Plasmodium vivax malaria: the epidemic could be largely underestimated in sub-Saharan Africa

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PLASMODIUM VIVAX MALARIA: THE EPIDEMIC COULD BE LARGELY UNDERESTIMATED IN SUB-SAHARAN AFRICA© Isabelle

PRESS RELEASE

06.12.2023

Researchers from the Institute of Parasitology and Tropical Pathology of the University of Strasbourg and the laboratory of Parasitology and Medical Mycology of the University Hospitals of Strasbourg, in collaboration with King's College London (England), the Institut Pasteur (Paris , France), the Pasteur Institute of Madagascar and the University of Addis Ababa (Ethiopia), reveal how Plasmodium vivax, one of the main agents of malaria, is capable of infecting populations in Africa. An astonishing discovery since these populations were until now considered naturally protected due to the absence of the Duffy protein on the surface of their red blood cells. These results suggest that a large number of individuals in Africa may be silent carriers of Plasmodium vivax and, therefore, that malaria may be largely underestimated in sub-Saharan Africa. The results of this work were published on December 5, 2023 in the journal Cell Host & Microbe .

Malaria kills nearly 600,000 people per year worldwide, mainly in sub-Saharan Africa. Epidemiological data have long suggested that Plasmodium vivax, the second most common Plasmodium species behind Plasmodium falciparum, could only infect young red blood cells (called reticulocytes) having the Duffy protein (or DARC for Duffy Antigen Receptor for Chemokines) on their surface. ). This particularity explained that Duffy-negative populations were naturally protected against infection by Plasmodium vivax, and therefore the absence of this parasite in sub-Saharan Africa, where populations are exclusively or overwhelmingly Duffy-negative. However, since the 2000s, thanks to the advent of new molecular diagnostic methods, many studies have revealed the ability of Plasmodium vivax to infect Duffy-negative subjects. A question therefore remained unanswered: how does the parasite penetrate young red blood cells in the absence of the Duffy protein?

To answer this question, Didier Ménard's team, in collaboration with scientists from King's College London (England), the Pasteur Institute, the Pasteur Institute of Madagascar and Addis Ababa University, examined, in vitro, the maturation process of red blood cells. Scientists have discovered that red blood cell precursor cells from Duffy-negative subjects temporarily express the Duffy protein during their development. However, only a small proportion of precursor cells that normally express the Duffy protein (1-3%) are likely to be infected by Plasmodium vivax. This study therefore confirms that whatever the status of the host (Duffy positive or negative), Plasmodium vivax is capable of replicating outside the blood circulation, in sites of red blood cell production, such as the bone marrow or the missed.

Beyond this discovery, these data raise new questions. It is indeed possible that a large number of Duffy negative individuals in sub-Saharan Africa are infected with Plasmodium vivax at red blood cell production sites without a detectable presence in the blood by traditional malaria diagnostic methods ( thin smear/thick smear and rapid diagnostic test). “This work suggests a little-known facet of Plasmodium vivax infection and an underestimate of the importance of this parasite in sub-Saharan Africa,” declares Didier Ménard, last author of the study. “Consequently, this must lead us to rethink strategies to combat this parasite,” he adds.

This research received financial support from the ANR, the Institut Pasteur, the “French Parasitology Alliance for Health Care” laboratory of excellence, the Excellence Initiative of the University of Strasbourg, and the Bill Foundation. and Melinda Gates, from the Foundation for Medical Research, the European Hematology Association, the Fondation de France (Prix Thérèse Lebrasseur) and the Marie Sklodowska-Curie research and innovation program of the European Union, Horizon 2020. This work was also supported by the Etablissement Français du Sang de Strasbourg (Sabine Haas) and the Center for Immunology and Infectious Diseases in Paris (Olivier Silvie).

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Source


Unveiling P. vivax invasion pathways in Duffy-negative individuals , Cell Host & Microbe, December 5, 2023
Isabelle Bouyssou, 1,2,3,12 Sara El Hoss,4,12,* Cécile Doderer-Lang, 5 Matthieu Schoenhals, 6
Lova Tsikiniaina Rasoloharimanana, 6 Inès Vigan-Womas, 7 Arsène Ratsimbasoa, 8 Andargie Abate, 9 Lemu Golassa , 9
Solenne Mabilotte, 5 Pascal Kessler, 10 Micheline Guillotte-Blisnick, 3 Francisco J. Martinez, 3 Chetan E. Chitnis, 3
John Strouboulis, 4,* and Didier Ménard 1,3,5,11,13,*

1Malaria Genetics and Resistance Unit, INSERM U1201, Institut Pasteur, Université Paris Cité, 75015 Paris, France
2E´ cole Doctorale ED515 ''Complexité du Vivant'', Sorbonne Université, 75005 Paris, France
3Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Université Paris Cité, 75015 Paris, France
4Red Cell Haematology Laboratory, Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London,
London SE5 9NU, UK
5Institute of Parasitology and Tropical Diseases, UR7292 Dynamics of Host-Pathogen Interactions, University of Strasbourg , 67000
Strasbourg, France
6Immunology of Infectious Diseases, Institut Pasteur of Madagascar, Antananarivo 101, Madagascar
7Institut Pasteur de Dakar, Dakar 220, Senegal
8Faculty of Medicine, University of Fianarantsoa, Fianarantsoa 301, Madagascar
9Aklilu Lemma Institute of Pathobiology, Addis Ababa University, PO Box 1176, Addis Ababa, Ethiopia
10Strasbourg Biomedicine Research Center, University of Strasbourg, 67000 Strasbourg, France
11Laboratory of Parasitology and Medical Mycology, CHU Strasbourg, 67000 Strasbourg, France
12These authors contributed equally
13Lead contact

DOI: https://doi.org/10.1016/j.chom.2023.11.007


https://www.pasteur.fr/fr/espace-pre...sub-saharienne