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1. CUREMA project: a further step towards malaria elimination among hard-to-reach and mobile populations

Author

Alice Sanna, Yann Lambert, Irene Jimeno Maroto, Muriel Suzanne Galindo, Lorraine Plessis, Teddy Bardon, Carlotta Carboni, Jane Bordalo, Helene Hiwat, Hedley Cairo, Lise Musset, Yassamine Lazrek, Stéphane Pelleau, Michael White, Martha Suárez Mutis, Stephen Vreden, and Maylis Douine

Subjects
Malaria, Elimination, Research protocol, Public health intervention, Cross-border, Mobility, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In most countries engaged on the last mile towards malaria elimination, residual transmission mainly persists among vulnerable populations represented by isolated and mobile (often cross-border) communities. These populations are sometimes involved in informal or even illegal activities. In regions with Plasmodium vivax transmission, the specific biology of this parasite poses additional difficulties related to the need for a radical treatment against hypnozoites to prevent relapses. Among hard-to-reach communities, case management, a pillar of elimination strategy, is deficient: acute malaria attacks often occur in remote areas, where there is limited access to care, and drugs acquired outside formal healthcare are often inadequately used for treatment, which typically does not include radical treatment against P. vivax. For these reasons, P. vivax circulation among these communities represents one of the main challenges for malaria elimination in many non-African countries. The objective of this article is to describe the protocol of the CUREMA study, which aims to meet the challenge of targeting malaria in hard-to-reach populations with a focus on P. vivax. Results CUREMA is a multi-centre, international public health intervention research project. The study population is represented by persons involved in artisanal and small-scale gold mining who are active and mobile in the Guiana Shield, deep inside the Amazon Forest. The CUREMA project includes a complex intervention composed of a package of actions: (1) health education activities; (2) targeted administration of treatment against P. vivax after screening against G6PD deficiency to asymptomatic persons considered at risk of silently carrying the parasite; (3) distribution of a self-testing and self-treatment kit (malakit) associated with user training for self-management of malaria symptoms occurring while in extreme isolation. These actions are offered by community health workers at settlements and neighbourhoods (often cross-border) that represent transit and logistic bases of gold miners. The study relies on hybrid design, aiming to evaluate both the effectiveness of the intervention on malaria transmission with a pre/post quasi-experimental design, and its implementation with a mixed methods approach. Conclusions The purpose of this study is to experiment an intervention that addresses both Plasmodium falciparum and P. vivax malaria elimination in a mobile and isolated population and to produce results that can be transferred to many contexts facing the same challenges around the world.

Published
2024
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2. Which diagnostic test to use for Testing and Treatment strategies in Plasmodium vivax low-transmission settings: a secondary analysis of a longitudinal interventional studyResearch in context

Author

Hélène Tréhard, Lise Musset, Yassamine Lazrek, Michael White, Stéphane Pelleau, Ivo Mueller, Felix Djossou, Alice Sanna, Jordi Landier, Jean Gaudart, and Emilie Mosnier

Subjects
Plasmodium vivax, Low transmission, Serology, Elimination, Relapse, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The lack of sensitive field tests to diagnose blood stages and hypnozoite carriers prevents Testing and Treatment (TAT) strategies to achieve Plasmodium vivax elimination in low-transmission settings, but recent advances in Polymerase Chain Reaction (PCR) and serology position them as promising tools. This study describes a PCR-based TAT strategy (PCRTAT) implemented in Saint Georges (SGO), French Guiana, and explores alternative strategies (seroTAT and seroPCRTAT) to diagnose and treat P. vivax carriers. Methods: The PALUSTOP cohort study implemented in SGO (September 2017 to December 2018) screened participants for P. vivax using PCR tests and treated positive cases. Serology was also performed. Passive detection of P. vivax infection occurred during follow-up. Participants were categorised into overlapping treatment groups based on 2017 PCR and serological results. Strategies were described in terms of participants targeted or missed, primaquine contraindications (pregnancy, G6PD severe or intermediate deficiency), and sociodemographic characteristics. Findings: In 2017, 1567 inhabitants were included, aged 0–92 years. A total of 90 (6%) were P. vivax carriers and 390 seropositive (25%). PCRTAT missed 282 seropositive individuals while seroTAT would have missed 21 PCR-positive cases. Primaquine contraindications ranged from 12% to 17% across strategies. Interpretation: Serology and PCR are promising tools for targeted treatment strategies in P. vivax low-transmission settings, when field compatible sensitive tests will be available. Both seem necessary to capture blood stages and potential hypnozoite carriers, while avoiding mass treatment. However, high primaquine contraindications rates need consideration for successful elimination. Funding: Supported by European Funds for Regional Development, French Guiana Regional Health Agency, Pan American Health Organization, WHO, French Ministry for Research.

Published
2024
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3. Kinetics of glucose-6-phosphate dehydrogenase (G6PD) activity during Plasmodium vivax infection: implications for early radical malaria treatment

Author

Laureen Dahuron, Juste Goungounga, Moustapha Drame, Maylis Douine, Mathieu Nacher, Théo Blaise, Emilie Mosnier, Lise Musset, Marie Fouillet, Félix Djossou, and Loïc Epelboin

Subjects
Plasmodium vivax, G6PD/Glucose-6-phosphase dehydrogenase, Malaria, Primaquine, French Guiana, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Plasmodium vivax relapses due to dormant liver hypnozoites can be prevented with primaquine. However, the dose must be adjusted in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. In French Guiana, assessment of G6PD activity is typically delayed until day (D)14 to avoid the risk if misclassification. This study assessed the kinetics of G6PD activity throughout P. vivax infection to inform the timing of treatment. Methods For this retrospective monocentric study, data on G6PD activity between D1 and D28 after treatment initiation with chloroquine or artemisinin-based combination therapy were collected for patients followed at Cayenne Hospital, French Guiana, between January 2018 and December 2020. Patients were divided into three groups based on the number of available G6PD activity assessments: (i) at least two measurements during the P. vivax malaria infection; (ii) two measurements: one during the current infection and one previously; (iii) only one measurement during the malaria infection. Results In total, 210 patients were included (80, 20 and 110 in groups 1, 2 and 3, respectively). Data from group 1 showed that G6PD activity remained stable in each patient over time (D1, D3, D7, D14, D21, D28). None of the patients with normal G6PD activity during the initial phase (D1–D3) of the malaria episode (n = 44) was categorized as G6PD-deficient at D14. Patients with G6PD activity

Published
2024
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4. Temporal and spatial dynamics of Plasmodium falciparum clonal lineages in Guyana.

Author

Mathieu Vanhove, Philipp Schwabl, Collette Clementson, Angela M Early, Margaret Laws, Frank Anthony, Célia Florimond, Luana Mathieu, Kashana James, Cheyenne Knox, Narine Singh, Caroline O Buckee, Lise Musset, Horace Cox, Reza Niles-Robin, and Daniel E Neafsey

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission settings, parasites recombine with themselves, and the clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive the persistence and abundance of Plasmodium falciparum clonal lineages in Guyana, a country with relatively low malaria transmission, but the only setting in the Americas in which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. We performed whole genome sequencing on 1,727 Plasmodium falciparum samples collected from infected patients across a five-year period (2016-2021). We characterized the relatedness between each pair of monoclonal infections (n = 1,409) through estimation of identity-by-descent (IBD) and also typed each sample for known or candidate drug resistance mutations. A total of 160 multi-isolate clones (mean IBD ≥ 0.90) were circulating in Guyana during the study period, comprising 13 highly related clusters (mean IBD ≥ 0.40). In the five-year study period, we observed a decrease in frequency of a mutation associated with artemisinin partner drug (piperaquine) resistance (pfcrt C350R) and limited co-occurence of pfcrt C350R with duplications of plasmepsin 2/3, an epistatic interaction associated with piperaquine resistance. We additionally observed 61 nonsynonymous substitutions that increased markedly in frequency over the study period as well as a novel pfk13 mutation (G718S). However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions, given that clones carrying drug resistance polymorphisms do not demonstrate enhanced persistence or higher abundance than clones carrying polymorphisms of comparable frequency that are unrelated to resistance. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation.

Published
2024
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5. Determination of different social groups’ level of knowledge about malaria in a multicultural Amazonian cross-border context

Author

Mélanie Gaillet, Lise Musset, Claire Cropet, Félix Djossou, Adeline Mallard, Guillaume Odonne, Damien Davy, Maylis Douine, Loic Epelboin, Yassamine Lazrek, Luana Mathieu, Mathieu Nacher, and Emilie Mosnier

Subjects
Malaria, Knowledge, Attitudes and practices survey, French Guiana, Amazonia, Border, Public aspects of medicine, RA1-1270
Abstract

Abstract Background A steady decline in the number of cases of malaria was observed in the 2000s in French Guiana. This enabled regional health policies to shift their public health goal from control to elimination. To include inhabitants in this strategy, the main objective of this study was to describe knowledge about malaria, and related attitudes and practices in persons living in the French Guiana border. Methods We conducted a survey in people over 15 years old living in the twelve neighbourhoods of Saint-Georges de l’Oyapock with the highest malaria incidence. It comprised a 147-item questionnaire which collected data on socio-demographic characteristics and included a Knowledge Attitude and Practices survey on malaria. Knowledge-related data were studied using exploratory statistical methods to derive summary variables. A binary variable assessing level of knowledge was proposed and then assessed using exploratory approaches. Results The mean age of the 844 participants was 37.2 years [15.8], the male/female sex ratio was 0.8. In terms of nationality, 485 (57.5%) participants were Brazilian and 352 (41.7%) French. One third (305, 36.1%) spoke Brazilian Portuguese as their native language, 295 (34.9%) the Amerindian language Palikur, 36 (4.3%) French. The symptoms of malaria and prevention means were poorly known by 213 (25.2%) and 378 (44.8%) respondents, respectively. A quarter (206, 24.4%) did not know that malaria can be fatal. Overall, 251 people (29.7%) had an overall poor level of knowledge about malaria. Being under 25 years old, living in a native Amerindian neighbourhood, having an Amerindian mother tongue language, having risk behaviours related to gold mining were significantly associated with a poor level of knowledge. Conclusions This study is the first to describe the poor level of knowledge about malaria in populations living in the malaria endemic border area along the Oyapock river in French Guiana. Results will allow to reinforce, to diversify and to culturally adapt prevention messages and health promotion to increase their effectiveness with a view to quickly reaching the goal of malaria elimination through empowerment.

Published
2023
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6. Emerging infectious diseases and new pandemics: dancing with a ghost! Lessons in inter- and transdisciplinary research in French Guiana, South America

Author

Jean-François Guégan, Loïc Epelboin, Maylis Douine, Paul Le Turnier, Olivier Duron, Lise Musset, Christine Chevillon, Philippe Quénel, Mark Eric Benbow, and Benoît de Thoisy

Subjects
Biomedical research, Public health, Interdisciplinarity, Transdisciplinarity, One Health, Infectious disease, Infectious and parasitic diseases, RC109-216
Abstract

In light of current international public health challenges, calls for inter- and transdisciplinary research are increasing, particularly in response to complex and intersecting issues. Although widely used under the One Health flag, it is still unclear how inter- and transdisciplinary science should be applied to infectious disease research, public health, and the different stakeholders. Here, we present and discuss our common scientific and biomedical experience in French Guiana, South America to conduct and enrich research in vector-borne and zoonotic infectious diseases, with the aim to translate findings to public health and political stakeholders. We highlight the successful progressive dissolution of disciplinary boundaries that go beyond One Health positive-driven assumptions and argue that specific local conditions, as well as strong support from research and medical institutions, have facilitated an emulsion toward inter- and transdisciplinary science. This argument is intended to improve responses to public health concerns in French Guiana and other countries and regions of the world.

Published
2023
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7. Molecular detection of human Plasmodium species using a multiplex real time PCR

Author

Yassamine Lazrek, Célia Florimond, Béatrice Volney, Manon Discours, Emilie Mosnier, Sandrine Houzé, Stéphane Pelleau, and Lise Musset

Subjects
Medicine, Science
Abstract

Abstract Molecular detection methods have revealed higher sensitivity and specificity than conventional microscopy or rapid diagnostic tests for malaria diagnosis. In this study, we implemented, evaluated and validated according to the ISO 15,189 requirements, a multiplex real-time PCR assay to detect and identify the five human malaria parasites. DNA samples were extracted from whole blood or dried blood spots drawn from patients. Based on the External Quality Assessment (whole blood), this method shows 100% sensitivity and specificity. This PCR detected P. vivax up to 0.25 p/µl, P. falciparum and P. knowlesi up to 0.5 p/µl, P. ovale up to 1 p/µl and P. malariae up to 5 p/µl of blood. From blood spots (extraction from four punches), it detected P. vivax at 5 p/µl, P. falciparum, P. ovale and P. knowlesi at 20 p/µl and P. malariae at 125 p/µl. In conclusion, this quantitative PCR shows excellent performance, is easy to use and DNA saver. It is especially useful to actively screen large population groups and identify the five human malaria parasites in a context of low malaria transmission.

Published
2023
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9. Novel Chronic Anaplasmosis in Splenectomized Patient, Amazon Rainforest

Author

Olivier Duron, Rachid Koual, Lise Musset, Marie Buysse, Yann Lambert, Benoît Jaulhac, Denis Blanchet, Kinan Drak Alsibai, Yassamine Lazrek, Loïc Epelboin, Pierre Deshuillers, Céline Michaud, and Maylis Douine

Subjects
anaplasmosis, Amazon rainforest, bacteria, vector-borne infections, zoonoses, French Guiana, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report a case of unusual human anaplasmosis in the Amazon rainforest of French Guiana. Molecular typing demonstrated that the pathogen is a novel Anaplasma species, distinct to all known species, and more genetically related to recently described Anaplasma spp. causing infections in rainforest wild fauna of Brazil.

Published
2022
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10. Resurgence risk for malaria, and the characterization of a recent outbreak in an Amazonian border area between French Guiana and Brazil

Author

Emilie Mosnier, Isabelle Dusfour, Guillaume Lacour, Raphael Saldanha, Amandine Guidez, Margarete S. Gomes, Alice Sanna, Yanouk Epelboin, Johana Restrepo, Damien Davy, Magalie Demar, Félix Djossou, Maylis Douine, Vanessa Ardillon, Mathieu Nacher, Lise Musset, and Emmanuel Roux

Subjects
Plasmodium vivax, Anopheles darlingi, French Guiana, Brazil, Transnational, Outbreak investigation, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In 2017, inhabitants along the border between French Guiana and Brazil were affected by a malaria outbreak primarily due to Plasmodium vivax (Pv). While malaria cases have steadily declined between 2005 and 2016 in this Amazonian region, a resurgence was observed in 2017. Methods Two investigations were performed according to different spatial scales and information details: (1) a local study on the French Guiana border, which enabled a thorough investigation of malaria cases treated at a local village health center and the entomological circumstances in the most affected neighborhood, and (2) a regional and cross-border study, which enabled exploration of the regional spatiotemporal epidemic dynamic. Number and location of malaria cases were estimated using French and Brazilian surveillance systems. Results On the French Guianese side of the border in Saint-Georges de l’Oyapock, the attack rate was 5.5% (n = 4000), reaching 51.4% (n = 175) in one Indigenous neighborhood. Entomological findings suggest a peak of Anopheles darlingi density in August and September. Two female An. darlingi (n = 1104, 0.18%) were found to be Pv-positive during this peak. During the same period, aggregated data from passive surveillance conducted by Brazilian and French Guianese border health centers identified 1566 cases of Pv infection. Temporal distribution during the 2007–2018 period displayed seasonal patterns with a peak in November 2017. Four clusters were identified among epidemic profiles of cross-border area localities. All localities of the first two clusters were Brazilian. The localization of the first cluster suggests an onset of the outbreak in an Indigenous reservation, subsequently expanding to French Indigenous neighborhoods and non-Native communities. Conclusions The current findings demonstrate a potential increase in malaria cases in an area with otherwise declining numbers. This is a transborder region where human mobility and remote populations challenge malaria control programs. This investigation illustrates the importance of international border surveillance and collaboration for malaria control, particularly in Indigenous villages and mobile populations.

Published
2020
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11. Self-diagnosis and self-treatment of malaria in hard-to-reach and mobile populations of the Amazon: results of Malakit, an international multicentric intervention research project.

Author

Maylis Douine, Yann Lambert, Muriel Suzanne Galindo, Louise Mutricy, Alice Sanna, Cassio Peterka, Paola Marchesini, Helene Hiwat, Mathieu Nacher, Antoine Adenis, Magalie Demar, Lise Musset, Yassamine Lazrek, Hedley Cairo, Jane Bordalo Miller, Stephen Vreden, and Martha Suarez-Mutis

Subjects
mobile population, malaria control, self-diagnosis, self-treatment, quasi-experimental design, interventional research, Public aspects of medicine, RA1-1270
Abstract

Background: Illegal gold miners are currently key hosts for malaria in French Guiana (FG), with a risk of emergence of resistance linked to improper use of artemisinin-based combination therapy (ACT). The remoteness of the mines and regulatory issues hinder their access to health care. Methods: A quasi-experimental researched project (Malakit) implemented in FG borders with Brazil and Suriname aimed at determining the effectiveness of distributed kits for self-diagnosis and self-treatment to illegal gold miners, after training, at strategic border staging areas. Evaluation relied on questionnaires at inclusion and follow-up visits, and pre/post intervention surveys. The primary outcome was the proportion of persons reporting a use of certified ACT after a positive malaria diagnosis. The secondary outcomes assessed antimalarial adherence, kit use and impact on malaria epidemiology. Findings: The proportion of patients reporting a use of certified ACT after a positive diagnosis increased after the intervention (OR 1.8, 95%CI [1.1-3.0]). From April 2018 to March 2020, 3,733 persons participated in the intervention. The kit was used correctly by 71.7% [65.8-77.7] of the 223 persons reporting having used a malakit during the follow-up visits. No serious adverse events related to the misuse of malakit have been reported. The intervention appears to have accelerated the decline in malaria incidence in the region by 42.9%. Interpretation: This innovative international project showed that people with low education can correctly self-manage their malaria symptoms. This strategy could be integrated in the malaria control programs of the countries involved and considered in other regions with residual malaria in remote areas. Funding: This project was funded by the European Union, the Global Fund, Brazil MoH, Cayenne Hospital and FG Health Regional Agency. Editor's note: This translation in French was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. The Lancet Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations. Contexte: Les chercheurs d'or illégaux sont actuellement un réservoir clé du paludisme en Guyane, avec un risque d'émergence de résistance lié à une mauvaise utilisation des combinaisons thérapeutiques à base d'artémisinine (ACT). L'isolement de ces sites miniers clandestins et des contraintes règlementaires entravent leur accès aux soins. Méthodes: Un projet de recherche opérationnelle quasi-expérimental (Malakit) a été mis en œuvre aux frontières de la Guyane avec le Brésil et le Suriname. Il visait à déterminer l'efficacité de la distribution de kits d'autodiagnostic et d'autotraitement à des orpailleurs illégaux, après une formation adaptée, dans des zones stratégiques transfrontalières. L'évaluation s'est appuyée sur des questionnaires lors des visites d'inclusion et de suivi, et sur des enquêtes pré/post intervention. L'indicateur principal était la proportion de personnes déclarant avoir utilisé une ACT certifiée après un diagnostic positif de paludisme. Les indicateurs secondaires reposaient sur l'adhérence aux traitements antipaludiques, l'utilisation des kits et l'impact sur l'épidémiologie du paludisme. Résultats: La proportion de patients déclarant une utilisation d'ACT certifiée après un diagnostic positif a augmenté après l'intervention (OR 1,8, 95%CI [1,1-3,0]). D'avril 2018 à mars 2020, 3 733 personnes ont participé à l'intervention. Le kit a été utilisé correctement par 71,7% [65,8-77,7] des 223 personnes revues en visites de suivi ayant déclaré avoir utilisé un malakit. Aucun événement indésirable grave lié à une mauvaise utilisation du malakit n'a été signalé. L'intervention semble avoir accéléré la diminution de l'incidence du paludisme dans la région de 42,9%. Interprétation: Ce projet international innovant a montré que les personnes ayant un faible niveau d'éducation peuvent se prendre en charge par eux-mêmes pour des symptômes de paludisme. Cette stratégie pourrait être intégrée dans les programmes de lutte contre le paludisme des pays impliqués et envisagée dans d'autres régions où du paludisme résiduel persiste dans des zones isolées. Financement: Ce projet a été financé par l'Union Européenne, le Fonds Mondial, le Ministère de la santé du Brésil, le Centre Hospitalier de Cayenne et l'Agence Régionale de Santé de Guyane.

Published
2021
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12. Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

Author

Luana C Mathieu, Horace Cox, Angela M Early, Sachel Mok, Yassamine Lazrek, Jeanne-Celeste Paquet, Maria-Paz Ade, Naomi W Lucchi, Quacy Grant, Venkatachalam Udhayakumar, Jean SF Alexandre, Magalie Demar, Pascal Ringwald, Daniel E Neafsey, David A Fidock, and Lise Musset

Subjects
Guyana, artemisinin resistance, evolution, kelch 13, South America, malaria, Medicine, Science, Biology (General), QH301-705.5
Abstract

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016–2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield.

Published
2020
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13. Human Plasmodium vivax diversity, population structure and evolutionary origin.

Author

Virginie Rougeron, Eric Elguero, Céline Arnathau, Beatriz Acuña Hidalgo, Patrick Durand, Sandrine Houze, Antoine Berry, Sedigheh Zakeri, Rashidul Haque, Mohammad Shafiul Alam, François Nosten, Carlo Severini, Tamirat Gebru Woldearegai, Benjamin Mordmüller, Peter Gottfried Kremsner, Lilia González-Cerón, Gustavo Fontecha, Dionicia Gamboa, Lise Musset, Eric Legrand, Oscar Noya, Tepanata Pumpaibool, Pingchai Harnyuttanakorn, Khadijetou Mint Lekweiry, Musab Mohamad Albsheer, Muzamil Mahdi Abdel Hamid, Ali Ould Mohamed Salem Boukary, Jean-François Trape, François Renaud, and Franck Prugnolle

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history.

Published
2020
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14. Malakit: an innovative pilot project to self-diagnose and self-treat malaria among illegal gold miners in the Guiana Shield

Author

Maylis Douine, Alice Sanna, Muriel Galindo, Lise Musset, Vincent Pommier de Santi, Paola Marchesini, Edgard Dias Magalhaes, Martha Suarez-Mutis, Helene Hiwat, Mathieu Nacher, Stephen Vreden, and Laure Garancher

Subjects
Malaria, Control strategies, Gold mining, Mobile population, Cross-border, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Illegal gold miners in French Guiana, a French overseas territory (‘département’) located in Amazonia, often carry malaria parasites (up to 46.8%). While the Guiana Shield Region aims at malaria elimination, the high prevalence of Plasmodium in this hard-to-reach population in conjunction with frequent incorrect use of artemisinin-based anti-malarials could favour the emergence of resistant parasites. Due to geographical and regulatory issues in French Guiana, usual malaria control strategies cannot be implemented in this particular context. Therefore, new strategies targeting this specific population in the forest are required. Methods Numerous discussions among health institutions and scientific partners from French Guiana, Brazil and Suriname have led to an innovative project based on the distribution of kits for self-diagnosis and self-treatment of Plasmodium infections. The kit-distribution will be implemented at “resting sites”, which are areas across the border of French Guiana regularly frequented by gold miners. The main objective is to increase the appropriate use and complete malaria treatment after a positive malaria diagnosis with a rapid test, which will be evaluated with before-and-after cross-sectional studies. Monitoring indicators will be collected from health mediators at the time of kit distribution and during subsequent visits, and from illegal gold miners themselves, through a smartphone application. The project funding is multisource, including Ministries of Health of the three countries, WHO/PAHO, and the European Union. Results This project will start in April 2018 as a 18 month pilot study led by the Clinical Investigation Centre of Cayenne. Results should be available at the end of 2019. Discussion This innovative approach may have several limitations which should be taken into account, as potential side effects, kit misuse or resale, declarative main criteria, or no Plasmodium vivax curative treatment. Close monitoring is thus needed. Conclusions This project may be the best available solution to a specific and important public health challenge in the Guiana Shield. If the use of self-diagnosis and self-treatment approach is effective, this strategy could be sustained by health institutions in the region.

Published
2018
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15. Antiplasmodial activities of dyes against Plasmodium falciparum asexual and sexual stages: Contrasted uptakes of triarylmethanes Brilliant green, Green S (E142), and Patent Blue V (E131) by erythrocytes

Author

Louis-Jérôme Leba, Jean Popovici, Yannick Estevez, Stéphane Pelleau, Eric Legrand, Lise Musset, and Christophe Duplais

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P. falciparum including chloroquine-resistant isolates. Herein we have studied the antimalarial activities of dyes with different scaffold and we report that the triarylmethane dye (TRAM) Brilliant green inhibits the growth of asexual stages (IC50 ≤ 2 μM) and has exflagellation-blocking activity (IC50 ≤ 800 nM) against P. falciparum reference strains (3D7, 7G8) and chloroquine-resistant clinical isolate (Q206). In a second step we have investigated the antiplasmodial activities of two polysulfonated triarylmethane food dyes. Green S (E142) is weakly active against P. falciparum asexual stage (IC50 ≃ 17 μM) whereas Patent Blue V (E131) is inactive in both antimalarial assays. By applying liquid chromatography techniques for the culture supernatant analysis after cell washings and lysis, we report the detection of Brilliant green in erythrocytes, the selective uptake of Green S (E142) by infected erythrocytes, whereas Patent Blue V (E131) could not be detected within non-infected and 3D7-infected erythrocytes. Overall, our results suggest that two polysulfonated food dyes might display different affinity with transporters or channels on infected RBC membrane. Keywords: Antimalarial dyes, Transmission blocking, Triarylmethanes, Drug uptake, Brilliant green, Food dyes

Published
2017
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16. Illegal gold miners in French Guiana: a neglected population with poor health

Author

Maylis Douine, Emilie Mosnier, Quentin Le Hingrat, Charlotte Charpentier, Florine Corlin, Louise Hureau, Antoine Adenis, Yassamine Lazrek, Florence Niemetsky, Anne-Laure Aucouturier, Magalie Demar, Lise Musset, and Mathieu Nacher

Subjects
Gold mining, French Guiana, Neglected population, Global health, Transborder, Hypertension, Public aspects of medicine, RA1-1270
Abstract

Abstract Background In French Guiana, a French overseas territory in South America, 6 to 10 thousands undocumented persons work illegally in gold mining sites in the Amazonian forest. Precarious life conditions lead to poor health but few data exist on the health status of illegal gold miners in French Guiana. The objective of this article was to describe the sociodemographic and health status of this vulnerable population. Method A prospective cross-sectional survey was conducted in 2015 on gold mine supply sites at the border between French Guiana and Suriname. Health status was assessed through medical examination, past medical history, haemoglobin concentration, and HIV and malaria testing. A questionnaire was used to collect data about the migration itinerary and life conditions on mining sites. Results Among the 421 adults included in the study, 93.8% (395/421) were Brazilian, mainly from Maranhão (55.7%, 220/395), the poorest Brazilian state. The sex ratio was 2.4. Overall, 48% of persons never went to school or beyond the primary level. The median time spent in gold mining was quite long (10 years), with a high turn-over. One third of the surveyed population (37.1%, 156/421) had high blood pressure, and only two had a medical follow-up. Most persons had experienced malaria (89.3%, 376/421). They declared frequent arboviroses and digestive disorders. Active leishmaniasis was observed in 8.3% of gold miners. Among women, 28.5% were anemic. Concerning HIV, 36.6% (154/421) of persons, mainly men, never got tested before and 6 were tested positive, which represented an HIV prevalence of 1.43% (95%CI =0.29–2.5). Conclusion These findings support the hypothesis that mining in remote areas is linked to several specific illnesses. Theoretically, gold miners would be presumed to start their economical migration to French Guiana as a healthy group. However, their strenuous working and living conditions there lead to poor health caused by infectious and non infectious diseases. This description of their health status is precious for health policy planners in French Guiana given the importance of controlling communicable disease, and the severity and range of specific illnesses acquired by this neglected population. Trial registration Clinical trial registration PRS N° NCT02903706 . Retrospectively registered 09/13/2016.

Published
2017
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17. Malaria Hyperendemicity and Risk for Artemisinin Resistance among Illegal Gold Miners, French Guiana

Author

Vincent Pommier de Santi, Félix Djossou, Nicolas Barthes, Hervé Bogreau, Georges Hyvert, Christophe Nguyen, Stéphane Pelleau, Eric Legrand, Lise Musset, Antoine Adenis, and Sébastien Briolant

Subjects
malaria, French Guiana, illegal gold mining, hyperendemicity, epidemiology, vector-borne infections, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

To assess the prevalence of malaria among illegal gold miners in the French Guiana rainforest, we screened 205 miners during May–June 2014. Malaria prevalence was 48.3%; 48.5% of cases were asymptomatic. Patients reported self-medication with artemisinin-based combination therapy. Risk for emergence and spread of artemisinin resistance among gold miners in the rainforest is high.

Published
2016
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18. Effects of Mefloquine Use on Plasmodium vivax Multidrug Resistance

Author

Nimol Khim, Voahangy Andrianaranjaka, Jean Popovici, Saorin Kim, Arsene Ratsimbasoa, Christophe Benedet, Celine Barnadas, Remy Durand, Marc Thellier, Eric Legrand, Lise Musset, Michela Menegon, Carlo Severini, Bakri Y.M. Nour, Magali Tichit, Christiane Bouchier, Odile Mercereau-Puijalon, and Didier Ménard

Subjects
Plasmodium vivax, drug resistance, mdr-1 gene, mefloquine, copy number, malaria, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Numerous studies have indicated a strong association between amplification of the multidrug resistance-1 gene and in vivo and in vitro mefloquine resistance of Plasmodium falciparum. Although falciparum infection usually is not treated with mefloquine, incorrect diagnosis, high frequency of undetected mixed infections, or relapses of P. vivax infection triggered by P. falciparum infections expose non–P. falciparum parasites to mefloquine. To assess the consequences of such unintentional treatments on P. vivax, we studied variations in number of Pvmdr-1 (PlasmoDB accession no. PVX_080100, NCBI reference sequence NC_009915.1) copies worldwide in 607 samples collected in areas with different histories of mefloquine use from residents and from travelers returning to France. Number of Pvmdr-1 copies correlated with drug use history. Treatment against P. falciparum exerts substantial collateral pressure against sympatric P. vivax, jeopardizing future use of mefloquine against P. vivax. A drug policy is needed that takes into consideration all co-endemic species of malaria parasites.

