Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes

Thomson-Luque, Richard; Votborg-Novél, Lasse; Ndovie, Wanangwa; Andrade, Carolina M.; Niangaly, Moussa; Attipa, Charalampos; Lima, Nathália F.; Coulibaly, Drissa; Doumtabé, Didier; Guindo, Boubacary; Tangara, Bourama; Maiga, Fayçal; Koné, Abdoulaye K.; Traore, Karim; Kayentao, Kassoum; Ongoïba, Aïssata; Doumbo, Safiatou; Théra, Mahamadou A.; Traoré, Boubacar; Seydel, Karl B.; Osório, Nuno S.; Portugal, Sílvia

doi:10.1038/s41467-021-25062-z

Cited by 34 publications

(32 citation statements)

References 57 publications

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“…The analyses only showed a significant relationship between first (Dim1) component scores and age; with PfEMP1 domains being the top contributing variables ( Figure 4 ; Table 2 ). This is consistent with a recent proposal suggesting that there are ordered acquisition of antibodies targeting PfEMP1 ( 50 ). Taken together, these findings suggest that antibodies to multiple proteins may be acquired with age, and continuous exposure is a key factor in protection against clinical disease and protective immunity ( 2 ).…”

Section: Discussionsupporting

confidence: 93%

Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens

Takashima

Kanoi²,

Nagaoka³

et al. 2022

Front. Immunol.

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Concerted efforts to fight malaria have caused significant reductions in global malaria cases and mortality. Sustaining this will be critical to avoid rebound and outbreaks of seasonal malaria. Identifying predictive attributes that define clinical malaria will be key to guide development of second-generation tools to fight malaria. Broadly reactive antibodies against variable surface antigens that are expressed on the surface of infected erythrocytes and merozoites stage antigens are targets of naturally acquired immunity and prime candidates for anti-malaria therapeutics and vaccines. However, predicting the relationship between the antigen-specific antibodies and protection from clinical malaria remains unresolved. Here, we used new datasets and multiple approaches combined with re-analysis of our previous data to assess the multi-dimensional and complex relationship between antibody responses and clinical malaria outcomes. We observed 22 antigens (17 PfEMP1 domains, 3 RIFIN family members, merozoite surface protein 3 (PF3D7_1035400), and merozoites-associated armadillo repeats protein (PF3D7_1035900) that were selected across three different clinical malaria definitions (1,000/2,500/5,000 parasites/µl plus fever). In addition, Principal Components Analysis (PCA) indicated that the first three components (Dim1, Dim2 and Dim3 with eigenvalues of 306, 48, and 29, respectively) accounted for 66.1% of the total variations seen. Specifically, the Dim1, Dim2 and Dim3 explained 52.8%, 8.2% and 5% of variability, respectively. We further observed a significant relationship between the first component scores and age with antibodies to PfEMP1 domains being the key contributing variables. This is consistent with a recent proposal suggesting that there is an ordered acquisition of antibodies targeting PfEMP1 proteins. Thus, although limited, and further work on the significance of the selected antigens will be required, these approaches may provide insights for identification of drivers of naturally acquired protective immunity as well as guide development of additional tools for malaria elimination and eradication.

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Section: Discussionsupporting

confidence: 93%

Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens

Takashima

Kanoi²,

Nagaoka³

et al. 2022

Front. Immunol.

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“…The decreased circulation time observed in CM may result in iE avoiding splenic clearance, leading to higher parasitemia [ 7 ], as we found in our dataset. A correlation between decreased circulation time and increased parasitemia was retrospectively demonstrated from different studies, by Thomson-Luque et al [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria

Guillochon

Fraering

Joste

et al. 2022

The Journal of Infectious Diseases

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Cerebral malaria (CM) is the severest form of Plasmodium falciparum infection. Children under 5 years old are those most vulnerable to CM, and they consequently have the highest risk of malaria-related death. Parasite-associated factors leading to CM are not yet fully elucidated. We therefore sought to characterize the gene expression profile associated with CM, using RNA-seq data from 15 CM and 15 uncomplicated malaria (UM) isolates from Benin. CM parasites displayed reduced circulation times, possibly related to higher cytoadherence capacity. Consistent with the latter, we detected increased var genes abundance in CM isolates. Differential expression analyses showed that distinct transcriptome profiles are signatures of malaria severity. Genes involved in adhesion, excluding variant surface antigens, were dysregulated, supporting the idea of increased cytoadhesion capacity of CM parasites. Finally, we found dysregulated expression of genes in the entry into host pathway that may reflect greater erythrocyte invasion capacity of CM parasites.

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“…infection provided evidence of a hidden parasite biomass 64,65 . Furthermore, recent studies conducted in Malian children in the context of highly seasonal and low transmission settings where the parasite may need to adapt to a low frequency of competent vectors demonstrated transcriptomic differences in P. falciparum parasites detected in the dry compared to wet (high‐transmission) season, accounting for longer circulation of infected erythrocytes and increased splenic clearance 66,67 . The authors hypothesize that these differences contribute to the reduced parasite densities observed during the dry season, allowing the parasite to avoid immune‐mediated clearance and persist until transmission conditions become more favorable.…”

Section: Maintenance Of Antimalarial Antibodies and Sub‐clinical Plas...mentioning

confidence: 96%

“… 64 , 65 Furthermore, recent studies conducted in Malian children in the context of highly seasonal and low transmission settings where the parasite may need to adapt to a low frequency of competent vectors demonstrated transcriptomic differences in P. falciparum parasites detected in the dry compared to wet (high‐transmission) season, accounting for longer circulation of infected erythrocytes and increased splenic clearance. 66 , 67 The authors hypothesize that these differences contribute to the reduced parasite densities observed during the dry season, allowing the parasite to avoid immune‐mediated clearance and persist until transmission conditions become more favorable. However, subclinically infected children did exhibit increased P. falciparum ‐specific IgG responses and memory B cell activity compared to uninfected children, indicating that some preexisting exposure is associated with carriage of subclinical infection in highly seasonal transmission settings.…”

Section: Maintenance Of Antimalarial Antibodies and Sub‐clinical ...mentioning

confidence: 99%

The role of naturally acquired antimalarial antibodies in subclinicalPlasmodiumspp. infection

O’Flaherty

Roe

Fowkes

2022

Journal of Leukocyte Biology

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Undetected subclinical Plasmodium spp. infections are a significant barrier to eliminating malaria. In malaria-endemic areas, naturally acquired antimalarial antibodies develop with repeated infection. These antibodies can confer protection against the clinical manifestations of Plasmodium spp. infection in highly exposed populations, and several distinct functional antibody mechanisms have been defined in the clearance of Plasmodium parasites. However, the role of antimalarial antibodies during subclinical infection is less well defined. In this review, we examine the development and maintenance of antibody responses and the functional mechanisms associated with clinical protection, highlighted by epidemiological studies investigating the association between human immunity and detection of subclinical infection across various malaria transmission intensities. Understanding the development and role of the antimalarial antibody response during subclinical Plasmodium spp. infection will be essential to furthering novel interventions including vaccines and immunological biomarkers that can be utilized for malaria surveillance and ultimately progress malaria elimination.

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Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes

Cited by 34 publications

References 57 publications

Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens

Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens

Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria

The role of naturally acquired antimalarial antibodies in subclinicalPlasmodiumspp. infection

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