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Biomedical subjects

J P Gangneux

Publications and source records attributed to J P Gangneux.

At least 19 recordsLinked to original sources

Experimental evaluation of antifungal and antiseptic agents against Rhodotorula spp.

We studied the susceptibility of 21 strains of Rhodotorula rubra and nine strains of R. glutinis to eight antifungals and tested eight antiseptic agents on one strain of R. rubra. The tested strains were susceptible to ketoconazole, 5-fluorocytosine, amphotericin B, and nystatin, intermediate to econazole and resistant to fluconazole, itraconazole and miconazole. After 5-min contact, six of the eight antiseptic agents tested showed a fungicidal activity on the tested R. rubra strain.

Amphotericin B↗

[Mycologic surveillance of the environment for preventive invasive aspergillosis. Proposals for standardization of the methodologies and implementation].

A MAJOR RISK: The infection of immunodepressed patients by Aspergillus-type fungi increases morbidity and mortality, particularly in hematology units or during solid organ transplantation. Although present diagnostic means benefit from the progress over the last years, they remain limited and chemoprophylaxis protocols have still not demonstrated significant efficacy. THE NEED FOR RECOMMENDATIONS: Today, the handling of environmental risks is the only strategy that has proved its efficacy and usefulness. On the basis of administrative recommendations and data from the literature, a multicentric and pluri-disciplinary task force, grouping clinicians, microbiologists and hygienists, has assessed different methods and has proposed recommendations for the standardization and optimization of fungal surveillance of the environment.

Air Microbiology↗

Assessment of Leishmania promastigote growth in vitro by means of nucleoside hydrolase activity determination.

Nucleoside hydrolases (NH) are involved in the purine salvage pathway of protozoan cells for the biosynthesis of nucleic acids. We developed a simple and reliable microassay based on N-ribohydrolase dosage using 4-nitrophenyl-beta-D-ribofuranoside (NPR) substrate for the quantification of Leishmania infantum. The free promastigote stage of L. infantum contains high amounts of NH capable of cleaving NPR, but the parasitic amastigote does not. The method allows reliable quantification of viable parasites over a wide range of concentrations (5 x 10(4) 2 x 10(8) parasites ml(-1)) in a single assay. No difference in NH activity was observed between various strains at equivalent concentrations and growth curves determined with NH dosage were similar to optical counts. Samples can be stored at -20 degrees C for weeks before use in this unique assay without significant loss of NH activity. The method is particularly simple and versatile and proves well adapted for the determination of growth characteristics and drug screening studies of L. infantum promastigotes in vitro.

Animals↗

Comparative performance of impactor air samplers for quantification of fungal contamination.

The aim of this study was to assess the performance of different impactor air samplers for fungal spore collection in the hospital environment. Four recent impactor air samplers were selected: Samplair (AES, Combourg, France); Air Test Omega (LCB, France); Air Samplair Mas-100 (Merck, France); and BioImpactor 100-08 (AES). They were compared with one another at three different hospital sites with varying levels of contaminated air. No significant difference in the efficiency of spore recovery was found between Air Test Omega, Mas-100 and BioImpactor, whereas Samplair was significantly less efficient. BioImpactor was then selected to represent the three superior impactors and was compared with the single-stage Andersen disposable sampler and the Collectron MD8 air sampler (Sartorius, France) and the High Flow Air Sample (BioTest, France), which are based on filtration and centrifugation methods, respectively. No significant difference was observed in terms of spore recovery. On the basis of their performance, unit sampling cost, autonomy and simplicity of use, we conclude that Air Test Omega, Air Samplair Mas-100 and BioImpactor 100-08 are suitable for routine indoor evaluation of fungal contamination of air in hospitals.

Air Microbiology↗

Virulence of Leishmania infantum is expressed as a clonal and dominant phenotype in experimental infections.

