Clinical trial NCT05878366: Understanding and Maximizing the Community Impact of Antimalarial Treatment (INDIE-SMC)
Official title: Understanding and Maximizing the Community Impact of Antimalarial Treatment (INDIE-SMC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Malaria,Falciparum
Keywords: Plasmodium falciparum
Seasonal Malaria Chemoprevention
Antimalarial treatment
Burkina Faso
SP+AQ
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Groupe de Recherche Action en Sante
name: Radboud University Medical Center
First posted: 2023-05-26
Enrollment: 2978
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study involves and Operational evaluation of a modified existing intervention delivered in independent clusters. The project and its implementation are prepared in direct interaction with the Ministry of Health (MoH) to tailor data collection to local needs.
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Parasite prevalence by quantitative PCR (qPCR) at the end of the transmission season in age groups targeted by seasonal malaria chemoprevention.
timeFrame: 4 weeks
Secondary outcomes:
measure: Parasite prevalence by microscopy at the end of the transmission season in all age groups
timeFrame: 4 weeks
measure: Parasite prevalence by qPCR at the end of the transmission season in all age groups
timeFrame: 4 weeks
measure: Parasite prevalence by microscopy prior to SMC rounds 2, 3 and 4 in SMC-targeted age groups
timeFrame: 8 weeks
measure: Rate of re-infection with P. falciparum at weeks 3, 4 and 5 after the last round of SMC, assessed in SMC-targeted age groups
timeFrame: 10 weeks
measure: Gametocyte prevalence by qRT-PCR at weeks 3, 4 and 5 after the last round of SMC, assessed in SMC-targeted age groups
timeFrame: 10 weeks
measure: Gametocyte prevalence by qRT-PCR at the end of the transmission season in all age groups
timeFrame: 8 weeks
measure: Plasma levels of AQ and DESAQ after the 4th round of SMC in children aged 3 months-9 years
timeFrame: 6 weeks
Other outcomes:
measure: Infectivity to mosquitoes, defined as the percentage of infected mosquitoes, in relation to gametocyte density and plasma drug levels of AQ and DESAQ
timeFrame: Up to 10 weeks
measure: Size and age-distribution of the infectious reservoir for malaria
timeFrame: Through study completion, an average of 10 months
measure: Prevalence of drug resistance markers in infected children aged 3 months-9 years assessed post each round of SMC (between arm comparison)
timeFrame: Through study completion, an average of 10 months
measure: Description of perceived social barriers to SMC uptake
timeFrame: Through study completion, an average of 10 months
measure: Quantification of SMC efficacy decay under programmatic conditions
timeFrame: Through study completion, an average of 10 months
Locations:
city: Ouagadougou
country: Burkina Faso
facility: Groupe de Recherche Action en Santé
Study officials:
affiliation: Groupe de Recherche Action en Sante
name: Alfred Tiono, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: