Acute febrile illness (AFI) is one of the most common reasons for seeking medical care in low-income and middle-income countries. Bacterial infections account for a relatively small proportion of AFIs; however, in the absence of a simple diagnostic test to guide clinical decisions, healthcare professionals often presume that a non-malarial febrile illness is bacterial in origin, potentially resulting in inappropriate antibiotic use. An accurate differential diagnostic tool for AFIs is thus essential, to both limit antibiotic use to bacterial infections and address the antimicrobial resistance crisis that is emerging globally, without resorting to multiple or complex pathogen-specific assays. The Biomarker for Fever-Diagnostic (BFF-Dx) study is one of the largest fever biomarker studies ever undertaken. We collected samples and classified disease aetiology in more than 1900 individuals, distributed among enrolment centres in three countries on two continents. Identical protocols were followed at each study site, and the same analyses were conducted in each setting, enabling like-with-like comparisons to be made among the large sample set generated. The BFF-Dx methodology can act as a model for other researchers, facilitating wider utility of the work in the future. The established sample collection is now accessible to researchers and companies and will facilitate the development of future fever-related diagnostic tests. Here, we outline the methodology used to determine the sample populations and to differentiate bacterial versus non-bacterial AFIs. Future publications will set out in more detail the study’s demographics, the causes of fever identified and the performance of selected biomarkers.
- diagnostics and tools
- public health
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Handling editor Alberto L Garcia-Basteiro
Contributors SD, BTT, WR, SG, AMS, STA, MML and TS contributed expertise for the clinical, epidemiological and diagnostic activities. SO and AM led the development of data management processes and the statistical analysis plan. VH, CE and SD contributed specialist expertise for laboratory and diagnostic activities. In Brazil, AMS contributed to adapting the protocol, reference testing and translation. In Gabon, STA and MML contributed to adapting the protocol and translations. In Malawi, SG contributed to adapting the protocol and the data management plan. VH, CE and SD drafted the publication. All authors contributed to the design and development of the BFF-Dx protocol and/or subsequent implementation, analysis and/or publication input. All authors critically revised the manuscript for important intellectual content, read and approved the final version and agreed to its submission.
Funding The BFF-Dx study was funded by the Dutch, Australian and UK governments.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval Ethical approval of the study protocol was obtained from all relevant institutional and national committees.
Brazil: Research Ethics Committee of INI-FIOCRUZ and Comissão Nacional de Ética em Pesquisa (CONEP); National Research Ethics Committee
Gabon: Comité National d'Ethique pour la Recherche (CNER)
Malawi: National Health Science Research Committee (NHSRC); Observational and Intervention Research Ethics Committee of the London School of Hygiene and Tropical Medicine (LSHTM), UK
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement There is no data in this work.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.