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

Richard Thomson-Luque, Lasse Votborg-Novél, Wanangwa Ndovie, Carolina M. Andrade, Moussa Niangaly, Charalampos Attipa, Nathalia F. Lima, Drissa Coulibaly, Didier Doumtabe, Bouréima Guindo, Bourama Tangara, Fayçal Maiga, Abdoulaye Kassoum Kone, Karim Traore, Kassoum Kayentao, Aissata Ongoiba, Safiatou Doumbo, Mahamadou A. Thera, Boubacar Traoré, Karl Seydel, Nuno S. Osório and Silvia Portugal ()
Additional contact information
Richard Thomson-Luque: Heidelberg University Hospital
Lasse Votborg-Novél: Heidelberg University Hospital
Wanangwa Ndovie: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Carolina M. Andrade: Heidelberg University Hospital
Moussa Niangaly: Max Planck Institute for Infection Biology
Charalampos Attipa: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Nathalia F. Lima: Heidelberg University Hospital
Drissa Coulibaly: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Didier Doumtabe: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Bouréima Guindo: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Bourama Tangara: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Fayçal Maiga: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Abdoulaye Kassoum Kone: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Karim Traore: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Kassoum Kayentao: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Aissata Ongoiba: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Safiatou Doumbo: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Mahamadou A. Thera: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Boubacar Traoré: Malaria Research and Training Centre (MRTC), University of Sciences Techniques and Technologies of Bamako
Karl Seydel: University of Malawi College of Medicine
Nuno S. Osório: University of Minho
Silvia Portugal: Heidelberg University Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.

Date: 2021
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DOI: 10.1038/s41467-021-25062-z

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