The Cytoadherence in Pediatric Malaria (CPM) Study

Study Overview
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Brief Summary
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The purpose of this study is to determine the importance of key blood group molecules in the clinical outcome of Plasmodium falciparum malaria infection in children.

Detailed Description
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Every year, nearly 2 million children die from infection with Plasmodium falciparum malaria. When red blood cells (RBC) become infected with malaria, a sticky parasite-derived knob protein, termed PfEMP-1, erupts on the RBC surfaces. PfEMP-1 attaches to several blood group molecules, including those found on other RBC, on blood vessels, and on the cells that normally help to stop bleeding (platelets). The cellular sticking results in a dangerous interruption in blood flow to vital organs, causing brain injury (cerebral malaria), systemic shock (lactic acidosis), and death. Depending on an individual's inherited blood groups of relevance, adhesion may be extensive or limited. In the laboratory, PfEMP-1 adheres to RBCs via the A or B (but not the O) antigens of the ABO blood group system, and to platelets and blood vessels via platelet glycoprotein IV (CD36) and ICAM-1. Consistent with the expected evolutionary advantage of being deficient in these binding targets, blood type O and low-expression of CD36 are found more frequently among Africans. The Cytoadherence in Pediatric Malaria (CPM) project is determining the distribution of adhesive blood group molecules in a cohort of 2000 Ugandan children according to the extent of malaria severity and death, and thus their ultimate clinical and evolutionary significance in malarial survival. This knowledge may serve as the grounds for developing targeted cytoadhesion-interruption therapies in our fight against malaria.

Official Title
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Clinical Outcomes in Pediatric Plasmodium Falciparum Malaria According to Host Cytoadherence Factors

Conditions
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Plasmodium Falciparum Malaria

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Plasmodium falciparum malaria infection Exclusion Criteria: HIV or significant malnutrition

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Cases: Severe inpatient malaria, survivors or decedents. Severe malaria consists of any one or combination of severe malarial anemia (SMA), cerebral malaria (CM), lactic acidosis (LA), or a respiratory distress syndrome with hypoxia. | |
| 2<br>Controls: Controls consist of mildly-affected children with P falciparum malaria who are either managed as inpatients or outpatients. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined severe morbidity & mortality |  | Discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory indices of potential cytoadhesion (lactate, cell counts) |  | Presentation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe malarial anemia (SMA), cerebral malarial (CM), lactic acidosis, hyperparasitemia, respiratory distress, hypoxia, death, transfusion