Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions.
Global risk of selection and spread of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions.
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恶性疟原虫富含组氨酸的蛋白 2 和 3 基因缺失的选择和传播的全球风险。
DOI：
10.1101/2023.10.21.23297352
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Gething,
中科院分区：
文献类型：
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作者：
Watson,OliverJ;Tran,ThuNguyen-Anh;Zupko,RobertJ;Symons,Tasmin;Thomson,Rebecca;Visser,Theodoor;Rumisha,Susan;Dzianach,PaulinaA;Hathaway,Nicholas;Kim,Isaac;Juliano,JonathanJ;Bailey,JeffreyA;Slater,Hannah;Okell,Lucy;Gething,
自2010年首次报告pfhrp 2缺失寄生虫以来的13年中，世界卫生组织（WHO）发现，全球47个国家中有40个国家报告了pfhrp 2/3基因缺失。由于pfhrp 2/3缺失导致假阴性HRP 2 RDT的高发生率，在过去五年中，厄立特里亚、吉布提和埃塞俄比亚已经转换或开始转换使用替代RDT，其靶向泛特异性pLDH或恶性疟原虫特异性pLDH单独或与HRP 2组合。然而，替代RDT的生产尚未达到规模，并且没有使用Pf-pLDH代替HRP 2检测恶性疟原虫的WHO资格预审组合检测。由于这些原因，pfhrp 2/3缺失的持续传播代表了日益严重的公共卫生危机，威胁到控制和消除恶性疟原虫疟疾的努力。国家疟疾控制规划，其执行伙伴和测试开发者拼命寻找pfhrp 2/3缺失数据，以告知他们当前和未来的资源分配。作为回应，我们使用数学建模方法来评估pfhrp 2/3缺失所带来的全球风险，并探讨缺失将如何继续在非洲蔓延的情况。我们将目前最好的估计流行的pfhrp 2/3缺失，并进行文献综述，以估计模型参数已知的影响选择pfhrp 2/3缺失为每个疟疾流行的国家。我们在全球范围内确定了20个国家，根据一旦建立pfhrp 2/3缺失的快速选择，优先进行监测和未来部署替代RDT。在旨在探索非洲缺失持续传播的情景中，我们确定了10个高威胁国家，这些国家最有可能发生缺失，既传播到又迅速被选择。如果基于HRP 2的RDT继续被依赖于疟疾病例管理，我们预测pfhrp 2缺失传播的主要途径是从非洲之角目前的热点向南传播，在未来20年内通过东非传播。我们通过广泛的参数敏感性分析探索了建模时间线的变化，尽管存在广泛的不确定性，但我们确定了三个尚未转换RDT的国家（塞内加尔，赞比亚和肯尼亚），这些国家被确定为pfhrp 2/3缺失的高风险。这些结果为pfhrp 2/3缺失的出现提供了一个改进和更新的预测模型，以帮助指导pfhrp 2/3政策，并优先考虑未来的监测工作和创新。
In the thirteen years since the first report of pfhrp2-deleted parasites in 2010, the World Health Organization (WHO) has found that 40 of 47 countries surveyed worldwide have reported pfhrp2/3 gene deletions. Due to a high prevalence of pfhrp2/3 deletions causing false-negative HRP2 RDTs, in the last five years, Eritrea, Djibouti and Ethiopia have switched or started switching to using alternative RDTs, that target pan-specific-pLDH or P. falciparum specific-pLDH alone of in combination with HRP2. However, manufacturing of alternative RDTs has not been brought to scale and there are no WHO prequalified combination tests that use Pf-pLDH instead of HRP2 for P. falciparum detection. For these reasons, the continued spread of pfhrp2/3 deletions represents a growing public health crisis that threatens efforts to control and eliminate P. falciparum malaria. National malaria control programmes, their implementing partners and test developers desperately seek pfhrp2/3 deletion data that can inform their immediate and future resource allocation. In response, we use a mathematical modelling approach to evaluate the global risk posed by pfhrp2/3 deletions and explore scenarios for how deletions will continue to spread in Africa. We incorporate current best estimates of the prevalence of pfhrp2/3 deletions and conduct a literature review to estimate model parameters known to impact the selection of pfhrp2/3 deletions for each malaria endemic country. We identify 20 countries worldwide to prioritise for surveillance and future deployment of alternative RDT, based on quickly selecting for pfhrp2/3 deletions once established. In scenarios designed to explore the continued spread of deletions in Africa, we identify 10 high threat countries that are most at risk of deletions both spreading to and subsequently being rapidly selected for. If HRP2-based RDTs continue to be relied on for malaria case management, we predict that the major route for pfhrp2 deletions to spread is south out from the current hotspot in the Horn of Africa, moving through East Africa over the next 20 years. We explore the variation in modelled timelines through an extensive parameter sensitivity analysis and despite wide uncertainties, we identify three countries that have not yet switched RDTs (Senegal, Zambia and Kenya) that are robustly identified as high risk for pfhrp2/3 deletions. These results provide a refined and updated prediction model for the emergence of pfhrp2/3 deletions in an effort to help guide pfhrp2/3 policy and prioritise future surveillance efforts and innovation.