BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

Beatriz E. Marciano; Chiung Yu Huang; Gyan Joshi; Nima Rezaei; Beatriz Costa Carvalho; Zoe Allwood; Aydan Ikinciogullari; Shereen M. Reda; Andrew Gennery; Vojtech Thon; Francisco Espinosa-Rosales; Waleed Al-Herz; Oscar Porras; Anna Shcherbina; Anna Szaflarska; Şebnem Kiliç; Jose L. Franco; Andrea C. Gómez Raccio; Persio Roxo; Isabel Esteves; Nermeen Galal; Anete Sevciovic Grumach; Salem Al-Tamemi; Alisan Yildiran; Julio C. Orellana; Masafumi Yamada; Tomohiro Morio; Diana Liberatore; Yoshitoshi Ohtsuka; Yu Lung Lau; Ryuta Nishikomori; Carlos Torres-Lozano; Juliana T.L. Mazzucchelli; Maria M.S. Vilela; Fabiola S. Tavares; Luciana Cunha; Jorge A. Pinto; Sara E. Espinosa-Padilla; Leticia Hernandez-Nieto; Reem A. Elfeky; Tadashi Ariga; Heike Toshio; Figen Dogu; Funda Cipe; Renata Formankova; M. Enriqueta Nuñez-Nuñez; Liliana Bezrodnik; Jose Gonçalo Marques; María I. Pereira; Viviana Listello; Mary A. Slatter; Zohreh Nademi; Danuta Kowalczyk; Thomas A. Fleisher; Graham Davies; Bénédicte Neven; Sergio D. Rosenzweig

doi:10.1016/j.jaci.2014.02.028

BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

Beatriz E. Marciano, Chiung Yu Huang, Gyan Joshi, Nima Rezaei, Beatriz Costa Carvalho, Zoe Allwood, Aydan Ikinciogullari, Shereen M. Reda, Andrew Gennery, Vojtech Thon, Francisco Espinosa-Rosales, Waleed Al-Herz, Oscar Porras, Anna Shcherbina, Anna Szaflarska, Şebnem Kiliç, Jose L. Franco, Andrea C. Gómez Raccio, Persio Roxo, Isabel EstevesNermeen Galal, Anete Sevciovic Grumach, Salem Al-Tamemi, Alisan Yildiran, Julio C. Orellana, Masafumi Yamada, Tomohiro Morio, Diana Liberatore, Yoshitoshi Ohtsuka, Yu Lung Lau, Ryuta Nishikomori, Carlos Torres-Lozano, Juliana T.L. Mazzucchelli, Maria M.S. Vilela, Fabiola S. Tavares, Luciana Cunha, Jorge A. Pinto, Sara E. Espinosa-Padilla, Leticia Hernandez-Nieto, Reem A. Elfeky, Tadashi Ariga, Heike Toshio, Figen Dogu, Funda Cipe, Renata Formankova, M. Enriqueta Nuñez-Nuñez, Liliana Bezrodnik, Jose Gonçalo Marques, María I. Pereira, Viviana Listello, Mary A. Slatter, Zohreh Nademi, Danuta Kowalczyk, Thomas A. Fleisher, Graham Davies, Bénédicte Neven, Sergio D. Rosenzweig^*

^*Corresponding author for this work

Child Health

Research output: Contribution to journal › Article › peer-review

156 Citations (Scopus)

Abstract

Background Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. Objectives We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≥1 month) showed an increased prevalence of complications (P =.006) and death caused by BCG-associated complications (P <.0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P =.001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P<.0001). Conclusions BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Original language	English
Pages (from-to)	1134-1141
Number of pages	8
Journal	Journal of Allergy and Clinical Immunology
Volume	133
Issue number	4
DOIs	https://doi.org/10.1016/j.jaci.2014.02.028
Publication status	Published - Apr 2014

Keywords

BCG
Primary immunodeficiency
hematopoietic stem cell transplant
immune reconstitution syndrome
mycobacteria
newborn screening
severe combined immunodeficiency
vaccine

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2014.02.028

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Marciano, B. E., Huang, C. Y., Joshi, G., Rezaei, N., Carvalho, B. C., Allwood, Z., Ikinciogullari, A., Reda, S. M., Gennery, A., Thon, V., Espinosa-Rosales, F., Al-Herz, W., Porras, O., Shcherbina, A., Szaflarska, A., Kiliç, Ş., Franco, J. L., Gómez Raccio, A. C., Roxo, P., ... Rosenzweig, S. D. (2014). BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies. Journal of Allergy and Clinical Immunology, 133(4), 1134-1141. https://doi.org/10.1016/j.jaci.2014.02.028

