Impact of Seasonal Malaria Chemoprevention on Immunity Against Malaria Among Children in Northern Benin (ISAMIMA)

Impact of Seasonal Malaria Chemoprevention on the Acquisition and Maintenance of Immunity Against Malaria Among Children in Northern Benin

This study aims to evaluate the effects of SMC 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, Glurp, Var and a panel of PfEMP1. qPCR will be used to detect the prevalence of malaria at this period and parasites infecting children will be caracterize during the follow up.

Study Overview

• Status: Completed
• Conditions: Determine the Impact of Treatment on the Acquisition of Anti-malarial Antibodies in Children Before, During and After the Intervention; Determine the Prevalence of Malarial Infection in Children Before, During and After Seasonal Malaria Chemoprevention
• Intervention / Treatment: Drug: saisonal malaria chimoprevention

Detailed Description

Study location and population The study will be conducted in parallel in two different sites, the health districts of Cobly and Tchaourou 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 are very similar in terms of malaria transmission characteristics and epidemiology, with the difference that SMC is implemented in Cobly but not yet in Tchaourou. Samples collected from children in Cobly health district will be included as the intervention group, whilst samples collected from children in Tchaourou will thus serve as controls, in particular with respect to the evolution of antibody responses. Participants will be fully counselled on the importance of SMC and written informed consent will be collected from the parent or guardian of each child. Participation will be entirely voluntary.

Study Design and procedures This is a study that focuses on the follow-up over 12 months of children aged 6 to 59 months who receive SMC, along with a control group not receiving SMC. The study will be conducted in collaboration with National Malaria Control Program (NMCP) of Benin. Demographic data supplied by the NMCP will allow for a random selection of children from random households. In both intervention and control sites, equal numbers of children will be included. The study team will visit each selected household to inform household members of the study and will hold monthly meetings with the community health workers. Children of consenting parents or guardians will be recruited and parents/guardians will be taken through a questionnaire administered by the researcher or an assistant (clinician). 1 ml of peripheral venous blood will be 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 will be prepared from each sample. Fifty microliters of blood will be transferred to Whatman 3MM filter paper and stored at room temperature for DNA extraction. The remaining whole blood will then be centrifuged, the plasma and red blood cells will be aliquoted aliquoted. Samples will be collected at 4 times from each child in both groups (children aged 6 to 59 months receiving or/not SMC) during the 12 months follow-up period. The first samples will be collected at the beginning of SMC (before children receive the SMC, the second 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 will be prepared from all samples at all times. Thinck smears will be fixed in methanol. All slides will be air dried and stained using Giemsa stain 3% for 45-60 min. Once dry, the stained thick and thin blood films will be examined microscopically using a routine procedure. Parasite densities will be recorded as the number of parasites/μl of blood assuming an average leukocyte count of 8,000/μl of blood. Dried blood spots on filter paper samples will be air dried and stored individually in small Ziploc bags with a desiccant. Plasmodium spp detection will be performed using a real time polymerase chain reaction (qPCR) in routine use with an Quantstudio instrument.

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 IgG will be 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. In addition the protein array includes, merozoite surface protein 1 (MSP1) and apical membrane antigen 1 (AMA1).

• Study Type: Observational
• Enrollment (Actual): 440

Contacts and Locations

Study Locations

• Benin
  • Parakou, Benin
    • Azizath MOUSSILIOU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

Inclusion Criteria:

1. Aged between 6 and 59 months
2. Living permanently in one of the households selected
3. Have been selected and accepted to receive SMC treatment (SP-AQ) in the intervention site and not in the control site
4. Parents or guardians have given written informed consent

Exclusion Criteria:

• Any child whose parents or sponsors will no longer consent at some point in the study for one reason or another
• Any child moved from selected sites within 2 weeks

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ISC; This group included children from 6 to 59 months living in Cobly and receiving the SMC treatment. The treatment is administered for three consecutives days for 4 months (from july to october). For children under 12 months: one dose of SP 250/12.5mg on day 1 AQ 75mg once daily for 3 days For children from 12 to 59 months: one dose of SP 500/25mg on day 1 AQ 150 mg once daily for 3 days	Drug: saisonal malaria chimoprevention; Investigation of the impact of saisonal malaria chimoprevention on children anti PfEMP1 construction and maintenance and their succeptibility to malaria infection
IST; This group included children from 6 to 59 months living inTchaourou and did not receiving the SMC treatment.	Drug: saisonal malaria chimoprevention; Investigation of the impact of saisonal malaria chimoprevention on children anti PfEMP1 construction and maintenance and their succeptibility to malaria infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPS reduces the natural acquisition of antimalarial antibodies, potentially increasing susceptibility to malaria episodes in older children who no longer receive CPS	Dynamic of PfEMP1 antibody profile and malaria prevalence before, during and after SMC intervention in children living in northern Benin.	January 2023

Collaborators and Investigators

• Sponsor: Université de Parakou
• Collaborators: University of Copenhagen; Hôpital Cochin; University of Ghana; Institut de Recherche pour le Developpement; Institut de Recherche Clinique du Bénin (IRCB)
• Investigators: Study Chair: Nicaise TIUKUE NDAM, Professor, Institut régional de développement IRD (UMR261); Study Chair: Adrian LUTY, Professor, Institut régional de développement IRD (UMR261)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: December 4, 2022
• First Submitted That Met QC Criteria: December 4, 2022
• First Posted (Actual): December 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 4, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: seasonal malaria chemoprevention, malaria, children, anti PfEMP1
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: University of Parakou

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Protocol and the informed consent will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No