Feasibility study of LGG in HIV-exposed, breastfeeding infants in Tanzania.

描述(申请人提供)：尽管有证据表明益生菌可以改善胃肠道炎症和调节粘膜表面的免疫防御，但几乎没有人知道它们对艾滋病毒-1在儿科人群中传播的潜在影响。在撒哈拉以南非洲，2004年儿童中艾滋病毒-1新感染率超过70万；其中三分之一到一半是通过母乳喂养感染的。流行病学研究表明，与纯母乳喂养的婴儿相比，同时摄入感染艾滋病毒的母乳和补充食物或液体的婴儿感染艾滋病毒-1的风险显著更高。虽然其潜在机制(S)尚不清楚，但据推测，暴露于外来食物抗原或肠道病原体后，新生儿肠道内的炎症反应会增加粘膜通透性，从而促进艾滋病毒-1的渗透和复制。拟议的项目将确定对益生菌乳杆菌GG(LGG)进行随机、双盲对照研究的可行性，作为一种饮食干预措施，通过母乳喂养和混合喂养做法减少接触艾滋病毒-1的婴儿的胃肠道炎症。这项研究将在坦桑尼亚的达累斯萨拉姆与穆亨比利大学健康科学学院合作进行。我们将测试这样一种假设，即给接触艾滋病毒的母乳喂养的婴儿口服添加免疫球蛋白的粥可以减少肠道粘膜炎症，并有可能降低艾滋病毒-1传播的风险。我们将通过两个具体的目标来解决这一假设：第一，确定在传统玉米粥中给随机参加干预的婴儿服用LGG的可行性，第二，确定添加LGG的粥在减少胃肠道炎症和肠道病原体定植方面的有效性。这项研究的主要结果是降低了肠道炎症的两种粪便生物标志物--肿瘤坏死因子-α和钙保护素的水平。次要结果是能够收集关于婴儿喂养做法和接触肠道病原体的支持性数据，以及评估产妇艾滋病毒-1病毒载量和婴儿艾滋病毒-1状况。总而言之，这些数据将被用来指导对感染艾滋病毒的母乳喂养婴儿进行免疫球蛋白的大规模临床试验，以确定这一干预措施在减少艾滋病毒-1母婴传播方面的效果。如果有效，使用LGG的益生菌干预有可能显著减少因感染艾滋病毒-1和其他传染性肠道病原体而导致的婴儿死亡。利用传统食品提供益生菌提供了一种负担得起、文化上可接受和随时可再生的干预措施，并将适用于撒哈拉以南非洲资源有限的国家。

DESCRIPTION (provided by applicant): Despite evidence probiotics can ameliorate gastrointestinal inflammation and modulate immune defenses at mucosal surfaces, virtually nothing is known of their potential to impact transmission of HIV-1 in pediatric populations. In Sub-Saharan Africa, the rate of new HIV-1 infections among children exceeded 700,000 in 2004; from one-third to one-half of these infections were acquired by breastfeeding. Epidemiologic studies indicate that infants ingesting both HIV-infected breast milk and supplemental foods or fluids are at significantly higher risk of HIV-1 transmission compared to their exclusively breastfed counterparts. While the underlying mechanism(s) for this are unknown, it is presumed that induction of inflammatory responses in the newborn gut following exposure to foreign food antigens or enteric pathogens increases mucosal permeability, thereby facilitating HIV-1 penetration and replication. The proposed project will determine the feasibility of conducting a randomized, double-blinded controlled study of the probiotic Lactobacillus GG (LGG) as a dietary intervention to reduce gastrointestinal inflammation in infants exposed to HIV-1 through breastfeeding and mixed-feeding practices. This study will be conducted in Dar es Salaam, Tanzania in collaboration with Muhimbili University College of Health Sciences. We will test the hypothesis that oral administration of LGG-supplemented porridge to HIV-exposed, breastfeeding infants reduces intestinal mucosal inflammation and has the potential decrease the risk of HIV-1 transmission. We will address this hypothesis through two specific aims: the first to determine the feasibility of administering LGG in a traditional maize porridge to infants randomized to this intervention, and the second to determine the effectiveness of LGG-supplemented porridge in reducing gastrointestinal inflammation and colonization with enteric pathogens. The primary outcome of the study is a reduction in the levels of two fecal biomarkers for intestinal inflammation, TNF-alpha and calprotectin. Secondary outcomes are the ability to collect supportive data on infant feeding practices and exposure to enteropathogens, and to assess maternal HIV-1 viral load and infant HIV-1 status. Taken together, these data will be used to guide the development of a large-scale clinical trial of LGG in HIV-exposed, breastfeeding infants to determine the efficacy of this intervention in reducing HIV-1 mother-to-child transmission. If effective, probiotic intervention with LGG has the potential to significantly reduce infant deaths due to infection with HIV-1 and other infectious enteric pathogens. Utilizing a traditional food for probiotic delivery provides an intervention that is affordable, culturally accepted and readily renewable, and would be amenable for use in resource-constrained countries in Sub-Saharan Africa.