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IgG against Plasmodium falciparum variant surface antigens and growth inhibitory antibodies in Mozambican children receiving intermittent preventive treatment with sulfadoxine-pyrimethamine
Authors:Quelhas Diana  Jiménez Alfons  Quintó Llorenç  Serra-Casas Elisa  Mayor Alfredo  Cisteró Pau  Puyol Laura  Wilson Danny W  Richards Jack S  Nhampossa Tacilta  Macete Eusebio  Aide Pedro  Mandomando Inacio  Sanz Sergi  Aponte John J  Alonso Pedro L  Beeson James G  Menéndez Clara  Dobaño Carlota
Affiliation:a Centro de Investigação em Saúde da Manhiça (CISM), Manhiça, Mozambique
b Instituto Nacional de Saúde (INS), Ministério da Saúde, Maputo, Mozambique
c Direcção Nacional de Saúde (DNS), Ministério da Saúde, Maputo, Mozambique
d Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Universitat de Barcelona, Spain
e Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia
Abstract:This study aimed to evaluate whether intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) had an effect on the acquisition of IgG against Plasmodium falciparum variant surface antigens (VSA) and growth-inhibitory antibodies in Manhiça, Mozambique. In addition, we assessed factors affecting the magnitude of these responses and the association between antibody levels and protection against malaria.IgG to VSA expressed by MOZ2, R29 and E8B parasite isolates were measured in plasma samples collected at 5, 9, 12 and 24 months of age by flow cytometry. Growth-inhibitory antibodies in dialyzed plasmas using GFP-D10 parasites were measured by flow cytometry at 12 and 24 months.IPTi-SP did not significantly modify the levels of IgG against VSA nor the growth-inhibitory capacity of antibodies up to 2 years of age. Age but not previous episodes of malaria influenced the magnitude of these responses. In addition, anti-VSA IgG levels were 7% higher in children with current P. falciparum infection and were associated with neighborhood of residence. Children aged 24 months had 10% less parasite growth than those aged 12 months (95% CI 0.88-0.93, P < 0.0001). Growth-inhibitory antibodies correlated with levels of IgG against AMA-1, when evaluating the 10% (R2 = 0.444, P = 0.049) and 20% (R2 = 0.230, P = 0.037) highest inhibitory samples. None of the responses were associated with subsequent risk of malaria.In conclusion, IPTi-SP does not negatively affect the development of antibody responses thought to be major contributors to the acquisition of immunity to malaria in infancy.
Keywords:AMA-1, apical membrane antigen 1   BSA, bovine serum albumin   CI, confidence intervals   DNA, deoxyribonucleic acid   DTP/OPV/Hep B, diphteria     tetanus     pertussis/oral polio vaccine/hepatitis B   EBA-175, erythrocyte binding antigen 175   EDTA, ethylenediaminetetraacetic acid   ELISA, enzyme-linked immunosorbent assay   EPI, expanded program on immunization   GFP, green fluorescence protein   GIA, growth inhibition assay   GM, geometric means   IE, infected erythrocytes   Ig, immunoglobulin   IPTi, intermittent preventive treatment in infants   ITC, insecticide-treated curtains   ITN, insecticide-treated bed nets   MFI, mean fluorescence intensity   MSP-1, merozoite surface protein 1   NAI, naturally acquired immunity   NIE, non-infected erythrocytes   P. falciparum, Plasmodium falciparum   PBS, phosphate buffered saline   PCR, polymerase chain reaction   pLDH, Plasmodium lactate dehydrogenase   SP, sulfadoxine-pyrimethamine   VSA, variant surface antigens
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