The Cytoadherence in Pediatric Malaria (CPM) Study

NCT ID: NCT00707200

Last Updated: 2010-01-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-11-30

Brief Summary

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

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.

Conditions

Plasmodium Falciparum Malaria

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

1

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.

No interventions assigned to this group

2

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

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of Plasmodium falciparum malaria infection

Exclusion Criteria

• HIV or significant malnutrition

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Toronto

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

University Health Network

Principal Investigators

Nicolette Nabukeera-Barungi, MBChB, MMEd

Role: STUDY_DIRECTOR

Mulago Hospital/Makerere University (lead local investigator)

Locations

Mulago Hospital Acute Care Unit & Makerere University Department of Paediatrics & Child Health

Kampala, , Uganda

Countries

Uganda

References

Cserti CM, Dzik WH. The ABO blood group system and Plasmodium falciparum malaria. Blood. 2007 Oct 1;110(7):2250-8. doi: 10.1182/blood-2007-03-077602. Epub 2007 May 14.

Reference Type: BACKGROUND

PMID: 17502454 (View on PubMed)

Cserti-Gazdewich CM, Dzik WH, Dorn ME, Quagliaroli RO, Xu S, Ssewanyana I, Nayyar R, Preffer FI. Quantitation of CD36 (platelet glycoprotein IV) expression on platelets and monocytes by flow cytometry: application to the study of Plasmodium falciparum malaria. Cytometry B Clin Cytom. 2009 Mar;76(2):127-34. doi: 10.1002/cyto.b.20443.

Reference Type: RESULT

PMID: 18671254 (View on PubMed)

Cserti-Gazdewich CM, Dhabangi A, Musoke C, Ssewanyana I, Ddungu H, Nakiboneka-Ssenabulya D, Nabukeera-Barungi N, Mpimbaza A, Dzik WH. Inter-relationships of cardinal features and outcomes of symptomatic pediatric Plasmodium falciparum MALARIA in 1,933 children in Kampala, Uganda. Am J Trop Med Hyg. 2013 Apr;88(4):747-756. doi: 10.4269/ajtmh.12-0668. Epub 2013 Jan 28.

Reference Type: DERIVED

PMID: 23358640 (View on PubMed)

Other Identifiers

HS 356

Identifier Type: -

Identifier Source: secondary_id

ISBT 777531237

Identifier Type: -

Identifier Source: secondary_id

07-0548-AE

Identifier Type: -

Identifier Source: org_study_id