Fazlollahi Mohammad Reza, Goudarzi Ali, Nourizadeh Maryam, Alizadeh Zahra, Tajik Shaghayegh, Badalzadeh Mohsen, Sarafzadeh Shokouh Azam, Mahlooji Rad Maryam, Adab Zeinab, Moradi Leila, Razaghian Anahita, Sabetkish Nastaran, Pourpak Zahra, Moin Mostafa
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
Front Immunol. 2024 Dec 5;15:1477499. doi: 10.3389/fimmu.2024.1477499. eCollection 2024.
According to the WHO's recommendation for developing countries, Bacillus Calmette-Guerin (BCG) vaccination has been implemented in some countries as part of national vaccination programs at birth. Although it is generally considered safe, some complications may occur; including BCGitis (local) or BCGosis (systemic), ranging from mild like local abscesses to fatal impediments like osteomyelitis and disseminated BCG infection. This study aimed to determine the spectrum of inborn errors of immunity (IEI) in BCG-vaccinated neonates experiencing local or systemic complications.
In this cross-sectional study, we investigated Iranian children referred to the Immunology, Asthma, and Allergy Research Institute (IAARI) between 2007-2023 for suspected immunodeficiency. Medical history was recorded, and primary screening tests for immunodeficiency were conducted for all cases. For suspected cases, more advanced immunologic investigations were performed to reach a definitive diagnosis. Furthermore, the study incorporated the documented genetic findings of the patients under investigation. All patients with inborn error of immunity who had a history of BCG vaccine complications within the first year of vaccination were enrolled in the study.
We investigated 3,275 cases suspected of IEI, identifying197 patients with both IEI and BCG vaccine complications. Among these, 127 (64.5%) were male. Symptoms began at or before 3 months of age in 64.8% of the cases, and parental consanguinity was reported in 79.2%. Genetic diagnoses were confirmed in 108 patients. Of the 197 patients, 108 (54.8%) had BCGitis, while 89 (45.2%) experienced systemic complications (BCGosis). A family history of IEI, BCG-related complications, and unexplained deaths were observed in 20.3%, 12.2%, and 29.9% of cases, respectively. Furthermore, 46.2% had at least one of these three risk factors in their history.
Early BCG vaccine complications may indicate an underlying immunodeficiency, particularly when there is a positive family history of BCG complications, immunodeficiency, or unexplained deaths. Nation-wide vaccination protocols should address this issue by delaying inoculation to allow for immunological screening of suspected immunodeficient patients, thereby preventing BCG vaccine-related morbidity and mortality.
根据世界卫生组织对发展中国家的建议，卡介苗（BCG）接种已在一些国家作为国家出生时疫苗接种计划的一部分实施。尽管通常认为它是安全的，但可能会出现一些并发症，包括卡介苗局部感染（局部性）或卡介苗播散感染（全身性），范围从轻微的局部脓肿到致命的障碍，如骨髓炎和播散性卡介苗感染。本研究旨在确定接种卡介苗后出现局部或全身并发症的新生儿免疫缺陷病（IEI）谱。
在这项横断面研究中，我们调查了2007年至2023年间因疑似免疫缺陷转诊至免疫、哮喘和过敏研究所（IAARI）的伊朗儿童。记录病史，并对所有病例进行免疫缺陷的初步筛查试验。对于疑似病例，进行更先进的免疫学检查以做出明确诊断。此外，该研究纳入了受调查患者的记录基因结果。所有在接种疫苗的第一年内有卡介苗疫苗并发症病史的免疫缺陷病患者均纳入本研究。
我们调查了3275例疑似IEI的病例，确定了197例患有IEI且有卡介苗疫苗并发症的患者。其中，127例（64.5%）为男性。64.8%的病例症状在3个月龄及以前开始，79.2%的病例有父母近亲结婚史。108例患者确诊了基因诊断。在197例患者中，108例（54.8%）有卡介苗局部感染，而89例（45.2%）出现全身并发症（卡介苗播散感染）。分别有20.3%、12.2%和29.9%的病例有IEI家族史、卡介苗相关并发症和不明原因死亡。此外，46.2%的病例在其病史中有这三个危险因素中的至少一个。
早期卡介苗疫苗并发症可能表明潜在的免疫缺陷，特别是当有卡介苗并发症、免疫缺陷或不明原因死亡的家族史阳性时。全国性的疫苗接种方案应通过推迟接种来解决这个问题，以便对疑似免疫缺陷患者进行免疫学筛查，从而预防卡介苗疫苗相关的发病率和死亡率。
