Centre for the Mathematical Modelling of Infectious Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK.
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK.
BMC Med. 2022 Mar 10;20(1):77. doi: 10.1186/s12916-022-02277-5.
Subnational heterogeneity in immunity to measles can create pockets of susceptibility and result in long-lasting outbreaks despite high levels of national vaccine coverage. The elimination status defined by the World Health Organization aims to identify countries where the virus is no longer circulating and can be verified after 36 months of interrupted transmission. However, since 2018, numerous countries have lost their elimination status soon after reaching it, showing that the indicators defining elimination may not be associated with lower risks of outbreaks.
We quantified the impact of local vaccine coverage and recent levels of incidence on the dynamics of measles in each French department between 2009 and 2018, using mathematical models based on the "Endemic-Epidemic" regression framework. After fitting the models using daily case counts, we simulated the effect of variations in the vaccine coverage and recent incidence on future transmission.
High values of local vaccine coverage were associated with fewer imported cases and lower risks of local transmissions, but regions that had recently reported high levels of incidence were also at a lower risk of local transmission. This may be due to additional immunity accumulated during recent outbreaks. Therefore, the risk of local transmission was not lower in areas fulfilling the elimination criteria. A decrease of 3% in the 3-year average vaccine uptake led to a fivefold increase in the average annual number of cases in simulated outbreaks.
Local vaccine uptake was a reliable indicator of the intensity of transmission in France, even if it only describes yearly coverage in a given age group, and ignores population movements. Therefore, spatiotemporal variations in vaccine coverage, caused by disruptions in routine immunisation programmes, or lower trust in vaccines, can lead to large increases in both local and cross-regional transmission. The incidence indicator used to define the elimination status was not associated with a lower number of local transmissions in France, and may not illustrate the risks of imminent outbreaks. More detailed models of local immunity levels or subnational seroprevalence studies may yield better estimates of local risk of measles outbreaks.
麻疹的免疫在次国家级存在异质性，这可能导致局部地区出现易感染人群，并导致尽管全国疫苗接种率很高，但仍会出现持续的暴发。世界卫生组织定义的消除状态旨在确定病毒不再传播的国家，并在中断传播 36 个月后可以得到验证。然而，自 2018 年以来，许多国家在达到消除状态后很快就失去了这一状态，这表明定义消除的指标可能与暴发风险降低无关。
我们使用基于“地方性-流行性”回归框架的数学模型，量化了 2009 年至 2018 年期间法国每个省的局部疫苗覆盖率和近期发病率对麻疹动态的影响。在使用每日病例数拟合模型后，我们模拟了疫苗覆盖率和近期发病率变化对未来传播的影响。
高局部疫苗覆盖率与输入病例减少和本地传播风险降低相关，但近期报告发病率较高的地区也具有较低的本地传播风险。这可能是由于最近暴发期间积累了额外的免疫力。因此，满足消除标准的地区的本地传播风险不一定较低。模拟暴发中，3 年平均疫苗接种率降低 3%会导致每年平均病例数增加五倍。
局部疫苗接种率是法国传播强度的可靠指标，即使它只描述了特定年龄组的年度覆盖率，并且忽略了人口流动。因此，常规免疫规划中断或对疫苗信任度降低导致的疫苗覆盖率的时空变化可能导致本地和跨地区传播的大幅增加。用于定义消除状态的发病率指标与法国本地传播次数的减少无关，也不能说明即将发生暴发的风险。对局部免疫水平或次国家级血清阳性率研究的更详细模型可能会更好地估计麻疹局部暴发的风险。
