Perceptions and priorities for the development of multiplex rapid diagnostic tests for acute non-malarial fever in rural South and Southeast Asia: an international modified e-Delphi survey
Authors: Chew Rusheng , Lohavittayavikant Salisa , Mayer Matthew , Day Nicholas PJ , Lubell Yoel 
Published: July 2022

Background

Fever is a common presenting symptom in low- and middle-income countries (LMICs). It was previously assumed that malaria was the cause in such patients, but its incidence has declined rapidly. The urgent need to develop point-of-care tests for the most important causes of non-malarial acute febrile illness is hampered by the lack of robust epidemiological data. We sought to obtain expert consensus on analytes which should be prioritized for inclusion in fingerprick blood-based multiplex lateral flow rapid diagnostic tests (LF-RDTs) targeted towards four categories of patients with acute non-malarial fever in South and Southeast Asian LMICs, stratified by age (paediatric vs. adult) and care setting (primary vs. secondary care).

Methodology/Principal Findings

We conducted a two-round modified e-Delphi survey. A total of 84 panellists were invited, consisting of seven each from 12 countries, divided into three regional panels (Mainland Southeast Asia, Maritime Southeast Asia, and South Asia). Panellists were asked to rank their top seven analytes for inclusion in LF-RDTs to be used in each patient category, justify their choices, and indicate whether such LF-RDTs should be incorporated into algorithm-based clinical decision support tools. Thirty-six panellists (43%) participated in the first round and 44 (52%) in the second. There was consensus that such LF-RDTs should be incorporated into clinical decision support tools. At a minimum, these LF-RDTs should be able to diagnose dengue and enteric fever in all patient categories. There was a clear preference to develop LF-RDTs for pathogens not readily detected by existing technologies, and for direct diagnosis through antigen detection. Pathogen biomarkers were prioritized over host inflammatory biomarkers, with CRP being the only one ranked consistently highly.

Conclusions/Significance

Our results provide guidance on prioritizing analytes for inclusion in context-specific multiplex LF-RDTs and similar platforms for non-malarial acute febrile illness, for which there is an urgent unmet need.

AUTHOR SUMMARY

In rural South and Southeast Asia, most acute febrile illness was previously attributable to malaria but the incidence of malaria is declining. To aid diagnosis and prognosis in patients presenting with the common symptom of acute fever with no localising features but in whom malaria has been excluded, there is an urgent need to develop minimally-invasive rapid diagnostic tests (RDTs) which can test for multiple pathogen and host biomarkers. Obtaining expert consensus opinions on what biomarkers these tests should detect will contribute greatly to their development, but there is a paucity of robust epidemiological data on the diverse non-malarial causes of acute fever. We determined the biomarkers which should be included in region-specific fingerprick blood-based RDTs tailored to four patient categories differentiated by age and level of care, in the form of seven-item lists ranked in decreasing order of priority. To provide context for these rank lists, we ascertained the principal factors influencing expert priority-setting and explored perceptions of the clinical utility of such RDTs. Our results provide essential region-specific guidance to aid development of RDTs for acute non-malarial fever, for which there was strong consensus for their inclusion in clinical decision-making tools for low- and semi-skilled healthcare staff.