Bacterial versus non-bacterial infections: a methodology to support use-case-driven product development of diagnostics

Abstract

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.

Clinical management and outcomes of acute febrile illness in children attending a tertiary hospital in southern Ethiopia

“…Blood smear microscopy is considered as the gold standard for malaria diagnosis [ 25 , 26 ], and, in Ethiopia, malaria RDTs are recommended only in rural settings where microscopy is unavailable. For participants presenting with respiratory illnesses, urine was tested for Streptococcus pneumoniae antigen [ 27 ] via Alere BinaxNOW® S. pneumoniae antigen RDT (Alere Scarborough Inc, USA) to understand the significance of a urine-based pneumococcal test in guiding the diagnosis and treatment of pneumonia.…”

Understanding complexities in the uptake of indigenously developed rapid point-of-care diagnostics for containment of antimicrobial resistance in India

“…For example, viral respiratory infections are recognised as the most common cause for unnecessary prescription of antibiotics, in community practice or urgent care settings. 25 However, no diagnostic focusing on respiratory bacterial pathogens had been developed or was under development in our survey. We, also, did not come across any test that can facilitate the rapid detection of fungal pathogens like Candida, and other endemic and re-emerging infections prevalent in India such as scrub typhus, murine typhus and leptospirosis, etc.…”

Analytical performance of 17 commercially available point-of-care tests for CRP to support patient management at lower levels of the health system

“…All patients from whom these samples were obtained gave consent for their samples to be stored in a biobank and used for research into diagnostic tools for fever management. Patients included in this study had fever at presentation and were aged from 2 to 65 years [28]. Standardized guidance for sample transport and storage prior to laboratory evaluation was followed [28], and all samples were preserved under temperature-controlled conditions at -20°C until CRP testing.…”

“…Patients included in this study had fever at presentation and were aged from 2 to 65 years [28]. Standardized guidance for sample transport and storage prior to laboratory evaluation was followed [28], and all samples were preserved under temperature-controlled conditions at -20°C until CRP testing.…”

“…Reference testing for CRP was conducted as part of the original sample characterization using Cobas 8000 Modular analyzer (Roche Diagnostics International AG, Rotkreuz, Switzerland) [28].…”