Sally Bee Leng Soh1, Phey Yen Han2, Kai Tong Tam2, Chee Fu Yung3, Woei Kang Liew4, Natalie Woon Hui Tan5, Chia Yin Chong5, Koh Cheng Thoon5. 1. Vigilance and Compliance Branch, Health Products Regulation Group, Health Sciences Authority, 11 Biopolis Way #11-01 Helios, Singapore 138667, Singapore. Electronic address: sally_soh@hsa.gov.sg. 2. Vigilance and Compliance Branch, Health Products Regulation Group, Health Sciences Authority, 11 Biopolis Way #11-01 Helios, Singapore 138667, Singapore. 3. Department of Clinical Epidemiology, Communicable Disease Centre, Institute of Infectious Disease and Epidemiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. 4. Department of Paediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore. 5. Department of Paediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; Duke-National University of Singapore Graduate Medical School, 8 College Road, Singapore 169857, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, National University Health System Building (NUH), Singapore 119228, Singapore.
Abstract
INTRODUCTION: From 2011 to 2012, we received an unexpectedly high number of reports of suppurative lymphadenitis following administration of a BCG vaccine used in our childhood vaccination programme in Singapore. We sought to determine the local incidence rates of BCG-associated suppurative lymphadenitis across the 2009 to 2012 vaccinated cohorts, and to analyse the potential factors contributing to this outbreak. METHODS: Reports of lymphadenitis following BCG vaccination from an AEFI active surveillance system at the KK Women's and Children's Hospital (KKH) and passive surveillance data from other healthcare institutions were reviewed. All valid reports received from January 2009 to December 2013 involving neonates vaccinated with the BCG vaccine in 2009 to 2012 that met case definitions were included in our analysis. Details of the demographics and vaccination history of the child, and statistics from the local vaccination programme were also obtained. Potential contributory factors were selected for further investigation based on a literature review of similar outbreaks overseas. RESULTS: We identified 283 cases of lymphadenitis, of which 76% were suppurative. A spike in suppurative lymphadenitis cases was seen in the 2011 vaccinated cohort, with an incidence rate of 3.16 per 1000 vaccinees, as compared to 0.71 to 0.85 per 1000 in the 2009, 2010 and 2012 cohorts. Our investigations identified the likely cause of the outbreak to be batch-related, arising from manufacturing issues encountered by the manufacturer, after ruling out vaccine administration-related and host-related factors. CONCLUSIONS: The three-fold spike in BCG-associated suppurative lymphadenitis cases observed in the 2011 vaccinated cohort, possibly due to batch-to-batch variation of the vaccine, highlights that manufacturing controls can continue to be a challenge. Development of a more sensitive assay to test the reactogenicity of the BCG vaccine may help reduce the occurrence of such outbreaks and improve public confidence in the nation's vaccination programme.
INTRODUCTION: From 2011 to 2012, we received an unexpectedly high number of reports of suppurative lymphadenitis following administration of a BCG vaccine used in our childhood vaccination programme in Singapore. We sought to determine the local incidence rates of BCG-associated suppurative lymphadenitis across the 2009 to 2012 vaccinated cohorts, and to analyse the potential factors contributing to this outbreak. METHODS: Reports of lymphadenitis following BCG vaccination from an AEFI active surveillance system at the KK Women's and Children's Hospital (KKH) and passive surveillance data from other healthcare institutions were reviewed. All valid reports received from January 2009 to December 2013 involving neonates vaccinated with the BCG vaccine in 2009 to 2012 that met case definitions were included in our analysis. Details of the demographics and vaccination history of the child, and statistics from the local vaccination programme were also obtained. Potential contributory factors were selected for further investigation based on a literature review of similar outbreaks overseas. RESULTS: We identified 283 cases of lymphadenitis, of which 76% were suppurative. A spike in suppurative lymphadenitis cases was seen in the 2011 vaccinated cohort, with an incidence rate of 3.16 per 1000 vaccinees, as compared to 0.71 to 0.85 per 1000 in the 2009, 2010 and 2012 cohorts. Our investigations identified the likely cause of the outbreak to be batch-related, arising from manufacturing issues encountered by the manufacturer, after ruling out vaccine administration-related and host-related factors. CONCLUSIONS: The three-fold spike in BCG-associated suppurative lymphadenitis cases observed in the 2011 vaccinated cohort, possibly due to batch-to-batch variation of the vaccine, highlights that manufacturing controls can continue to be a challenge. Development of a more sensitive assay to test the reactogenicity of the BCG vaccine may help reduce the occurrence of such outbreaks and improve public confidence in the nation's vaccination programme.