Prevention of neonatal infection in the Indian community setting using probiotics

描述(申请人提供)：新生儿败血症仍然是世界各地新生儿期发病率和死亡率的主要原因之一。印度是世界上人口最多的国家之一，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迅速增长的抗菌素耐药性问题，这越来越限制了医疗保健提供者的治疗选择。为了处理这些关键问题，在NICHD全球网络的支持下，我们对出生60天以下的婴儿进行了基于人群的败血症监测，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(属于正常肠道微生物区系一部分的友好细菌菌株)在特定的胃肠道状况下具有治疗和预防作用，可能对包括败血症在内的新生儿状况也具有治疗和预防作用。在我们的印度合作中心，我们使用一种定义明确的、商业化的植物乳杆菌补充剂(FDA在美国注册)进行了一项以医院为基础的研究，证明了这种菌株的安全性和定植能力，当口服给1个月和2个月的新生儿时，革兰氏(-)细菌载量(菌落计数)相应减少。相反，包括乳杆菌在内的革兰氏(+)细菌载量在1个月和2个月时较高，并持续到6个月。基于体外和动物研究，表明该菌株和类似的菌株阻止细菌跨肠粘膜的移位，我们推测，该菌株的使用将有助于更快地产生正常的肠道微生物群，并减少肠道细菌的移位，从而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，我们提议对223个已知新生儿败血症发生率较高的农村的8442名新生儿进行一项双盲、随机、对照试验。一个成功的结果将提供一种简单、当地可用和廉价的预防性疗法，极大地减少印度和其他发展中国家的新生儿感染，进而降低婴儿死亡率。

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.