Clinical trial NCT05650502: Impact of Seasonal Malaria Chemoprevention on Immunity Against Malaria Among Children in Northern Benin
Official title: Impact of Seasonal Malaria Chemoprevention on the Acquisition and Maintenance of Immunity Against Malaria Among Children in Northern Benin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Plasmodium Malariae Infection
SMC
Immune System Disease
Keywords: Seasonal malaria chemoprevention
Malaria
Children
Anti PfEMP1
Lead sponsor: Université de Parakou
Sponsor class: OTHER
Collaborators: name: Institut de Recherche pour le Developpement
name: University of Copenhagen
name: University of Ghana
name: Institut de Recherche Clinique du Bénin (IRCB)
name: Hôpital Cochin
First posted: 2022-12-14
Enrollment: 440
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Children who meet the inclusion and exclusion criteria, living in the communes of Cobly and Tchaourou located in northern Benin, whether or not they have received Saisonal malaria chimotreatment, will be recruited.

Brief summary: This study aims to evaluate the effects of SMC (Seasonal malaria chemoprevention) with Sulfadoxine-Pyrimethamine (SP) and Amodiaquine (AQ) on the evolution of anti-malarial immunity of children and their susceptibility to malarial infection.

This is a cross-sectional study on children aged 6 to 59 months with/without SMC in two villages in northern Benin. Sociodemographic and clinical data as well as repeated blood samples will be collected from 440 children (before, during and after treatment). Samples will be analyzed using a Luminex assay to investigate antibody responses to MSP (merozoite surface protein) , Glurp (Glutamate-Rich Protein) and a panel of PfEMP1. qPCR (quantitative polymerase chain reaction) will be used to detect the prevalence of malaria at this period and parasites infecting children will be characterize during the follow up.

Detailed description: Study location and population The study was conducted in parallel in two different sites, the health districts of Cobly and Tchaourou (two villages) located in northern Benin. These two districts have been chosen based on the Ministry of Health's programming for the implementation of SMC. The two sites were very similar in terms of malaria transmission characteristics and epidemiology, with the difference that SMC was implemented in Cobly but not in Tchaourou. Participants will be informed on the importance of SMC. A written informed consent was collected from parent or guardian of each child. Participation was entirely voluntary.

Study Design and procedures This is a case control study focuses on the follow-up over 12 months of children aged 6 to 59 months in northern Benin. The study was conducted in collaboration with National Malaria Control Program (NMCP). Demographic data generated by the NMCP had allow us for a random selection of children from random households. In both intervention and control sites, equal numbers of children were included. The study team visited each selected household to inform members. A monthly visit has been set up for monitoring. Children of consenting parents or guardians were recruited and parents/guardians were taken through a questionnaire administered by the researcher or an assistant (clinician). 1 ml of peripheral venous blood was collected into collection tubes and transferred to the Center for Expertise and Enhancing Research in Epidemiology and Public Health (CEEREPH) at the University of Parakou where a blood smear was prepared from each sample. Fifty microliters of blood have been transferred to Whatman 3MM filter paper and stored at room temperature for DNA extraction. The remaining whole blood have been centrifuged. The plasma and red blood cells were aliquoted. Samples was collected at 4 times during the 12 months follow-up period. The first samples were collected at the beginning of SMC implimentation (before children receive the first SMC dose), the second blood sample were collected at the day of the third dose of SMC, the third, at three month after the last dose of SMC and the fourth, six months after the last dose of SMC).

Malaria prevalence Thick and thin blood smears whave been prepared from all samples at all four times. Thick smears will be fixed in methanol. All slides were air dried and stained using Giemsa stain 3% for 45-60 min. Once dry, the stained thick and thin blood films were examined microscopically using a routine procedure. Parasite densities was recorded as the number of parasites/μl of blood assuming an average leukocyte count of 8,000/μl of blood. Dried blood spots were air dried and stored individually in small Ziploc bags with a desiccant. Plasmodium spp detection was performed using a real time polymerase chain reaction (qPCR).

Anti-PfEMP1 antibody response Plasmodium falciparum-encoded variant surface antigens (VSA) are expressed on the surface of infected erythrocytes (IE) and mediate binding to a range of endothelial cell receptors. The best characterized VSA are the var gene-encoded P. falciparum erythrocyte membrane protein 1 (PfEMP1) family in two exon units. Exon I codes for the extracellular and variable part of the protein as well as a transmembrane region and Exon II encodes the intracellular and relatively conserved acidic terminal segment (ATS). The most variable part of the protein contains a N-terminal segment followed by segments composed of three domain types; Duffy binding-like domains (DBL-domains): Cysteine-rich inter-domain regions (CIDRs) and C2. In this study, a panel of plasma antibody was quantified using microsphere bead-coupled proteins comprising 28 P. falciparum-derived antigens and tetanus toxoid, using the Luminex platform. The panel includes VAR2CSA (the VSA associated to placental malaria) and 25 HIS-tagged CIDR proteins representing all three main groups of PfEMP1, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1).

Eligibility criteria: Inclusion Criteria:

* Aged between 6 and 59 months
* Have been selected and accepted to receive SMC treatment (SP-AQ) in the intervention site and not in the control site
* Be able to take drugs

Exclusion Criteria:

* Child whose parents will no longer consent at some point in the study for one reason or another
* Children suffering from a chronic disease
* Intolerance to certain drugs

Primary outcomes:
measure: Efficiency of Seasonal malaria chemoprevention
timeFrame: January 2023
Secondary outcomes:
measure: Impact of Seasonal malaria chemoprevention
timeFrame: June 2023
Other outcomes:
Locations:
city: Parakou
country: Benin
facility: Azizath MOUSSILIOU
Study officials:
affiliation: Institut régional de développement IRD (UMR261)
name: Nicaise TIUKUE NDAM, Professor
role: STUDY_CHAIR
affiliation: Institut régional de développement IRD (UMR261)
name: Adrian LUTY, Professor
role: STUDY_CHAIR
References: