Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination
In our aim to eliminate malaria, more sensitive tools to detect residual transmission are quickly becoming essential. Antimalarial antibody responses persist in the blood after a malaria infection and provide a wider window to detect exposure to infection compared to parasite detection metrics. Here...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00928/full |
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| author | Lotus L. van den Hoogen Lotus L. van den Hoogen Gillian Stresman Jacquelin Présumé Ithamare Romilus Gina Mondélus Tamara Elismé Alexandre Existe Karen E. S. Hamre Karen E. S. Hamre Ruth A. Ashton Thomas Druetz Thomas Druetz Vena Joseph James G. Beeson James G. Beeson James G. Beeson Susheel K. Singh Susheel K. Singh Jacques Boncy Thomas P. Eisele Michelle A. Chang Jean F. Lemoine Kevin K. A. Tetteh Eric Rogier Chris Drakeley |
| author_facet | Lotus L. van den Hoogen Lotus L. van den Hoogen Gillian Stresman Jacquelin Présumé Ithamare Romilus Gina Mondélus Tamara Elismé Alexandre Existe Karen E. S. Hamre Karen E. S. Hamre Ruth A. Ashton Thomas Druetz Thomas Druetz Vena Joseph James G. Beeson James G. Beeson James G. Beeson Susheel K. Singh Susheel K. Singh Jacques Boncy Thomas P. Eisele Michelle A. Chang Jean F. Lemoine Kevin K. A. Tetteh Eric Rogier Chris Drakeley |
| author_sort | Lotus L. van den Hoogen |
| collection | DOAJ |
| description | In our aim to eliminate malaria, more sensitive tools to detect residual transmission are quickly becoming essential. Antimalarial antibody responses persist in the blood after a malaria infection and provide a wider window to detect exposure to infection compared to parasite detection metrics. Here, we aimed to select antibody responses associated with recent and cumulative exposure to malaria using cross-sectional survey data from Haiti, an elimination setting. Using a multiplex bead assay, we generated data for antibody responses (immunoglobulin G) to 23 Plasmodium falciparum targets in 29,481 participants across three surveys. This included one community-based survey in which participants were enrolled during household visits and two sentinel group surveys in which participants were enrolled at schools and health facilities. First, we correlated continuous antibody responses with age (Spearman) to determine which showed strong age-related associations indicating accumulation over time with limited loss. AMA-1 and MSP-119 antibody levels showed the strongest correlation with age (0.47 and 0.43, p < 0.001) in the community-based survey, which was most representative of the underlying age structure of the population, thus seropositivity to either of these antibodies was considered representative of cumulative exposure to malaria. Next, in the absence of a gold standard for recent exposure, we included antibody responses to the remaining targets to predict highly sensitive rapid diagnostic test (hsRDT) status using receiver operating characteristic curves. For this, only data from the survey with the highest hsRDT prevalence was used (7.2%; 348/4,849). The performance of the top two antigens in the training dataset (two-thirds of the dataset; n = 3,204)—Etramp 5 ag 1 and GLURP-R0 (area-under-the-curve, AUC, 0.892 and 0.825, respectively)—was confirmed in the test dataset (remaining one-third of the dataset; n = 1,652, AUC 0.903 and 0.848, respectively). As no further improvement was seen by combining seropositivity to GLURP-R0 and Etramp 5 ag 1 (p = 0.266), seropositivity to Etramp 5 ag 1 alone was selected as representative of current or recent exposure to malaria. The validation of antibody responses associated with these exposure histories simplifies analyses and interpretation of antibody data and facilitates the application of results to evaluate programs. |
| first_indexed | 2024-12-20T11:16:05Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T11:16:05Z |
| publishDate | 2020-05-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-61f57b0f9a77446aaa437b9fe364a30d2022-12-21T19:42:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00928539153Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria EliminationLotus L. van den Hoogen0Lotus L. van den Hoogen1Gillian Stresman2Jacquelin Présumé3Ithamare Romilus4Gina Mondélus5Tamara Elismé6Alexandre Existe7Karen E. S. Hamre8Karen E. S. Hamre9Ruth A. Ashton10Thomas Druetz11Thomas Druetz12Vena Joseph13James G. Beeson14James G. Beeson15James G. Beeson16Susheel K. Singh17Susheel K. Singh18Jacques Boncy19Thomas P. Eisele20Michelle A. Chang21Jean F. Lemoine22Kevin K. A. Tetteh23Eric Rogier24Chris Drakeley25Department of Infection Biology, London School of Hygiene & Tropical Medicine, London, United KingdomCenter for Applied Malaria Research and Evaluation, Tulane University School of Public Health & Tropical Medicine, New Orleans, LA, United StatesDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, United KingdomLaboratoire National de Santé Publique, Port-au-Prince, HaitiLaboratoire National de Santé Publique, Port-au-Prince, HaitiLaboratoire National de Santé Publique, Port-au-Prince, HaitiLaboratoire National de Santé Publique, Port-au-Prince, HaitiLaboratoire National de Santé Publique, Port-au-Prince, HaitiMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, United StatesCDC Foundation, Atlanta, GA, United StatesCenter for Applied Malaria Research and Evaluation, Tulane