Examination of Protective Factors Against Severe Malaria

NCT00342043 | Completed

• 2 other identifiers: 99990521405-I-N214
• Study Type: observational
• Target: 4,850
• Locations: 1 country
• Sites: 1

Brief Summary

This study, sponsored by the National Institutes of Health and the University of Bamako in Mali, Africa, will examine factors that may protect against progression of malaria from mild to severe disease. Infection with the malaria parasite causes disease ranging in severity from mild or no symptoms to severe. A better understanding of what factors protect against disease progression may help scientists develop improved methods of disease prevention and treatment. The objectives of this study are to:

• Identify differences in protective factors for severe malaria in Malinke children residing in two Mali villages, Kela and Kangaba. Genetic variations in hemoglobin proteins called HbS and HbC appear to confer protection against severe disease in some children but not others. HbC appears to protect young Malinke children living in Kela, but not in nearby Kangaba, while HbS protects children in Kangaba but not in Kela. In addition, deficiency of an enzyme produced by red blood cells called G6PD protects males, but not females, from severe malaria.
• Investigate how fetal hemoglobin (HbF) may protect against malaria in infants and determine how HbS, HbC, G6PD deficiency, and beta-thalassemia trait affect the rate of HbF decline during the first 2 years of life. Children under 11 years of age who seek medical care at Kangaba or Kela health centers for symptoms of malaria may be eligible for this study. Each will be screened with a medical history, physical examination and blood test. In addition, healthy infants born to women referred to field site clinics may be enrolled for the newborn study. Participants undergo the following procedures: Children with mild malaria are treated with artesunate and amodiaquine. Those with severe malaria are treated with quinine. Blood is collected by finger prick every day for 4 days to evaluate the response to treatment and for genetic testing. Some blood is stored for future research related to malaria. Newborns have a heel or finger prick at 1, 3 and 6 months to collect a small blood sample for genetic testing. In addition, at the time of birth, a small amount of blood is collected from one of the blood vessels of the placenta. Some infants may be followed up to 2 years, with additional drops of blood taken at 12, 18 and 24 months. Some of the blood is stored for future research related to malaria.

Conditions

Malaria; Severe Malaria

Keywords

Sickle Trait; Fetal Hemoglobin; Hemoglobin C; Beta-Thalassemia; Artesunate-Amodiaquine

Eligibility Criteria

• Age: Up to 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All malaria patients enrolled in the case-control study will be less than 11 years old.
• Uncomplicated malaria: Axillary temperature greater than 37.5 degrees Celsius or history of fever, signs and symptoms of malaria (e.g. headache, body aches, malaise), asexual parasite density less than 500,000 per microliter of blood, no criteria of severe malaria (see next paragraph), and no other etiologies of febrile illness (e.g. respiratory tract infection, cellulitis) on clinical examination.
• Severe malaria: Asexual parasite density greater than or equal to 100,000/uL or parasitemia of any density plus any one of the following: coma (defined as Blantyre coma score less than or equal to 2), convulsions (witnessed by investigator), severe prostration, severe anemia (hemoglobin less than 5 g/dL), respiratory distress, hypoglycemia (serum glucose less than 40 mg/dL), jaundice/icterus, shock (systolic blood pressure less than 50 mmHg, rapid pulse, cool extremities), cessation of eating and drinking, repetitive vomiting.

You may not qualify if:

• Patients who are parasitemic yet are found by clinical examination to have another etiology of febrile illness (e.g., respiratory tract infection, cellulitis) will not be formally enrolled into the protocol, but may be treated for both malaria and their coexisting infection by the study team.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Malaria Research and Training Center

Bamako, Mali

Location

Related Publications (3)

• Agarwal A, Guindo A, Cissoko Y, Taylor JG, Coulibaly D, Kone A, Kayentao K, Djimde A, Plowe CV, Doumbo O, Wellems TE, Diallo D. Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S. Blood. 2000 Oct 1;96(7):2358-63.

  PMID: 11001883 BACKGROUND

• Ayi K, Turrini F, Piga A, Arese P. Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood. 2004 Nov 15;104(10):3364-71. doi: 10.1182/blood-2003-11-3820. Epub 2004 Jul 27.

  PMID: 15280204 BACKGROUND

• Bard H. The postnatal decline of hemoglobin F synthesis in normal full-term infants. J Clin Invest. 1975 Feb;55(2):395-8. doi: 10.1172/JCI107943.

  PMID: 1127106 BACKGROUND

MeSH Terms

Conditions

Malaria; beta-Thalassemia

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 21, 2006
• Study Start: August 2, 2005
• Study Completion: April 16, 2009
• Last Updated: July 2, 2017

Record last verified: 2009-04-16

Locations

MA (1)