Ghislaine Prévot - Academia.edu (original) (raw)

Papers by Ghislaine Prévot

Research paper thumbnail of Outbreak of Cutaneous Leishmaniasis among military personnel in French Guiana, 2020: Clinical, phylogenetic, individual and environmental aspects

PLOS Neglected Tropical Diseases

Background Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadi... more Background Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadic. An outbreak signal was issued on May 15th 2020 with 15 suspected cases after a military training course in the rainforest. An outbreak investigation was carried out. Methodology/Principal findings Thirty cases were confirmed. Leishmania guyanensis was the most frequent species (90%). The most frequent presentation was ulcerative (90%). Lesions on the face and hands were frequent (40% each). Eight cases (26%) presented a poor outcome after treatment with pentamidine and required a second line with amphotericin B. Three of them required further treatments with meglumine antimoniate or miltefosine. Two spots within the training area were deemed as likely sites of contamination, due to illegal logging. The isolated Leishmania strains did not form a separate cluster. Participation in Week 13 of year 2020 was associated with infection (OR = 4.59 [1.10–19.83]; p = 0.016) while undergoing onl...

Research paper thumbnail of Modeling disease occurrence and response to environmental drivers for predicting the risk of cutaneous leishmaniasis in Amazonia

Research paper thumbnail of Biodiversity and vector‐borne diseases: host dilution and vector amplification occur simultaneously for Amazonian leishmaniases

Molecular Ecology, 2022

Changes in biodiversity may impact infectious disease transmission through multiple mechanisms. W... more Changes in biodiversity may impact infectious disease transmission through multiple mechanisms. We explored the impact of biodiversity changes on the transmission of Amazonian leishmaniases, a group of wild zoonoses transmitted by phlebotomine sand flies (Psychodidae), which represent an important health burden in a region where biodiversity is both rich and threatened. Using molecular analyses of sand fly pools and blood-fed dipterans, we characterized the disease system in forest sites in French Guiana undergoing different levels of human-induced disturbance. We show that the prevalence of Leishmania parasites in sand flies correlates positively with the relative abundance of mammal species known as Leishmania reservoirs. In addition, Leishmania reservoirs tend to dominate in less diverse mammal communities, in accordance with the dilution effect hypothesis. This results in a negative relationship between Leishmania prevalence and mammal diversity. On the other hand, higher mammal diversity is associated with higher sand fly density, possibly because more diverse mammal communities harbor higher biomass and more abundant feeding resources for sand flies, although more research is needed to identify the factors that shape sand fly communities. As a consequence of these antagonistic effects, decreased mammal diversity comes with an increase of parasite prevalence in sand flies, but has no detectable impact on the density of infected sand flies. These results represent additional evidence that biodiversity changes may simultaneously dilute and amplify vector-borne disease transmission through different mechanisms that need to be better understood before drawing generalities on the biodiversity-disease relationship.

Research paper thumbnail of Treating Leishmaniasis in Amazonia, Part 2: Multi-Target Evaluation of Widely Used Plants to Understand Medicinal Practices

SSRN Electronic Journal, 2021

Leishmaniasis are widely distributed among tropical and subtropical countries, and remains a cruc... more Leishmaniasis are widely distributed among tropical and subtropical countries, and remains a crucial health issue in Amazonia. Indigenous groups across Amazonia have developed abundant knowledge about medicinal plants related to this pathology. We intent to explore the weight of different pharmacological activities driving taxa selection for medicinal use in Amazonian communities. Our hypothesis is that specific activity against Leishmania parasites is only one factor along other (anti-inflammatory, wound healing, immunomodulating, antimicrobial) activities. The twelve most widespread plant species used against leishmaniasis in Amazonia, according to their cultural and biogeographical importance determined through a wide bibliographical survey (475 use reports), were selected for this study. Plant extracts were prepared to mimic their traditional preparations. Antiparasitic activity was evaluated against promastigotes of reference and clinical New-World strains of Leishmania (L. guyanensis, L. braziliensis and L. amazonensis) and L. amazonensis intracellular amastigotes. We concurrently assessed the extracts immunomodulatory properties on PHA-stimulated human PBMCs and RAW264.7 cells, and on L. guyanensis antigens-stimulated PBMCs obtained from Leishmania-infected patients, as well as antifungal activity and wound healing properties (human keratinocyte migration assay) of the selected extracts. The cytotoxicity of the extracts against various cell lines (HFF1, THP-1, HepG2, PBMCs, RAW264.7 and HaCaT cells) was also considered. The biological activity pattern of the extracts was represented through PCA analysis, and a correlation matrix was calculated. Spondias mombinL. bark and Anacardium occidentaleL. stem and leaves extracts displayed high anti-promatigotes activity, with IC50 ≤ 32 μg/mL against L. guyanensis promastigotes for S. mombin and IC50 of 67 and 47 μg/mL against L. braziliensis and L. guyanensis promastigotes, respectively, for A. occidentale. In addition to the antiparasitic effect, antifungal activity measured against C. albicans and T. rubrum (MIC in the 16-64 μg/mL range) was observed. However, in the case of Leishmania amastigotes, the most active species were Bixa orellana L. (seeds), Chelonantus alatus (Aubl.) Pulle (leaves), Jacaranda copaia (Aubl.) D. Don. (leaves) and Plantago major L. (leaves) with IC50 < 20 μg/mL and infection rates of 14-25% compared to the control. Concerning immunomodulatory activity, P. major and B. orellana were highlighted as the most potent species for the wider range of cytokines in all tested conditions despite overall contrasting results depending on the model. Most of the species led to moderate to low cytotoxic extracts except for C. alatus, which exhibited strong cytotoxic activity in almost all models. None of the tested extracts displayed wound healing properties. We highlighted pharmacologically active extracts either on the parasite or on associated pathophysiological aspects, thus supporting the hypothesis that antiparasitic activities are not the only biological factor useful for antileishmanial evaluation. This result should however be supplemented by in vivo studies, and attracts once again the attention on the importance of the choice of biological models for an ethnophamacologically consistent study. Moreover, plant cultural importance, ecological status and availability were discussed in relation with biological results, thus contributing to link ethnobotany, medical anthropology and biology.

