Abstract
BackgroundWith apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries.Methods and FindingsWe conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection.ConclusionsWe demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed.
Highlights
Fever is a common reason for seeking healthcare in low- and middle-income countries (LMICs) [1]
We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens
High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed
Summary
Fever is a common reason for seeking healthcare in low- and middle-income countries (LMICs) [1]. Fever etiology research [4,7,8] and the more widespread use of malaria diagnostic tests following changes to malaria treatment guidelines [9,10] have highlighted the problem of malaria over-diagnosis among patients with severe febrile illness. Comprehensive, standardized, and high quality, multi-center etiology research is being undertaken to understand the causes of severe childhood diarrhea and pneumonia [13,14] but such an approach has not been taken for fever. With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries
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