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Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 91 records · Page 5Linked to original sources
PubMed1996

Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group.

OBJECTIVE: To study the predictive value of anti-Toxoplasma gondii antibody titres for the occurrence of toxoplasmic encephalitis (TE) in HIV-infected patients. METHODS: Data from the placebo arm of a trial of primary prophylaxis for TE (ANRS 005/ACTG 154) were analysed. Patients included had CD4+ cell counts < 200 x 10(6)/l and a positive Toxoplasma serology. Immunoglobulin (Ig) G and IgM Toxoplasma antibody titres at entry were retrospectively determined by enzyme-linked immunosorbent assay and agglutination on serum samples in a single laboratory. Incidence of TE was estimated by Kaplan-Meier method and a Cox model was used to study the predictive value of antibody titres, adjusted for other covariates. RESULTS: All 164 patients studied were positive for IgG antibodies and one had IgM antibodies. After a mean follow-up of 16 months, 31 cases of TE were documented. One-year incidence of TE was significantly higher in patients with IgG titres > or = 150 IU/ml (23.7%) than in patients with titres < 150 IU/ml (7.7%; relative risk, 3.1; P < 0.003). IgG titres remained significantly associated with the occurrence of TE (relative risk, 3.3; P < 0.005) in the Cox model. Predictive value of IgG titres did not differ according to baseline CD4+ cell counts. CONCLUSIONS: In patients with CD4+ cell counts < 200 x 10(6)/l, IgG anti-Toxoplasma antibody titre is a prognostic factor of occurrence of TE, with a higher risk for titres > or = 150 IU/ml. This finding should reinforce the recommendation of specific prophylaxis in these patients.

AIDS-Related Opportunistic Infections↗
PubMed1996

Therapy of visceral leishmaniasis due to Leishmania infantum: experimental assessment of efficacy of AmBisome.

The tolerance and efficacy of amphotericin B (AmB) deoxycholate (Fungizone) were compared with those of liposomal AmB (AmBisome) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Control groups consisted of untreated mice and mice treated with a pentavalent antimonial (Glucantime). BALB/c mice were infected intravenously on day 0 with 10(7) promastigotes of L. infantum and then treated from day 7 to 17 (early treatment group) or from day 60 to 70 (delayed treatment group). The pentavalent antimonial was administered daily by intraperitoneal injection, whereas AmB formulations were administered intravenously on alternate days. On days 20, 60, and 120 (early treatment group) and on days 72 and 125 (delayed treatment group), parasite burdens in the liver, spleen, and lungs were determined by subculturings using a microtitration method. A dose range study showed that administration of AmBisome at the well-tolerated doses of 5 or 50 mg/kg of body weight completely eradicated the parasites from the tissues. At 0.8 mg/kg, AmBisome proved more efficacious than AmB deoxycholate administered at the same dose. We also compared the levels of AmB deoxycholate and AmBisome in plasma and tissue. Mice treated with AmBisome had levels of AmB in tissue much higher than did AmB deoxycholate-treated mice with persistent detectable levels 14 weeks after treatment. These results seem to account for the remarkable efficacy of the liposomal formulation of AmB in the treatment of visceral leishmaniasis due to L. infantum.

Amphotericin B↗
PubMed1996

In vitro and in vivo effects of rifabutin alone or combined with atovaquone against Toxoplasma gondii.