Human Leishmania infantum infection results in a spectrum of clinical expressions ranging from cutaneous to either asymptomatic or fatal visceral disease. In this context, characterization of parasite virulence appears to be relevant as a biological marker of intrinsic parasitic factors that can affect the pathology of leishmaniasis. Since parasite populations in naturally infected hosts are likely to be composed of multiclonal associations, we first explored the biodiversity of parasite virulence at the intrastrain level in vitro and in vivo by using 11 clones isolated from three strains previously known to express different virulence phenotypes in mice. Subsequently, we studied the course of infection in mice inoculated simultaneously or successively with strains or clones showing various virulence phenotypes. Analysis of in vitro growth characteristics showed no differences among clones from the different parental strains. By contrast, in vivo experiments evidenced a marked intrastrain heterogeneity of virulence to mice. One out of five clones obtained from a virulent strain showed a typical virulence phenotype, while the remaining four clones had low-virulence profiles, as did the six clones isolated from two low-virulence strains. In mixed multiclonal infections, the virulence phenotype was expressed as a dominant character over the associated low-virulence clones. After a challenge with either a homologous or a heterologous strain or clone, virulence phenotypes were conserved and expressed as in naive mice independently from the preexisting population. These results strongly suggest that parasite virulence in L. infantum visceral leishmaniasis is clonal and dominant in nature.

Animals↗

Evidence for determining parasitic factors in addition to host genetics and immune status in the outcome of murine Leishmania infantum visceral leishmaniasis.

C.B-17 SCID and congenic BALB/C mice were used to examine Leishmania infantum strain pathogenicity independently of host genetic factors. While parasite loads were significantly higher in immunodeficient mice than in immunocompetent mice, the kinetics of infection during a long-term follow-up were similar, suggesting that intrinsic parasitic factors also influence the outcome of L. infantum infection.

Animals↗

Fungal contamination of food in hematology units.

The prevalence of thermotolerant fungi on non-heat-sterilizable food was determined. Aspergillus spp. were noted in 100% of pepper and regular tea samples, 12 to 66% of fruits, 27% of herbal teas, and 20% of freeze-dried soup samples. All soft cheese samples were contaminated by Geotrichum and yeast (Candida norvegensis) but Candida albicans was never identified.

Aspergillus↗

[Treatment of visceral leishmaniasis: recent modalities].

AN ENDEMIC DISEASE: Visceral leishmaniasis is an endemic disease in 47 countries and continues to be a difficult therapeutic challenge. The emergence of Leishmania strains resistant to pentavalent antimony derivatives and the growing incidence of visceral leishmaniasis among AIDS patients in the Mediterranean area emphasizes the need for optimal therapeutic management. MORE EFFECTIVE STRATEGIES: During the last few years, alternatives to pentavalent antimony derivatives has disclosed the contribution of amphotericin B, more specifically of lipid formulations of amphotericin B, well tolerated and highly effective drugs [corrected]. Aminosidine, inhibitors of ergosterol synthesis, metronidazole, allupurinol, or miltefosine are also under evaluation. Results have been variable to date. NEW STRATEGIES: It is well demonstrated that the susceptibility of Leishmania to different drugs is species-dependent. Drugs should thus be chosen in accordance with the presumed species in an endemic zone. New strategies based on adapting therapy to the causal species of the parasite, multi-drug regimens, drug vectorization, or restoring immune function in association with secondary prophylaxis in immunodepressed subjects should provide more effective treatment and a lower relapse rate, particularly in patients co-infected with the human immunodeficiency virus.2

AIDS-Related Opportunistic Infections↗

[Evolutive visceral malaria and hyperimmune palustral splenomegaly: a difficult distinction].

One case of hyperreactive malarial splenomegaly is reported for a Comores Island patient living in France and having thus lost his protective immunity. Plasmodium falciparum was detected in a bone marrow aspiration, whereas peripheral venous blood samples were negative. A three-month treatment of sulfadoxine + pyrimethamine was effective with a complete regression of splenomegaly and biological disorders.

Adult↗

Effects of immunosuppressive therapy on murine Leishmania infantum visceral leishmaniosis.

We evaluated the effect of immunosuppressive therapy on the course of infection, the spleen cell immunophenotype and cytokine production during murine Leishmania infantum visceral leishmaniosis (VL). Rousseau et al. [1] recently reported that prolonged administration of dexamethasone induces limited reactivation of chronic murine visceral leishmaniosis, with no clear Th1-Th2 cytokine patterns. We found that another glucocorticoid, hydrocortisone acetate, had similar effects during acute visceral leishmaniosis, i.e. an increase in parasite burden in the spleen, but not the liver, of infected mice. A significant increase in parasite burden in both the liver and the spleen was only achieved when mice were treated with combined dexamethasone + pentoxifylline immunotherapy; increases in parasite burden were never associated with a specific spleen cell immunophenotype or a Th1-Th2 cytokine secretion profile.

