MMV Medicines for Malaria Venture, 20 Route de Pré-Bois, 1215, Geneva 15, Switzerland.
Magenta Communications Ltd, Abingdon, UK.
Malar J. 2024 Sep 27;23(1):287. doi: 10.1186/s12936-024-05112-9.
Plasmodium vivax malaria remains a global health challenge, with approximately 6.9 million estimated cases in 2022. The parasite has a dormant liver stage, the hypnozoite, which reactivates to cause repeated relapses over weeks, months, or years. These relapses erode patient health, contribute to the burden of malaria, and promote transmission. Radical cure to prevent relapses requires administration of an 8-aminoquinoline, either primaquine or tafenoquine. However, malaria treatment guidelines updated by the World Health Organization (WHO) in October 2023 restrict primaquine use for women breastfeeding children < 6 months of age, or women breastfeeding older children if their child is G6PD deficient or if the child's G6PD status is unknown. Primaquine restrictions assume that 8-aminoquinoline exposures in breast milk would be sufficient to cause haemolysis in the nursing infant should they be G6PD deficient. WHO recommendations for tafenoquine are awaited. Notably, the WHO recommends that infants are breastfed for the first 2 years of life, and exclusively until 6 months old. Repeated pregnancies, followed by extended breastfeeding leaves women in P. vivax endemic regions potentially vulnerable to relapses for many years. This puts women's health at risk, increases the malaria burden, and perpetuates transmission, hindering malaria control and elimination. The benefits of lifting restrictions on primaquine administration to breastfeeding women are significant, avoiding the adverse consequences of repeated episodes of acute malaria, such as severe anaemia. Recent data challenge the restriction of primaquine in breastfeeding women. Clinical pharmacokinetic data in breastfeeding infants ≥ 28 days old show that the exposure to primaquine is very low and less than 1% of the maternal exposure, indicating negligible risk to infants, irrespective of their G6PD status. Physiologically-based pharmacokinetic modelling complements the clinical data, predicting minimal primaquine exposure to infants and neonates via breast milk from early post-partum. This article summarizes the clinical and modelling evidence for a favourable benefit:risk evaluation of P. vivax radical cure with primaquine for breastfeeding women without the need for infant G6PD testing, supporting a change in policy. This adjustment to current treatment guidelines would support health equity in regard to effective interventions to protect women and their children, enhance malaria control strategies, and advance P. vivax elimination.
间日疟原虫疟疾仍然是一个全球性的健康挑战，据估计，2022 年有 690 万例。该寄生虫具有休眠的肝脏阶段，即休眠子，它会重新激活，导致数周、数月或数年内反复发作。这些复发侵蚀了患者的健康，加重了疟疾负担，并促进了传播。为了防止复发，根治需要使用 8-氨基喹啉，即伯氨喹或他非诺喹。然而，世界卫生组织（世卫组织）于 2023 年 10 月更新的疟疾治疗指南限制了伯氨喹在哺乳期妇女中的使用，这些妇女的婴儿年龄小于 6 个月，或者婴儿年龄较大但患有 G6PD 缺乏症，或者婴儿的 G6PD 状态未知。伯氨喹的限制假设是，如果婴儿患有 G6PD 缺乏症，母乳中的 8-氨基喹啉暴露量足以导致哺乳婴儿发生溶血。世卫组织对他非诺喹的建议仍在等待中。值得注意的是，世卫组织建议婴儿在生命的前 2 年进行母乳喂养，并在 6 个月之前进行纯母乳喂养。反复怀孕和随后的延长母乳喂养时间使间日疟原虫流行地区的妇女多年来容易受到复发的影响。这使妇女的健康处于危险之中，增加了疟疾负担，并使传播持续下去，阻碍了疟疾的控制和消除。解除对哺乳期妇女使用伯氨喹的限制的好处是显著的，可以避免反复发作急性疟疾的不良后果，如严重贫血。最近的数据对限制哺乳期妇女使用伯氨喹提出了挑战。对 28 天以上哺乳期婴儿的临床药代动力学数据显示，伯氨喹的暴露量非常低，不到母体暴露量的 1%，表明婴儿的风险可以忽略不计，无论其 G6PD 状态如何。基于生理学的药代动力学模型补充了临床数据，预测了通过产后早期母乳向婴儿和新生儿传递的最小伯氨喹暴露量。本文总结了支持在无需检测婴儿 G6PD 的情况下，对哺乳期妇女进行间日疟根治性治疗的伯氨喹的临床和建模证据，进行了有利风险评估，支持改变政策。这一调整将支持在有效干预措施方面的健康公平性，以保护妇女及其子女，加强疟疾控制战略，并推进间日疟原虫的消除。
