Long-term effects of increased adoption of artemisinin combination therapies in Burkina Faso.
Long-term effects of increased adoption of artemisinin combination therapies in Burkina Faso.
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DOI：
10.1371/journal.pgph.0000111
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发表时间：
2022
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青蒿素联合疗法（ACT）是世界卫生组织推荐的治疗无并发症的恶性疟原虫疟疾的一线疗法。青蒿素耐药基因型的出现和传播是全球主要的公共卫生问题，因为它导致治疗失败率增加。这对于布基纳法索等世界卫生组织指定的“高负担高影响”（HBHI）国家尤其重要，这些国家越来越重视改善当地疟疾应对措施的指导、战略和协调，以努力减少恶性疟疾的流行。为了探讨增加 ACT 的采用可能如何影响布基纳法索的 HBHI 疟疾环境，我们在经过验证的基于个体的恶性疟原虫传播随机模型中添加了空间结构，并评估了增加 ACT 的使用的长期影响。我们探讨了在私人市场药物被淘汰或部署多种一线疗法 (MFT) 的情况下，青蒿素耐药基因型（例如 pfkelch13 580Y）如何从头出现。我们发现，与现状（13.11%）相比，消除私人市场药物将导致治疗失败率降低（11.98% 至 12.90% 之间）。然而，将 MFT 与同等部署的蒿甲醚-本芴醇 (AL) 和双氢青蒿素-哌喹 (DHA-PPQ) 结合的方案可能会加速近期耐药性（2038 年模型中 580Y 频率范围在 0.62 至 0.84 之间）和治疗失败率（2038 年为 26.69% 至 34.00%），因为早期失败和治疗效果大幅降低。哌喹耐药基因型。重新平衡的 MFT 方法（90% AL，10% DHA-PPQ）与单独使用 AL 的长期结果大致相同，但在实践中可能难以实施。
Artemisinin combination therapies (ACTs) are the WHO-recommended first-line therapies for uncomplicated Plasmodium falciparum malaria. The emergence and spread of artemisinin-resistant genotypes is a major global public health concern due to the increased rate of treatment failures that result. This is particularly germane for WHO designated ‘high burden to high impact’ (HBHI) countries, such as Burkina Faso, where there is increased emphasis on improving guidance, strategy, and coordination of local malaria response in an effort to reduce the prevalence of P. falciparum malaria. To explore how the increased adoption of ACTs may affect the HBHI malaria setting of Burkina Faso, we added spatial structure to a validated individual-based stochastic model of P. falciparum transmission and evaluated the long-term effects of increased ACT use. We explored how de novo emergence of artemisinin-resistant genotypes, such as pfkelch13 580Y, may occur under scenarios in which private-market drugs are eliminated or multiple first-line therapies (MFT) are deployed. We found that elimination of private market drugs would result in lower treatment failures rates (between 11.98% and 12.90%) when compared to the status quo (13.11%). However, scenarios incorporating MFT with equal deployment of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) may accelerate near-term drug resistance (580Y frequency ranging between 0.62 to 0.84 in model year 2038) and treatment failure rates (26.69% to 34.00% in 2038), due to early failure and substantially reduced treatment efficacy resulting from piperaquine-resistant genotypes. A rebalanced MFT approach (90% AL, 10% DHA-PPQ) results in approximately equal long-term outcomes to using AL alone but may be difficult to implement in practice.