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Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 109 records · Page 6Linked to original sources
PubMed1994

Toxoplasma gondii: kinetics of lymphocyte subsets in blood and spleen of perorally infected mice.

The blood and spleen lymphocyte subsets and parasite burdens in blood, lungs, and brain were determined serially in C57B1/6 mice infected with an avirulent strain of Toxoplasma gondii. Five mice were sacrificed at various time points after infection; Thy1-2+, Ly5+, CD4+, CD8+, and Ly6c+ lymphocyte subsets and macrophages were determined in blood and spleen by cytofluorometry and parasite burdens were quantified in blood, lungs, and brain by means of a tissue culture method. In infected mice, a large increase in the percentage of CD8+ lymphocytes in blood was observed from Day 14, peaking at Day 21; the percentage of CD4+ lymphocytes was not significantly modified compared with uninfected controls. Analysis of Ly6 antigen expression on T lymphocytes showed that CD8+Ly6c+ cells were largely predominant at the different stages of infection. Similar results were obtained for spleen cells. The marked increase in CD8+Ly6c+ cells in the early phase of infection was associated with the clearance of parasites from the lungs. Furthermore, the proportion of CD8+Ly-6c+ remained high until Day 162, when the infection was at the chronic stage. These results suggest that CD8+Ly6c+ lymphocytes may be involved in the control of toxoplasmosis in the acute phase and in the containment of the infection in the chronic stage.

Animals↗
PubMed1994

Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis.

Prophylactic efficacy of antimicrobial agents against pneumocystosis and toxoplasmosis was examined in a model of concurrent Pneumocystis carinii and Toxoplasma gondii infections in rats. Corticosteroid-treated rats naturally infected by P. carinii were challenged with the RH strain of T. gondii. Infection was assessed by counting P. carinii cysts in lung and by titration of T. gondii in tissues by tissue culture. Untreated rats died after challenge, with P. carinii infection in lungs and T. gondii infection in liver, spleen, lungs, and brain. In rats that received trimethoprim-sulfamethoxazole or pyrimethamine plus dapsone, T. gondii was eradicated and P. carinii pneumonia prevented. Roxithromycin, 200 or 400 mg/kg, provided significant protection against toxoplasmosis but had no efficacy against P. carinii. Atovaquone, 100 or 200 mg/kg, had only partial efficacy against pneumocystosis and toxoplasmosis. These results definitively confirm use of trimethoprim-sulfamethoxazole and pyrimethamine plus dapsone for prophylaxis against combined infection in immunocompromised hosts.

Animals↗
PubMed1994

Interactions between murine AIDS (MAIDS) and toxoplasmosis in co-infected mice.

We coinfected C57B1/6 mice with LP-BM5 murine leukaemia viruses, responsible for murine AIDS (MAIDS), and an avirulent strain of Toxoplasma gondii. Virus-infected mice were infected perorally on day 30 with 10 cysts of T. gondii, and T. gondii-infected mice were challenged with LP-BM5 on day 20, 30 or 60 after parasite inoculation. Uninfected and singly infected mice were used as controls. The kinetics of parasite burden in blood, lungs and brain, together with blood lymphocyte subsets, and spleen and lymph node weights, were serially determined in each group of mice. The kinetics of parasite counts in mice infected by LP-BM5 then by T. gondii were similar to those in mice infected by T. gondii only, except for lung counts, which reached higher values than in animals infected with T. gondii alone, then fell and re-increased until the end of the experiment. The only significant change in parasite burdens when mice were first infected by T. gondii and then by LP-BM5, compared with T. gondii controls, was an increase in lung counts in mice challenged with LP-BM5 20 days after T. gondii inoculation. Whatever the schedule of co-infection, the kinetics of lymphocyte subsets in co-infected mice differed from those in T. gondii- or LP-BM5-infected mice; in dually infected mice CD4+ and CD8+ cell counts were intermediate between values in mice singly infected by the parasite or the virus. Enlargement of spleen and lymph nodes, which is a major criterion of MAIDS progression, was significantly less marked in co-infected mice than in mice infected with LP-BM5 alone. These data point to cross-regulation of T. gondii and LP-BM5 infections, which results in increased susceptibility to T. gondii, and may alter the progression of MAIDS.

