Coordinated Response to Imported Vaccine-Derived Poliovirus Infection, Barcelona, Spain, 2019–2020 Dolores 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 In 2019, the Public Health Agency of Barcelona, Spain, was childhood vaccination and eventually removing OPV notified of a vaccine-derived poliovirus infection. The pa- from global use (3). This transition began in 2016 with tient had an underlying common variable immunodeficiency the replacement of trivalent OPV with bivalent OPV and no signs of acute flaccid paralysis. We describe the on- types 1 and 3 (4). going coordinated response to contain the infection, which After WHO declared a Public Health Emergency included compassionate-use treatment with pocapavir. of International Concern regarding WPV in 2014 (5), worldwide eradication of indigenous WPV serotype I n the nearly 30 years since the inception of the Glob- al Polio Eradication Initiative (GPEI) by the World Health Organization (WHO), polio eradication efforts 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 have decreased the number of wild poliovirus (WPV) 2012 (7). Nonetheless, endemic transmission of WPV cases by more than 99%, from 350,000 worldwide in serotype 1 continues to cause cases in Afghanistan 1988 to only 143 reported cases in 2019 (1). The triva- and Pakistan (9). lent Sabin vaccine (oral polio vaccine [OPV]), chosen In Spain, the last endemic case of WPV occurred for the eradication program, results in a temporary in- in 1988, which prompted improvement in polio vac- testinal infection in immunocompetent persons. These cination coverage and replacement of OPV with IPV vaccine-derived strains can revert to being neuroviru- in 2004. Although the WHO’s European Region has lent after vaccination, especially in immunocompro- been certified polio-free since 2002, the risk for im- mised patients, leading to vaccine-associated paralytic ported cases of WPV or vaccine-derived polioviruses poliomyelitis or chronic poliovirus infection (2). (VDPVs) from other countries still exists. The Polio Eradication and Endgame Strategic Primary immunodeficiencies are a heterogeneous Plan 2013–2018 established by the GPEI proposed in- group of disorders with a substantial hereditary com- troducing inactivated polio vaccine (IPV) into routine ponent. In patients with primary immunodeficien- cies, the immune response to microbial pathogens Author affiliations: Public Health Agency of Barcelona, Barcelona, is defective, leading to higher susceptibility to infec- Spain. (D. Álamo-Junquera, J. Politi, P. Simón, E. Molinero, tions, which can then become chronic (9). These pa- C. Rius); Parc de Salut Mar, Barcelona (J. Politi); Hospital tients can become infected by immunization if they Universitari Vall d’Hebron, Barcelona (R. Dieli-Crimi, R. Pujol receive live vaccines (10), and these infections can Borrel, R. Colobran, M. Martínez-Gallo, M. Campins, A. Antón, pose a risk to immunodeficient contacts and poten- J. Esperelba, M. Gema Codina, E. Polverino); Universitat tially jeopardize the success of the GPEI (11). Autònoma de Barcelona, Barcelona (R. Colobran, M. Martínez-Gallo, M. Campins, A. Antón, J. Esperelba, M. Gema Case Report Codina); Institut Català de la Salut, Barcelona (M.R. Narciso); In May 2019, the Public Health Agency of Barcelona Centro de Investigación Biomédica en Red de Epidemiología y (PHAB) was notified about a poliovirus infection Salud Pública, Barcelona (C. Rius) in an asymptomatic person with a primary immu- DOI: https://doi.org/10.3201/eid2705.204675 nodeficiency, identified through ongoing nonpolio Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021 1513 DISPATCHES enterovirus surveillance at Vall d’Hebron Hospi- information and stool samples and to explain how to tal (Barcelona), which conducted VP1 sequencing prevent transmission. National public health authori- of all detected enteroviruses (Figure). The patient, ties also were notified. a 26-year-old man, tested positive for enterovirus The patient’s stool samples were positive for po- (identified as poliovirus types 1 and 3) in a pharyn- liovirus types 1 and 3. The grade of divergence to the geal swab specimen. His medical history included a parent Sabin strain (2.7% for type 1 and 1.5% for type common variable immunodeficiency that had been 3) was consistent with a 2-year reproduction time. diagnosed in 2012 and treated with intravenous im- A recovered respiratory sample collected from the munoglobulin-replacement therapy. patient in January 2019 also tested positive for both Born in Pakistan, the patient had lived in Barce- strains. In contrast, the stool samples of the 4 house- lona since 2010, and the household included 4 family hold members tested negative for poliovirus. members (parents, partner, and child). He was a cook To coordinate the epidemiologic investigation at a local restaurant. The patient was adequately vac- and determine future actions, PHAB convened all cinated with 3 polio vaccine doses in 1993 in Pakistan the healthcare professionals involved in the pa- (probably trivalent OPV) and 1 dose of IPV in 2015 tient’s follow-up, including primary-care clini- in Barcelona. His child was