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Biomedical subjects

F Derouin

Publications and source records attributed to F Derouin.

At least 145 records · Page 8Linked to original sources
PubMed1989

In vitro effects of folate inhibitors on Toxoplasma gondii.

Three sulfonamides and four dihydrofolate reductase inhibitors were tested alone and in combination to determine their in vitro effects on two strains of Toxoplasma gondii grown in MRC5 fibroblast tissue culture. Toxoplasma growth was quantitated by an enzyme immunoassay performed directly on the fixed cultures, and linear regression models were used to quantify the relationship between the optical density values generated by the enzyme-linked immunosorbent assay and the concentrations of the antimicrobial agents in the culture medium. The cytopathic effects of antimicrobial agents on T. gondii were examined in Giemsa-stained cultures. Sulfonamides and dihydrofolate reductase inhibitors exhibited similar patterns of inhibition, consisting of an important increase of the inhibitory effect within a narrow range of concentrations. Sulfadiazine, sulfamethoxazole, and sulfisoxazole were all found to have important inhibitory effects on T. gondii; the 50% inhibitory concentrations estimated from the regression models were 2.5 micrograms/ml for sulfadiazine, 1.1 micrograms/ml for sulfamethoxazole, and 6.4 micrograms/ml for sulfisoxazole. This inhibition of growth was associated with a reduction of the number of parasitized cells and intracellular parasites that were morphologically normal. With dihydrofolate reductase inhibitors, including pyrimethamine, trimethoprim, trimetrexate-glycuronate, and piritrexim, a strong inhibition of Toxoplasma growth was observed, which was associated with striking morphological changes of the parasites. The 50% inhibitory concentrations were 0.04 microgram/ml for pyrimethamine, 2.3 micrograms/ml for trimethoprim, 0.16 ng/ml for trimetrexate-glycuronate, and 6.9 ng/ml for piritrexim. When sulfonamides and dihydrofolate reductase inhibitors were used in combination, a synergistic effect was observed with sulfadiazine combined with pyrimethamine, trimetrexate-glycuronate, and piritrexim; sulfisoxazole combined with pyrimethamine; and trimethoprim combined with sulfamethoxazole. These results were analyzed in comparison with human pharmacokinetics data.

Animals↗
PubMed1989

Laboratory diagnosis of pulmonary toxoplasmosis in patients with acquired immunodeficiency syndrome.

In four cases of pulmonary toxoplasmosis occurring in patients with acquired immunodeficiency syndrome, Toxoplasma sp. was discovered in bronchoalveolar-lavage fluid (three cases) and in lung biopsy specimen (one case) by using the following methods: direct examination of smears stained with eosine-methylene blue fast stain, indirect immunofluorescence assay, and inoculation of MRC5 fibroblast cell line in tissue culture.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. I. A comparative double-blind study of 220 patients with onchocerciasis treated with a single oral dose of 100, 150 or 200 mcg/kg].

Two hundred and twenty adult males living in endemic onchocerciasis areas in Ivory Coast, with a mean of 59 to 64 mf/mg of skin microfilariae, having or not ocular lesions, were divided into 4 homogeneous groups and treated by placebo or by a single oral dose of 100, 150 or 200 mcg/kg of ivermectin. Parasitological, clinical, ophthalmological, biological data were gathered before treatment (J less than 1) and at day 4 and 3, 6, 12 months post treatment. The doses of 150 to 200 mcg/kg gave the best results with a reduction of microfilariae of 75 to 79% at day 4 and of 97 to 99% at 3 months. A slight increase appears at six months reaching to 10% of the initial level, at 12 months. These posologies reduce also the number of ocular microfilariae 12 months after treatment. The percentage of patients presenting microfilariae in the cornea varies from 4 to 14% according to the given dose whereas it was initially between 26 and 33%, and in the anterior chamber from 22 to 16% instead of 62 to 67%. In patients who were still positive after treatment the detected number of ocular microfilariae was very small. Side effects starting 12 to 24 hours after treatment are similar to those appearing during the normal evolution of onchocerciasis. They were observed in 36% of subjects receiving a placebo and 56 to 65% of treated subjects. Statistically they are neither correlated with the intensity of parasitism nor to the given posology and disappear spontaneously few days later or after administration of aspirin and/or antihistaminic. Ivermectin given at a single oral dosage of 150 to 200 mcg/kg is a powerful microfilaricidal drug with a rapid and prolonged action and without major side effects.

