In 2019, the Public Health Agency of Barcelona, Spain, was notifi ed of a vaccine-derived poliovirus infection. The patient had an underlying common variable immunodefi ciency and no signs of acute fl accid paralysis. We describe the ongoing coordinated response to contain the infection, which included compassionate-use treatment with pocapavir

Andrés, C.

Antón, A.

Borrell, R.P.

Campins Martí, Magda

Codina, M.G.

Colobran, R.

Dieli-Crimi, Romina

Esperalba, J.

Martínez-Gallo, M.

Molinero, Emilia

Politi, J.

Polverino, E.

Rius i Gibert, Maria Cristina

Rosa Narciso, M.

Simón, Pere

Universitat Autònoma de Barcelona

Álamo-Junquera, Dolores

English

Politi, Julieta

Simón Vivan, Pere

Borrell, Ricardo Pujol

Colobrán Oriol, Roger

Antón Pagarolas, Andrés, 1976-

Esperalba, Juliana

Andrés, Cristina

Codina, María Gema

Diposit Digital de Documents de la UAB

In the nearly 30 years since the inception of the Glob-al Polio Eradication Initiative (GPEI) by the World Health Organization (WHO), polio eradication efforts have decreased the number of wild poliovirus (WPV) cases by more than 99%, from 350,000 worldwide in 1988 to only 143 reported cases in 2019 (1). The triva-lent Sabin vaccine (oral polio vaccine [OPV]), chosen for the eradication program, results in a temporary in-testinal infection in immunocompetent persons. These vaccine-derived strains can revert to being neuroviru-lent after vaccination, especially in immunocompro-mised patients, leading to vaccine-associated paralytic poliomyelitis or chronic poliovirus infection (2).The Polio Eradication and Endgame Strategic Plan 2013–2018 established by the GPEI proposed in-troducing inactivated polio vaccine (IPV) into routine childhood vaccination and eventually removing OPV from global use (3). This transition began in 2016 with the replacement of trivalent OPV with bivalent OPV types 1 and 3 (4). After WHO declared a Public Health Emergency of International Concern regarding WPV in 2014 (5), worldwide eradication of indigenous WPV serotype 2 was declared in 2015 (6). Worldwide eradication of WPV serotype 3 was achieved in 2019, after the last case of WPV serotype 3 was reported in Nigeria in 2012 (7). Nonetheless, endemic transmission of WPV serotype 1 continues to cause cases in Afghanistan and Pakistan (9).In Spain, the last endemic case of WPV occurred in 1988, which prompted improvement in polio vac-cination coverage and replacement of OPV with IPV in 2004. Although the WHO’s European Region has been certifi ed polio-free since 2002, the risk for im-ported cases of WPV or vaccine-derived polioviruses (VDPVs) from other countries still exists.Primary immunodefi ciencies are a heterogeneous group of disorders with a substantial hereditary com-ponent. In patients with primary immunodefi cien-cies, the immune response to microbial pathogens is defective, leading to higher susceptibility to infec-tions, which can then become chronic (9). These pa-tients can become infected by immunization if they receive live vaccines (10), and these infections can pose a risk to immunodefi cient contacts and poten-tially jeopardize the success of the GPEI (11).Case ReportIn May 2019, the Public Health Agency of Barcelona (PHAB) was notifi ed about a poliovirus infection in an asymptomatic person with a primary immu-nodefi ciency, identifi ed through ongoing nonpolio Coordinated Response to Imported Vaccine-Derived Poliovirus Infection, Barcelona, Spain, 2019–2020Dolores Álamo-Junquera, Julieta Politi, Pere Simón, Romina Dieli-Crimi, Ricardo Pujol Borrell, Roger Colobran, Monica Martínez-Gallo, Magda Campins, Andrés Antón, Juliana Esperalba, Cristina Andrés, María Gema Codina, Eva Polverino, M. Rosa Narciso, Emilia Molinero, Cristina Rius Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021 1513Author affi  liations: Public Health Agency of Barcelona, Barcelona, Spain. (D. Álamo-Junquera, J. Politi, P. Simón, E. Molinero, C. Rius); Parc de Salut Mar, Barcelona (J. Politi); Hospital Universitari Vall d’Hebron, Barcelona (R. Dieli-Crimi, R. PujolBorrel, R. Colobran, M. Martínez-Gallo, M. Campins, A. Antón, J. Esperelba, M. Gema Codina, E. Polverino); Universitat Autònoma de Barcelona, Barcelona (R. Colobran, M. Martínez-Gallo, M. Campins, A. Antón, J. Esperelba, M. Gema Codina); Institut Català de la Salut, Barcelona (M.R. Narciso); Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona (C. Rius)DOI: https://doi.org/10.3201/eid2705.204675In 2019, the Public Health Agency of Barcelona, Spain, was notifi ed of a vaccine-derived poliovirus infection. The pa-tient had an underlying common variable immunodefi ciency and no signs of acute fl accid paralysis. We describe the on-going coordinated response to contain the infection, which included compassionate-use treatment with pocapavir.DISPATCHESenterovirus surveillance at Vall d’Hebron Hospi-tal (Barcelona), which conducted VP1 sequencing of all detected enteroviruses (Figure). The patient, a 26-year-old man, tested positive for enterovirus (identified as poliovirus types 1 and 3) in a pharyn-geal swab specimen. His medical history included a common variable immunodeficiency that had been diagnosed in 2012 and treated with intravenous im-munoglobulin-replacement therapy.Born in Pakistan, the patient had lived in Barce-lona since 2010, and the household included 4 family members (parents, partner, and child). He was a cook at a local restaurant. The patient was adequately vac-cinated with 3 polio vaccine doses in 1993 in Pakistan (probably trivalent OPV) and 1 dose of IPV in 2015 in Barcelona. His child was correctly vaccinated with IPV, in accordance with the vaccine schedule of Cata-lunya, of which Barcelona is the capital. His parents reported previous vaccination with 3 OPV doses in Pakistan. His partner recalled receiving their most re-cent OPV dose in February 2017 before leaving Paki-stan for Barcelona; they had also received 3 doses of OPV as a child in Pakistan.Neither the patient nor his 4 household members reported recent travel to polio-endemic areas. How-ever, they recalled receiving visits by relatives and friends who frequently traveled to Pakistan.After the notification, a public health nurse visit-ed the patient and his family to collect epidemiologic information and stool samples and to explain how to prevent transmission. National public health authori-ties also were notified.The patient’s stool samples were positive for po-liovirus types 1 and 3. The grade of divergence to the parent Sabin strain (2.7% for type 1 and 1.5% for type 3) was consistent with a 2-year reproduction time. A recovered respiratory sample collected from the patient in January 2019 also tested positive for both strains. In contrast, the stool samples of the 4 house-hold members tested negative for poliovirus.To coordinate the epidemiologic investigation and determine future actions, PHAB convened all the healthcare professionals involved in the pa-tient’s follow-up, including primary-care clini-cians and hospital specialists. Polio immunization coverage in the patient’s surrounding community was confirmed to be >95%, and environmental samples did not show any evidence of circulation in the community. Contact tracing, beyond fam-ily members, included work contacts, healthcare personnel, and other patients. A total of 59 per-sons exposed were vaccinated with IPV. In addi-tion, a contact-precautions alert was added to the patient’s electronic medical record. Because he worked as a food handler, and given the possibil-ity of a long excretion period, PHAB authorized a medical leave and suggested a reorientation of his professional career.1514 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021Figure. Timeline of public health actions in response to an imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019–2020. PID, primary immunodeficiency.Response to Imported Poliovirus, Barcelona, SpainFurther testing of the patient was indicated after the first meeting. Massive parallel sequencing identi-fied a mutation supporting the diagnosis of CTLA-4 deficiency, a dominant monogenic disease, specifi-cally an autoimmune lymphoproliferative syndrome, type V, which is treatable. Abatacept (a recombinant soluble form of CTLA-4) was started in August 2019 and resulted in substantial clinical improvement. Specific treatment with pocapavir (authorized for compassionate use) was provided by ViroDefense