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Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 55 records · Page 3Linked to original sources

Genetic diversity among Trichophyton mentagrophytes isolates using random amplified polymorphic DNA method.

Trichophyton mentagrophytes is a common cosmopolitan dermatophyte species composed of two varieties: T. mentagrophytes var. interdigitale (anthropophilic form) and T. mentagrophytes var. mentagrophytes (zoophilic form). We used a random amplified polymorphic DNA (RAPD) method to study the genetic diversity of 46 clinical isolates of the T. mentagrophytes complex collected from 38 patients with different geographical origins (Europe, Africa, South America). The T. mentagrophytes were isolated either from a unique lesion for 31 patients, including two patients living together, or from at least two sites for seven patients. Only one primer of 15 primers tested showed DNA polymorphism in the isolates, producing 23 distinct patterns belonging to three clusters. There was no specific cluster grouping isolates from the same geographical origin. The same pattern is shared by all the four T. mentagrophytes var. mentagrophytes and 13 of 42 T. mentagrophytes var. interdigitale. An identity of strains responsible for several lesions in seven individuals suggests an homogeneous T. mentagrophytes population in the case of multiple lesions. In contrast, the dissimilarity of two strains recovered from two patients living together argues against person-to-person transmission in that case. This study indicates that RAPD can be successfully applied to show genetic diversity among T. mentagrophytes isolates.

Africa↗

Molecular search of new active drugs against Toxoplasma gondii.

Molecular connectivity has been applied to the search of new compounds with activity against the protozoan Toxoplasma gondii, using a stepwise linear discriminant analysis (SLDA) which is able to classify a compound according its activity either as active or as inactive. Among the selected compounds, andrographolide and dibenzotiophene sulfone stand out, both with IC50 values lower than 1 microgram/ml, which are comparable to these of drugs such as sulfamethoxazole, pyrimethamine and trimethoprim, with IC50 values equal to 1.1, 0.04 and 2.31 micrograms/ml, respectively. These results confirm the usefulness of our topological approach for the selection and design of new-lead drugs active against Toxoplasma gondii.

Animals↗

Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation.

To determine prognostic factors for survival in bone marrow transplant recipients with invasive aspergillosis (IA), we retrospectively reviewed 27 IA cases observed in our bone marrow transplantation unit between January 1994 and October 1994. On 30 September 1997, six patients were alive and disease-free. The median survival after IA diagnosis was 36 days. Of eight variables found to be related to survival according to the univariate analysis, graft-versus-host disease (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose taken during the week preceding IA diagnosis (CPDlw) (P < .0001) were selected by a backward stepwise Cox regression model. A three-stage classification was established: CPD1w of < or =7 mg/kg (3 of 8 patients died; 60-day survival rate, 88%), CPD1w of >7 mg/kg and no GVHD (9 of 10 patients died; 60-day survival rate, 20%), and CPD1w of >7 mg/kg and active acute grade 2 or more or extensive chronic GVHD (9 of 9 patients died; 30-day survival rate, 0) (P < .0001).

Adolescent↗

Incidence and risk factors of toxoplasmosis in a cohort of human immunodeficiency virus-infected patients: 1988-1995. HEMOCO and SEROCO Study Groups.

The incidence of cerebral and extracerebral toxoplasmosis among 1,699 HIV-infected patients followed in the SEROCO and HEMOCO cohorts (1988-1995) was studied. It increased from 0.7 per 100 person-years in 1988 to 2.1 per 100 person-years in 1992, as a result of the increasing prevalence of patients with CD4 cell counts below 200/microL. It decreased thereafter to 0.2 per 100 person-years in 1995, while the proportion of patients receiving specific prophylaxis was increasing. A Toxoplasma antibody titer of >150 IU/mL was an important predictor of toxoplasmosis (adjusted relative risk [aRR], 3.6 [95% confidence interval, 2.1-6.0]), independent of a CD4+ cell count of <200/microL (aRR, 20.8) and specific prophylaxis (aRR, 0.2 [0.1-0.3]). The median CD4+ cell count was 389/microL at the time the antibody titer was first noted to be >150 IU/mL, while the median CD4 cell count at onset of toxoplasmosis was 58/microL. Thus, disease was diagnosed 10 days to 74 months after the rise in Toxoplasma antibody titers. While the risk factors for development of toxoplasmosis remain incompletely defined, the importance of specific prophylaxis for patients with low CD4 cell counts and high Toxoplasma antibody titers is supported by these findings.

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↗

Determination of the inhibitory effect on Toxoplasma growth in the serum of AIDS patients during acute therapy for toxoplasmic encephalitis.

In 26 AIDS patients treated for toxoplasmic encephalitis, the inhibitory effect on Toxoxplasma growth of sequential sera taken before and after initiation of therapy was determined using a culture-based immunoassay and compared with pyrimethamine blood levels. A marked inhibition of Toxoplasma growth was observed 1 day after initiation of therapy with pyrimethamine plus sulfadiazine and was maintained between 67% and 93% throughout the 15-day follow-up period. The degree of inhibition was not correlated to pyrimethamine blood levels and seemed highly potentiated when sulfadiazine rather than macrolides was given in combination with pyrimethamine.

