An assessment of the supply, programmatic use, and regulatory issues of single low-dose primaquine as a Plasmodium falciparum gametocytocide for sub-Saharan Africa
An assessment of the supply, programmatic use, and regulatory issues of single low-dose primaquine as a Plasmodium falciparum gametocytocide for sub-Saharan Africa
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DOI：
10.1186/s12936-015-0714-3
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发表时间：
2015-05-15
期刊：
影响因子：
3
通讯作者：
Rooney, Luke
中科院分区：
文献类型：
--
作者：
Chen, Ingrid;Poirot, Eugenie;Rooney, Luke
背景：全球消除疟疾的雄心正在增强，这突显了对传播阻断工具的迫切需求。2012年，世界卫生组织建议使用0.25毫克/公斤的单一低剂量伯喹来阻止恶性疟原虫的传播。为了确保SLD伯喹在需要该工具的国家获得，需要更多关于SLD伯喹推广的供应、规划和监管障碍的信息。方法：通过对三家伯喹制造商、来自埃塞俄比亚、塞内加尔、斯威士兰、赞比亚和坦桑尼亚的43名关键信息者以及16名疟疾研究专家的半结构化定性访谈，确定了SLD伯喹在撒哈拉以南非洲推广的挑战。结果：赛诺菲和Remedica是仅有的两个适合国际捐助者采购的SRA批准的伯喹来源。两家制造商都没有生产出适合传播阻断指示的伯喹药片强度。在国内的主要信息提供人透露，世卫组织关于使用SLD伯喹的基于体重的建议在实际现场环境中实施具有挑战性。疟疾方案表达了对葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症患者使用伯喹的安全性关切，以及伯喹与共病之间的潜在相互作用，以及药物与艾滋病毒和/或结核病治疗之间的相互作用。监管程序是推出SLD伯喹的主要障碍，需要在国家和全球层面采取多个步骤。尽管存在这些障碍，但对SLD伯喹的需求仍在增长，疟疾研究人员对通过大规模筛查和治疗和/或大规模药物管理活动部署伯喹感兴趣。结论：伯喹作为传播阻滞剂的需求迅速增长，但SLD伯喹的使用存在多个障碍。需要研究确定治疗剂量范围，以指导现场给药方案，为新的、低强度伯喹片剂和/或制剂的开发提供信息(S)，并减轻G6PD缺乏症患者的程序性安全性担忧。伯氨喹与合并症和治疗方法之间的潜在相互作用应加以探讨。为了最大限度地减少监管延误，各国需要在早期阶段为产品注册做准备，应寻求世卫组织对合适的伯喹药片强度和/或新配方的资格预审，同时应仅使用严格的监管机构(SRA)批准的伯喹。
Background: Global ambitions to eliminate malaria are intensifying, underscoring a critical need for transmission blocking tools. In 2012, the WHO recommended the use of 0.25 mg/kg of single low-dose (SLD) primaquine to stop Plasmodium falciparum transmission. To ensure the availability of SLD primaquine to countries in need of this tool, more information on the supply, programmatic, and regulatory barriers to the rollout of SLD primaquine is required.Methods: Challenges to the rollout of SLD primaquine in sub-Saharan Africa were established through semi-structured qualitative interviews with three primaquine manufacturers, 43 key informants from Ethiopia, Senegal, Swaziland, Zambia, and Tanzania, and 16 malaria research experts.Results: Sanofi and Remedica are the only two sources of SRA-approved primaquine suitable for procurement by international donors. Neither manufacturer produces primaquine tablet strengths suitable for the transmission blocking indication. In-country key informants revealed that the WHO weight-based recommendation to use SLD primaquine is challenging to implement in actual field settings. Malaria programmes expressed safety concerns of SLD primaquine use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as well as potential interactions between primaquine and co-morbidities, and drug-drug interactions with HIV and/or tuberculosis treatments. Regulatory processes are a major barrier to the rollout of SLD primaquine, requiring multiple steps at both the country and global level. Despite these barriers, demand for SLD primaquine is growing, and malaria researchers are interested in primaquine deployment through mass screen and treat and/or mass drug administration campaigns.Conclusion: Demand for primaquine as a transmission blocking agent is growing rapidly yet multiple barriers to SLD primaquine use exist. Research is needed to define the therapeutic dose range, which will guide dosing regimens in the field, inform the development of new, lower strength primaquine tablets and/or formulation(s), and allay programmatic safety concerns in individuals with G6PD deficiency. Potential interactions between primaquine and co-morbidities and treatments should be explored. To minimize regulatory delays, countries need to prepare for product registration at an early stage, WHO prequalification for suitable primaquine tablet strengths and/or new formulations should be sought, and in the meanwhile only Stringent Regulatory Authority (SRA)-approved primaquine should be used.