title: Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus.
abstract: Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv) minimal sample collection needs (50-100μL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
authors: Foundation for Innovative New Diagnostics (FIND), 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Sabine
authors: S
authors: Dittrich
authors: Foundation for Innovative New Diagnostics (FIND), 9 Chemin des Mines, 1202 Geneva, Switzerland.|Special Programme for Research & Training in Tropical Diseases (TDR), World Health Organization, Avenue Appia 20, 1211, Geneva 27, Switzerland.|Hawassa University, College of Medicine and Health Sciences, Department of Pediatrics, Hawassa, Ethiopia.
authors: Birkneh Tilahun
authors: BT
authors: Tadesse
authors: World Health Organization, 20 Avenue Appia, 1211, Geneva 27, Switzerland.
authors: Francis
authors: F
authors: Moussy
authors: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore.
authors: Arlene
authors: A
authors: Chua
authors: ReAct Europe, Uppsala University, Box 256, 751 05, Uppsala, Sweden.
authors: Anna
authors: A
authors: Zorzet
authors: ReAct Europe, Uppsala University, Box 256, 751 05, Uppsala, Sweden.
authors: Thomas
authors: T
authors: Tängdén
authors: Foundation for Innovative New Diagnostics (FIND), 9 Chemin des Mines, 1202 Geneva, Switzerland.|World Health Organization, 20 Avenue Appia, 1211, Geneva 27, Switzerland.|Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore.
authors: David L
authors: DL
authors: Dolinger
authors: Epidemiology and Population Health, Epicentre, Paris, France.
authors: Anne-Laure
authors: AL
authors: Page
authors: Centre for International Health, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.|Duke Global Health Institute, Box 90519, Duke University, Durham, NC, 27708, United States of America.|Division of Infectious Diseases and International Health, Box 102359, Duke University Medical Center, Durham, NC, 27710, United States of America.
authors: John A
authors: JA
authors: Crump
authors: Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.|Department of Ambulatory Care and Community Medicine, University of Lausanne, Bugnon 44, 1011, Lausanne, Switzerland.
authors: Valerie
authors: V
authors: D'Acremont
authors: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
authors: Quique
authors: Q
authors: Bassat
authors: Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.|Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Yoel
authors: Y
authors: Lubell
authors: Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom.|Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Vientiane, Lao PDR.
authors: Paul N
authors: PN
authors: Newton
authors: Division for Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany; German Center for Infection Research, Munich partner site, Leopoldstr 5, D-80802, Munich, Germany.
authors: Norbert
authors: N
authors: Heinrich
authors: Foundation for Innovative New Diagnostics (FIND), 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Timothy J
authors: TJ
authors: Rodwell
authors: Foundation for Innovative New Diagnostics (FIND), 9 Chemin des Mines, 1202 Geneva, Switzerland.
authors: Iveth J
authors: IJ
authors: González
mesh_terms: D001424:Bacterial Infections / Q000175:diagnosis*; D032921:Consensus; D003906:Developing Countries; D003937:Diagnosis, Differential; D005334:Fever / Q000175:diagnosis*; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000191:economics / Q000379:methods / Q000592:standards*; D017410:Practice Guidelines as Topic; D011933:Reagent Kits, Diagnostic / Q000191:economics / Q000592:standards*; D012680:Sensitivity and Specificity
chemical_list: D011933:Reagent Kits, Diagnostic