Incidence, Risk Factors and Outcomes of BCGosis Following BCG Vaccination in Infants: A Systematic Review and Meta-Analyses

Fathima Raahima Riyas Mohamed¹Mudasir Nisar²Ismail Saeed¹Mohammed Rushdhi Irfan¹Ahlaam Khalid³Muneeb Faiz⁴Ahmed F Younis⁵Shahan Javed¹Arya Sen⁶Asma Azam⁷Muhabat Raji¹Abrar Barakzai¹Atef M Shibl¹Garwin Kim Sing^1*

• ¹College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
• ²Department of Medicine, Services Institute of Medical Sciences, Lahore, Punjab, Pakistan
• ³Gomal Medical College, Dera Ismail Khan, Pakistan, Dera Ismail Khan, Pakistan
• ⁴King Edward Medical University, Lahore, Punjab, Pakistan
• ⁵Faculty of Medicine in Damietta, Al-Azhar University, New Damietta, Egypt
• ⁶Medical College Kolkata, Kolkata, West Bengal, India
• ⁷Karachi Medical and Dental College, Karachi, Sindh, Pakistan

This systematic review and meta-analysis examines the incidence, risk factors, and outcomes of BCGosis following Bacille Calmette-Guérin (BCG) vaccination in infants, a rare but severe complication that disproportionately affects immunocompromised children. The BCG vaccine is widely administered in countries with high tuberculosis (TB) prevalence to protect against severe forms of childhood TB, such as meningitis and miliary TB. Despite its efficacy, the vaccine can lead to adverse effects like BCGosis, a condition marked by systemic granulomatous inflammation that occurs when the attenuated BCG bacteria disseminate beyond the injection site. Through a systematic review of current literature, this analysis seeks to determine the global incidence of BCGosis and identify critical risk factors associated with its onset. The findings indicate that BCGosis is most prevalent in infants with underlying genetic immunodeficiencies, such as severe combined immunodeficiency (SCID) and chronic granulomatous disease (CGD). Additionally, genetic mutations affecting immune pathways, notably those in NADPH oxidase function and interferon-gamma signaling, are strongly correlated with BCGosis incidence. Consanguinity, prevalent in certain populations, is also a risk factor due to the increased likelihood of inheriting recessive immune defects. Factors like early neonatal vaccination (often within the first week of life) and variations in BCG strains may also influence BCGosis risk, though more research is needed in these areas. The outcomes underscore an urgent need for enhanced pre-vaccination screening for genetic and immunologic vulnerabilities in infants at high risk for BCGosis. In populations with high consanguinity rates or where immunodeficiency screening is accessible, these findings suggest a potential benefit in exploring alternative vaccination schedules or postponing BCG immunization until immune competency can be confirmed. This analysis aims to guide clinical practice, support the development of tailored vaccination policies, and highlight avenues for further research on optimizing BCG vaccination in immunologically vulnerable infants, ultimately reducing the incidence and severity of BCGosis and improving patient outcomes.