The efficacy of rifabutin (RIFA) alone or in combination with atovaquone (ATO) was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of Toxoplasma growth by enzyme-linked immunosorbent assay. For in vivo studies, mice were acutely infected with 10(4) tachyzoites of the virulent RH strain and were then treated perorally for 10 days from day 1 or day 4 postinfection. The efficacy of each drug regimen was assessed by determination of survival rates and sequential titration of parasites in blood, brain, and lungs by a tissue culture method. In vitro, RIFA was inhibitory for Toxoplasma growth at concentrations between 0.5 and 20 micrograms/ml; the 50% inhibitory concentration was estimated to be 1.68 micrograms/ml. When RIFA and ATO were combined, synergistic effects were noted for RIFA at 20 micrograms/ml combined with ATO at 0.01 or 0.02 microgram/ml and RIFA at 1, 2, or 5 micrograms/ml combined with ATO at 0.02 microgram/ml. In vivo, administration of RIFA at 200 mg/kg of body weight per day from day 1 to day 10 resulted in a 100% protection during treatment, with clearance of parasites from the blood, brain, and lungs. After the cessation of therapy, relapses occurred in the brain and lungs; the mortality was 46% at the end of the experiment (day 30). Among the mice treated with RIFA at 200 mg/kg/day from day 4 to day 14, no death was recorded during the treatment period and a marked reduction in parasite burdens was observed in blood and tissues; however, relapses occurred and 10% of mice survived until day 30. Administration of RIFA at 200 mg/kg/day in combination with ATO at 100 mg/kg/day resulted in a marked prolongation of survival compared with that for mice that received ATO or RIFA alone. However, in mice receiving the combination, parasite burdens in blood and organs were similar to those in mice treated with RIFA alone. These results confirmed the activity of RIFA in the treatment of acute toxoplasmosis and the potential of the combination of RIFA-ATO since the two drugs act synergistically against Toxoplasma gondii.

Animals↗
PubMed1996

Combination of PS-15, epiroprim, or pyrimethamine with dapsone in prophylaxis of Toxoplasma gondii and Pneumocystis carinii dual infection in a rat model.

In a rat model of dual infection, we studied such dihydrofolate reductase (DHFR) inhibitors as PS-15 (25 mg/kg of body weight), epiroprim (100 mg/kg), and pyrimethamine (3 mg/kg) alone or in combination with various doses of dapsone (50, 25, or 5 mg/kg) for the prevention of pneumocystosis and toxoplasmosis. Rats latently infected with Pneumocystis carinii were immunosuppressed by corticosteroids for 7 weeks, and the drugs were administered from the initiation of the corticosteroid treatment. At week 5, the rats were inoculated intraperitoneally with the RH strain of Toxoplasma gondii. Infections were monitored by the counting of P. carinii cysts in lung homogenates and the titration of T. gondii in organs by quantitative culture and an indirect immunofluorescence assay. Fourteen of the 15 untreated rats died after T. gondii challenge, with P. carinii infection in the lungs and T. gondii infection in the lungs, liver, spleen, and brain. Of the three tested DHFR inhibitors, only PS-15 exhibited anti-P. carinii activity; none prevented toxoplasmosis in 100% of the rats. After the DHFR inhibitors were combined with dapsone (50 or 25 mg/kg), both pneumocystosis and toxoplasmosis were completely prevented. On the basis of these results, PS-15 and epiroprim combined with dapsone are candidates for use for the prevention of both pneumocystosis and toxoplasmosis.

Animals↗
PubMed1996

Detection by PCR of Toxoplasma gondii in blood in the diagnosis of cerebral toxoplasmosis in patients with AIDS.

The polymerase chain reaction (PCR) for amplification of Toxoplasma gondii DNA was performed prospectively in the blood of 19 patients with AIDS and cerebral toxoplasmosis. The B1 gene and TGR1E sequence were used as targets and results were confirmed by hybridisation. Controls consisted of 24 HIV infected patients with tissue culture proven T gondii parasitaemia and 57 HIV infected patients without toxoplasmosis. PCR was positive with both targets in 20 of 24 samples (84%) from patients with parasitaemia. Three of 57 samples (5%) from patients without toxoplasmosis were PCR positive with either target, but none was positive with both targets. Only three of the 19 patients (16%) with cerebral toxoplasmosis had a positive PCR with both targets before the start of specific treatment. PCR performed in blood is of little diagnostic value in cases of cerebral toxoplasmosis but could be useful in patients with disseminated infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Nosocomial invasive aspergillosis. Diagnosis, prevention and means of control integrated in a hospital setting].

Nosocomial invasive aspergillosis has emerged as a major infectious complication in patients with profound immunodeficiency. Thus, preventive measures must be instautred in hospital wards "at risk for aspergillosis" (mainly haematology, bone marrow transplant and organ transplant units) in order to prevent the outer risk of contamination. These comprise a sequential follow-up of air and surface contamination and molecular analysis of isolated fungal strains for further analysis of the epidemiology of Aspergillus in the hospital environment. We also recommend that biological, clinical and environmental data should be centralized and analyzed monthly by a specialized staff composed of physicians, mycologists, heath care and administrative personnel in order to define the optimum strategy for prevention within the hospital.

