The Cytoadherence in Pediatric Malaria (CPM) Study

University Health Network, Toronto

Status: Completed

Conditions: Plasmodium Falciparum Malaria

Study type: Observational

Funder types: Other

Identifiers

NCT00707200

07-0548-AE

ISBT 777531237

HS 356

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 2,000 estimated patients

Sex: All

Ages: 6 months to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Clinical diagnosis of Plasmodium falciparum malaria infection

Exclusion criteria

• HIV or significant malnutrition

Trial design

2,000 participants in 2 patient groups

1

Description:

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

Description:

Controls: Controls consist of mildly-affected children with P falciparum malaria who are either managed as inpatients or outpatients.