Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure

Assessment of serological Plasmodium falciparum–specific antibodies in highly endemic areas provides valuable information about malaria status and parasite exposure in the population. Although serological evidence of Plasmodium exposure is commonly determined by Plasmodium-specific immunoglobulin G...

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Main Authors: Paloma Abad, Patricia Marín-García, Marcos Heras, Julius N. Fobil, Alfred G. Hutchful, Amalia Diez, Antonio Puyet, Armando Reyes-Palomares, Isabel G. Azcárate, José M. Bautista
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.934321/full
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author Paloma Abad
Patricia Marín-García
Marcos Heras
Julius N. Fobil
Alfred G. Hutchful
Amalia Diez
Antonio Puyet
Armando Reyes-Palomares
Isabel G. Azcárate
José M. Bautista
author_facet Paloma Abad
Patricia Marín-García
Marcos Heras
Julius N. Fobil
Alfred G. Hutchful
Amalia Diez
Antonio Puyet
Armando Reyes-Palomares
Isabel G. Azcárate
José M. Bautista
author_sort Paloma Abad
collection DOAJ
description Assessment of serological Plasmodium falciparum–specific antibodies in highly endemic areas provides valuable information about malaria status and parasite exposure in the population. Although serological evidence of Plasmodium exposure is commonly determined by Plasmodium-specific immunoglobulin G (IgG) levels; IgM and IgA are likely markers of malaria status that remain relatively unexplored. Previous studies on IgM and IgA responses have been based on their affinity for single antigens with shortage of immune responses analysis against the whole Plasmodium proteome. Here, we provide evidence of how P. falciparum infection triggers the production of specific IgM and IgA in plasma and its relationship with parasite density and changes in hematological parameters. A total of 201 individuals attending a hospital in Breman Asikuma, Ghana, were recruited into this study. Total and P. falciparum–specific IgM, IgA, and IgG were assessed by ELISA and examined in relation to age (0–5, 14–49, and ≥50 age ranges); infection (submicroscopic vs. microscopic malaria); pregnancy and hematological parameters. Well-known IgG response was used as baseline control. P. falciparum–specific IgM and IgA levels increased in the population with the age, similarly to IgG. These data confirm that acquired humoral immunity develops by repeated infections through the years endorsing IgM and IgA as exposure markers in endemic malaria regions. High levels of specific IgA and IgM in children were associated with microscopic malaria and worse prognosis, because most of them showed severe anemia. This new finding shows that IgM and IgA may be used as diagnostic markers in this age group. We also found an extremely high prevalence of submicroscopic malaria (46.27% on average) accompanied by IgM and IgA levels indistinguishable from those of uninfected individuals. These data, together with the observed lack of sensitivity of rapid diagnostic tests (RDTs) compared to PCR, invoke the urgent need to implement diagnostic markers for submicroscopic malaria. Overall, this study opens the potential use of P. falciparum–specific IgM and IgA as new serological markers to predict malaria status in children and parasite exposure in endemic populations. The difficulties in finding markers of submicroscopic malaria are highlighted, emphasizing the need to explore this field in depth.
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spelling doaj.art-47eff08e37044a29b1cc728d90b342562022-12-22T04:01:00ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.934321934321Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposurePaloma Abad0Patricia Marín-García1Marcos Heras2Julius N. Fobil3Alfred G. Hutchful4Amalia Diez5Antonio Puyet6Armando Reyes-Palomares7Isabel G. Azcárate8José M. Bautista9Department of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainFaculty of Health Sciences, Rey Juan Carlos University, Alcorcón, SpainDepartment of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainDepartment of Biological, Environmental and Occupational Health Sciences, School of Public Health, College of Health Sciences, University of Ghana, Legon, Accra, GhanaLaboratory of Hematology and Infectious Diseases, Our Lady of Grace Hospital, Breman-Asikuma, GhanaDepartment of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainDepartment of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainDepartment of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainFaculty of Health Sciences, Rey Juan Carlos University, Alcorcón, SpainDepartment of Biochemistry and Molecular Biology and Research Institute Hospital 12 de Octubre (Imas12), Universidad Complutense de Madrid, Madrid, SpainAssessment of serological Plasmodium falciparum–specific antibodies in highly endemic areas provides valuable information about malaria status and parasite exposure in the population. Although serological evidence of Plasmodium exposure is commonly determined by Plasmodium-specific immunoglobulin G (IgG) levels; IgM and IgA are likely markers of malaria status that remain relatively unexplored. Previous studies on IgM and IgA responses have been based on their affinity for single antigens with shortage of immune responses analysis against the whole Plasmodium proteome. Here, we provide evidence of how P. falciparum infection triggers the production of specific IgM and IgA in plasma and its relationship with parasite density and changes in hematological parameters. A total of 201 individuals attending a hospital in Breman Asikuma, Ghana, were recruited into this study. Total and P. falciparum–specific IgM, IgA, and IgG were assessed by ELISA and examined in relation to age (0–5, 14–49, and ≥50 age ranges); infection (submicroscopic vs. microscopic malaria); pregnancy and hematological parameters. Well-known IgG response was used as baseline control. P. falciparum–specific IgM and IgA levels increased in the population with the age, similarly to IgG. These data confirm that acquired humoral immunity develops by repeated infections through the years endorsing IgM and IgA as exposure markers in endemic malaria regions. High levels of specific IgA and IgM in children were associated with microscopic malaria and worse prognosis, because most of them showed severe anemia. This new finding shows that IgM and IgA may be used as diagnostic markers in this age group. We also found an extremely high prevalence of submicroscopic malaria (46.27% on average) accompanied by IgM and IgA levels indistinguishable from those of uninfected individuals. These data, together with the observed lack of sensitivity of rapid diagnostic tests (RDTs) compared to PCR, invoke the urgent need to implement diagnostic markers for submicroscopic malaria. Overall, this study opens the potential use of P. falciparum–specific IgM and IgA as new serological markers to predict malaria status in children and parasite exposure in endemic populations. The difficulties in finding markers of submicroscopic malaria are highlighted, emphasizing the need to explore this field in depth.https://www.frontiersin.org/articles/10.3389/fcimb.2022.934321/fullPlasmodiumIgMIgAIgGantibodyimmunity
spellingShingle Paloma Abad
Patricia Marín-García
Marcos Heras
Julius N. Fobil
Alfred G. Hutchful
Amalia Diez
Antonio Puyet
Armando Reyes-Palomares
Isabel G. Azcárate
José M. Bautista
Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
Frontiers in Cellular and Infection Microbiology
Plasmodium
IgM
IgA
IgG
antibody
immunity
title Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
title_full Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
title_fullStr Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
title_full_unstemmed Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
title_short Microscopic and submicroscopic infection by Plasmodium falciparum: Immunoglobulin M and A profiles as markers of intensity and exposure
title_sort microscopic and submicroscopic infection by plasmodium falciparum immunoglobulin m and a profiles as markers of intensity and exposure
topic Plasmodium
IgM
IgA
IgG
antibody
immunity
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.934321/full
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