Combatting AntiMicrobial Resistance in Africa Using Data Science (CAMRA)

利用数据科学对抗非洲的抗菌素耐药性 (CAMRA)

• 批准号: 10316285
• 负责人: Derrick E Fouts
• 金额: $ 114.59万
• 依托单位: REDEEMER'S UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10316285
• 关键词: Acute; Address; Africa; African; Aminoglycosides; Ampicillin Resistance; Antibiotics; Antimicrobial Resistance; Archives; Area; Awareness; Bacteria; Bacterial Infections; Bacterial Proteins; Bioinformatics; Biomedical Engineering; Blood; Blood Circulation; Caring; Case Fatality Rates; Cause of Death; Child; Chloramphenicol; Clinical; Collection; Communities; Comparative Study; Complex; Country; Dangerousness; Data; Data Science; Demographic and Health Surveys; Diagnostic; Diagnostic Services; Diarrhea; Disease Outbreaks; Enrollment; Enterobacteriaceae; Etiology; Evaluation; Extended-spectrum β-lactamase; Genomics; Genotype; Geography; Goals; Growth; Healthcare; High Prevalence; Human; Human Development; Human Resources; Incubators; Individual; Infection; Knowledge; Laboratories; Live Birth; Maternal Mortality; Microbe; Microbiology; Molecular; Molecular Epidemiology; Morbidity - disease rate; Multi-Drug Resistance; Multiple Bacterial Drug Resistance; Newborn Infant; Nigeria; Nigerian; Pathway interactions; Periodicity; Pharmacy facility; Phenotype; Pneumonia; Population; Prevalence; Prevention strategy; Program Development; Research Proposals; Resources; Rwanda; Salmonella typhi; Scientist; Screening procedure; Sentinel; Sepsis; Site; Sputum; Stream; Syndrome; Tobramycin; Training; Treatment Efficacy; Trimethoprim-Sulfamethoxazole; United Nations; Urine; Veterinarians; War; Woman; age group; aged; antimicrobial; antimicrobial peptide; bacterial resistance; bactericide; carbapenem resistance; clinical care; clinical epidemiology; comparative; health care service; indexing; inflammatory marker; mortality; multidisciplinary; novel; pathogenic bacteria; portability; programs; resistance gene; resistant Klebsiella pneumoniae; transmission process; trend

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.

细菌感染非常普遍，导致发病率和死亡率显着增加 涵盖所有年龄组，但由于适当的微生物诊断服务是非 存在或非常有限，确定具体的病因和真实的患病率 抗菌素耐药性 (AMR) 是非洲面临的一项重大挑战，但客观数据有限。 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 (S. Typhi) 患病率高达 45% 多重耐药性的普遍存在，b) 超广谱 β-内酰胺酶的普遍存在- 产生肠杆菌科 (ESBL-E) 血流感染，c) 母体定植 女性分娩时的 ESBL-E 与她们的高全因发病率和死亡率相关。 新生儿与未接触 ESBL 的婴儿相比，以及 d) 周期性爆发 新生儿病房中耐碳青霉烯类肺炎克雷伯菌败血症的病死率 我们对 2,750 种不同物种中的约 500 种进行了初步分子表征。 我们收集的血液细菌分离株此外，我们还可以获得一系列的细菌。 来自我们尼日利亚哨点实验室的 2,500 多种血液、痰液和尿液的临床分离物 和卢旺达，这是我们与 AMR 基因相关的独特观察结果的一部分。 我们在存档的分离株中确定的这些构成了本研究提案的基础。 该应用程序的总体策略侧重于三个主题领域：1）。 对存档和当代临床分离株进行表型和基因型研究，以了解趋势 AMR 和传播动力学 2) 纳入急性炎症标志物。 严重的细菌感染和耐药细菌的基因产物进入便携式筛查 临床护理工具和 3) 探索氨基糖苷类药物（妥布霉素）的潜在益处。 与抗菌肽缀合，增强对多种药物的杀菌活性 我们组建了一支由临床和耐药肠杆菌组成的多学科团队。 分子微生物学家、赞助人、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、西非以及其他国家实施该项目 东非卢旺达成功提供具有非洲地理代表性的数据。 完成该计划后，我们将利用细菌数据科学平台 基因组学和抗菌素耐药性，以提高对非洲抗菌素耐药性范围的认识， 提供优化抗生素经验使用的新途径，并培训了少数年轻人 细菌基因组学和生物信息学领域的非洲科学家。