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

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.