Department of Quantitative Health Sciences; Department of Pediatrics
Adult; Age Factors; Animals; Antibodies, Protozoan; Antigens, Protozoan; Cells, Cultured; Child; Child, Preschool; Growth Inhibitors; Humans; Kenya; Life Cycle Stages; Malaria, Falciparum; Middle Aged; Parasitemia; Plasmodium falciparum; Seroepidemiologic Studies; Time Factors
Biostatistics | Epidemiology | Health Services Research | Immunology and Infectious Disease | Pediatrics
BACKGROUND: Antibodies that impair Plasmodium falciparum merozoite invasion and intraerythrocytic development are one of several mechanisms that mediate naturally acquired immunity to malaria. Attempts to correlate anti-malaria antibodies with risk of infection and morbidity have yielded inconsistent results. Growth inhibition assays (GIA) offer a convenient method to quantify functional antibody activity against blood stage malaria.
METHODS: A treatment-time-to-infection study was conducted over 12-weeks in a malaria holoendemic area of Kenya. Plasma collected from healthy individuals (98 children and 99 adults) before artemether-lumefantrine treatment was tested by GIA in three separate laboratories.
RESULTS: Median GIA levels varied with P. falciparum line (D10, 8.8%; 3D7, 34.9%; FVO, 51.4% inhibition). The magnitude of growth inhibition decreased with age in all P. falciparum lines tested with the highest median levels among children <4 years compared to adults (e.g. 3D7, 45.4% vs. 30.0% respectively, p = 0.0003). Time-to-infection measured by weekly blood smears was significantly associated with level of GIA controlling for age. Upper quartile inhibition activity was associated with less risk of infection compared to individuals with lower levels (e.g. 3D7, hazard ratio = 1.535, 95% CI = 1.012-2.329; p = 0.0438). Various GIA methodologies had little effect on measured parasite growth inhibition.
CONCLUSION: Plasma antibody-mediated growth inhibition of blood stage P. falciparum decreases with age in residents of a malaria holoendemic area. Growth inhibition assay may be a useful surrogate of protection against infection when outcome is controlled for age.
DOI of Published Version
PLoS One. 2008;3(10):e3557. Epub 2008 Oct 29. Link to article on publisher's site
Dent, Arlene E.; Bergmann-Leitner, Elke S.; Wilson, Danny W.; Tisch, Daniel J.; Kimmel, Rhonda; Vulule, John M.; Sumba, Peter Odada; Beeson, James G.; Angov, Evelina; Moormann, Ann M.; and Kazura, James W., "Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults" (2008). Quantitative Health Sciences Publications and Presentations. 405.