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

Fekrvand, Saba; Yazdani, Reza; Olbrich, Peter; Gennery, Andrew R.; Rosenzweig, Sergio D.; Condino‐Neto, Antônio; Azizi, Gholamreza; Rafiemanesh, Hosein; Hassanpour, Gholamreza; Rezaei, Nima; Abolhassani, Hassan; Aghamohammadi, Asghar

doi:10.1016/j.jaip.2020.01.038

Cited by 61 publications

(70 citation statements)

References 207 publications

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“…Indeed, post-HSCT, BCG-related complications have been reported in T cell deficiencies [ 3 , 18 – 35 ] but have not so far been described in phagocytic defects. Despite the well-known association between CGD and BCG [ 6 , 7 , 13 , 36 ], none of our 7 BCG-vaccinated CGD patients, including a patient with pre-transplant BCGosis, developed post-HSCT complications. These findings, in agreement with previous reports [ 13 , 37 ], point to the central role of T cells in control of chronic mycobacterial infection and in mycobacterial-related IRIS [ 38 ].…”

Section: Discussionmentioning

confidence: 75%

“…Since BCG is a live attenuated vaccine, complication rates are significantly increased in immunodeficient individuals [ 3 , 6 – 11 ], especially so in patients with T cell defects, mendelian susceptibility to mycobacterial disease (MSMD), or chronic granulomatous disease (CGD) [ 5 – 7 , 11 ], reflecting the main mechanisms of defense against mycobacteria. For T cell defects, this susceptibly is related to the inability to produce an effective Th1 response [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…For T cell defects, this susceptibly is related to the inability to produce an effective Th1 response [ 3 ]. MSMD patients suffer from defects in the interleukin (IL)-12/IL-23/interferon (IFN) γ circuit [ 12 ] and CGD, caused by defects in the NADPH oxidase complex, adversely affect the macrophage’s and neutrophil’s ability to kill phagocytosed bacilli [ 6 , 13 ]. Severe combined immunodeficiency (SCID) is the most common diagnosis among BCG-complicated primary immunodeficiency (PID) patients [ 3 , 6 ] (42–51% of BCG-vaccinated SCID patients), with the highest mortality rate (41.2%) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…MSMD patients suffer from defects in the interleukin (IL)-12/IL-23/interferon (IFN) γ circuit [ 12 ] and CGD, caused by defects in the NADPH oxidase complex, adversely affect the macrophage’s and neutrophil’s ability to kill phagocytosed bacilli [ 6 , 13 ]. Severe combined immunodeficiency (SCID) is the most common diagnosis among BCG-complicated primary immunodeficiency (PID) patients [ 3 , 6 ] (42–51% of BCG-vaccinated SCID patients), with the highest mortality rate (41.2%) [ 6 ]. Lower T cell counts, younger age at vaccination [ 3 ], and natural killer (NK)-SCID [ 6 ] are risk factors for BCG-related complications.…”

Section: Introductionmentioning

confidence: 99%

“…Severe combined immunodeficiency (SCID) is the most common diagnosis among BCG-complicated primary immunodeficiency (PID) patients [ 3 , 6 ] (42–51% of BCG-vaccinated SCID patients), with the highest mortality rate (41.2%) [ 6 ]. Lower T cell counts, younger age at vaccination [ 3 ], and natural killer (NK)-SCID [ 6 ] are risk factors for BCG-related complications.…”

Section: Introductionmentioning

confidence: 99%

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Bacillus Calmette–Guerin (BCG) Vaccine-associated Complications in Immunodeficient Patients Following Stem Cell Transplantation

et al. 2020

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Purpose Bacillus Calmette–Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency diseases (PID) before and after hematopoietic stem cell transplantation (HSCT). We aim to investigate risk factors of post-HSCT BCG-related complications in PID patients. Methods A retrospective analysis of pediatric PID patients who had received the BCG vaccine and underwent HSCT at Hadassah-Hebrew University Medical Center, between 2007 and 2019. Results We found 15/36 (41.67%) patients who developed post-HSCT BCG-related complications. The most significant risk factor for developing BCG-related complications was T cell deficiency (47.6% of the non-complicated vs 83.3% of the BCGitis and 100% of the BCGosis groups had T cell lymphopenia, p = 0.013). None of the chronic granulomatous patients developed BCG-related manifestation post-transplant. Among T cell–deficient patients, lower NK (127 vs 698 cells/μl, p = 0.04) cell counts and NK-SCID were risk factors for ongoing post-HSCT BCGosis, as was pretransplant disseminated BCGosis (33.3% of patients with BCGosis vs none of the non-BCGosis patients, p = 0.04). Immune reconstitution inflammatory syndrome (IRIS) was observed in 3/5 patients with Omenn syndrome. Prophylactic antimycobacterial treatment was not proven effective. Conclusion BCG vaccination can cause significant morbidity and mortality in the post-transplant T cell–deficient patient, especially in the presence of pre-transplant disease. Taking a detailed medical history prior to administering, the BCG vaccine is crucial for prevention of this complication.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bacillus Calmette–Guerin (BCG) Vaccine-associated Complications in Immunodeficient Patients Following Stem Cell Transplantation

et al. 2020

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Vaccination with Live Vaccines

Blanchard-Rohner

Pittet

2022

In Clinical Practice

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Vaccination of immune compromised children—an overview for physicians

Pittet

Posfay‐Barbe

2021

Eur J Pediatr

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Immune compromised children are threatened by a higher risk of infections; some of these are preventable by vaccination. Primary care physicians play a fundamental role in optimising vaccination status. In this narrative review, we present the evidence on vaccine safety and immunogenicity in immune compromised children and discuss in which conditions live-attenuated vaccines can possibly be used. Vaccination schedules differ in some of these conditions, including the use of vaccines with higher antigenic contents (e.g. high-dose hepatitis B vaccine), additional vaccine doses (e.g. 2-dose schedule meningococcal vaccine), more frequent booster doses (e.g. life-long pneumococcal vaccine booster), supplementary vaccines (e.g. meningococcal B vaccine) and use of vaccines beyond the age of usual recommendation (e.g. Haemophilus influenza type b vaccine after 5 years of age). Serological monitoring is a useful tool for customizing vaccination schedule in immune compromised children, confirming adequate vaccine response and documenting seroprotection (especially against measles and varicella). Finally, verification of vaccination status of all household members can prevent them being vector of transmission of an infection to the immune compromised children. Conclusion: Intensified information strategies are needed to improve trust, rectify perceived risks and improve vaccine acceptability; primary physicians can play a critical role in the latter. What is Known:• Physician’s awareness is key to success, since it repeatedly correlates with higher vaccination rates What is New:• The vaccination status of immunocompromised children is rarely up-to-date• Knowing the latest vaccine recommendations is challenging, as they differ for each medical condition and change periodically• This review summarises the vaccine recommendations for children with compromised immune systems and highlights how paediatricians play a key role in coordinating their application

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

Cited by 61 publications

References 207 publications

Bacillus Calmette–Guerin (BCG) Vaccine-associated Complications in Immunodeficient Patients Following Stem Cell Transplantation

Bacillus Calmette–Guerin (BCG) Vaccine-associated Complications in Immunodeficient Patients Following Stem Cell Transplantation

Vaccination with Live Vaccines

Vaccination of immune compromised children—an overview for physicians

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