Research paper thumbnail of American cutaneous leishmaniasis in French Guiana: an epidemiological update and study of environmental risk factors

International Journal of Dermatology, 2019

Background American cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology i... more Background American cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology is evolving, notably because of immigration, anthropization of natural areas, and new microbiological methods. Our first objective was to update epidemiological data. Our second objective was to look for risk factors of ACL. Methods This multicentric study was conducted from October 2017 to June 2018 in French Guiana. Patients with suspicion of mucocutaneous leishmaniasis were included in case of positive smear, culture, or PCR-RFLP on skin biopsy. Results One hundred and twenty-three patients met the inclusion criteria. Among those patients, 59.3% were Brazilian, mostly gold miners. Most of them (58%) were between 16 and 40 years old, and 69% were male. A large proportion of patients lived in traditional wooden houses (51%). Patients living in coastal towns were usually infected during trips to the primary forest (60%) and had a shorter time to diagnosis than workers of the hinterland. Among environmental risk factors, the presence of a water spring (40%) and dogs around houses (40%) were frequently reported. Leishmania guyanensis represented 80% of cases, followed by Leishmania braziliensis (6%), Leishmania naiffi (2%), and Leishmania amazonensis (1%). Conclusions Gold mining and trips to the primary forest represent high-risk situations for ACL in French Guiana, where the population of infected patients is dominated by Brazilian immigrants. Possible environmental risk factors such as the presence of dogs, water sources, and traditional wooden houses require further investigation.

Research paper thumbnail of Chemical composition and antifungal activity of the essential oil ofVarronia schomburgkii(DC.) Borhidi (Cordiaceae) from plants cultivated in French Guiana

Journal of Essential Oil Research, 2017

Abstract This study reports for the first time the chemical composition of the essential oil of V... more Abstract This study reports for the first time the chemical composition of the essential oil of Varronia schomburgkii (DC.) Borhidi cultivated in French Guiana. This essential oil was examined by a combination of GC/FID and GC-MS techniques and was further tested for antifungal activity against several Candida strains, as well as for anti-leishmanial activity against the reference strain Leishmania guyanensis. A total of 45 components accounting for 93.61% of the total GC/FID chromatogram were identified. The essential oil is dominated by sesquiterpenes and oxygenated sesquiterpenes among which β-caryophyllene (46.99 ± 0.32%) is the major one. No anti-leishmania activity could be assessed, while a strong antimicrobial activity of this essential oil was evidenced in vitro against a Candida albicans strain by the definition of a MIC value of 250 μg/mL. V. schomburgkii essential oil might hence be considered in the future for the development of natural antifungal agents.

Research paper thumbnail of Unraveling the genetic diversity and phylogeny of Leishmania RNA virus 1 strains of infected Leishmania isolates circulating in French Guiana

PLoS neglected tropical diseases, 2017

Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in Sout... more Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now. We subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%-23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five...

