Malaria Clinical Trial
Official title:
Multidisciplinary Studies of Malaria Protection by Hemoglobinopathies and G6PD Deficiency in Mali
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.
Our previous case-control study (protocol #01-I-N020) established that hemoglobin (Hb) C protects against severe malaria in the Dogon ethnic group of Mali, West Africa. We believe that abnormal display of major parasite virulence antigens (PfEMP-1) on the surface of HbC erythrocytes accounts for this protection. Whether this mechanism mediates protection by other mutant erythrocytes remains to be investigated. The principal objective of the current protocol has been to investigate whether HbC also protects against severe malaria in the Malinke of Kela, which historically gave rise to the Dogon. Our preliminary data from protocol #02-I-N285 suggest that HbC but not HbS (sickle trait) protects the young Malinke children of Kela, with the opposite being true for the Malinke children of Kangaba, a nearby village. To confirm these novel preliminary findings and to investigate candidate mechanisms of protection, our ongoing case-control study requires an additional 150 severe malaria patients who are less than 5 years old, of Malinke ethnicity, reside in either Kangaba or Kela villages, and have normal G6PD activity. Children less than 11 years old and diagnosed with either severe (case) or uncomplicated (control) malaria will be tested for hemoglobinopathies and G6PD deficiency. Severe and uncomplicated malaria patients will be treated with parenteral quinine or oral artemisinin combination therapies, respectively, which are standard of care in Mali. Principal outcome measures will include a comparison of the frequency of HbC, HbS, and G6PD deficiency between cases and controls; with odds ratios and 95% confidence intervals determining the degree and statistical significance of severe malaria protection. ;
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