Marciano, BE, Huang, CY, Joshi, G, Rezaei, N, Carvalho, BC, Allwood, Z, Ikinciogullari, A, Reda, SM, Gennery, A, Thon, V, Espinosa-Rosales, F, Al-Herz, W, Porras, O, Shcherbina, A, Szaflarska, A, Kiliç, Ş, Franco, JL, Gómez Raccio, AC, Roxo, P, Esteves, I, Galal, N, Grumach, AS, Al-Tamemi, S, Yildiran, A, Orellana, JC, Yamada, M, Morio, T, Liberatore, D, Ohtsuka, Y, Lau, YL, Nishikomori, R, Torres-Lozano, C, Mazzucchelli, JTL, Vilela, MMS, Tavares, FS, Cunha, L, Pinto, JA, Espinosa-Padilla, SE, Hernandez-Nieto, L, Elfeky, RA, Ariga, T, Toshio, H, Dogu, F, Cipe, F, Formankova, R, Nuñez-Nuñez, ME, Bezrodnik, L, Marques, JG, Pereira, MI, Listello, V, Slatter, MA, Nademi, Z, Kowalczyk, D, Fleisher, TA, Davies, G, Neven, B & Rosenzweig, SD 2014, 'BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies', Journal of Allergy and Clinical Immunology, vol. 133, no. 4, pp. 1134-1141. https://doi.org/10.1016/j.jaci.2014.02.028

@article{f7246497a0a54cf9811d70e7eb81d6c6,

title = "BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies",

abstract = "Background Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. Objectives We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≥1 month) showed an increased prevalence of complications (P =.006) and death caused by BCG-associated complications (P <.0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P =.001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P<.0001). Conclusions BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.",

keywords = "BCG, Primary immunodeficiency, hematopoietic stem cell transplant, immune reconstitution syndrome, mycobacteria, newborn screening, severe combined immunodeficiency, vaccine",

author = "Marciano, {Beatriz E.} and Huang, {Chiung Yu} and Gyan Joshi and Nima Rezaei and Carvalho, {Beatriz Costa} and Zoe Allwood and Aydan Ikinciogullari and Reda, {Shereen M.} and Andrew Gennery and Vojtech Thon and Francisco Espinosa-Rosales and Waleed Al-Herz and Oscar Porras and Anna Shcherbina and Anna Szaflarska and {\c S}ebnem Kili{\c c} and Franco, {Jose L.} and {G{\'o}mez Raccio}, {Andrea C.} and Persio Roxo and Isabel Esteves and Nermeen Galal and Grumach, {Anete Sevciovic} and Salem Al-Tamemi and Alisan Yildiran and Orellana, {Julio C.} and Masafumi Yamada and Tomohiro Morio and Diana Liberatore and Yoshitoshi Ohtsuka and Lau, {Yu Lung} and Ryuta Nishikomori and Carlos Torres-Lozano and Mazzucchelli, {Juliana T.L.} and Vilela, {Maria M.S.} and Tavares, {Fabiola S.} and Luciana Cunha and Pinto, {Jorge A.} and Espinosa-Padilla, {Sara E.} and Leticia Hernandez-Nieto and Elfeky, {Reem A.} and Tadashi Ariga and Heike Toshio and Figen Dogu and Funda Cipe and Renata Formankova and Nu{\~n}ez-Nu{\~n}ez, {M. Enriqueta} and Liliana Bezrodnik and Marques, {Jose Gon{\c c}alo} and Pereira, {Mar{\'i}a I.} and Viviana Listello and Slatter, {Mary A.} and Zohreh Nademi and Danuta Kowalczyk and Fleisher, {Thomas A.} and Graham Davies and B{\'e}n{\'e}dicte Neven and Rosenzweig, {Sergio D.}",

note = "Funding Information: Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease . V.T. was supported by the European Community{\textquoteright}s Seventh Framework Program FP7/2007-2013 under grant agreement no. 201549 (EURO-PADnet HEALTH-F2-2008-201549). Funding Information: Disclosure of potential conflict of interest: N. Rezaei is employed by and has received research support from Tehran University Med Sci , has received royalties from Springer , and has been supported by an American Academy of Allergy, Asthma & Immunology (AAAAI) Young Investigator Award . B. Costa Carvalho has received payment for development of educational presentations from the Federal University of Sao Paulo (FAPESP) and has received travel support from Octapharma. V. Thon has received research support from EURO-PADnet HEALTH ( F2-2008-201549 ). J. L. Franco has received consultancy fees from Baxter and Kedrion and has received lecture fees from Grifols . A. Sevciovic Grumach is a board member for Latin American Society for Immunodeficiencies and has received consultancy fees and lecture fees from SHIRE and CSL . T. Morio has received grant-in-aids for scientific research from the Japan Science and Technology Agency ; the Ministry of Education, Culture, and Sport ; and the Ministry of Health, Labour, and Welfare in Japan and has received lecture fees from Abbvie , CSL Behring , Chugai Pharmaceutical , Meiji Pharmaceuticals , Teijin Pharma , and Toray Medical . S. D. Rosenzweig has received consultancy fees from InPractice and UpToDate . The rest of the authors declare that they have no relevant conflicts of interest. ",

year = "2014",

month = apr,

doi = "10.1016/j.jaci.2014.02.028",

language = "English",

volume = "133",

pages = "1134--1141",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "4",

}

TY - JOUR

T1 - BCG vaccination in patients with severe combined immunodeficiency

T2 - Complications, risks, and vaccination policies

AU - Marciano, Beatriz E.

