Evaluation of MDR-TB Treatment Strategies in Lima, Peru

描述（由申请人提供）：Sonya Shin，医学博士已在布里格姆妇女和马萨诸塞州综合医院完成传染病奖学金。自1996年以来，她一直担任秘鲁耐多药结核病项目的临床顾问。Paul Farmer、Edward Nardell和Michael Hughes博士将担任本研究的导师。Shin博士计划发展她作为独立临床研究者的技能，同时获得流行病学和决策分析研究方面的进一步正式培训。她最终希望在结核病临床试验和项目管理方面追求独立的职业生涯。 哈佛医学院的几个地点将为候选人提供研究环境。布莱根妇女医院社会正义和健康不平等部门以及哈佛公共卫生学院将为候选人的专业发展提供充足的环境。Socios en Salud和秘鲁利马卫生部将提供额外的监督和资源。 耐多药结核病仍然是全球健康威胁。使用简单的方法快速鉴定耐多药结核菌株可能会加快治疗反应。本研究的具体目的是比较两种快速药敏试验（DST）方法，荧光素酶报告分枝杆菌噬菌体（LRM）法和硝酸盐还原酶比色法（Griess）的敏感性和特异性，传统的DST;和2）比较随机接受个体化治疗的高危病例中耐多药结核病患者的培养转换时间，一种新的快速DST方法（Griess或荧光素酶），2）BACTEC或3）常规DST。我们的假设是：1）LRM和Griess方法将提供可接受的敏感性和特异性替代传统药物敏感性测试; 2）与传统DST相比，使用快速药物敏感性测试筛查耐多药结核高危受试者并指导个体化治疗将缩短耐多药结核病例的培养转换时间。

DESCRIPTION (provided by applicant): Sonya Shin, M.D. has completed an Infectious Disease fellowship at Brigham and Women's and Massachusetts General Hospitals. She has served as a Clinical Consultant on a multidrug-resistant tuberculosis (MDR-TB) project in Peru since 1996. Drs. Paul Farmer, Edward Nardell, and Michael Hughes will serve as mentors for this study. Dr. Shin plans to develop her skills as an independent clinical investigator, while gaining further formal training in epidemiology and decision analysis research. She ultimately hopes to pursue an independent career in TB clinical trials and program management. Several sites at the Harvard Medical School will provide a research environment for the candidate. Both the Division of Social Justice and Health Inequalities at the Brigham and Women's Hospital and the Harvard School of Public Health, will provide ample environment for the candidate's professional development. Socios en Salud and the Ministry of Health in Lima, Peru will provide additional supervision and resources. MDR-TB remains a global health threat. Use of simple methods to rapidly identify multidrug-resistant tuberculosis strains will likely hasten treatment response. The specific aims of this study are to compare the sensitivity and specificity of two rapid drug susceptibility testing (DST) methods, the Luciferase Reporter Mycobacteriophage (LRM) method and a nitrate-reductase colorimetric (Griess) method, to conventional DST; and 2) to compare time to culture conversion among MDR-TB patients among high-risk cases randomized to receive individualized treatment based on either 1) a novel rapid DST method (Griess or Luciferase), 2) BACTEC or 3) conventional DST. Our hypotheses are that 1) the LRM and Griess methods will provide acceptably sensitive and specific alternatives to conventional drug susceptibility testing; and 2) use of rapid drug susceptibility testing compared with conventional DST to screen subjects at high risk for MDR-TB and guide individualized therapy will shorten time to culture-conversion among MDR-TB cases.