用作季节性疟疾预防的长效注射剂的模型指导目标产品概况。

Model-informed target product profiles of long-acting-injectables for use as seasonal malaria prevention.

作者信息

Burgert Lydia, Reiker Theresa, Golumbeanu Monica, Möhrle Jörg J, Penny Melissa A

机构信息

Swiss Tropical and Public Health Institute, Basel, Switzerland.

University of Basel, Basel, Switzerland.

出版信息

PLOS Glob Public Health. 2022 Mar 14;2(3):e0000211. doi: 10.1371/journal.pgph.0000211. eCollection 2022.

Abstract

Seasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine (SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, show LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimising LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process.

摘要

季节性疟疾化学预防(SMC)已被证明在降低疟疾发病率方面非常有效。然而,SMC的持续成功受到对其主要预防成分之一磺胺多辛-乙胺嘧啶(SP)耐药性的传播、给药操作挑战以及对方案依从性不完全的威胁。通过一项基于个体的疟疾动态模型的模拟研究,我们提供了定量证据来评估长效注射剂(LAIs)作为SMC的潜在替代方案。我们探讨了一系列新型预防性LAIs在临床试验后期和实施阶段作为三个月至五岁儿童季节性预防工具的预测影响。LAIs在传播季节开始时与一种血液阶段清除药物联合给药一次。我们发现,由于干预措施的高覆盖率,在临床试验阶段要确定LAIs相对于标准的3或4轮含SP-阿莫地喹的SMC的非劣效性具有挑战性。然而,我们对可实现的SMC覆盖率低得多的实施环境的分析表明,每个季节就诊次数较少的LAIs可能是SMC的合适替代品。如果LAIs的保护期覆盖传播季节的持续时间,那么作为具有更高影响的替代品是有可能的。此外,在SMC覆盖率为60%的环境中通过模拟分析优化LAIs覆盖率和保护效力半衰期,揭示了保护效力衰减与部署覆盖率之间的重要权衡。我们的分析还强调,对于LAIs的季节性部署,有必要在临床开发期间尽早研究保护效力衰减情况,以确保有充分信息的候选药物选择过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02e0/10021282/fb5875e7b3ee/pgph.0000211.g001.jpg

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