AU - Huang, Chiung Yu

AU - Joshi, Gyan

AU - Rezaei, Nima

AU - Carvalho, Beatriz Costa

AU - Allwood, Zoe

AU - Ikinciogullari, Aydan

AU - Reda, Shereen M.

AU - Gennery, Andrew

AU - Thon, Vojtech

AU - Espinosa-Rosales, Francisco

AU - Al-Herz, Waleed

AU - Porras, Oscar

AU - Shcherbina, Anna

AU - Szaflarska, Anna

AU - Kiliç, Şebnem

AU - Franco, Jose L.

AU - Gómez Raccio, Andrea C.

AU - Roxo, Persio

AU - Esteves, Isabel

AU - Galal, Nermeen

AU - Grumach, Anete Sevciovic

AU - Al-Tamemi, Salem

AU - Yildiran, Alisan

AU - Orellana, Julio C.

AU - Yamada, Masafumi

AU - Morio, Tomohiro

AU - Liberatore, Diana

AU - Ohtsuka, Yoshitoshi

AU - Lau, Yu Lung

AU - Nishikomori, Ryuta

AU - Torres-Lozano, Carlos

AU - Mazzucchelli, Juliana T.L.

AU - Vilela, Maria M.S.

AU - Tavares, Fabiola S.

AU - Cunha, Luciana

AU - Pinto, Jorge A.

AU - Espinosa-Padilla, Sara E.

AU - Hernandez-Nieto, Leticia

AU - Elfeky, Reem A.

AU - Ariga, Tadashi

AU - Toshio, Heike

AU - Dogu, Figen

AU - Cipe, Funda

AU - Formankova, Renata

AU - Nuñez-Nuñez, M. Enriqueta

AU - Bezrodnik, Liliana

AU - Marques, Jose Gonçalo

AU - Pereira, María I.

AU - Listello, Viviana

AU - Slatter, Mary A.

AU - Nademi, Zohreh

AU - Kowalczyk, Danuta

AU - Fleisher, Thomas A.

AU - Davies, Graham

AU - Neven, Bénédicte

AU - Rosenzweig, Sergio D.

N1 - Funding Information: Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease . V.T. was supported by the European Community’s Seventh Framework Program FP7/2007-2013 under grant agreement no. 201549 (EURO-PADnet HEALTH-F2-2008-201549). Funding Information: Disclosure of potential conflict of interest: N. Rezaei is employed by and has received research support from Tehran University Med Sci , has received royalties from Springer , and has been supported by an American Academy of Allergy, Asthma & Immunology (AAAAI) Young Investigator Award . B. Costa Carvalho has received payment for development of educational presentations from the Federal University of Sao Paulo (FAPESP) and has received travel support from Octapharma. V. Thon has received research support from EURO-PADnet HEALTH ( F2-2008-201549 ). J. L. Franco has received consultancy fees from Baxter and Kedrion and has received lecture fees from Grifols . A. Sevciovic Grumach is a board member for Latin American Society for Immunodeficiencies and has received consultancy fees and lecture fees from SHIRE and CSL . T. Morio has received grant-in-aids for scientific research from the Japan Science and Technology Agency ; the Ministry of Education, Culture, and Sport ; and the Ministry of Health, Labour, and Welfare in Japan and has received lecture fees from Abbvie , CSL Behring , Chugai Pharmaceutical , Meiji Pharmaceuticals , Teijin Pharma , and Toray Medical . S. D. Rosenzweig has received consultancy fees from InPractice and UpToDate . The rest of the authors declare that they have no relevant conflicts of interest.

PY - 2014/4

Y1 - 2014/4

N2 - Background Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. Objectives We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≥1 month) showed an increased prevalence of complications (P =.006) and death caused by BCG-associated complications (P <.0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P =.001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P<.0001). Conclusions BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

AB - Background Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. Objectives We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≥1 month) showed an increased prevalence of complications (P =.006) and death caused by BCG-associated complications (P <.0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P =.001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P<.0001). Conclusions BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

KW - BCG

KW - Primary immunodeficiency

KW - hematopoietic stem cell transplant

KW - immune reconstitution syndrome

KW - mycobacteria

KW - newborn screening

KW - severe combined immunodeficiency

KW - vaccine

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BCG vaccination in patients with severe combined immunodeficiency: Complications, risks, and vaccination policies

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