correctly vaccinated with cians and hospital specialists. Polio immunization IPV, in accordance with the vaccine schedule of Cata- coverage in the patient’s surrounding community lunya, of which Barcelona is the capital. His parents was confirmed to be >95%, and environmental reported previous vaccination with 3 OPV doses in samples did not show any evidence of circulation Pakistan. His partner recalled receiving their most re- in the community. Contact tracing, beyond fam- cent OPV dose in February 2017 before leaving Paki- ily members, included work contacts, healthcare stan for Barcelona; they had also received 3 doses of personnel, and other patients. A total of 59 per- OPV as a child in Pakistan. sons exposed were vaccinated with IPV. In addi- Neither the patient nor his 4 household members tion, a contact-precautions alert was added to the reported recent travel to polio-endemic areas. How- patient’s electronic medical record. Because he ever, they recalled receiving visits by relatives and worked as a food handler, and given the possibil- friends who frequently traveled to Pakistan. ity of a long excretion period, PHAB authorized a After the notification, a public health nurse visit- medical leave and suggested a reorientation of his ed the patient and his family to collect epidemiologic professional career. Figure. Timeline of public health actions in response to an imported vaccine-derived poliovirus infection, Barcelona, Spain, 2019–2020. PID, primary immunodeficiency. 1514 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021 Response to Imported Poliovirus, Barcelona, Spain Further testing of the patient was indicated after screening by including serial stool samples for all the first meeting. Massive parallel sequencing identi- newly identified patients with primary immuno- fied a mutation supporting the diagnosis of CTLA-4 deficiency. Results from stool specimen screening deficiency, a dominant monogenic disease, specifi- should be included in a global poliovirus surveil- cally an autoimmune lymphoproliferative syndrome, lance reporting system (13). type V, which is treatable. Abatacept (a recombinant Antivirals represent a potential means to man- soluble form of CTLA-4) was started in August 2019 age immunodeficiency-related VDPV excretors and and resulted in substantial clinical improvement. the risk their conditions represent to eradication ef- Specific treatment with pocapavir (authorized for forts (14). Currently, pocapavir is being considered compassionate use) was provided by ViroDefense for use in poliovirus-excreting patients with primary Inc. (Chevy Chase, MD, USA) and was started in immunodeficiency on a compassionate-use basis (15). January 2020. The case-patient we describe has been treated with To date, the patient’s poliovirus excretion is pocapavir, although viral excretion remained active monitored by monthly stool samples and pharyngeal at the time of this report. Further research is needed swab specimens every 6 months. Although the most to identify effective antiviral drugs. In conclusion, in recent pharyngeal swab specimens was negative, certified polio-free countries, clinical and virologic stool samples remain intermittently positive. Stool surveillance guidelines must address asymptomatic samples provided by household members every 6 poliovirus carriers and the need for screening in im- months continue to be negative. No onward trans- munocompromised persons. mission has been identified. About the Author Conclusions Dr. Álamo-Junquera is a public health technical officer at We report a chronic vaccine-derived poliovirus ex- the Epidemiology Service of the Public Health Agency of cretion in a person with a primary immunodeficiency Barcelona, Spain. Her main research interests are surveil- who was living in a polio-free country. Immunodefi- lance, prevention, and control of infectious diseases. cient patients have a high risk for becoming chronic primary immunodeficiency carriers and face an in- References creased risk for VDPV complications. In a nonendem- 1. Global Polio Eradication Initiative. Global wild poliovirus ic area, the most likely infection source is secondary 2014–2019 [cited 2021 Jan 10]. https://polioeradication.org/ exposure to vaccine-related strains imported by per- wp-content/uploads/2020/01/Weekly-GPEI-Polio- Analyses-wpv-20191231.pdf sons vaccinated in countries that have ongoing vac- 2. Dunn G, Klapsa D, Wilton T, Stone L, Minor PD, Martin J. cination with OPV. Twenty-eight years of poliovirus replication in an Because patients with antibody deficiency are immunodeficient individual: impact on the Global Polio susceptible to vaccine-associated paralytic poliomy- Eradication Initiative. PLoS Pathog. 