Wageningen University, Cell Biology and Immunology Group, Wageningen, The Netherlands.
PLoS Med. 2011 Nov;8(11):e1001125. doi: 10.1371/journal.pmed.1001125. Epub 2011 Nov 22.
It is uncertain to what extent oral supplementation with zinc can reduce episodes of malaria in endemic areas. Protection may depend on other nutrients. We measured the effect of supplementation with zinc and other nutrients on malaria rates.
In a 2×2 factorial trial, 612 rural Tanzanian children aged 6-60 months in an area with intense malaria transmission and with height-for-age z-score≤-1.5 SD were randomized to receive daily oral supplementation with either zinc alone (10 mg), multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Intervention group was indicated by colour code, but neither participants, researchers, nor field staff knew who received what intervention. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. The primary outcome, an episode of malaria, was assessed among children reported sick at a primary care clinic, and pre-defined as current Plasmodium infection with an inflammatory response, shown by axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥ 8 mg/L. Nutritional indicators were assessed at baseline and at 251 days (median; 95% reference range: 191-296 days). In the primary intention-to-treat analysis, we adjusted for pre-specified baseline factors, using Cox regression models that accounted for multiple episodes per child. 592 children completed the study. The primary analysis included 1,572 malaria episodes during 526 child-years of observation (median follow-up: 331 days). Malaria incidence in groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child-year, respectively. There was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93-1.18 and 1.10, 0.97-1.24 respectively). The prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation.
We found no evidence from this trial that zinc supplementation protected against malaria.
ClinicalTrials.gov NCT00623857
目前尚不清楚口服补锌能在多大程度上减少流行地区疟疾的发作次数。保护作用可能取决于其他营养素。我们测量了补锌和其他营养素补充对疟疾发病率的影响。
在一项 2×2 的析因试验中，612 名年龄在 6-60 个月的坦桑尼亚农村儿童，居住在疟疾高度流行地区，身高与年龄的 Z 评分≤-1.5 SD，他们被随机分为每日口服补锌（10 毫克）、不含锌的多种营养素、含锌的多种营养素或安慰剂。干预组用颜色代码表示，但参与者、研究人员和现场工作人员都不知道谁接受了哪种干预。基线时患有疟原虫感染的儿童接受青蒿琥酯-甲氟喹治疗。主要结局是在初级保健诊所报告患病的儿童中出现的疟疾发作，定义为当前的疟原虫感染伴有炎症反应，表现为腋窝温度≥37.5°C 或全血 C 反应蛋白浓度≥8mg/L。营养指标在基线和 251 天（中位数；95%参考范围：191-296 天）进行评估。在主要的意向治疗分析中，我们使用 Cox 回归模型调整了预先指定的基线因素，该模型考虑了每个儿童的多次发作。592 名儿童完成了研究。主要分析包括 1572 次疟疾发作，观察了 526 名儿童年（中位随访：331 天）。接受锌、不含锌的多种营养素、含锌的多种营养素和安慰剂的儿童的疟疾发病率分别为 2.89/儿童年、2.95/儿童年、3.26/儿童年和 2.87/儿童年。没有证据表明多种营养素会影响锌的作用（反之亦然）。锌和多种营养素都没有影响疟疾的发病率（边缘分析；调整后的 HR，95%CI：1.04，0.93-1.18 和 1.10，0.97-1.24）。基线时缺锌（血浆锌浓度<9.9µmol/L）的患病率很高（总体 67%；无炎症者 60%），补锌可显著降低缺锌的患病率。
我们从这项试验中没有发现补锌能预防疟疾的证据。
ClinicalTrials.gov NCT00623857