Acute Disease↗

Changing patterns of disease and treatment of opportunistic parasitic infections in patients with AIDS.

In the past 18 months, the significant effect of highly active antiretroviral therapy and immune reconstitution on the incidence of opportunistic protozoan infections, mainly cryptosporidiosis and microsporidiosis, has been demonstrated in HIV-infected patients. The major therapeutic advances of the past 18 months concern microsporidiosis, for which the efficacies of fumagillin and albendazole have been assessed against Enterocytozoon bieneusi and Encephalitozoon infections, respectively. The efficacy of macrolides is still uncertain for the treatment of cryptosporidiosis; however, promising results were obtained with nitazoxanide. The incidence of toxoplasmosis has markedly decreased as a result of the efficacy of specific prophylaxis, and visceral leishmaniasis is still considered as an emerging opportunistic disease during AIDS.

Journal Article↗

Influence of the host and parasite strain in a mouse model of visceral Leishmania infantum infection.

We investigated the respective roles of the host and parasite strain in a murine model of visceral leishmaniasis. Balb/c and C57Bl/6 mice were selected for their respective 'non cure' and 'cure' haplotypes vis-a-vis Leishmania major. Mice were infected with 10(7) stationary-phase promastigotes of four strains of Leishmania infantum with different infection profiles in mice: visceralization or regulation, as established by Sulahian et al. (Sulahian et al. (1998) FEMS Immunol. Med. Microbiol. 17, 131-138). The infection was monitored by measuring parasite load in the liver and spleen on days 9, 22, 44 and 87 post-infection, using a sensitive microtitration technique. Similar profiles (visceralizing or regulating) were observed in the two mouse strains, suggesting a predominant role of the Leishmania strain in the visceralization process. The host response was assessed by analyzing the granulomatous response in the liver and by quantifying specific IgG, IgG1 and IgG2a as a marker of the Th1/Th2 immune response. A granulomatous response was observed in both strains of mice but was more pronounced with visceralizing strains of L. infantum and in C57Bl/6 mice compared to Balb/c mice. The kinetics of anti-Leishmania IgG antibody production was similar in all the groups, but the distribution of IgG1 and IgG2a isotypes was different between the two mouse strains: Balb/c mice had a predominantly Th2-like response whereas C57Bl/6 had a mixed Th1/Th2-like response. This study demonstrates the determining role of both the parasite and mouse strain in the outcome of L. infantum infection. The Th1/Th2 concept does not seem to explain susceptibility and resistance to infection in our model of visceral L. infantum infection, contrary to the L. major model.

Animals↗

Efficacy of aminosidine administered alone or in combination with meglumine antimoniate for the treatment of experimental visceral leishmaniasis caused by Leishmania infantum.

BALB/c mice with an experimental visceral leishmaniasis produced by Leishmania infantum were treated with aminosidine sulphate alone or combined with meglumine antimoniate. Parasite burdens in the liver and spleen were determined by subculturings using a sensitive microtitration method. Treatments with aminosidine alone decreased the parasite burdens compared with those observed in the untreated mice, but were less efficacious than meglumine antimoniate. Aminosidine combined with meglumine antimoniate resulted in an increased efficacy compared with either drug given alone. However, these regimens were associated with toxicities and with persistence of hepatic and splenic leishmanial foci after drug administrations.

Animals↗

Activity of IFN-gamma in experimental Leishmania infantum murine visceral leishmaniasis.

The effect of recombinant interferon-gamma (rIFN-gamma) on Leishmania infantum infection was investigated in vivo. BALB/c mice were injected intravenously (i.v.) with 10(7) promastigotes of Leishmania infantum. rIFN-gamma, 10(6) U given intraperitoneally (i.p.) daily on 3 consecutive days or 4 times on alternate days from day 7 (d7) post infection, had no detectable effect on the parasite burdens in liver, spleen, and lungs as compared to untreated mice. However rIFN-gamma enhanced the activity of Glucantime (50 mg/kg/d intraperitoneally for 7 days) in the liver and in the lungs. The additive effect of rIFN-gamma was still observed at day 30 post-infection, i.e. 15 days after cessation of therapy. By contrast the combination of the two drugs had no activity against splenic parasites.

Animals↗