Research paper thumbnail of Antifungal activities and chemical composition of the essential oil of Lippia micromera (Verbenaceae) cultivated in French Guiana

Planta medica, 2016

French Guyana is a part of the Amazonia rainforest identified as a biodiversity hotspot for both ... more French Guyana is a part of the Amazonia rainforest identified as a biodiversity hotspot for both animal and plant species threatened with extinction [1]. With the generalized awareness of this endangered richness a number of conservation and promotion actions have been undertaken over the last years. In collaboration with the Guyaromes society, the potential valorization of essential oils from local plants on the international market is assessed. Lippia micromera Schauer (Verbenaceae family) is a strong aromatic shrub with many branched and white tiny flowers with yellow throat. Its origin is not well established but it is assumed that the plant is from northern South America (Colombia, Venezuela and Guiana), the Caribbean and Nicaragua. [2] It is one of the selected plants for such a valorization action. The species is well known for culinary seasoning, anti-inflamatory, anti-microbial and antioxidant activities [3]. The present poster reports for the first time the analysis of the chemical composition by GC-FID and GC-MS of the essential oil of L. micromera organically cultivated in French Guiana. A total of thirty-one components accounting for 97% of the total GC-FID chromatogram were identified. The evaluation of its antimicrobial and antiparasitic activities against strains of several Candida spp. (MIC) and Leishmania guyanensis (IC50) respectively shows a strong antimicrobial activity ranging from 125 µg/ml to 500 µg/ml according to the Candida species tested, while the anti-leishmania activity seems negligible. Thus the EO was assessed for its anti-ageing and antioxidant properties (in vitro tests in 96-wells plates) and revealed also a strong percentage of inhibition (more than 60%) for elastase and lipoxygenase assays.

Research paper thumbnail of Leishmania-RNA virus presence in L. guyanensis parasites increases the risk of first-line treatment failure and symptomatic relapse

The Journal of infectious diseases, Jan 29, 2015

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasi... more Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pent...

Research paper thumbnail of High Intralesional Interleukin‐10 Messenger RNA Expression in Localized Cutaneous Leishmaniasis Is Associated with Unresponsiveness to Treatment

The Journal of Infectious Diseases, 2001

The intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-g) wa... more The intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-g) was analyzed in 65 patients with localized cutaneous leishmaniasis due to Leishmania guyanensis before specific treatment with pentamidine isethionate. The local expression of IL-10 was significantly higher in patients who responded poorly to treatment than in patients whose lesions were regressing. When an IL-10 level .10 (ratio of the concentration of IL-10 [pg/mL] to that of b-actin [pg/mL]) was used as an indicator of treatment failure, the sensitivity of this test was 78.6, and the specificity was 72.5. Thus, high intralesional expression of IL-10 might predict a poor response to conventional treatment.

Research paper thumbnail of Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin

International Journal of Antimicrobial Agents, 2003

The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the... more The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the treatment of mice experimentally infected by Mycobacterium ulcerans and the risk of relapse after the treatment was evaluated. After 7 weeks of treatment with RIF or with the combination of AMK/RIF and 8 weeks with AMK alone, no viable bacilli were found in the infected tissues and these remained uninfected during the following 6 months. Among the mice treated with AMK alone, three mice relapsed, but the minimal inhibitory concentration of AMK for these isolates remained unchanged. With RIF alone, two mice relapsed and the minimal inhibitory concentration of these isolated strains was higher. However, with all the mice treated with both RIF and AMK, no relapse was observed.

Research paper thumbnail of Th1 Cell Development Induced by Cysteine Proteinases A and B in Localized Cutaneous Leishmaniasis Due to Leishmania guyanensis

Infection and Immunity, 2003

The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with... more The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis . Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species.

Research paper thumbnail of Differential Production of Systemic and Intralesional Gamma Interferon and Interleukin-10 in Nodular and Ulcerative Forms of Buruli Disease

Infection and Immunity, 2004

Buruli disease, caused by Mycobacterium ulcerans , is the third most important mycobacterial dise... more Buruli disease, caused by Mycobacterium ulcerans , is the third most important mycobacterial disease in humans besides tuberculosis and leprosy. We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease. Gamma interferon (IFN-γ) levels in response to whole M. ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts. Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures. IFN-γ production after stimulation with M. ulcerans was significantly lower ( P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules. On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response t...

Research paper thumbnail of LACK-Specific CD4 + T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection

Infection and Immunity, 2002

The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue... more The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis . Gamma interferon (IFN-γ) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4 + cells producing IFN-γ were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4 + T cells producing IFN-γ and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA − CCR7 − CD4 + T cells. CD4 + T cells producing IFN-γ are CD62L − , and CD4 + T cells producing IL-10 are CD62L + , indicating that these cells have different tissue-ho...