Published
2014
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19. Malaria on the Guiana Shield: a review of the situation in French Guiana

Author

Lise Musset, Stéphane Pelleau, Romain Girod, Vanessa Ardillon, Luisiane Carvalho, Isabelle Dusfour, Margarete SM Gomes, Félix Djossou, and Eric Legrand

Subjects
malaria, French Guiana, drug resistance, epidemiology, vector control, control strategy, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract

In a climate of growing concern that Plasmodium falciparum may be developing a drug resistance to artemisinin derivatives in the Guiana Shield, this review details our current knowledge of malaria and control strategy in one part of the Shield, French Guiana. Local epidemiology, test-treat-track strategy, the state of parasite drug resistance and vector control measures are summarised. Current issues in terms of mobile populations and legislative limitations are also discussed.

Published
2014
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20. Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology.

Author

Stanislaw J Gabryszewski, Satish K Dhingra, Jill M Combrinck, Ian A Lewis, Paul S Callaghan, Matthew R Hassett, Amila Siriwardana, Philipp P Henrich, Andrew H Lee, Nina F Gnädig, Lise Musset, Manuel Llinás, Timothy J Egan, Paul D Roepe, and David A Fidock

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens.

Published
2016
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21. Development of a single nucleotide polymorphism barcode to genotype Plasmodium vivax infections.

Author

Mary Lynn Baniecki, Aubrey L Faust, Stephen F Schaffner, Daniel J Park, Kevin Galinsky, Rachel F Daniels, Elizabeth Hamilton, Marcelo U Ferreira, Nadira D Karunaweera, David Serre, Peter A Zimmerman, Juliana M Sá, Thomas E Wellems, Lise Musset, Eric Legrand, Alexandre Melnikov, Daniel E Neafsey, Sarah K Volkman, Dyann F Wirth, and Pardis C Sabeti

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Plasmodium vivax, one of the five species of Plasmodium parasites that cause human malaria, is responsible for 25-40% of malaria cases worldwide. Malaria global elimination efforts will benefit from accurate and effective genotyping tools that will provide insight into the population genetics and diversity of this parasite. The recent sequencing of P. vivax isolates from South America, Africa, and Asia presents a new opportunity by uncovering thousands of novel single nucleotide polymorphisms (SNPs). Genotyping a selection of these SNPs provides a robust, low-cost method of identifying parasite infections through their unique genetic signature or barcode. Based on our experience in generating a SNP barcode for P. falciparum using High Resolution Melting (HRM), we have developed a similar tool for P. vivax. We selected globally polymorphic SNPs from available P. vivax genome sequence data that were located in putatively selectively neutral sites (i.e., intergenic, intronic, or 4-fold degenerate coding). From these candidate SNPs we defined a barcode consisting of 42 SNPs. We analyzed the performance of the 42-SNP barcode on 87 P. vivax clinical samples from parasite populations in South America (Brazil, French Guiana), Africa (Ethiopia) and Asia (Sri Lanka). We found that the P. vivax barcode is robust, as it requires only a small quantity of DNA (limit of detection 0.3 ng/μl) to yield reproducible genotype calls, and detects polymorphic genotypes with high sensitivity. The markers are informative across all clinical samples evaluated (average minor allele frequency > 0.1). Population genetic and statistical analyses show the barcode captures high degrees of population diversity and differentiates geographically distinct populations. Our 42-SNP barcode provides a robust, informative, and standardized genetic marker set that accurately identifies a genomic signature for P. vivax infections.

Published
2015
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22. Whole genome sequencing of field isolates reveals a common duplication of the Duffy binding protein gene in Malagasy Plasmodium vivax strains.

Author

Didier Menard, Ernest R Chan, Christophe Benedet, Arsène Ratsimbasoa, Saorin Kim, Pheaktra Chim, Catherine Do, Benoit Witkowski, Remy Durand, Marc Thellier, Carlo Severini, Eric Legrand, Lise Musset, Bakri Y M Nour, Odile Mercereau-Puijalon, David Serre, and Peter A Zimmerman

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes.Through recent whole genome sequencing we obtained ≥ 70× coverage of the P. vivax genome from five field-isolates, resulting in ≥ 93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP) gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported.The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion is rapidly evolving, possibly in response to constraints imposed by erythrocyte Duffy negativity in some human populations.

Published
2013
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23. High performance of histidine-rich protein 2 based rapid diagnostic tests in French Guiana are explained by the absence of pfhrp2 gene deletion in P. falciparum.

Author

Mélanie Trouvay, Georges Palazon, Franck Berger, Béatrice Volney, Denis Blanchet, Emilie Faway, Damien Donato, Eric Legrand, Bernard Carme, and Lise Musset

Subjects
Medicine, Science
Abstract

BACKGROUND: Care for malaria patients in endemic areas has been improved through the increasing use of Rapid Diagnostic Tests (RDTs). Most RDTs target the histidine-rich protein-2 antigen (PfHRP2) to detect P. falciparum, as it is abundant and shows great heat stability. However, their use in South America has been widely questioned following a recent publication that pinpoints the high prevalence of Peruvian field isolates lacking the gene encoding this protein. In the remote rural health centers of French Guiana, RDTs are the main diagnosis tools. Therefore, a study of PfHRP2 RDT performances and pfhrp2 genotyping was conducted to determine whether a replacement of the current pLDH-based kit could be considered. METHODS: The performance study compared the SD Malaria Ag test P.f/Pan® kit with the current gold standard diagnosis by microscopy. The prevalence of pfhrp2 and pfhrp3 deletions were evaluated from 221 P. falciparum isolates collected between 2009 and 2011 in French Guiana. RESULTS: Between January 2010 and August 2011, 960 suspected cases of malaria were analyzed using microscopy and RDTs. The sensitivity of the SD Malaria Ag test P.f/Pan® for detection of P. falciparum was 96.8% (95% CI: 90.9-99.3), and 86.0% (95% CI: 78.9-91.5) for the detection of P. vivax. No isolates (95% CI: 0-4.5) lacking either exon of the pfhrp2 gene were identified among the 221 P. falciparum isolates analyzed, but 7.4% (95% CI: 2.8-15.4) lacked the exon 2 part of the pfhrp3 gene. CONCLUSIONS: Field isolates lacking either exon of the pfhrp2 gene are absent in this western part of South America. Despite its sensibility to detect P. vivax, the SD Malaria Ag test P.f/Pan® kit is a satisfying alternative to microscopy in remote health centers, where it is difficult to provide highly skilled microscopists and to maintain the necessary equipment.

Published
2013
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24. Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum.

Author

Stephanie G Valderramos, Juan-Carlos Valderramos, Lise Musset, Lisa A Purcell, Odile Mercereau-Puijalon, Eric Legrand, and David A Fidock

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Mutant forms of the Plasmodium falciparum transporter PfCRT constitute the key determinant of parasite resistance to chloroquine (CQ), the former first-line antimalarial, and are ubiquitous to infections that fail CQ treatment. However, treatment can often be successful in individuals harboring mutant pfcrt alleles, raising questions about the role of host immunity or pharmacokinetics vs. the parasite genetic background in contributing to treatment outcomes. To examine whether the parasite genetic background dictates the degree of mutant pfcrt-mediated CQ resistance, we replaced the wild type pfcrt allele in three CQ-sensitive strains with mutant pfcrt of the 7G8 allelic type prevalent in South America, the Oceanic region and India. Recombinant clones exhibited strain-dependent CQ responses that ranged from high-level resistance to an incremental shift that did not meet CQ resistance criteria. Nonetheless, even in the most susceptible clones, 7G8 mutant pfcrt enabled parasites to tolerate CQ pressure and recrudesce in vitro after treatment with high concentrations of CQ. 7G8 mutant pfcrt was found to significantly impact parasite responses to other antimalarials used in artemisinin-based combination therapies, in a strain-dependent manner. We also report clinical isolates from French Guiana that harbor mutant pfcrt, identical or related to the 7G8 haplotype, and manifest a CQ tolerance phenotype. One isolate, H209, harbored a novel PfCRT C350R mutation and demonstrated reduced quinine and artemisinin susceptibility. Our data: 1) suggest that high-level CQR is a complex biological process dependent on the presence of mutant pfcrt; 2) implicate a role for variant pfcrt alleles in modulating parasite susceptibility to other clinically important antimalarials; and 3) uncover the existence of a phenotype of CQ tolerance in some strains harboring mutant pfcrt.

Published
2010
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25. EVALUATION OF CIRCUMSPOROZOITE PROTEIN OF Plasmodium vivax TO ESTIMATE ITS PREVALENCE IN OIAPOQUE , AMAPÁ STATE, BRAZIL, BORDERING FRENCH GUIANA

Author

Margarete do Socorro Mendonça GOMES, José Luiz Fernandes VIEIRA, Gustavo Capatti CASSIANO, Lise MUSSET, Eric LEGRAND, Mathieu NACHER, Vanja Suely Calvosa D'Almeida COUTO, Ricardo Luiz Dantas MACHADO, and Álvaro Augusto Ribeiro D'Almeida COUTO

Subjects
Plasmodium vivax, Circumsporozoite protein, Brazil-French Guiana border, Genetic marker, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

SUMMARY Malaria is a major health problem for people who live on the border between Brazil and French Guiana. Here we discuss Plasmodium vivax distribution pattern in the town of Oiapoque, Amapá State using the circumsporozoite (CS) gene as a marker. Ninety-one peripheral blood samples from P. vivax patients have been studied. Of these, 64 individuals were from the municipality of Oiapoque (Amapá State, Brazil) and 27 patients from French Guiana (August to December 2011). DNA extraction was performed, and a fragment of the P. vivax CS gene was subsequently analyzed using PCR/RFLP. The VK210 genotype was the most common in both countries (48.36% in Brazil and 14.28% in French Guiana), followed by the P. vivax-like (1.10% in both Brazil and French Guiana) and VK247 (1.10% only in Brazil) in single infections. We were able to detect all three CS genotypes simultaneously in mixed infections. There were no statistically significant differences either regarding infection site or parasitaemia among individuals with different genotypes. These results suggest that the same genotypes circulating in French Guiana are found in the municipality of Oiapoque in Brazil. These findings suggest that there may be a dispersion of parasitic populations occurring between the two countries. Most likely, this distribution is associated with prolonged and/or more complex transmission patterns of these genotypes in Brazil, bordering French Guiana.

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26. Declines in prevalence alter the optimal level of sexual investment for the malaria parasite

Author

Angela M, Early, Flavia, Camponovo, Stéphane, Pelleau, Gustavo C, Cerqueira, Yassamine, Lazrek, Béatrice, Volney, Manuela, Carrasquilla, Benoît, de Thoisy, Caroline O, Buckee, Lauren M, Childs, Lise, Musset, and Daniel E, Neafsey

Subjects
Antimalarials, Gene Frequency, Plasmodium falciparum, Prevalence, Animals, Humans, Malaria, Falciparum, Models, Biological
Abstract

Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite's optimal life history strategy. Here, we explore whether declining infection rates can alter

Published
2022

27. Malaria in Gold Miners in the Guianas and the Amazon: Current Knowledge and Challenges

Author

Gilberto Gilmar Moresco, Stephen Vreden, Juan F. Sanchez, Paola Marchesini, Yann Lambert, Liana Reis Blume, Martha Cecilia Suárez-Mutis, Horace Cox, Vincent Pommier de Santi, Helene Hiwat, Alice Sanna, Leopoldo Villegas, Maylis Douine, Lise Musset, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de Parasitologie [Cayenne, Guyane française], National Malaria Programme [Suriname]], Ministry of Health [Paramaribo, Suriname], Ministry of Health, Brazilia, Brazil, Ministry of Public Health [Georgetown, Guyana], U.S. Naval Medical Research Unit No. 6 (NAMRU-6), Global Development One, Silver Spring, USA, Asociacion Civil Impacto Social, Bolivar, Venezuela, Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Health Regional Agency [Cayenne], Foundation for the Advancement of Scientific Research in Suriname [Paramaribo] (SWOS), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Ministry of Health [Brasília, Brazil], Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)

Subjects
Gold mining, Latin Americans, 030231 tropical medicine, Context (language use), 03 medical and health sciences, 0302 clinical medicine, Malaria transmission, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Deforestation, parasitic diseases, medicine, Immunology and Allergy, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Significant risk, Socioeconomics, Amazon rainforest, business.industry, 1. No poverty, medicine.disease, 3. Good health, Infectious Diseases, Geography, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Malaria
Abstract

Purpose of Review Following Paraguay and Argentina, several countries from the Amazon region aim to eliminate malaria. To achieve this, all key affected and vulnerable populations by malaria, including people working on gold mining sites, must be considered. What is the situation of malaria in these particular settings and what are the challenges? This literature review aims to compile knowledge to answer these questions. Recent Findings The contexts in which gold miners operate are very heterogeneous: size and localization of mines, links with crime, administrative status of the mines and of the miners, mobility of the workers or national regulations. The number of malaria cases has been correlated with deforestation (Brazil, Colombia), gold production (Colombia), gold prices (Guyana), or location of the mining region (Peru, Colombia, Venezuela, Guyana). The burden of malaria in gold mines differs between territories: significant in Guyana, French Guiana, or Venezuela; lower in Brazil. Although Plasmodiumvivax causes 75% of malaria cases in the Americas, P. falciparum is predominant in several gold mining regions, especially in the Guiana Shield. Because of the remoteness from health facilities, self-medication with under-the-counter antimalarials is frequent. This constitutes a significant risk for the emergence of new P. falciparum parasites resistant to antimalarial drugs. Summary Because of the workers’ mobility, addressing malaria transmission in gold mines is essential, not only for miners, but also to prevent the (re-)emergence of malaria. Strategies among these populations should be tailored to the context because of the heterogeneity of situations in different territories. The transnational environment favoring malaria transmission also requires transborder and regional cooperation, where innovative solutions should be considered and evaluated.

Published
2020
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28. Sharp decrease in malaria incidence among the French armed forces in French Guiana

Author

Guillaume Velut, Franck de Laval, François Delon, Albane d’Oléon, Maylis Douine, Emilie Mosnier, Bakridine Mmadi Mrenda, Aissata Dia, Lise Musset, Sébastien Briolant, Vincent Pommier de Santi, Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Direction Interarmées du Service de Santé en Guyane, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and The authors have declared no sources of funding.

