Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi; Center for Global Vaccine Research, University of Liverpool, Liverpool, UK; International Vaccine Access Center, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi; NIHR Global Health Research Unit on Mucosal Pathogens, Research Department of Infection, Division of Infection and Immunity, University College London, London, UK.
Lancet Glob Health. 2021 Jul;9(7):e989-e998. doi: 10.1016/S2214-109X(21)00165-0.
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.
肺炎球菌结合疫苗（PCV）的人群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，我们研究了其对疫苗合格年龄和不合格年龄儿童和成人的疫苗和非疫苗血清型侵袭性肺炎球菌病的影响。
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 日期间政府医院基于实验室的监测数据。这一时期包括 PCV13 引入前 6 年和引入后 7 年。我们使用负二项回归，评估了 PCV13 引入前后疫苗血清型和非疫苗血清型侵袭性肺炎球菌病的时间趋势调整发病率比（IRR）。我们比较了在没有疫苗的假设情况下的预测反事实发病率与疫苗引入后实际观察到的发病率。病例对照研究评估了疫苗的有效性，将疫苗合格年龄侵袭性肺炎球菌病病例与匹配的社区对照病例中的疫苗接种情况进行了比较。
监测覆盖了 10281476 人年的观察期，共进行了 140498 次血液和 63291 次脑脊液培养。侵袭性肺炎球菌病总发病率（疫苗血清型加非疫苗血清型）在 PCV 引入前就出现了下降：婴儿（<1 岁）下降 19%（IRR 0.81，95%CI 0.74 至 0.88，p<0.0001），儿童（1 至 4 岁）下降 14%（0.86，0.80 至 0.93，p<0.0001），青少年和成年人（≥15 岁）下降 8%（0.92，0.83 至 1.01，p=0.084）。在 5 至 14 岁的儿童中，侵袭性肺炎球菌病总发病率增加了 2%（1.02，0.93 至 1.11，p=0.72）。与反事实预测的发病率相比，1 至 4 岁儿童的 PCV13 后疫苗血清型侵袭性肺炎球菌病发病率降低了 74%（95%CI 70 至 78），5 至 14 岁儿童降低了 79%（76 至 83），但婴儿仅降低了 38%（37 至 40），青少年和成年人降低了 47%（44 至 51）。尽管自 2015 年以来，非疫苗血清型侵袭性肺炎球菌病的发病率有所上升，但观察到的发病率仍然较低。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球菌病的有效性为 80.7%（-73.7 至 97.9）。
在一个高死亡率、高艾滋病毒流行率的非洲环境中，侵袭性肺炎球菌病的发病率在疫苗引入前就出现了显著下降。在 PCV 引入 7 年后，虽然疫苗合格年龄儿童的疫苗归因影响显著，但对未接种疫苗的婴儿和成年人的间接影响并不显著。政策决策应考虑多种替代策略来降低疾病负担，包括在婴儿扩大免疫规划之外针对弱势群体进行有针对性的疫苗接种。
比尔及梅琳达·盖茨基金会、惠康信托基金会和英国国家卫生研究院。
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