Research paper thumbnail of Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

Journal of Clinical Microbiology, 2014

In French Guiana, leishmaniasis is an essentially cutaneous infection. It constitutes a major pub... more In French Guiana, leishmaniasis is an essentially cutaneous infection. It constitutes a major public health problem, with a real incidence of 0.2 to 0.3%. Leishmania guyanensis is the causal species most frequently encountered in French Guiana. The treatment of leishmaniasis is essentially drug based, but the therapeutic compounds available have major side effects (e.g., liver damage and diabetes) and must be administered parenterally or are costly. The efficacy of some of these agents has declined due to the emergence of resistance in certain strains of Leishmania . There is currently no vaccine against leishmaniasis, and it is therefore both necessary and urgent to identify new compounds effective against Leishmania . The search for new drugs requires effective tests for evaluations of the leishmanicidal activity of a particular molecule or extract. Microculture tetrazolium assays (MTAs) are colorimetric tests based on the use of tetrazolium salts. We compared the efficacies of th...

Research paper thumbnail of Leishmania naiffi and lainsoni in French Guiana: Clinical features and phylogenetic variability

PLOS Neglected Tropical Diseases

Research paper thumbnail of Antibiotic Treatment in Anopheles coluzzii Affects Carbon and Nitrogen Metabolism

Pathogens

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host... more The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness; it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of Anopheles coluzzii provided with a sugar-meal or a non-infectious blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified pathways which may participate in microbiota-Plasmodium interactions via meta...

Research paper thumbnail of Ecology, evolution, and epidemiology of zoonotic and vector-borne infectious diseases in French Guiana: Transdisciplinarity does matter to tackle new emerging threats

Infection, Genetics and Evolution

Research paper thumbnail of Validation of Swab Sampling and SYBR Green-Based Real-Time PCR for the Diagnosis of Cutaneous Leishmaniasis in French Guiana

Journal of Clinical Microbiology

Recent studies have highlighted the interest in noninvasive sampling procedures coupled with real... more Recent studies have highlighted the interest in noninvasive sampling procedures coupled with real-time PCR methods for the detection of Leishmania species in South America. In French Guiana, the sampling method still relied on skin biopsies. Noninvasive protocols should be tested on a large annual cohort to improve routine laboratory diagnosis of cutaneous leishmaniasis. Therefore, we evaluated the performance of a new Leishmania detection and species identification protocol involving cotton swabs and SYBR green-based real-time PCR of the Hsp70 gene, coupled with Sanger sequencing.

Research paper thumbnail of Ecological niche modelling for predicting the risk of cutaneous leishmaniasis in the Neotropical moist forest biome

PLOS Neglected Tropical Diseases

A major challenge of eco-epidemiology is to determine which factors promote the transmission of i... more A major challenge of eco-epidemiology is to determine which factors promote the transmission of infectious diseases and to establish risk maps that can be used by public health authorities. The geographic predictions resulting from ecological niche modelling have been widely used for modelling the future dispersion of vectors based on the occurrence records and the potential prevalence of the disease. The establishment of risk maps for disease systems with complex cycles such as cutaneous leishmaniasis (CL) can be very challenging due to the many inference networks between large sets of host and vector species, with considerable heterogeneity in disease patterns in space and time. One novelty in the present study is the use of human CL cases to predict the risk of leishmaniasis occurrence in response to anthropogenic, climatic and environmental factors at two different scales, in the Neotropical moist forest biome (Amazonian basin and surrounding forest ecosystems) and in the surrounding region of French Guiana. With a consistent data set never used before and a conceptual and methodological framework for interpreting data cases, we obtained risk maps with high statistical support. The predominantly identified human CL risk areas are those where the human impact on the environment is significant, associated with less contributory climatic and ecological factors. For both models this study highlights the importance of considering the anthropogenic drivers for disease risk assessment in human, although CL is mainly linked to the sylvatic and peri-urban cycle in Meso and South America.

Research paper thumbnail of Outbreak of Cutaneous Leishmaniasis among military personnel in French Guiana, 2020: Clinical, phylogenetic, individual and environmental aspects

PLOS Neglected Tropical Diseases

Background Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadi... more Background Cutaneous Leishmaniasis (CL) is endemic in French Guiana but cases are usually sporadic. An outbreak signal was issued on May 15th 2020 with 15 suspected cases after a military training course in the rainforest. An outbreak investigation was carried out. Methodology/Principal findings Thirty cases were confirmed. Leishmania guyanensis was the most frequent species (90%). The most frequent presentation was ulcerative (90%). Lesions on the face and hands were frequent (40% each). Eight cases (26%) presented a poor outcome after treatment with pentamidine and required a second line with amphotericin B. Three of them required further treatments with meglumine antimoniate or miltefosine. Two spots within the training area were deemed as likely sites of contamination, due to illegal logging. The isolated Leishmania strains did not form a separate cluster. Participation in Week 13 of year 2020 was associated with infection (OR = 4.59 [1.10–19.83]; p = 0.016) while undergoing onl...

