Algorithm Using a Rapid Diagnostic Test for the Management of Childhood Febrile Diseases.

NCT05285657 | Completed DMC

• 1 other identifier: TMA2019CDF 2697
• Study Type: interventional
• Target: 1,176
• Locations: 1 country
• Sites: 2

Brief Summary

In Sub-Saharan Africa (SSA), fever remains a major public health problem in children. The introduction of malaria rapid diagnostic tests (RDTs) in routine healthcare has greatly improved the management of malaria. However, despite the good attitude of healthcare workers to adhere to malaria RDT test results, persisting hrp2antigen and low sensitivity of pLDH RDT negatively affect antimalarials and antibiotics prescriptions practices. This is one of the main causes of antimicrobial resistance (AMR) and inappropriate management of febrile diseases. To improve the diagnosis of febrile diseases and subsequent prescription of antimicrobials, it is hypothesized that the implementation of an algorithm including a two-step malaria RDT PfHRP2/pLDH supported by point-of-care tests (POCTs) for C-reactive protein, oximetry, and bacterial infection such as Group A Streptococcus, and Salmonella/Shigella, will significantly improve the management of febrile diseases and thereby tackling AMR. To assess the value of the proposed algorithm, an open-label randomized controlled trial with three arms, enrolling febrile children under 5 years is proposed.

• In the control arm, febrile children will benefit from a complete clinical examination. Treatment will be done according to the national guideline.
• In RDTs decisional algorithm (RDT-DA) arm (intervention), the complete clinical examination will be supported by two-step malaria RDT and bacterial infections RDTs. Prescription will be left to the discretion of the healthcare workers.
• In e-algorithm arm (intervention), the complete clinical examination and the outcomes of RDTs (malaria and bacterial infections) will be digitalized. Diagnostic and prescription will be done by the algorithm. A final follow-up visit (day7) will be scheduled for all participants. Patients will be asked to return to the health facilities in case of no improvement. Primary study outcomes will be the proportion of curative case and antimicrobial(s) prescribed in each arm. Secondary outcomes include: (i) adherence of healthcare workers to the algorithm; (ii) adherence of parents/guardian to treatment; (iii) accuracy of the algorithm for the diagnostic of malaria. This project will serve as a path of policy change in the management of febrile diseases and AMR. By relying on existing RDTs available, the implementation of this algorithm will tackle AMR and provide better care. If successful, the project will equip the lead applicant to establish himself as an independent researcher with ability to further build his own research team. The project will also offer training opportunities to young scientists, and further strengthen already existing capacities of the home institute.

Conditions

Antimicrobial Resistance

Keywords

Malaria; Diagnostic; Antimalarial; Antibiotic

Outcome Measures

Primary Outcomes (2)

• Determine the rate acute febrile cases with favorable outcome at Day 7 visit

  Favorable outcome is defined as being alive and absence of symptoms

  7 days follow-up

• Determine the proportion of antibiotic and antimalarial prescriptions in acute febrile cases.

  Proportion of antibiotic prescription for acute febrile cases at the health facility.

  7 days follow-up

Secondary Outcomes (2)

• Determine the proportion of participants who adhered to antimalarial and antibiotic prescription

  7 days follow-up

• Determine the accuracy of the algorithm for the diagnostic of malaria

  Enrollment (Day 0)

Study Arms (3)

Control Arm

NO INTERVENTION

Febrile children will be managed according to the IMCI (integrative management of childhood illnesses) and the guideline of diagnostic and treatment (GDT), which are part of the routine system existing in Burkina Faso. Treatment will be done according to the national guideline.

RDTs decisional Arm

ACTIVE COMPARATOR

The clinical examination based on IMIC will be supported by two-step malaria RDT and bacterial infections RDTs. Prescription will be left to the discretion of the healthcare workers.