Subjects
History, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Polymers and Plastics, Malaria incidence, Public Health, Environmental and Occupational Health, Gold miners, Business and International Management, Chemoprophylaxis, Armed Forces, Industrial and Manufacturing Engineering, French Guiana
Abstract

International audience

Published
2023
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29. Kelch13 mutations in Plasmodium falciparum and risk of spreading in Amazon basin countries

Author

Paola Marchesini, Maria-Paz Ade, Maylis Douine, Marcus V. G. Lacerda, Angel Manuel Alvarez, Luana Mathieu, Magda Magris, Yassamine Lazrek, Magalie Demar, Gisely Cardoso de Melo, Lise Musset, Prabhjot Singh, Wuelton Marcelo Monteiro, Horace Cox, Jean S F Alexandre, Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Ecole Doctorale 587 : Diversités, santé et développement en Amazonie (ED 587), Université de Guyane (UG), Réseau International des Instituts Pasteur (RIIP), Pan American Health Organization [Washington] (PAHO), Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), Universidade do Estado do Amazonas (UEA), Servicio Autónomo Centro Amazónico de Investigación y Control de Enfermedades Tropicales 'Simón Bolívar' (SACAICET), Ministry of Public Health [Georgetown, Guyana], Ministry of Health [Brasília, Brazil], Pan American Health Organization [Georgetown, Guyana] (PAHO), Pan American Health Organization - Organización Panamericana de la Salud [Caracas, Venezuela] (PAHO - OPS), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Instituto Leônidas e Maria Deane - Fiocruz Amazônia [Manaus, Brésil] (ILMD), Fundação Oswaldo Cruz (FIOCRUZ), This work was supported by Global Malaria Program (World Health Organization), Communicable Diseases and Environmental Determinants of Health Department (Pan American Health Organization), Guyamazon 3 Program, French Ministry for Research, European Commission Grant (Regional Fund for Development, Synergie GY0012082), Santé Publique France as National Reference Centre for Malaria and Investissement d’Avenir grant managed by Agence Nationale de la Recherche [CEBA (ref. ANR-10-LABX-25–01)]. L.C.M. received funding support from the Centre National d’Etudes Spatiales (CNES). The Manaus team was funded by Fundação de Amparo à Pesquisa do Estado do Amazonas-FAPEAM (PAPAC 005/2019, Posgrad and Pró-Estado). W.M.M. and M.V.G.L. are research fellows from CNPq., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Musset, Lise, Laboratoires d'excellence - CEnter of the study of Biodiversity in Amazonia - - CEBA2010 - ANR-10-LABX-0025 - LABX - VALID, CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)

Subjects
Veterinary medicine, Drug Resistance, Protozoan Proteins, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Pharmacology (medical), Malaria, Falciparum, Original Research, Sanger sequencing, 0303 health sciences, education.field_of_study, Human migration, 3. Good health, AcademicSubjects/MED00290, Infectious Diseases, symbols, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Brazil, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Amazon basin, Microbiology (medical), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Plasmodium falciparum, 030231 tropical medicine, Population, Biology, Kelch Repeat, Antimalarials, 03 medical and health sciences, symbols.namesake, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], parasitic diseases, Humans, AcademicSubjects/MED00740, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, 030304 developmental biology, Pharmacology, business.industry, Artemisinin resistance, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Mutation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, AcademicSubjects/MED00230, business
Abstract

Background The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. Objectives This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. Methods Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. Results No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%–0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%–52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. Conclusions There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.

Published
2021
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30. When local phytotherapies meet biomedicine. Cross-sectional study of knowledge and intercultural practices against malaria in Eastern French Guiana

Author

Mélanie Gaillet, Marc-Alexandre Tareau, Loïc Epelboin, Claire Cropet, Paul Brousse, Céline Michaud, F. Djossou, Maylis Douine, Emilie Mosnier, P. Travers, Lise Musset, B. Philogene, Damien Davy, Yassamine Lazrek, Guillaume Odonne, Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], DAAC - NGO [Saint Georges de l’Oyapock], Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Biome Tropical et Immuno-Pathophysiologie = Tropical Biome and ImmunoPhysiopathology [Lille] (TBIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Guyane (UG), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was funded by: European Funds for Regional Development (Synergie: n°GY0012082), the Regional Agency for Health of French Guiana, Cayenne Hospital, the French Ministry for Research and Santé Publique France through the Institut Pasteur de la Guyane. It was also supported by 'Investissement d’Avenir' grants managed by the Agence Nationale de la Recherche (Labex DRIIHM/IRDHEI: ANR-11-LABX-0010 and Labex CEBA: ANR-10-LABX-25-01)., ANR-11-LABX-0010,DRIIHM / IRDHEI,Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux(2011), ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Service des maladies infectieuses, Hopital Andree Rosemond, Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG), Musset, Lise, Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux - - DRIIHM / IRDHEI2011 - ANR-11-LABX-0010 - LABX - VALID, Laboratoires d'excellence - CEnter of the study of Biodiversity in Amazonia - - CEBA2010 - ANR-10-LABX-0025 - LABX - VALID, Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens [LEEISA], Centre National de Référence du Paludisme [Cayenne, Guyane française] [CNR - laboratoire associé], Centre d'Investigation Clinique Antilles-Guyane [CIC - Antilles Guyane], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale [SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD], Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), and Observatoire Hommes Milieux (OHM) Oyapock-Labex DRIIHM ANR-11-LABX-0010

Subjects
Male, Health Knowledge, Attitudes, Practice, Cross-sectional study, Ethnic group, Medical pluralism, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SHS]Humanities and Social Sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, education.field_of_study, Rapid diagnostic test, Amazon rainforest, 3. Good health, French Guiana, Geography, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Knowledge attitudes and practices, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Adult, medicine.medical_specialty, Fever, Integrated community survey, Population, 03 medical and health sciences, Antimalarials, Young Adult, Medicinal plants, Amazonia, Environmental health, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, education, Traditional phytotherapies, Biomedicine, 030304 developmental biology, Pharmacology, Plants, Medicinal, business.industry, Public health, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SHS.ANTHRO-SE]Humanities and Social Sciences/Social Anthropology and ethnology, medicine.disease, Malaria, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, OHM Oyapock, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, medicinal plants, traditional phytotherapies, integrated community survey, medical pluralism, knowledge attitudes and practices, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Medicine, Traditional, business, Phytotherapy
Abstract

International audience; Ethnopharmacological relevance: In French Guiana, traditional phytotherapies are an important part of self-healthcare, however, a precise understanding of the interactions between local phytotherapies and biomedicine is lacking. Malaria is still endemic in the transition area between French Guiana and Brazil, and practices of self-treatment, although difficult to detect, have possible consequences on the outcome of public health policies.Aim of the study: The objectives of this research were 1) to document occurences of co-medication (interactions between biomedicine and local phytotherapies) against malaria around Saint-Georges de l’Oyapock (SGO), 2) to quantify and to qualify plant uses against malaria, 3) and to discuss potential effects of such co-medications, in order to improve synergy between community efforts and public health programs in SGO particularly, and in Amazonia more broadly.Materials and methods: This cross-sectional study was conducted in 2017 in SGO. Inhabitants of any age and nationality were interviewed using a questionnaire (122 questions) about their knowledge and habits regarding malaria, and their use of plants to prevent and treat it. They were invited to show their potential responses on a poster illustrating the most common antimalarial plants used in the area. In order to correlate plant uses and malaria epidemiology, all participants subsequently received a medical examination, and malaria detection was performed by Rapid Diagnostic Test (RDT) and Polymerase Chain Reaction (PCR).Results: A total of 1566 inhabitants were included in the study. Forty-six percent of them declared that they had been infected by malaria at least once, and this rate increased with age. Every person who reported that they had had malaria also indicated that they had taken antimalarial drugs (at least for the last episode), and self-medication against malaria with pharmaceuticals was reported in 142 cases. A total of 550 plant users was recorded (35.1% of the interviewed population). Among them 95.5% associated pharmaceuticals to plants. All plants reported to treat malaria were shared by every cultural group around SGO, but three plants were primarily used by the Palikur: Cymbopogon citratus, Citrus aurantifolia and Siparuna guianensis. Two plants stand out among those used by Creoles: Eryngium foetidum and Quassia amara, although the latter is used by all groups and is by far the most cited plant by every cultural group. Cultivated species accounts for 91.3% of the use reports, while wild taxa account for only 18.4%.Conclusions: This study showed that residents of SGO in French Guiana are relying on both traditional phytotherapies and pharmaceutical drugs to treat malaria. This medical pluralism is to be understood as a form of pragmatism: people are collecting or cultivating plants for medicinal purposes, which is probably more congruent with their respective cultures and highlights the wish for a certain independence of the care process. A better consideration of these practices is thus necessary to improve public health response to malaria.

Published
2021
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31. Ecology, evolution, and epidemiology of zoonotic and vector-borne infectious diseases in French Guiana: Transdisciplinarity does matter to tackle new emerging threats

Author

Anne Lavergne, Marine Ginouves, Florian Binetruy, Claude Flamand, Mathieu Nacher, Emmanuel Roux, Roxane Schaub, Sébastien Gourbière, Benoit de Thoisy, Pierre Couppié, Arthur Kocher, Lise Musset, Philippe Quénel, Sourakhata Tirera, Luisiane Carvalho, Jérôme Murienne, Sébastien Briolant, Magalie Demar, Yanouk Epelboin, Ghislaine Prévot, Olivier Duron, Isabelle Dusfour, Benjamin Roche, Maylis Douine, Stéphane Pelleau, Luana Mathieu, Agathe Chavy, Loïc Epelboin, Alain Franc, Paul Le Turnier, Pauline Thill, Jean-François Guégan, Emeline Houël, Dominique Rousset, Stanislas Talaga, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Réseau International des Instituts Pasteur (RIIP), Centre de Recherche en Ecologie et Evolution de la Santé (CREES), Institut de Recherche pour le Développement (IRD)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Parasitologie [Cayenne, Guyane française], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Santé publique France Guyane, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Université de Guyane (UG), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Département de Santé Globale - Department Global Health, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Unité d'Epidémiologie [Cayenne, Guyane française], Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biome Tropical et Immuno-Pathophysiologie = Tropical Biome and ImmunoPhysiopathology [Lille] (TBIP), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG), Ecologie des forêts de Guyane (UMR ECOFOG), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute for the Science of Human History (MPI-SHH), Max-Planck-Gesellschaft, Evolution et Diversité Biologique (EDB), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris] (IP), UMR 228 Espace-Dev, Espace pour le développement, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), LMI Sentinela [Rio de Janeiro], Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Service Universitaire des Maladies Infectieuses et du Voyageur [Tourcoing], Centre Hospitalier Tourcoing, Centre Hospitalier Gustave Dron [Tourcoing], Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This work has benefited from three 'Investissement d’Avenir' grants managed by Agence Nationale de la Recherche (CEBA: ANR-10-LABX-25-01, TULIP: ANR-10-LABX-0041, DRIIHM: ANR-11-LABX-0010). The two lead coauthors received European funding through the European Regional Development Fund Operational Program FEDER RESERVOIRS Project (BdT) and a US NSF-NIH (NSF#1911457) Ecology of infectious diseases award (J-FG). J-FG is also supported by IRD, INRAE, and Université of Montpellier. OD thanks l’Office français de la biodiversité, le Groupe d'Étude et de Protection des Oiseaux en Guyane (GEPOG), la Direction de l'Alimentation, de l'Agriculture et de la Forêt de Guyane (DAAF). AL acknowledges European funding through the European Regional Development Fund Operational Program FEDER RESERVOIRS, CAROLLIA, EFAG and VIRUSES projects. LM is supported by European funding through the European Regional Development Fund Operational Program FEDER ELIMALAR project and Santé publique France as the National Reference Center for Malaria. PQ thanks Publique France/Cire Guyane, CNR sur les arboviroses, CNR du paludisme. EH and ID acknowledge European funding through the European Regional Development Fund Operational Program FEDER CONTROLE Projet, the French Guiana Regional Council and the Air Liquide Foundation. SB is supported by the French Army (Grant LR607e). ER is grateful for European funding through the European Regional Development Fund Operational Program FEDER OSE-Guyamapa project, the French Embassy in Brazil, the Guyamazon program ('GAPAM-Sentinela' project), CNES, and the Bill and Melinda Gates Foundation., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), ANR-10-LABX-0041,TULIP,Towards a Unified theory of biotic Interactions: the roLe of environmental(2010), ANR-11-LABX-0010,DRIIHM / IRDHEI,Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux(2011), Génétique et évolution des maladies infectieuses (GEMI), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz (FIOCRUZ), Dusfour, Isabelle, Laboratoires d'excellence - CEnter of the study of Biodiversity in Amazonia - - CEBA2010 - ANR-10-LABX-0025 - LABX - VALID, Towards a Unified theory of biotic Interactions: the roLe of environmental - - TULIP2010 - ANR-10-LABX-0041 - LABX - VALID, Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux - - DRIIHM / IRDHEI2011 - ANR-11-LABX-0010 - LABX - VALID, Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Guyane (UG), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)

Subjects
0301 basic medicine, Microbiology (medical), Emerging and reemerging infectious diseases, Ecology (disciplines), media_common.quotation_subject, [SDV]Life Sciences [q-bio], [SDE.MCG]Environmental Sciences/Global Changes, 030106 microbiology, Immigration, Interdisciplinary Research, Wildlife, Vector Borne Diseases, Animals, Wild, Anthropogenic pressures, Biology, Microbiology, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Zoonoses, Genetics, Prevalence, Animals, Humans, Human Activities, Molecular Biology, Epidemiologic transition, Global change, Ecology, Evolution, Behavior and Systematics, Ecosystem, media_common, Demography, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Resistance (ecology), Ecology, Incidence, Outbreak, 15. Life on land, French Guiana, [SDV] Life Sciences [q-bio], Epidemiological transition, [SDE.MCG] Environmental Sciences/Global Changes, 030104 developmental biology, Infectious Diseases, Promiscuity, Vector (epidemiology), [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract

International audience; French Guiana is a European ultraperipheric region located on the northern Atlantic coast of South America. It constitutes an important forested region for biological conservation in the Neotropics. Although very sparsely populated, with its inhabitants mainly concentrated on the Atlantic coastal strip and along the two main rivers, it is marked by the presence and development of old and new epidemic disease outbreaks, both research and health priorities. In this review paper, we synthetize 15 years of multidisciplinary and integrative research at the interface between wildlife, ecosystem modification, human activities and sociodemographic development, and human health. This study reveals a complex epidemiological landscape marked by important transitional changes, facilitated by increased interconnections between wildlife, land-use change and human occupation and activity, human and trade transportation, demography with substantial immigration, and identified vector and parasite pharmacological resistance. Among other French Guianese characteristics, we demonstrate herein the existence of more complex multi-host disease life cycles than previously described for several disease systems in Central and South America, which clearly indicates that today the greater promiscuity between wildlife and humans due to demographic and economic pressures may offer novel settings for microbes and their hosts to circulate and spread. French Guiana is a microcosm that crystallizes all the current global environmental, demographic and socioeconomic change conditions, which may favor the development of ancient and future infectious diseases.