AIDS-Related Opportunistic Infections↗
PubMed1994

In vitro model to assess effect of antimicrobial agents on Encephalitozoon cuniculi.

We have developed a new micromethod to study the effect of drugs on microsporidia, using MRC5 fibroblasts infected by 10(5) spores of Encephalitozoon cuniculi. After 3 days of incubation with various concentrations of drugs, parasitic foci were counted in stained cultures. The inhibition of microsporidial growth exceeding 90% with albendazole (0.005 microgram/ml), fumagillin (0.001 microgram/ml), 5-fluorouracil (3 micrograms/ml), and sparfloxacin (30 micrograms/ml) was observed. Chloroquine, pefloxacin, azithromycin, and rifabutin were partially effective, at high concentrations. Arprinocid, metronidazole, minocycline, doxycycline, itraconazole, and difluoromethylornithine were not evaluable, since concentrations that inhibited microsporidia were also toxic for fibroblasts. Pyrimethamine, piritrexim, sulfonamides, paromomycin, roxithromycin, atovaquone, and flucytosine were ineffective. Our results confirm that albendazole and fumagillin have marked activity against E. cuniculi and show the antimicrosporidial activity of 5-fluorouracil and sparfloxacin. These data may form the basis for treatment of Encephalitozoon hellem and Septata intestinalis infections and represent an attempt to identify drugs effective against Enterocytozoon bieneusi.

Animals↗
PubMed1994

Molecular epidemiology of nosocomial invasive aspergillosis.

Moderately repeated DNA sequences were used to fingerprint strains of Aspergillus fumigatus isolated from patients with invasive aspergillosis and their hospital environment. Most strains sampled from the environment displayed different Southern blot hybridization patterns. A temporal survey of air contaminants showed that some strains can persist in the same environment for at least 6 months. Patients with invasive aspergillosis were infected by a single strain. In two patients, a nosocomial origin of infection was suggested.

Aspergillosis↗
PubMed1994

Prophylaxis of toxoplasmosis infection with pyrimethamine/sulfadoxine (Fansidar) in bone marrow transplant recipients.

Prophylaxis against toxoplasmosis with weekly administration of pyrimethamine/sulfadoxine (Fansidar) was assessed for efficacy and toxicity in bone marrow transplant (BMT) recipients over a 21 month period. Sixty-nine of 90 consecutive seropositive patients were evaluable. Fansidar was administered from the time of established engraftment (median day 40, range days 13-100). Medication was scheduled to be continued until 6 months or longer in cases of continued immunosuppression (median 10 months, range day 72 to 22 months). No proven case of toxoplasmosis occurred in patients receiving prophylaxis. In addition, there were no cases of Pneumocystis carinii. Side-effects included BM suppression requiring cessation (n = 4) or interruption (n = 8) of therapy and rash (n = 1). To evaluate toxicity associated with prolonged therapy, 42 evaluable patients were assessed at 6 months following transplant (or at least 4 months of continuous treatment). Haematological toxicity was minimal and compounded in three patients showing moderate derangement by cytomegalovirus infection and graft-versus-host disease. Fansidar is an effective prophylactic agent against toxoplasmosis in BMT patients.

Adolescent↗
PubMed1994

[Multicenter study of toxoplasma serology using various commercial ELISA reagents. Work Group Toxoplasmosis of the National Agency for Quality Control in Parasitology].

