in the primary de VPOb. Entre les différentes doses de la série primaire, il faut with active transmission of a wild or vaccine-derived pays où s’opère la transmission active de poliovirus sauvages series should be separated by 4–8 weeks depending on prévoir un intervalle de 4-8 semaines selon le risque d’exposi- poliovirus should have completed a full course of polio ou dérivés d’une souche vaccinale devront avoir reçu une série the risk of exposure to poliovirus in early childhood. tion au poliovirus dans la petite enfance. vaccination in compliance with the national schedule, complète de vaccinations antipoliomyélitiques en conformité and received one dose of IPV or bOPV within 4 weeks avec le calendrier national, ainsi qu’une dose de VPI ou de VPOb IPV-only schedule Calendrier «tout VPI» to 12 months of travel, in order to boost intestinal dans les 4 semaines à 12 mois précédant le voyage, afin de An IPV-only schedule may be considered in countries Il est possible d’envisager un calendrier «tout VPI» dans les mucosal immunity and reduce the risk of poliovirus renforcer l’immunité mucosale intestinale et de réduire le risque with sustained high vaccination coverage and very low pays où la couverture vaccinale est durablement forte et où le shedding. Some polio-free countries may require resi- d’excrétion de poliovirus. Certains pays exempts de poliomyé- risk of both WPV importation and transmission. IPV is risque d’importation et de transmission de PVS est très bas. Le dent travellers from polio-infected countries to be lite peuvent exiger des voyageurs en provenance de pays infec- usually given by intramuscular injection as it is less VPI est habituellement administré par voie intramusculaire car vaccinated against polio in order to obtain an entry tés par cette maladie dans lesquels ils résident, qu’ils soient reactogenic than when given by subcutaneous injection, il est ainsi moins réactogène qu’en injection sous-cutanée et visa, or they may require that travellers receive an addi- vaccinés contre elle pour obtenir un visa d’entrée ou qu’ils and it may be included as a component of combination peut entrer dans la composition d’un vaccin combiné. On admi- tional dose on arrival, or both. Travellers to infected reçoivent une dose supplémentaire en arrivant, voire imposer vaccines. A primary series of 3 doses of IPV should be nistrera une série primaire de 3 doses de VPI en commençant administered beginning at 2 months of age. If the à 2 mois. Si la série primaire débute plus tôt (calendrier d’ad- 99 Potential for importation is considered very high in countries bordering endemic 99 Le potentiel d’importation est considéré comme très important dans les pays limitrophes des primary series begins earlier (e.g. with a 6, 10 and ministration à 6, 10 et 14 semaines, par exemple), il faudra countries or countries that have recurrent outbreaks; the potential is considered pays d’endémie qui subissent des flambées récurrentes; comme important en présence d’anté- high if there is a history of importation plus high traffic across the border; the poten- cédents d’importation et d’un trafic dense à travers la frontière; et comme moyen dans le reste tial is considered moderate in the rest of the world. du monde. 100 <15% (or <750 for infants <12 months, <500 for those 1 through 5 years and <200 100 <15% (ou <750 chez les nourrissons <12 mois, <500 chez les enfants de 1 à 5 ans et <200 chez 98 No. 50, 2015, pp. 681–700. 98 No 50, 2015, pp. 681-700. for those ≥6 years). ceux de ≥6 ans). 166 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016 RELEVE EPIDEMIOLOGIQUE HEBDOMADAIRE, No 12, 25 MARS 2016 167 areas should be vaccinated according to their national l’une et l’autre conditions. Les voyageurs à destination des schedules. zones touchées devront être vaccinés conformément à leur calendrier national.

Vaccination of health-care workers Vaccination du personnel soignant All health-care workers worldwide should have Tous les soignants dans le monde devront avoir reçu une completed a full course of primary vaccination against série complète de doses de primovaccination contre la polio- poliomyelitis.  myélite. 

WHO web sites on infectious diseases – Sites internet de l’OMS sur les maladies infectieuses

Avian influenza http://www.who.int/csr/disease/avian_influenza/en/ Grippe aviaire Buruli ulcer http://www.who.int/buruli/en/ Ulcère de Buruli Child and adolescent health and development http://www.who.int/child_adolescent_health/en/ Santé et développement des enfants et des adolescents Cholera http://www.who.int/cholera/en/ Choléra Deliberate use of biological and chemical agents http://www.who.int/csr/delibepidemics/ Usage délibéré d’agents chimiques et biologiques informationresources/en/ Dengue (DengueNet) http://apps.who.int/globalatlas/ Dengue (DengueNet) Epidemic and pandemic surveillance and response http://www.who.int/csr/en/ Alerte et action en cas d’épidémie et de pandémie Eradication/elimination programmes http://www.who.int/topics/infectious_diseases/en/ Programmes d’éradication/élimination Fact sheets on infectious diseases http://www.who.int/topics/infectious_diseases/factsheets/en/ Aide-mémoires sur les maladies infectieuses Filariasis http://www.filariasis.org Filariose Geographical information systems (GIS) http://gamapserver.who.int/mapLibrary/ Systèmes d’information géographique Global atlas of infectious diseases http://apps.who.int/globalatlas/ Atlas mondial des maladies infectieuses Global Outbreak Alert and Response http://www.who.int/csr/outbreaknetwork/en/ Réseau mondial d’alerte et d’action en cas Network (GOARN) d’épidémie (GOARN) Health topics http://www.who.int/topics/en La santé de A à Z Human African trypanosomiasis http://www.who.int/trypanosomiasis_african/en/ Trypanosomiase humaine africaine Influenza http://www.who.int/csr/disease/influenza/en/ Grippe Influenza network (FluNet) http://who.int/flunet Réseau grippe (FluNet) International Health Regulations http://www.who.int/ihr/en/ Règlement sanitaire international International travel and health http://www.who.int/ith/en/ Voyages internationaux et santé Leishmaniasis http://www.who.int/leishmaniasis/en Leishmaniose Leprosy http://www.who.int/lep/en Lèpre Lymphatic filariasis http://www.who.int/lymphatic_filariasis/en/ Filiariose lymphatique Malaria http://www.who.int/malaria/en Paludisme Neglected tropical diseases http://www.who.int/neglected_diseases/en/ Maladies tropicales négligées Outbreak news http://www.who.int/csr/don/en Flambées d’épidémies Poliomyelitis http://www.polioeradication.org/casecount.asp Poliomyélite Rabies http://www.who.int/rabies/en Rage Global Foodborne Infections Network (GFN) http://www.who.int/gfn/en Réseau mondial d’infections d’origine alimentaire Smallpox http://www.who.int/csr/disease/smallpox/en Variole Schistosomiasis http://www.who.int/schistosomiasis/en/ Schistosomiase Soil-transmitted helminthiases http://www.who.int/intestinal_worms/en/ Géohelminthiases Tropical disease research http://www.who.int/tdr/ Recherche sur les maladies tropicales Tuberculosis http://www.who.int/tb/en and/et http://www.stoptb.org Tuberculose Immunization, Vaccines and Biologicals http://www.who.int/immunization/en/ Vaccination, Vaccins et Biologiques Weekly Epidemiological Record http://www.who.int/wer/ Relevé épidémiologique hebdomadaire WHO Lyon Office for National Epidemic Bureau OMS de Lyon pour la préparation Preparedness and Response http://www.who.int/ihr/lyon/en/index.html et la réponse des pays aux épidémies WHO Pesticide Evaluation Scheme (WHOPES) http://www.who.int/whopes/en Schéma OMS d’évaluation des pesticides (WHOPES) WHO Mediterranean Centre Centre Méditerranéen de l’OMS pour for Vulnerability Reduction, Tunis http://wmc.who.int/ la Réduction de la Vulnérabilité à Tunis (WMC)

Yellow fever http://www.who.int/csr/disease/yellowfev/en/ Fièvre jaune 168 WEEKLY EPIDEMIOLOGICAL RECORD, NO 12, 25 MARCH 2016

The introduction of IPV, the OPV switch, and risk mitigation

Information Note Version: 11 April 2016

In the context of the current supply constraints for Inactivated Polio Vaccine (IPV), this document provides a summary of the rationale for the introduction of IPV, in relation to the switch in Oral Polio Vaccines (OPV) that is scheduled for April 2016.

