Abstract：
A programme of vaccination with the four-component serogroup B meningococcal (4CMenB) vaccine was introduced in South Australia for infants and children aged 0-3 years on Oct 1, 2018, and for senior school students in school years 10 and 11 (aged 15-16 years) and young adults aged 17-20 years on Feb 1, 2019. We aimed to evaluate vaccine effectiveness and impact on serogroup B meningococcal disease and gonorrhoea 2 years after implementation of the programme.
We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme.
4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls.
4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme\'s second year.
SA Health, Government of South Australia.
We did a cohort and case-control study among those targeted by the South Australia 4CMenB vaccination programme. We obtained disease notification data from SA Health, Government of South Australia, and vaccine coverage data from the South Australian records of the Australian Immunisation Register. Vaccine effectiveness was estimated as the reduction in the odds of infection using the screening and case-control methods. Vaccine impact was estimated as incidence rate ratios (IRRs), obtained by comparing case numbers in each year following the start of the vaccination programme with cases in the equivalent age cohort during the pre-vaccination programme years. We used Poisson or negative binomial models, as appropriate, with adjustment for changes in the incidence of serogroup B meningococcal disease in age cohorts not eligible for vaccination through the state programme.
4CMenB vaccine coverage 2 years after introduction of the childhood vaccination programme was 94·9% (33 357 of 35 144 eligible individuals) for one dose, 91·4% (26 443 of 28 922) for two doses, and 79·4% (15 440 of 19 436) for three doses in infants. The one-dose (77·1%, 16 422 of 21 305) and two-dose (69·0%, 14 704 of 21 305) coverage was highest in adolescents born in 2003 (approximately year 10 students). 2 years after implementation of the childhood vaccination programme, incidence of serogroup B meningococcal disease was significantly reduced compared with before programme implementation in infants aged 12 weeks to 11 months (adjusted IRR [aIRR] 0·40 [95% CI 0·23-0·69], p=0·0011), but not in those aged 1 year (0·79 [0·16-3·87], p=0·77), 2 years (0·75 [0·18-3·14], p=0·70), or 4 years (3·00 [0·47-18·79], p=0·24). aIRRs were not calculable in those aged 3 or 5 years because of no cases occurring after programme implementation. aIRR for serogroup B meningococcal disease was 0·27 (0·06-1·16, p=0·078) in adolescents aged 15-18 years 2 years after implementation of the adolescent and young adult programme, and 1·20 (0·70-2·06, p=0·51) in those aged 19-21 years in the first year. Two-dose vaccine effectiveness against serogroup B meningococcal disease was estimated to be 94·2% (95% CI 36·6-99·5) using the screening method and 94·7% (40·3-99·5) using the case-control method in children, and 100% in adolescents and young adults (no cases reported after implementation). Estimated two-dose vaccine effectiveness against gonorrhoea in adolescents and young adults was 32·7% (8·3-50·6) based on the case-control method using age-matched individuals with chlamydia infection as controls.
4CMenB vaccine shows sustained effectiveness against serogroup B meningococcal disease 2 years after introduction in infants and adolescents, and moderate effectiveness against gonorrhoea in adolescents. The high vaccine effectiveness against serogroup B meningococcal disease is likely due to high coverage in the target age groups and close antigenic match between the 4CMenB vaccine and the disease-associated serogroup B meningococcal strains circulating in South Australia. COVID-19-related physical distancing policies might have contributed to further declines in serogroup B meningococcal disease cases during the programme\'s second year.
SA Health, Government of South Australia.
