Department of Medicine, Section of Genetic Medicine, The University of Chicago, Chicago, IL, 60637, USA.
Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, NC, 27599, USA.
Malar J. 2019 Jun 24;18(1):205. doi: 10.1186/s12936-019-2842-7.
Heterogeneity in the immune response to parasite infection is mediated in part by differences in host genetics, gender, and age group. In infants and young children, ongoing immunological maturation often results in increased susceptibility to infection and variable responses to drug treatment, increasing the risk of complications. Even though significant age-associated effects on host cytokine responses to Plasmodium falciparum infection have been identified, age-associated effects on uncomplicated malaria infection and anti-malarial treatment remain poorly understood.
In samples of whole blood from a cohort of naturally infected malaria-positive individuals with non-severe falciparum malaria in Malawi (n = 63 total; 34 infants and young children < 2 years old, 29 adults > 18 years old), blood cytokine levels and monocyte and dendritic cell frequencies were assessed at two timepoints: acute infection, and 4 weeks post anti-malarial treatment. The effects of age group, gender, and timepoint were modeled, and the role of these factors on infection and treatment outcomes was evaluated.
Regardless of treatment timepoint, in this population age was significantly associated with overall blood haemoglobin, which was higher in adults, and plasma nitric oxide metabolites, IL-10, and TNF levels, which were higher in young children. There was a significant effect of age on the haemoglobin treatment response, whereby after treatment, levels increased in young children and decreased in adults. Furthermore, there were significant age-associated effects on treatment response for overall parasite load, IFN-γ, and IL-12(p40), and these effects were gender-dependent. Significant age effects on the overall levels and treatment response of myeloid dendritic cell frequencies were observed. In addition, within each age group, results showed continuous age effects on gametocyte levels (Pfs16), TNF, and nitric oxide metabolites.
In a clinical study of young children and adults experiencing natural falciparum malaria infection and receiving anti-malarial treatment, age-associated signatures of infection and treatment responses in peripheral blood were identified. This study describes host markers that may indicate, and potentially contribute to, differential post-treatment outcomes for malaria in young children versus adults.
寄生虫感染的免疫反应存在异质性，部分原因是宿主遗传、性别和年龄组的差异。在婴儿和幼儿中，持续的免疫成熟通常会导致对感染的易感性增加，以及对药物治疗的反应变化，从而增加并发症的风险。尽管已经确定了年龄对宿主细胞因子对恶性疟原虫感染反应的显著影响，但年龄对无并发症疟疾感染和抗疟治疗的影响仍知之甚少。
在马拉维一个自然感染疟疾阳性个体的队列中，采集了全血样本，这些个体患有非严重恶性疟（共 63 例，包括 34 例<2 岁的婴儿和幼儿，29 例>18 岁的成年人），在两个时间点评估了血液细胞因子水平和单核细胞和树突状细胞频率：急性感染和抗疟治疗后 4 周。对年龄组、性别和时间点的影响进行建模，并评估这些因素对感染和治疗结果的作用。
无论治疗时间点如何，在该人群中，年龄与整体血液血红蛋白显著相关，成年人的血红蛋白水平较高，而儿童的血浆一氧化氮代谢物、IL-10 和 TNF 水平较高。年龄对血红蛋白治疗反应有显著影响，治疗后儿童的血红蛋白水平升高，而成人的血红蛋白水平降低。此外，年龄对总寄生虫负荷、IFN-γ和 IL-12(p40)的治疗反应有显著的相关性，并且这些相关性与性别有关。年龄对髓样树突状细胞频率的总体水平和治疗反应也有显著的影响。此外，在每个年龄组内，结果显示年龄对配子体水平（Pfs16）、TNF 和一氧化氮代谢物的连续影响。
在一项对经历自然恶性疟感染并接受抗疟治疗的幼儿和成年人的临床研究中，确定了外周血感染和治疗反应的年龄相关特征。本研究描述了宿主标志物，这些标志物可能表明并可能有助于解释儿童与成人疟疾治疗后结果的差异。
