Validation of Promising Biomarker Assays to Assess Their Diagnostic Performance Characteristics

NCT03047642 | Completed DMC

• 1 other identifier: AFI_01
• Study Type: observational
• Target: 2,000
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Acute Febrile Illnesses

Keywords

biomarker; low and middle income countries; fever; antimicrobial resistance; diagnostic

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Malawi febrile patients

Children and adults with fever presenting at the outpatient department

Diagnostic Test: Biomarker assay

Brazil febrile patients

Children and adults with fever presenting at the outpatient department

Diagnostic Test: Biomarker assay

Gabon febrile patients

Children with fever or with a recent history of fever presenting at the outpatient department

Diagnostic Test: Biomarker assay

Interventions

Biomarker assay DIAGNOSTIC_TEST

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; Gabon febrile patients; Malawi febrile patients

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (3)

Instituto Nacional de Infectologia Evandro Chagas - Fiocruz (INIEC)

Rio de Janeiro, Brazil

Location

CERMEL

Lambaréné, Gabon

Location

Karonga Prevention Study

Chilumba, Karonga District, Malawi

Location

Related Publications (1)

• Fernandez-Carballo BL, Atzeni M, Escadafal C, Vettoretti M, Geis S, Agnandji ST, Siqueira AM, Malava JK, Banda L, Kabwende AL, Alabi A, Ondo JCB, Massinga-Loembe M, Essone PN, Moreira J, da Rocha Matos A, Caetano BC, Siqueira MM, Bispo de Filippis AM, Dos Santos Ribeiro da Silva EA, Lourenco MCS, Haring J, Gunther A, Jakobi M, Schneiderhan-Marra N, Hoogland C, Brasil P, Pokharel S, Ongarello S, Harris V, Mace A, Lee SJ, Di Camillo B, Dittrich S. Cross-sectional evaluation of host biomarkers for guiding antibiotic use in bacterial and non-bacterial acute febrile illness in low- and middle-income tropical settings. BMJ Open. 2025 Feb 13;15(2):e086912. doi: 10.1136/bmjopen-2024-086912.

  PMID: 39947818 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples of whole blood, plasma, serum and urine are stored to establish a biobank of characterized samples for further development and testing of diagnostic tools for differential diagnosis of multiple febrile diseases in endemic areas.

MeSH Terms

Conditions

Fever; Disease

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: February 9, 2017
• Study Start: April 27, 2017
• Primary Completion: October 27, 2018
• Study Completion: November 27, 2019
• Last Updated: February 16, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

BR (1); GA (1); MA (1)