Dataset Information

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/?L 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/?L. 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.

SUBMITTER: Marciano BE

PROVIDER: S-EPMC4015464 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Marciano Beatriz E BE Huang Chiung-Yu CY Joshi Gyan G Rezaei Nima N Carvalho Beatriz Costa BC Allwood Zoe Z Ikinciogullari Aydan A Reda Shereen M SM Gennery Andrew A Thon Vojtech V Espinosa-Rosales Francisco F Al-Herz Waleed W Porras Oscar O Shcherbina Anna A Szaflarska Anna A Kiliç Şebnem Ş Franco Jose L JL Gómez Raccio Andrea C AC Roxo Persio P Esteves Isabel I Galal Nermeen N Grumach Anete Sevciovic AS Al-Tamemi Salem S Yildiran Alisan A Orellana Julio C JC Yamada Masafumi M Morio Tomohiro T Liberatore Diana D Ohtsuka Yoshitoshi Y Lau Yu-Lung YL Nishikomori Ryuta R Torres-Lozano Carlos C Mazzucchelli Juliana T L JT Vilela Maria M S MM Tavares Fabiola S FS Cunha Luciana L Pinto Jorge A JA Espinosa-Padilla Sara E SE Hernandez-Nieto Leticia L Elfeky Reem A RA Ariga Tadashi T Toshio Heike H Dogu Figen F Cipe Funda F Formankova Renata R Nuñez-Nuñez M Enriqueta ME Bezrodnik Liliana L Marques Jose Gonçalo JG Pereira María I MI Listello Viviana V Slatter Mary A MA Nademi Zohreh Z Kowalczyk Danuta D Fleisher Thomas A TA Davies Graham G Neven Bénédicte B Rosenzweig Sergio D SD

The Journal of allergy and clinical immunology 20140401 4

<h4>Background</h4>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.<h4>Objectives</h4>We sought to describe the complications and risks associated with BCG vaccination in patients with SCID.<h4>Methods</h4>An extensive standardized questionna ...[more]

PMID: 24679470

Similar Datasets

Project description:Background: Severe combined immunodeficiency (SCID) is characterized by arrested T lymphocyte production and B lymphocyte dysfunction, resulting in life-threatening infections. Early diagnosis of SCID through population-based newborn screening (NBS) optimizes clinical management and outcomes, and also permits identification of previously unknown factors essential for human lymphocyte development. Methods: SCID was detected, prior to onset of infections, by NBS of T cell receptor excision circles, a biomarker for thymic output. Upon confirmation, the affected baby was treated by allogeneic hematopoietic cell transplantation (HCT). The genetic cause was sought by exome sequencing of the patient and parents, followed by functional analysis of a prioritized candidate gene using human hematopoietic stem cells (HSC) and zebrafish embryos. Results: An infant with leaky SCID, craniofacial and dermal abnormalities, and absent corpus callosum had his immune deficit fully corrected by HCT. Exome sequencing revealed a heterozygous, de novo, missense mutation pN441K in BCL11B. The mutant Bcl11b protein had dominant negative activity, abrogating the ability of wild type Bcl11b to bind DNA, arresting T cell lineage development and disrupting HSC migration, revealing a novel function of Bcl11b. The patientâs defects, recapitulated in Bcl11b-deficient zebrafish, were reversed by ectopic expression of intact, but not mutant, human BCL11B. Conclusions: Newborn screening facilitated treatment and identification of a novel etiology for human SCID. Coupling exome sequencing with candidate gene evaluation in human HSC and in zebrafish revealed that a constitutional BCL11B mutation causes human multisystem anomalies with SCID, while also revealing a novel, pre-thymic role for Bcl11b in hematopoietic progenitors. 3 samples were analyzed in duplicate, Sample 1 was human HSC transduced with GFP only lentivirus which served as controls, Sample 2 was human HSC transduced with lentivirus expressing FLAG-tagged WT BCL11B and GFP, Sample 3 was human HSC transduced with lentivirus expressing FLAG-tagged mutant BCL11B and GFP

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets