Monitoring of Molecular Markers of Artemisinin Resistance Through Repeated Cross-sectional Assessments in DR Congo, Nigeria and Uganda

NCT04037332 | Completed

• 1 other identifier: P 001-18-2.0
• Study Type: observational
• Target: 916
• Locations: 3 countries
• Sites: 7

Brief Summary

Currently, 16 African countries include the use of pre-referral rectal artesunate (RAS) in their treatment policies. However, guidelines for RAS use vary widely across countries and inappropriate use of RAS as a monotherapy and consequential development of resistances against artemisinin based treatments is of particular concern. In the frame of the Unitaid-funded "Community Access to Rectal Artesunate for Malaria" (CARAMAL) Project, quality-assured RAS will be rolled in selected areas of the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Approximately 3,000 treatments of RAS will be dispensed by trained community health workers to children \<5 years of age in each project country per year. Linked to the tracking of (severe) malaria patients in the frame of the CARAMAL project, this study will assess the frequency of artemisinin resistance markers in the study settings and tentatively assess whether the introduction of RAS could increase the selection of resistant P. falciparum strains. The study will be conducted in close collaboration with the Global Malaria Programme of the WHO. Finger-prick blood samples will be collected from children \< 5 years of age with signs of severe febrile illness and a positive mRDT presenting to community-based providers and referral facilities before and after the pilot roll-out of pre-referral RAS at community level.

Conditions

Severe Malaria

Outcome Measures

Primary Outcomes (1)

• K13-propeller sequence polymorphisms in P. falciparum

  Prevalence of molecular markers of artemisinin resistance in P. falciparum, namely K13-propeller sequence polymorphisms - before, after introduction of RAS in respective study area

  Through study completion, up to one year

Study Arms (4)

Pre-RAS roll-out . Group I

I. Children presenting directly to a referral health facility without prior administration of RAS (pre-RAS): provides a baseline assessment of artemisinin resistance marker prevalence before the introduction of RAS

Other: Blood sample (combined with malaria RDT) followed by gentoyping analysis

Post-RAS roll-out - Group II

II. Children presenting directly to a referral health facility without prior administration of RAS (post-RAS): group not receiving pre-referral RAS and hence having baseline pressure for K13 resistance markers.

Other: Blood sample (combined with malaria RDT) followed by gentoyping analysis

Post-RAS roll-out - Group III

III. Children receiving pre-referral RAS from community-based provider and successfully referred to a referral health facility: group receiving pre-referral RAS (monotherapy).

Other: Blood sample (combined with malaria RDT) followed by gentoyping analysis

Post-RAS roll-out - Group IV

IV. Children receiving pre-referral RAS from community-based provider but not completing referral to a referral health facility, followed-up at their home on day 28: children malaria-positive on Day 28 may have an increased chance of harboring a resistant infection.

Other: Blood sample (combined with malaria RDT) followed by gentoyping analysis

Interventions

Blood sample (combined with malaria RDT) followed by gentoyping analysis OTHER

Finger-prick blood samples collected from children with signs of severe febrile illness and a positive mRDT presenting to community-based providers and referral facilities ; analysis for mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domain

Post-RAS roll-out - Group II; Post-RAS roll-out - Group III; Post-RAS roll-out - Group IV; Pre-RAS roll-out . Group I

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

All children \<5 years in the Health Districts / Health Zones included into the "Community Access to Rectal Artesunate for Malaria" (CARAMAL) Project in the Democratic Republic of the Congo (DRC), Nigeria and Uganda and matching the eligibility criteria will be included

You may qualify if:

• age below 5 years
• enrolled in CARAMAL Project
• history of fever plus danger signs indicative of severe febrile illness / suspected severe malaria, according to local iCCM guidelines
• positive malaria test result by RDT or microscopy
• written informed consent from a parent or guardian

You may not qualify if:

• no current malaria infection
• mixed or mono-infection with a non-P. falciparum species known prior to sample collection
• no permanent residence in project area

Sponsors & Collaborators

• Swiss Tropical & Public Health Institute: lead
• Clinton Health Access Initiative, Nigeria: collaborator
• Akena Associates Ltd.: collaborator
• Kinshasa School of Public Health: collaborator
• Makerere University: collaborator

Study Sites (7)

Health Zone of Kenge

Kenge, Kwango, Democratic Republic of the Congo

Location

Health Zone of Ipamu

Ipamu, Kwilu, Democratic Republic of the Congo

Location

Health Zone of Kingandu

Kingandu, Kwilu, Democratic Republic of the Congo

Location

Adamawa State, selected LGAs

Yola, Adamawa, Nigeria

Location

Apac District

Lira, Apac, Uganda

Location

Kole District

Lira, Kole, Uganda

Location

Oyam District

Lira, Oyam, Uganda

Location

Related Links

• Registration info on major study into which drug resistance monitoring is nested

Biospecimen

Retention: SAMPLES WITH DNA

Bloodspot from finger prick (performed for malaria RDT), dried on filter paper and analyzed for mutations of P. falciparum gene encoding kelch (K13)-propeller domains

MeSH Terms

Conditions

Malaria

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Christian Burri

  Swiss TPH, Department of Medicine

  PRINCIPAL INVESTIGATOR

• Christian Lengeler, PhD

  Swiss TPH, Department of Epidemiology and Public Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 30, 2019
• Study Start: July 27, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: January 29, 2021

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

UG (3); NG (1); DE (3)