This document also outlines the implications of the delays on all product presentations that are procured through UNICEF and the PAHO Revolving Fund, including actions being taken to proactively manage and minimize the consequences.

Importantly, for countries affected by the supply constraints, there is an overview of the risk management rationale and mitigating strategies, as endorsed by the Strategic Advisory Group of Experts on immunization (SAGE) to WHO.

Contents Global Challenge: IPV Shortage As part of the Polio Endgame Strategy and as recommended by the WHO, all 126 countries 1. Background and rationale for IPV ...... 2 which at the start of 2013 were only using OPV, were required to introduce at least 1 dose of IPV 2. The position of SAGE on IPV and the OPV switch in April 2016 ...... 3 into routine immunisation schedules. 3. Overview of the supply constraints for IPV ...... 4 In March 2016, the largest IPV supplier to the Global Polio Eradication Initiative (GPEI) announced 4. Risk management rationale and mitigating strategies ...... 6 an approximately 40% reduction in supply for 2016 and 2017, which are related to production scale up issues. The shortage in IPV supply is being managed globally, with prioritisation of IPV delivery to countries at highest risk. An alternative to the intramuscular injection of a full IPV dose, countries may choose the implementation of a two-dose fractional dose schedule (using 1/5 of a full dose), via the intradermal (ID) route.

1

1. Background and rationale for IPV 2. The position of SAGE on IPV and the OPV switch in April 2016

As part of the Polio Eradication and Endgame Strategic Plan (the Polio Endgame) 2013-2018, and as recommended by WHO, all 126 countries which, at the start of 2013 were only using OPV, were as conr t oa stc at ro r to ay required to introduce at least 1 dose of the IPV into routine immunization schedules as part of preparations for the global withdrawal of the type 2 containing OPV now confirmed for April 2016. n er e raei visry rup pers n immuniain me an reviee ype Vaine erive Plivirus VPV epiemily an all reainess rieria r e The level of commitment from countries to meet this timeline has been exceptional. Almost all countries si reairme pril r e lally rinae iraal ype nainin ral using only OPV at the start of 2013 had committed to introduce IPV before the end of 2015 and 941 (out Pli Vaine PV y siin rm use rivalen PV PV ivalen PV PV of a total of 126) have already introduced IPV as of 1 April 2016. Unfortunately the rapid scale-up of IPV production required has encountered multiple challenges, leading to a global shortage. conr tat ry country sou sto usn t an ntrouc on a sn ay o ts coosn tn r an ay tn ro a stocs o t tn to s o tat Based on the assessment of scenarios at 6 April 2016 following additional reductions in supply, current at an conr ts roa ro src ry onts to constraints mean that approximately 20 countries that have not already received their first IPV shipment through UNICEF and are considered at low risk for circulating vaccine-derived poliovirus SAGE’s landmark decision follows the endorsement by the World Health Assembly (WHA) in May 2015, (cVDPV) type 2 outbreaks will not be able to introduce IPV in 2016. These countries are expected to en inisers eal rm emer aes ape a resluin n e lal er receive their first IPV shipments in the fourth quarter of 2017. eraiae pli

In addition, shipments to approximately 25 countries that have already introduced IPV and considered In a milesne ars e si il plivirus PV ype as elare as eraiae rlie at low risk for type 2 outbreaks will not receive additional supply before the fourth quarter of 2017. in epemer PV ype as n een eee lally sine vemer an e nly These delays, while unfortunate and leading to stock-outs, are unavoidable. As soon as a decision is remainin enemi PV ype srains are n resrie Paisan an anisan made on supply allocation, affected countries will be immediately notified by WHO and UNICEF. e iraal ype nainin PV ill ulimaely eliminae e ris e emerene ne Regardless of a country’s IPV introduction date, it was confirmed by SAGE at its October meeting2 that VPV in e uure an ill preven upars ases vaine assiae paralyi all countries must implement the globally synchronized switch from trivalent OPV (tOPV) to bivalent plimyeliis a urrenly ur ea year as a resul e ype mpnen in rivalen PV e OPV (bOPV) in April 2016. lally synrnise si ill erere e rea siniiane r e pli eraiain prramme i remenus puli eal eneis What is the role of IPV in the Endgame Strategy?

IPV’s primary value is in minimising the occurrence of paralytic disease from any type 2 VDPV after the OPV switch in April 2016. t ts tn n ctor conr a nur o y onts suar o

The short term risk of a cVDPV2 outbreak after the switch is higher in countries with low routine to no or stc ntaton immunization coverage or a history of cVDPV2 or wild polio virus outbreaks, as well as in countries • e lally synrnie si ill ae plae ro r to ay sharing borders with higher risk countries. This risk has being reduced by boosting population immunity • ll unries mus implemen e PV si in pril rearless IPV through ongoing high quality tOPV campaigns before the switch to bOPV. inruin ae • ven in e even urer anes in IPV supply e si ae ill n e ane In tier 1 and 2 countries at risk of cVDPV2, should an outbreak of cVDPV2 occur after the switch, having • iss ninue PV use is reaer an e riss siin PV a is sae IPV already introduced will enable a more effective and rapid outbreak response, due to IPV’s role in priming the immune system for a more rapid and robust response to OPV. IPV will also help to protect aocaton rocss or t aaa suy o r urer eails see pae against paralytic polio and to boost immunity to polio infection. rs anant ratona r urer eails see pae In the event of a VDPV2 being detected in any country after the switch, a global stockpile of monovalent type 2 OPV (mOPV2) and IPV will be available for outbreak response3.

