title: Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.
abstract: Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69(+) NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4(+) lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Wilson L
authors.initials: WL
authors.lastname: Mandala
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Chisomo L
authors.initials: CL
authors.lastname: Msefula
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Esther N
authors.initials: EN
authors.lastname: Gondwe
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford, United Kingdom Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Gilchrist
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi Centre for International Child Health, University of Melbourne Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Graham
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Paul
authors.initials: P
authors.lastname: Pensulo
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi.
authors.forename: Grace
authors.initials: G
authors.lastname: Mwimaniwa
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi.
authors.forename: Meraby
authors.initials: M
authors.lastname: Banda
authors.affiliation: Blantyre Malaria Project, Blantyre, Malawi Department of Internal Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Molyneux
authors.affiliation: School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Ward
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, United Kingdom Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Wellcome Trust Sanger Institute, Cambridge, United Kingdom calman.maclennan@ndm.ox.ac.uk.
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
mesh_terms: D000740:Anemia / Q000453:epidemiology / Q000276:immunology / Q000401:mortality / Q000469:parasitology; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology*; D016779:Malaria, Cerebral / Q000453:epidemiology / Q000276:immunology* / Q000401:mortality / Q000469:parasitology; D016778:Malaria, Falciparum / Q000150:complications / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008295:Malawi / Q000453:epidemiology; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*