Antibody-Mediated Growth Inhibition of Plasmodium falciparum: Relationship to Age and Protection from Parasitemia in Kenyan Children and Adults

被引:65
作者
Dent, Arlene E. [1 ]
Bergmann-Leitner, Elke S. [2 ]
Wilson, Danny W. [3 ,4 ]
Tisch, Daniel J. [1 ]
Kimmel, Rhonda [1 ]
Vulule, John [5 ]
Sumba, Peter Odada [5 ]
Beeson, James G. [3 ]
Angov, Evelina [2 ]
Moormann, Ann M. [1 ]
Kazura, James W. [1 ]
机构
[1] Case Western Reserve Univ, Cleveland, OH 44106 USA
[2] Walter Reed Army Inst Res, Silver Spring, MD USA
[3] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia
[4] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia
[5] Kenya Govt Med Res Ctr, Kisumu, Kenya
来源
PLOS ONE | 2008年 / 3卷 / 10期
基金
英国医学研究理事会;
关键词
D O I
10.1371/journal.pone.0003557
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:10
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