Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLoS Med. 2010 May 25;7(5):e1000283. doi: 10.1371/journal.pmed.1000283.
The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A-) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection.
A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06-0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037).
G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.
在非洲以外地区最常见的疟疾形式是间日疟原虫（Plasmodium vivax），由于其潜伏的肝脏休眠阶段，它比恶性疟原虫（P. falciparum）更难控制，这会导致多次复发并提供传染性储存库。非洲（A-）型葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症对严重的恶性疟原虫感染有部分保护作用。最近的证据表明，这种缺乏症也对间日疟原虫有保护作用，这可以解释它在人类群体中的广泛地理分布。这种缺乏症与抗复发治疗（如 8-氨基喹啉类药物如伯氨喹）有严重的相互作用。如果保护水平足够高，抗复发治疗可能会更广泛地应用。因此，我们检验了 G6PD 缺乏症对间日疟感染有保护作用的假设。
我们在巴基斯坦的阿富汗难民中进行了病例对照研究设计。比较了间日疟患者和过去两年内未患疟疾的对照者的表型和基因型 G6PD 缺乏症的频率。表型 G6PD 缺乏症在病例中的发生率低于对照组（病例：4/372[1.1%]vs.对照组 42/743[5.7%]；调整后的优势比[AOR]0.18[95%置信区间（CI）0.06-0.52]，p=0.001）。基因分析表明，所鉴定的 G6PD 缺乏等位基因（地中海型）与半合子缺乏男性的保护作用相关（AOR=0.12[95%CI 0.02-0.92]，p=0.041）。携带该缺陷基因的女性作为杂合子或纯合子也具有保护作用（汇总 AOR=0.37[95%CI 0.15-0.94]，p=0.037）。
无论通过表型还是基因型来衡量，G6PD 缺乏症（地中海型）都为该人群中的间日疟感染提供了显著的保护作用，这表明间日疟原虫在选择性保留人类群体中的 G6PD 缺乏症特征方面可能具有进化作用。需要进一步研究与其他类型 G6PD 缺乏症相关的基因型保护作用，并开发简单的即时检测技术，在进行抗复发治疗之前检测到它。
