Understanding and Maximizing the Community Impact of Antimalarial Treatment (INDIE-SMC)

London School of Hygiene and Tropical Medicine

Status: Completed

Conditions: Malaria,Falciparum; Malaria

Treatments: Other: Seasonal Malaria Chemoprophylaxis (under 5 years old) with DOT; Other: Seasonal Malaria Chemoprophylaxis (under 10 years old) with DOT; Other: Seasonal Malaria Chemoprophylaxis (under 5 year old) implemented by the MoH without DOT

Study type: Interventional

Funder types: Other

Identifiers

NCT05878366

29193

INV-053846 (Other Grant/Funding Number)

Details and patient eligibility

About

Seasonal Malaria Chemoprophylaxis (SMC) is a fundamental component of malaria control. The SMC program involves that sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is given to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. Yet, its efficacy is increasingly below expectations.

This study involves an Operational evaluation of a modified existing intervention and its implementation are prepared in direct interaction with the Ministry of Health (MoH) to tailor data collection to local needs. The main questions it aims to answer are:

1. what are the reasons for the continued high infection rates in the SMC-targeted population;
2. what are the implications for transmission of sub-optimal SMC in children less than 5 years old;
3. can the impact of SMC be improved by including older age groups that would both expand the population that experiences direct chemoprophylactic benefits and concurrently reduce transmission to the wider community

Researchers will:

i) Compare SMC effectiveness as implemented by the national malaria control program and SMC implemented in a research context where all doses are directly observed.

ii) Quantify the infectious reservoir and the contribution of different age groups to transmission with conventional SMC (<5 years) and extended SMC (<10 years) iii) Determine the impact of drug resistance and drug absorption on SMC efficacy iv) Understand social barriers and enablers interfering with SMC efficacy and how SMC uptake is related to health equity with special attention to gender inequalities.

v) Quantify SMC efficacy decay under programmatic conditions and key drivers of this decay.

Full description

Seasonal Malaria Chemoprophylaxis is a well established method of malaria control. Sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is given to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. Whilst highly effective in controlled research studies, the impact of SMC in terms of reducing infection prevalence is less following operational delivery. It is currently unclear why and what drivers of SMC coverage and uptake play a role. In addition, the relative importance of parasite drug resistance, limited adherence, poor drug absorption and frequent re-infections remain largely unexplored.

Lastly, the World Health Organization has recently widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to all children below 10 years of age; the impact of SMC on clinical incidence and parasite prevalence in this population with markedly different immunity is unknown. Moreover, this older age group is known to be highly relevant for onward malaria transmission, making it important to quantify the impact of SMC on the human infectious reservoir for malaria and broader benefits to the community.

The investigators propose a cluster-randomized trial in Saponé Health District, Burkina Faso, with three study arms:

i. SMC in children under the age of 5 years, implemented by the MoH without directly observed treatment for the full course of SMC ii. SMC in children under the age of 5 years, with directly observed treatment for the full course of SMC iii. SMC in children under the age of 10 years, with directly observed treatment for the full course of SMC The investigators will deliver the different arms of the intervention to 40 clusters of 3 households/compounds (i.e. 120 compounds per arm). The primary endpoint is parasite prevalence at the end of the malaria transmission season, secondary endpoints include the impact of SMC on clinical incidence, gametocyte carriage and potential for onward parasite transmission to mosquitoes. As relevant factors in determining these efficacies, drivers of SMC uptake and treatment adherence will be determined, as well as drug concentrations, parasite resistance markers and transmission of parasites to mosquitoes.

Enrollment: 2,978 patients

Sex: All

Ages: 3+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

The study population will be derived from individuals aged 3 months to up to 10 years old eligible for SMC.

Inclusion criteria:

• Eligible for chemoprevention for SMC as per the current recommendations
• Age 3- 59 months for arms i. and ii.
• Age 60 months up to 10 years old for arm iii.
• Absence of symptomatic falciparum malaria, defined by fever on enrolment
• Absence of other non-P. falciparum species on blood film
• No evidence of acute severe or chronic disease
• Able and willing to comply with the study protocol and follow-up schedule
• Parent or guardian provides written, informed consent on behalf of child

Exclusion criteria:

• Symptoms of malaria (axillary fever ≥ 37.5 °C and/or history of fever in the past 48 hours)
• Previous reaction to study drugs / known allergy to study drugs
• Signs of severe malaria, including hyperparasitemia (defined as asexual parasitemia > 100,000 parasites / µL)
• Signs of acute or chronic illness, including hepatitis
• The use of other medication (except for paracetamol and/or aspirin)
• Presence of severe malnutrition according to WHO's child growth standards

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,978 participants in 3 patient groups

Arm 1

Active Comparator group

Description:

SMC in children under the age of 5 years, implemented by the MoH without directly observed treatment for the full course of SMC

Treatment:

Other: Seasonal Malaria Chemoprophylaxis (under 5 year old) implemented by the MoH without DOT

Arm 2

Experimental group

Description:

SMC in children under the age of 5 years, with directly observed treatment for the full course of SMC

Treatment:

Other: Seasonal Malaria Chemoprophylaxis (under 5 years old) with DOT

Arm 3

Experimental group

Description:

SMC in children under the age of 10 years, with directly observed treatment for the full course of SMC

Treatment:

Other: Seasonal Malaria Chemoprophylaxis (under 10 years old) with DOT