Department of Biological Sciences and Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA.
Unité Malaria: Parasites et Hôtes, Département Parasites et Insectes Vecteur, Institut Pasteur, Paris, France.
Malar J. 2021 Dec 20;20(1):479. doi: 10.1186/s12936-021-04017-1.
Plasmodium vivax blood-stage relapses originating from re-activating hypnozoites are a major barrier for control and elimination of this disease. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy estimates ranging from 65 to 94%, with substantial variation across trial sites.
An analysis of simulated trial data using a transmission model was performed to demonstrate that variation in efficacy estimates across trial sites can arise from differences in the conditions under which trials are conducted.
The analysis revealed that differences in transmission intensity, heterogeneous exposure and relapse rate can yield efficacy estimates ranging as widely as 12-78%, despite simulating trial data under the uniform assumption that treatment had a 75% chance of clearing hypnozoites. A longer duration of prophylaxis leads to a greater measured efficacy, particularly at higher transmission intensities, making the comparison between the protection of different radical cure treatment regimens against relapse more challenging. Simulations show that vector control and parasite genotyping offer two potential means to yield more standardized efficacy estimates that better reflect prevention of relapse.
Site-specific biases are likely to contribute to variation in efficacy estimates both within and across clinical trials. Future clinical trials can reduce site-specific biases by conducting trials in low-transmission settings where re-infections from mosquito bite are less common, by preventing re-infections using vector control measures, or by identifying and excluding likely re-infections that occur during follow-up, by using parasite genotyping methods.
源自休眠子重新激活的间日疟原虫血液期复发是控制和消除这种疾病的主要障碍。根治治疗是一种能够解决这个问题的治疗方法。最近根治治疗的临床试验得出的疗效估计值在 65%到 94%之间，不同试验地点的疗效估计值存在很大差异。
使用传播模型对模拟试验数据进行分析，以证明试验地点疗效估计值的差异可能源于试验进行条件的差异。
分析表明，尽管模拟试验数据的假设条件是治疗有 75%的机会清除休眠子，但在不同的传播强度、不均匀的暴露和复发率条件下，疗效估计值的差异范围可以从 12%到 78%不等。更长的预防持续时间会导致更高的疗效测量值，尤其是在更高的传播强度下，这使得比较不同根治治疗方案对复发的保护作用更加具有挑战性。模拟结果表明，病媒控制和寄生虫基因分型是两种可能的方法，可以产生更标准化的疗效估计值，更好地反映对复发的预防作用。
试验地点的具体偏倚可能导致临床试验内部和之间疗效估计值的差异。未来的临床试验可以通过在低传播环境中进行试验来减少试验地点的偏倚，在这种环境中，由蚊子叮咬引起的再感染不太常见；通过使用病媒控制措施来预防再感染；或者通过使用寄生虫基因分型方法来识别和排除随访期间发生的可能再感染，从而减少试验地点的偏倚。