Acquired Immunodeficiency Syndrome↗

The Th1 to Th2 shift induced by Schistosoma mansoni does not exacerbate murine aids (MAIDS).

Schistosoma mansoni infection in mice is associated with a switch from a Th1 to a Th2-type cytokine response. The role of Th1 and Th2 responses in immune dysregulations associated with AIDS and murine AIDS (MAIDS) is controversial, but a Th2 bias could be associated with disease progression, raising the hypothesis that helminth infections might accelerate the retroviral disease progression. Here, we used the murine model of AIDS to evaluate the course of the viral disease during co-infection with S. mansoni. C57BL/6 mice were infected with S. mansoni cercariae 8 weeks before intravenous challenge with the LP-BM5 retroviral complex. MAIDS did not progress faster in co-infected mice, in terms of spleen and inguinal lymphadenopathy size, ecotropic virus titres in the spleen, or in vitro proliferative responses to mitogen. Th2 cytokine production was not enhanced in co-infected animals, except for an isolated increase in IL-4 production 21 weeks after LP-BM5 infection. Co-infected animals had significantly lower lymph node and spleen weights than mice infected with LP-BM5 only. MAIDS did not influence the granulomatous response to S. mansoni in the liver of co-infected mice. Finally, infection with S. mansoni neither enhanced Th2 cytokine production nor accelerated MAIDS progression in animals subsequently challenged with LP-BM5.

Animals↗

Assessment of the activity of atovaquone-loaded nanocapsules in the treatment of acute and chronic murine toxoplasmosis.

The aim of this work was to develop a new pharmaceutical form of atovaquone and to study its activity against Toxoplasma gondii in vitro and in vivo. Nanocapsules were chosen as the oral dosage form of administration. An analytical method was developed to determine the drug content in nanocapsules. The stability of these nanocapsules were assessed by following drug content, size, pH and osmolarity for a period of six months. The in vitro activity of atovaquone-loaded nanocapsules against tachyzoites of T. gondii (RH stain) was comparable to its suspension form. In vivo studies were carried out in murine models of acute and chronic toxoplasmosis. Mice acutely infected with the virulent RH strain were orally treated with a dose regimen of 15 mg/kg/day for 10 days, starting from day 1 post-infection. 75% of the mice receiving atovaquone-loaded nanocapsules survived 30 days post-infection, compared to none of untreated controls and none of mice treated with the suspension with the same dose regimen. In mice chronically infected by the COUL or the ME49 strain (Type II strains), then treated for six weeks, treatment with atovaquone (15 mg/kg/d, nanoparticles or suspension) resulted in a decrease of brain parasitic burden, which was significantly more pronounced in ME49-infected mice and in those treated with drug-loaded nanocapsules. These results show that the sensibility of T. gondii to atovaquone is different according to the strains and that the activity of atovaquone in the treatment of toxoplasmosis is enhanced when administered in nanoparticular form.

Acute Disease↗

Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial.

A double-blind placebo-controlled trial was conducted to assess the efficacy and safety of albendazole (400 mg twice daily for 3 weeks) for the treatment of Encephalitozoon intestinalis infection in patients with AIDS. Clearance of microsporidia from the intestinal tract was obtained in 4 of 4 patients in the albendazole group versus 0 of 4 in the control group (P = .01, one-sided Fisher's exact test) and was associated with significant clinical benefit. All 4 controls subsequently cleared microsporidia following open-labeled albendazole treatment. To investigate the effect of albendazole in preventing relapse, these 8 patients were then randomly assigned to receive either albendazole (400 mg twice daily) or no treatment for the next 12 months. Albendazole significantly delayed the occurrence of relapse (P = .04, one-sided log-rank test). In human immunodeficiency virus-infected patients with E. intestinalis infection, albendazole has parasitologic and clinical efficacy and reduces the risk of relapse.

AIDS-Related Opportunistic Infections↗

Risk factors for intestinal microsporidiosis in patients with human immunodeficiency virus infection: a case-control study.

A prospective unmatched case-control study was conducted to determine risk factors for intestinal microsporidiosis in persons infected with human immunodeficiency virus (HIV) who had < or = 200 CD4 cells/mm3. In multivariate analysis, case-patients (n = 30) were more likely than were control-subjects (n = 56) to have < or = 100 CD4 cells/mm3 (odds ratio [OR], 6.5; 95% confidence interval [CI], 1-42), to report male homosexual preference (OR, 7.6; 95% CI, 1-59.5), and to report swimming in a pool in the previous 12 months (OR, 9.2; 95% CI, 2.1-38.9). In summary, intestinal microsporidiosis in persons with HIV infection and < or = 200/mm3 CD4 cells is associated with male homosexuality and swimming in pools, suggesting fecal-oral transmission, including sexual and waterborne routes.

