Combatting AntiMicrobial Resistance in Africa Using Data Science (CAMRA)

细菌感染非常普遍，对发病率和死亡率有很大影响。 但因为适当的微生物诊断服务不是 存在或非常有限，确定特定的病原体和真实的流行情况 在非洲，抗菌素耐药性(AMR)是一个重大挑战，因为那里的客观数据有限。 来自非洲人口最多的国家尼日利亚的初步观察包括 A)伤寒沙门氏菌高流行率(45%) 多药耐药的流行，b)超广谱β-内酰胺酶的高流行- 产生肠杆菌科(ESBL-E)血液感染，c)母体定植 产后妇女的ESBL-E与其高全因发病率和死亡率有关 新生儿与未暴露于ESBL的婴儿的比较和d)周期性暴发 新生儿病房耐碳青霉烯类肺炎克雷伯菌败血症，病死率为 高达45%。我们已经初步掌握了2750种不同物种中约500种的分子特征 我们收集的血液细菌分离物。此外，我们还可以访问一组 来自尼日利亚哨兵实验室的2500多个血液、痰和尿液临床分离株 和卢旺达，这两个国家有部分的特点。我们对AMR基因的独特观察 我们在存档中确定的菌株构成了这项研究建议的基础。我们的 本应用的总体策略集中在三个主题领域：1)。比较 对存档和当代临床分离株的表型和基因分型研究以提供趋势信息 在AMR和传播动力学方面。2)急性炎症标志物的掺入 将严重细菌感染和基因产物从耐药菌转入便携式筛查 临床护理的工具和3)。探索氨基糖苷(妥布霉素)的潜在益处 偶联抗菌肽增强对多种药物的杀菌活性 耐药肠杆菌。我们已经组建了一个多学科的临床和医疗团队 分子微生物学家、临床医生、生物医学工程师、环境微生物学家、 兽医和实业家在尼日利亚、西非以及 卢旺达，东非，提供具有非洲地理代表性的数据。成功后 这个项目的完成，我们将利用细菌的数据科学平台 基因组学和抗菌素耐药性，以提高对非洲AMR范围的认识， 为优化抗生素的经验性使用提供了新的途径，并培训了少数年轻人 细菌基因组学和生物信息学方面的非洲科学家。

Bacterial infections are highly prevalent and contribute significantly to morbidity and mortality across all age-groups but because appropriate microbiologic diagnostic services are non- existent or very limited, ascertaining the specific etiologic agents and the true prevalence of antimicrobial resistance (AMR) is a major challenge in Africa, where objective data is limited. Preliminary observations from Nigeria, the most populous country in Africa include the following; a) High prevalence of Salmonella enterica serovar Typhi (S. Typhi) with 45% prevalence of multidrug resistance, b) High prevalence of Extended Spectrum β-Lactamase- producing Enterobacteriaceae (ESBL-E) blood stream infections, c) Maternal colonization by ESBL-E in women at delivery is associated with high all-cause morbidity and mortality in their newborn babies compared to ESBL-unexposed babies and d) Periodic outbreaks of carbapenem-resistant Klebsiella pneumoniae sepsis in newborn units with case fatality rates as high as 45%. We have preliminary molecular characterization of about 500 of the 2,750 diverse bloodstream bacterial isolates in our collection. In addition, we have access to a collection of over 2,500 clinical isolates of blood, sputum and urine from our sentinel laboratories in Nigeria and Rwanda that are partially characterized. Our unique observations related to AMR genes that we have identified in our archived isolates form the basis for this research proposal. Our overall strategy in this application focuses on three thematic areas: 1). Comparative phenotypic and genotypic studies of archived and contemporary clinical isolates to inform trends in AMR and dynamics of transmission. 2) Incorporation of acute inflammatory markers of serious bacterial infection and gene products from resistant bacteria into a portable screening tool for clinical care and 3). Explore the potential benefit of an aminoglycoside (Tobramycin) conjugated to an antimicrobial peptide for enhanced bactericidal activity against multi-drug resistant enterobacteriales. We have assembled a multidisciplinary team of clinical and molecular microbiologists, clinicians, biomedical engineers, environmental microbiologists, veterinarians, and industrialists to implement this project in Nigeria, West Africa and also Rwanda, East Africa to provide data with geographic representation for Africa. Upon successful completion of this program, we would have utilized the data science platform for bacteria genomics and antimicrobial resistance to raise awareness on the scope of AMR in Africa, provide novel pathways for optimizing empiric use of antibiotics and trained a handful of young African scientists in bacterial genomics and bioinformatics.