One dose of IPV will therefore induce an immunity base to poliovirus type 2 and overall serve as a risk mitigation tool. e nlusins an remmenains e meein in er are pulise in e Weekly Epidemiological Record eemer pinererp

1 Data on IPV introductions, updated monthly, is available at: www.who.int/immunization/diseases/poliomyelitis/endgame_objective2/en/ 2 Meeting of the Strategic Advisory Group of Experts on immunization, October 2015: conclusions and recommendations. Weekly Epid. Record, 90. (December 2015). Available at: http://www.who.int/wer/2015/wer9050.pdf 3 In this case, mOPV and IPV will be used per the Type 2 Outbreak Protocol, to be published April 2016: http://www.polioeradication.org/ 2

3. Overview of the supply constraints for IPV rc as runty n ct as t an ur aanst ntroucton ut t no ss suy s t rary ostac as tr nsucnt ocus on o ar t anuacturrs no y ar tr suy constrants auat suy

n March 201, E issed awards to two manfactrers (Sanofi aster and ilthoen ioloicals) hen the sith as eing panned prie as seen as the argest ostae to goa root o one for the sly of in 1, 5 and 10 dose ials, and lon term sly areements were established dose o IPV in the PVon sing ontries most o hom are o and midde inome ontries it throh to 201 hese were the only two manfactrers which offered sbstantie antities from the as arond times more epensive per dose than tPV. he arge vome made it possie to ahieve start of the roramme in resonse to UNICEF’s tender and agreed to provide IPV to the UNICEF market. a prie hih aoed the programme to proeed ith the reommendation to introde dose o IPV nly ilthoen ioloicals is slyin the AH eolin nd domented in the Position Paper on poio pished in Ferar .

oth manfactrers hae reorted redced aailability de to technical challenes in scalin blk oever de to the arge vome o IPV needed on to manatrers ere in the proess o saing rodction and the associated ality control testin and releases p their prodtion apait to meet the inrease in the goa reirements and thereore oered to spp the reired vaine to the UNICEF and P markets. his as aso onirmed throgh constran stuaton s roct to ran trou or a rouct rsntatons independent assessments. In ear these manatrers onirmed that enogh IPV od e rocur trou t on un an natona ornnts his is a lobal made avaiae to meet the needs o the Endgame Pan at an aordae prie. sitation, all markets are affected, and manfactrers hae reaffirmed to WH that is not bein redistribted to more rofitable markets In arh the argest IPV sppier to the PEI annoned an approimate redtion in spp or and . his redtion is reated to prodtion sae p isses and not to priing. elar dates will be shared with WH and E reional staff, contry offices, oernments and artners as soon as new information becomes aailable o s t aaa suy n aocat y as t aocaton o suy to countrs runty can he avaiae IPV spp is eing managed goa prioritiing deiver o IPV to ontries at highest risk. n the third arter of 201, manfactrers informed E and AH that they wold not be able to meet their commitments to slyin in 2015 n 2015, manfactrers also adised of frther hen the Poio Endgame trateg as anhed ontries ere divided into or tiers primari or delays on sly in 201 prposes o panning and prioritiation. hese tiers represent each country’s eve o risk tier eing at highest risk or a VPV otreak ater the sith rom tPV to PV. n ebrary and March 201, manfactrers annonced added sbstantial decreases in aailability for 201 and 201, as well as delays to the timin of delieries hese redctions—which reslt in r ar our crtra us to trn t casscaton o ac country an tror tr aroimately 0 less than the oriinal commitments—mean that not all contries will be able to rortaton or t aocaton o suy ountrs ar consr to n a r rs tr introdce by the time of the switch in Aril 201 he transmission o id poiovirs has not et een interrpted he ontr has a histor o VPV otreaks accine manfactrers had initially been confident that the scale of rodction wold ensre here are onsistent o eves o rotine immniation overage and thereore popation sfficient caacity to meet the lobal demand for Howeer, oer the ast two years, manfactrers immnit to tpe hae reeatedly reorted isses with their scale, resltin in diminished sly he reortin has he ontr shares orders ith higher risk ontries been incremental, and reslted in a roressie deterioration of the sly sitation In the rrent ontet o the onstraints this groping o ontries into tiers is a primar onsideration his series of chanes has also meant that some contries hae rerettably been informed of chanes to or spp aoation and ontries at higher risk o VPV otreaks are eing prioritied. their shiment at last minte and on more than one occasion n a few cases, delays hae also occrred in order to allow time for the roramme to ealate how the se of eistin stocks can meet In toer E emphasied that even in the event o rther hanges in IPV spp the sith the lobal blic health need most effectiely date i not e hanged. t this time E aso reested its Poio orking rop to provide rgent gidane on the optima management o IPV spp i it is again reded. reent discssions hae taken lace between WH, E and manfactrers to identify any stes to manae the redctions WH, E and artners are also takin all actions to limit the nmber of In ear pri ooing the sstantia dereases to spp avaiaiit the Poio versight oard P contries imacted by the delays and minimise the conseences of this chanin sitation revieed the overa goa sitation inding the needs o endemi ontries otreak response and rotine IPV immniation. cson on t aocaton o suy us on as tr an assssnt o rss rat to t ra sca u o at t start rconatons t t na aroac ar as oos First ensring the introdtion and sstained se o IPV or rotine immniation in tier and o t na an an at t t o tnrn anuacturrs ontries aking stoks avaiae or Is in endemi ontries and or otreak response ater the sith rior to the tender, analysis condcted confirmed that the caacity of manfactrers was sfficient to inimiing deas in introdtion in rotine immniation and stokots in tier and ontries. rodce enoh accine to enable the introdction of one fll dose of into all rotine immniation systems (arond 0 million doses annally)he offers oriinally receied eceeded this demand

at s t act on natona unaton roras suy stuaton rans ynac an s n cosy ontor ase on the atest inoration ro anuacturers on suppy aaiaiity an the ost optiu scenarios at east countries out o – incuin aost a tier an countries – hae receie their irst shipent in tie to introuce the accine eore the en o act y t ays at can a country o to tat rss or countrs tat a not yt ntrouc the o ris countries approiatey countries i eperience eays in eieries he aority o these countries i e eaye unti the ourth uarter o a a orts to ot ty ouaton unty ror to t stc or countrs tat rnc ays to tr rsuy or routn unaton pproiatey countries that hae areay introuce i not receie aitiona suppy unti the ourth uarter o his roup o countries is consiere at o ris or type outreas oornat ntaton o t stc n a y ct an ty annr The above information is based on the assessment of scenarios as of 4 April 2016, and is expected to fluctuate over coming months. All efforts are being made to minimize the number of countries delayed. nsur tat raratons or ntroucton ar cot n aanc WHO and UNICEF will coordinate closely with countries affected on the related implications.

ocunt r oss a ss os o to actat any atr tracn an oo u countries aecte are receiin irect counications ro uppy iision an aout or nants or atr t stc the tiin o their shipent his i ao or pannin o the introuction or restart o accination or eiie inants as soon as possie ater the receipt o accines nce aaiae suppy is conire an reiona an country oices i aciitate iscussions ith countries to nanc suranc systs ientiy ne aunch ates an support any austents to proraes rar a rsons an 4. Risk management rationale and mitigating strategies

at s t o rs or t countrs tout osy ontor stocs at a s to rort aaa suy to atrs ouatons he consiere the ooin as a copein ris anaeent rationae an to has a iite roe in preentin eerence hoeer is ery eectie in preentin paraytic isease in any outrea his aue i increase ith tie ater the sitch as the irth nsur strct arnc to accnatn crn ony n t tart rou cohorts that hae not receie ein to accuuate he aority o countries aecte y the eay are in o ris tiers an opuation iunity y t utos a ocy aainst type is hih in these countries ue to consistenty hih routine iunisation coerae so the ris o eerence an sprea is inia s accnaton cars an rstrs cty he ris o eerence is principay reuce y ensurin hih coerae an ay incue hih uaity t s eore the sitch in countriescounities ith iunity aps n aition to t s aost a hihest ris tier an tier countries i hae introuce countrs n any stuaton ay in routine iuniation eore the sitch coos t ntaton o a toos ractona os scu oa stoc o c s rua an is aaiae or outrea response in the eent o etection ater the sitch ountries shou hae a echanis in pace or eerency authoriation o use in an outrea

he concue that the puic heath riss associate ith the continue use o t ar outeih the ris o ne eerence ater use o t is stoppe een in countries here introuction is eaye eetin o the trateic isory roup o perts on iuniation ctoer concusions an recoenations Weekly Epid. Record Weekly Epid. Record eceer aiae at httphointererp

at actors sou countrs consr n raton to t toos ractona os scu or

building on the “primeboost” model for protection

s cns or us as a ractona os anstr a ncton

Additional programmatic guidance on strategies related vaccination of eligible infants who may have missed a scheduled dose of IPV after the OPV switch in April 2016 will be issued in coming weeks.