Published
2021
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32. Field Performance of Mass PCR Screening and Targeted Treatment in an Amazonian Low Malaria Transmission Setting

Author

Yassamine Lazrek, Carbunar A, Lise Musset, Gaudart J, Loïc Epelboin, Emmanuel Roux, Stéphane Pelleau, R. Priam, Céline Michaud, F. Djossou, Emilie Mosnier, Mélanie Gaillet, M. Demar, J. Landier, Luana Mathieu, M. Douine, and Mathieu Nacher

Subjects
Geography, Malaria transmission, Field (physics), Amazonian, parasitic diseases, Cartography
Abstract

The three main obstacles to the elimination of malaria in French Guiana are asymptomatic carriers of Plasmodium vivax, relapses and, to a lesser extent, Plasmodium falciparum. This study aims to assess the impact of PCR-based mass screening and treatment (MSAT) interventions in this malaria-endemic area.Two MSAT interventions were conducted twelve months apart in inhabitants of Saint Georges de l’Oyapock village, which has the highest malaria burden in French Guiana. Symptomatic malaria incidence was also passively monitored through the local health center from 12 months before the first intervention until the end of the second intervention.At the time of the first intervention, malaria prevalence was 6.7% [CI95 5.4-7.9%], including 90% of Plasmodium vivax cases and 10% Plasmodium falciparum (n=1,501 participants). Twelve months later, it had decreased by 53.7% to a value of 2.5% [CI95 2.0-3.9%] (pPlasmodium vivax and Plasmodium falciparum carriage, respectively. Similarly, the passive malaria detection carried out by the health center during the 12-month surveillance period that followed the first MSAT noted a decrease in symptomatic Plasmodium spp..This study suggests that the implementation of mass PCR testing and the subsequent malaria treatment of positive cases could reduce the prevalence of both symptomatic and asymptomatic malaria infections in the Amazonian context.

Published
2021
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33. Self-Diagnosis and Self-Treatment of Malaria in Hard-to-Reach and Mobile Populations of the Amazon: Results of Malakit, a Multicentric Intervention Research Project. Towards a Paradigm Shift?

Author

Jane Bordalo Miller, Helene Hiwat, Stephen Vreden, Muriel Galindo, Paola Marchesini, Martha Cecilia Suárez-Mutis, Alice Sanna, Mathieu Nacher, Yann Lambert, Magalie Demar, Maylis Douine, Hedley Cairo, Antoine Adenis, Lise Musset, Cassio Peterka, Louise Mutricy, and Yassamine Lazrek

Subjects
medicine.medical_specialty, business.industry, Conflict of interest, Declaration, Certification, medicine.disease, Family medicine, Intervention (counseling), General Data Protection Regulation, Health care, medicine, media_common.cataloged_instance, European union, business, Malaria, media_common
Abstract

Background: Illegal gold miners are currently a key reservoir for malaria in French Guiana (FG), with a risk of emergence of resistance linked to improper use of artemisinin-based combination therapy (ACT). The remoteness of the mines and regulatory issues hinder their access to health care. Methods: An intervention researched project (Malakit) implemented in FG borders with Brazil and Suriname aimed at determining the effectiveness of distributed kits for self-diagnosis and self-treatment to illegal gold miners, after training, at strategic border staging areas. Evaluation relied on questionnaires at inclusion and follow-up visits, and pre/post intervention surveys. The primary outcome was the proportion of persons reporting a use of certified ACT after a positive malaria diagnosis. The secondary outcomes assessed antimalarial adherence, kit use and impact on malaria epidemiology. Findings: The proportion of patients reporting a use of certified ACT after a positive diagnosis increased after the intervention (OR 1.8, 95%CI [1.1-3.0]). From April 2018 to March 2020, 3,733 persons participated in the intervention. The kit was used correctly by 71.7% [65.8-77.7] of the 223 persons reporting having used a malakit during the follow-up visits. The intervention could have accelerated the decline in malaria incidence in the region by 42.9%. InterpretationThis innovative international project showed that people with low education can correctly self-manage their malaria symptoms. This strategy could be integrated in the malaria control programs of the countries involved and considered in other regions with residual malaria in remote areas. Funding: This project was funded by the European Union, the Global Fund, PAHO, Brazil MoH, Cayenne Hospital and FG Health Regional Agency. Declaration of Interest: Any authors declare to have no conflict of interest. Ethical Approval: Each participant gave a written consent after clear and appropriate information. Ethics approvals were obtained from countries where the project was implemented (Table 1). The project was the subject of a Normal CNIL Declaration on 24 May 2018 (Declaration Number 2188949 v 0) for data analysis according to the General Data Protection Regulation (European Union Regulation 2016/679).

Published
2021
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34. Spatio-Temporal Dynamics of Plasmodium falciparum and Plasmodium vivax in French Guiana: 2005–2019

Author

Jenna Scully, Jean Gaudart, Félix Djossou, Mathieu Nacher, Emmanuel Roux, A. Carbunar, Emilie Mosnier, Alice Sanna, Lise Musset, Magalie Demar, Nicolas Garceran, Roux, Emmanuel, Mailman School of Public Health, Columbia University [New York], Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Centres Délocalisés de Prévention et de Soins (CDPS), UMR 228 Espace-Dev, Espace pour le développement, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), LMI Sentinela [Rio de Janeiro], Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut Pasteur de la Guyane, Laboratoire de Parasitologie [Cayenne, Guyane française], Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Réseau International des Instituts Pasteur (RIIP), Agence Régionale de la Santé [Cayenne, Guyane française] (ARS), Laboratoire Hospitalo-Universitaire de Parasitologie et Mycologie [Cayenne, Guyane Française], Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Aix Marseille Université (AMU), Unité des biostatistiques et des technologies de l'information et de la communication [AP-HM Hôpital La Timone], Hôpital de la Timone [CHU - APHM] (TIMONE), Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), and Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé)

Subjects
Plasmodium, Health, Toxicology and Mutagenesis, Plasmodium vivax, lcsh:Medicine, law.invention, 0302 clinical medicine, falciparum, [STAT.AP] Statistics [stat]/Applications [stat.AP], law, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Autoregressive integrated moving average, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], ComputingMilieux_MISCELLANEOUS, 0303 health sciences, [STAT.AP]Statistics [stat]/Applications [stat.AP], biology, Amazon rainforest, Incidence (epidemiology), 3. Good health, Plasmodium falciparum, French Guiana, [STAT]Statistics [stat], Transmission (mechanics), Geography, Cartography, Spatial stability, meteorological factors, 030231 tropical medicine, malaria, 03 medical and health sciences, Amazonia, parasitic diseases, medicine, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, lcsh:R, Public Health, Environmental and Occupational Health, medicine.disease, biology.organism_classification, [SDE.ES]Environmental Sciences/Environmental and Society, [STAT] Statistics [stat], 13. Climate action, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, hotspots, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDE.ES] Environmental Sciences/Environmental and Society, Malaria
Abstract

Aims: This study examines the dynamics of malaria as influenced by meteorological factors in French Guiana from 2005 to 2019. It explores spatial hotspots of malaria transmission and aims to determine the factors associated with variation of hotspots with time. Methods: Data for individual malaria cases came from the surveillance system of the Delocalized Centers for Prevention and Care (CDPS) (n = 17) from 2005&ndash, 2019. Meteorological data was acquired from the NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) database. The Box&ndash, Jenkins autoregressive integrated moving average (ARIMA) model tested stationarity of the time series, and the impact of meteorological indices (issued from principal component analysis&mdash, PCA) on malaria incidence was determined with a general additive model. Hotspot characterization was performed using spatial scan statistics. Results: The current sample includes 7050 eligible Plasmodium vivax (n = 4111) and Plasmodium falciparum (n = 2939) cases from health centers across French Guiana. The first and second PCA-derived meteorological components (maximum/minimum temperature/minimum humidity and maximum humidity, respectively) were significantly negatively correlated with total malaria incidence with a lag of one week and 10 days, respectively. Overall malaria incidence decreased across the time series until 2017 when incidence began to trend upwards. Hotspot characterization revealed a few health centers that exhibited spatial stability across the entire time series: Saint Georges de l&rsquo, Oyapock and Antecume Pata for P. falciparum, and Saint Georges de l&rsquo, Oyapock, Antecume Pata, R&eacute, gina and Camopi for P. vivax. Conclusions: This study highlighted changing malaria incidence in French Guiana and the influences of meteorological factors on transmission. Many health centers showed spatial stability in transmission, albeit not temporal. Knowledge of the areas of high transmission as well as how and why transmission has changed over time can inform strategies to reduce the transmission of malaria in French Guiana. Hotspots should be further investigated to understand other influences on local transmission, which will help to facilitate elimination.

Published
2021
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35. Resurgence risk for malaria, and the characterization of a recent outbreak in an Amazonian border area between French Guiana and Brazil

Author

Emmanuel Roux, Yanouk Epelboin, Isabelle Dusfour, Guillaume Lacour, Félix Djossou, Mathieu Nacher, Maylis Douine, Lise Musset, Magalie Demar, Amandine Guidez, Damien Davy, Vanessa Ardillon, Margarete do Socorro Mendonça Gomes, Johana Restrepo, Alice Sanna, Emilie Mosnier, Raphael de Freitas Saldanha, Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Altopictus [Biarritz], Institute of Scientific and Technological Communication and Information in Health / Instituto de Comunicação e Informação Científica e Tecnológica em Saúde [Rio de Janeiro] (ICICT), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Superintendência de Vigilância em Saúde do Amapá (SVS-AP), Health Regional Agency [Cayenne], Collectivité Territoriale de Guyane (CTG), Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire Hospitalo-Universitaire de Parasitologie et Mycologie [Cayenne, Guyane Française], Université de Guyane (UG), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Cellule interrégionale d'épidémiologie Antilles-Guyane [CIRE], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), UMR 228 Espace-Dev, Espace pour le développement, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), LMI Sentinela [Rio de Janeiro], Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz (FIOCRUZ), Vectopôle Amazonien Emile Abonnenc [Cayenne, Guyane française], Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Laboratoire de Parasitologie [Cayenne, Guyane française], Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Universidade de Brasilia [Brasília] (UnB), Agence Régionale de la Santé [Cayenne, Guyane française] (ARS), Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe]-CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Guyane (UG)-Université des Antilles (UA)-Université de Montpellier (UM), OHM Oyapock, ANR-11-LABX-0010,DRIIHM / IRDHEI,Dispositif de recherche interdisciplinaire sur les Interactions Hommes-Milieux(2011), Roux, Emmanuel, and Aix Marseille Université (AMU)

Subjects
Male, [SDV]Life Sciences [q-bio], [SHS.GEO] Humanities and Social Sciences/Geography, Plasmodium vivax, Attack rate, Distribution (economics), [SHS]Humanities and Social Sciences, Disease Outbreaks, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], Residence Characteristics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles darlingi, 030212 general & internal medicine, Socioeconomics, [STAT.AP]Statistics [stat]/Applications [stat.AP], biology, Amazon rainforest, Incidence, Transnational, [SHS.GEO]Humanities and Social Sciences/Geography, 3. Good health, French Guiana, Indigenous south Americans, Infectious Diseases, Geography, Female, Seasons, Brazil, Research Article, medicine.medical_specialty, Adolescent, 030231 tropical medicine, Outbreak investigation, Mosquito Vectors, Indigenous, lcsh:Infectious and parasitic diseases, Young Adult, 03 medical and health sciences, Spatio-Temporal Analysis, Amazonia, Anopheles, parasitic diseases, Malaria, Vivax, medicine, Animals, Humans, lcsh:RC109-216, business.industry, Outbreak, biology.organism_classification, medicine.disease, Malaria, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Tropical medicine, OHM Oyapock, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

BackgroundIn 2017, inhabitants along the border between French Guiana and Brazil were affected by a malaria outbreak primarily due toPlasmodium vivax(Pv). While malaria cases have steadily declined between 2005 and 2016 in this Amazonian region, a resurgence was observed in 2017.MethodsTwo investigations were performed according to different spatial scales and information details: (1) a local study on the French Guiana border, which enabled a thorough investigation of malaria cases treated at a local village health center and the entomological circumstances in the most affected neighborhood, and (2) a regional and cross-border study, which enabled exploration of the regional spatiotemporal epidemic dynamic. Number and location of malaria cases were estimated using French and Brazilian surveillance systems.ResultsOn the French Guianese side of the border in Saint-Georges de l’Oyapock, the attack rate was 5.5% (n = 4000), reaching 51.4% (n = 175) in one Indigenous neighborhood. Entomological findings suggest a peak ofAnopheles darlingidensity in August and September. Two femaleAn. darlingi(n = 1104, 0.18%) were found to bePv-positive during this peak. During the same period, aggregated data from passive surveillance conducted by Brazilian and French Guianese border health centers identified 1566 cases ofPvinfection. Temporal distribution during the 2007–2018 period displayed seasonal patterns with a peak in November 2017. Four clusters were identified among epidemic profiles of cross-border area localities. All localities of the first two clusters were Brazilian. The localization of the first cluster suggests an onset of the outbreak in an Indigenous reservation, subsequently expanding to French Indigenous neighborhoods and non-Native communities.ConclusionsThe current findings demonstrate a potential increase in malaria cases in an area with otherwise declining numbers. This is a transborder region where human mobility and remote populations challenge malaria control programs. This investigation illustrates the importance of international border surveillance and collaboration for malaria control, particularly in Indigenous villages and mobile populations.

Published
2020
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36. Resurgence risk for malaria, characterization of a recent outbreak in a Amazonian border area -French Guiana/Brazil

Author

Emmanuel Roux, Yanouk Epelboin, Vanessa Ardillon, Emilie Mosnier, Damien Davy, Magalie Demar, Raphael de Freitas Saldanha, Mathieu Nacher, Félix Djossou, Isabelle Dusfour, Johana Restrepo, Guillaume Lacour, Alice Sanna, Margarete do Socorro Mendonça Gomes, Lise Musset, Maylis Douine, and Amandine Guidez

Subjects
Geography, Amazonian, parasitic diseases, medicine, Outbreak, Socioeconomics, medicine.disease, Malaria
Abstract

Background In 2017, inhabitants along the border between French Guiana and Brazil were affected by a malaria outbreak primarily due to Plasmodium vivax ( Pv ). While malaria cases have steadily declined between 2005-2016 in this Amazonian region, a resurgence was observed in 2017. Methods Two investigations were performed according to two different spatial scales and type of information details. Firstly, a local study on the French Guiana border, which enabled a thorough investigation of the malaria cases treated at the local village health center and of the entomological situation in the most affected neighborhood and secondly a regional and cross-border study, which enabled exploration of the regional spatial-temporal epidemic dynamic. Number and location of malaria cases were estimated using French and Brazilian surveillance systems. Results On the French Guiana side of the border in Saint Georges de l’Oyapock, the attack rate was 5.5% (n=219/4000), reaching 51.4% (n=90/175) in one Amerindian neighborhood. Entomological findings suggest a peak of Anopheles darlingi density in August and September. Two female An. darlingi (n=2/1104, 0.18%) were found Pv -positive during this peak. During the same period, aggregated data from passive surveillance conducted by Brazilian and French Guianese border health centers identified 1,566 cases of Pv infection. Temporal distribution during the 2007-2018 period displayed seasonal patterns with a peak in November 2017. Four clusters were identified among the epidemic profiles of the localities of the cross-border area. All localities of the first two clusters were Brazilian. The localization of the first cluster suggests an onset of the outbreak in the Amerindian reservation, subsequently expanding to French Amerindian neighborhoods and to non-Native communities. Conclusions The current findings demonstrate a potential increase in malaria cases in an area with otherwise declining numbers. This is a transborder area where human mobility and remote populations challenge malaria control programs. This investigation illustrates the importance of international border surveillance and collaboration for malaria control, particularly in Amerindian villages and mobile populations.

