How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis.

IF 3.4 2区 医学 Q1 PARASITOLOGY
PLoS Neglected Tropical Diseases Pub Date : 2025-06-02 eCollection Date: 2025-06-01 DOI:10.1371/journal.pntd.0012624
John R Ellis, Nyamai Mutono, Andreia Vasconcelos, Samuel M Thumbi, T Déirdre Hollingsworth, Roy M Anderson
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引用次数: 0

Abstract

Schistosomiasis affects more than 230 million people worldwide. Control and elimination of this parasitic infection is based on mass drug administration of praziquantel (PZQ), which has been in use for several decades. Because of the limitations of the efficacy of PZQ especially against juvenile worms, and the threat of the emergence of resistance, there is a need to consider alternative formulations or delivery methods, or new drugs that could be more efficacious. We use an individual-based stochastic model of parasite transmission to investigate the effects of possible improvements to drug efficacy. We consider an increase in efficacy compared to PZQ, as well as additional efficacy against the juvenile life stage of schistosome parasites in the human host, and a slow-release formulation that would provide long-lasting efficacy for a period of time following treatment. Analyses suggest a drug with a high efficacy of 99%, or with efficacy lasting 24 weeks after treatment, are the two most effective individual improvements to the drug profile of PZQ. A drug with long lasting efficacy is most beneficial when MDA coverage is low. However, when prevalence of infection has already been reduced to a low level, a high efficacy is the most important factor to accelerate interruption of transmission. Our results indicate that increased efficacy against juvenile worms can only result in modest benefits, but the development of a new drug formulation with higher efficacy against adult worms or long-lasting efficacy would create an improvement to the community impact over the currently used formulation.

改善药物有效性如何影响控制和消除血吸虫病的大规模药物管理。
血吸虫病影响全世界2.3亿多人。控制和消除这种寄生虫感染的基础是大量使用吡喹酮(PZQ),这种药物已经使用了几十年。由于PZQ的功效有限,特别是对幼虫的功效有限,而且存在出现耐药性的威胁,因此有必要考虑替代配方或给药方法,或可能更有效的新药。我们使用基于个体的寄生虫传播随机模型来研究可能改善药物疗效的影响。我们认为,与PZQ相比,该药物的疗效有所提高,对人类宿主体内血吸虫寄生虫的幼年期也有额外的疗效,并且缓释制剂可以在治疗后的一段时间内提供持久的疗效。分析表明,99%的高疗效药物,或治疗后持续24周的疗效药物,是两种最有效的个体改善PZQ药物谱的药物。当丙二醛覆盖率较低时,长效药物是最有益的。然而,当感染流行率已经降至较低水平时,高效率是加速阻断传播的最重要因素。我们的研究结果表明,提高对幼虫的功效只能带来适度的好处,但开发一种对成虫具有更高功效或持久功效的新药物配方将比目前使用的配方产生更好的社区影响。
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来源期刊
PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases PARASITOLOGY-TROPICAL MEDICINE
自引率
10.50%
发文量
723
期刊介绍: PLOS Neglected Tropical Diseases publishes research devoted to the pathology, epidemiology, prevention, treatment and control of the neglected tropical diseases (NTDs), as well as relevant public policy. The NTDs are defined as a group of poverty-promoting chronic infectious diseases, which primarily occur in rural areas and poor urban areas of low-income and middle-income countries. Their impact on child health and development, pregnancy, and worker productivity, as well as their stigmatizing features limit economic stability. All aspects of these diseases are considered, including: Pathogenesis Clinical features Pharmacology and treatment Diagnosis Epidemiology Vector biology Vaccinology and prevention Demographic, ecological and social determinants Public health and policy aspects (including cost-effectiveness analyses).
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