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April 2017 Use of fractional dose IPV in routine immunization programmes:

Considerations for decision-making

Purpose: This document provides a brief overview of the scientific basis and key programmatic considerations to guide national decision-making on the use of fractional dose IPV (fIPV), administered intradermally, in routine immunization programmes. Further details on the available evidence, key studies, and resources for implementation and training that are described in this document are available here. Background: Based on the progress made towards the global eradication of poliovirus, in April 2016 a switch from trivalent to bivalent oral polio vaccine (OPV) was implemented. In the lead-up to the switch, all OPV-only using countries committed to introducing IPV. In March 2014, long term supply agreements were established with two manufacturers to meet the projected global requirements for IPV, however since 2015 both manufacturers have reported a series of challenges in scaling up bulk production. This has led to a severe global shortage of IPV and only 105/126 of these countries have been able to introduce the vaccine to date. For more information on the background to the IPV supply constraints, please refer to the Information Note posted on this page. A. Evidence base Efficacy of fractional dose IPV: fIPV has been researched since the 1990s. In recent years, the evidence has grown to conclusively demonstrate that two fractional doses administered via the intradermal (ID) route offer higher immunogenicity compared to one full intramuscular (IM) dose of IPV [1,2,3,4]. As a result, a two-dose fIPV schedule has been strongly recommended to countries by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) [5,6], and in the WHO Position Paper on polio vaccines [7].  A fractional dose is one-fifth (1/5, 0.1 ml) of a full dose of IPV, injected via the intradermal (ID) route  fIPV is safe, effective and immunogenic  fIPV can be given alone, or at the same time as any other vaccine  In children also receiving oral polio vaccine (OPV), two doses of fIPV given at 6 and 14 weeks will help to “boost” their mucosal immunity against polioviruses [8] Fractional Dose  fIPV can be used in all types of polio immunization activities: in routine immunization, in supplementary immunization activities (SIAs), and in outbreak response [9] IPV (fIPV) and Immunogenicity: Results from multiple clinical trials (Cuba, Oman and Bangladesh), using IPV from different suppliers, demonstrated superior immunogenicity against all poliovirus serotypes, following the administration of two ID fIPV doses compared to one IM full IPV dose, when the ID dose was properly delivered. For the purposes of this guidance its Efficacy note, we focus on protection against poliovirus type 2.

Intradermal IPV administration with frac- Table 1. Summary comparison of two ID fIPV doses with one full IM IPV dose Schedule Seroconversion (%) Publication Country tional doses of IPV (0.1 mL or 1/5 of a full 2 fractional 2 fractional (Year) 1 full dose 1 full dose dose) offers potential cost reduction and doses doses this dose sparing method could ensure that Resik S, et al. (2010) [1] Cuba 6, 10 weeks 6 weeks 55 36 more eligible infants receive IPV and results Mohammed AJ, et al. Oman 2, 4 months 2 months 72 32 in better immunogenicity than a single full (2010) [2] dose of IPV. Resik S, et al. (2013) [3] Cuba 4, 8 months 4 months 98 63 Anand A, et al. (2015) [4] Bangladesh 6, 14 weeks 6 weeks 81 39 In order to ensure early protection, a sched- ule of fractional intradermal doses adminis- Regulatory considerations: IPV is not currently licensed by manufacturers for fractional use, and there are no plans at this tered at 6 and 14 weeks from birth may be time for IPV suppliers to pursue a label change for fIPV. Therefore, any move to fractional IPV will involve off-label use of considered, ascertaining that the two frac- IPV, and should require a decision by the Ministry of Health of the country, following recommendations from National Technical Advisory Groups on Immunization (NITAGs), or equivalent. It is not unusual for countries to make evidence- tional doses are separated by a minimum based decisions for vaccine administration that may differ from the labelled indications (for example, hepatitis A, human interval of 4 weeks. papillomavirus, pneumococcal conjugate, Haemophilus influenza type b, rotavirus, and yellow fever vaccine). Given the current supply situation and the high efficacy of a two-dose fIPV schedule, SAGE has encouraged countries to move to fIPV despite the off-label use, citing the studies above. [6] B. Programmatic considerations liil tils he eostte the opetiol esibilit o iistei two oses o i helth e setti itio oties sh s i i he le sessll itoe ito thei otie poes i oe to iie thei stos o eh ot to popel elte whethe se o tiol is opetioll esible i the tiol otet e o poti tos st be osiee s hihlihte i the tble below the iotio o e osietios sh s i sppot the ole o optio o i pioititio o sppl will be she oe ilble Factor Two doses of intradermal fIPV Licensing eisio eie b tiol elto thoit o eilet to ept o lbel se o Age of eoee t wees o eest ott o ost oties this will ot eie administration itiol isit ol itiol ietio t these otts oties shol ell ssess thei opot te betwee the wee wee isit oties with le opot tes ee to ble the esibilit o twoose shele ese tht hile will eeie both o the eie oses Vaccine tel ietio si l sies — itiol tii will be eie elth woe tii administration teils ob is e ilble hee Technologies to t o sties lesh b the bi ite ttes ist eostte tht si facilitate ietio eies sh s eele ptos o eeleee et ietos is ell ioei s whe administration si sie loe is lel peee b helth woes o ese o iisttio etl thee pots e eistee o se with peliitio epete i el itiol iitio eies e e eelopet o eisttio be osiee i the te the iotio bot eies to ilitte itel ietio be o hee Vaccine vial he sept o the ils toletes ltiple ptes withot lee st b hs presentations eostte tht septs eet the peoe tets o the hopeil oetio o ettio to beo ptes owee se o st ose ils e eoee whe ipleeti i otie poe ieli p to oses espetiel Multi-dose Vial otis the pesetie pheoethol whih es tht e eti oitios s esibe Policy i the lti ose il oli the opee ils be ept se o p to s te opei he si ose il will iel p to oses s oseee the ie pesettio o is ipott hoie s the i be o oses st be ose withi the tiee Cold chain o ll ie pesettios si tiol ose will eie o the ol hi pit pe ll ose s ope to wht is tpill eie o ose ll shele Data ll os o t eoi shol be pte ie eistes eos hoebse s et to ote the iisttio o two oses o Communications oitio pl will be eie to oe the eisio to ll e lol steholes ili eil ssoitios helth woes eies eplii the beeits o ephsii the eiee showi the oieioit o tiol ose Training ill eie tii o helth woes i be o es pope itel ietio tehie bilit to esse eies oet tii o iisttio oet t eoi o the two oses elth woe tii teils ob is e ilble hee Cost eet lsis b shows tht the estite ost o two oses plus eies wol ot to – pe iie hil his is opble to the et iisttio ost o oe ll ose Post-marketing hee is o eiee o iese ese eets ollowi iitio s with se o the tiol AEFI surveillance ose t oitoi epoti shol be i ple s o ll ies

