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      Naturally acquired antibody responses to more than 300 Plasmodium vivax proteins in three geographic regions

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          Abstract

          Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific. Naturally acquired antibody responses against multiple P. vivax proteins have been described in numerous countries, however, direct comparison of these responses has been difficult with different methodologies employed. We measured antibody responses against 307 P. vivax proteins at the time of P. vivax infection, and at 2–3 later time-points in three countries. We observed that seropositivity rates at the time of infection were highest in Thailand, followed by Brazil then PNG, reflecting the level of antigenic input. The majority of sero-reactive antigens in all sites induced short-lived antibody responses with estimated half-lives of less than 6 months, although there was a trend towards longer-lived responses in PNG children. Despite these differences, IgG seropositivity rates, magnitude and longevity were highly and significantly rank-correlated between the different regions, suggesting such features are reflective of the individual protein.

          Author summary

          In the pursuit of eliminating all species of malaria, Plasmodium vivax presents one of the most substantial challenges, particularly in countries in Asia, the Western-Pacific and South America. This is primarily due to the ability of P. vivax to cause relapse infections months to years after the initial infectious bite. In areas with low levels of malaria transmission, serology has become an increasingly useful tool for surveillance, as anti- Plasmodium antibodies can be detected in individuals long after blood-stage parasites have cleared. In this study, we provide a detailed characterisation of the antibody response generated following P. vivax infection by measuring antibodies to over 300 P. vivax antigens in three different populations in Thailand, Brazil and Papua New Guinea. The individuals in these populations were followed for up to nine months allowing us to estimate the rate at which antibodies decay over time. This improved understanding of the magnitude and dynamics of the antibody response, validated in multiple populations, will contribute to the development of serological surveillance tools needed for enhanced control and elimination of P. vivax.

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          Most cited references36

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          Fitting Linear Mixed-Effects Models Using lme4

          Maximum likelihood or restricted maximum likelihood (REML) estimates of the parameters in linear mixed-effects models can be determined using the lmer function in the lme4 package for R. As for most model-fitting functions in R, the model is described in an lmer call by a formula, in this case including both fixed- and random-effects terms. The formula and data together determine a numerical representation of the model from which the profiled deviance or the profiled REML criterion can be evaluated as a function of some of the model parameters. The appropriate criterion is optimized, using one of the constrained optimization functions in R, to provide the parameter estimates. We describe the structure of the model, the steps in evaluating the profiled deviance or REML criterion, and the structure of classes or types that represents such a model. Sufficient detail is included to allow specialization of these structures by users who wish to write functions to fit specialized linear mixed models, such as models incorporating pedigrees or smoothing splines, that are not easily expressible in the formula language used by lmer. Journal of Statistical Software, 67 (1) ISSN:1548-7660
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            Limit of blank, limit of detection and limit of quantitation.

            * Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) are terms used to describe the smallest concentration of a measurand that can be reliably measured by an analytical procedure. * LoB is the highest apparent analyte concentration expected to be found when replicates of a blank sample containing no analyte are tested. LoB = mean(blank) + 1.645(SD(blank)). * LoD is the lowest analyte concentration likely to be reliably distinguished from the LoB and at which detection is feasible. LoD is determined by utilising both the measured LoB and test replicates of a sample known to contain a low concentration of analyte. * LoD = LoB + 1.645(SD (low concentration sample)). * LoQ is the lowest concentration at which the analyte can not only be reliably detected but at which some predefined goals for bias and imprecision are met. The LoQ may be equivalent to the LoD or it could be at a much higher concentration.
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              Gamma-globulin and acquired immunity to human malaria.

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draft
                Role: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                11 September 2017
                September 2017
                : 11
                : 9
                : e0005888
                Affiliations
                [1 ] Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
                [2 ] Department of Medical Biology, University of Melbourne, Melbourne, Australia
                [3 ] Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
                [4 ] MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
                [5 ] Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan
                [6 ] Vector Borne Diseases Unit, PNG Institute of Medical Research, Madang, Papua New Guinea
                [7 ] ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clinic-Universitat de Barcelona, Barcelona, Spain
                [8 ] Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
                [9 ] Instituto de Pesquisas Leônidas e Maria Deane, Manaus, Amazonas, Brazil
                [10 ] Malaria: Parasites & Hosts Unit, Department of Parasites & Insect Vectors, Institut Pasteur, Paris, France
                Johns Hopkins Bloomberg School of Public Health, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-7472-4138
                Article
                PNTD-D-17-00662
                10.1371/journal.pntd.0005888
                5614652
                28892517
                d0c299a1-f736-4d14-8140-8f2725f2aa77
                © 2017 Longley et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 April 2017
                : 21 August 2017
                Page count
                Figures: 6, Tables: 1, Pages: 15
                Funding
                Funded by: Global Health Innovation Technology Fund
                Award ID: T2015-142
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: 5R01 AI 104822
                Award Recipient :
                Funded by: Bill and Melinda Gates Foundation (US)
                Award ID: TransEPI
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 1021544
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001711, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung;
                Award ID: 310030_134889
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: U19 AI089686
                Award Recipient :
                The Thai study was funded by the National Institute of Allergy and Infectious Diseases (NIH grant 5R01 AI 104822 to JS); and the PNG field study was supported by the TransEPI consortium funded by the Bill & Melinda Gates, the NHMRC (#1021544) Foundation Swiss National Science Foundation Grant [grant 310030_134889], the Cellex Foundation and International Centers of Excellence in Malaria Research [grant U19 AI089686).IM is supported by an NHMRC Senior Research Fellowship (1043345), CTF was supported by the University of Melbourne – Melbourne International Postgraduate Scholarship (MIPS) and LJR was supported by an NHMRC Early Career Fellowship (1016443). TT was supported in part by JSPS KAKENHI (JP15H05276, JP16K15266) in Japan. This work has been supported by FIND with funding from the Australian Government and by the Global Health Innovative Technology Fund (T2015-142). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Parasitology
                Parasite Groups
                Apicomplexa
                Plasmodium
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antibodies
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antibodies
                Biology and Life Sciences
                Immunology
                Immune Response
                Antibody Response
                Medicine and Health Sciences
                Immunology
                Immune Response
                Antibody Response
                People and Places
                Geographical Locations
                Asia
                Thailand
                People and places
                Geographical locations
                South America
                Brazil
                Biology and Life Sciences
                Physiology
                Immune Physiology
                Antigens
                Medicine and Health Sciences
                Physiology
                Immune Physiology
                Antigens
                Biology and Life Sciences
                Immunology
                Immune System Proteins
                Antigens
                Medicine and Health Sciences
                Immunology
                Immune System Proteins
                Antigens
                Biology and Life Sciences
                Biochemistry
                Proteins
                Immune System Proteins
                Antigens
                Earth Sciences
                Geography
                Regional Geography
                Medicine and Health Sciences
                Parasitic Diseases
                Malaria
                Medicine and Health Sciences
                Tropical Diseases
                Malaria
                Custom metadata
                vor-update-to-uncorrected-proof
                2017-09-26
                Data available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.qc7n5.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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