Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil
Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil
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DOI：
10.1128/aac.01965-18
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发表时间：
2019-05-01
影响因子：
4.9
通讯作者：
Ferreira, Marcelo U.
中科院分区：
文献类型：
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作者：
Ladeia-Andrade, Simone;Menezes, Maria Jose;Ferreira, Marcelo U.
间日疟原虫对氯喹(CQ)的新抗药性可能会破坏南美洲消除疟疾的努力。在主要港口城市马瑙斯发现了耐CQ的间日疟原虫，但在巴西亚马逊盆地的主要疟疾热点地区没有发现，在那里，CQ经常与伯马喹(PQ)联合使用，以根治间日疟。在这里，我们随机分配了204名来自巴西西北部朱鲁瓦山谷的无并发症间日疟患者，接受序贯(组1)或伴随(组2)CQ-PQ治疗。因为PQ可能会协同CQ的血液杀裂作用，并掩盖低水平的CQ抵抗，所以我们监测了仅在28天随访结束时服用PQ的ARM 1受试者的CQ疗效。我们发现在分配给ARM 2的所有受试者中都有足够的临床和寄生虫学反应。然而，在ARM 1患者中，2.2%的患者在第28天有显微镜检测到的寄生虫复发。当考虑到第28天的PCR检测到的寄生虫病时，第1组和第2组的应答率分别降至92.1%和98.8%。治疗性CQ水平在8例复发中有6例被记录下来，与体内真实的CQ抵抗相一致。相比之下，在所分析的49个地方间日疟原虫分离株中，体外试验没有提供CQ耐药性的证据。在180天的监测中，没有发现CQ-PQ联合应用增强PQ的抗复发效果；然而，我们建议需要更大的研究来检验CQ-PQ相互作用是否以及如何在不同的间日疟原虫感染人群中调节根治疗效。
Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Jurua Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo. In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax-infected populations.