Community-based interventions to reduce mortality from neonatal infection

描述（由申请人提供）：本申请提供的证据表明，美国负责人和高级外国研究者在参与全球网络活动以及设计、实施和发表单中心和通用方案研究和临床试验方面具有既定的领导记录。在接下来的5年周期中，提出了两项关于疑似严重细菌感染婴儿抗生素治疗的严格设计的随机临床试验。感染是婴儿死亡的主要原因之一，约占全球新生儿死亡率的36%。目前世界卫生组织（WHO）对疑似严重细菌感染婴儿的治疗建议包括注射抗生素治疗，但在发展中国家的许多社区，静脉或肌肉注射抗生素的能力有限。由于到医院的机会有限，生病的婴儿往往不可能住院。即使在某些设施中，注射抗生素也很难管理。此外，感染或脓肿形成以及人类免疫缺陷病毒、肝炎或其他病原体的传播在发展中国家更为常见。口服抗生素方案对患有肺炎的较大婴儿和儿童有效，但对疑似严重细菌感染的新生儿和幼儿无效。世卫组织指导下的专家顾问建议评估仅口服抗生素方案，作为疑似严重细菌感染婴儿注射抗生素的替代方案。因此，迫切需要评估早期识别和创新但简单的抗生素方案治疗低收入和中等收入国家疑似严重细菌感染的幼儿的有效性。如果发现口服抗生素方案对疑似严重细菌感染的幼儿有效，则对疑似严重细菌感染的幼儿进行抗生素治疗可能会导致全球新生儿和婴儿死亡率和发病率的显著降低。拟议的研究人员团队将与NICHD和全球妇女和儿童健康研究网络的其他网站合作，设计，优先考虑，计划，实施，分析，解释和报告可能提高孕产妇和儿童生存率并减少重要发病率的创新随机试验和观察性研究。如果允许该研究中心继续参与全球网络，美国主要研究者、高级外国研究者以及赞比亚研究者和工作人员团队的资质和明确承诺，以及赞比亚政府、赞比亚大学和伯明翰亚拉巴马大学的充分认可将确保该研究中心的上级性能。

DESCRIPTION (provided by applicant): This application provides evidence that the U.S. Principal and the Senior Foreign Investigator have an established leadership record in participation in the Global Network activities as well as in the design, implementation, and publication of single site and common protocol studies and clinical trials. For the next 5 year cycle, two rigorously-designed randomized clinical trials of antibiotic treatment of infants with suspected serious bacterial infection are proposed. Infection is one of the main causes of death in infants, accounting for about 36% of neonatal mortality worldwide. Current World Health Organization (WHO) recommendations for the treatment of infants with suspected serious bacterial infection include injectable antibiotic therapy but there is limited capacity for intravenous or intramuscular antibiotic administration in many communities in developing countries. Hospitalization of ill infants is not possible frequently because of limited access to hospitals. Injectable antibiotics can be difficult to administer even in some facilities. Furthermore, infection or abscess formation as well as transmission of human immunodeficiency virus, hepatitis, or other pathogens is more common in developing countries. Oral antibiotic regimens have been an effective intervention in older infants and children with pneumonia but not in neonates and young infants with suspected serious bacterial infection. Expert consultants under the direction of WHO have recommended evaluating oral-only antibiotic regimes as alternatives to injectable antibiotics for infants with suspected serious bacterial infection. Thus, there is an urgent need to evaluate the effectiveness of early identification and innovative but simple antibiotic regimens to treat young infants with suspected serious bacterial infection in low and middle income countries. If an oral antibiotic regimen is found to be effective in young infants with suspected serious bacterial infection, antibiotic treatment to young infants with suspected serious bacterial infection may result in an important reduction in neonatal and infant mortality and morbidity worldwide. The proposed team of investigators will work with the NICHD and other sites of the Global Network for Women's and Children's Health Research to design, prioritize, plan, implement, analyze, interpret, and report innovative randomized trials and observational studies that are likely to improve maternal and childhood survival and reduce important morbidities. The qualifications and unequivocal commitment of the U.S. Principal Investigator, the Senior Foreign Investigator, and the team of investigators and staff in Zambia, as well as the full endorsement of the Government of Zambia, the University of Zambia, and the University of Alabama at Birmingham will ensure superior performance if this site is allowed to continue participation in the Global Network.