Published
2020
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37. Human Plasmodium vivax diversity, population structure and evolutionary origin

Author

Peter G. Kremsner, A. Berry, Ali Ould Mohamed Salem Boukary, Tamirat Gebru Woldearegai, Lise Musset, Eric Legrand, Benjamin Mordmüller, Franck Prugnolle, Carlo Severini, Jean-François Trape, François Renaud, Patrick Durand, Pingchai Harnyuttanakorn, Mohammad Shafiul Alam, Lilia González-Cerón, Khadijetou Mint Lekweiry, Beatriz Acuña Hidalgo, Dionicia Gamboa, François Nosten, Eric Elguero, Gustavo Fontecha, Virginie Rougeron, Oscar Noya, Céline Arnathau, Tepanata Pumpaibool, Sandrine Houzé, Sedigheh Zakeri, Rashidul Haque, Musab M. Ali Albsheer, Muzamil Mahdi Abdel Hamid, Health, Emergence, Adaptation and Transmission (MIVEGEC-HEAT), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Malaria and Vector Research Group (MVRG), Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Dipartimento di Malattie infettive = Department of Infectious Diseases [Rome, Italie] (DMI), Istituto Superiore di Sanità (ISS), Institute for Tropical Medicine = Institut für Tropenmedizin, Reisemedizin, Humanparasitolgie [Tübingen, Allemagne] (ITM), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, German Center for Infectious Research - partner site Tübingen [Tübingen, Allemagne] (DZIF), College of Health and Medical Sciences [Harar, Ethiopie], Haramaya University (HU), Centro Regional de Investigación en Salud Pública = Regional Centre of Research in Public Health [Tapachula, Mexique] (CRISP), National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Microbiology Research Institute = Instituto de Investigaciones en Microbiología [Tegucigalpa, Honduras] (IIM), Universidad Nacional Autónoma de Honduras (UNAH), Instituto de Medicina Tropical 'Alexander von Humboldt' (IMT AvH), Universidad Peruana Cayetano Heredia (UPCH), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Laboratoire de Parasitologie [Cayenne, Guyane française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP), Centro para Estudios Sobre Malaria [Venezuela], Instituto de Altos Estudios en Salud Dr. Arnoldo Gabaldón, Instituto de Medicina Tropical [Caracas, Venezuela} (IMT), Universidad Central de Venezuela (UCV), Graduate School [Bangkok, Thailande], Chulalongkorn University [Bangkok], College of Public Health Science [Bangkok, Thailande], Department of Biology, Faculty of Science [Bangkok, Thailande], Faculté des Sciences et Techniques [Nouakchott, Mauritania], University of Khartoum, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Authors thank the ANR Tremplin EVAD 2017, IRD and CNRS-INEE., ANR-17-ERC3-0002,EVAD,Histoire évolutive et adaptation génétique de Plasmodium vivax(2017), Laboratoire MIVEGEC (Université de Montpellier-CNRS-IRD), CREES, Montpellier, France., Génétique et évolution des maladies infectieuses (GEMI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Génétique et évolution des maladies infectieuses (GEMI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Superiore di Sanita [Rome], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Legrand, Eric, Histoire évolutive et adaptation génétique de Plasmodium vivax - - EVAD2017 - ANR-17-ERC3-0002 - TERC - VALID, Service de Parasitologie et Mycologie, Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], University of Oxford [Oxford]-University of Oxford [Oxford], Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], and Institut Pasteur [Paris]

Subjects
Evolutionary Genetics, 0301 basic medicine, Plasmodium, MESH: Plasmodium vivax / isolation & purification, Genotyping Techniques, Population genetics, [SDV]Life Sciences [q-bio], RC955-962, Plasmodium vivax, MESH: Global Health, Global Health, Microsatellite Loci, Geographical Locations, MESH: Genotype, 0302 clinical medicine, Arctic medicine. Tropical medicine, Global health, MESH: Genetic Variation, MESH: Plasmodium vivax / genetics, Species diversity, education.field_of_study, Ecology, biology, MESH: Plasmodium vivax / classification, 3. Good health, Infectious Diseases, Parasite evolution, Public aspects of medicine, RA1-1270, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, purl.org/pe-repo/ocde/ford#3.03.06 [https], Research Article, Microsatellite loci, Asia, Genotype, Ecological Metrics, 030231 tropical medicine, Population, MESH: Malaria, Vivax / parasitology, Evolutionary genetics, 03 medical and health sciences, Gene Types, MESH: Genotyping Techniques, Parasite Groups, parasitic diseases, Malaria, Vivax, Genetics, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Parasite Evolution, education, Evolutionary Biology, MESH: Humans, Population Biology, Human evolutionary genetics, Ecology and Environmental Sciences, Public Health, Environmental and Occupational Health, Genetic Variation, Biology and Life Sciences, Species Diversity, Plasmodium falciparum, biology.organism_classification, medicine.disease, 030104 developmental biology, Evolutionary biology, People and Places, Africa, Parasitology, Apicomplexa, Population Genetics, Malaria
Abstract

More than 200 million malaria clinical cases are reported each year due to Plasmodium vivax, the most widespread Plasmodium species in the world. This species has been neglected and understudied for a long time, due to its lower mortality in comparison with Plasmodium falciparum. A renewed interest has emerged in the past decade with the discovery of antimalarial drug resistance and of severe and even fatal human cases. Nonetheless, today there are still significant gaps in our understanding of the population genetics and evolutionary history of P. vivax, particularly because of a lack of genetic data from Africa. To address these gaps, we genotyped 14 microsatellite loci in 834 samples obtained from 28 locations in 20 countries from around the world. We discuss the worldwide population genetic structure and diversity and the evolutionary origin of P. vivax in the world and its introduction into the Americas. This study demonstrates the importance of conducting genome-wide analyses of P. vivax in order to unravel its complex evolutionary history., Author summary Among the five Plasmodium species infecting humans, P. vivax is the most prevalent parasite outside Africa. To date, there has been less research on this species than for Plasmodium falciparum, a more lethal species, principally because of the lack of an in vitro culture system and also because P. vivax is considered relatively benign. Nevertheless, P. vivax is responsible for severe and incapacitating clinical symptoms with significant effects on human health. The emergence of new drug resistance and the discovery of severe and even fatal cases due to P. vivax question the benign status of P. vivax malaria. In recent years, there has been increased interest in characterizing the distribution of genetic variation in P. vivax. However, these studies either generated genetic information from a regional geographic scale or combine genetic datasets generated in different molecular platforms, which is known to generate biased results. In this study, we used a single genotyping platform to genotype 14 microsatellite markers in 834 samples of P. vivax obtained from 28 locations in 20 countries from around the world, including several populations from East and West Africa. We discuss the worldwide population genetic structure and the evolutionary origins of P. vivax, as well as its introduction into the Americas.

Published
2020
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38. Author response: Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

Author

Naomi W. Lucchi, Horace Cox, Magalie Demar, Daniel E. Neafsey, Lise Musset, Sachel Mok, Yassamine Lazrek, Jeanne-Celeste Paquet, Angela M. Early, Pascal Ringwald, Luana Mathieu, David A. Fidock, Venkatachalam Udhayakumar, Jean S F Alexandre, Quacy Grant, and Maria-Paz Ade

Subjects
Artemisinin resistance, Mutant, Plasmodium falciparum, Biology, biology.organism_classification, Virology, In vitro
Published
2020
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39. Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

Author

Venkatachalam Udhayakumar, Sachel Mok, Daniel E. Neafsey, Jeanne-Celeste Paquet, Luana Mathieu, Lise Musset, Magalie Demar, Horace Cox, Maria-Paz Ade, David A. Fidock, Quacy Grant, Angela M. Early, Pascal Ringwald, Yassamine Lazrek, Jean S F Alexandre, Naomi W. Lucchi, Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ecole Doctorale 587 : Diversités, santé et développement en Amazonie (ED 587), Université de Guyane (UG), Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Parasitologie [Cayenne, Guyane française], Ministry of Public Health [Georgetown, Guyana], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Columbia University Irving Medical Center (CUIMC), Pan American Health Organization [Washington] (PAHO), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Pan American Health Organization [Georgetown, Guyana] (PAHO), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Columbia University Medical Center (CUMC), Columbia University [New York], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), and Musset, Lise

Subjects
0301 basic medicine, QH301-705.5, Science, 030231 tropical medicine, Mutant, malaria, Drug resistance, artemisinin resistance, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Genome, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], evolution, parasitic diseases, medicine, Parasite hosting, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Biology (General), Allele, Genetics, General Immunology and Microbiology, biology, General Neuroscience, kelch 13, Plasmodium falciparum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, South America, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, Infectious disease (medical specialty), [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Guyana, Malaria, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract

International audience; Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016-2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield.

Published
2020
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40. Prevalence of Plasmodium spp. in the Amazonian border context (French Guiana-Brazil) : associated factors and spatial distribution

Author

Lise Musset, Emilie Mosnier, Emmanuel Roux, Olivier Moriceau, Maylis Douine, Stéphane Pelleau, Mélanie Gaillet, Luana Mathieu, Magalie Demar, Céline Michaud, Claire Cropet, Mathieu Nacher, Félix Djossou, Yassamine Lazrek, Guillaume Odonne, Pôle des Centres Délocalisés de Prévention et de Soins [CH Andrée Rosemon, Guyane Française], Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), UMR 228 Espace-Dev, Espace pour le développement, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Institute of Scientific and Technological Communication and Information in Health / Instituto de Comunicação e Informação Científica e Tecnológica em Saúde [Rio de Janeiro] (ICICT), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut Pasteur de la Guyane, Laboratoire Hospitalier et Universitaire Parasitologie Mycologie, Laboratoire Ecologie, Evolution, Interactions des Systèmes amazoniens (LEEISA), Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Unité des Maladies Infectieuses et Tropicales (UMIT), This study was funded by European Funds for Regional Development, N° Synergie: GY0012082, the Regional Agency for Health of French Guiana, Cayenne Hospital, the French Ministry for Research and Sante Publique France through the Institut Pasteur de la Guyane., We are grateful to the study participants in STG, French Guiana, the NGO, DAAC, provided culturally adapted mediators, offering crucial support throughout this study, and Franck De Laval, Gaelle Walter, Bastien Bidaud, Loıc Epelboin, Alessia Melzani, and Mylene Cebe also contributed to data collection., Roux, Emmanuel, Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Guyane (UG)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), and Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé)

Subjects
Adult, Male, Multivariate analysis, Adolescent, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, Context (language use), Plasmodium, 03 medical and health sciences, Young Adult, 0302 clinical medicine, [STAT.AP] Statistics [stat]/Applications [stat.AP], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, parasitic diseases, medicine, Malaria, Vivax, Humans, Malaria, Falciparum, Child, Rapid diagnostic test, [STAT.AP]Statistics [stat]/Applications [stat.AP], biology, Infant, Articles, medicine.disease, biology.organism_classification, 3. Good health, French Guiana, Infectious Diseases, Carriage, Geography, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Malaria, Brazil, Demography
Abstract

International audience; To implement future malaria elimination strategies in French Guiana, a characterization of the infectious reservoir is recommended. A cross-sectional survey was conducted between October and December 2017 in the French Guianese municipality of St Georges de l'Oyapock, located along the Brazilian border. The prevalence of Plasmodium spp. was determined using a rapid diagnostic test (RDT) and a polymerase chain reaction (PCR). Demographic, house locations, medical history, and biological data were analyzed. Factors associated with Plasmodium spp. carriage were analyzed using logistic regression, and the carriage localization was investigated through spatial cluster analysis. Of the 1,501 samples analyzed with PCR, positive results totaled 90 and 10 for Plasmodium vivax and Plasmodium falciparum, respectively. The general PCR prevalence was 6.6% [5.3-7.9], among which 74% were asymptomatic. Only 13/1,549 were positive by RDT. In multivariate analysis, participants older than 15 years, living in a remote neighborhood, with a prior history of malaria, anemia, and thrombocytopenia were associated with an increased odds of Plasmodium spp. carriage. High-risk clusters of P. vivax carriage were detected in the most remote neighborhoods on the village outskirts and two small foci in the village center. We also detected a hot spot for both P. vivax and P. falciparum symptomatic carriers in the northwestern part of the village. The present study confirms a wide-scale presence of asymptomatic P. falciparum and P. vivax carriers in this area. Although they were more often located in remote areas, their geographic distribution was spatially heterogeneous and complex.

Published
2020
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41. Self-diagnosis and self-treatment of malaria in hard-to-reach and mobile populations of the Amazon: results of Malakit, an international multicentric intervention research project

Author

Mathieu Nacher, Jane Bordalo Miller, Yassamine Lazrek, Maylis Douine, Muriel Galindo, Yann Lambert, Hedley Cairo, Louise Mutricy, Lise Musset, Stephen Vreden, Cassio Peterka, Alice Sanna, Helene Hiwat, Paola Marchesini, Antoine Adenis, M. Demar, Martha Cecilia Suárez-Mutis, Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Biome Tropical et Immuno-Pathophysiologie = Tropical Biome and ImmunoPhysiopathology [Lille] (TBIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Université de Guyane (UG), Agence Régionale de la Santé [Cayenne, Guyane française] (ARS), Ministry of Health [Brasília, Brazil], National Malaria Programme [Suriname]], Ministry of Health [Paramaribo, Suriname], Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de Parasitologie [Cayenne, Guyane française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Réseau International des Instituts Pasteur (RIIP), DPAC-Fronteira [Oiapoque, Brazil], Foundation for the Advancement of Scientific Research in Suriname [Paramaribo] (SWOS), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), The CHC, as sponsor, directly managed most of the project funds. Half of the funding was by the European Regional Development Fund (FEDER) via the Interregional Amazon Cooperation Program (IACP) 2014-2020 (N° Presage 3949), supplemented with self-funding from the CHC, funds from the French Guiana Regional Health Agency and contributions in kind from the (Global Fund to Fight AIDs, Tuberculosis and Malaria) and the Ministry of Health of Brazil., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Guyane (UG), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Fundação Oswaldo Cruz (FIOCRUZ), and Musset, Lise

Subjects
Self-treatment, Low education, 030231 tropical medicine, Library science, malaria control, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, self-diagnosis, 03 medical and health sciences, Amazon forest, 0302 clinical medicine, quasi-experimental design, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Political science, Internal Medicine, medicine, self-treatment, media_common.cataloged_instance, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, European union, media_common, Amazon rainforest, Health Policy, Public Health, Environmental and Occupational Health, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, interventional research, mobile population, medicine.disease, 3. Good health, Neutral position, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, vulnerable population, Intervention research, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public aspects of medicine, RA1-1270, Americas, Malaria control, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria
Abstract

