Prevention of neonatal infection in the Indian community setting using probiotics

描述（由申请人提供）：新生儿败血症仍然是世界各地新生儿期发病和死亡的主要原因之一。印度是世界上人口最多的国家之一，但仍在与极高的婴儿和新生儿死亡率作斗争。败血症占社区出生婴儿死亡的50%（占医院出生婴儿死亡的20%）。与此密切相关的是一个新兴的问题，抗菌素耐药性，这是越来越多地限制医疗保健提供者的治疗选择。为了解决这些关键问题，在NICHD全球网络的支持下，我们对60天以下婴儿的败血症进行了基于人群的监测，并记录了90%以上的死亡是由于迟发性败血症。实验室和临床数据表明，益生菌（正常肠道微生物菌群的一部分，友好的细菌菌株）的管理在特定的胃肠道疾病中具有治疗和预防作用，并可能在新生儿疾病，包括败血症。使用定义明确的、市售的植物乳杆菌补充剂（在美国FDA注册），我们在印度的合作中心进行了一项以医院为基础的研究，该研究证明了新生儿口服该菌株的安全性和定殖能力，在第1个月和第2个月时，革兰氏（-）细菌负荷（菌落计数）相应减少。相反，包括乳酸杆菌在内的革兰氏（+）细菌负荷在第1个月和第2个月较高，并持续至第6个月。基于体外和动物研究，这表明，这种菌株和类似的菌株阻止细菌移位穿过肠粘膜，我们假设，这种菌株的管理将有助于更快地产生正常的肠道微生物菌群，并减少细菌从肠道的移位，相应地降低迟发性新生儿败血症的发生率。为了验证这一假设，在目前的拨款中，我们建议在223个已知新生儿败血症发病率高的农村村庄的8442名新生儿中进行一项双盲、随机、对照试验。一个成功的结果将提供一个简单的，当地可用的，廉价的预防性治疗，大大减少新生儿感染，从而降低印度和其他发展中国家的婴儿死亡率。

DESCRIPTION (provided by applicant): Neonatal sepsis continues to be one of the major causes of morbidity and mortality in the newborn period around the world. India, with one of the world's largest populations, continues to struggle with extremely high infant and neonatal mortality rates. Sepsis accounts for 50% of deaths among community- born (and 20% of mortality among hospital-born) infants. Closely linked with this is a burgeoning problem with antimicrobial resistance, which is increasingly restricting the therapeutic options for medical care providers. To deal with these critical issues, under the auspices of the NICHD Global Network, we have conducted population-based surveillance of sepsis in babies up to 60 days of age and have documented that more than 90% of deaths are due to late onset sepsis. Laboratory and clinical data suggest that administration of Probiotics (friendly bacterial strains that are part of the normal intestinal microflora) has a therapeutic and prophylactic role in specific gastrointestinal conditions, and, possibly, in neonatal conditions including sepsis. Using a well-defined, commercially available supplement of Lactobacillus plantarum (FDA registered in the U.S.), we have performed a hospital- based study at our Indian collaborating centers that has demonstrated safety and colonizing ability of this strain when administered orally to neonates with a corresponding reduction in Gram (-) bacterial load (colony count) at month 1 and 2. To the contrary, Gram (+) bacterial load including Lactobacillus was higher at month 1 and 2 and continued through month 6. Based on in vitro and animal studies, which suggest that this and similar strains block bacterial translocation across the intestinal mucosa, we hypothesize that administration of this strain will facilitate more rapid generation of normal intestinal microflora, and reduced translocation of bacteria from the intestine with a corresponding decrease in the rate of late onset neonatal sepsis. To test this hypothesis, in the current grant, we are proposing to conduct a double blind, randomized, controlled trial of this preparation in 8442 newborn infants in 223 rural villages known to have high rates of neonatal sepsis. A successful outcome would provide a simple, locally available, and inexpensive preventive therapy for dramatically reducing neonatal infections, and in turn, infant mortality in India and other developing countries.