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Cayenne, French Guiana

Cockburn J.J.B.,Institute Pasteur Paris | Cockburn J.J.B.,French National Center for Scientific Research | Navarro Sanchez M.E.,Institute Pasteur Paris | Navarro Sanchez M.E.,French National Center for Scientific Research | And 12 more authors.
EMBO Journal | Year: 2012

The four serotypes of dengue virus (DENV-1 to-4) cause the most important emerging viral disease. Protein E, the principal viral envelope glycoprotein, mediates fusion of the viral and endosomal membranes during virus entry and is the target of neutralizing antibodies. However, the epitopes of strongly neutralizing human antibodies have not been described despite their importance to vaccine development. The chimpanzee Mab 5H2 potently neutralizes DENV-4 by binding to domain I of E. The crystal structure of Fab 5H2 bound to E from DENV-4 shows that antibody binding prevents formation of the fusogenic hairpin conformation of E, which together with in-vitro assays, demonstrates that 5H2 neutralizes by blocking membrane fusion in the endosome. Furthermore, we show that human sera from patients recovering from DENV-4 infection contain antibodies that bind to the 5H2 epitope region on domain I. This study, thus, provides new information and tools for effective vaccine design to prevent dengue disease. © 2012 European Molecular Biology Organization | All Rights Reserved.

Dormoi J.,Institute Of Recherche Biomedicale Des Armees | Dormoi J.,Aix - Marseille University | Briolant S.,Institute Of Recherche Biomedicale Des Armees | Briolant S.,Aix - Marseille University | And 4 more authors.
Malaria Journal | Year: 2013

Background: Proveblue®, a methylene blue dye that complies with European Pharmacopoeia and contains limited organic impurities and heavy metals of recognized toxicity, showed in vitro synergy against Plasmodium falciparum when combined with atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl- Coenzyme A reductase. The objective of this study was to evaluate the in vivo efficacy of Proveblue® when combined with atorvastatin in a murine model of experimental cerebral malaria. Methods. Forty female C57Bl6/N mice were divided into four groups (control, atorvastatin 40 mg/kg for seven days, Proveblue® 10 mg/kg for five days and atorvastatin combined with Proveblue®), infected with Plasmodium berghei ANKA parasites by intraperitoneal inoculation and observed for 45 days. Results: Treatment with atorvastatin alone did not demonstrate an effect significantly different from no treatment (p = 0.0573). All the mice treated by atorvastatin alone died. Treatment with Proveblue® or a combination of Proveblue® and atorvastatin was significantly increased survival of cerebral malaria (p = 0.0011 and 0.0002, respectively). Although there was only one death in the atorvastatin and Proveblue® combination treatment group (10%) versus two deaths (22%) with Proveblue® treatment, the effect on cerebral malaria was not significant (p = 0.283). Conclusions: The present work demonstrated, for the first time, the high efficacy of Proveblue® in preventing cerebral malaria. Atorvastatin alone or in combination appears to possess limited use for preventing cerebral malaria. Combination of atorvastatin with lower doses of Proveblue® (<10 mg/kg/day) should be evaluated to show potential synergistic effects in cerebral malaria prevention. © 2013 Dormoi et al.; licensee BioMed Central Ltd.

Dormoi J.,Institute Of Recherche Biomedicale Des Armees | Dormoi J.,Aix - Marseille University | Briolant S.,Institute Of Recherche Biomedicale Des Armees | Briolant S.,Aix - Marseille University | And 4 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

Although 100% of untreated mice infected with Plasmodium berghei died with specific signs of cerebral malaria and 100% of mice treated with 3 mg/kg dihydroartemisinin, the active metabolite of artesunate, which is used as the first-line treatment for severe malaria, also died but showed no specific signs of cerebral malaria, 78% of mice treated with 10 mg/kg Proveblue (methylene blue) and 78% of mice treated with a combination of 3 mg dihydroartemisinin and 10 mg/kg Proveblue survived and showed no specific signs of cerebral malaria or detectable parasites. Copyright © 2013, American Society for Microbiology.

Valderramos S.G.,Columbia University | Valderramos S.G.,Yeshiva University | Valderramos J.-C.,Yeshiva University | Musset L.,Yeshiva University | And 5 more authors.
PLoS Pathogens | Year: 2010

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 artemisininbased 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. © 2010 Valderramos et al.

Simonnet C.,Institute Pasteur Of La Guyane | Berger F.,Institute Pasteur Of La Guyane | Gantier J.-C.,Institute Pasteur Paris
Medical Mycology | Year: 2011

A three-year retrospective analysis of fungi isolated from specimens of patients with superficial fungal infections in French Guiana is presented. Clinical samples from 726 patients with presumptive diagnoses of onychomycosis (28.2% of the patients), tinea capitis (27.8%), superficial cutaneous mycoses of the feet (22.0%), and of other areas of the body (21.9%), were assessed by microscopic examination and culture. Dermatophytes accounted for 59.2% of the isolates, followed by yeasts (27.5%) and non-dermatophytic molds (13.1%). Trichophyton rubrum was the most common dermatophyte recovered from cases of onychomycosis (67.4%), tinea pedis (70.6%) and tinea corporis (52.4%). In contrast, Trichophyton tonsurans was the predominant species associated with tinea capitis (73.9%). Yeasts were identified as the principal etiologic agents of onychomycosis of the fingernails (74.2%), whereas molds were found mainly in cases of onychomycosis of the toenails. In such instances, Neoscytalidium dimidiatum (70.8%) was the most common mold recovered in culture. In conclusion, the prevalence of T. rubrum and the occurrence of onychomycosis and fungal infections of the feet in French Guiana are similar to results reported from Europe, whereas the frequency of tinea capitis and the importance of T. tonsurans in such infections are similar to the situation in the Americas. © 2011 ISHAM.

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