BackgroundIllegal gold miners are currently key hosts for malaria in French Guiana (FG), with a risk of emergence of resistance linked to improper use of artemisinin-based combination therapy (ACT). The remoteness of the mines and regulatory issues hinder their access to health care.MethodsA quasi-experimental researched project (Malakit) implemented in FG borders with Brazil and Suriname aimed at determining the effectiveness of distributed kits for self-diagnosis and self-treatment to illegal gold miners, after training, at strategic border staging areas. Evaluation relied on questionnaires at inclusion and follow-up visits, and pre/post intervention surveys. The primary outcome was the proportion of persons reporting a use of certified ACT after a positive malaria diagnosis. The secondary outcomes assessed antimalarial adherence, kit use and impact on malaria epidemiology.FindingsThe proportion of patients reporting a use of certified ACT after a positive diagnosis increased after the intervention (OR 1.8, 95%CI [1.1-3.0]). From April 2018 to March 2020, 3,733 persons participated in the intervention. The kit was used correctly by 71.7% [65.8-77.7] of the 223 persons reporting having used a malakit during the follow-up visits. No serious adverse events related to the misuse of malakit have been reported. The intervention appears to have accelerated the decline in malaria incidence in the region by 42.9%.InterpretationThis innovative international project showed that people with low education can correctly self-manage their malaria symptoms. This strategy could be integrated in the malaria control programs of the countries involved and considered in other regions with residual malaria in remote areas., ContexteLes chercheurs d'or illégaux sont actuellement un réservoir clé du paludisme en Guyane, avec un risque d'émergence de résistance lié à une mauvaise utilisation des combinaisons thérapeutiques à base d'artémisinine (ACT). L'isolement de ces sites miniers clandestins et des contraintes règlementaires entravent leur accès aux soins.MéthodesUn projet de recherche opérationnelle quasi-expérimental (Malakit) a été mis en œuvre aux frontières de la Guyane avec le Brésil et le Suriname. Il visait à déterminer l'efficacité de la distribution de kits d'autodiagnostic et d'autotraitement à des orpailleurs illégaux, après une formation adaptée, dans des zones stratégiques transfrontalières. L'évaluation s'est appuyée sur des questionnaires lors des visites d'inclusion et de suivi, et sur des enquêtes pré/post intervention. L'indicateur principal était la proportion de personnes déclarant avoir utilisé une ACT certifiée après un diagnostic positif de paludisme. Les indicateurs secondaires reposaient sur l'adhérence aux traitements antipaludiques, l'utilisation des kits et l'impact sur l'épidémiologie du paludisme.RésultatsLa proportion de patients déclarant une utilisation d'ACT certifiée après un diagnostic positif a augmenté après l'intervention (OR 1,8, 95%CI [1,1-3,0]). D'avril 2018 à mars 2020, 3 733 personnes ont participé à l'intervention. Le kit a été utilisé correctement par 71,7% [65,8-77,7] des 223 personnes revues en visites de suivi ayant déclaré avoir utilisé un malakit. Aucun événement indésirable grave lié à une mauvaise utilisation du malakit n'a été signalé. L'intervention semble avoir accéléré la diminution de l'incidence du paludisme dans la région de 42,9%.InterprétationCe projet international innovant a montré que les personnes ayant un faible niveau d'éducation peuvent se prendre en charge par eux-mêmes pour des symptômes de paludisme. Cette stratégie pourrait être intégrée dans les programmes de lutte contre le paludisme des pays impliqués et envisagée dans d'autres régions où du paludisme résiduel persiste dans des zones isolées.

Published
2021
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42. Emergence of Plasmodium vivax Resistance to Chloroquine in French Guiana

Author

Christophe Heugas, Béatrice Volney, Pascal Houzé, Lise Musset, Félix Djossou, Philippe Abboud, Eric Legrand, G. Walter, Richard Naldjinan, Pascal Ringwald, Stéphane Pelleau, Yassamine Lazrek, Denis Blanchet, Loïc Epelboin, Magalie Demar, Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported by Santé Publique France (French Ministry of Health) and the French Ministry for National Education, Higher Education and Research. The Regional Health Agency of French Guiana financed C.H. We acknowledge an Investisse- ment d’Avenir grant from the Agence Nationale de la Recherche (CEBA: ANR-10-LABX- 25-01)., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Réseau International des Instituts Pasteur (RIIP), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Parasitologie [Cayenne, Guyane française], Legrand, Eric, and Laboratoires d'excellence - CEnter of the study of Biodiversity in Amazonia - - CEBA2010 - ANR-10-LABX-0025 - LABX - VALID

Subjects
Male, Primaquine, Plasmodium vivax, Drug Resistance, pvcrt-o, Parasitemia, chloroquine, 0302 clinical medicine, Chloroquine, P. vivax, Pharmacology (medical), Child, 0303 health sciences, biology, Middle Aged, humanities, 3. Good health, French Guiana, Treatment Outcome, Infectious Diseases, Child, Preschool, Plasma concentration, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, medicine.drug, Adult, medicine.medical_specialty, pvmdr1, Adolescent, 030231 tropical medicine, Clinical Therapeutics, World health, resistance, Antimalarials, Young Adult, 03 medical and health sciences, Amazonia, Internal medicine, Vivax infection, parasitic diseases, Malaria, Vivax, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Chloroquine resistance, Aged, Retrospective Studies, 030304 developmental biology, Pharmacology, business.industry, medicine.disease, biology.organism_classification, Guiana Shield, business
Abstract

In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of therapeutic efficacy with an analysis of recurrent parasitemia from any patients. Patients with P. vivax infection, confirmed by microscopy and a body temperature of ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015., In South America, Plasmodium vivax resistance to chloroquine was recently reported in Brazil and Bolivia. The objective of this study was to collect data on chloroquine resistance in French Guiana by associating a retrospective evaluation of therapeutic efficacy with an analysis of recurrent parasitemia from any patients. Patients with P. vivax infection, confirmed by microscopy and a body temperature of ≥37.5°C, were retrospectively identified at Cayenne Hospital between 2009 and 2015. Follow-up and treatment responses were performed according to the World Health Organization protocol. Parasite resistance was confirmed after dosage of a plasma concentration of chloroquine and microsatellite characterization. The pvmdr1 and pvcrt-o genes were analyzed for sequence and gene copy number variation. Among the 172 patients followed for 28 days, 164 presented adequate clinical and parasitological responses. Eight cases of treatment failures were identified (4.7%; n = 8/172), all after 14 days. The therapeutic efficacy of chloroquine was estimated at 95.3% (95% confidence interval [CI], 92.5 to 98.1%; n = 164/172). Among the eight failures, five were characterized: two cases were true P. vivax chloroquine resistance (1.2%; 95% CI, 0 to 2.6%; n = 2/172), and three cases were found with subtherapeutic concentrations of chloroquine. No particular polymorphism in the Plasmodium vivax pvmdr1 and pvcrt-o genes was identified in the resistant parasites. This identified level of resistance of P. vivax to chloroquine in French Guiana does not require a change in therapeutic recommendations. However, primaquine should be administered more frequently to limit the spread of resistance, and there is still a need for a reliable molecular marker to facilitate the monitoring of P. vivax resistance to chloroquine.

Published
2019
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43. Local emergence in Amazonia of

Author

Luana C, Mathieu, Horace, Cox, Angela M, Early, Sachel, Mok, Yassamine, Lazrek, Jeanne-Celeste, Paquet, Maria-Paz, Ade, Naomi W, Lucchi, Quacy, Grant, Venkatachalam, Udhayakumar, Jean Sf, Alexandre, Magalie, Demar, Pascal, Ringwald, Daniel E, Neafsey, David A, Fidock, and Lise, Musset

Subjects
Microbiology and Infectious Disease, Whole Genome Sequencing, Genes, Protozoan, Plasmodium falciparum, kelch 13, Drug Resistance, Protozoan Proteins, malaria, artemisinin resistance, South America, P. falciparum, Artemisinins, Antimalarials, Epidemiology and Global Health, Haplotypes, parasitic diseases, Mutation, evolution, Humans, Genetic Fitness, Guyana, Malaria, Falciparum, Research Article
Abstract

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016–2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield., eLife digest All recommended treatments against malaria include a drug called artemisinin or some of its derivatives. However, there are concerns that Plasmodium falciparum, the parasite that causes most cases of malaria, will eventually develop widespread resistance to the drug. A strain of P. falciparum partially resistant to artemisinin was seen in Cambodia in 2008, and it has since spread across Southeast Asia. The resistance appears to be frequently linked to a mutation known as pfk13 C580Y. Southeast Asia and Amazonia are considered to be hotspots for antimalarial drug resistance, and the pfk13 C580Y mutation was detected in the South American country of Guyana in 2010. To examine whether the mutation was still circulating in this part of the world, Mathieu et al. collected and analyzed 854 samples across Guyana between 2016 and 2017. Overall, 1.6% of the samples had the pfk13 C580Y mutation, but this number was as high as 8.8% in one region. Further analyses revealed that the mutation in Guyana had not spread from Southeast Asia, but that it had occurred in Amazonia independently. To better understand the impact of the pfk13 C580Y mutation, Mathieu et al. introduced this genetic change into non-resistant parasites from a country neighbouring Guyana. As expected, the mutation made P. falciparum highly resistant to artemisinin, but it also slowed the growth rate of the parasite. This disadvantage may explain why the mutation has not spread more rapidly through Guyana in recent years. Artemisinin and its derivatives are always associated with other antimalarial drugs to slow the development of resistance; there are concerns that reduced susceptibility to artemisinin leads to the parasites becoming resistant to the partner drugs. Further research is needed to evaluate how the pfk13 C580Y mutation affects the parasite’s response to the typical combination of drugs that are given to patients.

Published
2019

44. Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System (Preprint)

Author

Raphael Saldanha, Émilie Mosnier, Christovam Barcellos, Aurel Carbunar, Christophe Charron, Jean-Christophe Desconnets, Basma Guarmit, Margarete Do Socorro Mendonça Gomes, Théophile Mandon, Anapaula Martins Mendes, Paulo César Peiter, Lise Musset, Alice Sanna, Benoît Van Gastel, and Emmanuel Roux

Subjects
parasitic diseases
Abstract

BACKGROUND Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. OBJECTIVE This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. METHODS Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. RESULTS A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. CONCLUSIONS This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Published
2019
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45. Combinatorial Genetic Modeling ofpfcrt-Mediated Drug Resistance Evolution inPlasmodium falciparum

Author

Charin Modchang, Thanat Chookajorn, Stanislaw J. Gabryszewski, David A. Fidock, Lise Musset, Columbia University Irving Medical Center (CUIMC), Mahidol University [Bangkok], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP), Department of Clinical Tropical Medicine [Bangkok, Thailand] (Faculty of Tropical Medicine), Columbia University Medical Center (CUMC), Columbia University [New York], Laboratoire de Parasitologie [Cayenne, Guyane française], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Microbiology [New York, NY, USA], New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)

Subjects
pfcrt chloroquine resistance transporter, 0301 basic medicine, Plasmodium falciparum, Protozoan Proteins, Amodiaquine, Drug resistance, Biology, evolutionary genetics, Polymorphism, Single Nucleotide, Antimalarials, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Chloroquine, parasitic diseases, Genetics, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria, Falciparum, Allele, Artemisinin, Molecular Biology, Discoveries, Alleles, Ecology, Evolution, Behavior and Systematics, Plasmodium falciparum malaria, drug resistance, Models, Genetic, Haplotype, Membrane Transport Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, biology.organism_classification, 3. Good health, 030104 developmental biology, transfection, Haplotypes, Mutation, Quinolines, Malaria, medicine.drug
Abstract

International audience; The emergence of drug resistance continuously threatens global control of infectious diseases, including malaria caused by the protozoan parasite Plasmodium falciparum. A critical parasite determinant is the P. falciparum chloroquine resistance transporter (PfCRT), the primary mediator of chloroquine (CQ) resistance (CQR), and a pleiotropic modulator of susceptibility to several first-line artemisinin-based combination therapy partner drugs. Aside from the validated CQR molecular marker K76T, P. falciparum parasites have acquired at least three additional pfcrt mutations, whose contributions to resistance and fitness have been heretofore unclear. Focusing on the quadruple-mutant Ecuadorian PfCRT haplotype Ecu1110 (K76T/A220S/N326D/I356L), we genetically modified the pfcrt locus of isogenic, asexual blood stage P. falciparum parasites using zinc-finger nucleases, producing all possible combinations of intermediate pfcrt alleles. Our analysis included the related quintuple-mutant PfCRT haplotype 7G8 (Ecu1110 þ C72S) that is widespread throughout South America and the Western Pacific. Drug susceptibilities and in vitro growth profiles of our combinatorial pfcrt-modified parasites were used to simulate the mutational trajectories accessible to parasites as they evolved CQR. Our results uncover unique contributions to parasite drug resistance and growth for mutations beyond K76T and predict critical roles for the CQ metabolite monodesethyl-CQ and the related quinoline-type drug amodiaquine in driving mutant pfcrt evolution. Modeling outputs further highlight the influence of parasite proliferation rates alongside gains in drug resistance in dictating successful trajectories. Our findings suggest that P. falciparum parasites have navigated constrained pfcrt adaptive landscapes by means of probabilistically rare mutational bursts that led to the infrequent emergence of pfcrt alleles in the field.

Published
2016
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46. Contributing to Elimination of Cross-Border Malaria Through a Standardized Solution for Case Surveillance, Data Sharing, and Data Interpretation: Development of a Cross-Border Monitoring System

Author

Benoît van Gastel, Margarete do Socorro Mendonça Gomes, Lise Musset, Emmanuel Roux, Emilie Mosnier, Raphael de Freitas Saldanha, A. Carbunar, Christovam Barcellos, Alice Sanna, Théophile Mandon, Paulo Cesar Peiter, Christophe Charron, Anapaula Martins Mendes, Jean-Christophe Desconnets, B. Guarmit, Institute of Scientific and Technological Communication and Information in Health / Instituto de Comunicação e Informação Científica e Tecnológica em Saúde [Rio de Janeiro] (ICICT), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), LMI Sentinela [Rio de Janeiro], Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz (FIOCRUZ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Centres Délocalisés de Prévention et de Soins (CDPS), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pôle des Centres Délocalisés de Prévention et de Soins [Cayenne, Guyane française], UMR 228 Espace-Dev, Espace pour le développement, Université de Guyane (UG)-Université des Antilles (UA)-Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM), Superintendência de Vigilância em Saúde do Amapá (SVS-AP), Universidade Federal do Amapá [Oiapoque, Brésil] (UNIFAP), Réseau International des Instituts Pasteur (RIIP), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Institut Pasteur de la Guyane, Agence Régionale de la Santé [Cayenne, Guyane française] (ARS), This work was funded by the following entities: the Fighting malaria: from 'global war' to 'local guerrillas' at international borders project, part of the Grand Challenges Explorations Round 18 program funded by the Bill and Melinda Gates Foundation (investment ID OPP1171795), the GAPAM-Sentinela (Guyane Française – Amapá – Amazonas – Malária: Sítio Sentinela Transfronteiriça do Observatório Clima e Saúde) project, part of the Guyamazon program funded by the French National Research Institute for Sustainable Development (Institut de Recherche pour le Développement [IRD]), CIRAD (Centre de Coopération Internationale en Recherche Agronomique pour le Développement), the French Guiana territorial collectivity, the French Embassy in Brazil, FAPEMA (Fundação de Amparo à Pesquisa do Estado do Maranhão), FAPEAP (Fundação de Amparo à Pesquisa do Estado do Amapá), and FAPEAM (Fundação de Amparo à Pesquisa do Estado do Amazonas), the ODYSSEA (Observatory of the Dynamics of Interactions Between Societies and Environment in the Amazon) project, part of the European Union’s Horizon 2020 Research and Innovation Program funded by the European Union (Marie Skłodowska Curie grant agreement No. 691053), the Joint International Laboratory (Laboratoire Mixte International [LMI]) Cross-border observatories of climate, environment and vector-borne diseases - Sentinel site of the Brazilian Climate and Health Observatory (LMI Sentinela), under the leadership of the IRD, Fiocruz, and Brasilia University, Fiocruz and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) - Brazil - Finance Code 001, and Santé Publique France. We are also grateful for support from PrInt (Programa de Internacionalização) Fiocruz-CAPES Program., The authors are grateful to Frédéric Théveny (IRD, Cayenne IRD Center, French Guiana) for his technical assistance in the operational implementation of the system. The authors are also very grateful to Mathilde Isar, Julie Margaillan, and Pierre Bos, from the legal department of the IRD, for their assistance in obtaining the authorization from the French data protection authority (CNIL)., Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Institut de Recherche pour le Développement (IRD)-Universidade de Brasilia [Brasília] (UnB)-Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Institut de Recherche pour le Développement (IRD)-Université de Perpignan Via Domitia (UPVD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Université de Guyane (UG)-Université des Antilles (UA), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Laboratoire de Parasitologie [Cayenne, Guyane française], Centre Collaborateur OMS pour la surveillance de la résistance aux antipaludiques [Cayenne, Guyane française] (CCOMS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and Roux, Emmanuel