Research paper thumbnail of Modeling disease occurrence and response to environmental drivers for predicting the risk of cutaneous leishmaniasis in Amazonia

Research paper thumbnail of Biodiversity and vector‐borne diseases: host dilution and vector amplification occur simultaneously for Amazonian leishmaniases

Molecular Ecology, 2022

Changes in biodiversity may impact infectious disease transmission through multiple mechanisms. W... more Changes in biodiversity may impact infectious disease transmission through multiple mechanisms. We explored the impact of biodiversity changes on the transmission of Amazonian leishmaniases, a group of wild zoonoses transmitted by phlebotomine sand flies (Psychodidae), which represent an important health burden in a region where biodiversity is both rich and threatened. Using molecular analyses of sand fly pools and blood-fed dipterans, we characterized the disease system in forest sites in French Guiana undergoing different levels of human-induced disturbance. We show that the prevalence of Leishmania parasites in sand flies correlates positively with the relative abundance of mammal species known as Leishmania reservoirs. In addition, Leishmania reservoirs tend to dominate in less diverse mammal communities, in accordance with the dilution effect hypothesis. This results in a negative relationship between Leishmania prevalence and mammal diversity. On the other hand, higher mammal diversity is associated with higher sand fly density, possibly because more diverse mammal communities harbor higher biomass and more abundant feeding resources for sand flies, although more research is needed to identify the factors that shape sand fly communities. As a consequence of these antagonistic effects, decreased mammal diversity comes with an increase of parasite prevalence in sand flies, but has no detectable impact on the density of infected sand flies. These results represent additional evidence that biodiversity changes may simultaneously dilute and amplify vector-borne disease transmission through different mechanisms that need to be better understood before drawing generalities on the biodiversity-disease relationship.

Research paper thumbnail of Treating Leishmaniasis in Amazonia, Part 2: Multi-Target Evaluation of Widely Used Plants to Understand Medicinal Practices

SSRN Electronic Journal, 2021

Leishmaniasis are widely distributed among tropical and subtropical countries, and remains a cruc... more Leishmaniasis are widely distributed among tropical and subtropical countries, and remains a crucial health issue in Amazonia. Indigenous groups across Amazonia have developed abundant knowledge about medicinal plants related to this pathology. We intent to explore the weight of different pharmacological activities driving taxa selection for medicinal use in Amazonian communities. Our hypothesis is that specific activity against Leishmania parasites is only one factor along other (anti-inflammatory, wound healing, immunomodulating, antimicrobial) activities. The twelve most widespread plant species used against leishmaniasis in Amazonia, according to their cultural and biogeographical importance determined through a wide bibliographical survey (475 use reports), were selected for this study. Plant extracts were prepared to mimic their traditional preparations. Antiparasitic activity was evaluated against promastigotes of reference and clinical New-World strains of Leishmania (L. guyanensis, L. braziliensis and L. amazonensis) and L. amazonensis intracellular amastigotes. We concurrently assessed the extracts immunomodulatory properties on PHA-stimulated human PBMCs and RAW264.7 cells, and on L. guyanensis antigens-stimulated PBMCs obtained from Leishmania-infected patients, as well as antifungal activity and wound healing properties (human keratinocyte migration assay) of the selected extracts. The cytotoxicity of the extracts against various cell lines (HFF1, THP-1, HepG2, PBMCs, RAW264.7 and HaCaT cells) was also considered. The biological activity pattern of the extracts was represented through PCA analysis, and a correlation matrix was calculated. Spondias mombinL. bark and Anacardium occidentaleL. stem and leaves extracts displayed high anti-promatigotes activity, with IC50 ≤ 32 μg/mL against L. guyanensis promastigotes for S. mombin and IC50 of 67 and 47 μg/mL against L. braziliensis and L. guyanensis promastigotes, respectively, for A. occidentale. In addition to the antiparasitic effect, antifungal activity measured against C. albicans and T. rubrum (MIC in the 16-64 μg/mL range) was observed. However, in the case of Leishmania amastigotes, the most active species were Bixa orellana L. (seeds), Chelonantus alatus (Aubl.) Pulle (leaves), Jacaranda copaia (Aubl.) D. Don. (leaves) and Plantago major L. (leaves) with IC50 < 20 μg/mL and infection rates of 14-25% compared to the control. Concerning immunomodulatory activity, P. major and B. orellana were highlighted as the most potent species for the wider range of cytokines in all tested conditions despite overall contrasting results depending on the model. Most of the species led to moderate to low cytotoxic extracts except for C. alatus, which exhibited strong cytotoxic activity in almost all models. None of the tested extracts displayed wound healing properties. We highlighted pharmacologically active extracts either on the parasite or on associated pathophysiological aspects, thus supporting the hypothesis that antiparasitic activities are not the only biological factor useful for antileishmanial evaluation. This result should however be supplemented by in vivo studies, and attracts once again the attention on the importance of the choice of biological models for an ethnophamacologically consistent study. Moreover, plant cultural importance, ecological status and availability were discussed in relation with biological results, thus contributing to link ethnobotany, medical anthropology and biology.

