Reducing morbidity and mortality from acute febrile illness by improved diagnosis

通过改进诊断降低急性发热性疾病的发病率和死亡率

• 批准号: 8241158
• 负责人: Megan Elizabeth Reller
• 金额: $ 13.55万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-12 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241158
• 关键词: Acute; Adult; Africa; Africa South of the Sahara; Algorithms; Antimicrobial Resistance; Archives; Area; Asia; Autopsy; Bacteremia; Biological Assay; Blood; Caring; Cessation of life; Child; Clinical; Collaborations; Costs and Benefits; Country; Data; Decision Analysis; Decision Making; Dengue; Derivation procedure; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Epidemiology; Etiology; Failure; Fever; Goals; Gold; Guide prevention; Health Care Costs; Impact evaluation; Infection; Laboratories; Lead; Leptospirosis; Life; Low income; Malaria; Measures; Medical; Methodology; Methods; Molecular; Molecular Diagnostic Techniques; Morbidity - disease rate; Multi-Drug Resistance; New Agents; Outcome; Patients; Performance; Prevention; Probability; Provider; Public Health; Randomized; Research; Research Personnel; Resources; Rickettsia; Schools; Seasonal Variations; Sentinel; Serologic tests; Serological; Severities; Specimen; Sri Lanka; Sum; Techniques; Testing; Time; Training; Translational Research; Typhoid Fever; Uncertainty; Undifferentiated; Validation; Work; antimicrobial; arm; biothreat; career; career development; clinical Diagnosis; cohort; cost; cost effective; diagnosis standard; evidence base; follow-up; forging; health inequalities; improved; interest; mortality; multidisciplinary; neglect; new technology; novel diagnostics; pathogen; prevent; prospective; prototype; rapid diagnosis; skills; skills training; tool; years of life lost

DESCRIPTION (provided by applicant): An estimated 10 million children die yearly in low-income countries, the majority from infections easily prevented, diagnosed, and treated in wealthy countries. The actual sum and etiologic fractions are unknown, since few are diagnosed in life or classified by autopsy thereafter. Fever is often attributed erroneously to malaria in sub-Saharan Africa and to typhoid in South Asia. Limited cross-sectional data suggest that misdiagnosis is costly and deadly. Data to guide prevention and management of acute, undifferentiated fever in Sri Lanka are lacking. Our overarching hypothesis is that the development and rational use of new diagnostic tools will improve clinical outcomes and limit costs from acute febrile illness in resource-poor settings such as Sri Lanka. We posit that determination of the causal agents will inform public health efforts, improve clinical diagnosis, and reduce unnecessary morbidity, mortality, and costs by enabling the development of evidence-based clinical algorithms that include focused diagnostic testing. Therefore, we have the following specific aims: 1) To investigate the distribution and determinants of acute febrile illness in Sri Lanka, 2) To investigate new strategies for the diagnosis of acute febrile illness in Sri Lanka, and 3) To prospectively validate the prediction rules and to assess use and performance of the algorithm and related clinical outcomes and costs. The second aim will involve the validation of a multiplex real-time PCR assay for rickettsiae as a prototype for the rapid identification of difficult-to-culture emerging infections, derivation of a clinical prediction rule to assess etiology of acute fever in Sri Lanka, and use of decision analysis to evaluate strategies for managing acute febrile illness. The proposed 5-year career development period includes activities to provide the recipient with the additional training and skills required for her to conduct translational research and lead a multidisciplinary team as an independent investigator. The research will advance the field through integrated study of 1) traditional methods to define the epidemiology of acute febrile illness, 2) new molecular and analytic decision-making tools for rapid diagnosis of acute febrile illness and 3) feasibility and outcomes (health and costs) related to use of an algorithm to manage acute febrile illness in Sri Lanka. This work will provide data essential for prevention and management of acute febrile illness in Sri Lanka, a molecular diagnostic method for an emerging pathogen of worldwide importance (rickettsiae), and a general methodology for assessing approaches to improved diagnostic testing and related outcomes in resource-poor settings. . Globally many die with fever from infections that are never diagnosed. We will develop and study new tools to improve the diagnosis of infections characterized by fever, with the goal of reducing sickness and death from these infections and the cost of related medical care. The proposed 5-year training period will allow the applicant to gain skills and forge new collaborations to support a career in this neglected area.

描述（由申请人提供）：据估计，低收入国家每年有 1000 万儿童死亡，其中大多数死于富裕国家容易预防、诊断和治疗的感染。实际的总和和病因分数尚不清楚，因为很少有人在生前被诊断出或通过尸检进行分类。发烧常常被错误地归因于撒哈拉以南非洲的疟疾和南亚的伤寒。有限的横截面数据表明误诊的代价高昂且致命。斯里兰卡缺乏指导预防和管理急性未分化发热的数据。我们的总体假设是，新诊断工具的开发和合理使用将改善斯里兰卡等资源匮乏地区的临床结果并限制急性发热性疾病的成本。我们认为，确定致病因素将为公共卫生工作提供信息，改善临床诊断，并通过开发包括重点诊断测试在内的基于证据的临床算法来减少不必要的发病率、死亡率和成本。因此，我们有以下具体目标：1）调查斯里兰卡急性发热性疾病的分布和决定因素，2）研究斯里兰卡急性发热性疾病诊断的新策略，3）前瞻性验证预测规则并评估算法的使用和性能以及相关的临床结果和成本。第二个目标将涉及验证立克次体多重实时 PCR 检测作为快速识别难以培养的新发感染的原型，推导临床预测规则以评估斯里兰卡急性发热的病因，以及使用决策分析来评估管理急性发热性疾病的策略。拟议的 5 年职业发展期包括为接受者提供进行转化研究和作为独立研究者领导多学科团队所需的额外培训和技能的活动。该研究将通过综合研究 1）定义急性发热性疾病流行病学的传统方法，2）用于快速诊断急性发热性疾病的新分子和分析决策工具，以及 3）与使用算法管理斯里兰卡急性发热性疾病相关的可行性和结果（健康和成本）来推进该领域的发展。这项工作将为斯里兰卡预防和管理急性发热性疾病提供必要的数据，为世界范围内重要的新兴病原体（立克次体）提供分子诊断方法，以及评估资源匮乏地区改进诊断测试和相关结果的方法的通用方法。 。全球许多人因从未确诊的感染而发烧而死亡。我们将开发和研究新工具来改进以发烧为特征的感染的诊断，目标是减少这些感染引起的疾病和死亡以及相关医疗费用。拟议的 5 年培训期将使申请人能够获得技能并建立新的合作，以支持这一被忽视领域的职业生涯。

项目成果

Unsuspected rickettsioses among patients with acute febrile illness, Sri Lanka, 2007.

斯里兰卡，2007 年，急性发热性疾病患者中意外发现立克次体病。

• DOI: 10.3201/eid1805.111563
• 发表时间: 2012
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Reller,MeganE;Bodinayake,Champica;Nagahawatte,Ajith;Devasiri,Vasantha;Kodikara-Arachichi,Wasantha;Strouse,JohnJ;Flom,JudithE;Østbye,Truls;Woods,ChristopherW;Dumler,JStephen
• 通讯作者: Dumler,JStephen