Subjects
surveillance, cross-border malaria, Computer science, Reuse, Scientific evidence, 0302 clinical medicine, data interoperability, [SHS.STAT] Humanities and Social Sciences/Methods and statistics, [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], data visualization, 030212 general & internal medicine, education.field_of_study, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, Emigration and Immigration, Reference Standards, French Guiana, 3. Good health, Population Surveillance, Public aspects of medicine, RA1-1270, Raw data, Brazil, [INFO.INFO-WB] Computer Science [cs]/Web, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, 030231 tropical medicine, Population, Health Informatics, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, Data visualization, parasitic diseases, medicine, Humans, Disease Eradication, education, Original Paper, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], Information Dissemination, business.industry, [INFO.INFO-WB]Computer Science [cs]/Web, Public Health, Environmental and Occupational Health, medicine.disease, Data science, Malaria, Visualization, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Data quality, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

Background Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. Objective This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. Methods Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. Results A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. Conclusions This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

Published
2020
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47. Profil épidémiologique des infections à Plasmodium vivax dans une région endémique en Guyane, étude de cohorte, 2007–2018

Author

Lise Musset, A. Carbunar, Emmanuel Roux, J. Landier, M. Demar, F. Djossou, Emilie Mosnier, Yassamine Lazrek, Jean Gaudart, and R. Priam

Subjects
Infectious Diseases
Abstract

Introduction En Amazonie, Plasmodium vivax (Pv) est devenu l’espece majoritaire des infections palustres. Il est essentiel de bien comprendre les profils epidemiologiques de ces infections, reviviscences et recurrences afin de mieux guider les programmes de controle. L’objectif de ce travail est de decrire les facteurs de risque d’infection a Pv et leurs profils de reviviscences. Materiels et methodes Une cohorte de 1566 habitants de 13 des 16 quartiers de Saint Georges de l’Oyapock, commune situe sur la frontiere avec le Bresil, a ete suivie sur plus de 10 ans (2007–2018). Les cas symptomatiques d’infection ont ete detectes par Test de Diagnostic Rapide et/ou Frottis Goutte Epaisse. Les infections recurrentes a Pv ont ete definies comme un test positif survenu apres 90 jours au moins apres un test diagnostique et un traitement antipaludeen. Afin de discriminer les reviviscences probables, celles-ci ete definies comme un test positif survenu dans les 7 jours apres un test et un traitement a Pv et avant 90 jours d’une nouvelle infection, selon les resultats d’un travail deja realise et publie sur cette zone. Une regression logistique a ete faite afin de connaitre les facteurs associes aux infections a Pv. Des courbes de Kaplan–Meir ont ete realisees afin de determiner les intervalles des reviviscences par groupe d’âge. Resultats Sur la periode d’etude, l’incidence cumulee de nouvelles infections palustre etait de 36,3 % (n = 569/1566, dont 443 Pv et 126 infections a Plasmodium falciparum-Pf-) sur un total de 335 personnes. Dans 7,9 % des cas les infections etaient recurrentes (n = 123, 106 Pv, 24 Pf et 7 infections mixtes Pv/Pf) et dans 6,4 % (n = 101) il existait des reviviscences a Pv. Les facteurs associes aux infections a Pv en analyse multivariee etaient le fait d’appartenir a une ethnie amerindienne, un nombre eleve d’habitants dans le meme foyer et le haut niveau scolaire. L’intervalle moyen entre la premiere infection et la premiere reviviscence etait de 39,7 jours [36,7–42,7]. Cet intervalle augmentait significativement avec le nombre de reviviscences (p Conclusion Les personnes presentant des infections recurrentes et des reviviscences jouent un role important dans le maintien de la transmission de paludisme. L’acces et la delivrance rapide de traitement par primaquine notamment chez les enfants et les amerindiens doit etre centrale dans les programmes de controle du paludisme a Pv en Guyane afin d’en reduire la dynamique de transmission.

Published
2020
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48. Stratégie de dépistage du paludisme par PCR et traitement ciblé en population générale, en zone de transmission, en Guyane

Author

Mélanie Gaillet, Maylis Douine, R. Priam, Emilie Mosnier, Yassamine Lazrek, Lise Musset, F. Djossou, A. Carbunar, Loïc Epelboin, and M. Demar

Subjects
Infectious Diseases
Abstract

Introduction Plasmodium vivax (Pv) et Plasmodium falciparum (Pf) sont les principales especes presentes en Guyane. Les principales difficultes d’elimination du paludisme dans la region sont la prevalence d’infections a Pv, a l’origine de reviviscences, ainsi que la presence de porteurs de gametocytes asymptomatiques representant un reservoir important de la maladie. Le but de cette etude etait d’evaluer l’impact de campagnes de depistage et de traitement bases sur la PCR pour la lutte contre le paludisme en population generale dans une zone d’endemie palustre. Materiels et methodes Une etude avant-apres a ete menee dans 13 des 16 quartiers les plus touches (2727/4033 habitants) de la commune de Guyane la plus impactee par le paludisme, Saint Georges de l’Oyapock. Deux interventions de depistage de masse et de traitement cible ont ete mises en oeuvre a un an d’intervalle. Celles-ci reposaient sur la PCR pour la detection des cas et etaient suivie d’un traitement uniquement pour les personnes positives symptomatique ou non. Les participants ayants eu un test de diagnostic rapide (TDR) et/ou une PCR positive ont recu de l’artemether-lumefantrine pour le traitement des infections a Pf ou de la chloroquine et, en l’absence de contre-indication, de la primaquine pour le traitement des infections a Pv. L’incidence des cas de paludisme symptomatique a ete surveillee passivement par l’unique centre de sante un an avant la premiere intervention jusqu’a la fin de la deuxieme intervention. Resultats Plus de la moitie des habitants appartenant aux quartiers selectionnes (1566/2727; 57,4 %) ont ete inclus dans l’etude, 1501 ont beneficie du premier depistage par PCR. Parmi ces derniers, 1276 (81,5 %) ont put etre suivis et participer egalement au deuxieme depistage. Au cours de la premiere intervention, le taux de prevalence par PCR etait de 6,7 % (6,0 % Pv, 0,7 % Pf avec 73 % de portage asymptomatique), contre 2,9 % (2,4 % Pv 0,5 % Pf avec 88 % de portage asymptomatique) au cours du deuxieme intervention (p Conclusion En Guyane, les interventions de depistage de masse par PCR et de traitement sont faisable sur le plan operationnel et pourraient participer a reduire le portage et l’incidence des infections a Plasmodium sp. Les limites de cette etude comprennent les variations saisonnieres, le nombre de participants a l’etude, et la mobilite des habitants, qui peuvent avoir limites l’impact de l’intervention. Les strategies de control du paludisme qui utilise uniquement des TDR ou qui traitent uniquement les cas symptomatiques sont susceptibles de negliger une grande partie du reservoir.

Published
2020
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49. Évolution épidémiologique du paludisme au niveau mondial et national, 2000–2015

Author

Marc Thellier, Lise Musset, F. Simard, M. Cot, Guillaume Velut, Eric Kendjo, Bruno Pradines, Centre National de Référence du Paludisme [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Laboratoire de Parasitologie, Centre National de Référence du Paludisme - Région Antilles-Guyane, WHO Collaborating Center for Surveillance of Antimalarial Drug Resistance-Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre d'épidémiologie et de santé publique des armées (CESPA), Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Centre National de Référence du Paludisme [IRBA, Marseille] (CNRP), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), The authors are also grateful to Santé publique France for its long-term financial support via the French National Reference Center for Malaria., The authors would like to thank all the partners of the French National Reference Center for Malaria (CNR Paludisme) involved in monitoring malaria in mainland France and French overseas territories. A considerable portion of the data discussed would not exist without their involvement., CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Institut Pasteur de la Guyane, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), and Institut de Recherche pour le Développement (IRD)-Université de Paris (UP)

Subjects
Paludisme, Time Factors, Plasmodium vivax, Plasmodium falciparum, Travelers, Global Health, World health, 03 medical and health sciences, Malaria transmission, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Communicable Diseases, Imported, Environmental health, parasitic diseases, Medicine, Animals, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Malaria epidemiology, Imported malaria, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, 030306 microbiology, business.industry, Incidence, Anopheles, Voyageurs, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Malaria, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, business
Abstract

International audience; In 2015, 212 million new cases of malaria were reported, causing 429,000 deaths. The World Health Organization (WHO) estimated a 41% decrease in the number of new cases worldwide between 2000 and 2015. The number of deaths from malaria fell by 62% worldwide and by 71% in Africa. In mainland France, malaria is mainly imported by travelers or migrants from endemic areas, in particular sub-Saharan Africa (95%). In France, the number of imported malaria cases, mainly due to Plasmodium falciparum (85%), was estimated at about 82,000 for the period 2000-2015. Over the same period, 6,468 cases of malaria were reported in the French armed forces, of which 2,430 cases (37.6%) were considered as imported because occurring outside of endemic areas. The number of malaria cases also fell between 2000 and 2015 in Mayotte and French Guiana, a malaria transmission zone. Mayotte has entered the elimination of malaria with less than 15 cases per year. In French Guiana, between 300 and 500 cases have been reported annually in recent years. The decline in morbidity and mortality is usually attributed to vector control measures and improved access to effective treatments. However, the Anopheles mosquitoes that transmit the disease have developed resistance against most insecticides. Similarly, malaria parasites have developed resistance against most of the antimalarial drugs used as prevention or treatment, even the latest marketed combinations such as artemisinin-based combination therapies.; En 2015, 212 millions de nouveaux cas de paludisme étaient répertoriés, causant 429 000 morts. L’Organisation mondiale de la santé (OMS) estimait la réduction de nouveaux cas entre 2000 et 2015 à 41 % pour l’ensemble du monde. Les décès dus au paludisme chutaient parallèlement de 62 % dans le monde et de 71 % en Afrique. Le paludisme est essentiellement importé par des voyageurs ou migrants en provenance de zones endémiques, essentiellement d’Afrique subsaharienne (95 %) pour la France métropolitaine. Ce nombre de cas de paludisme d’importation, majoritairement dû à Plasmodium falciparum (85 %), a été estimé à environ 82 000 pour la période 2000–2015. Pour la même période, 6468 cas de paludisme ont été déclarés dans les armées, dont 2430 (37,6 %) importés hors zone d’endémie. Le nombre de cas de paludisme a aussi chuté entre 2000 et 2015 à Mayotte et en Guyane, zone de transmission du paludisme. Mayotte est en phase d’élimination (˂ 15 cas par an). En Guyane, le nombre de cas déclarés se situent entre 300 et 500 cas par an ces dernières années. La baisse de morbidité et de mortalité est attribuée à la lutte antivectorielle et à l’accès généralisé à des traitements efficaces. Mais les anophèles, insectes vecteurs de la maladie développent des résistances contre la plupart des insecticides. Les parasites du paludisme développent aussi des résistances contre la plupart des antipaludiques utilisés en prévention ou traitement, même aux dernières associations commercialisées comme les combinaisons thérapeutiques à base d’artémisinine.

Published
2018
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50. Identifier les groupes sociaux à faible niveau de connaissance du paludisme afin de mieux cibler les programmes d’éducation dans un contexte amazonien, multiculturel et transfrontalier

Author

Lise Musset, Mathieu Nacher, A. Mallard, Céline Michaud, Emilie Mosnier, Claire Cropet, Mélanie Gaillet, F. Djossou, and O. Moriceau

Subjects
Infectious Diseases
Abstract

Introduction Malgre une diminution constante du nombre de cas de paludisme observes depuis les annees 2000 en Guyane, des foyers endemiques persistent notamment a sa frontiere avec le Bresil. Les objectifs de ce travail etaient de decrire les connaissances des habitants de la commune frontaliere de Saint-Georges de l’Oyapock (STG) vis a vis du paludisme. Dans un deuxieme temps, les caracteristiques socio-demographiques et les comportements de ceux ayant un bon niveau de connaissances ont ete compares a ceux ayant un mauvais niveau afin d’adapter secondairement les politiques publiques de prevention. Materiels et methodes L’etude a ete conduite entre septembre et decembre 2017 dans les quartiers de STG ou l’incidence du paludisme etait la plus elevee les trois annees precedentes. L’enquete portait sur les connaissances, attitudes et pratiques (CAP) vis a vis du paludisme des habitants de STG âges de plus de 15 ans. Les donnees ont ete collectees grâce a un questionnaire administre par des mediateurs formes et issus des communautes. Les donnees relatives aux connaissances ont ete etudiees a l’aide de methodes statistiques exploratoires. Elles ont ete resumees, testees puis ont fait l’objet d’etudes bivariees. Resultats L’âge moyen des 844 habitants de STG inclus etait de 37,2 ans (15,8). Le sex-ratio etait de 0,7 et 485 personnes (57,5 %) se declaraient de nationalite bresilienne. Au total, 251/844 (29,7 %) avaient un faible niveau de connaissances. Les symptomes de la maladie etaient mal connus pour 213/844 personnes (25,2 %), les mesures de prevention pour 378/844 (44,7 %) et 206/844 (24,4 %) ne savaient pas qu’on pouvait mourir du paludisme. Les personnes âgees de moins de 25 ans, vivant dans un quartier amerindien ou parlant une langue amerindienne, les agriculteurs, les personnes retraites ou restant a domicile, les personnes en lien avec l’exploitation aurifere avaient niveau de connaissances significativement moins bon. Conclusion L’etude des connaissances d’une population de Guyane francaise vivant en zone d’endemie a permis de montrer pour la premiere fois un niveau de connaissance tres limite vis a vis du paludisme. Ce niveau de connaissance etant, par ailleurs, essentiellement et paradoxalement observe chez les populations les plus a risque notamment les populations autochtones, les jeunes et les orpailleurs. Il est donc souhaitable de renforcer, diversifier et adapter aux differentes cultures les messages de prevention et de promotion de la sante pour les rendre plus efficaces.

Published
2019
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