Primary Immunodeficiency Diseases and Bacillus Calmette-Guérin (BCG)-Vaccine-Derived Complications: A Systematic Review

Saba Fekrvand; Reza Yazdani; Peter Olbrich; Andrew Gennery; Sergio D Rosenzweig; Antonio Condino-Neto; Gholamreza Azizi; Hosein Rafiemanesh; Gholamreza Hassanpour; Nima Rezaei; Hassan Abolhassani; Asghar Aghamohammadi

doi:10.1016/j.jaip.2020.01.038

Primary Immunodeficiency Diseases and Bacillus Calmette-Guérin (BCG)-Vaccine-Derived Complications: A Systematic Review

J Allergy Clin Immunol Pract. 2020 Apr;8(4):1371-1386. doi: 10.1016/j.jaip.2020.01.038. Epub 2020 Jan 30.

Authors

Affiliations

¹ Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
² Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. Electronic address: reza_yazdani86@yahoo.com.
³ Sección de Infectología e Inmunopatología, Unidad de Pediatría, Hospital Virgen del Rocío/Instituto de Biomedicina de Sevilla, Seville, Spain.
⁴ Institute of Cellular Medicine, Newcastle University, and Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
⁵ Immunology Service, Department of Laboratory Medicine, National Institutes Clinical Center, National Institutes of Health, Bethesda, Md.
⁶ Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁷ Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
⁸ Student Research Committee, Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁹ Center for Research of Endemic Parasites of Iran, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Network for Immunology in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network, Tehran, Iran.
¹¹ Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden; Research Center for Primary Immunodeficiencies, Iran University of Medical Sciences, Tehran, Iran.
¹² Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. Electronic address: aghamohammadi@sina.tums.ac.ir.

PMID: 32006723
DOI: 10.1016/j.jaip.2020.01.038

Abstract

Background: Bacillus Calmette-Guérin (BCG) vaccine is a live attenuated bacterial vaccine derived from Mycobacterium bovis, which is mostly administered to neonates in regions where tuberculosis is endemic. Adverse reactions after BCG vaccination are rare; however, immunocompromised individuals and in particular patients with primary immunodeficiencies (PIDs) are prone to develop vaccine-derived complications.

Objective: To systematically review demographic, clinical, immunologic, and genetic data of PIDs that present with BCG vaccine complications. Moreover, we performed a meta-analysis aiming to determine the BCG-vaccine complications rate for patients with PID.

Methods: We conducted electronic searches on Embase, Web of Science, PubMed, and Scopus (1966 to September 2018) introducing terms related to PIDs, BCG vaccination, and BCG vaccine complications. Studies with human subjects with confirmed PID, BCG vaccination history, and vaccine-associated complications (VACs) were included.

Results: A total of 46 PIDs associated with BCG-VAC were identified. Severe combined immunodeficiency was the most common (466 cases) and also showed the highest BCG-related mortality. Most BCG infection cases in patients with PID were reported from Iran (n = 219 [18.8%]). The overall frequency of BCG-VAC in the included 1691 PID cases was 41.5% (95% CI, 29.9-53.2; I² = 98.3%), based on the results of the random-effect method used in this meta-analysis. Patients with Mendelian susceptibility to mycobacterial diseases had the highest frequency of BCG-VACs with a pooled frequency of 90.6% (95% CI, 79.7-1.0; I² = 81.1%).

Conclusions: Several PID entities are susceptible to BCG-VACs. Systemic neonatal PID screening programs may help to prevent a substantial amount of BCG vaccination complications.

Keywords: Adverse events following immunization (AEFI); BCGitis; BCGosis; Bacillus Calmette-Guérin; Mycobacterium bovis; Primary immunodeficiency diseases.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

BCG Vaccine / adverse effects
Humans
Infant, Newborn
Mycobacterium bovis*
Primary Immunodeficiency Diseases*
Tuberculosis* / epidemiology
Vaccination

Substances

BCG Vaccine