PlasmoDynEvol (The adaptative value of a novel marker of drug susceptibility in Amazonian Plasmodium falciparum parasites) is a project selected in the 2014 CEBA annual call of proposals.
From a conversation on August 28, 2014
LabEx CEBA: What led you to parasitology?
Stéphane Pelleau: I did a research master in parasitology at the University Paris V. Then after, I did a thesis on malaria *, under the joint supervision of the Mediterranean University and the Pasteur Institute of Dakar, regarding the involvement of some elements of the immune system within the severity of disease. Then I spent a year at the Institute of Biomedical Research of the Health Service of the Armed Forces as an engineer to study the parasite resistance to antimalarials. I have been working on this issue in post-doctorate since 2012 at the Pasteur Institute in French Guiana (IPG), which hosts the National Reference Center for Malaria (CNRP), associated laboratory for the French West Indies and French Guiana.
Lise Musset: I completed my secondary schooling at Félix Eboué high school in Cayenne, and then I studied pharmacy in Reims and did a thesis on malaria and resistance to antimalarials at the University Paris V, linked to the laboratory of parasitology at the Bichat-Claude Bernard Hospital. After that, I did my post-doctorate at Columbia University in New York, in a laboratory specialized also in the study of resistance to antimalarials. I was hired by the IPG at the end of 2007 in my current position.
LC: What is your research topic?
SP: We have the same theme of research, which is to understand the mechanisms of resistance developed by the different species of parasites present in Guyana ** at various antimalarial drugs. We also conduct related work linked to the activities of the CNRP.
LM: Yes, in fact, it is monitoring parasites sensitivity to antimalarials. More specifically in the laboratory, we bring together parasites and antimalarial drugs at different doses, and watch which dose allows to kill parasites. This process has been carried out routinely for several years, and has allowed us to have a perspective on the evolution over time of the sensitivity of parasites. At the same time, we characterize the parasites at the genetic level.
Culture of Plasmodium falciparum © IPG
LC: In which scientific issue is PlasmoDynEvol project included?
SP: Plasmodium falciparum is able to develop resistance to all antimalarials., It’s therefore a race against this parasite. Different antimalarial drugs have been or are used for the treatment of malaria in Guyana. Chloroquine is one of them. It has been used for about 40 years to treat Plasmodium falciparum and then abandoned in the 90s because the parasites have become resistant to the molecule. Looking backabout this treatment, it seems to be the best model to study the phenomena of adaptation. This resistance results from a genetic mutation in the parasite ***. A few years later, it was discovered that the parasite populations were back to chloroquine-sensitive, not by re-emergence of the original susceptible strains, but by acquiring a second mutation that cancels the effect of the first. In the field, it is a novel phenomenon. In fact, Guyana parasites followed their own way! In general, the project has been trying to understand how resistance develop and disappear.
LM: The aim of the project is to understand why and how doubly mutated strains have become the majority today. What are the, internal, external factors and which is the advantage they have over other allowing them this release? Are these strains increasing faster? Are there more of their descendants? Are they better transmitted to mosquitoes (vectors of the disease)?
LC: Why is French Guiana an exceptional site for anchoring your project?
SP and LM: This type of “double mutation” was observed only in French Guiana. French Guiana is necessarily the anchor project area. The great advantage is that the IPG also hosts the CNRP, which provides a stable research on this topic in the region and therefore, to rely on i) a large collection of strains, ii) studies and results already obtained. This gives us a perspective on parasite strains circulating since the 90s in the region, a temporality that rarely exists in other endemic areas. In addition, we have been partnering with diagnostic centers throughout French Guiana who regularly send us their samples. We therefore study “natural” Guyanese strains.
LC: What makes this project so innovative for research on tropical terrestrial biodiversity?
LC: This project is innovative because it focuses on a mutation that had never been studied before and a phenomenon that has presently been observed in the region.
LC: Does the project involve people from other disciplines apart from yours?
SP: The third member of the project, Professor David Fidock of the immunology and microbiology department at Columbia University in New York, is a well- expert in genetic manipulation of parasites. It is part of the project, and is very intrigued by what has been happening over here!
LC: What will be the positive benefits of your project for the community?
SP: In the current context of a risk of a multi-resistant Asian parasites spreading to all malaria- prone areas, the project will contribute to a better understanding of how parasites adapt to changes in medicinal pressures. This will enable to better consider what may happen to other antimalarials.
LM: Chloroquine is part of a family of very large molecule, some of which are used today in other areas to treat malaria. The results will also provide a feedback that can potentially be used in these cases, but also for the development of new antimalarial drugs.
LC: How do you think about the CEBA’s added value ?
SP: We are part of the CEBA ‘s”health and biodiversity” axis, however we are aware that we do not have a “pure” ecological approach. While most researchers work to understand biodiversity in a conservation perspective, we stand rather with a view to elimination! Nevertheless, there is some similarity approach in studies to understand population trends regarding techniques and the way to think and analyze, whether the scale is microscopic or not. CEBA allows us to network with other researchers and create connections which we could not have necessarily achieved without it.
