Search PubMed⌕ Search

Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 73 records · Page 4Linked to original sources

[First case of cutaneous leishmaniasis from Leishmania infantum in Corsica].

Canine leishmaniasis is endemic in Corsica. Sporadic cases of visceral leishmaniasis due to Leishmania infantum have been reported in humans, but no case of cutaneous leishmaniasis has been reported to date. In August 1994, a 42-year-old woman living in Orleans (France) presented with two nodular lesions on the face. These lesions appeared two months after a stay near the Gulf of Ajaccio in Corsica. Histopathological examination revealed intracellular amastigotes. The culture isolate was identified as Leishmania infantum zymodeme MON-29. Epidemiological data and climatic conditions prevailing during the patient's stay suggest that contamination took place in Corsica.

Adult↗

High seroprevalence of Encephalitozoon species in immunocompetent subjects.

Encephalitozoon species are important pathogens in human immunodeficiency virus-infected patients. However, in immunocompetent persons, little is known about Encephalitozoon infections, mainly because of the lack of reliable diagnostic tests. To improve diagnosis, three serologic techniques that use Encephalitozoon intestinalis as antigen were developed: an ELISA, an immunofluorescence technique (IFAT), and a counterimmunoelectrophoresis (CIE) method. The serologic response against E. intestinalis was studied in sera from 300 Dutch blood donors and 276 pregnant French women. For confirmation of specificity, sera from 150 subjects with various infectious and noninfectious diseases were examined. ELISA, IFAT, and CIE were specific for microsporidia infections, and IFAT and CIE were specific for Encephalitozoon infections. High antibody titers against Encephalitozoon organisms were found in 24 (8%) of 300 Dutch blood donors and in 13 (5%) of 276 pregnant French women. The high seroprevalence against Encephalitozoon species in Dutch blood donors and French women suggests that Encephalitozoon infection is common in immunocompetent subjects.

Adolescent↗

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↗

Diagnosis of infections caused by Enterocytozoon bieneusi and Encephalitozoon intestinalis using polymerase chain reaction in stool specimens.

OBJECTIVE: To study the usefulness of polymerase chain reaction (PCR) for the species identification of microsporidia in stool specimens obtained from HIV-infected patients with Enterocytozoon bieneusi or Encephalitozoon intestinalis infections. SETTING: Infectious disease clinic in a university hospital. PATIENTS: Thirty-seven stool specimens from 29 HIV-infected patients with microsporidiosis were tested. The diagnosis of microsporidian infection was made by light microscopy of stool specimens and species identification was made by transmission electron microscopy of duodenal biopsies. Sixty-one stool specimens from 45 HIV-infected patients without microsporidiosis served as controls. METHODS: PCR was performed using DNA extracted from stools with two primers sets, one specific for E. bieneusi and one specific for E. intestinalis. RESULTS: A 1265 base-pair fragment of the small subunit ribosomal RNA (rrs) gene could be amplified from all 31 stool specimens infected with E. bieneusi. In addition, a 930 base-pair fragment of the rrs gene could be amplified from all six stool specimens infected with E. intestinalis. The 61 control stools were negative with both primers. CONCLUSIONS: These results suggest that a PCR based assay using species-specific primers sets can be used successfully for microsporidian species differentiation from stool specimens, thus obviating the need for invasive biopsy procedures.

AIDS-Related Opportunistic Infections↗

Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group.

OBJECTIVE: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a frequent cause of chronic diarrhoea in patients with HIV infection for which there is no available therapy. This study was designed to search for a drug with activity against this organism. DESIGN: Prospective open-labelled Phase II multicentre study. SETTING: University hospitals. PATIENTS: Sixty HIV-infected men with intestinal E. bieneusi infection. INTERVENTIONS: Ten drug regimens were consecutively tested orally for 3 weeks: albendazole plus metronidazole, sulphadiazine plus pyrimethamine, atovaquone, doxycycline plus nifuroxazide, itraconazole, flubendazole, chloroquine, paromomycin, sparfloxacin and fumagillin. Nine evaluable patients per regimen were required, but each patient could be enrolled up to three times in the study. OUTCOME MEASURE: Efficacy was assessed primarily by the clearance of E. bieneusi from stools and intestinal biopsies. The safety of each regimen was also assessed. RESULTS: Only purified fumagillin was able to clear E. bieneusi from stools as well as intestinal biopsies, whereas all other regimens failed to show antiparasitic efficacy. However, only four patients received fumagillin because of drug-induced thrombocytopenia. The four patients who received fumagillin remained free of E. bieneusi infection after a mean follow-up of 10 months. CONCLUSION: Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.