摘要：
2018年10月1日，南澳大利亚为0-3岁的婴儿和儿童以及10和11岁（15-16岁）的高中生和2019年2月1日17-20岁的年轻人引入了四组分血清群B脑膜炎球菌（4CMenB）疫苗接种计划。我们旨在评估该计划实施2年后疫苗的有效性以及对血清群B脑膜炎球菌疾病和淋病的影响。
我们在南澳大利亚4CMenB疫苗接种计划的目标人群中进行了一项队列和病例对照研究。我们从SAHealth获得了疾病通知数据，南澳大利亚政府,和疫苗覆盖率数据来自澳大利亚免疫登记册的南澳大利亚记录。疫苗有效性估计为使用筛查和病例对照方法降低感染几率。疫苗影响估计为发病率比率(IRR)，通过将疫苗接种计划开始后每年的病例数与疫苗接种计划前几年同等年龄队列中的病例数进行比较获得。我们使用泊松或负二项模型，在适当的情况下,调整了不符合通过国家计划接种疫苗资格的年龄组血清B群脑膜炎球菌病发病率的变化。
实施儿童疫苗接种计划2年后的4CMenB疫苗覆盖率为94·9%（35144名合格个体中的33357名），一剂91·4%（26443/28922），和79·4%（19436中的15440）的三个剂量的婴儿。一剂(77·1%，16422of21305)和两次剂量(69·0%，14704/21305）在2003年出生的青少年（大约10年级学生）中的覆盖率最高。儿童疫苗接种计划实施2年后，与计划实施前相比，12周至11个月大的婴儿血清B群脑膜炎球菌病的发病率显着降低（调整后的IRR[aIRR]0·40[95％CI0·23-0·69]，p=0·0011），但不是在1岁的人(0·79[0·16-3·87]，p=0·77)，2年（0·75[0·18-3·14]，p=0·70)，或4年(3·00[0·47-18·79]，p=0·24）。aIRRs是不可计算的年龄在3或5年,因为没有案件发生后的方案实施。在实施青少年和年轻成人方案2年后，15-18岁青少年的血清B群脑膜炎球菌疾病的IRR为0·27(0·06-1·16，p=0·078)，第一年19-21岁的人群为1·20（0·70-2·06，p=0·51）。使用筛查方法，两剂疫苗对血清B群脑膜炎球菌病的有效性估计为94·2％（95％CI36·6-99·5），使用病例对照方法，儿童为94·7％（40·3-99·5），和100％在青少年和年轻人（实施后无病例报告）。根据病例对照方法，使用年龄匹配的衣原体感染个体作为对照，估计青少年和年轻人的两剂疫苗对淋病的有效性为32·7％（8·3-50·6）。
4CMenB疫苗在婴儿和青少年中引入2年后显示出对血清群B脑膜炎球菌疾病的持续有效性，对青少年淋病有中等效果。针对血清群B脑膜炎球菌疾病的高疫苗有效性可能是由于目标年龄组的高覆盖率以及4CMenB疫苗与南澳大利亚流行的疾病相关血清群B脑膜炎球菌菌株之间的紧密抗原匹配。在该计划的第二年，与COVID-19相关的身体距离政策可能导致血清群B脑膜炎球菌疾病病例进一步下降。
SA健康，南澳大利亚政府。
我们在南澳大利亚4CMenB疫苗接种计划的目标人群中进行了一项队列和病例对照研究。我们从SAHealth获得了疾病通知数据，南澳大利亚政府,和疫苗覆盖率数据来自澳大利亚免疫登记册的南澳大利亚记录。疫苗有效性估计为使用筛查和病例对照方法降低感染几率。疫苗影响估计为发病率比率(IRR)，通过将疫苗接种计划开始后每年的病例数与疫苗接种计划前几年同等年龄队列中的病例数进行比较获得。我们使用泊松或负二项模型，在适当的情况下,调整了不符合通过国家计划接种疫苗资格的年龄组血清B群脑膜炎球菌病发病率的变化。
实施儿童疫苗接种计划2年后的4CMenB疫苗覆盖率为94·9%（35144名合格个体中的33357名），一剂91·4%（26443/28922），和79·4%（19436中的15440）的三个剂量的婴儿。一剂(77·1%，16422of21305)和两次剂量(69·0%，14704/21305）在2003年出生的青少年（大约10年级学生）中的覆盖率最高。儿童疫苗接种计划实施2年后，与计划实施前相比，12周至11个月大的婴儿血清B群脑膜炎球菌病的发病率显着降低（调整后的IRR[aIRR]0·40[95％CI0·23-0·69]，p=0·0011），但不是在1岁的人(0·79[0·16-3·87]，p=0·77)，2年（0·75[0·18-3·14]，p=0·70)，或4年(3·00[0·47-18·79]，p=0·24）。aIRRs是不可计算的年龄在3或5年,因为没有案件发生后的方案实施。在实施青少年和年轻成人方案2年后，15-18岁青少年的血清B群脑膜炎球菌疾病的IRR为0·27(0·06-1·16，p=0·078)，第一年19-21岁的人群为1·20（0·70-2·06，p=0·51）。使用筛查方法，两剂疫苗对血清B群脑膜炎球菌病的有效性估计为94·2％（95％CI36·6-99·5），使用病例对照方法，儿童为94·7％（40·3-99·5），和100％在青少年和年轻人（实施后无病例报告）。根据病例对照方法，使用年龄匹配的衣原体感染个体作为对照，估计青少年和年轻人的两剂疫苗对淋病的有效性为32·7％（8·3-50·6）。
4CMenB疫苗在婴儿和青少年中引入2年后显示出对血清群B脑膜炎球菌疾病的持续有效性，对青少年淋病有中等效果。针对血清群B脑膜炎球菌疾病的高疫苗有效性可能是由于目标年龄组的高覆盖率以及4CMenB疫苗与南澳大利亚流行的疾病相关血清群B脑膜炎球菌菌株之间的紧密抗原匹配。在该计划的第二年，与COVID-19相关的身体距离政策可能导致血清群B脑膜炎球菌疾病病例进一步下降。
SA健康，南澳大利亚政府。