esi et l oie otolle liil til o tiol oses o itite poliois ie iistee itell b eeleee eie i b ol o etios iseses ohe et l tiol oses o itite poliois ie i ew l ol o eiie esi et l ii te tiol ose o tite oliois ie l e et l l ii with tite oliois ie tel tiol ose iistee b ioeele eie oie otolle il ie eeti o the ttei iso op o pets o itio pil – olsios eoetios esse t wwwwhoitwewee eeti o the ttei iso op o pets o itio tobe – olsios eoetios esse t wwwwhoitwewee olio ies positio ppe h esse t wwwwhoitwewee i et l i o itite poliois ie i i iee hl et l tiol ose tite oliois ie itio pi – el tte i e ob otl l ep esi et l e esposes te tiol oses o tite oliois ie si ewl eelope tel et ietos oie otolle liil til i b ie le et l et ioeiit o itite poliois ie whe ie with eslesbell obie ie ellow ee ie whe ie i ieet iisttio otes phse oise oieioit til i he bi et lobl elth e o et l opiso o the ioeiit o ios booste oses o itite polio ie eliee itell ess itsll to iete lts ol o etios iseses lee tel iisttio o tiol ose o itite poliois ie si itel ptes s sie pblishe s et l tel iisttio o tiol oses o itite poliois ie osespi optio o polio iitio ol o etios iseses i pess blitio pei oli tteet ltiose il oli eisio esse t httpppswhoitiisbitsteep Landscape Analysis

Trends in vaccine availability and novel vaccine delivery technologies: 2008–2025

July 2008

Challenges with Administration Bâtiment Avant Centre Phone: 33.450.28.00.49 of fIPV 13 Chemin du Levant Fax: 33.450.28.04.07 01210 Ferney Voltaire www.path.org Intradermal delivery of fIPV using needle and syringe can be performed using the Mantoux France www.who.int technique, wherein the needle is inserted at a narrow angle from the skin surface and the vaccine deposited underneath the skin. Generally, the procedure is considered to be slow and technically challenging, especially when vaccinating an infant. Intradermal vaccine delivery systems with the use of needle-free injectors could potentially alleviate this concern.

Tropis® Intradermal Injection System uses jet injector technology that propels liquid at high pressure to deliver vaccines through the skin without utilising needles, providing dose sparing effect and greater safety from needle stick injuries. Vaccine delivery technologies surveyed Category Technology Primary potential benefits

Eleven broad categories of delivery technologies were included in the survey (Table 6), ranging from ▪ Reduced waste. ways to deliver vaccines more safely and/or more easily, to ease those that simplify the reconstitution process. Other technologies engage a different type of immune response using lower doses of antigen. 6 Microneedles ▪ Reduction in sharps. ▪ Available in unit doses. Each technology has been assigned a unique identifier (T001–T130), which is used to refer to 6.1 Hollow microneedles. ▪ Integrated vaccine and device (6.2, 6.3, 6.4). technologies in the text. A full summary of the technologies reviewed is presented in Annex 2. 6.2 Solid microneedles. ▪ Dose-sparing. 6.3 Vaccine-coated microneedles. ▪ Reduced pain. The output of the survey includes many more technologies that are not currently used for delivery of 6.4 Dissolvable/biodegradable microneedles. ▪ Reduced waste. vaccines and/or may not be appropriate for vaccine delivery in LMICs because of cost or complexity. However, information has been recorded for these devices, because if they have potential to be 7 Inhalation/pulmonary delivery ▪ No sharps. developed into technologies appropriate for use in low-resource settings, the expertise and intellectual ▪ Available in unit doses. property is most likely to reside with the developers of these expensive and complex devices. 7.1 Liquid inhalation. ▪ Potential for integrated vaccine and device. 7.2 Powder inhalation. ▪ Reduced pain. The survey of vaccine delivery technologies relied primarily on publicly available information, supplemented with documentation provided by experts, including PATH and WHO staff members, 8 Intranasal delivery ▪ No sharps. and an independent consultant (see References for details). ▪ Available in unit doses. 8.1 Nasal spray (powder). ▪ Integrated vaccine and device. Table 6. Categorization of vaccine delivery technologies and associated benefits. 8.2 Nasal spray (liquid). ▪ Ease of administration. ▪ Reduced pain. Category Technology Primary potential benefits 9 Transdermal delivery ▪ Reduced sharps. ▪ Unit dose. 1 Injection safety devices ▪ Safer administration; reuse prevention and ▪ Integrated vaccine and device. needlestick prevention. 9.1 Transdermal patches (microneedle-free). 9.2 Transdermal patches with micro-electrodes. ▪ Reduced pain. 1.1 Auto-disable syringes. ▪ Can be used with any liquid vaccine. ▪ Reduced waste. 1.2 Anti-stick syringes. ▪ Readily available. 10 Intradermal needle delivery ▪ Available in unit doses. 2 Prefilled reconstitution devices ▪ Prevents reconstitution errors. ▪ Potential for integrated vaccine and device. ▪ Available in unit doses. 10.1 Needle depth limiters. ▪ Dose-sparing. 2.1 Prefilled reconstitution syringes. ▪ Integrated vaccine and device. 2.2 Prefilled reconstitution vials/pouches. 11 Prefilled containers ▪ Prevents dosing errors. ▪ Unit dose. 3 Implants ▪ Integrated vaccine and device. 11.1 Prefilled syringes. ▪ Reuse prevention. ▪ Safer administration; no sharps for disposal. 11.2 Prefilled cartridges. ▪ Integrated vaccine and device. ▪ Unit dose. 3.1 Biodegradable implants. ▪ Ease of administration. ▪ Potential for schedule reduction, dose- sparing (i.e., delivery of a reduced dose intradermally), and thermostability (no evidence yet). Out of scope of the survey

4 Jet injectors ▪ No sharps. Novel adjuvants and stabilization developments were excluded from this survey, but they are ▪ Available in unit doses. discussed briefly where they are relevant to potential use of the other delivery technologies. 4.1 Disposable cartridge jet injectors with ▪ Integrated vaccine and device (4.3). Information on the potential costs of the various devices was not included, as many are still in early prefilled unit dose cartridges. ▪ Dose-sparing possible. research and development phases and a thorough analysis of offsetting factors for each vaccine and 4.2 Disposable cartridge jet injectors: end-user delivery technology pairing would be essential in order to take into account cost-saving factors such 4.3 filling. as reductions in vaccine wastage due to unit dose formats. 4.4 Single-use disposable jet injectors. Solid particle jet injectors.

5 Sublingual/buccal delivery ▪ No sharps. ▪ Available in unit doses. 5.1 Dissolvable tablets/wafers. ▪ Integrated vaccine and device. 5.2 Buccal/oral sprays. ▪ Ease of administration. 5.3 Oral patches. ▪ Reduced pain.

Excerpts from page 12 - 13 Page 12 Excerpts from page 12 - 13 Page 13 Use of bioneedles will require reformulation of existing vaccines. Delivery of the implants could be needle-free and might involve reduced pain compared with N-S (due to the high velocity of injection),7 but will require specialized devices with compressed air or spring-powered mechanisms.8,9

• The Bioneedle Group™ (T024) and Solid Dose Injector™ (Glide Pharma, T026) are probably the leaders in this field regarding formulation and delivery of vaccines.

