Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.
Quantitative assessment of the impact of partially protective anti-schistosomiasis vaccines.
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DOI：
10.1371/journal.pntd.0005544
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发表时间：
2017-04
影响因子：
3.8
通讯作者：
King C
中科院分区：
文献类型：
--
作者：
Alsallaq RA;Gurarie D;Ndeffo Mbah M;Galvani A;King C
吡喹酮的大规模药物管理（MDA）一直是抗血吸虫病的首选干预措施，但在阻断传播方面的成功有限。抗血吸虫疫苗的研制正在进行中。我们的目标是量化抗血吸虫疫苗单独使用和与大规模药物管理（MDA）相结合时对人群水平的影响，并确定疫苗设计和公共卫生实施中优化疫苗接种在血吸虫病控制和消除中的作用的因素。我们开发了一个确定性房室模型模拟血吸虫病传播的高风险肯尼亚社区，包括分层的年龄，寄生虫负担，和疫苗接种状态。模型血吸虫病疫苗不同的疫苗保护期（耐久性）和三个生物学效力。这三种效应分别是降低人对血吸虫病易感性的疫苗敏感性效应（SE）、降低已建立的虫体负担的疫苗死亡率效应（ME）和降低成熟蠕虫释放卵的疫苗繁殖力效应（FE）。我们在不同的疫苗接种计划（儿童与大规模运动）下量化了20年来疫苗接种的人口水平影响，不同的年龄目标场景，不同的风险设置，以及与MDA的联合干预。我们还评估了我们的预测模型参数的不确定性的敏感性。二十多年来，我们的基础病例疫苗具有80%的SE、FE和ME效力，10年的持久性，通过每10年一次的大规模疫苗接种提供，将宿主患病率、平均强度、发病率和无症状蜗牛患病率从地方病状态值71%、152、3.3、20个卵/10 ml样本/人、0.87个虫/人-年和0.74%降低到31%、20个卵/10 ml样本/人、0.87个虫/人-年和0.74%。和0.98%。当覆盖范围不包括所有潜在污染物时，发现影响较低，仅儿童期疫苗接种计划显示出延迟和较低的影响。在较低的流行率环境中，基础病例疫苗产生的影响相对较小。当每5年提供一次MDA +大规模疫苗接种时，产生了显著更大的疫苗计划效应，只有每年提供一次药物，才能通过仅MDA计划实现。疫苗对血吸虫病传播的影响对许多参数敏感，包括疫苗效力、人与水的接触率、人密度、未闭螺的开放率和寿命以及对螺的感染力。为了取得成功，基于疫苗的控制策略将需要一种中度至高度有效的制剂，结合对潜在污染物的早期接种和在多轮大规模接种中的积极覆盖。与仅使用MDA的方案相比，疫苗接种结合MDA通过减少新蠕虫的获得和减少残留蠕虫的卵释放来加速和消除影响。一些实验性的抗血吸虫病疫苗正在研制中。我们的研究结果对疫苗的设计和实施有影响。设计图：为了在种群水平上产生最佳影响，我们发现最好的疫苗是那些大大减少新蠕虫获得并以高效力杀死现有蠕虫的疫苗。在人群水平上产生最佳影响的下一个最佳疫苗是那些既能显著减少新蠕虫的获得又能减少残留蠕虫产卵的疫苗。实施情况：为了对传播产生最好的影响，我们发现，在重复的回合中，需要以小于疫苗诱导的免疫力的平均持久性的间隔进行大规模覆盖。如果疫苗不能有效地杀死现有的蠕虫，在这些实施回合中将疫苗与MDA结合使用将起到补偿作用。如果没有疫苗接种，MDA计划必须以五倍的频率和更长的时间提供，以便在人口水平上产生可比的影响。
Mass drug administration (MDA) of praziquantel has been the intervention of choice against schistosomiasis but with limited success in interrupting the transmission. The development of anti-Schistosoma vaccines is underway. Our objective is to quantify the population-level impact of anti-Schistosoma vaccines when administered alone and in combination with mass drug administration (MDA) and determine factors in vaccine design and public health implementation that optimize vaccination role in schistosomiasis control and elimination. We developed a deterministic compartmental model simulation of schistosomiasis transmission in a high-risk Kenyan community, including stratification by age, parasite burden, and vaccination status. The modeled schistosomiasis vaccines differed in terms of vaccine duration of protection (durability) and three biological efficacies. These are vaccine susceptibility effect (SE) of reducing person’s susceptibility to Schistosoma acquisition, vaccine mortality effect (ME) of reducing established worm burden and vaccine fecundity effect (FE) of reducing egg release by mature worms. We quantified the population-level impact of vaccination over two decades under diverse vaccination schemes (childhood vs. mass campaigns), with different age-targeting scenarios, different risk settings, and with combined intervention with MDA. We also assessed the sensitivity of our predictions to uncertainties in model parameters. Over two decades, our base case vaccine with 80% SE, FE, and ME efficacies, 10 years’ durability, provided by mass vaccination every 10 years, reduced host prevalence, mean intensity, incidence, and patent snail prevalence to 31%, 20 eggs/10-ml sample/person, 0.87 worm/person-year, and 0.74%, from endemic-state values of 71%, 152, 3.3, and 0.98%, respectively. Lower impact was found when coverage did not encompass all potential contaminators, and childhood-only vaccination schemes showed delayed and lower impact. In lower prevalence settings, the base case vaccine generated a proportionately smaller impact. A substantially larger vaccine program effect was generated when MDA + mass vaccination was provided every 5 years, which could be achieved by an MDA-only program only if drug was offered annually. Vaccine impact on schistosomiasis transmission was sensitive to a number of parameters including vaccine efficacies, human contact rates with water, human density, patent snails’ rate of patency and lifespan, and force of infection to snails. To be successful a vaccine-based control strategy will need a moderately to highly effective formulation combined with early vaccination of potential contaminators and aggressive coverage in repeated rounds of mass vaccination. Compared to MDA-only program, vaccination combined with MDA accelerates and prolongs the impact by reducing the acquisition of new worms and reducing egg release from residual worms. A number of experimental anti-schistosomiasis vaccines are under development. Our results have implications on the vaccines’ design and implementation. Design: For optimal impact at the population-level we found that the best vaccines are the ones that substantially reduce the acquisition of new worms and that kill existing worms with high potency. The next best vaccines for optimal impact at the population-level were those that both markedly reduced acquisition of new worms and reduced the shedding of eggs from residual worms. Implementation: For the best impact on transmission, we found that mass coverage in repeated rounds is required at an interval less than the mean durability of the vaccine-induced immunity. If the vaccine does not effectively kill existing worms, combining vaccine with MDA in these implementation rounds would compensate. Without vaccination, MDA programs have to be offered at five times higher frequency and for longer periods in order to get comparable impact at the population level.