A collaborative study conducted by the French National Agency for Quality Control in Parasitology (CNQP) and various manufacturers of ELISA kits, represented by the Association of Laboratory Reagent Manufacturers (SFRL) compared the toxoplasmosis IgG antibody titres obtained with different ELISA-IgG kits and determined the relationships between the titres obtained by these techniques and the titre defined in international units (IU). Fifty-one serum samples with toxoplasmosis antibody titres ranging from 0 to 900 IU were tested in two successive studies with 16 ELISA-IgG kits. For the negative sera, false-positive reactions were observed with one kit. For the positive sera, the titres observed in ELISA were generally higher than those expressed in IU. Above 250 IU, the very wide variability of the titres found with the different ELISA kits renders any comparative analysis impossible. For titres below 250 IU, the results are sufficiently homogeneous to permit the use of regression analysis to study how the results for each ELISA kit compare with the mean results for the other kits. The slope of the line of regression shows a tendency to over-titration or under-titration compared with the results of the other manufacturers; the ordinate at the origin reflects the positivity threshold of the reaction and can be used to assess the risk of a lack of sensitivity (high threshold) or of specificity (threshold too low). On the whole, the trends revealed for a given manufacturer are constant from one study to the other. Within this range of titres, regression analysis also reveals the general tendency of ELISA kits to overestimate the titres by comparison with immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Intestinal microsporidiosis in human immunodeficiency virus-infected patients with chronic unexplained diarrhea: prevalence and clinical and biologic features.

Eighteen patients infected with human immunodeficiency virus and with chronic unexplained diarrhea were prospectively studied to investigate the prevalence and clinical and biologic features of intestinal microsporidiosis. All patients underwent extensive evaluation for bacterial, viral, and parasitic pathogens. Enterocytozoon bieneusi was found in 9 patients (50%; 95% confidence interval, 27-73) in stools and duodenal and jejunal biopsies. In 8 patients, it was the sole pathogen found. Other pathogens were also isolated from the intestinal tracts of 4 patients, but diarrhea remained unexplained in 6. Patients with intestinal microsporidiosis had significantly lower mean Karnofsky scores (69.4 vs. 85.5, P = .009), CD4 cell counts (18.6 vs. 209.8/microL, P = .02), and D-xylose absorption tests (0.13 vs. 0.36 g/L, P < .001) than did patients without intestinal microsporidiosis. Intestinal microsporidiosis appears to be a frequent cause of unexplained chronic diarrhea in patients with AIDS and is associated with diminished D-xylose absorption.

AIDS-Related Opportunistic Infections↗
PubMed1993

In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii.

The efficacy of atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, and minocycline 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 acutely infected intraperitoneally with 10(4) tachyzoites of the virulent RH strain and then treated perorally for 10 days from day 1 postinfection. The following drug regimens were investigated: atovaquone at 100 and 50 mg/kg of body weight per day and the combinations of atovaquone at 50 mg/kg with sulfadiazine at 200 mg/kg, pyrimethamine at 12.5 mg/kg, clarithromycin at 200 mg/kg, or minocycline at 50 mg/kg. Efficacy was assessed by determination of survival rates and sequential determination of parasite burdens in blood, brain, and lungs. In vitro, atovaquone inhibited Toxoplasma growth at a concentration of > or = 0.02 mg/liter; the 50% inhibitory concentration was estimated to be 0.023 mg/liter. No synergistic effect was observed when it was combined with sulfadiazine, clarithromycin, or minocycline, whereas a significant antagonistic effect was noted for the combination of atovaquone with pyrimethamine. In vivo, administration of atovaquone at 100 or 50 mg/kg/day for 10 days resulted in prolonged survival compared with that in untreated mice; this survival was associated with a reduction of parasite burdens in blood and tissues during the course of treatment. The combinations of atovaquone with pyrimethamine, clarithromycin, or sulfadiazine were more efficient than each drug administered alone, in terms of survival, but parasite burdens in blood and organs were not reduced compared with those in mice treated with any of the agents alone. These experimental results confirmed the activity of atovaquone against Toxoplasma gondii, but no marked improvement in efficacy was observed in vitro and in vivo when this drug was combined with pyrimethamine, sulfadiazine, minocycline, or clarithromycin.

Animals↗
PubMed1993

Interaction between human immunodeficiency virus and Toxoplasma gondii replication in dually infected monocytoid cells.