Table 9. Potential opportunities from use of biodegradable implants.

Opportunities Opportunities Barriers to use 2008–2015 2015–2025

▪ The introduction of a ▪ They might be compatible ▪ Delivery devices might be biodegradable implant vaccine by with thermostable vaccine complex and costly. 2015 is unlikely. formulations. ▪ Will require reformulation of ▪ Controlled release of vaccine existing vaccines. might reduce the number of booster doses required, but this concept has not yet been proven.

4. Jet injectors DCJI design features DCJIs consist of an “injector device” or “handpiece” that contains the propellant mechanism or power Jet injectors propel liquid at high pressure to deliver medications through the skin without needles. 10 source (such as a spring) into which disposable single-use cartridges are inserted. Each cartridge (or They have been used to deliver hundreds of millions of doses of vaccines over the past 50 years. needle-free syringe) has its own sterile orifice and nozzle. • The vast majority of these were delivered using multi-use-nozzle jet injectors (MUNJIs). • The majority of DCJIs are used for self-administration of insulin and other hormones, and this However, concerns that MUNJIs could be responsible for transmission of bloodborne 10 has driven their design. The notable exception is the Biojector® 2000 (T069), which is used pathogens between consecutive vaccine recipients led to the discontinuation of their use. to administer approximately 1 million vaccine doses per year at private, public, and US Navy Attempts to circumvent these problems by incorporating disposable caps have not been and Coast Guard immunization clinics.10 successful.10 • DCJIs that have been developed for delivery of vaccines can generally be adapted to deliver • Therefore, devices currently being developed and considered in this analysis are either vaccines SC, IM, or ID by incorporating spacers that alter the distance between the nozzle and disposable cartridge jet injectors (DCJIs—see below), or single-use disposable jet injectors the skin. The Biojector® 2000 (T069) has been used in ID dose reduction studies in Cuba (6-, where the whole device is discarded after a single use. 10-, and 14-week-old infants), Oman (2-, 4-, and 6-month-old infants), and the Dominican • Jet injectors for delivery of DNA vaccines are also being developed (PowderMed, T126). Republic (6- to 24-month-old infants). • No currently available DCJI has a design appropriate for vaccine delivery in LMICs. Draft Jet injectors offer the benefits of needle-free vaccine delivery and the potential for dose-sparing by design specifications for DCJIs have, however, been produced by WHO.11 virtue of the fact that delivery can be targeted to the intradermal layer. Currently, DCJIs have regulatory approval only for SC or IM delivery of vaccines. Local adverse effects following jet DCJI evaluation injection are generally comparable to or slightly higher than those associated with N-S, particularly A number of prototype or development DCJI devices meet the majority of the proposed WHO design with vaccines containing alum adjuvants. Surveys of usage of the Biojector® 2000 (T069) in the requirements, including: United States have found its usage characteristics to be acceptable for adult and pediatric vaccinees. 10 Injection-site bleeding and ecchymosis are rare, but occur more often than with N-S. However, jet • Zetajet™ (Bioject, T070). injectors could, in theory, be suitable for all inactivated, subunit, or conjugate vaccines currently • E-Jet500™ (Euroject, T060). delivered by N-S. One outstanding concern is the potential reactogenicity of alum-adjuvanted • Pharmajet™ (PharmaJet, Inc., T064). vaccines, particularly when delivered intradermally. This will be evaluated as part of the DCJI • evaluation project being undertaken by PATH, WHO, and the US Centers for Disease Control and Lectrajet® M3RA (D’Antonio Consultants International, T068). Prevention (CDC). Some or all of these will be evaluated as part of a four-year collaborative project led by PATH, Single-use disposable jet injectors are likely to be too expensive for widespread use in LMICs and are involving the CDC, WHO, and others, to demonstrate the feasibility of using DCJIs to deliver routine not considered further. PowderMed’s jet injectors are also fully disposable and are being developed EPI vaccines at the current dose via the existing route, whether ID, SC, or IM. The program will also specifically for DNA vaccines coated onto gold particles and so would likely not be affordable for explore the potential for dose-sparing by delivery of reduced doses by the ID route. LMICs. Table 10. Potential opportunities from use of jet injectors.

Opportunities Opportunities Barriers to use 2008–2015 2015–2025 Page 16 ▪ The aim of the PATH DCJI ▪ Reduction of sharps, sharps ▪ Ideally require prefilling of evaluation project is to have a waste, and needlestick injuries cartridges by vaccine fully validated, WHO and associated costs. manufacturers. prequalified, production-ready ▪ Simplified SC, IM, and ID ▪ Use of prefilled cartridges technology ready for adoption by delivery. requires regulatory approval of LMICs no later than 2011. ▪ Reformulation of existing the device and vaccine vaccines is not needed. combination product, rather ▪ Cartridges might have lower than approval of the device transportation costs than only. prefilled syringes.11 ▪ Use of prefilled cartridges ▪ Potential for dose-sparing via could also be dependent on ID delivery, leading to adoption of industry-standard improved accessibility for high- designs for cartridges, which cost vaccines and vaccines for would need strong links which manufacturing capacity is between vaccine and DCJI limited. manufacturers.

Abbreviations used: DCJI: disposable cartridge jet injectors; ID: intradermal; IM: intramuscular; SC: subcutaneous; LMICs: low- and middle-income countries; WHO: World Health Organization.

Excerpts from page 16 - 17 Excerpts from page 16 - 17 Page 17 Table 15. Potential opportunities from use of transdermal technology.

Opportunities Opportunities Barriers to use 2008–2015 2015–2025

▪ Likely development of needle- ▪ Likely development of TCI- ▪ LT is expressed by only 53% free TCI ETEC vaccine, based on based cholera vaccine. of ETEC isolates30; vaccination LT. takes approximately 6 hours. ▪ The approach might be applicable only to a very small subset of proteins.

Abbreviations used: ETEC: enterotoxigenic E. coli; LT: heat-labile toxin of E. coli; TCI: transcutaneous immunization.

10. Intradermal needle delivery ID delivery using N-S can be performed using the Mantoux technique; however, this is considered to be slow and technically difficult. Modification of N-S so that they can be easily used for ID delivery might provide some of the benefits associated with dose-sparing.

• The Soluvia™ device (Becton Dickinson, T019) represents one approach to achieve this end, by developing a syringe with a single microneedle. • Another approach actively being pursued in a collaboration between PATH and SID Technologies (T018) is the development of an adapter that can be used with standard needles. The approach should be low cost and simple to develop.

Table 16. Potential opportunities from use of ID needle delivery.

Opportunities Opportunities Barriers to use 2008–2015 2015–2025

▪ Delivery of existing (or ▪ Likely to be increased ▪ Continued use of sharps. concentrated) formulations of evaluation and uptake of hollow ▪ Possible reactogenicity of liquid vaccines could have microneedle technology for adjuvants. potential dose-sparing benefits, delivery of novel and existing assuming reactogenicity profiles liquid vaccines. are acceptable. ▪ Likely to be delivery of novel vaccines with liquid formulation, especially if developed for ID delivery.

Abbreviation used: ID: intradermal.

