Diagnostic tools for tackling febrile illness and enhancing patient management

Abstract

A B S T R A C TMost patients with acute infectious diseases develop fever, which is frequently a reason to visit health facilities in resource-limited settings. The symptomatic overlap between febrile diseases impedes their diagnosis on clinical grounds. Therefore, the World Health Organization promotes an integrated management of febrile illness. Along this line, we present an overview of endemic and epidemic etiologies of fever and state-of-the-art diagnostic tools used in the field. It becomes evident that there is an urgent need for the development of novel technologies to fulfill end-users' requirements. This need can be met with point-of-care and near-patient diagnostic platforms, as well as e-Health clinical algorithms, which co-assess test results with key clinical elements and biosensors, assisting clinicians in patient triage and management, thus enhancing disease surveillance and outbreak alerts. This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach

“…From the listed technologies, only few are focusing on malaria and/or generally tropical infections for human diagnostics, and only one focuses on both human and vector diagnostics; that is why we choose to elaborate only on these in the current review. Mitsakakis et al are preparing a more comprehensive overview of all these technologies [ 93 ]. For malaria diagnostic technologies at lower readiness levels, an overview is given in the 2016 UNITAID Malaria Diagnostics Technology and Market Landscape Report [ 33 ].…”

“…A detailed description of eHealth tools that have been/are being used for the management of fever is available at Mitsakakis et al [ 93 ]. Some examples of such algorithms are as follows ( Figure 3 ): The e-IMCI (“Integrated Management of Childhood Illness”), the computerized version of the IMCI developed by the WHO and UNICEF [ 101 , 102 ].…”

Fully automated point-of-care differential diagnosis of acute febrile illness

“…These methods are in general more specific, suitable for a large number of diseases, and have been integrated in some point-of-care (POC) or near-patient systems already on the market or in near-commercialization phase, such as the GeneXpert, FilmArray, ID NOW, cobas Liat, Liaison MDX, GenePOC. Most of them provide various degrees of multiplexity, time-to-result, and integration, as reviewed by Mitsakakis/D’Acremont et al [ 20 ], but do not usually cover the malaria/non-malaria febrile illness panel.…”

“…This is a non-exhaustive list of fever-related pathogens that could potentially be detected on the platform. The combination of the target pathogens was selected among many others [ 20 ] for feasibility demonstration with the criteria to include: (i) the three main types of pathogens, namely, bacteria, viruses and parasites; (ii) vector-borne diseases; and (iii) bacterial diseases that are common in tropical areas and associated with antimicrobial resistance.…”

RespiDisk: a point-of-care platform for fully automated detection of respiratory tract infection pathogens in clinical samples

“…On the other hand, those platforms that aim at a broader panel such as the FilmArray® (bioMérieux), the Verigene® (Luminex Corp.), the VerePLEX™ Biosystem (Veredus Laboratories), the QIAstat-Dx (QIAGEN) and the Unyvero A50 (Curetis) use technically complex cartridges, costly and bulky equipment, which make them more suitable for laboratory settings than for point-of-care use. 20 The RespiDisk system we use in the present study is based on previously presented centrifugal microfluidic platform, the LabDisk, [21][22][23] which combines: (i) molecular diagnostics (realtime PCR); (ii) a two layer monolithically and easy-to-manufacture disposable cartridge, aiming at scalable cost-effective manufacturing; (iii) fully integrated reagents for a sample-toanswer analysis, aiming to minimize hands-on intervention; (iv) a point-of-care compatible (compact, lightweight) processing device (the LabDisk Player); (v) a broad pathogen panel currently consisting of 4 bacteria and 15 viruses/subtypes (which can be extended), aiming to demonstrate the system's capability to detect and differentiate main pathogens that lead to RTIs.…”