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1. Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia

Author

Balotin Fogang, Lionel Lellouche, Sukai Ceesay, Sainabou Drammeh, Fatou K. Jaiteh, Marc-Antoine Guery, Jordi Landier, Cynthia P. Haanappel, Janeri Froberg, David Conway, Umberto D’Alessandro, Teun Bousema, and Antoine Claessens

Subjects
Plasmodium falciparum, Asymptomatic, Clinical malaria, Seasonal transmission, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. Methods In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. Results Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p

Published
2024
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2. Design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple Plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes

Author

Sachel Mok, Archna P. Gupta, Zbynek Bozdech, J. Alexandra Rowe, Ashfaq Ghumra, and Antoine Claessens

Subjects
clone (Java method), Genetics, rho GTP-Binding Proteins, lcsh:Arctic medicine. Tropical medicine, Microarray, lcsh:RC955-962, Research, Gene Expression Profiling, Plasmodium falciparum, Context (language use), Antigens, Protozoan, Biology, biology.organism_classification, Genome, lcsh:Infectious and parasitic diseases, Gene expression profiling, Transcriptome, Infectious Diseases, Antigens, Surface, parasitic diseases, Parasitology, lcsh:RC109-216, Gene, Oligonucleotide Array Sequence Analysis
Abstract

Background The cytoadherence of Plasmodium falciparum is thought to be mediated by variant surface antigens (VSA), encoded by var, rif, stevor and pfmc-2tm genes. The last three families have rarely been studied in the context of cytoadherence. As most VSA genes are unique, the variability among sequences has impeded the functional study of VSA across different P. falciparum strains. However, many P. falciparum genomes have recently been sequenced, allowing the development of specific microarray probes for each VSA gene. Methods All VSA sequences from the HB3, Dd2 and IT/FCR3 genomes were extracted using HMMer software. Oligonucleotide probes were designed with OligoRankPick and added to the 3D7-based microarray chip. As a proof of concept, IT/R29 parasites were selected for and against rosette formation and the transcriptomes of isogenic rosetting and non-rosetting parasites were compared by microarray. Results From each parasite strain 50-56 var genes, 125-132 rif genes, 26-33 stevor genes and 3-8 pfmc-2tm genes were identified. Bioinformatic analysis of the new VSA sequences showed that 13 rif genes and five stevor genes were well-conserved across at least three strains (83-100% amino acid identity). The ability of the VSA-supplemented microarray chip to detect cytoadherence-related genes was assessed using P. falciparum clone IT/R29, in which rosetting is known to be mediated by PfEMP1 encoded by ITvar9. Whole transcriptome analysis showed that the most highly up-regulated gene in rosetting parasites was ITvar9 (19 to 429-fold up-regulated over six time points). Only one rif gene (IT4rifA_042) was up-regulated by more than four fold (five fold at 12 hours post-invasion), and no stevor or pfmc-2tm genes were up-regulated by more than two fold. 377 non-VSA genes were differentially expressed by three fold or more in rosetting parasites, although none was as markedly or consistently up-regulated as ITvar9. Conclusions Probes for the VSA of newly sequenced P. falciparum strains can be added to the 3D7-based microarray chip, allowing the analysis of the entire transcriptome of multiple strains. For the rosetting clone IT/R29, the striking transcriptional upregulation of ITvar9 was confirmed, and the data did not support the involvement of other VSA families in rosette formation.

Published
2011
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