11. Prefilled syringes Prefilled syringes are already used for some vaccines, e.g., HepB, tetanus, DTP-HepB (Ecovac4™, Panacea) (all in Uniject™ devices); HepA, dT, HepB, HPV, MenC, MenACW135Y, rabies, typhoid, and VZV. Prefilled syringes reduce vaccine wastage, avoid the need for preservatives, simplify delivery, and reduce vaccine administration errors.

Page 24

Excerpts from page 24 Received: 7 July 2017 Feasibility of conducting Revised: 15 August 2017 Accepted: intradermal vaccination 23 August 2017 Cite as: campaign with inactivated Mohammad Tahir Yousafzai, Ali Faisal Saleem, Ondrej Mach, Attaullah Baig, poliovirus vaccine using Tropis Roland W. Sutter, Anita K.M. Zaidi. Feasibility of conducting intradermal intradermal needle free vaccination campaign with inactivated poliovirus vaccine using Tropis intradermal needle free injection system, injection system, Karachi, Karachi, Pakistan. Heliyon 3 (2017) e00395. doi: 10.1016/j.heliyon.2017. Pakistan e00395

Mohammad Tahir Yousafzai a, Ali Faisal Saleem a,*, Ondrej Mach b, Attaullah Baig a, Roland W. Sutter b, Anita K.M. Zaidi a,c

a Aga Khan University, Karachi, Pakistan b Polio Eradication Department, World Health Organization, Geneva, Switzerland c Bill and Melinda Gates Foundation, Seattle, USA

* Corresponding author at: Paediatric Infectious Diseases, Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan. E-mail address: [email protected] (A.F. Saleem).

Abstract

Background: Administration of intradermal fractional dose of inactivated ® poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its Benefits of Tropis Needle-Free Injection intradermal application using needle and syringe is technically difficult and System for fIPV Administration requires trained personnel. Methods: We assessed feasibility of conducting an intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis needle-free injector. During A recent study assessed the feasibility of using the Tropis® Needle-Free Injection System for the one-day fIPV campaign, we measured average application time to administer an intradermal fIPV campaign. In this study, eleven vaccinator teams underwent a two-day “ ” fIPV with Tropis, collected ergonomic information and measured vaccine wastage. training and immunized 582 children between 4 months and 5 years of age. Application time was defined as time period from charging of the device till disposal of the used syringe. The Results: Eleven vaccinator teams, after two-day training, immunized 582 children average application time was 48 seconds which decreased towards campaign completion. between 4 months and 5 years of age. Average “application time” ranged from

The time of application of the vaccine using Tropis® Needle-Free Injection System is likely to be considerably shorter than traditional intradermal injections, though a head-to- http://dx.doi.org/10.1016/j.heliyon.2017.e00395 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license head comparison has not been done. The vaccinators reported that filling the device and (http://creativecommons.org/licenses/by-nc-nd/4.0/). administration of the injection was easy. There was also no vaccine loss during the entire study. The authors concluded that it is feasible, safe and efficient to use the Tropis® Needle- Free Injection System for the administration of fIPV in a campaign setting. Article No~e00395 Article No~e00395

35–75 seconds; the “application time” decreased with the number of children challenges, a successful fIPV campaign with BCG needle and syringe was carried vaccinated from 68 to 38 seconds between 1st and 30th child. 10/11 (91%) out in India and in Pakistan in 2016 [15]. vaccinator teams found no ergonomic issues; 1/11 (9%) assessed that it was not In order to overcome the perceived difficulties with use of BCG needle and syringe easy to remove air bubbles when filling the device. There was 0% vaccine loss in campaign settings, new intradermal administration methods are being explored, reported. No adverse events following immunizations were reported. including Tropis needle-free injection system manufactured by Pharmajet®, Interpretation: We demonstrated that it is feasible, safe and efficient to use Tropis (Colorado, USA) (Tropis). This device has been previously tested in polio studies for the administration of fIPV in a campaign setting. in Cuba and the Gambia. In these studies Tropis has demonstrated its ability to Keywords: Infectious disease, Public health, Vaccines, Immunology induce equal immunogenicity and injection quality when compared with other intradermal methods; and no safety concerns were identified [7, 16]. So far, 1. Background however, Tropis has not been evaluated for program feasibility, and safety in campaign setting. The objective of this study was to evaluate the feasibility and In the last several years, the Global Polio Eradication Initiative (GPEI) has made safety of Tropis for administering fIPV in campaign setting among children aged remarkable strides towards successfully eradicating polioviruses globally. As of 4–59 months in polio high risk area of Karachi, Pakistan. April 18, 2017, only 5 cases of poliomyelitis caused by wild poliovirus (WPV) were reported in 2017 from two endemic countries (Afghanistan and Pakistan) 2. Methods while no cases have been reported from the third endemic country (Nigeria) [1]. In order to declare poliovirus eradicated, not only WPV but also polioviruses Karachi is the biggest metropolitan city of Pakistan and is divided into 18 emanating from the use of oral poliovirus vaccine (OPV) need to be eradicated. administrative towns. The study was conducted in one of the low-income areas, This includes OPV (or Sabin) polioviruses as well as vaccine derived polioviruses. Ibrahim Hyderi in Bin-Qasim town − a peri-urban neighborhood, with estimated Therefore, the use of OPV has to be replaced with inactivated poliovirus vaccine population of about 150,000. The department of pediatrics and child health of the (IPV). As a first step in the Polio Eradication and Endgame Strategic Plan Aga Khan University (AKU) operates primary healthcare center (PHC) in this area. 2013–2018, Sabin strain of poliovirus type 2 contained in the trivalent OPV AKU has well-established demographic surveillance, which captures pregnancies (tOPV) was withdrawn globally in April 2016; and tOPV was replaced by bivalent and new births. The PHC provides Expanded Programme of Immunization (EPI) OPV (bOPV) containing Sabin strains 1 and 3. In addition, at least one dose of IPV services in liaison with the local town health officer. Children aged 4 to 59 months, was supposed to be introduced in all countries for risk mitigation purposes [2], living in Ibrahim Hyderi for at least 3 months, whose parent or legal guardian however, an unanticipated reduction in manufacturing capacities resulted in an provided informed consent were eligible to be enrolled in this study. acute shortage of IPV that affected 43 countries and caused either delayed IPV A group of “vaccinators” without any formal training regarding health or injection introduction or stock-outs in countries that had already introduced IPV [3, 4]. This administration but with at least secondary school certificates were hired. AKU global IPV shortage is predicted to last for several years and therefore GPEI started provided two-day training regarding the study protocol, consent taking procedure, exploring options of how to stretch the existing IPV supply. IPV, cold chain maintenance, and how to use Tropis. Eleven teams were formed Intradermal administration of 1/5th of full dose IPV (0.1 mL instead of 0.5 mL), (each team composed of 2 community mobilisers, 1 vaccinator and 1 assistant). referred to as fractional IPV (fIPV) has demonstrated good safety and We conducted a one day campaign on December 29, 2016. As per WHO immunogenicity [5, 6, 7, 8, 9, 10, 11, 12]; and can be considered as an important recommendations, temporary outreach vaccination centers in health houses, strategy to combat the shortage of IPV by dose sparing in routine immunization or religious institutions, schools, or offices of the local organizations and houses of for outbreak response campaigns [13]. the local leaders were established [14]. Vaccinators and their assistants set up While the use of full dose intramuscular administration of IPV in campaigns was vaccination stations in the temporary outreach centers in different locations in the successfully demonstrated in Africa, Pakistan and Afghanistan [14], the area, while their respective community mobilizers started house-to-house visits to intradermal use of fIPV in campaign settings was considered to be technically bring children to the temporary vaccination stations. The assistant in each team challenging with traditional BCG needles and syringes (considered as “classical obtained informed consent. If consent was provided, one dose of fIPV was intradermal administration performed by insertion of a 26–27 gauge needle nearly administered to the selected children using Tropis. The vaccine used was produced parallel to and solely into the skin to raise a visible bleb”). Despite these by Bilthoven Biologicals, Netherlands and was presented in one-full-dose vials