Aspergillosis↗
PubMed1996

[Contribution of Trichrome Blue in the diagnosis of microsporidiosis].

Detection of microsporidia belongs to the usual coprologic and urine detection of parasites from HIV seropositive patients. To improve the identification of microsporidial spores, several stains have been used. Trichrome Blue stain has been evaluated in this study. We first compared Trichrome Blue stain to Weber's trichrome for the detection of microsporidia in smears of stools received from HIV seropositive patients. No difference of sensibility has been demonstrated between the two stains, and Uvitex 2B used on the same samples has confirmed these results. Then, Trichrome Blue stain has been used for the detection of microsporidial spores in other specimens (40 samples of nasal mucus, conjonctival samples, duodenal biopsy and urine), also Giemsa and Uvitex 2B. The advantage of Trichrome Blue stain is its ready-to-use presentation, and faster realisation at higher temperature. Trichrome Blue stain is interesting as a confirmation technique or for laboratories which do not have fluorescent microscopy equipment.

Animals↗
PubMed1995

Detection of Toxoplasma gondii parasitemia by polymerase chain reaction in perorally infected mice.

Sequential blood samples collected from mice infected perorally with an avirulent strain of T. gondii were analysed for parasite DNA by a polymerase chain reaction method (PCR). Two pairs of primers specific for gene B1 and the repetitive DNA sequence TGR1E were used for DNA amplification. Amplified products were detected by means of electrophoresis with ethidium bromide staining. Parasitemia was also determined by cell culture. Parasitemia was never detected by the tissue culture method, whereas parasite DNA was continuously detected with PCR from day 2 to day 21. These results confirm the high sensitivity of PCR for T. gondii DNA in blood, and show that circulating DNA is present for long periods in mice following primary infection.

Animals↗
PubMed1995

[Experimental models of toxoplasmosis. Pharmacological applications].

Toxoplasma gondii is an ubiquitous protozoan parasite causing severe or life-threatening infections in immunocompromised patients and in congenitally infected infants. Animal models have been extensively used to describe the pathology of infection and to identify new effective drugs for the treatment of congenital infections, chrorioretinitis and toxoplasmic encephalitis. Although inherent differences between man and animal can reduce the relevance of data obtained experimentally, animal models have greatly improved our knowledge on the various aspects of toxoplasmosis. Toxoplasma infection can be easily obtained in most laboratory animals, with exception of rats which are partially resistant. According to the strain used, the resulting infection may be acute, subacute or chronic, and can be monitored either by the survival of animals, the histopathological examination of lesions or, preferably, by titration of parasites in infected tissues using subinoculation to mice or tissue culture. This latter method has proved particularly useful to describe the kinetics of infection in host tissues and to assess the efficacy of drugs, according to their pharmacokinetics and tissue distribution. The relevance of results obtained in animal models of congenital toxoplasmosis and of chrorioretinitis is more questionable, due to the marked differences between the mode of infection in humans and in animals. Experiments performed in primates provided valuable informations for the management of therapy of congenital toxoplasmosis but were of limited interest for ocular toxoplasmosis. The pathogeny of toxoplasmic encephalitis is still poorly understood, and no experimental model is fully satisfactory to produce focal encephalitic lesions as observed in immunocompromised humans. Acute infections with highly virulent strains induce disseminated infection with major pulmonary and brain involvement, and thus can be used to assess the efficacity of drugs in these tissues. Direct inoculation of tachyzoites into brain tissue can induce focal encephalitis but this model is of difficult use for large scale studies. Although cellular immunity is mainly responsible for the control of toxoplasmosis at the chronic stage, administration of immunosuppressive drugs does not usually result in focal brain reactivation; such reactivation can only be obtained using antibodies against CD8 and CD4 T lymphocytes or interferon gamma. Another experimental approach is the use of genetically immunodeficient animals: these models are of limited interest for pharmacological research since infection of nude or T depleted mice usually results in a dissemination of infection; however, using these models it could be clearly demonstrated that immunity plays a major adjunctive role in the control of acute infection. Concurrent infections between viruses and parasites is a common feature in immunocompromised patients and especially during AIDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Disseminated microsporidiosis due to Septata intestinalis in patients with AIDS: clinical features and response to albendazole therapy.

