REASEARCH PROJECT 2: Mycotoxin Biomarkers and Children's Health in Africa (Wild)

撒哈拉以南非洲的儿童发病率和死亡率很高， 5岁以下儿童和每1 000名活产死亡175人，而工业化国家每1 000名活产死亡6人。 nations.大多数儿童死亡和发病是由于传染病，特别是腹泻， 肺炎和疟疾。这些问题与贫困有关，包括数量不足和质量差 粮食短缺导致营养不良率很高。事实上，营养不足和增长步履蹒跚一直是 被确定为约50%与传染病有关的儿童死亡的根本原因 在这个地区。在我们之前的工作中，我们发现黄曲霉毒素生物标志物水平与 西非儿童的生长迟缓;此外，有证据表明， 生物标志物水平很高因此，从饮食中接触这种真菌毒素可能会对 儿童发病率和死亡率。该项目的第一个目标是描述 真菌毒素暴露在生命早期（产前和产后），以生长蹒跚和健康结果。我们将测试 黄曲霉毒素暴露的生物标志物和肠道通透性之间的关联，作为是否 黄曲霉毒素可通过这种机制影响生长。玉米是超过50%的美国人的主要主食。 在西非的人群中，经常受到黄曲霉毒素和另一类真菌毒素的共同污染， 伏马菌素因此，第二个项目目标是验证伏马菌素暴露生物标志物， 评价黄曲霉毒素和伏马菌素对儿童生长的联合作用。最后，我们将进行采后 采用低技术方法对玉米进行干预研究， 减少人类接触这些环境毒素，包括通过玉米为基础的断奶食品， 对幼儿的霉菌毒素负担有很大影响。总的来说，这些研究将相互联系 与项目1中的生物标志物研究相结合，为靶向化学预防的应用奠定基础 项目4中描述的策略。

Child morbidity and mortality is high in sub-Saharan Africa with some 4.5 million deaths annually among children aged <5 years and 175 deaths per 1000 live births compared to 6 deaths per 1000 in industrialized nations. The majority of the childhood mortality and morbidity is due to infectious diseases, notably diarrhea, pneumonia and malaria. These problems are associated with poverty, including insufficient and poor quality food resulting in a high prevalence of malnutrition. Indeed under-nutrition and growth faltering has been identified as an underlying cause of around 50% of the deaths associated with infectious diseases in children in this region. In our previous work we found a strong association between aflatoxin biomarker levels and growth faltering in West African children; in addition, there was evidence of altered immunity in individuals with high biomarker levels. Dietary exposure to this mycotoxin may therefore make a significant contribution to childhood morbidity and mortality. The first goal of this project is to characterize the contribution of mycotoxin exposure early in life (pre- and post-natal) to growth faltering and health outcomes. We will test for an association between biomarkers of aflatoxin exposure and intestinal permeability as a first test of whether aflatoxin may affect growth via this mechanism. Maize is the main dietary staple for over 50% of the population in West Africa and is frequently co-contaminated with aflatoxins and another class of mycotoxins, the fumonisins. A second project goal is therefore to validate fumonisin exposure biomarkers to permit an evaluation of the combined effects of aflatoxins and fumonisins on child growth. Finally we will conduct postharvest intervention studies on maize using low technology approaches to assess their effectiveness in reducing human exposure to these environmental toxins, including via maize-based weaning foods that contribute much to the mycotoxin burden in young children. Collectively these studies will collaboratively link with biomarker research in Project 1 and lay the groundwork for application of targeted chemoprevention strategies described in Project 4.