Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials.
Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials.
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DOI：
10.1186/1475-2875-10-241
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发表时间：
2011-08-17
期刊：
影响因子：
3
通讯作者：
Waitumbi JN
中科院分区：
文献类型：
--
作者：
Carter N;Pamba A;Duparc S;Waitumbi JN
葡萄糖-6-磷酸脱氢酶（G6 PD）缺乏症在疟疾流行区的人群中很常见。G6 PD基因型和表型确定疟疾患者入组的氯丙胍-氨苯砜-青蒿琥酯（CDA）III期临床试验计划。研究参与者年龄> 1岁，经显微镜确诊为无并发症恶性疟原虫疟疾，血红蛋白≥ 70 g/L或红细胞压积≥ 25%，被招募到在6个非洲国家（布基纳法索、加纳、肯尼亚、尼日利亚、坦桑尼亚、马里）进行的两项临床试验中。确定了三种最常见的非洲型的G6 PD基因型，G6 PD *B、G6 PD *A（A376 G）和G6 PD *A-（G202 A、A542 T、G680 T和T968 C），并用于频率估计。使用NADPH荧光试验定性评估G6 PD表型。探索性分析研究了G6 PD状态对基线血红蛋白浓度、体温、无性寄生虫血症和CDA 2/2.5/4 mg/kg或氯丙胍胺-氨苯砜2/2.5 mg/kg（均每日一次给药，持续3天）或6剂蒿甲醚-苯芴醇治疗后的抗疟疾疗效的影响。在2264例入组的疟疾患者中，2045例具有可用的G6 PD基因型，并构成主要分析人群（1018例男性，1027例女性）。G6 PD缺乏症患病率为9.0%（184/2045; 7.2% [N = 147]男性半合子+1.8% [N = 37]女性纯合子），13.3%（273/2045）的患者为杂合子女性，77.7%（1588/2045）的患者为G6 PD正常。所有缺陷型G6 PD *A-基因型均为A376 G/G202 A。64.5%（1319/2045）的患者可获得G6 PD表型：10.2%（134/1319）为G6 PD缺陷型，9.6%（127/1319）为中间型，80.2%（1058/1319）为正常型。表型试验检测半合子男性的特异性为70.7%（70/99），检测纯合子女性的特异性为48.0%（12/25）。Logistic回归发现G6 PD基因型对校正的平均基线血红蛋白（p = 0.154）、校正的平均基线体温（p = 0.9617）或校正的对数平均基线寄生虫血症（p = 0.365）无显著影响。G6 PD基因型（p = 0.490）或表型（p = 0.391）对疟疾复发率或再感染率（分别为p = 0.134和p = 0.354）没有影响。G6 PD缺乏症在非洲疟疾患者中很常见，在可靠和简单的G6 PD测试可用之前，8-氨基喹啉的使用仍然存在问题。G6 PD状态不影响基线血红蛋白，寄生虫血症或温度或抗疟疾治疗的结果。Clinicaltrials.gov：NCT 00344006和NCT 00371735。
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA) phase III clinical trial programme. Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali). G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G), and G6PD*A- (G202A, A542T, G680T and T968C), were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days) or six-dose artemether-lumefantrine. Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females). G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous), 13.3% (273/2045) of patients were heterozygous females, 77.7% (1588/2045) were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045) of patients: 10.2% (134/1319) were G6PD deficient, 9.6% (127/1319) intermediate, and 80.2% (1058/1319) normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99) and 48.0% (12/25) for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154), adjusted mean baseline temperature (p = 0.9617), or adjusted log mean baseline parasitaemia (p = 0.365). There was no effect of G6PD genotype (p = 0.490) or phenotype (p = 0.391) on the rate of malaria recrudescence, or reinfection (p = 0.134 and p = 0.354, respectively). G6PD deficiency is common in African patients with malaria and until a reliable and simple G6PD test is available, the use of 8-aminoquinolines will remain problematic. G6PD status did not impact baseline haemoglobin, parasitaemia or temperature or the outcomes of anti-malarial therapy. Clinicaltrials.gov: NCT00344006 and NCT00371735.
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DOI：
10.1038/ejhg.2009.8
发表时间：
2009-08
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
通讯作者：
--
影响因子：
168.9
作者：
Alloueche, A;Bailey, W;Winstanley, PA
通讯作者：
Winstanley, PA
影响因子：
15.8
作者：
Guindo A;Fairhurst RM;Doumbo OK;Wellems TE;Diallo DA
通讯作者：
Diallo DA
影响因子：
2.7
作者：
Burchard, GD;Browne, ENL;Meyer, CG
通讯作者：
Meyer, CG
DOI：
10.1073/pnas.85.11.3951
发表时间：
1988-06-01
影响因子：
11.1
作者：
HIRONO, A;BEUTLER, E
通讯作者：
BEUTLER, E