A lack of simple, inexpensive, and rapid diagnostic tests for febrile illnesses other than malaria leads to overtreatment with antibiotics for those who test negative for malaria, and contributes to the global rise in antimicrobial resistance. New tests for the detection of host biomarkers provide promising tools to differentiate bacterial from non-bacterial infections in febrile patients. However, most available biomarker tests are not currently used in resource-limited settings, and very few evaluations have been performed in low- and middle-income country populations with non-severe febrile illness. As a result, our knowledge of the performance of these tests in settings with high prevalence of infectious and poverty-related diseases such as malaria, HIV, malnutrition and intestinal parasites is poor. This paper describes challenges faced during the process of getting to an approved test, including difficulties in selecting the most appropriate fever biomarkers; suitable study designs and sites for test evaluations; lack of available reference tests to evaluate the performance of new tests; and lack of clear regulatory pathways to introduce such tests. As many new biomarker assays are in development, understanding these challenges will better enable those working in this area to address them during product development.
Keywords: biomarker; challenges; diagnostic; diagnostic tests; febrile illness; fever; low- and middle-income countries; resource-limited setting.