Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, London, UK; Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Lancet Public Health. 2024 Oct;9(10):e766-e775. doi: 10.1016/S2468-2667(24)00181-6. Epub 2024 Sep 26.
Among people infected with measles in England between 2010 and 2019, the proportion of cases who had previously received two doses of vaccine has increased, especially among young adults. Possible explanations include rare infections in vaccinated individuals who did not gain immunity upon vaccination, made more common because fewer individuals in the population were born in the endemic era, before vaccination was introduced, and exposed as part of endemic transmission, or the waning of vaccine-induced immunity, which would present new challenges for measles control in near-elimination settings. We aimed to evaluate whether measles dynamics observed in England between 2010 and 2019 were in line with a waning of vaccine-induced immunity.
We used a compartmental mathematical model stratified by age group, region, and vaccine status, fitted to individual-level case data reported in England from 2010 to 2019 and collected by the UK Health Security Agency. The deterministic model was fitted using Monte Carlo Markov Chains under three scenarios: without the waning of vaccine-induced immunity, with waning depending on time since vaccination, and with waning depending on time since vaccination, starting in 2000. We generated stochastic simulations from the fitted parameter sets to evaluate which scenarios could replicate the transmission dynamics observed in vaccinated cases in England.
The scenario without waning overestimated the number of one-dose recipients among measles cases, and underestimated the number of two-dose recipients among cases older than 15 years (median 75 cases [95% simulation interval (SI) 44-124] in simulations without waning, 196 [95% SI 122-315] in simulations when waning was included, 188 [95% SI 118-301] in simulations when waning started in 2000, and 202 observed cases). The number of onward transmissions from vaccinated cases was 83% (95% credible interval 72-91%) of the number of transmissions from unvaccinated cases. The estimated waning rate was slow (0·039% per year of age; 95% credible interval 0·034-0·044% per year in the best-fitting scenario with waning starting in 2000), but sufficient to increase measles burden.
Measles case dynamics in England are consistent with scenarios assuming the waning of vaccine-induced immunity. Since measles is highly infectious, slow waning leads to a heightened burden in outbreaks, increasing the number of measles cases in people who are both vaccinated and unvaccinated. Our findings show that although the vaccine remains highly protective against measles infections for decades and most transmission is connected to people who are unvaccinated, breakthrough infections are increasingly frequent for individuals aged 15 years and older who have been vaccinated twice.
National Institute for Health and Care Research and Wellcome Trust.
在 2010 年至 2019 年期间感染麻疹的英格兰人群中，既往接受过两剂疫苗的病例比例有所增加，尤其是在年轻成年人中。可能的解释包括疫苗接种者中罕见的感染，这些人在接种疫苗后没有获得免疫力，因为在引入疫苗之前出生的人群中，接触过麻疹的人较少，而且在流行传播过程中接触过麻疹，或者疫苗诱导的免疫力逐渐减弱，这将给接近消除麻疹的环境中的麻疹控制带来新的挑战。我们旨在评估 2010 年至 2019 年期间在英格兰观察到的麻疹动态是否与疫苗诱导的免疫力减弱相符。
我们使用按年龄组、地区和疫苗接种状况分层的房室数学模型，对 2010 年至 2019 年期间英国卫生安全局报告的英格兰个体病例数据进行拟合。确定性模型使用蒙特卡罗马尔可夫链进行拟合，共分为三种情况：不考虑疫苗诱导的免疫力减弱、考虑疫苗诱导的免疫力减弱且随时间变化、考虑疫苗诱导的免疫力减弱且自 2000 年起随时间变化。我们从拟合的参数集中生成随机模拟，以评估哪些情况可以复制在英格兰接种疫苗者中观察到的传播动态。
不考虑免疫力减弱的情况高估了一剂疫苗接种者在麻疹病例中的数量，低估了 15 岁以上病例中两剂疫苗接种者的数量（无减弱情况下模拟的中位数为 75 例[95%置信区间（CI）44-124]，包括减弱情况下为 196 例[95%CI 122-315]，从 2000 年开始减弱时为 188 例[95%CI 118-301]，观察到的实际病例为 202 例）。从接种疫苗者传播的病例数占未接种疫苗者传播病例数的 83%（72%-91%，95%可信区间）。估计的衰减率较慢（每年 0.039%；在最佳拟合情况下，2000 年开始衰减的情况下为 0.034-0.044%/年），但足以增加麻疹负担。
英格兰麻疹病例动态与假设疫苗诱导的免疫力减弱的情况相符。由于麻疹具有高度传染性，因此衰减缓慢会导致暴发期间负担加重，增加已接种疫苗和未接种疫苗人群中麻疹病例的数量。我们的研究结果表明，尽管疫苗在数十年内对麻疹感染仍具有高度保护作用，且大多数传播与未接种疫苗者有关，但 15 岁及以上已接种两剂疫苗的个体突破性感染的频率越来越高。
英国国家卫生与保健研究院和惠康基金会。
