Anastasia Phillips1, Megan Hickie2, James Totterdell3, Julia Brotherton4, Aditi Dey5, Richard Hill2, Tom Snelling6, Kristine Macartney5. 1. The University of Sydney, School of Public Health, Sydney, New South Wales 2006, Australia; National Centre for Immunisation Research and Surveillance, Westmead, New South Wales 2145, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia 6009, Australia. Electronic address: aphi7007@uni.sydney.edu.au. 2. Therapeutic Goods Administration, Department of Health, Woden, Australian Capital Territory 2606, Australia. 3. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia 6009, Australia. 4. Victorian Cytology Service Foundation, Carlton, Victoria 3053, Australia; University of Melbourne, Parkville, Victoria 3010, Australia. 5. National Centre for Immunisation Research and Surveillance, Westmead, New South Wales 2145, Australia; The University of Sydney, Discipline of Child and Adolescent Health, Sydney, New South Wales 2006, Australia. 6. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Western Australia 6009, Australia; Perth Children's Hospital, Nedlands, Western Australia 6009, Australia; Curtin University, School of Public Health, Bentley, Western Australia 6102, Australia; Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
Abstract
BACKGROUND: Australia was the first country to implement a fully funded vaccination program with quadrivalent human papillomavirus vaccine (4vHPV) in 2007, including males from 2013. We examined adverse events (AE) following vaccination with 4vHPV from 11 years of post-marketing data, focusing on a period of enhanced surveillance and adverse events of special interest (AESI). METHODS: AE following 4vHPV doses administered between April 2007 and December 2017 reported to Australia's national regulator, the Therapeutic Goods Administration, were examined; reports collected during enhanced surveillance in 2013 and 2014 were analyzed separately. Age and sex-specific rates, using denominator data from the national HPV vaccination register, were determined. Pre-specified AESI were identified using Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms and examined in detail. FINDINGS: Following nine million doses of 4vHPV vaccine administered in Australia, 4551 AE reports were identified. The crude reporting rate was 39.8 per 100 000 doses in the funded cohorts, excluding the enhanced surveillance period. The reported rate of syncope in 12 to 13-year-old males and females was 29.6 per 100 000 doses during enhanced surveillance and 7.1 per 100 000 doses during the remaining study period; rates of syncope were higher in younger compared to older adolescents. The rate of anaphylaxis (0.32 per 100 000 doses) was consistent with published rates. Other AESI including autoimmune disease, postural orthostatic tachycardia syndrome, primary ovarian insufficiency, Guillain-Barré syndrome, complex regional pain syndrome and venous thromboembolism, were reported at low rates and analysis did not reveal unexpected patterns that would suggest causal association. INTERPRETATION: AESI, apart from syncope, were reported rarely. The higher rate of syncope among younger adolescents highlights the need for management protocols to prevent syncope-related injury. Analysis of this large, longitudinal dataset in a country with high vaccine uptake, including a period of enhanced surveillance, affirms the safety profile of 4vHPV.
BACKGROUND: Australia was the first country to implement a fully funded vaccination program with quadrivalent human papillomavirus vaccine (4vHPV) in 2007, including males from 2013. We examined adverse events (AE) following vaccination with 4vHPV from 11 years of post-marketing data, focusing on a period of enhanced surveillance and adverse events of special interest (AESI). METHODS: AE following 4vHPV doses administered between April 2007 and December 2017 reported to Australia's national regulator, the Therapeutic Goods Administration, were examined; reports collected during enhanced surveillance in 2013 and 2014 were analyzed separately. Age and sex-specific rates, using denominator data from the national HPV vaccination register, were determined. Pre-specified AESI were identified using Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms and examined in detail. FINDINGS: Following nine million doses of 4vHPV vaccine administered in Australia, 4551 AE reports were identified. The crude reporting rate was 39.8 per 100 000 doses in the funded cohorts, excluding the enhanced surveillance period. The reported rate of syncope in 12 to 13-year-old males and females was 29.6 per 100 000 doses during enhanced surveillance and 7.1 per 100 000 doses during the remaining study period; rates of syncope were higher in younger compared to older adolescents. The rate of anaphylaxis (0.32 per 100 000 doses) was consistent with published rates. Other AESI including autoimmune disease, postural orthostatic tachycardia syndrome, primary ovarian insufficiency, Guillain-Barré syndrome, complex regional pain syndrome and venous thromboembolism, were reported at low rates and analysis did not reveal unexpected patterns that would suggest causal association. INTERPRETATION: AESI, apart from syncope, were reported rarely. The higher rate of syncope among younger adolescents highlights the need for management protocols to prevent syncope-related injury. Analysis of this large, longitudinal dataset in a country with high vaccine uptake, including a period of enhanced surveillance, affirms the safety profile of 4vHPV.
Authors: Kalyani Sonawane; Yueh-Yun Lin; Haluk Damgacioglu; Yenan Zhu; Maria E Fernandez; Jane R Montealegre; Cecilia Ganduglia Cazaban; Ruosha Li; David R Lairson; Ying Lin; Anna R Giuliano; Ashish A Deshmukh Journal: JAMA Netw Open Date: 2021-09-01
Authors: Cristyn Davies; Helen S Marshall; Gregory Zimet; Kirsten McCaffery; Julia M L Brotherton; Melissa Kang; Suzanne Garland; John Kaldor; Kevin McGeechan; S Rachel Skinner Journal: JAMA Netw Open Date: 2021-11-01