Five patients with AIDS had disseminated infection due to Septata intestinalis, a recently described organism. S. intestinalis infection was suspected after detection of spores in stools and urine and confirmed by transmission electron microscopy of duodenal biopsies or of cell culture of urine sediment. Clinical features included chronic diarrhea that was usually associated with fever, cholangitis, sinusitis, bronchitis, or mild bilateral conjunctivitis. Mean CD4 cell count was 22/microL. Patients treated with albendazole (400 mg orally twice a day) for a mean of 19 days had a dramatic and rapid clinical response to therapy. Significant reduction of parasite shedding was also observed during therapy; S. intestinalis was cleared from stools of all patients and from urine of 3. In 2 patients, however, microsporidian spores were detected in feces during follow-up and mild diarrhea recurred. Therefore, albendazole seems to have a significant but transient effect in treatment of S. intestinalis infection.

AIDS-Related Opportunistic Infections↗
PubMed1995

In-vitro and in-vivo activities of roxithromycin in combination with pyrimethamine or sulphadiazine against Toxoplasma gondii.

The efficacy of roxithromycin alone or in combination with pyrimethamine or sulphadiazine was examined in vitro and in a murine model of acute toxoplasmosis. In-vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of toxoplasma growth by an enzyme-linked immunosorbent assay. For in-vivo studies, mice were infected with 10(4) tachyzoites of the virulent RH strain and then treated perorally for 10 days from day 1 after infection. The efficacy of each drug regimen was assessed by determination of survival rates and sequential titration of parasites in blood, brain and lungs, using a tissue culture method. In vitro, roxithromycin inhibited toxoplasma growth at a concentration of > or = 0.02 mg/L; the 50% inhibitory concentration was estimated to be 1.34 mg/L. No synergistic effect was observed when it was combined with pyrimethamine or sulphadiazine. In vivo, roxithromycin alone at 50 or 200 mg/kg/day slightly prolonged survival compared with untreated mice, but a striking synergistic effect was observed when roxithromycin was administered in combination with pyrimethamine or sulphadiazine at subtherapeutic doses, i.e., 12.5 and 100 mg/kg/day, respectively. Combination regimens consistently resulted in a marked reduction fo the parasite burdens in blood and tissue, compared with those in mice treated with any of the agents alone. These results suggest that in-vivo activities of either pyrimethamine or sulphadiazine against T. gondii are reinforced by roxithromycin and such combinations should be considered in development of alternative treatments for human toxoplasmosis.

Animals↗
PubMed1995

Protective effect of low doses of an anti-IL-4 monoclonal antibody in a murine model of acute toxoplasmosis.

Treatment with an anti-IL-4 monoclonal antibody protected susceptible C57BL/6 mice against challenge with an avirulent strain of T. gondii. Antibody therapy with 100 micrograms on days 0 and 7 post infection resulted in 100% survival of C57/BL6 mice infected orally. Survival was dose-dependent. Treatment prolonged parasitaemia but did not alter tissue parasite load. Increased serum IgG2a and IFN-gamma levels, together with low levels of IgG1, in mice treated with anti-IL-4 or an isotype control, indicated a trend towards a predominant Th1 response in all survivors. The persistence of an IgE response after treatment suggests that endogenous IL-4 was only partly neutralized or that other factors can induce the production of IgE in murine toxoplasmosis.

Acute Disease↗
PubMed1995

Early kinetics of Toxoplasma gondii infection in mice infected orally with cysts of an avirulent strain.

We determined the early kinetics of Toxoplasma gondii infection in Swiss Webster mice inoculated with the avirulent C strain by counting parasites in the blood, spleen, Peyer's patches, liver, lungs, and brain. Animals were orally inoculated with cysts on day zero (D0), and parasites were counted using a tissue culture method at 12, 24, and 36 hr and 2, 3, 7, 10, 14, 21, 30, 50, and 72 days postinfection. The spleen and Peyer's patches were the first organs found parasitized, on D2 and D3, respectively, followed by the lungs and liver on D7 and the brain on D10. No parasitemia was detected. This suggests that early dissemination of this avirulent strain from the intestine into the general circulation occurs essentially via the lymphatic system. Parasites persisted at a high level in the brain during the chronic phase. In the lungs, parasites were no longer detected by D72, while parasite numbers initially declined in the spleen and Peyer's patches but then showed a second peak, possibly due to recirculation of T. gondii. These results suggest that lymphoid organs play a key role in T. gondii dissemination during the acute phase and may also constitute a persistent source of parasite resurgence.

