Medicine - Pathology
Reducing Morbidity and Mortality from Acute Febrile Illness by Improved Diagnosis.
Globally many children die from infections easily prevented, diagnosed, and/or treated in wealthy countries and many productive years of life are lost. The actual sum and etiologic fractions are unknown, since few are diagnosed in life or classified by autopsy thereafter. Yet, where resources are limited, diagnosis is especially critical to quantify disease and limit costly or ineffective therapies. No diagnostic failure exceeds that of acute febrile illness. Undifferentiated fever is assumed to be malaria in Africa and typhoid fever in South Asia. However, sentinel studies have shown marked geographical and seasonal variations in pathogens and identified new ones. A common problem is limited serologic follow-up and serologic cross-reactions, either of which can preclude definitive diagnosis of pathogens such as dengue, leptospirosis, and rickettsiae. Our overarching hypothesis is that the deployment of new diagnostic strategies for acute febrile illness will improve health and prove cost-effective in resource-poor settings such as Sri Lanka. Our long-term goal is to decrease suffering by improving diagnosis in resource-poor settings, which serves domestic interests by identifying emerging pathogens, curbing antimicrobial resistance through prudent antimicrobial use, and reducing health inequalities. The proposed work will produce a widely-applicable rapid, accurate multiplex real-time PCR assay for globally-distributed rickettsiae, an externally validated clinical prediction rule, and information needed to set locally-appropriate thresholds for testing and treatment. This pilot work would enable us to design, and solicit funding for, a clinical trial to assess outcomes associated with use of a prediction-rule guided algorithm to manage patients with acute febrile illness.
Harold Lehmann, MD, PhD, Public Health, Health Policy and Management; J. Stephen Dumler, MD, Medicine, Pathology