G6PD deficiency at Sumba in Eastern Indonesia is prevalent, diverse and severe: implications for primaquine therapy against relapsing Vivax malaria.
G6PD deficiency at Sumba in Eastern Indonesia is prevalent, diverse and severe: implications for primaquine therapy against relapsing Vivax malaria.
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DOI：
10.1371/journal.pntd.0003602
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发表时间：
2015-03
影响因子：
3.8
通讯作者：
Baird JK
中科院分区：
文献类型：
--
作者：
Satyagraha AW;Sadhewa A;Baramuli V;Elvira R;Ridenour C;Elyazar I;Noviyanti R;Coutrier FN;Harahap AR;Baird JK
间日疟原虫的安全治疗需要诊断感染和红细胞葡萄糖-6-磷酸脱氢酶（G6 PD）活性的状态，因为抗复发的杀催眠虫治疗需要伯氨喹，伯氨喹会导致G6 PD缺陷患者出现轻度至重度急性溶血性贫血。许多国家的疟疾控制计划建议伯氨喹治疗没有G6 PD筛查，但由于广泛缺乏G6 PD缺乏症筛查能力的监测。这样做的风险程度取决于任何给定区域中存在的变体之间的残留G6 PD活性水平。我们在印度尼西亚东部的松巴岛进行了研究，以评估伯氨喹治疗而不进行G6 PD筛查所造成的潜在威胁。我们对松巴西部三个不同地区的2，033名居民进行了G6 PD活性定量采样，其中104名（5.1%）为表型缺陷（<4.6U/gHb;中位数正常10 U/gHb）。那些村庄处于两种截然不同的生态系统中，沿海和内陆。疟疾患病率与G6 PD缺乏症呈正相关：沿海地区为5.9%，内地为0.2%（P<0.001）; G6 PD缺乏症患病率沿海地区为6.7%，内地为3.1%（P<0.001）。G6 PD缺乏症的优势基因型为Vanua Lava、维昂占和查塔姆，占基因分型的98.5%。表达显性基因型的受试者的酶活性均低于正常值的10%，因此被视为重度变异。在Sumba盲目给予抗复发伯氨喹治疗可能会造成严重伤害的风险。G6 PD缺乏症影响全球超过4亿人。这种极其多样的疾病在暴露于氧化化学物质时引起急性溶血性贫血，例如，萘，一些磺胺类药物和某些抗疟药，包括伯氨喹。G6 PD缺乏症的主要公共卫生问题涉及后者药物，这是唯一一种可用于根治间日疟和卵形疟的药物。如果没有伯氨喹治疗，患者将在初次发作后的两年内遭受多次复发性发作，称为复发。伯氨喹在G6 PD缺陷患者中引发轻度至重度急性溶血性贫血，这取决于给药剂量和涉及的特定变体。在严重缺陷的变体中，相对高的治疗剂量将威胁生命。关于伯氨喹的疟疾治疗政策和实践可能取决于G6 PD缺乏症的患病率和严重程度，权衡避免复发风险和伴随的发病率、死亡率和继续传播的治疗益处。在目前的研究中，我们的目的是通过描述印度尼西亚东部一个岛屿上持续存在地方性间日疟传播的人群中发生的G6 PD缺乏症的频率和类型来告知这种权衡。研究结果推断，对G6 PD状态未知的居民使用伯氨喹可能会造成严重伤害。
Safe treatment of Plasmodium vivax requires diagnosis of both the infection and status of erythrocytic glucose-6-phosphate dehydrogenase (G6PD) activity because hypnozoitocidal therapy against relapse requires primaquine, which causes a mild to severe acute hemolytic anemia in G6PD deficient patients. Many national malaria control programs recommend primaquine therapy without G6PD screening but with monitoring due to a broad lack of G6PD deficiency screening capacity. The degree of risk in doing so hinges upon the level of residual G6PD activity among the variants present in any given area. We conducted studies on Sumba Island in eastern Indonesia in order to assess the potential threat posed by primaquine therapy without G6PD screening. We sampled 2,033 residents of three separate districts in western Sumba for quantitative G6PD activity and 104 (5.1%) were phenotypically deficient (<4.6U/gHb; median normal 10U/gHb). The villages were in two distinct ecosystems, coastal and inland. A positive correlation occurred between the prevalence of malaria and G6PD deficiency: 5.9% coastal versus inland 0.2% for malaria (P<0.001), and 6.7% and 3.1% for G6PD deficiency (P<0.001) at coastal and inland sites, respectively. The dominant genotypes of G6PD deficiency were Vanua Lava, Viangchan, and Chatham, accounting for 98.5% of the 70 samples genotyped. Subjects expressing the dominant genotypes all had less than 10% of normal enzyme activities and were thus considered severe variants. Blind administration of anti-relapse primaquine therapy at Sumba would likely impose risk of serious harm. G6PD deficiency affects over 400 million people worldwide. This enormously diverse disorder causes acute hemolytic anemia upon exposure to oxidizing chemicals, e.g., naphthalene, some sulfa drugs, and certain antimalarials, including primaquine. The primary public health concern with G6PD deficiency involves that latter drug, the only one available for the radical cure of vivax and ovale malarias. Absent primaquine therapy, patients will suffer multiple recurrent attacks called relapses in the two years following the primary attack. Primaquine in G6PD-deficient patients triggers a mild to severe acute hemolytic anemia, depending upon dose administered and the specific variant involved. Relatively high therapeutic doses in severely deficient variants will threaten life. Malaria therapeutic policy and practice regarding primaquine may hinge upon the prevalence and severity of G6PD deficiency weighed against the therapeutic benefit of averting risk of relapse and attendant morbidity, mortality and onward transmission. In the current study we aimed to inform that weighing by characterizing the frequency and type of G6PD deficiency occurring in populations enduring endemic vivax malaria transmission on a single island in eastern Indonesia. The findings infer risk of serious harm caused by primaquine administered to residents of unknown G6PD status.
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影响因子：
4.9
作者：
Eziefula, Alice C.;Pett, Helmi;Drakeley, Chris
通讯作者：
Drakeley, Chris
DOI：
10.1073/pnas.0704451104
发表时间：
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