Research paper thumbnail of American cutaneous leishmaniasis in French Guiana: an epidemiological update and study of environmental risk factors

International Journal of Dermatology, 2019

Background American cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology i... more Background American cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology is evolving, notably because of immigration, anthropization of natural areas, and new microbiological methods. Our first objective was to update epidemiological data. Our second objective was to look for risk factors of ACL. Methods This multicentric study was conducted from October 2017 to June 2018 in French Guiana. Patients with suspicion of mucocutaneous leishmaniasis were included in case of positive smear, culture, or PCR-RFLP on skin biopsy. Results One hundred and twenty-three patients met the inclusion criteria. Among those patients, 59.3% were Brazilian, mostly gold miners. Most of them (58%) were between 16 and 40 years old, and 69% were male. A large proportion of patients lived in traditional wooden houses (51%). Patients living in coastal towns were usually infected during trips to the primary forest (60%) and had a shorter time to diagnosis than workers of the hinterland. Among environmental risk factors, the presence of a water spring (40%) and dogs around houses (40%) were frequently reported. Leishmania guyanensis represented 80% of cases, followed by Leishmania braziliensis (6%), Leishmania naiffi (2%), and Leishmania amazonensis (1%). Conclusions Gold mining and trips to the primary forest represent high-risk situations for ACL in French Guiana, where the population of infected patients is dominated by Brazilian immigrants. Possible environmental risk factors such as the presence of dogs, water sources, and traditional wooden houses require further investigation.

Research paper thumbnail of Chemical composition and antifungal activity of the essential oil ofVarronia schomburgkii(DC.) Borhidi (Cordiaceae) from plants cultivated in French Guiana

Journal of Essential Oil Research, 2017

Abstract This study reports for the first time the chemical composition of the essential oil of V... more Abstract This study reports for the first time the chemical composition of the essential oil of Varronia schomburgkii (DC.) Borhidi cultivated in French Guiana. This essential oil was examined by a combination of GC/FID and GC-MS techniques and was further tested for antifungal activity against several Candida strains, as well as for anti-leishmanial activity against the reference strain Leishmania guyanensis. A total of 45 components accounting for 93.61% of the total GC/FID chromatogram were identified. The essential oil is dominated by sesquiterpenes and oxygenated sesquiterpenes among which β-caryophyllene (46.99 ± 0.32%) is the major one. No anti-leishmania activity could be assessed, while a strong antimicrobial activity of this essential oil was evidenced in vitro against a Candida albicans strain by the definition of a MIC value of 250 μg/mL. V. schomburgkii essential oil might hence be considered in the future for the development of natural antifungal agents.

Research paper thumbnail of Unraveling the genetic diversity and phylogeny of Leishmania RNA virus 1 strains of infected Leishmania isolates circulating in French Guiana

PLoS neglected tropical diseases, 2017

Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in Sout... more Leishmania RNA virus type 1 (LRV1) is an endosymbiont of some Leishmania (Vianna) species in South America. Presence of LRV1 in parasites exacerbates disease severity in animal models and humans, related to a disproportioned innate immune response, and is correlated with drug treatment failures in humans. Although the virus was identified decades ago, its genomic diversity has been overlooked until now. We subjected LRV1 strains from 19 L. (V.) guyanensis and one L. (V.) braziliensis isolates obtained from cutaneous leishmaniasis samples identified throughout French Guiana with next-generation sequencing and de novo sequence assembly. We generated and analyzed 24 unique LRV1 sequences over their full-length coding regions. Multiple alignment of these new sequences revealed variability (0.5%-23.5%) across the entire sequence except for highly conserved motifs within the 5' untranslated region. Phylogenetic analyses showed that viral genomes of L. (V.) guyanensis grouped into five...

Research paper thumbnail of Antifungal activities and chemical composition of the essential oil of Lippia micromera (Verbenaceae) cultivated in French Guiana