AIDS-Related Opportunistic Infections↗

Cryptococcus neoformans infection in mice previously infected with LP-BM5 MuLV, the agent of murine AIDS (MAIDS).

We studied susceptibility to experimental systemic cryptococcosis in mice previously infected with the retroviral complex LP-BM5 (responsible for murine AIDS). LP-BM5 was inoculated to C57B1/6 mice by intravenous (i.v.) injection 8 weeks before an i.v. challenge with 4 x 10(3) CFU of Cryptococcus neoformans. Uninfected and singly infected mice were used as controls. LP-BM5 infection did not result in a significant increase in fungal burdens in the lungs or brains of co-infected animals compared to mice infected with C. neoformans alone. However, mortality was enhanced in the co-infected animals. The kinetics of splenocyte subsets differed in co-infected mice and LP-BM5-infected mice; the increase in CD4+, CD8+ and Ly5+ cells was only moderate in the former. Cytokine production by concanavalin A (Con A)-stimulated splenocytes from co-infected mice showed a marked decrease in the Th1 response (IFN-gamma, IL-2) and an increase in the Th2 response (IL-4, IL-10). Furthermore, cryptococcosis altered the course of MAIDS, inhibiting splenomegaly. This effect was not related to a decrease in ecotropic virus titres in the spleen or to improved in vitro responsiveness of spleen cells to Con A. The marked decrease in IFN-gamma production in co-infected animals could partly explain the inhibition of LP-BM5-induced splenomegaly. This model of murine retroviral infection does not seem to be suitable for studying cryptococcosis in immunosuppressed animals, but remains valuable for investigating in vivo interactions between two pathogens.

AIDS-Related Opportunistic Infections↗

Experimental pathogenicity of viscerotropic and dermotropic isolates of Leishmania infantum from immunocompromised and immunocompetent patients in a murine model.

The pathogenicity of 22 strains of Leishmania infantum from 11 HIV-infected and 11 immunocompetent patients with visceral (VL, n = 16) or cutaneous (CL, n = 6) leishmaniasis, belonging to 3 zymodemes (MON-1, n = 14; MON-29, n = 5; MON-33, n = 3), was studied using a murine model. For each strain 16-20 BALB/c mice were infected at day 0 (d0) by i.v. injection of 10(7) stationary-phase promastigotes. Parasite burdens were quantified in the spleen and liver of 4-5 mice of each strain at d7, d20, d60 and d90 or d100, using a sensitive culture microtitration technique. A great variability of infection profiles between strains was observed: (i) six strains showed a progressive infection, with a predominance of hepatic parasites at d7 or d20 (10(4)-10(6) g-1), then a continuous rise of splenic parasites reaching 10(5)-10(7) g-1 at d90 or d100 contrasting with a stagnation or decrease in the liver; (ii) ten strains gave a controlled infection with hepatic parasite burden reaching 10(4)-10(5) g-1 at d7 or d20, followed by a more or less rapid decline leading frequently to no detectable parasites; (iii) six strains resulted in other profiles, i.e., undetectable infection (n = 1) or low parasite loads (n = 4), or late occurrence of parasites in the spleen (n = 1). No relationship was observed between profile and growth characteristics in vitro or zymodeme of the strain. Strains originating from CL never gave a visceralizing pattern in mice, but belonged more frequently to the avirulent type compared to VL strains. Strains from HIV-infected patients were not less virulent than those from immunocompetent individuals. These results showed that the course of L. infantum infection varies markedly with intrinsic parasite factors that display striking intraspecific variability.

