title: Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for International Health, Dunedin School of Medicine, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Namrata
authors.initials: N
authors.lastname: Prasad
authors.affiliation: Department of Pathology, University of Otago Christchurch, 2 Riccarton Avenue, PO Box 4345, Christchurch, 8011, New Zealand.
authors.forename: David R
authors.initials: DR
authors.lastname: Murdoch
authors.affiliation: Department of Disease Control, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom.
authors.forename: Hugh
authors.initials: H
authors.lastname: Reyburn
authors.affiliation: Centre for International Health, Dunedin School of Medicine, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: John A
authors.initials: JA
authors.lastname: Crump
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000150:complications / Q000175:diagnosis; D019049:Developed Countries; D003906:Developing Countries; D005334:Fever / Q000209:etiology*; D014943:Global Health; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008288:Malaria / Q000150:complications / Q000175:diagnosis; D009181:Mycoses / Q000150:complications / Q000175:diagnosis; D011446:Prospective Studies; D014777:Virus Diseases / Q000150:complications / Q000175:diagnosis; D015047:Zoonoses / Q000150:complications / Q000175:diagnosis