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10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity.

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Title: 10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity.
Authors: Addy, John W. G.1 john.addy@rothamsted.ac.uk, Bediako, Yaw1,2, Ndungu, Francis M.3, Valetta, John Joseph4, Reid, Adam J.5, Mwacharo, Jedida3, Ngoi, Joyce Mwongeli3, Wambua, Joshua3, Otieno, Edward3, Musyoki, Jennifer3, Mohammed, Khadija Said3, Berriman, Matthew5, Marsh, Kevin6, Bejon, Philip3, Recker, Mario7, Langhorne, Jean1 Jean.Langhorne@crick.ac.uk
Source: Wellcome Open Research. 2022, Vol. 7, p1-22. 22p.
Subject Terms: *Malaria, *Immunity, Plasmodium falciparum, Antigens, Cohort analysis
Abstract: Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations. [ABSTRACT FROM AUTHOR]
Copyright of Wellcome Open Research is the property of Wellcome Trust and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: 10-year longitudinal study of malaria in children: Insights into acquisition and maintenance of naturally acquired immunity.
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  Data: <searchLink fieldCode="AR" term="%22Addy%2C+John+W%2E+G%2E%22">Addy, John W. G.</searchLink><relatesTo>1</relatesTo><i> john.addy@rothamsted.ac.uk</i><br /><searchLink fieldCode="AR" term="%22Bediako%2C+Yaw%22">Bediako, Yaw</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ndungu%2C+Francis+M%2E%22">Ndungu, Francis M.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Valetta%2C+John+Joseph%22">Valetta, John Joseph</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Reid%2C+Adam+J%2E%22">Reid, Adam J.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Mwacharo%2C+Jedida%22">Mwacharo, Jedida</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ngoi%2C+Joyce+Mwongeli%22">Ngoi, Joyce Mwongeli</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Wambua%2C+Joshua%22">Wambua, Joshua</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Otieno%2C+Edward%22">Otieno, Edward</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Musyoki%2C+Jennifer%22">Musyoki, Jennifer</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Mohammed%2C+Khadija+Said%22">Mohammed, Khadija Said</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Berriman%2C+Matthew%22">Berriman, Matthew</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Marsh%2C+Kevin%22">Marsh, Kevin</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Bejon%2C+Philip%22">Bejon, Philip</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Recker%2C+Mario%22">Recker, Mario</searchLink><relatesTo>7</relatesTo><br /><searchLink fieldCode="AR" term="%22Langhorne%2C+Jean%22">Langhorne, Jean</searchLink><relatesTo>1</relatesTo><i> Jean.Langhorne@crick.ac.uk</i>
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  Data: <searchLink fieldCode="JN" term="%22Wellcome+Open+Research%22">Wellcome Open Research</searchLink>. 2022, Vol. 7, p1-22. 22p.
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  Data: *<searchLink fieldCode="DE" term="%22Malaria%22">Malaria</searchLink><br />*<searchLink fieldCode="DE" term="%22Immunity%22">Immunity</searchLink><br /><searchLink fieldCode="DE" term="%22Plasmodium+falciparum%22">Plasmodium falciparum</searchLink><br /><searchLink fieldCode="DE" term="%22Antigens%22">Antigens</searchLink><br /><searchLink fieldCode="DE" term="%22Cohort+analysis%22">Cohort analysis</searchLink>
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  Data: Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Wellcome Open Research is the property of Wellcome Trust and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: Malaria
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      – SubjectFull: Plasmodium falciparum
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