Impact of Fascioliasis among Children in the Peruvian Highlands

描述（由申请人提供）：片吸虫病是一种被忽视的人畜共患感染，具有全球卫生重要性，特别是在秘鲁高地，儿童患病率是世界上最高的。大多数片形吸虫感染可能是亚临床的，并且可以多年未被诊断出来。慢性筋膜吸虫病的一系列病例与贫血和体重减轻有关，这对儿童以后的认知发展和生产能力造成毁灭性的后果。与片形吸虫相关的这些疾病的流行病学尚不清楚。虽然慢性炎症被认为是常见的潜在机制，但这些并发症的标志物和临床过程尚未得到很好的描述。我们假设，亚临床片形吸虫病是高流行地区最常见的表现，并导致很少归因于寄生虫的并发症，如贫血和营养不良。我们还假设慢性炎症是这些并发症的原因，新描述的标记物将揭示片形吸虫病的致病机制。为了检验这些假设，我们打算对秘鲁南部高地儿童的贫血和营养状况进行全面评估。通过横断面研究，将对大量儿童进行片形吸虫病、贫血和营养不良以及其他肠道蠕虫的筛查。确定贫血机制的病例对照研究将包括铁研究和炎症标志物（包括新描述的hepcidin标志物，它在慢性疾病贫血中起关键作用）。研究将评估对营养的影响以及与减肥相关的机制（使用神经肽Y作为能量平衡负转移的标志）。将进行一项为期一年的队列研究，以评估疾病的严重程度、贫血和营养不良对筋膜吸虫病和其他蠕虫治疗的反应以及与筋膜吸虫病相关的标志物。我们的研究结果将为了解片形吸虫相关性贫血和营养不良提供重要的流行病学和病理生理学信息。将这些信息与目前的疾病干预措施结合起来，将有助于更好地规划和利用资源。但最重要的是，将强调早期诊断和治疗筋膜吸虫病的必要性，以避免儿童的长期并发症。

DESCRIPTION (provided by applicant): Fascioliasis is a neglected zoonotic human infection with global health importance, especially in the Peruvian highlands where the prevalence in children is among the highest in the world. Most infections by Fasciola are likely to be subclinical and can remain undiagnosed for many years. Case series of chronic fascioliasis have associated the infection with anemia and weight loss, which carry devastating consequences for children's cognitive development and productivity later in life. The epidemiology of these conditions associated with Fasciola is not well understood. Although, chronic inflammation has been postulated as the common underlying mechanism, the markers and clinical course of these complications have not been well described. We hypothesize that subclinical fascioliasis is the most common presentation in highly endemic areas and is responsible for complications rarely attributed to the parasite like anemia and malnutrition. We also hypothesize that chronic inflammation is responsible for these complications and that newly described markers will shed light into fascioliasis pathogenic mechanisms. To test these hypotheses we intend to perform a comprehensive evaluation of anemia and nutrition among children in the southern highlands of Peru. Through cross-sectional studies a large number of children will be screened for fascioliasis, anemia and malnutrition, and other intestinal helminths. A case-control study to define the mechanism of anemia will include iron studies and markers of inflammation (including a newly described marker called hepcidin that play a key role in anemia of chronic disease). Studies to evaluate the impact on nutrition and the mechanisms associated with weight lost will be performed (using Neuropeptide Y as a marker for negative shifts in energy balance). A one year cohort study to evaluate the severity of illnesses, response of anemia and malnutrition to treatment of fascioliasis and other helminths, and markers associated with fascioliasis will be performed. Our results will provide important epidemiologic and pathophysiologic information adding to the understanding of Fasciola associated anemia and malnutrition. The integration of this information with current disease interventions will lead to better planning and use of resources. But most importantly, will stress the need for early diagnosis and treatment of fascioliasis to avoid long term complications in children.