Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006-18: prospective observational time-series and case-control studies.
Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006-18: prospective observational time-series and case-control studies.
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DOI：
10.1016/s2214-109x(21)00165-0
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发表时间：
2021-07
期刊：
影响因子：
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通讯作者：
VacSurv Consortium
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作者：
Bar-Zeev N;Swarthout TD;Everett DB;Alaerts M;Msefula J;Brown C;Bilima S;Mallewa J;King C;von Gottberg A;Verani JR;Whitney CG;Mwansambo C;Gordon SB;Cunliffe NA;French N;Heyderman RS;VacSurv Consortium
肺炎球菌结合疫苗(PCV)对人群的影响取决于直接和间接保护。在马拉维于2011年引入13价PCV(PCV13)之后，我们审查了其对符合疫苗资格年龄和不符合疫苗资格年龄的儿童和成人中的疫苗和非疫苗血清型侵袭性肺炎球菌疾病的影响。我们进行了前瞻性观察时间序列分析和病例对照研究。我们使用了2006年1月1日至2018年12月31日期间马拉维一家政府医院的实验室监测数据。这一时期包括采用13号疫苗之前的6年和之后的7年。采用负二项回归方法，对疫苗血清型和非疫苗血清型侵袭性肺炎在引入PCV前后的长期趋势调整发病率比(IRR)进行评估。我们比较了假想缺乏疫苗时预测的反事实发病率与疫苗引入后的经验观察发病率。这项病例对照研究评估了疫苗的有效性，比较了符合疫苗资格年龄的侵袭性肺炎病例与匹配的社区对照病例中PCV的摄取情况。监测10个 281个 476人年，取血140个 498个，脑脊液培养63个 291个。在接种卡介苗前，侵袭性肺炎球菌疾病的总发病率(疫苗血清型和非疫苗血清型)下降：婴儿(1岁)中19%(IRR0.81，95%CI 0.74至0.88，p<；0.0001)，1-4岁儿童中14%(0.86，0.80至0.93，p<；0.0001)，青少年和成人(≥15岁)中8%(0.92，0.83至1.01，p=0.084)。在5-14岁的儿童中，侵袭性肺炎球菌疾病的总数增加了2%(1.02，0.93至1.11，p=0.72)。与预测发病率相比，1~4岁儿童和5~14岁儿童PCV13疫苗后血清型侵袭性肺炎发病率分别降低74%(95%CI 70~78)和79%(76~83%)，但婴儿发病率仅降低38%(37~40%)，青少年和成人发病率降低47%(44~51%)。尽管自2015年以来，非疫苗血清型侵袭性肺炎球菌疾病的发病率有所增加，但观察到的发病率仍然很低。病例对照研究(19例病例和76例对照)显示，疫苗对疫苗血清型侵袭性肺炎的有效率为80.7%(-73.7%~97.9%)。在非洲高死亡率、高艾滋病毒流行率的环境中，接种疫苗前侵袭性肺炎球菌疾病的发病率显著降低。在引入PCV 7年后，尽管疫苗合格年龄儿童的疫苗归因性影响显著，但对未接种疫苗的婴儿和成年人的间接影响并不显著。政策决定应考虑减少疾病负担的多种替代战略，包括在婴儿扩大免疫方案之外进行有针对性的疫苗接种，以造福弱势人群。比尔和梅琳达·盖茨基金会、惠康信托基金和国家健康研究所。
The population impact of pneumococcal conjugate vaccines (PCVs) depends on direct and indirect protection. Following Malawi's introduction of the 13-valent PCV (PCV13) in 2011, we examined its impact on vaccine and non-vaccine serotype invasive pneumococcal disease among vaccine-eligible-age and vaccine-ineligible-age children and adults. We did a prospective observational time-series analysis and a case-control study. We used data from between Jan 1, 2006, and Dec 31, 2018, from laboratory-based surveillance at a government hospital in Malawi. This period included 6 years before and 7 years after introduction of PCV13. By use of negative-binomial regression, we evaluated secular trend-adjusted incidence rate ratio (IRR) in vaccine serotype and non-vaccine serotype invasive pneumococcal disease before and after introduction of PCV. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. The case-control study assessed vaccine effectiveness, comparing PCV uptake among cases of vaccine-eligible-age invasive pneumococcal disease versus matched community controls. Surveillance covered 10 281 476 person-years of observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. A reduction in total (vaccine serotype plus non-vaccine serotype) invasive pneumococcal disease incidence preceded introduction of PCV: 19% (IRR 0·81, 95% CI 0·74 to 0·88, p<0·0001) among infants (<1 year old), 14% (0·86, 0·80 to 0·93, p<0·0001) among children aged 1–4 years, and 8% (0·92, 0·83 to 1·01, p=0·084) among adolescents and adults (≥15 years old). Among children aged 5–14 years there was a 2% increase in total invasive pneumococcal disease (1·02, 0·93 to 1·11, p=0·72). Compared with the counterfactually predicted incidence, incidence of post-PCV13 vaccine serotype invasive pneumococcal disease was 74% (95% CI 70 to 78) lower among children aged 1–4 years and 79% (76 to 83) lower among children aged 5–14 years, but only 38% (37 to 40) lower among infants and 47% (44 to 51) lower among adolescents and adults. Although non-vaccine serotype invasive pneumococcal disease has increased in incidence since 2015, observed incidence remains low. The case-control study (19 cases and 76 controls) showed vaccine effectiveness against vaccine serotype invasive pneumococcal disease of 80·7% (–73·7 to 97·9). In a high-mortality, high-HIV-prevalence setting in Africa, there were significant pre-vaccine reductions in the incidence of invasive pneumococcal disease. 7 years after PCV introduction, although vaccine-attributable impact among vaccine-eligible-age children was significant, indirect effects benefitting unvaccinated infants and adults were not. Policy decisions should consider multiple alternative strategies for reducing disease burden, including targeted vaccination outside infant Expanded Programme of Immunization to benefit vulnerable populations. Bill & Melinda Gates Foundation, Wellcome Trust, and National Institute for Health Research.