Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
Int J Parasitol. 2012 Nov;42(12):1107-13. doi: 10.1016/j.ijpara.2012.10.001. Epub 2012 Oct 17.
Despite consistent evidence of a protective effect of α(+)-thalassemia against severe Plasmodium falciparum disease, the mechanisms underlying this protection remain unknown. An increase in risk of Plasmodium vivax malaria in early childhood resulting in a cross-species protection against severe P. falciparum malaria has been proposed as a possible mechanism in Melanesian children. The association of α(+)-thalassemia genotypes with a risk of P. falciparum and P. vivax infection and uncomplicated illness was reassessed in a cohort of 1,112 Papua New Guinean children, followed from 3 to 21 months of age. Three hundred and eighty-nine (35.0%) children were homozygous for α(+)-thalassemia (-α/-α), 506 (45.5%) heterozygous (αα/-α) and 217 (19.5%) homozygous for the wild-type allele. No significant differences in the incidence of P. falciparum (Pf) or P. vivax (Pv) malaria were observed between α(+)-thalassemia homozygote (Pf: incidence rate ratio (IRR)=1.13, CI(95) (0.82, 1.56), P=0.45, Pv: IRR=1.15, CI(95) (0.88, 1.50), P=0.31), heterozygote (Pf: IRR=0.98, CI(95) (0.71, 1.34), P=0.93, Pv: IRR=1.14, CI(95) (0.88, 1.48), P=0.33) and wild-type children. The prevalence of infection with either species did not differ between α(+)-thalassemia genotypes, although densities of P. vivax (but not of P. falciparum) infections were significantly higher in α(+)-thalassemia homozygote and heterozygote children. An excessive risk of moderate-to-severe anemia (Hb<8 g/dl) was observed in α(+)-thalassemia homozygote children (IRR=1.54, CI(95) (1.12, 2.11), P=0.008). This study therefore failed to confirm an increased risk of P. vivax or P. falciparum malaria in very young, α(+)-thalassemic children without significant levels of acquired immunity. This confirms the lack of protection by α(+)-thalassemia against uncomplicated P. falciparum and challenges the hypothesis of immunological cross-protection between P. falciparum and P. vivax as a mechanism underlying α(+)-thalassemia protection against severe P. falciparum disease in Melanesian children.
尽管有一致的证据表明α(+)-地中海贫血对严重恶性疟原虫病具有保护作用，但这种保护作用的机制仍不清楚。有人提出，在美拉尼西亚儿童中，幼年时期感染间日疟原虫的风险增加，从而对严重恶性疟原虫病产生交叉物种保护，这可能是一种机制。在对 1112 名巴布亚新几内亚儿童进行的队列研究中，重新评估了α(+)-地中海贫血基因型与恶性疟原虫和间日疟原虫感染及无并发症疾病的风险之间的关联，这些儿童从 3 至 21 个月大时开始接受研究。389 名儿童（35.0%）为α(+)-地中海贫血纯合子（-α/-α），506 名儿童（45.5%）为杂合子（αα/-α），217 名儿童（19.5%）为野生型等位基因纯合子。α(+)-地中海贫血纯合子（Pf：发病率比（IRR）=1.13，CI（95）（0.82，1.56），P=0.45，Pv：IRR=1.15，CI（95）（0.88，1.50），P=0.31）、杂合子（Pf：IRR=0.98，CI（95）（0.71，1.34），P=0.93，Pv：IRR=1.14，CI（95）（0.88，1.48），P=0.33）和野生型儿童之间，恶性疟原虫（Pf）或间日疟原虫（Pv）疟疾的发病率没有显著差异。虽然间日疟原虫感染（但恶性疟原虫感染没有）的密度α(+)-地中海贫血纯合子和杂合子儿童中明显更高，但两种疟原虫的感染率在α(+)-地中海贫血基因型之间没有差异。α(+)-地中海贫血纯合子儿童发生中度至重度贫血（Hb<8 g/dl）的风险过高（IRR=1.54，CI（95）（1.12，2.11），P=0.008）。因此，本研究未能证实非常年幼的、无获得性免疫的α(+)-地中海贫血儿童感染间日疟原虫或恶性疟原虫的风险增加。这证实了α(+)-地中海贫血对无并发症的恶性疟原虫和间日疟原虫感染没有保护作用，并挑战了α(+)-地中海贫血对恶性疟原虫严重疾病的保护作用是通过恶性疟原虫和间日疟原虫之间的免疫交叉保护机制的假设。
