Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017.
Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017.
复制标题
DOI：
10.1186/s12936-018-2290-9
复制
发表时间：
2018-04-03
期刊：
影响因子：
3
通讯作者：
Plucinski MM
中科院分区：
文献类型：
--
作者：
Davlantes E;Dimbu PR;Ferreira CM;Florinda Joao M;Pode D;Félix J;Sanhangala E;Andrade BN;Dos Santos Souza S;Talundzic E;Udhayakumar V;Owens C;Mbounga E;Wiesner L;Halsey ES;Martins JF;Fortes F;Plucinski MM
安哥拉政府建议使用三种青蒿素类复方药物治疗无并发症的恶性疟原虫疟疾：蒿甲醚-苯芴醇（AL）、青蒿琥酯-阿莫地喹（ASAQ）和双氢青蒿素-哌喹（DP）。由于新出现的抗疟疾药物耐药性的威胁，必须定期监测青蒿素类复方疗法的疗效。本研究评估了这些药物在本格拉、南隆达和扎伊尔省的治疗效果。入组时间为2017年3月至7月。研究参与者是来自每个省会的恶性疟原虫单一感染儿童。参与者接受了为期3天的质量保证青蒿素为基础的组合，并监测了28天（AL和ASAQ组）或42天（DP组）。在两个省对每个首都直辖区进行了评估。主要研究终点为：（1）随访无并发症和（2）治疗无效或复发恶性疟原虫感染。对每例复发感染患者的寄生虫进行基因分型，以区分新发感染和持续性寄生虫血症复发。还分析了这些寄生虫与ACT耐药相关的分子标志物。在参加研究的608名儿童中，540名（89%）达到了主要研究终点。所有受试者的寄生虫血症均在给药后3天内清除，未观察到早期治疗失败。排除再感染后，AL的校正疗效在扎伊尔为96%（91- 100%，95%置信区间），在南隆达为97%（93-100%）。在本格拉和扎伊尔，ASAQ的校正有效性分别为100%（97-100%）和93%（88-99%）。DP的校正功效在本格拉为100%（96-100%），在南隆达为100%。在38例复发性恶性疟原虫感染病例中未发现与青蒿素耐药相关的pfk 13基因突变。AL组和ASAQ组的所有33例治疗失败者在失败当天分别携带与本芴醇和阿莫地喹耐药相关的pfmdr 1或pfcrt突变。AL、ASAQ和DP在安哥拉的这些省份继续对恶性疟原虫疟疾有效。快速的寄生虫清除和缺乏青蒿素耐药性的遗传证据与对青蒿素衍生物的完全敏感性是一致的。定期监测体内药效仍然是安哥拉的一项优先例行活动。本文的在线版本（10.1186/s12936-018-2290-9）包含补充材料，可供授权用户使用。
The Angolan government recommends three artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria: artemether–lumefantrine (AL), artesunate–amodiaquine (ASAQ), and dihydroartemisinin–piperaquine (DP). Due to the threat of emerging anti-malarial drug resistance, it is important to periodically monitor the efficacy of artemisinin-based combination therapy (ACT). This study evaluated these medications’ therapeutic efficacy in Benguela, Lunda Sul, and Zaire Provinces. Enrollment occurred between March and July 2017. Study participants were children with P. falciparum monoinfection from each provincial capital. Participants received a 3-day course of a quality-assured artemisinin-based combination and were monitored for 28 (AL and ASAQ arms) or 42 days (DP arm). Each ACT was assessed in two provinces. The primary study endpoints were: (1) follow-up without complications and (2) failure to respond to treatment or development of recurrent P. falciparum infection. Parasites from each patient experiencing recurrent infection were genotyped to differentiate new infection from recrudescence of persistent parasitaemia. These parasites were also analysed for molecular markers associated with ACT resistance. Of 608 children enrolled in the study, 540 (89%) reached a primary study endpoint. Parasitaemia was cleared within 3 days of medication administration in all participants, and no early treatment failures were observed. After exclusion of reinfections, the corrected efficacy of AL was 96% (91–100%, 95% confidence interval) in Zaire and 97% (93–100%) in Lunda Sul. The corrected efficacy of ASAQ was 100% (97–100%) in Benguela and 93% (88–99%) in Zaire. The corrected efficacy of DP was 100% (96–100%) in Benguela and 100% in Lunda Sul. No mutations associated with artemisinin resistance were identified in the pfk13 gene in the 38 cases of recurrent P. falciparum infection. All 33 treatment failures in the AL and ASAQ arms carried pfmdr1 or pfcrt mutations associated with lumefantrine and amodiaquine resistance, respectively, on day of failure. AL, ASAQ, and DP continue to be efficacious against P. falciparum malaria in these provinces of Angola. Rapid parasite clearance and the absence of genetic evidence of artemisinin resistance are consistent with full susceptibility to artemisinin derivatives. Periodic monitoring of in vivo drug efficacy remains a priority routine activity for Angola. The online version of this article (10.1186/s12936-018-2290-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
与柬埔寨恶性疟原虫疟疾双氢青蒿素-哌喹失败相关的遗传标记：基因型-表型关联研究。
DOI：
10.1016/s1473-3099(16)30409-1
发表时间：
2017-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amato R;Lim P;Miotto O;Amaratunga C;Dek D;Pearson RD;Almagro-Garcia J;Neal AT;Sreng S;Suon S;Drury E;Jyothi D;Stalker J;Kwiatkowski DP;Fairhurst RM
通讯作者：
Fairhurst RM
柬埔寨恶性疟原虫疟疾中的双氢青蒿素-哌喹抗药性：一项多地点前瞻性队列研究。
DOI：
10.1016/s1473-3099(15)00487-9
发表时间：
2016-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amaratunga C;Lim P;Suon S;Sreng S;Mao S;Sopha C;Sam B;Dek D;Try V;Amato R;Blessborn D;Song L;Tullo GS;Fay MP;Anderson JM;Tarning J;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
4.9
作者：
Kredo, T.;Mauff, K.;Barnes, K. I.
通讯作者：
Barnes, K. I.
DOI：
10.1016/j.trstmh.2004.11.010
发表时间：
2005-07-01
影响因子：
2.2
作者：
Guthmann, JP;Ampuero, J;Legros, D
通讯作者：
Legros, D
影响因子：
6.4
作者：
Alam, Md Tauqeer;de Souza, Dziedzom K.;Koram, Kwadwo A.
通讯作者：
Koram, Kwadwo A.