Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins in order to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Our findings show that children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against the PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in the Gambia, as compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses show a negative correlation between antibody levels and malaria transmission intensity for two PHIST antigens, Pf3D7_1102500 and Pf3D7_1401600. However, we report a correlation in antibody responses between schizont extract and Pf3D7_0532400 (p=0.00582). Acquisition of anti-PHIST antibodies was correlated with exposure to malaria for PHISTb protein Pf3D7_0532400 (p=0.009) but not the other PHIST antigens Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels, but the responses do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore potential for these parasite antigens as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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Molecular characterization of Plasmodium falciparum PHISTb proteins as potential targets of naturally-acquired immunity against malaria

Wellcome Open Research ◽

10.12688/wellcomeopenres.15919.2 ◽

2021 ◽

Vol 5 ◽

pp. 136

Author(s):

Tony I. Isebe ◽

Joel L. Bargul ◽

Bonface M. Gichuki ◽

James M. Njunge ◽

James Tuju ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Negative Correlation ◽

The Gambia ◽

Antibody Responses ◽

Transmission Intensity ◽

Parasite Development ◽

Malaria Transmission Intensity ◽

Transmission Region ◽

Antibody Levels

Background: Plasmodium falciparum causes the deadliest form of malaria in humans. Upon infection, the host’s infected red blood cells (iRBCs) are remodelled by exported parasite proteins to provide a niche for parasite development and maturation. Methods: Here we analysed the role of three PHISTb proteins Pf3D7_0532400, Pf3D7_1401600, and Pf3D7_1102500 by expressing recombinant proteins and evaluated antibody responses against these proteins using immune sera from malaria-exposed individuals from Kenya and The Gambia in Africa. Results: Children and adults from malaria-endemic regions recognized the three PHISTb proteins. Responses against PHISTb proteins varied with malaria transmission intensity in three different geographical sites in Kenya (Siaya and Takaungu) and The Gambia (Sukuta). Antibody responses against PHISTb antigens Pf3D7_1102500 and Pf3D7_1401600 were higher in Sukuta, a low transmission region in Gambia, compared to Siaya, a high transmission region in western Kenya, unlike Pf3D7_0532400. Anti-PHIST responses indicate negative correlation between antibody levels and malaria transmission intensity for Pf3D7_1102500 and Pf3D7_1401600. We report a correlation in antibody responses between schizont and gametocyte extract, but this is not statistically significant (cor=0.102, p=0.2851, CI=95%) and, Pf3D7_0532400 (cor=0.11, p=0.249, CI=95%) and Pf3D7_1401600 (cor=0.02, p=0.7968, CI=95%). We report a negative correlation in antibody responses between schizont and Pf3D7_1102500 (cor=-0.008, p=0.9348, CI=95%). There is a correlation between gametocyte extract and Pf3D7_1401600 (cor=-0.0402, p=0.6735, CI=95%), Pf3D7_1102500 (cor=0.0758, p=0.4271, CI=95%) and Pf3D7_0532400 (cor=0.155, p=0.1028, CI=95%). Acquisition of anti-PHIST antibodies correlates with exposure to malaria for Pf3D7_0532400 (p=0.009) but not Pf3D7_1102500 and Pf3D7_1401600 (p=0.507 and p=0.15, respectively, CI=95%). Children aged below 2 years had the lowest antibody levels which do not correlate with age differences. Conclusions: Collectively, these findings provide evidence of natural immunity against PHISTb antigens that varies with level of malaria exposure and underscore their potential as possible serological markers to P. falciparum infection aimed at contributing to malaria control through vaccine development.

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The Diversity, Multiplicity of Infection and Population Structure of P. falciparum Parasites Circulating in Asymptomatic Carriers Living in High and Low Malaria Transmission Settings of Ghana

Genes ◽

10.3390/genes10060434 ◽

2019 ◽

Vol 10 (6) ◽

pp. 434 ◽

Cited By ~ 8

Author(s):

Zakaria Abukari ◽

Ruth Okonu ◽

Samuel B. Nyarko ◽

Aminata C. Lo ◽

Cheikh C. Dieng ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Population Structure ◽

Malaria Transmission ◽

Parasite Prevalence ◽

Transmission Intensity ◽

Multiplicity Of Infection ◽

Malaria Transmission Intensity ◽

Ms Analysis ◽

Greater Accra Region ◽

Low Malaria Transmission

Background: Diversity in Plasmodium falciparum poses a major threat to malaria control and elimination interventions. This study utilized 12 polymorphic microsatellite (MS) markers and the Msp2 marker to examine diversity, multiplicity of infection (MOI) as well as the population structure of parasites circulating in two sites separated by about 92 km and with varying malaria transmission intensities within the Greater Accra Region of Ghana. Methods: The diversity and MOI of P. falciparum parasites in 160 non-symptomatic volunteers living in Obom (high malaria transmission intensity) and Asutsuare (low malaria transmission intensity) aged between 8 and 60 years was determined using Msp2 genotyping and microsatellite analysis. Results: The prevalence of asymptomatic P. falciparum carriers as well as the parasite density of infections was significantly higher in Obom than in Asutsuare. Samples from Asutsuare and Obom were 100% and 65% clonal, respectively, by Msp2 genotyping but decreased to 50% and 5%, respectively, when determined by MS analysis. The genetic composition of parasites from Obom and Asutsuare were highly distinct, with parasites from Obom being more diverse than those from Asutsuare. Conclusion: Plasmodium falciparum parasites circulating in Obom are genetically more diverse and distinct from those circulating in Asutsuare. The MOI in samples from both Obom and Asutsuare increased when assessed by MS analysis relative to MSP2 genotyping. The TA40 and TA87 loci are useful markers for estimating MOI in high and low parasite prevalence settings.

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High Levels of Asymptomatic and Subpatent Plasmodium falciparum Parasite Carriage at Health Facilities in an Area of Heterogeneous Malaria Transmission Intensity in the Kenyan Highlands

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.14-0355 ◽

2014 ◽

Vol 91 (6) ◽

pp. 1101-1108 ◽

Cited By ~ 19

Author(s):

Gillian H. Stresman ◽

Elizabeth Marube ◽

Teun Bousema ◽

Jonathan Cox ◽

Jennifer C. Stevenson ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Transmission ◽

Health Facilities ◽

Transmission Intensity ◽

Malaria Transmission Intensity ◽

Plasmodium Falciparum Parasite ◽

Falciparum Parasite

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Functional analysis of Plasmodium falciparum merozoite antigens: implications for erythrocyte invasion and vaccine development

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2001.1010 ◽

2002 ◽

Vol 357 (1417) ◽

pp. 25-33 ◽

Cited By ~ 17

Author(s):

Alan F. Cowman ◽

Deborah L. Baldi ◽

Manoj Duraisingh ◽

Julie Healer ◽

Kerry E. Mills ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Vaccine Development ◽

Loss Of Function ◽

Parasite Life Cycle ◽

Erythrocyte Invasion ◽

New Information ◽

Falciparum Merozoite ◽

Merozoite Antigens ◽

New Strategies

Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium , and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain–of–function and loss–of–function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.

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