2015;11:e1005114. https://doi.org/10.1371/journal.ppat.1005114 elitis, OPV and other live vaccines are contraindi- 3. Li L, Ivanova O, Driss N, Tiongco-Recto M, da Silva R, cated in such persons. However, the diagnosis of an Shahmahmoodi S, et al. Poliovirus excretion among persons antibody deficiency often is delayed, making this rec- with primary immune deficiency disorders: summary of ommendation challenging. a seven-country study series. J Infect Dis. 2014;210(Suppl 1):S368–72. https://doi.org/10.1093/infdis/jiu065 The grade of divergence to the parent Sabin strain 4. Duintjer Tebbens RJ, Hampton LM, Thompson KM. is estimated to occur at a rate of 1.1% per year for the Implementation of coordinated global serotype 2 oral capsid protein (VP1) region, which for this case is poliovirus vaccine cessation: risks of potential non- consistent with a 2-year excretion. This finding, along synchronous cessation. BMC Infect Dis. 2016;16:231. https://doi.org/10.1186/s12879-016-1536-9 with the OPV vaccination of the patient’s partner in 5. World Health Organization. WHO statement on the meeting 2017, supports secondary exposure to be the most of the International Health Regulations Emergency likely source of infection. Committee concerning the international spread of wild po- In a polio-free country, the occurrence of vac- liovirus [cited 2020 Feb 15]. https://www.who.int/ mediacentre/news/statements/2014/polio- 20140505/en/ cine-derived carriers is infrequent. However, per- #.XkeU7O5-dMM.mendeley sons with immunodeficiency-related VDPV infection 6. Global Polio Eradication Initiative. Global eradication can maintain prolonged excretions while remaining of wild poliovirus type 2 declared [cited 2020 Nov 15]. asymptomatic (12). Detection of asymptomatic po- https://polioeradication.org/news-post/global-eradication- of-wild-poliovirus-type-2-declared liovirus infections entails difficulties, as in the case 7. World Health Organization. Poliomyelitis [cited 2020 Nov we have described. Physicians treating patients with 15]. https://www.who.int/news-room/fact-sheets/detail/ primary immunodeficiency might encourage their poliomyelitis Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021 1515 DISPATCHES 8. Makoni M. Africa eradicates wild polio. Lancet Microbe. 13. Global Polio Eradication Initiative. Guidelines for 2020;1:e243. https://doi.org/10.1016/S2666-5247(20)30152-X implementing poliovirus surveillance among patients with 9. Picard C, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, primary immunodeficiency disorders (PIDs) [cited 2020 Conley ME, et al. Primary immunodeficiency diseases: an Nov 15]. https://polioeradication.org/wp-content/ update on the classification from the International Union uploads/2020/12/Guidelines-for-Implementing-PID- of Immunological Societies Expert Committee for Primary Suveillance-3.3-20201215.pdf Immunodeficiency 2015. J Clin Immunol. 2015;35:696–726. 14. Duintjer Tebbens RJ, Pallansch MA, Thompson KM. https://doi.org/10.1007/s10875-015-0201-1 Modeling the prevalence of immunodeficiency-associated 10. Eibl MM, Wolf HM. Vaccination in patients with primary long-term vaccine-derived poliovirus excretors and the immune deficiency, secondary immune deficiency and potential benefits of antiviral drugs. BMC Infect Dis. autoimmunity with immune regulatory abnormalities. 2015;15:379. https://doi.org/10.1186/s12879-015-1115-5 Immunotherapy. 2015;7:1273–92. https://doi.org/10.2217/ 15. Aghamohammadi A, Abolhassani H, Kutukculer N, IMT.15.74 Wassilak SG, Pallansch MA, Kluglein S, et al.; JMF 11. Shaghaghi M, Shahmahmoodi S, Abolhassani H, Centers Network Investigators and Study Collaborators. Soleyman-Jahi S, Parvaneh L, Mahmoudi S, et al. Patients with primary immunodeficiencies are a reservoir Vaccine-derived polioviruses and children with primary of poliovirus and a risk to polio eradication. Front immunodeficiency, Iran, 1995–2014. Emerg Infect Dis. Immunol. 2017;8:685. https://doi.org/10.3389/ 2016;22:1712–9. https://doi.org/10.3201/eid2210.151071 fimmu.2017.00685 12. Macklin G, Liao Y, Takane M, Dooling K, Gilmour S, Mach O, et al.; iVDPV Working Group. Prolonged excretion Address for correspondence: Dolores Álamo-Junquera, of poliovirus among individuals with primary Epidemiology Service, Public Health Agency of Barcelona, immunodeficiency disorder: an analysis of the World Health Organization registry. Front Immunol. 2017;8:1103. Barcelona, Spain. Pl. de Lesseps, 1, 08023 Barcelona, Spain; https://doi.org/10.3389/fimmu.2017.01103 email: lola.alamo@gmail.com prions Kaposi Eptesicus fuscus Plasmodium knowlesi cholera tularemia syncytium Klebsiella Vibrio vulnificus yaws Leptospira Quinine sapovirus Rickettsia variola Campylobacter Chagas disease rotavirus Aspergillus Lyssavirus Acinetobacter botulism Escherichia coli syphilis knemidocoptic mange Babesia hemozoin Naegleria fowlerii Ehrlichia Leishmaniasis etymologiarabies Bordetella Anopheles Verona integron Zika virus Herpesvirus vaccination Artemisinin Dengue Shigella Borna disease virus Ebola Franciscella tularensis typhus Rickettsia orf Coxiella burnetii kobuvirus Candida Orientia tsutsugamushi Norovirus tuberculosis Bocavirus chimera QBrucella fever Malaria measles quarantine Mange tetanus Chikungunya pertactin Borrelia Leprosyinfluenza Calcivirus quarantine Peste des petits ruminants meliodosis Diphtheria O’nyong-nyong virus Pseudoterranova Bonferroni correction azarasi pertussis Merkel cells Ignatzschineria Glanders Yersinia featured monthly in http://wwwnc.cdc.gov/eid/articles/etymologia 1516 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 5, May 2021