Animals↗

Determination of genotypes of Toxoplasma gondii strains isolated from patients with toxoplasmosis.

To determine the genotypes of Toxoplasma gondii strains associated with human toxoplasmosis, we developed a sensitive approach for typing parasites grown from clinical samples by short-term in vitro culture. A newly described nested PCR assay was capable of amplifying genomic DNA from as few as five parasites in the presence of host tissues. Typing was based on DNA polymorphisms at the SAG2 locus, encoding tachyzoite surface antigen p22. Restriction fragment length polymorphisms in PCR-amplified SAG2 products were used to classify strains into one of the three major lineages of T. gondii. This approach was successfully used to determine the genotypes of 68 of 72 samples that had been previously isolated from patients with congenital, cerebral, and disseminated toxoplasmosis. Type II strains of T. gondii were found in a majority of the samples, accounting for 55 (81%) of the 68 toxoplasmosis cases. In contrast, type I and III strains were found in only 7 (10%) and 6 (9%) of the 68 cases, respectively. The results of this study support the previous finding that type II strains are most often associated with human toxoplasmosis. Nested PCR analysis at the SAG2 locus provides rapid assignment of T. gondii to a specific genotype that should be useful in analyzing a variety of clinical samples.

AIDS-Related Opportunistic Infections↗

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↗

Altered trimethoprim-sulfamethoxazole ratios for prophylaxis and treatment of Toxoplasma gondii and Pneumocystis carinii dual infections in rat model.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line drug for prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP) and for prophylaxis of toxoplasmosis in HIV-infected patients. Evidence indicating intolerance related to the dose of SMX led us to examine the efficacy of altered TMP-SMX ratios in a corticosteroid-treated rat model. Infections were assessed by counting P. carinii cysts in lung and by titration of Toxoplasma gondii burdens in tissue culture. For prophylaxis, the reference regimen of 20 mg/kg TMP plus 100 mg/kg SMX was effective. Reduced doses of SMX (5 and 20 mg/kg) effective against PCP were effective against toxoplasmosis, provided the TMP dose was increased to 100 mg/kg. For curative treatment, the reversed ratio of 100 mg/kg TMP plus 20 mg/kg SMX was not effective. These results may provide a basis for altering the TMP-SMX ratios in setting of prophylaxis for both infections, especially in HIV infected patients who often poorly tolerate sulfonamides.

Animals↗

Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis.

Aspergillus antigenemia was followed up in 215 consecutively observed bone marrow transplant (BMT) patients over a period of two years, using both a latex agglutination test and a sandwich immunocapture enzyme immunoassay (EIA) with a rat antigalactomannan monoclonal antibody as capture and detector antibody. For each patient, sequential sera (3 to 20) were obtained before and after BMT. No positivity was observed before BMT. After BMT, the EIA and latex agglutination test were positive in 19 and 4 patients respectively of 25 patients with confirmed aspergillosis and 14 and 7 of 15 patients with probable aspergillosis. In 19 of 25 patients with confirmed aspergillosis and 9 of 15 patients with probable aspergillosis, the EIA was more sensitive and detected infection earlier than the latex test. In all positive cases, antigenemia rapidly increased in sequential samples and remained strongly positive. In 31 of 169 (19%) BMT patients without clinical signs of aspergillosis, the EIA was occasionally positive in samples taken within the first month after BMT, giving a specificity of 81% in these patients. In non-BMT patients suffering from other diseases (n = 77), the specificity was 98.7%. The overall positive and negative predictive values for the EIA were 54% and 95% respectively. These results favour the use of EIA for early diagnosis and monitoring of aspergillosis in BMT patients, although the predictive value of transient positivity remains to be ascertained.

Animals↗

Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis.

