Toward Rapid, Non-Invasive, Highly Sensitive, Multiplex Detection of Respiratory Pathogens

实现呼吸道病原体的快速、非侵入性、高灵敏度、多重检测

• 批准号: 9005094
• 负责人: Jane HIll
• 金额: $ 25.24万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-10 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9005094
• 关键词: Acute; Address; Adenoviruses; Adult; Affect; Age; Animal Model; Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotic susceptibility; Bacterial Infections; Bacterial Pneumonia; Biological Markers; Breath Tests; Bronchoalveolar Lavage; Cause of Death; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinic; Clinical; Clinical assessments; Communicable Diseases; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Engineering; Etiology; Evaluation; Exhalation; Fever; Generations; Haemophilus influenzae; Health; Human; Human Development; Immune system; Infection; Infectious Agent; Influenza A virus; Klebsiella pneumonia bacterium; Legionella pneumophila; Life; Lung; Measurable; Measures; Mission; Molecular; Monitor; Moraxella (Branhamella) catarrhalis; National Institute of Allergy and Infectious Disease; Organism; Outcome; Pathogen detection; Patients; Phenotype; Pneumonia; Population; Production; Pseudomonas aeruginosa; Public Health; Research; Research Project Grants; Resistance profile; Respiratory System; Respiratory Tract Infections; Respiratory syncytial virus; Rodent; Rodent Model; Sampling; Schools; Series; Specificity; Sputum; Staphylococcus aureus; Streptococcus pneumoniae; Techniques; Technology; Time; United States National Institutes of Health; Vermont; Viral; Virus Diseases; Work; base; clinically relevant; co-infection; improved; innovation; interest; mouse model; multiplex detection; novel; novel strategies; outcome forecast; pathogen; personalized diagnostics; public health relevance; rapid diagnosis; research study; respiratory; response; sample collection; tool

 DESCRIPTION (provided by applicant): Current clinical diagnostic methods for pneumonia typically take days or weeks and always require a sample from the patient, typically sputum. If sputum cannot be produced, it can sometimes be induced or lung lavage can be taken, both invasive techniques. Pneumonia is still one of the world's leading causes of death for children under the age of 5 according to the WHO and one of the top killers for adults in the USA, according to the CDC. Hence, there is a critical need for improved diagnostic tools to detect lung infections. Research groups at Dartmouth's Thayer School of engineering and the Vermont Lung Center have developed a technique allowing for rapid, non-invasive diagnosis of airway infections by analyzing infection-specific volatiles in the exhaled breath for singular infections, which can generate a diagnosis within minutes. The proposed work will complete the remaining experiments necessary before this technology is taken to a human population. The hypothesis is that that exhaled breath volatiles can be used to diagnose infections of the lung, and specifically, to distinguish between different pathogens, even during co-infection, for acute febrile illnesses. The hypothesis will be addressed in two specific aims: SA1: To determine whether breath volatile molecules can be used to distinguish between respiratory bacterial infections during clinical-relevant scenarios in a murine model. These experiments will demonstrate that a subset of breath molecules reflect infection etiology. The validity and specificity of the approach will be determined using confounding scenarios such as bacterial co-infection (in the lung and elsewhere) as well as during antibiotic treatment. This aim will also demonstrate determination of antibiotic susceptibility using breath for two organisms of high clinical interest (K. pneumoniae and S. aureus). SA2: To establish the utility of breath volatile molecules to distinguish between viral and bacterial infections. It will be determined how bacterial and viral co-infection affects the diagnostic precision of the exhaled breath analysis. Using influenza A virus, adenovirus and respiratory syncytial virus, it will be demonstrated that the immune system response to viral infection leads to the generation of molecules that can be detected in the breath and are diagnostic of infection etiology. All bacterial and viral experiment will use known human pathogens and will take place in well-developed animal models. The research in this proposal is innovative because it utilizes the best tools currently available to measure breath molecules in a systematic series of clinically-relevant experimental scenarios. The outcomes will represent a robust and substantial step towards a novel conceptual system for respiratory pathogen detection. The data from this study is expected to support forthcoming studies in humans and the development of an analytical device for use in the clinic. Ultimately, the technology shows promise for radically improved patient diagnosis, monitoring, and prognosis.