EAEC Infection in HIV-infected Patients in Haiti

描述（由申请方提供）：肠聚集性大肠杆菌（EAEC）是在资源有限的环境中感染人类免疫缺陷病毒（HIV）的患者慢性腹泻的一种新的病因。EAEC感染与儿童营养不良和体重减轻有关。在艾滋病毒感染者中，即使接受抗逆转录病毒治疗，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可能发挥作用，但目前EAEC感染对接受ART治疗的HIV感染患者的影响尚不清楚，也没有既定的管理策略。我最近评估了Au Prince港一项病例对照研究中患者的粪便样本。EAEC首次成为海地艾滋病腹泻患者中最常见的病原体。此外，EAEC与治疗第一个月的体重减轻有关。拟议的研究将仔细检查EAEC感染的艾滋病毒感染的成人开始ART。我假设，腹泻患者感染EAEC将有更糟糕的临床结果相比，腹泻患者，但未感染EAEC和那些没有腹泻。主要结局是每组中1个月时体重减轻的患者百分比，这是死亡率的重要预测因素。次要结局将包括48周的生存期。此外，我将评估细菌和患者基因型是否与结果相关。评价的因素将包括编码细菌毒力因子的基因的流行率、细菌生物膜的产生、赋予患者对EAEC感染易感性的单核苷酸多态性（SNP）的流行率以及患者肠道炎症标志物的产生。在该奖项的前三年，我将在资源有限的环境中进行细菌原因和肠道感染宿主反应评估以及临床试验设计和研究伦理方面的培训。主办方和共同主办方在这些领域拥有丰富的经验，并将指导本次培训。与此同时，我将利用与海地同事建立的关系，建立和开展拟议的研究。该研究的结果将确定EAEC感染对资源有限国家艾滋病毒感染患者的影响，并为制定临床策略提供信息。

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.