Planta medica, 2016

French Guyana is a part of the Amazonia rainforest identified as a biodiversity hotspot for both ... more French Guyana is a part of the Amazonia rainforest identified as a biodiversity hotspot for both animal and plant species threatened with extinction [1]. With the generalized awareness of this endangered richness a number of conservation and promotion actions have been undertaken over the last years. In collaboration with the Guyaromes society, the potential valorization of essential oils from local plants on the international market is assessed. Lippia micromera Schauer (Verbenaceae family) is a strong aromatic shrub with many branched and white tiny flowers with yellow throat. Its origin is not well established but it is assumed that the plant is from northern South America (Colombia, Venezuela and Guiana), the Caribbean and Nicaragua. [2] It is one of the selected plants for such a valorization action. The species is well known for culinary seasoning, anti-inflamatory, anti-microbial and antioxidant activities [3]. The present poster reports for the first time the analysis of the chemical composition by GC-FID and GC-MS of the essential oil of L. micromera organically cultivated in French Guiana. A total of thirty-one components accounting for 97% of the total GC-FID chromatogram were identified. The evaluation of its antimicrobial and antiparasitic activities against strains of several Candida spp. (MIC) and Leishmania guyanensis (IC50) respectively shows a strong antimicrobial activity ranging from 125 µg/ml to 500 µg/ml according to the Candida species tested, while the anti-leishmania activity seems negligible. Thus the EO was assessed for its anti-ageing and antioxidant properties (in vitro tests in 96-wells plates) and revealed also a strong percentage of inhibition (more than 60%) for elastase and lipoxygenase assays.

Research paper thumbnail of Leishmania-RNA virus presence in L. guyanensis parasites increases the risk of first-line treatment failure and symptomatic relapse

The Journal of infectious diseases, Jan 29, 2015

Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasi... more Treatment failure and symptomatic relapse are major concerns in American tegumentary leishmaniasis (ATL). Such complications are seen frequently in L.guyanensis infections where patients respond variously to first-line anti-leishmanials and are more prone to develop chronic cutaneous leishmaniasis. The factors underlying this pathology, however, are unknown. Recently ,: we reported that a dsRNA virus (LRV1) nested within L.guyanensis parasites is able to exacerbate experimental murine leishmaniasis by inducing a hyper-inflammatory response. This report investigates the prevalence of LRV1 in human L.guyanensis infection and its effect on treatment efficacy as well as its correlation to symptomatic relapses after the first-line treatment. In our cohort of 75 patients diagnosed with primary-localised ATL, the prevalence of LRV1+ infection was elevated to 58%. All patients infected with LRV1-negative L.guyanensis were cured after one (22/31 i.e.71%) or two (31/31 i.e.100%) doses of pent...

Research paper thumbnail of High Intralesional Interleukin‐10 Messenger RNA Expression in Localized Cutaneous Leishmaniasis Is Associated with Unresponsiveness to Treatment

The Journal of Infectious Diseases, 2001

The intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-g) wa... more The intralesional expression of cytokines (interleukin [IL]-4, IL-13, IL-10, and interferon-g) was analyzed in 65 patients with localized cutaneous leishmaniasis due to Leishmania guyanensis before specific treatment with pentamidine isethionate. The local expression of IL-10 was significantly higher in patients who responded poorly to treatment than in patients whose lesions were regressing. When an IL-10 level .10 (ratio of the concentration of IL-10 [pg/mL] to that of b-actin [pg/mL]) was used as an indicator of treatment failure, the sensitivity of this test was 78.6, and the specificity was 72.5. Thus, high intralesional expression of IL-10 might predict a poor response to conventional treatment.

Research paper thumbnail of Susceptibility of Mycobacterium ulcerans to a combination of amikacin/rifampicin

International Journal of Antimicrobial Agents, 2003

The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the... more The effectiveness of rifampicin (RIF), amikacin (AMK) and their combination were estimated in the treatment of mice experimentally infected by Mycobacterium ulcerans and the risk of relapse after the treatment was evaluated. After 7 weeks of treatment with RIF or with the combination of AMK/RIF and 8 weeks with AMK alone, no viable bacilli were found in the infected tissues and these remained uninfected during the following 6 months. Among the mice treated with AMK alone, three mice relapsed, but the minimal inhibitory concentration of AMK for these isolates remained unchanged. With RIF alone, two mice relapsed and the minimal inhibitory concentration of these isolated strains was higher. However, with all the mice treated with both RIF and AMK, no relapse was observed.

Research paper thumbnail of Th1 Cell Development Induced by Cysteine Proteinases A and B in Localized Cutaneous Leishmaniasis Due to Leishmania guyanensis

Infection and Immunity, 2003

The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with... more The cysteine proteinases CPA and CPB from Leishmania major induced Th1 responses in patients with leishmaniasis due to Leishmania guyanensis . Furthermore, cysteine proteinases induced neither interleukin 4 (IL-4) nor IL-13 and low levels of IL-10 in controls and patients. The results suggest that CPs would be quite good candidates for a vaccine against different Leishmania species.