THP-1 monocytoid cells, either not infected or chronically infected with human immunodeficiency virus type 1 (HIV-1), were challenged with Toxoplasma gondii. Parasitic growth, as assessed by trophozoite counting and measurement of supernatant p30 membrane antigen, was similar in HIV-infected and noninfected THP-1 cells. Also, T. gondii did not affect HIV replication. These experiments therefore failed to demonstrate any interaction between HIV-1 and T. gondii replication in concurrently infected monocytoid cells.

Animals↗
PubMed1993

Detection of Toxoplasma gondii in venous blood from AIDS patients by polymerase chain reaction.

Detection of Toxoplasma gondii in blood by means of the polymerase chain reaction (PCR) may facilitate the diagnosis and follow-up of cerebral toxoplasmosis in patients with AIDS. We evaluated this approach with seven patients with tissue culture-proven parasitemia, 14 patients with presumptive cerebral toxoplasmosis, and 17 healthy human immunodeficiency virus-positive controls. Each sample of blood was assayed on three different occasions by a PCR assay based on detection of the gene encoding the P30 surface protein. A positive PCR diagnosis required positivity in at least two of the three PCR tests. None of the controls had a positive PCR diagnosis, but six of the seven patients with parasitemia did. Cerebral toxoplasmosis was confirmed in 13 of the 14 patients with a presumptive diagnosis; diagnosis by PCR was positive before treatment for 9 of these 13 patients, whereas tissue culture was positive for only 1 patient. During treatment, blood samples were taken from 14 patients at regular intervals until day 12. PCR diagnosis became negative on ethidium-stained gels, but persistent signals were observed after hybridization, in some cases, for up to 12 days after initiation of therapy. PCR on venous blood could thus be a sensitive and noninvasive method for the diagnosis of cerebral and disseminated toxoplasmosis in AIDS patients and could be a potential tool for monitoring the effects of treatment.

AIDS-Related Opportunistic Infections↗
PubMed1993

Epidemiology and diagnosis of invasive pulmonary aspergillosis in bone marrow transplant patients: results of a 5 year retrospective study.

Of 322 patients undergoing allogeneic BMT, 18 developed invasive pulmonary aspergillosis at a mean of 115 days post-transplant, with a mortality rate of 82%. Pulmonary localization was common but cerebral involvement was seen in 10 of 18 patients. The diagnosis was made ante mortem in 11 patients by direct examination of pathological samples or culture and A. fumigatus was the only species isolated. Specific antibodies were not demonstrated before or at the time of clinical symptoms and Aspergillus antigen was only seen in one patient a few days before death.

Adult↗
PubMed1992

[Isolation of Toxoplasma gondii by cellular culture in HIV infected patients].

Nine hundred and eight biological samples obtained from HIV-infected patients were examined for Toxoplasma gondii by a tissue culture method. Sixty-two isolations of Toxoplasma gondii were made in 43 patients. Fourteen isolations were made from tissue biopsies (brain 4, striated muscle 2, liver 1), bone marrow aspirates (4 cases), pericardial or pleural effusions (3 cases) and vitreous body (1). In 6 cases, a parasitic dissemination was evidenced by the demonstration of Toxoplasma in blood or other tissues or body fluids. Toxoplasma organisms were demonstrated in the bronchoalveolar lavage fluid of 19 patients; this was associated with a parasitaemia in 6 of the 10 patients whose blood sample was cultured at the same time. Among 273 blood samples cultured, 29 were positive for Toxoplasma (24 patients); all patients with parasitaemia had clinical symptoms, but only 8 of them had clinical or radiological symptoms suggestive of a cerebral localization; this suggests that the presence of a parasitaemia is fairly indicative of an extra cerebral localization of toxoplasmosis. In 11 patients, blood was examined after treatment was initiated; in 8 patients parasitaemia was undetectable at the first examination after treatment (1 to 15 days after initiation of therapy), whereas in 3 patients sampled 1, 4 or 6 days respectively after treatment a persistent parasitaemia could be demonstrated. These results clearly show that the tissue culture method is efficient and sensitive to provide an early evidence of infection (4 days), and may prove useful to evaluate therapeutic effectiveness.

AIDS-Related Opportunistic Infections↗