Animals↗
PubMed1995

[Current diagnostic aspects of toxoplasmosis].

Biological diagnosis of toxoplasmosis is now based more widely on combined use of serology and techniques for detection of the parasite or its constituents. Serologic methods endeavour to describe more reliably the antibodies involved in the humoral response and define their specific antigenic properties. Use of purified parasite proteins and characterization of isotypes having short-lived kinetics now make it possible to be more precise about the date of contamination in the case of first infections; however, serology remains of limited interest for diagnosis of toxoplasmosis in immunodepressed patients. Techniques for detection of the parasite by cell culture, or of parasite DNA by polymerase chain reaction, now represent the alternatives of choice to direct search or animal inoculation. These techniques are more specifically indicated where the immune response is abnormal or absent, particularly in immunodepressed patients and in the fetus. The results, obtained in a few days, provide a reliable diagnosis and enable specific treatment to be instituted.

Animals↗
PubMed1995

[New pathogens and mode of action of azithromycin: Toxoplasma gondii].

Azithromycin can inhibit the growth of Toxoplasma gondii tachyzoïtes in vitro, but the effect is only observed with prolonged incubation with the drug, reflecting the delayed mode of action of this macrolide on the parasite. Azithromycin is probably acting by inhibition of protein synthesis but the site of action and fixation in the parasite has not been demonstrated. Azithromycin is also effective against intracystic bradyzoïtes in vitro, but long term administration of azithromycin to chronically infected mice failed to reduce the mean number of brain cysts. In models of acute toxoplasmosis, azithromycin was found to have a limited effect on brain infection, whereas parasites were cleared from blood and lungs of infected mice, resulting in a significant protection of treated mice comparatively to untreated controls. When azithromycin is combined with pyrimethamine or sulfadiazine, an additive effect is observed in vitro, and a remarkable synergistic effect is observed in vivo in the treatment of acute toxoplasmosis. Together, these results are in favor of the use of azithromycin in combined therapies for the treatment and/or prophylaxis of toxoplasmosis.

Animals↗
PubMed1994

[Microsporidioses].

Microsporidia are worldwide ubiquitous intracellular protozoan parasites infecting most major groups of the animal kingdom. In humans, microsporidiosis has recently emerged as a significant cause of morbidity in immunocompromised patients, and particularly in patients with acquired immunodeficiency syndrome (AIDS). Parasites of the genus Encephalitozoon cause keratoconjunctivitis and disseminated infections. In 15 to 30% of patients with advanced stage AIDS, Enterocytozoon bieneusi is the causative agent of major chronic diarrhoea. Clinical manifestations include numerous (2 to 8) and abundant, irregular liquid or semi-liquid stools without evidence of intestinal haemorrhage. Impaired absorption is aggravated by food intake causing the patients to restrain from eating and subsequent weight loss is progressive and irreversible. The diarrhoea becomes permanent and leads to dehydration ad malnutrition. Spontaneous remissions have been observed but are always of short duration. Microsporidiosis has also been found in ocular localizations in patients with AIDS; these keratopathies may be due to Encephalitozoon cuniculi, the only known species in mammals but E. hellem, a morphologically identical but antigenically different species has been identified. Other visceral localizations have been observed. Diagnosis of microsporidiosis relies on the demonstration of spores and/or intracellular parasites in stools, urine or tissue biopsies. The responsible agent can generally be identified by light microscopy, but differentiation between species still requires electron microscopy. New light and fluorescent microscopic techniques have been proposed for easier recognition of spores in various pathological samples. Immunodiagnostic techniques are limited due to the lack of correlation between antibodies detection and clinical manifestations. Although the parasite can be identified and although its cycle has been carefully studied, no prophylactic action can be taken because the mode of transmission remains largely unknown. Many treatment protocols have been tried but none have been found to be effective. Very little pharmacological data has been accumulated. Microsporidiosis is, and will remain, a major opportunistic infectious disease causing uncontrollable debilitating malnutrition in AIDS patients unless an effective treatment can be found, a major challenge for medical science.

AIDS-Related Opportunistic Infections↗