Anstey N M, Weinberg J B, Wang Z, Mwaikambo E D, Duffy P E, Granger D L
Tropical Medicine and International Health Unit, and Biostatistics Unit, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Am J Trop Med Hyg. 1999 Aug;61(2):253-8. doi: 10.4269/ajtmh.1999.61.253.
Age appears to influence not only the acquisition of clinical immunity to malaria but also the susceptibility to and clinical manifestations of severe malaria. Asymptomatic malaria-exposed Tanzanian children have high production of nitric oxide (NO) and universal expression of leukocyte NO synthase type 2 (NOS2), which may protect against disease. To determine the effects of age and parasitemia on NO production, we measured urine and plasma NO metabolites and leukocyte NOS2 expression in 45 fasting, asymptomatic, malaria-exposed children of different ages, stratifying parasitemia by thick film and polymerase chain reaction (PCR) analysis. Although NO production was significantly higher in thick film-positive children than in thick film-negative children, after adjusting for age and gender, we were unable to detect a difference in NO production in thick film-negative children between those who were PCR positive and PCR negative. The relationship between age and NO production was determined using a generalized additive model adjusted for the effects of gender and parasitemia. Production of NO using all three measures was highest in infancy, decreasing after the first year of life, and then increasing again after 5 years of age. This pattern of age-related NO production is the reverse of the pattern of age-related morbidity from cerebral malaria in coastal Tanzanian children. Elevated production of NO in both infants and older children may be related to age per se and malaria infection respectively, and may be one of the mediators of the anti-disease immunity found most commonly in these two age groups.
年龄似乎不仅会影响对疟疾临床免疫力的获得，还会影响对重症疟疾的易感性和临床表现。坦桑尼亚无症状且接触过疟疾的儿童一氧化氮（NO）产量高，且普遍表达白细胞型2一氧化氮合酶（NOS2），这可能起到预防疾病的作用。为了确定年龄和寄生虫血症对NO产生的影响，我们对45名不同年龄、空腹、无症状且接触过疟疾的儿童测量了尿液和血浆中的NO代谢产物以及白细胞NOS2表达，并通过厚涂片和聚合酶链反应（PCR）分析对寄生虫血症进行分层。尽管厚涂片阳性儿童的NO产量显著高于厚涂片阴性儿童，但在对年龄和性别进行校正后，我们未能检测出厚涂片阴性儿童中PCR阳性和PCR阴性者之间NO产量的差异。使用广义相加模型确定年龄与NO产生之间的关系，并对性别和寄生虫血症的影响进行校正。使用所有三种测量方法得出的NO产量在婴儿期最高，在1岁后下降，然后在5岁后再次上升。这种与年龄相关的NO产生模式与坦桑尼亚沿海地区儿童脑型疟疾的年龄相关发病模式相反。婴儿和大龄儿童中NO产量升高可能分别与年龄本身和疟疾感染有关，并且可能是在这两个年龄组中最常见的抗病免疫力的介导因素之一。