2 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 3 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (http://creativecommons.org/licenses/by-nc-nd/4.0/). Article No~e00395 Article No~e00395

(0.5 mL). The vaccine was administered in the upper arm of the child. The assistant The average “application time” was 48 seconds. The average “application time” in each team advised the parents to report to the PHC in case of any adverse effect decreased with the number of children vaccinated. When taking into account the such as unusual pain on the injection site, swelling, redness, rash, fever, vomiting, first 30 children, the average “application time” was 68 seconds for the first child seizures or any other illness. In addition, the families were visited by AKU workers and 38 seconds for the 30th child (Fig. 2). one and two weeks after the immunization to assess whether any adverse events The average number of fIPV doses drawn from one IPV vial was 5.3. A total of following immunization were present. 110 vials were used to vaccinate 582 children. There was no vaccine loss rather 32/ We defined “application time” as timer period from charging of the Tropis until the 582 (5.5%) more children were vaccinated with recommended dose. disposal of the used syringe into a safety box. The “application time” was recorded All the vaccinators reported that crying among children was less common, filling by the team assistant after each injection. We counted the number of fIPV doses the device was easy, device was appropriate size, and giving the injection was easy. drawn from each IPV vial. After the end of the campaign, each vaccinator filled in One vaccinator reported that air bubbles were not easy to remove (Table 1). a questionnaire evaluating ergonomic features of Tropis. No adverse events related to the fIPV administration were observed either Approvals from Ethical Review committee of AKU and WHO Geneva were immediately after immunization or during the weekly monitoring visits for two obtained. weeks after the campaign.

3. Results 4. Discussion The community mobilizers approached 688 households, 63/688 (9.15%) house- holds refused to consent, 19/688(2.76%) households were locked at the time of This study demonstrated that it is feasible, safe and efficient to use Tropis for the visit, 24/688 (3.49%) households had no eligible child and 582/688(84.6%) administration of fIPV in a campaign setting. The average “application time” and consented to participate in the study. Among the households who consented to vaccine wastage was superior when compared to other methods of intradermal participate, 582 children were vaccinated. administration such as BCG needle and syringe or intradermal needle adaptors [17]. There were differences in the total number of children vaccinated by each team. The team with lowest number of vaccinated children immunized 30 children; the Training on how to use Tropis was straightforward and could be completed in highest immunized 75 (Fig. 1). several hours. The skills required to use Tropis are easy to understand and do not need any formal health background or prior training in injection administration. [(Fig._1)TD$IG] The decreasing “application time” with the number of vaccinated children further 80 80 demonstrated that the experience with the device translates into better efficacy 70 70 [(Fig._2)TD$IG] 60 60 80

50 50 70 Time in seconds 40 40 60

30 30 50

20 20 40 30 10 10 20 0 0 1234567891011 10 Total Children Vaccinated Average time of vaccine administration of each team (seconds) 0 Child 2 Child 3 Child 4 Child 6 Child 7 Child 8 Child 9 Child 5 Child 1 Child 10 Child 11 Child 12 Child 13 Child 14 Child 16 Child 17 Child 18 Child 19 Child 20 Child 21 Child 22 Child 23 Child 24 Child 25 Child 26 Child 28 Child 29 Child 30 Total number of children vaccinated = 582, Average time of vaccine filling to administration = 48 seconds Child 15 Child 27 Stake bar represents teams (n=11 teams) Fig. 2. Average application time to vaccinate first 30 children with fIPV using Tropis intradermal Fig. 1. Total number of children vaccinated and average time of each team during campaign. device.

4 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 5 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (http://creativecommons.org/licenses/by-nc-nd/4.0/). Article No~e00395 Article No~e00395

Table 1. Ergonomic features of Pharmajet Tropis needle free injection device. Declarations

Results Author contribution statement N(%) Mohammad Tahir Yousafzai, Ali Faisal Saleem, Ondrej Mach, Attaullah Baig, Number of vaccinators using device n= 11 Roland W. Sutter, Anita K.M. Zaidi: Conceived and designed the experiments; Filling Filling the syringe is easy 11(100%) Performed the experiments; Analyzed and interpreted the data; Contributed Ability to fill with correct dosage 11(100%) reagents, materials, analysis tools or data; Wrote the paper. Is the device appropriate size 11(100%) Air bubbles easy to see 11(100%) Easy to remove air bubbles 10(90.9%) Funding statement Comfort while filling syringe 10(5) 1(4) (scale:1 = lowest, 5 = highest) This work was supported by The World Health Organization. Dr. Ali F Saleem Delivery Giving injection is easy 11(100%) received research training support from the National Institute of Health’s 127 Comfort while administering injection 9 (5) 2(4) Fogarty International Center (1 D43 TW007585-01). (scale:1 = lowest, 5 = highest) Did device hurt wrist or hand 0 (0%) Competing interest statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.

indicating fast learning curve. Unlike campaigns with orally administered OPV the Acknowledgements main hindrance for IPV campaigns is the unavailability of large number of health We thank Mr Salim Charania and Mr Asad Khawaja from Peads Research Office workforce trained in administration, therefore our finding may have important of the Aga Khan University for providing excellent logistic support at the field site. implications for polio program. We also thank councilor of union council Ibrahim Hydri, local police station, There was 0% vaccine loss reported, possibly due to the fact that the IPV provincial polio emergency operation center, and town health officer Bin Qasim manufacturer slightly overfilled the vials with IPV resulting in >5 fIPV doses Town Karachi for providing full support in conducting the campaign in the high drawn from 1 vial; and also because the mechanism of Tropis limits the amount of risk area of Ibrahim Hydri. vaccine drawn into the device-syringe at 0.1 mL. Disclaimer: The findings and conclusions in this report are those of the author(s) There were some technical difficulties that occurred with several Tropis devices. and do not necessarily represent the views of CDC and other contributing agencies. There were 2 devices with failure in the ejection button (the mechanism to eject the used disposable syringe after injection administration), and 5 devices with either References failure of the charging button (the mechanism to charge the device for administration of vaccine using the pressure) alone or both charging and ejection [1] Cases of Wild Poliovirus by Country and Year Accessed 30/03/2017, http:// buttons. After this study, the manufacturer of Tropis addressed the identified www.polioeradication.org/Dataandmonitoring/Poliothisweek/Wildpoliovirus- issues. list.aspx.

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6 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 7 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (http://creativecommons.org/licenses/by-nc-nd/4.0/). Article No~e00395 Article No~e00395

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8 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 9 http://dx.doi.org/10.1016/j.heliyon.2017.e00395 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license 2405-8440/© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). (http://creativecommons.org/licenses/by-nc-nd/4.0/). REFERENCES:

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