Validation of Promising Biomarker Assays to Assess Their Diagnostic Performance Characteristics

Validation of Promising Biomarker Assays to Assess Their Diagnostic Performance Characteristics in Africa and Latin America

This project aims to evaluate the performance characteristics of rapid tests to differentiate bacterial from non-bacterial infection in febrile adults and children presenting at OPDs (outpatient departments) i.e.("fever triage assays") in three LMICs. The evaluation will include a different commercial biomarker combinations as well as individual biomarkers to assess their individual or combined value in the target population. Markers will be evaluated onsite in ELISA or RDT format, as appropriate. Further, this study aims to contribute to a centralized biobank of well-characterized specimens for use by IVD companies and academic institutions for the development and evaluation of emerging assays.

Study Overview

• Status: Completed
• Conditions: Acute Febrile Illnesses
• Intervention / Treatment: Diagnostic test: Biomarker assay

• Study Type: Observational
• Enrollment (Actual): 2000

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Instituto Nacional de Infectologia Evandro Chagas - Fiocruz (INIEC)
• Gabon
  • Lambaréné, Gabon
    • CERMEL
• Malawi
  • Karonga District
    • Chilumba, Karonga District, Malawi
      • Karonga Prevention Study

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Any non-severely ill subject presenting with acute fever defined as: temperature of more than 38°C at initial evaluation of less than 7 days of symptoms at presentation.

For recruitment purposes, subjects will be classified into two groups:

• Children 2-17 years of age
• Adults 18-65 years of age

Description

Inclusion Criteria:

Any non-severely ill subject presenting with acute fever defined as: temperature of more than 38°C at initial evaluation of less than 7 days of symptoms at presentation.

Inclusion criteria:

• Children 2-17 years of age
• Adults 18-65 years of age
• Signed written informed consent for study participation. For recruitment purposes, subjects will be classified into two groups, children and adults. For children, age >2 years is the minimum cut-off, based on the amount of blood volume to be obtained in the study. WHO guidelines for allowable blood volume in 24 hours recommend that no more than 1-5% of total blood volume (75-80 ml/kg for older children) be obtained. Applying the average weight of a 2 year old toddler =12 kg, the allowable blood volume to be drawn in 24 hours at 1-5% of the total blood volume is 9.6 - 48 mL .

For minors, caregivers will provide informed consent. Documented assent for children of 12 to 16 years of age will be required for their participation.

Exclusion Criteria:

• Subjects who are felt to be in critical condition (based on clinician assessment or the presence of any general signs of critical illness as defined by WHO guidelines (for children: extensive vomiting, active seizure or recent history of seizures, altered mentation, inability to feed, or any of the severe IMNCI classifications; for adults: impending airway obstruction, central cyanosis, severe respiratory distress, feeble pulse, active seizure or recent history of seizures, or unconsciousness) because the target population for the study is non-severe febrile subjects.
• Subjects can only be enrolled once into the study.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Malawi febrile patients; Children and adults with fever presenting at the outpatient department	Diagnostic test: Biomarker assay; There is no intervention on the patients but biomarker assays are being evaluated for their performance to distinguish bacterial infection from non-bacterial infections in febrile patients
Brazil febrile patients; Children and adults with fever presenting at the outpatient department	Diagnostic test: Biomarker assay; There is no intervention on the patients but biomarker assays are being evaluated for their performance to distinguish bacterial infection from non-bacterial infections in febrile patients
Gabon febrile patients; Children with fever or with a recent history of fever presenting at the outpatient department	Diagnostic test: Biomarker assay; There is no intervention on the patients but biomarker assays are being evaluated for their performance to distinguish bacterial infection from non-bacterial infections in febrile patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic sensitivity and specificity to determine bacterial infections compared to clinical and microbiological results aggregated in a study database.	Microbiological testing (blood culture positive/negative, malaria pos/neg, S. Tyhpi RDT pos/neg) and clinical assessments of symptoms (respiratory, gastro, no foci) will be recorded and reviewed by a clinical panel upon completion of the study to assign a final category (bacterial or non-bacterial). These categories are used in the evaluation of the biomarker assays to evaluate their performance in differentiating bacterial from non-bacterial infections. Where applicable, the same categories will be used to determine the area under the curve by employing receiver operator characteristics (ROC) analysis of quantitative markers.	1year

Collaborators and Investigators

• Sponsor: Foundation for Innovative New Diagnostics, Switzerland
• Collaborators: Centre de Recherche Médicale de Lambaréné; Instituto Nacional de Infectologia Evandro Chagas; Malawi Epidemiology and Intervention Research Unit

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 27, 2017
• Primary Completion (ACTUAL): October 27, 2018
• Study Completion (ACTUAL): November 27, 2019

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (ESTIMATE): February 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: biomarker; fever; diagnostic; low and middle income countries; antimicrobial resistance
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: AFI_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: As appropriate data will be made available to the scientific community and/or commercial partners to support product development activities.