Diagnostic Test: Two-step malaria RDT detecting PfHRP2/pLDH (SD Ag Bioline Malaria Ag P.f/Pan: Standard Diagnostics, Hagal-Dong, Korea)

e-algorithm Arm

ACTIVE COMPARATOR

Artificial intelligence integrating multiple layers of clinical information such as clinical examination, signs/symptoms and medical history, and laboratory information such as outcomes of biomarkers (CRP and WBC) and pathogen specific POCT (malaria and bacterial infections) and oximetry will be developed. The e-algorithm will serve to guide the diagnostic and management of febrile infections in children from 2 to 59 months.

Diagnostic Test: Two-step malaria RDT detecting PfHRP2/pLDH (SD Ag Bioline Malaria Ag P.f/Pan: Standard Diagnostics, Hagal-Dong, Korea)

Interventions

Two-step malaria RDT detecting PfHRP2/pLDH (SD Ag Bioline Malaria Ag P.f/Pan: Standard Diagnostics, Hagal-Dong, Korea) DIAGNOSTIC_TEST

The interpretation of the two-step malaria RDT will be done as follow: * PfHRP2(+)/pLDH(+): falciparum malaria or co-infection with non-falciparum malaria; * PfHRP2(-)/pLDH(+): non-falciparum malaria or falciparum malaria with deletion of hrp2; * PfHRP2(-)/pLDH(-): negative results * PfHRP2(+)/pLDH(-): inconclusive results and information on previous antimalarial treatment is needed to differentiate: Within the past 28 days: * If previous antimalarial treatment is reported, the malaria diagnosis is reported as negative result. Nonetheless, the antimalarial treatment decision will be based on malaria microscopy; * If previous antimalarial treatment is not reported, the malaria diagnosis is reported as positive result. Other PoC tests for bacterial infections The two-step malaria RDT will be supported by PoC test listed above to diagnose bacterial or viral infection in all patients.

Also known as: C-reactive protein (CRP) test (SD Biosensor Standard F 100 quantitative CRP), HemoCue® WBC DIFF System, Urine dipstick (UroColor, Standard Diagnostic Inc, Korea), Oximetry (BESCO Fingertip Pulse oximeter, BES 500D), Pharyngitis: Streptococcus A throat test (SD BIOLINE Strep A), Salmonella and Shigella tests for diarrheal/dysentery (CERTEST Biotech, Salmonella detection kit and Shigella detection kit)

RDTs decisional Arm; e-algorithm Arm

Eligibility Criteria

• Age: 2 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children from 2 to 59 months of age;
• Acute fever (axillary temperature over or equal to 37.5°) or history of fever within the past 7 days;
• Available to return for the follow-up visit at the health facility on day 7 (±2).
• Written informed consent obtained from parents/legal guardian.

You may not qualify if:

• Children less than 2 months or over 59 months;
• Presence of signs and symptoms of severe infections;
• Children with chronic febrile infections.

Sponsors & Collaborators

• Institut de Recherche en Sciences de la Sante, Burkina Faso: lead

Study Sites (2)

Institut de Recherche en Sciences de la Santé-Clinical Research Unit of Nanoro

Nanoro, Boulkiemde, 11 BP 218 Ouaga CMS 11, Burkina Faso

Location

Health District of Nanoro

Nanoro, Boulkiemde, Burkina Faso

Location

Related Publications (1)

• Kiemde F, Compaore A, Koueta F, Some AM, Kabore B, Valia D, Rouamba T, Bocoum FY, Sawadogo S, Nana M, Some DY, Kone NA, Pagbeleguem V, Sangare I, Bere AW, Bonko MDA, Tougri G, Youl SY, Schallig H, Tinto H. Development and evaluation of an electronic algorithm using a combination of a two-step malaria RDT and other rapid diagnostic tools for the management of febrile illness in children under 5 attending outpatient facilities in Burkina Faso. Trials. 2022 Sep 15;23(1):779. doi: 10.1186/s13063-022-06717-8.

  PMID: 36109766 DERIVED

MeSH Terms

Conditions

Malaria; Disease

Interventions

Oximetry

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Gas Analysis; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: March 17, 2022
• Study Start: February 28, 2022
• Primary Completion: February 28, 2022
• Study Completion: November 30, 2023
• Last Updated: June 17, 2024

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

BU (2)