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

Abstract

Background SCID is a syndrome characterized by profound T cell deficiency. BCG vaccine is contraindicated in SCID patients. Because most countries encourage BCG vaccination at birth, a high percent of SCID patients are vaccinated before their immune defect is detected. Objectives To describe the complications and risks associated with BCG vaccination in SCID patients. Methods An extensive standardized questionnaire evaluating complications, therapeutics, and outcome regarding BCG in patients diagnosed with SCID was widely distributed. Summary statistics and association analysis was performed. Results Data on 349 BCG vaccinated SCID patients from 28 centers in 17 countries was analyzed. Fifty-one percent of the patients developed BCG 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=0.006) and death due to BCG complications (p<0.0001). The odds of experiencing complications among patients with T cells ≤ 250/uL at diagnosis was 2.1 times higher (95% CI, 1.4-3.4; p = 0.001) than among those with T cells > 250/uL. BCG complications were reported in 2/78 patients who received anti-mycobacterial therapy while asymptomatic and no deaths due to BCG complications occurred in this group. In contrast 46 BCG-associated deaths were reported among 160 patients treated with anti-mycobacterial therapy for a symptomatic BCG infection (p<0.0001). Conclusions BCG vaccine has a very high rate of complications in SCID patients, which increase morbidity and mortality rates. Until safer and more efficient anti-tuberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Local Cutaneous Complications After Bacille Calmette-Guerin Vaccine: Experience of a Single Center

“…Marciano et al reported after vaccination various BCG associated manifestations were seen in half of the patients with SCID. Localized disease occurred in one-third of patients and disseminated disease was seen in two-thirds [3]. In the above studies, primer immunodeficiencies were detected frequently causative for BCG complications.…”

“…Several complications have been reported after the routine immunization program of BCG vaccine. Although some of these are normal vaccine reactions, unexpected complications have been noted [3][4][5][6][7][8][9]. Adverse reactions may be affected with some factors like patient's age, vaccine strains, dosage, erroneous administration, and disturbance of cellular immunity [11].…”

“…These lesions heal with scar in approximately 3 months. Although BCG vaccine complications are so rare, in literature erythema, soreness, abscess formation, purulent drainage, ulcer, keloid scar, blistering, regional lymphadenopathy, disseminated BCG-itis, osteomyelitis and osteitis have been reported in some cases [3][4][5][6][7][8][9]. There is no consensus on the treatment of local complications of BCG vaccine.…”

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade's Experience

“…In this study, the median age at the onset of symptoms and the age of diagnosis were 40 and 110 days, respectively. According to a previous report from Iran in 2008 [5], the mean age of diagnosis in Iranian SCID patients was 150 (20) days, which has fallen to less than 4 months during the last decade. Therefore, reducing the age at diagnosis to lower than 4 months in Iran is a valuable achievement compared with other countries such as Canada (4.2 months), Brazil (6.1 months), and Serbia (4 months) [14][15][16].…”

Newborn Screening for Severe Combined Immunodeficiency in Taiwan

“…Because of the burden of tuberculosis (TB) in Taiwan, all newborns receive Bacillus Calmette-Guérin (BCG) vaccination at birth to avoid TB meningitis [11]. However, this policy has also put newborns with primary immunodeficiencies, such as SCID, at a higher risk for disseminated BCGitis [12][13][14].…”