Impact of Fascioliasis among Children in the Peruvian Highlands

描述(申请人提供)：肝片吸虫病是一种被忽视的人畜共患传染病，具有全球卫生重要性，特别是在秘鲁高地，那里的儿童流行率是世界上最高的之一。大多数片吸虫感染可能是亚临床感染，可能在很多年内都没有得到诊断。慢性肝片吸虫病的病例系列将感染与贫血和体重减轻联系在一起，这对儿童以后的认知发展和生产力具有毁灭性的后果。这些与片状吸虫有关的疾病的流行病学还不是很清楚。虽然慢性炎症被认为是共同的潜在机制，但这些并发症的标志物和临床过程还没有得到很好的描述。我们推测，亚临床肝片吸虫病是高度流行地区最常见的表现，是引起贫血和营养不良等寄生虫罕见并发症的原因。我们还假设慢性炎症是导致这些并发症的原因，新描述的标志物将有助于阐明肝片吸虫病的发病机制。为了验证这些假设，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，将对大量儿童进行肝片吸虫病、贫血和营养不良以及其他肠道蠕虫的筛查。一项确定贫血机制的病例对照研究将包括铁研究和炎症标记物(包括一种新描述的标记物，称为海普西丁，它在慢性病贫血中发挥关键作用)。将进行评估对营养的影响和与减肥相关的机制的研究(使用神经肽Y作为能量平衡负面变化的标志)。将进行一项为期一年的队列研究，以评估疾病的严重性、贫血和营养不良对治疗肝片吸虫病和其他蠕虫的反应，以及与肝片吸虫病相关的标志物。我们的结果将提供重要的流行病学和病理生理学信息，增加对片吸虫相关性贫血和营养不良的了解。将这些信息与目前的疾病干预措施相结合，将导致更好地规划和使用资源。但最重要的是，将强调早期诊断和治疗肝片吸虫病的必要性，以避免儿童出现长期并发症。

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.