Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.
Lancet Infect Dis. 2012 Jun;12(6):457-68. doi: 10.1016/S1473-3099(12)70055-5. Epub 2012 Mar 23.
Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity.
We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study.
Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P. falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06-0·12), haemoglobin CC (0·27, 0·11-0·63), haemoglobin AC (0·83, 0·67-0·96), homozygous α-thalassaemia (0·63, 0·48-0·83), and heterozygous α-thalassaemia (0·83, 0·74-0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61-0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P. vivax malaria, or pregnancy-associated malaria.
Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity.
US National Institute of Allergy and Infectious Diseases.
血红蛋白病可降低疟疾综合征的风险。我们旨在量化不同血红蛋白突变与疟疾保护之间的关系，以加强疟疾发病机制和免疫的转化研究基础。
我们系统地检索了截至 2011 年 9 月 9 日在 Medline 和 Embase 数据库中评估有和无血红蛋白病患者疟疾风险的研究，并从参考文献列表中确定了其他研究。我们纳入了主要纳入儿童或孕妇的研究，且这些研究具有以下结局：恶性疟原虫疟疾、无并发症疟疾、无症状寄生虫血症或妊娠相关疟疾、间日疟疟疾。两位评审员独立地确定研究、评估研究质量并提取数据。我们对病例对照研究计算比值比（OR；95%CI），对前瞻性研究计算发病率比值比（IRR；95%CI）。当一项研究中报告了多个等效结局时，我们采用随机效应模型进行荟萃分析。
在 62 项已识别的研究中，44 项报告了血红蛋白 AS 的数据，19 项报告了血红蛋白 AC 和 CC 的数据，18 项报告了α-地中海贫血的数据。对病例对照研究的荟萃分析表明，血红蛋白 AS（OR 0·09，95%CI 0·06-0·12）、血红蛋白 CC（0·27，0·11-0·63）、血红蛋白 AC（0·83，0·67-0·96）、纯合子α-地中海贫血（0·63，0·48-0·83）和杂合子α-地中海贫血（0·83，0·74-0·92）个体发生严重恶性疟原虫疟疾的风险降低。仅在对前瞻性试验的荟萃分析中，血红蛋白 AS 一直与无并发症疟疾的保护作用相关（IRR 0·69，95%CI 0·61-0·79）；没有血红蛋白病与无症状寄生虫血症的持续保护作用相关。少数临床研究调查了β-地中海贫血、血红蛋白 E、间日疟疟疾或妊娠相关疟疾。
血红蛋白 AS、CC 和 AC 基因型以及纯合子和杂合子α-地中海贫血显著降低严重疟疾综合征的风险，但这些血红蛋白病在提供的保护程度上有很大差异，并且对无并发症疟疾和无症状寄生虫血症几乎没有或没有保护作用。通过减轻疟疾的严重程度，血红蛋白病可以作为疟疾发病机制和免疫机制研究的模型。
美国国家过敏和传染病研究所。
