title: Transmission-reducing immunity is inversely related to age in Plasmodium falciparum gametocyte carriers.
abstract: Immunity to the sexual stages of Plasmodium falciparum is induced during natural infections and can significantly reduce the transmission of parasites to mosquitoes (transmission reducing activity; TRA) but little is known about how these responses develop with increasing age/exposure to malaria. Routinely TRA is measured in the standard membrane feeding assay (SMFA). Sera were collected from a total of 199 gametocyte carriers (median age 4 years, quartiles 2 and 9 years) near Ifakara, Tanzania; 128 samples were tested in the SMFA and generated TRA data classified as a reduction of > 50% and > 90% of transmission. TRA of > 50% was highest in young children (aged 1-2) with a significant decline with age (chi(2) trend = 5.79, P = 0.016) and in logistic regression was associated with prevalence of antibodies to both Pfs230 and Pfs48/45 (OR 4.03, P = 0.011 and OR 2.43 P = 0.059, respectively). A TRA of > 90% reduction in transmission was not age related but was associated with antibodies to Pfs48/45 (OR 2.36, P = 0.055). Our data confirm that antibodies are an important component of naturally induced TRA. However, whilst a similar but small proportion of individuals at all ages have TRA > 90%, the gradual deterioration of TRA > 50% with age suggests decreased antibody concentration or affinity. This may be due to decreased exposure to gametocytes, probably as a result of increased asexual and/or gametocyte specific immunity.
authors.affiliation: Ifakara Health Research and Development Centre, Ifakara, Tanzania. chris.drakeley@lshtm.ac.uk
authors.forename: C J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: J T
authors.initials: JT
authors.lastname: Bousema
authors.forename: N I J
authors.initials: NI
authors.lastname: Akim
authors.forename: K
authors.initials: K
authors.lastname: Teelen
authors.forename: W
authors.initials: W
authors.lastname: Roeffen
authors.forename: A H
authors.initials: AH
authors.lastname: Lensen
authors.forename: M
authors.initials: M
authors.lastname: Bolmer
authors.forename: W
authors.initials: W
authors.lastname: Eling
authors.forename: R W
authors.initials: RW
authors.lastname: Sauerwein
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000913:Antibodies, Protozoan / Q000097:blood; D002353:Carrier State / Q000276:immunology / Q000469:parasitology* / Q000635:transmission; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology / Q000635:transmission*; D008297:Male; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan