Antibodies to chondroitin sulfate A-binding infected erythrocytes: dynamics and protection during pregnancy in women receiving intermittent preventive treatment.
BACKGROUND
Plasmodium falciparum parasites that cause malaria in pregnancy express unique variant surface antigens (VSAs). Levels of immunoglobulin G (IgG) antibody to pregnancy-associated VSAs measured at delivery are gravidity dependent, and they have been associated with protection from disease. It is not known how these IgG responses develop in pregnant women receiving intermittent preventive treatment during pregnancy (IPTp) or whether IgG levels in early pregnancy predict pregnancy outcomes.


METHODS
We performed longitudinal measurements of IgG antibody to VSAs by flow cytometric analysis of serum samples obtained from 549 Malawian women receiving IPTp. We examined fluctuations in IgG levels over time and associated the IgG levels noted at study enrollment with clinical outcomes.


RESULTS
Levels of IgG antibody to pregnancy-associated VSAs were gravidity dependent. Overall, levels decreased while women were receiving IPTp, but the levels of the individuals were highly dynamic. Primigravidae developed low levels of pregnancy-specific IgG, which were often boosted during second pregnancies. The prevalence of parasites was low (8.4% at enrollment and 2.4% in late pregnancy). Antibody levels at enrollment did not predict birth weight, duration of gestation at delivery, or the maternal hemoglobin level in late pregnancy.


CONCLUSIONS
Levels of IgG antibody to pregnancy-specific VSAs decrease during receipt of IPTp. Antibody levels in early pregnancy did not predict clinical outcome. IPTp and decreasing malaria prevalence pose challenges for the evaluation of novel interventions for malaria during pregnancy.
Aitken
Elizabeth H
EH
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria 3052, Australia. e.aitken@ugrad.unimelb.edu.au
Mbewe
Bernard
B
Luntamo
Mari
M
Maleta
Ken
K
Kulmala
Teija
T
Friso
Marc-James
MJ
Fowkes
Freya J I
FJ
Beeson
James G
JG
Ashorn
Per
P
Rogerson
Stephen J
SJ
D000293:Adolescent; D000328:Adult; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004338:Drug Combinations; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008295:Malawi; D010298:Parity; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology / Q000517:prevention & control*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000913:Antibodies, Protozoan; D000954:Antigens, Surface; D000962:Antimalarials; D004338:Drug Combinations; D007074:Immunoglobulin G; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002809:Chondroitin Sulfates; D011739:Pyrimethamine