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含青蒿素衍生物的疗法与异常血红蛋白:我们是否需要调整治疗方案?

Artemisinin derivative-containing therapies and abnormal hemoglobin: Do we need to adapt the treatment?

机构信息

Unité de Paludologie, Institut Pasteur Côte d'Ivoire, 01 BP 490, Abidjan 01, Côte d'Ivoire.

Institut Pierre Richet/Programme National de Lutte contre le Paludisme, BP 1500 Bouaké, Côte d'Ivoire.

出版信息

Parasite. 2021;28:67. doi: 10.1051/parasite/2021063. Epub 2021 Sep 27.

DOI:10.1051/parasite/2021063
PMID:34569928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8475499/
Abstract

BACKGROUND

Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016.

RESULTS

A total of 770 patients in Côte d'Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p < 0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group.

CONCLUSION

Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin.

摘要

背景

在血红蛋白异常的疟疾患者中使用青蒿素类药物治疗可能无效,因为他们的遗传特殊性可能导致耐药性。本研究的主要目的是根据红细胞变异评估青蒿素衍生物对体内寄生虫清除的影响。通过回顾性数据评估体内反应,这些数据是在 2012 年至 2016 年进行的为期 42 天的青蒿琥酯-甲氟喹/青蒿琥酯-阿莫地喹疗效方案中获得的。

结果

在科特迪瓦,共有 770 名在阿努科瓦库特(阿比让)、佩蒂特巴黎(科霍戈)、利伯维尔(曼)、达累斯萨拉姆(布瓦凯)、阿亚梅和亚穆苏克罗的医院就诊的急性无并发症恶性疟疾病人接受了成功的血红蛋白分型。发现了 HbAS、HbSS、HbAC 和 HbSC 基因型。获得了 414 名患者的寄生虫清除时间。在血红蛋白异常的人群中,与 HbAA 相比,HbSC 组的寄生虫密度在入院时和寄生虫清除率显著较低(p = 0.02 和 p = 0.007)。在第 42 天进行 PCR 校正后,每个组的急性治疗率均为 100%。对于 HbSC 组,寄生虫半衰期和初始寄生虫血症下降 50%和 99%的时间更长(p < 0.05)。该研究还调查了不同血红蛋白基因型组中 K13 推进器多态性的流行情况。在 HbAA 组和异常血红蛋白患者中,分别对 185 和 63 个样本进行了测序。仅在 HbAA 组中发现了两个非同义突变 D559N 和 V510M。

结论

尽管本研究证明了青蒿琥酯-甲氟喹和青蒿琥酯-阿莫地喹在治疗血红蛋白异常的无并发症恶性疟疾病人中的疗效良好,但寄生虫清除的延迟增加可能对这些患者的健康构成威胁,与镰状细胞危象有关,这可能支持对青蒿素耐药的寄生虫的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ab/8475499/99b0673d265e/parasite-28-67-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ab/8475499/f417378bc6e6/parasite-28-67-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ab/8475499/99b0673d265e/parasite-28-67-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ab/8475499/f417378bc6e6/parasite-28-67-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38ab/8475499/99b0673d265e/parasite-28-67-fig2.jpg

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