Research paper thumbnail of Differential Production of Systemic and Intralesional Gamma Interferon and Interleukin-10 in Nodular and Ulcerative Forms of Buruli Disease

Infection and Immunity, 2004

Buruli disease, caused by Mycobacterium ulcerans , is the third most important mycobacterial dise... more Buruli disease, caused by Mycobacterium ulcerans , is the third most important mycobacterial disease in humans besides tuberculosis and leprosy. We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease. Gamma interferon (IFN-γ) levels in response to whole M. ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts. Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures. IFN-γ production after stimulation with M. ulcerans was significantly lower ( P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules. On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response t...

Research paper thumbnail of LACK-Specific CD4 + T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection

Infection and Immunity, 2002

The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue... more The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis . Gamma interferon (IFN-γ) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4 + cells producing IFN-γ were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4 + T cells producing IFN-γ and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA − CCR7 − CD4 + T cells. CD4 + T cells producing IFN-γ are CD62L − , and CD4 + T cells producing IL-10 are CD62L + , indicating that these cells have different tissue-ho...

Research paper thumbnail of Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

Journal of Clinical Microbiology, 2014

In French Guiana, leishmaniasis is an essentially cutaneous infection. It constitutes a major pub... more In French Guiana, leishmaniasis is an essentially cutaneous infection. It constitutes a major public health problem, with a real incidence of 0.2 to 0.3%. Leishmania guyanensis is the causal species most frequently encountered in French Guiana. The treatment of leishmaniasis is essentially drug based, but the therapeutic compounds available have major side effects (e.g., liver damage and diabetes) and must be administered parenterally or are costly. The efficacy of some of these agents has declined due to the emergence of resistance in certain strains of Leishmania . There is currently no vaccine against leishmaniasis, and it is therefore both necessary and urgent to identify new compounds effective against Leishmania . The search for new drugs requires effective tests for evaluations of the leishmanicidal activity of a particular molecule or extract. Microculture tetrazolium assays (MTAs) are colorimetric tests based on the use of tetrazolium salts. We compared the efficacies of th...

Research paper thumbnail of Leishmania naiffi and lainsoni in French Guiana: Clinical features and phylogenetic variability

PLOS Neglected Tropical Diseases

Research paper thumbnail of Antibiotic Treatment in Anopheles coluzzii Affects Carbon and Nitrogen Metabolism

Pathogens

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host... more The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness; it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of Anopheles coluzzii provided with a sugar-meal or a non-infectious blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified pathways which may participate in microbiota-Plasmodium interactions via meta...

Research paper thumbnail of Ecology, evolution, and epidemiology of zoonotic and vector-borne infectious diseases in French Guiana: Transdisciplinarity does matter to tackle new emerging threats

Infection, Genetics and Evolution

Research paper thumbnail of Validation of Swab Sampling and SYBR Green-Based Real-Time PCR for the Diagnosis of Cutaneous Leishmaniasis in French Guiana

Journal of Clinical Microbiology

Recent studies have highlighted the interest in noninvasive sampling procedures coupled with real... more Recent studies have highlighted the interest in noninvasive sampling procedures coupled with real-time PCR methods for the detection of Leishmania species in South America. In French Guiana, the sampling method still relied on skin biopsies. Noninvasive protocols should be tested on a large annual cohort to improve routine laboratory diagnosis of cutaneous leishmaniasis. Therefore, we evaluated the performance of a new Leishmania detection and species identification protocol involving cotton swabs and SYBR green-based real-time PCR of the Hsp70 gene, coupled with Sanger sequencing.

Research paper thumbnail of Ecological niche modelling for predicting the risk of cutaneous leishmaniasis in the Neotropical moist forest biome

PLOS Neglected Tropical Diseases

A major challenge of eco-epidemiology is to determine which factors promote the transmission of i... more A major challenge of eco-epidemiology is to determine which factors promote the transmission of infectious diseases and to establish risk maps that can be used by public health authorities. The geographic predictions resulting from ecological niche modelling have been widely used for modelling the future dispersion of vectors based on the occurrence records and the potential prevalence of the disease. The establishment of risk maps for disease systems with complex cycles such as cutaneous leishmaniasis (CL) can be very challenging due to the many inference networks between large sets of host and vector species, with considerable heterogeneity in disease patterns in space and time. One novelty in the present study is the use of human CL cases to predict the risk of leishmaniasis occurrence in response to anthropogenic, climatic and environmental factors at two different scales, in the Neotropical moist forest biome (Amazonian basin and surrounding forest ecosystems) and in the surrounding region of French Guiana. With a consistent data set never used before and a conceptual and methodological framework for interpreting data cases, we obtained risk maps with high statistical support. The predominantly identified human CL risk areas are those where the human impact on the environment is significant, associated with less contributory climatic and ecological factors. For both models this study highlights the importance of considering the anthropogenic drivers for disease risk assessment in human, although CL is mainly linked to the sylvatic and peri-urban cycle in Meso and South America.