Inc. (Chevy Chase, MD, USA) and was started in January 2020.To date, the patient’s poliovirus excretion is monitored by monthly stool samples and pharyngeal swab specimens every 6 months. Although the most recent pharyngeal swab specimens was negative, stool samples remain intermittently positive. Stool samples provided by household members every 6 months continue to be negative. No onward trans-mission has been identified.ConclusionsWe report a chronic vaccine-derived poliovirus ex-cretion in a person with a primary immunodeficiency who was living in a polio-free country. Immunodefi-cient patients have a high risk for becoming chronic primary immunodeficiency carriers and face an in-creased risk for VDPV complications. In a nonendem-ic area, the most likely infection source is secondary exposure to vaccine-related strains imported by per-sons vaccinated in countries that have ongoing vac-cination with OPV.Because patients with antibody deficiency are susceptible to vaccine-associated paralytic poliomy-elitis, OPV and other live vaccines are contraindi-cated in such persons. However, the diagnosis of an antibody deficiency often is delayed, making this rec-ommendation challenging. The grade of divergence to the parent Sabin strain is estimated to occur at a rate of 1.1% per year for the capsid protein (VP1) region, which for this case is consistent with a 2-year excretion. This finding, along with the OPV vaccination of the patient’s partner in 2017, supports secondary exposure to be the most likely source of infection.In a polio-free country, the occurrence of vac-cine-derived carriers is infrequent. However, per-sons with immunodeficiency-related VDPV infection can maintain prolonged excretions while remaining asymptomatic (12). Detection of asymptomatic po-liovirus infections entails difficulties, as in the case we have described. Physicians treating patients with primary immunodeficiency might encourage their screening by including serial stool samples for all newly identified patients with primary immuno-deficiency. Results from stool specimen screening should be included in a global poliovirus surveil-lance reporting system (13).Antivirals represent a potential means to man-age immunodeficiency-related VDPV excretors and the risk their conditions represent to eradication ef-forts (14). Currently, pocapavir is being considered for use in poliovirus-excreting patients with primary immunodeficiency on a compassionate-use basis (15). The case-patient we describe has been treated with pocapavir, although viral excretion remained active at the time of this report. Further research is needed to identify effective antiviral drugs. In conclusion, in certified polio-free countries, clinical and virologic surveillance guidelines must address asymptomatic poliovirus carriers and the need for screening in im-munocompromised persons.About the AuthorDr. Álamo-Junquera is a public health technical officer at the Epidemiology Service of the Public Health Agency of Barcelona, Spain. Her main research interests are surveil-lance, prevention, and control of infectious diseases.References  1. Global Polio Eradication Initiative. Global wild poliovirus 2014–2019 [cited 2021 Jan 10]. https://polioeradication.org/wp-content/uploads/2020/01/Weekly-GPEI-Polio- Analyses-wpv-20191231.pdf  2. Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J. Twenty-eight years of poliovirus replication in an  immunodeficient individual: impact on the Global Polio Eradication Initiative. PLoS Pathog. 2015;11:e1005114. https://doi.org/10.1371/journal.ppat.1005114  3. Li L, Ivanova O, Driss N, Tiongco-Recto M, da Silva R, Shahmahmoodi S, et al. Poliovirus excretion among persons with primary immune deficiency disorders: summary of a seven-country study series. J Infect Dis. 2014;210(Suppl 1):S368–72. https://doi.org/10.1093/infdis/jiu065  4. Duintjer Tebbens RJ, Hampton LM, Thompson KM.  Implementation of coordinated global serotype 2 oral  poliovirus vaccine cessation: risks of potential non- synchronous cessation. BMC Infect Dis. 2016;16:231.  