EAEC Infection in HIV-infected Patients in Haiti

描述(由申请人提供)：肠聚集性大肠杆菌(EAEC)是在资源有限的情况下感染人类免疫缺陷病毒(HIV)患者的一种新的慢性腹泻原因。感染EAEC与儿童营养不良和体重减轻有关。在艾滋病毒感染者中，即使接受了抗逆转录病毒疗法(ART)，营养不良和体重减轻也是死亡率的重要预测因素。确定导致艾滋病毒感染者营养不良和体重减轻的因素至关重要。EAEC可能起到一定作用，但目前EAEC感染对接受抗逆转录病毒治疗的HIV感染者的影响尚不清楚，也没有既定的管理策略。我最近在太子港的一项病例对照研究中评估了患者的粪便样本。EAEC首次成为海地艾滋病腹泻患者最常见的病原体。此外，在治疗的第一个月，EAEC与体重减轻有关。这项拟议的研究将仔细检查开始抗逆转录病毒治疗的艾滋病毒感染成人中的EAEC感染情况。我推测，与未感染EAEC的腹泻患者和未感染EAEC的腹泻患者相比，感染EAEC的腹泻患者的临床结局会更差。主要结果将是每组患者在一个月内体重减轻的百分比，这是死亡率的重要预测因素。次要结果将包括存活到48周。此外，我还将评估细菌和患者的基因分型是否与结果相关。评估的因素将包括编码细菌毒力因子的基因的流行率、细菌生物被膜的产生、使患者对EAEC感染易感性的单核苷酸多态(SNP)的流行率，以及患者产生的肠道炎症标志物。在获奖的头三年，我将继续接受评估细菌病因和宿主对肠道感染反应的培训，以及在资源有限的情况下进行临床试验设计和研究伦理方面的培训。发起人和共同发起人在这些领域拥有丰富的经验，并将指导这次培训。同时，我将在与海地同事已建立的关系的基础上，建立和开展拟议的研究。这项研究的结果将确定在一个资源有限的国家，EAEC感染对艾滋病毒感染者的影响，并为制定临床战略提供信息。

DESCRIPTION (provided by applicant): Enteroaggregative Escherichia coli (EAEC) is an emerging cause of chronic diarrhea in patients infected with human immunodeficiency virus (HIV) in resource-limited settings. Infection with EAEC is associated with malnutrition and weight loss in children. In HIV-infected patients, even with antiretroviral therapy (ART), malnutrition and weight loss are important predictors of mortality. Establishing factors that contribute to malnutrition and weight loss in HIV-infected patients is essential. EAEC may play a role, but currently the impacts of EAEC infection on HIV-infected patients treated with ART are not clear nor are there established management strategies. I recently evaluated stool samples from patients in a case-control study in Port au Prince. For the first time, EAEC was the most commonly identified pathogen in Haitian AIDS patients with diarrhea. In addition, EAEC was associated with weight loss in the first month of therapy. The proposed study will carefully examine EAEC infection in HIV-infected adults initiating ART. I hypothesize that patients with diarrhea who are infected with EAEC will have worse clinical outcomes when compared to patients with diarrhea but uninfected with EAEC and to those without diarrhea. The primary outcome will be % of patients in each group with weight loss at one month, an important predictor of mortality. Secondary outcomes will include survival to 48 weeks. In addition, I will evaluate whether bacterial and patient genotypes correlate with outcomes. The factors evaluated will include the prevalence of genes encoding bacterial virulence factors, the production of bacterial biofilm, the prevalence of single nucleotide polymorphisms (SNP) that confer susceptibility to EAEC infection in the patients, and patient production of intestinal inflammatory markers. In the first three years of the award, I will pursue training in the evaluation of bacterial causes and host responses to enteric infections and in clinical trial design and research ethics in resource-limited settings. The sponsor and cosponsor have significant experience in these areas and will guide this training. Concurrently, I will build on established relationships with Haitian colleagues to set up and carry out the proposed study. The results of the study will establish the impact of EAEC infection on HIV-infected patients in a resource-limited country and inform the development of clinical strategies to manage it.