To evaluate the potential risk of dissemination or reactivation of toxoplasmosis following the administration of immunosuppressive therapy we examined the effect of corticoids, azathioprine, and cyclosporine given alone or in combination on the course of murine acute and chronic toxoplasmic infection. Swiss Webster mice were infected perorally with a high-level inoculum of cysts of the C strain of Toxoplasma gondii. The evolution of the kinetics of parasite loads in the blood, brain, and lungs of infected and immunosuppressed mice was then sequentially followed. In mice with orally acquired infections initiated 2 days after the beginning of drug treatment, immunosuppression led to the persistence of parasites, especially in the lungs, which was most marked in mice treated with azathioprine and/or cortisol acetate. Administration of immunosuppressive therapy in mice previously infected with T. gondii resulted in a brief resurgence of parasite loads when treatment was started early after infection. Finally, under our experimental conditions we found that the immunosuppressive drugs that were given altered the natural course of infection with a prolonged persistence of parasites in the lungs but did not significantly affect parasite loads in the brain or lead to disseminated infection with detectable parasitemia.

Acute Disease↗

Lack of activity of artemether for prophylaxis and treatment of Toxoplasma gondii and Pneumocystis carinii infections in rat.

Artemisinin and its derivatives have been found effective in vivo against Plasmodium and in vitro against Toxoplasma gondii and Pneumocystis carinii. We tested the activity of artemether for prophylaxis and treatment in the rat model of concurrent T. gondii and P. carinii infection. Artemether at doses of 18 and 100 mg/kg administered (s.c.) in prophylaxis did not prevent toxoplasmosis or pneumocystosis, while trimethoprimsulfamethoxazole (reference treatment) was effective for prevention of both infections. Similar results were obtained in curative studies. These results do not support the use of artemether for prevention or treatment of toxoplasmosis or pneumocystosis.

Animals↗

Therapeutic effect of reference antileishmanial agents in murine visceral leishmaniasis due to Leishmania infantum.

A sensitive, culture-based, microtitration technique has recently been developed for determining parasite burdens in organs recovered from Balb/c mice infected with Leishmania infantum. In the present study, this technique was used to examine the efficacy of three, first-line, antileishmanial agents in reducing parasite burdens and eradicating parasites from target organs in mice. Treatment with meglumine antimoniate (50 mg SbV/kg.day) significantly reduced the parasite burdens in the livers and lungs (by about 10-fold and > 100-fold, respectively) but not those in the spleens. Although use of a higher dose of meglumine antimoniate (200 mg SbV/kg.day) resulted in an even more dramatic reduction in the parasite burdens in the livers, it had no significant effect on the burdens in the spleens. Treatment with amphotericin B (0.8 mg/kg every other day) resulted in significant reductions in the parasite burdens in the livers, spleens and lungs of infected mice. Although low doses of aminosidine (20 mg/kg.day) had no effect, high doses (200 mg/kg.day) resulted in undetectable parasite burdens in the livers, for at least 100 days post-treatment, and marked reductions in burdens in the spleens. These results are consistent with previous data from studies using animal models of visceral leishmaniasis. Thanks to the sensitivity of the technique, culture microtitration revealed that none of the drug schedules achieved the elimination of all parasites in all target organs. The murine model used mimics some important features of HIV/Leishmania infantum co-infections in humans.

Amphotericin B↗

Detection and species identification of intestinal microsporidia by polymerase chain reaction in duodenal biopsies from human immunodeficiency virus-infected patients.

Polymerase chain reaction (PCR) was used for the detection of microsporidian DNA in duodenal biopsies obtained from 28 human immunodeficiency virus (HIV)-infected patients with intestinal microsporidiosis. Duodenal biopsies from 23 HIV-infected patients without microsporidiosis served as controls. A generic primer set for human microsporidia was used at first for the PCR. Amplified products were detected in 26 (93%) of 28 biopsies from patients with intestinal microsporidiosis. All control biopsies were negative. Microsporidia species were identified using Southern blot hybridization with specific probes for Enterocytozoon bieneusi and Encephalitozoon intestinalis. This technique confirmed the transmission electron microscopy-based species identification. Similar results were obtained using PCR with species-specific primer sets for E. bieneusi and E. intestinalis. PCR testing of intestinal biopsy specimens can be used successfully for rapid detection and species differentiation of intestinal microsporidia and thus could be a valuable alternative to transmission electron microscopy.

AIDS-Related Opportunistic Infections↗