Prevention of neonatal infection in the Indian community setting using probiotics

使用益生菌预防印度社区环境中的新生儿感染

• 批准号: 7433325
• 负责人: PINAKI PANIGRAHI
• 金额: $ 44.7万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7433325
• 关键词: Accounting; Address; Age; American Type Culture Collection; Animals; Antimicrobial Resistance; Attention; Bacteria; Bacterial Translocation; Bioinformatics; Caring; Cessation of life; Clinical; Clinical Data; Clinical Microbiology; Communities; Condition; Core Facility; Count; Country; Daily; Data; Data Analyses; Data Coordinating Center; Developed Countries; Developing Countries; Disease; Double-Blind Method; Drops; End Point; Epidemiologist; Generations; Government; Grant; Home environment; Hospitals; Human Resources; In Vitro; Incidence; India; Infant; Infant Mortality; Infection; International; Intestinal Mucosa; Intestines; Laboratories; Lactobacillus; Lactobacillus plantarum; Life; Link; Marketing; Maryland; Measures; Medical; Medical Surveillance; Monitor; Monitoring Clinical Trials; Morbidity - disease rate; Mothers; National Institute of Child Health and Human Development; Neonatal; Neonatal Mortality; Newborn Infant; Oral; Oral Administration; Outcome; Physicians; Population; Preparation; Prevention; Preventive; Probiotics; Provider; Randomized Controlled Trials; Rate; Research Design; Research Personnel; Risk Factors; Role; Role playing therapy; Rural; Safety; Sepsis; Services; Site; System; Testing; Therapeutic; Training; United States; United States Food and Drug Administration; Universities; Week; Weight Gain; base; cofactor; concept; day; design; gastrointestinal; mortality; neonate; programs; prophylactic; prospective; randomized placebo controlled trial

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.

描述（由申请人提供）：新生儿败血症仍然是全球新生儿时期发病和死亡率的主要原因之一。印度是世界上最大的人口之一，他继续以极高的婴儿和新生儿死亡率挣扎。败血症占社区出生（医院出生中死亡率的20％）死亡的50％。与此密切相关的是抗菌耐药性的新兴问题，这越来越多地限制了医疗服务提供者的治疗选择。为了解决这些关键问题，在NICHD全球网络的主持下，我们已经对60天大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（属于正常肠道菌群的友好细菌菌株）在特定的胃肠道情况下具有治疗性和预防作用，并且可能在包括败血症在内的新生儿条件下。我们使用植物乳杆菌的定义明确，可商购的补充剂（在美国注册），我们在印度的合作中心进行了基于医院的研究，该研究表明，当对新生儿的Neonation口头施用该菌株的安全性和殖民能力，并在gram（colam locarony in Coled（ - collam）中均纳入新生儿（+），在1月和2个月份中均为1和2。基于体外和动物研究，乳杆菌在第1个月和第2个月较高，并且持续到第6个月。这表明这种菌株阻止了整个肠粘膜的细菌易位，我们假设该菌株的给药将有助于更快地产生正常的肠菌株，并降低了与小细胞相对多的疾病的衰减率降低的衰落率，该疾病的衰落率是相应的。为了检验这一假设，在当前的赠款中，我们提议在223个已知有新生儿败血症发生率高的农村村庄中的8442名新生婴儿中对这项制剂进行双盲，随机对照试验。成功的结果将提供一种简单，本地可用且廉价的预防疗法，可大大减少新生儿感染，进而在印度和其他发展中国家的婴儿死亡率。