https://doi.org/10.1186/s12879-016-1536-9  5. World Health Organization. WHO statement on the meeting of the International Health Regulations Emergency  Committee concerning the international spread of wild po-liovirus [cited 2020 Feb 15]. https://www.who.int/ mediacentre/news/statements/2014/polio- 20140505/en/ #.XkeU7O5-dMM.mendeley  6. Global Polio Eradication Initiative. Global eradication  of wild poliovirus type 2 declared [cited 2020 Nov 15].  https://polioeradication.org/news-post/global-eradication-of-wild-poliovirus-type-2-declared  7. World Health Organization. Poliomyelitis [cited 2020 Nov 15]. https://www.who.int/news-room/fact-sheets/detail/poliomyelitis  Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021 1515DISPATCHES  8. Makoni M. Africa eradicates wild polio. Lancet Microbe. 2020;1:e243. https://doi.org/10.1016/S2666-5247(20)30152-X  9. Picard C, Al-Herz W, Bousfi ha A, Casanova JL, Chatila T, Conley ME, et al. Primary immunodefi ciency diseases: an update on the classifi cation from the International Union of Immunological Societies Expert Committee for Primary Immunodefi ciency 2015. J Clin Immunol. 2015;35:696–726. https://doi.org/10.1007/s10875-015-0201-110. Eibl MM, Wolf HM. Vaccination in patients with primary immune defi ciency, secondary immune defi ciency and autoimmunity with immune regulatory abnormalities. Immunotherapy. 2015;7:1273–92. https://doi.org/10.2217/IMT.15.7411. Shaghaghi M, Shahmahmoodi S, Abolhassani H, Soleyman-Jahi S, Parvaneh L, Mahmoudi S, et al. Vaccine-derived polioviruses and children with primary immunodefi ciency, Iran, 1995–2014. Emerg Infect Dis. 2016;22:1712–9. https://doi.org/10.3201/eid2210.15107112. Macklin G, Liao Y, Takane M, Dooling K, Gilmour S, Mach O, et al.; iVDPV Working Group. Prolonged excretion of poliovirus among individuals with primary immunodefi ciency disorder: an analysis of the World Health Organization registry. Front Immunol. 2017;8:1103. https://doi.org/10.3389/fi mmu.2017.0110313. Global Polio Eradication Initiative. Guidelines for implementing poliovirus surveillance among patients with primary immunodefi ciency disorders (PIDs) [cited 2020 Nov 15]. https://polioeradication.org/wp-content/uploads/2020/12/Guidelines-for-Implementing-PID-Suveillance-3.3-20201215.pdf14. Duintjer Tebbens RJ, Pallansch MA, Thompson KM. Modeling the prevalence of immunodefi ciency-associated long-term vaccine-derived poliovirus excretors and the potential benefi ts of antiviral drugs. BMC Infect Dis. 2015;15:379. https://doi.org/10.1186/s12879-015-1115-515. Aghamohammadi A, Abolhassani H, Kutukculer N, Wassilak SG, Pallansch MA, Kluglein S, et al.; JMF Centers Network Investigators and Study Collaborators. Patients with primary immunodefi ciencies are a reservoir of poliovirus and a risk to polio eradication. Front Immunol. 2017;8:685. https://doi.org/10.3389/fi mmu.2017.00685Address for correspondence: Dolores Álamo-Junquera, Epidemiology Service, Public Health Agency of Barcelona, Barcelona, Spain. Pl. de Lesseps, 1, 08023 Barcelona, Spain; email: lola.alamo@gmail.com1516 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021etymologiaprionsNaegleria fowleriiPseudoterranova azarasiDengueBorna disease virusLeprosyBocavirustuberculosisShigellaChikungunyatetanusEscherichia coliIgnatzschineriaBonferroni correctionZika virusPeste des petits ruminantsbotulismRickettsiaYersiniarabiesinfluenzaChagas diseaseMalariaBrucellaArtemisininMangeOrientia tsutsugamushisyphilisquarantinesapoviruschimeraLeishmaniasisEbolaCoxiella burnetiiBorreliaorfBabesiaKaposiVibrio vulnificusyawsvariolavaccinationrotavirusQ feverPlasmodium knowlesimeliodosisFranciscella tularensischolerafeatured monthly inMerkel cellsmeaslesknemidocoptic mangetularemiakobuvirusRickettsiaEptesicus fuscus syncytiumCampylobacterpertussisBordetellaQuinineAcinetobacterCalcivirusHerpesvirusNorovirusLeptospiraEhrlichiapertactinVerona integronAnophelesquarantineKlebsiellatyphusCandidaLyssavirusGlandershemozoinAspergillusDiphtheriaO’nyong-nyong virushttp://wwwnc.cdc.gov/eid/articles/etymologia 

Coordinated response to imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019-2020

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Coordinated response to imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019-2020

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