Baseline Cohort Malaria Morbidity Study

Study Overview
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Brief Summary
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The BLOOMy study is a longitudinal prospective cohort study of healthy children to assess the incidence of clinical malaria over the main transmission season. Participants will undergo baseline clinical and biological assessments then will receive a curative dose of either artesunate or dihydroartemisinin-piperaquine to clear any existing parasitemia. Clearance of parasites will be confirmed 3 weeks later by Polymerase chain reaction (PCR) and only participants with negative PCR will be definitively enrolled for the longitudinal follow up. Both active and passive case detection will be used to ensure that capture of a high proportion of infections in the cohort is achieved. Blood samples for immunological assessments will be obtained at Day 0 of each positive blood smear episode before treatment and at Weeks 4 post treatment. Participants will be followed for a minimum of six months throughout the malaria peak transmission season.

Detailed Description
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The BLOOMy study has two co-Primary objectives: To assess the incidence of clinical malaria meeting the primary case definition in children aged 1.5 to 12 years living in the study area over the main transmission season To assess the occurrence of reinfection following the radical cure of existing parasitemia. The secondary objectives are: To assess the incidence of clinical malaria meeting various secondary cases definition in children aged 1.5 to 12 years living in the study area over the main transmission season To measure the immune responses (humoral and cell-mediated) to a panel of malaria vaccine candidate antigens To assess the molecular force of infection To pilot and standardize malaria morbidity assessment in three phase 2 malaria vaccine testing sites.

Official Title
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Baseline Cohort Study to Assess the Malaria Morbidity in Children Living in Future Malaria Vaccine Candidate Trial Sites

Conditions
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Malaria

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged 1.5 to 12 years Residence in the study area or surroundings for the period of the study Written informed consent from parents/legally acceptable representatives and an assent for children Exclusion Criteria: Complicated symptomatic malaria (defined according to standard World Health Organization criteria) Anaemia (Hb<8g/dL), Any (chronic) illness that requires immediate clinical care. Family history of sudden death or of congenital or clinical conditions known to prolong QTcB or QTcF interval or e.g. family history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or severe cardiac disease Any treatment which can induce a lengthening of QT interval Known history of hypersensitivity or allergic reactions to piperaquine or other aminoquinolones Receipt of any blood transfusion or immunoglobulins within 3 months Known history of hypersensitivity or allergic reactions to artesunate Severe malnutrition (weight-for-height being below -3 standard deviation or less than 70% of median of the World Health Organization (WHO) normalized reference values). Weight below 5 kg Current or previous participation in malaria vaccine trials Current active participation in any trial involving administration of investigational drug.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of clinical malaria episodes per child-year at risk meeting the primary case definition | The primary case definition: Positive P. falciparum parasitemia at a density > 0 detected by microscopy associated with measured fever (Axillary temperature ≥37.5°C/Tympanic ≥38°C or Forehead temperature ≥37.5°C using non-contact infrared thermometer)) | 6 months | 
| Time to P. falciparum infection detected by positive thick blood smear within 6 months after the enrolment in African children under natural exposure to P. falciparum by treatment group |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of clinical malaria episodes per child-year at risk meeting the following secondary cases definition | Second Secondary case definition: Measured fever (Axillary temperature ≥37.5°C/Tympanic ≥38°C or Forehead temperature ≥37.5°C using non-contact infrared thermometer) AND parasitemia of >5,000 parasites (p) / μl | 6 months | 
| Number of new P. falciparum clones acquired over time |  | 6 months | 
| Immune responses to malaria candidate vaccines in the consortium portfolio | Panel of malaria vaccine candidate's antigens such as PfSPZ CVAC, ME-TRAP, R21 (Pre erythrocytic stage antigens) and PfRH5, NPC-SE36 (Blood stage antigens) will be used to assess antibody responses at day 0 and 28 of confirmed episodes of clinical malaria. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Cohort, Children, Epidemiology