University School of Public Health & Tropical Medicine, New Orleans, LA, United StatesCenter for Applied Malaria Research and Evaluation, Tulane University School of Public Health & Tropical Medicine, New Orleans, LA, United StatesDepartment of Social and Preventive Medicine, University of Montreal School of Public Health, Montreal, QC, CanadaCenter for Applied Malaria Research and Evaluation, Tulane University School of Public Health & Tropical Medicine, New Orleans, LA, United StatesBurnet Institute, Melbourne, VIC, AustraliaDepartment of Medicine, The University of Melbourne, Melbourne, VIC, AustraliaCentral Clinical School and Department of Microbiology, Monash University, Clayton, VIC, Australia0Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark1Department of Immunology and Microbiology, Centre for Medical Parasitology, University of Copenhagen, Copenhagen, DenmarkLaboratoire National de Santé Publique, Port-au-Prince, HaitiCenter for Applied Malaria Research and Evaluation, Tulane University School of Public Health & Tropical Medicine, New Orleans, LA, United StatesMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, United States2Ministère de la Santé Publique et de la Population, Port-au-Prince, HaitiDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, United KingdomMalaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, United StatesDepartment of Infection Biology, London School of Hygiene & Tropical Medicine, London, United KingdomIn our aim to eliminate malaria, more sensitive tools to detect residual transmission are quickly becoming essential. Antimalarial antibody responses persist in the blood after a malaria infection and provide a wider window to detect exposure to infection compared to parasite detection metrics. Here, we aimed to select antibody responses associated with recent and cumulative exposure to malaria using cross-sectional survey data from Haiti, an elimination setting. Using a multiplex bead assay, we generated data for antibody responses (immunoglobulin G) to 23 Plasmodium falciparum targets in 29,481 participants across three surveys. This included one community-based survey in which participants were enrolled during household visits and two sentinel group surveys in which participants were enrolled at schools and health facilities. First, we correlated continuous antibody responses with age (Spearman) to determine which showed strong age-related associations indicating accumulation over time with limited loss. AMA-1 and MSP-119 antibody levels showed the strongest correlation with age (0.47 and 0.43, p < 0.001) in the community-based survey, which was most representative of the underlying age structure of the population, thus seropositivity to either of these antibodies was considered representative of cumulative exposure to malaria. Next, in the absence of a gold standard for recent exposure, we included antibody responses to the remaining targets to predict highly sensitive rapid diagnostic test (hsRDT) status using receiver operating characteristic curves. For this, only data from the survey with the highest hsRDT prevalence was used (7.2%; 348/4,849). The performance of the top two antigens in the training dataset (two-thirds of the dataset; n = 3,204)—Etramp 5 ag 1 and GLURP-R0 (area-under-the-curve, AUC, 0.892 and 0.825, respectively)—was confirmed in the test dataset (remaining one-third of the dataset; n = 1,652, AUC 0.903 and 0.848, respectively). As no further improvement was seen by combining seropositivity to GLURP-R0 and Etramp 5 ag 1 (p = 0.266), seropositivity to Etramp 5 ag 1 alone was selected as representative of current or recent exposure to malaria. The validation of antibody responses associated with these exposure histories simplifies analyses and interpretation of antibody data and facilitates the application of results to evaluate programs.https://www.frontiersin.org/article/10.3389/fimmu.2020.00928/fullmalariaimmunoglobulin G (IgG)multiplex bead assaysero-surveillanceeliminationETRAMP |
| spellingShingle | Lotus L. van den Hoogen Lotus L. van den Hoogen Gillian Stresman Jacquelin Présumé Ithamare Romilus Gina Mondélus Tamara Elismé Alexandre Existe Karen E. S. Hamre Karen E. S. Hamre Ruth A. Ashton Thomas Druetz Thomas Druetz Vena Joseph James G. Beeson James G. Beeson James G. Beeson Susheel K. Singh Susheel K. Singh Jacques Boncy Thomas P. Eisele Michelle A. Chang Jean F. Lemoine Kevin K. A. Tetteh Eric Rogier Chris Drakeley Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination Frontiers in Immunology malaria immunoglobulin G (IgG) multiplex bead assay sero-surveillance elimination ETRAMP |
| title | Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination |
| title_full | Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination |
| title_fullStr | Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination |
| title_full_unstemmed | Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination |
| title_short | Selection of Antibody Responses Associated With Plasmodium falciparum Infections in the Context of Malaria Elimination |
| title_sort | selection of antibody responses associated with plasmodium falciparum infections in the context of malaria elimination |
| topic | malaria immunoglobulin G (IgG) multiplex bead assay sero-surveillance elimination ETRAMP |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00928/full |
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