AIDS-Related Opportunistic Infections↗

Experimental evaluation of roxithromycin combined with dapsone or sulphamethoxazole on Pneumocystis carinii and Toxoplasma gondii dual infections in a rat model.

We have developed a dual infection model in immunosuppressed rats for evaluating drugs against Pneumocystis carinii and Toxoplasma gondii, two important opportunistic pathogens in patients with AIDS. Using this model, we reported that the macrolide roxithromycin was effective at a daily dose of 400 mg/kg in preventing the development of T. gondii infection but did not have a prophylactic effect against P. carinii in the same rats. A lower dose (200 mg/kg/day) had only marginal effects. Extending these experiments, we have now shown that roxithromycin at doses of 400 or 200 mg/kg/day combined with dapsone at doses of 5, 25 or 50 mg/kg/day completely prevented the development of T. gondii infection, with no parasites being detected in any of the tissues sampled. Roxithromycin at either dose combined with dapsone at 25 or 50 mg/kg/day was also effective in preventing the development of P. carinii infection in the lungs. The lowest dose of dapsone (5 mg/kg/day) was not fully effective. Pyrimethamine-dapsone, a combination used clinically, was tested in the same experiment, and gave results comparable to those with roxithromycin-dapsone combinations. In a further experiment combining roxithromycin with sulphamethoxazole, roxithromycin was effective in preventing the T. gondii infection, even when given at only 200 mg/kg/day with 20 mg/kg/day of sulphamethoxazole. When the dose of sulphamethoxazole was reduced to 2 mg/kg/day and given with roxithromycin 200 mg/kg/day, T. gondii infection developed in two of the five rats treated. P. carinii infection was prevented by sulphamethoxazole at 20 mg/kg/day but not completely by 2 mg/kg/day. Roxithromycin also has activity against Mycobacterium avium, another important cause of opportunistic infections in AIDS patients, and the compound penetrates mammalian cells well. Taken together with the favourable pharmacokinetic profile of roxithromycin, these results suggest that it may have a clinical utility, when used with other agents, in controlling the development of opportunistic infections caused by M. avium complex, T. gondii and P. carinii in HIV-infected individuals.

Animals↗

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↗

Drug evaluation of concurrent Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium complex infections in a rat model.

We present a new experimental model for the simultaneous evaluation of the activities of drugs against Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium complex infections. Rats latently infected with P. carinii were challenged with the MO-1 strain of M. avium and then immunosuppressed with corticosteroids for 7 weeks. At week 5 the RH strain of T. gondii was intraperitoneally injected. Organs were examined for the three pathogens after death or killing of the animals at week 7. Without treatment, rats challenged with T. gondii died with pulmonary P. carinii infection and disseminated T. gondii and M. avium infections. In order to assess the value of the model for evaluation of the activities of drugs, we administered by oral gavage for 7 weeks drugs or combinations of drugs selected for their individual efficacies against at least one pathogen. We found that clarithromycin with sulfamethoxazole, clarithromycin with atovaquone, roxithromycin with sulfamethoxazole or dapsone, and rifabutin with atovaquone were effective against the three infections, whereas PS-15 with dapsone and trimethoprim with sulfamethoxazole were active against Toxoplasma and Pneumocystis infections only. This triple-infection rat model offers a new tool for the simultaneous evaluation of the activities of drugs against three of the major opportunistic infections occurring in immunosuppressed individuals.

Animals↗

Determination of types of Enterocytozoon bieneusi strains isolated from patients with intestinal microsporidiosis.

To determine the types of Enterocytozoon bieneusi strains associated with intestinal microsporidiosis, we developed a rapid and efficient approach for typing parasites obtained from stool specimens by PCR-restriction fragment length polymorphism (PCR-RFLP). Typing was based on DNA polymorphism of the ribosomal DNA internal transcribed spacer (ITS) region of E. bieneusi. RFLPs generated with two restriction enzymes (NlaIII and Fnu4HI) in PCR-amplified ITS products were used to classify strains into different lineages. This approach was successfully used to differentiate 78 strains that had been obtained from the stools of 65 patients with intestinal microsporidiosis. Among the 78 strains, we found four genetically unrelated lineages, showing the genetic diversity of E. bieneusi. Type I strains of E. bieneusi were found in a majority of the samples, accounting for 51 (78%) of the 65 microsporidiosis cases. In contrast, type II, III, and IV strains were found in only 8 (12%), 3 (5%), and 3 (5%) cases, respectively. All strains of E. bieneusi we have tested so far fall into one of four different lineages, and this study shows that human intestinal microsporidiosis is most often associated with type I strains. PCR-RFLP analysis of the ITS region of E. bieneusi should be useful for epidemiological studies.

AIDS-Related Opportunistic Infections↗