Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

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.

Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings

“…15 We hypothesised that improved malaria diagnosis to reduce use of antimalarials, a widely used antimicrobial class, could paradoxically drive an increase in untargeted use of other antimicrobials, such as antibiotics, particularly when test results for malaria are negative. 16 Little is known about the causes of non-malaria febrile illness in many malaria endemic countries, 17 where microbiological diagnostic facilities are limited or non-existent in most settings. Health workers can resort only to educated guesswork and empirical treatment for febrile patients who do not have malaria.…”

The assessment of fever in under-five children in the Ekounou Health Area of Yaounde, Cameroon: Usefulness of rapid diagnostic tests

“…Most importantly, the delays in the etiological diagnosis of non-malarial fevers can have serious consequences on the patient (Amexo et al, 2004;Barnish et al, 2004;Nankabirwa et al, 2009). Many other diseases such as typhoid fever, pneumonia, toxoplasmosis, rubella and other bacteraemia are very often misdiagnosed for malaria because of their very similar clinical manifestations, making their differentiation difficult (Redd et al, 1992;Prasad et al, 2015). With reports of the decline in the incidence of malaria in many African countries (Bouyou-Akotet et al, 2009;Delacollette et al, 2009;Satoguina et al, 2009), it is imperative that parasite confirmation of malaria be scaled up in all age groups.…”

Rickettsia felis Infection in Febrile Children, Ghana

“…2 Besides typhus group and spotted fever group rickettsiae, Rickettsia felis has recently been found to be potentially widespread in SSA, where R. felis-specific circulating DNA has been detected in the blood of up to 15% of febrile patients from Mali, Senegal, Gabon, and Kenya. [3][4][5] However, its role as a pathogen is still unclear and data on the geographical distribution, epidemiology, and clinical features of R. felis are limited.…”