Medical Technology Program, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat 80160, Thailand.
Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Nutrients. 2023 Nov 10;15(22):4749. doi: 10.3390/nu15224749.
Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the association between copper levels and malaria pathogenesis, providing a deeper understanding of copper's role in the disease. A systematic review was conducted following the registered protocol in PROSPERO (CRD42023439732). Multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, and Google Scholar, were searched for relevant studies reporting blood copper levels in patients with malaria. The Joanna Briggs Institute critical appraisal checklist was used for assessing methodological quality. Qualitative and quantitative syntheses were employed, organizing, and summarizing the findings of the included studies. To calculate the standardized mean difference (Hedge's g) and 95% confidence intervals (CIs), a random-effects model was used. After screening the databases, 16 studies were included. Most studies (52.9%) reported that individuals with malaria had significantly higher copper levels than uninfected controls. The meta-analysis, based on 16 studies, showed no significant difference in copper levels between patients with malaria and uninfected controls overall ( = 0.39; Hedges' g, 0.38; 95% CI, -0.48 to 1.25; , 98.73%). Subgroup analysis showed a significant difference in copper levels between patients with malaria and uninfected controls among studies conducted in Asia ( < 0.01; Hedges' g, 1.74; 95% CI, 1.04 to 2.44; , 90.88%; five studies) and studies employing plasma blood samples ( < 0.01; Hedges' g, 1.13; 95% CI, 0.60 to 2.07; , 93.11%; four studies). The qualitative synthesis of the reviewed studies suggests a complex relationship between copper levels and malaria. The meta-analysis results showed no significant difference in copper levels between patients with malaria and uninfected controls overall. However, subgroup analyses based on various factors, including continent and blood sample type, showed copper level variations. These findings highlight the need for further research to better understand the role of copper in malaria pathogenesis by considering geographical factors and the blood sample type used for copper level measurement.
微量营养素不足与疟疾发病机制有关。然而，铜在疟疾中的作用仍不确定。本研究旨在调查铜水平与疟疾发病机制之间的关系，以更深入地了解铜在该疾病中的作用。按照 PROSPERO 注册方案（CRD42023439732）进行系统综述。通过 Embase、MEDLINE、Ovid、PubMed、Scopus 和 Google Scholar 等多个数据库，检索报道疟疾患者血铜水平的相关研究。采用 Joanna Briggs 研究所的批判性评价清单评估方法学质量。采用定性和定量综合方法，对纳入研究的结果进行组织和总结。采用随机效应模型计算标准化均数差值（Hedge's g）和 95%置信区间（CI）。对数据库进行筛选后，纳入了 16 项研究。大多数研究（52.9%）表明，疟疾患者的铜水平明显高于未感染对照者。基于 16 项研究的荟萃分析显示，疟疾患者与未感染对照者的铜水平总体无显著差异（ = 0.39；Hedges' g，0.38；95%CI，-0.48 至 1.25； ，98.73%）。亚组分析显示，在亚洲进行的研究（ < 0.01；Hedges' g，1.74；95%CI，1.04 至 2.44； ，90.88%；五项研究）和采用血浆血样的研究（ < 0.01；Hedges' g，1.13；95%CI，0.60 至 2.07； ，93.11%；四项研究）中，疟疾患者与未感染对照者的铜水平存在显著差异。对纳入研究的定性综合表明，铜水平与疟疾之间存在复杂关系。荟萃分析结果显示，疟疾患者与未感染对照者的铜水平总体无显著差异。然而，基于地理位置因素和用于测量铜水平的血样类型等各种因素的亚组分析显示，铜水平存在差异。这些发现强调需要进一步研究，通过考虑地理因素和用于测量铜水平的血样类型，更好地了解铜在疟疾发病机制中的作用。
