Clinical trial NCT00707200: The Cytoadherence in Pediatric Malaria (CPM) Study
Official title: Clinical Outcomes in Pediatric Plasmodium Falciparum Malaria According to Host Cytoadherence Factors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Plasmodium Falciparum Malaria
Keywords: severe malarial anemia (SMA)
cerebral malarial (CM)
lactic acidosis
hyperparasitemia
respiratory distress
hypoxia
death
transfusion
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: University of Toronto
First posted: 2008-06-30
Enrollment: 2000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children, age 6 months to 12 years, with symptomatic malaria and (asexual) Plasmodium falciparum parasitemia.

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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of Plasmodium falciparum malaria infection

Exclusion Criteria:

* HIV or significant malnutrition

Primary outcomes:
measure: Combined severe morbidity & mortality
timeFrame: Discharge
Secondary outcomes:
measure: Laboratory indices of potential cytoadhesion (lactate, cell counts)
timeFrame: Presentation
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Mulago Hospital Acute Care Unit & Makerere University Department of Paediatrics & Child Health
Study officials:
affiliation: Mulago Hospital/Makerere University (lead local investigator)
name: Nicolette Nabukeera-Barungi, MBChB, MMEd
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.