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

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

Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project.

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will begin in Bangladesh, Cambodia, Lao PDR, and Myanmar and will define the epidemiological baseline of febrile illness in five remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future. [Abstract copyright: Copyright: © 2021 Chandna A et al.

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.

BackgroundFever 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 findingsWe 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/significanceOur 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

Defining the burden of febrile illness in rural South and Southeast Asia: an open letter to announce the launch of the Rural Febrile Illness project.

In rural areas of South and Southeast Asia malaria is declining but febrile illnesses still account for substantial morbidity and mortality. Village health workers (VHWs) are often the first point of contact with the formal health system, and for patients with febrile illnesses they can provide early diagnosis and treatment of malaria. However, for the majority of febrile patients, VHWs lack the training, support and resources to provide further care. Consequently, treatable bacterial illnesses are missed, antibiotics are overused and poorly targeted, and patient attendance wanes along with declining malaria. This Open Letter announces the start of a new initiative, the Rural Febrile Illness (RFI) project, the first in a series of projects to be implemented as part of the South and Southeast Asian Community-based Trials Network (SEACTN) research programme. This multi-country, multi-site project will run in Bangladesh, Cambodia, Lao PDR, Thailand, and Myanmar. It will define the epidemiological baseline of febrile illness in nine remote and underserved areas of Asia where malaria endemicity is declining and access to health services is limited. The RFI project aims to determine the incidence, causes and outcomes of febrile illness; understand the opportunities, barriers and appetite for adjustment of the role of VHWs to include management of non-malarial febrile illnesses; and establish a network of community healthcare providers and facilities capable of implementing interventions designed to triage, diagnose and treat patients presenting with febrile illnesses within these communities in the future