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

2021 ◽  
Vol 6 ◽  
pp. 79
Author(s):  
John W.G. Addy ◽  
Yaw Bediako ◽  
Francis M. Ndungu ◽  
John Joseph Valetta ◽  
Adam J. Reid ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Symptoms ◽  
Clinical Malaria ◽  
Multiple Infections ◽  
Acquired Immunity ◽  
Large Variability ◽  
Antibody Titres ◽  
Using Data ◽  
Malaria Episodes

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.

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

2021 ◽  
Vol 6 ◽  
pp. 79
Author(s):  
John W.G. Addy ◽  
Yaw Bediako ◽  
Francis M. Ndungu ◽  
John Joseph Valetta ◽  
Adam J. Reid ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Symptoms ◽  
Clinical Malaria ◽  
Multiple Infections ◽  
Acquired Immunity ◽  
Large Variability ◽  
Antibody Titres ◽  
Using Data ◽  
Malaria Episodes

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.

scholarly journals Interferon-γ and Interleukin-10 Responses during Clinical Malaria Episodes in Infants Aged 0–2 Years Prenatally Exposed to Plasmodium falciparum: Tanzanian Birth Cohort

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Boniphace Sylvester ◽  
Dinah B. Gasarasi ◽  
Said Aboud ◽  
Donath Tarimo ◽  
Siriel Masawe ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Prenatal Exposure ◽  
Geometric Mean ◽  
Placental Malaria ◽  
Clinical Malaria ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
Prenatally Exposed ◽  
Malaria Episodes

Background. Infants born to mothers with placental malaria are prenatally exposed to Plasmodium falciparum antigens. However, the effect of that exposure to subsequent immune responses has not been fully elucidated. This study aimed at determining the effect of prenatal exposure to P. falciparum on Interleukin-10 and Interferon-γ responses during clinical malaria episodes in the first 24 months of life. Methods. This prospective cohort study involved 215 infants aged 0-2 years born to mothers with or without placental malaria. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of IL-10 and IFN-γ in infants and detect IgM in cord blood. Data were analyzed using SPSS version 20. Findings. Geometric mean for IFN-γ in exposed infants was 557.9 pg/ml (95% CI: 511.6-604.1) and in unexposed infants it was 634.4 pg/ml (95% CI: 618.2-668.5) (P=0.02). Mean IL-10 was 22.4 pg/ml (95% CI: 19.4-28.4) and 15.1 pg/ml (95%CI: 12.4-17.6), respectively (P=0.01). Conclusions. Prenatal exposure to P. falciparum antigens significantly affects IL-10 and IFN-γ responses during clinical malaria episodes in the first two years of life.

Seasonal changes in the Plasmodium falciparum population in individuals and their relationship to clinical malaria: a longitudinal study in a Sudanese village

Parasitology ◽  
1998 ◽  
Vol 116 (6) ◽  
pp. 501-510 ◽  
Author(s):  
C. ROPER ◽  
W. RICHARDSON ◽  
I. M. ELHASSAN ◽  
H. GIHA ◽  
L. HVIID ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Malaria ◽  
Dry Season ◽  
Malaria Episode ◽  
Allelic Polymorphism ◽  
Cross Sectional ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Polymerase Chain ◽  
Malaria Episodes

Residents of Daraweesh village in Sudan were monitored for Plasmodium falciparum infection and malaria morbidity in 3 malaria seasons from 1993 to 1996. Malaria parasites were detected microscopically and by polymerase chain reaction (PCR) in a series of cross-sectional surveys. PCR revealed submicroscopical infections during the dry season, particularly among individuals who had recovered from a malaria episode following successful drug treatment. Clinical and subclinical infections were contrasted by assaying for allelic polymorphism at 2 gene loci, MSP-1 and GLURP and 2 hypotheses examined with reference to these data: that clinical malaria is associated with infection with novel parasite genotypes not previously detected in that host, or alternatively, that clinical malaria episodes are associated with an increased number of clones in an infection. We detected more mixed infections among clinical isolates, but people carrying parasites during the dry season were not found to have an increased risk of disease in the following malaria season. There was a clear association of disease with the appearance of novel parasite genotypes.

Different Genetic Characteristics of Plasmodium falciparum Isolates Collected During Successive Clinical Malaria Episodes in Senegalese Children

1996 ◽  
Vol 54 (6) ◽  
pp. 632-643 ◽  
Author(s):  
Hugues Contamin ◽  
Lassana Konate ◽  
Jean-Francois Trape ◽  
Odile Mercereau-Puijalon ◽  
Christophe Rogier ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clinical Malaria ◽  
Genetic Characteristics ◽  
Malaria Episodes

scholarly journals Immunoglobulin G Antibody Reactivity to a Group A Plasmodium falciparum Erythrocyte Membrane Protein 1 and Protection from P. falciparum Malaria

2007 ◽  
Vol 75 (5) ◽  
pp. 2415-2420 ◽  
Author(s):  
Pamela A. Magistrado ◽  
John Lusingu ◽  
Lasse S. Vestergaard ◽  
Martha Lemnge ◽  
Thomas Lavstsen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Antibody Responses ◽  
Acquired Immunity ◽  
Erythrocyte Membrane Protein ◽  
Variant Surface Antigens ◽  
Group A ◽  
Falciparum Erythrocyte Membrane Protein ◽  
Malaria Episodes

ABSTRACT Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2β domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2β-reactive antibodies might be involved in protection against malaria episodes.

scholarly journals Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

2013 ◽  
Vol 210 (2) ◽  
pp. 389-399 ◽  
Author(s):  
Matthias F. Muellenbeck ◽  
Beatrix Ueberheide ◽  
Borko Amulic ◽  
Alexandra Epp ◽  
David Fenyo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
B Cells ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Memory Function ◽  
Clinical Malaria ◽  
Memory B Cells ◽  
Gene Repertoire ◽  
Memory B Cell

Antibodies can protect from Plasmodium falciparum (Pf) infection and clinical malaria disease. However, in the absence of constant reexposure, serum immunoglobulin (Ig) levels rapidly decline and full protection from clinical symptoms is lost, suggesting that B cell memory is functionally impaired. We show at the single cell level that natural Pf infection induces the development of classical memory B cells (CM) and atypical memory B cells (AtM) that produce broadly neutralizing antibodies against blood stage Pf parasites. CM and AtM contribute to anti-Pf serum IgG production, but only AtM show signs of active antibody secretion. AtM and CM were also different in their IgG gene repertoire, suggesting that they develop from different precursors. The findings provide direct evidence that natural Pf infection leads to the development of protective memory B cell antibody responses and suggest that constant immune activation rather than impaired memory function leads to the accumulation of AtM in malaria. Understanding the memory B cell response to natural Pf infection may be key to the development of a malaria vaccine that induces long-lived protection.

scholarly journals Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans

mBio ◽  
2021 ◽  
Author(s):  
Anastasia K. Pickford ◽  
Lucas Michel-Todó ◽  
Florian Dupuy ◽  
Alfredo Mayor ◽  
Pedro L. Alonso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Functional Properties ◽  
Human Blood ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Malaria Parasites ◽  
Adaptive Process ◽  
Variant Genes

The ability of malaria parasites to adapt to changes in the human blood environment, where they produce long-term infection associated with clinical symptoms, is fundamental for their survival. CVGs, regulated at the epigenetic level, play a major role in this adaptive process, as changes in the expression of these genes result in alterations in the antigenic and functional properties of the parasites.

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