Adult↗
PubMed1989

[A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. II. Evaluation in the light of mass campaigns on the effect of yearly or half-yearly administration of single oral doses of 100, 150 or 200 mcg/kg].

One hundred and twenty patients out of 220 in a previous study were retreated after 6 months or one year with doses of 100, 150 or 200 mcg/kg of ivermectin. The tolerance was excellent due probably to the small number of skin microfilariae obtained with the first treatment. The annual treatment with 150 to 200 mcg/kg, better than with 100 mcg/kg, keeps for the year following the second treatment the microfilariae number between 6 and 11% of the initial level. The half-yearly administration keeps it between 1 and 7% and especially 94 to 100% of these retreated patients have a level of microfilariae less than 5 mf/mg. The results obtained with the half-yearly treatment show a considerable reduction of the number of microfilariae in the anterior chamber of the eye and the percentage of positive patients. Ivermectin is a very efficient microfilaricidal drug for the treatment of onchocerciasis and the prevention of ocular complications. Its rational use in mass campaigns should reduce, if not interrupt, the transmission of this parasitic disease.

Administration, Oral↗
PubMed1989

[A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. III. The tolerance and efficacy of a single oral dose of 150 mcg/kg in children].

One hundred and three male and female children of 6 to 14 years old with onchocerciasis, having or not ocular involvement and a mean skin microfilariae level of 36.1 mf/mg, received, in October 1986, a single oral dose of 150 mcg/kg ivermectin and controlled at day 4, 3 months, 6 months and 12 months post treatment. After the last control they were retreated with the same dose. The skin microfilariae count fell down to 94% of the initial level at day 4 and to 99% at 3 months. At 6 months the microfilariae count was 2% of the initial level and 5% at 12 months. The percentage of patients having microfilariae in the anterior chamber of the eye which was 33% before treatment fell down to 6% at 12 months. The percentage of patients having microfilariae in the cornea was 39% before treatment and 18% at 12 months. In the cornea and anterior chamber there was a very reduced number of microfilariae still present. 65% of the children had lesions of keratitis before treatment and 34% two months later. Adverse effects (fever, headache, pruritus, oedemas, myalgias, arthralgias) occurred in 64% of children after the first treatment and 50% after the second. They were of weak or moderate intensity and receded rapidly after administration of aspirin and/or anti-histaminic. The administration of ivermectin is an efficient and well tolerated drug in children above 5 years old.

Administration, Oral↗
PubMed1989

Impaired in vitro lymphocyte response to toxoplasma antigen in HIV1 infected patients.

The containment of Toxoplasma gondii infection is largely dependent of T cell mediated immunity. In this study, in vitro lymphocyte responsiveness to T. gondii antigen was examined in 59 HIV1 infected individuals and in 58 HIV non-infected controls. Of the 45 patients with serological evidence of past Toxoplasma infection, a significant proliferative response was found in only 18, whereas responses were present in 48 out of 51 controls with anti-Toxoplasma antibodies. In the 27 non-responder patients, the lack of proliferative response to T. gondii antigen was correlated with the loss of CD4+ cells, and the impairment of proliferative responses to other microbial antigens, whereas responsiveness to phytohaemagglutinin and concanavalin A were not significantly diminished. Results are consistent with impairment of cell mediated immunity to T. gondii in patients at risk for reactivation of chronic Toxoplasma infection. Of note, in the one year clinical following, 2 of the 27 non-responder patients developed toxoplasmic encephalitis compared to 0 of 18 with a Toxoplasma specific proliferative response.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Longitudinal study of the specific humoral and cellular response to Toxoplasma gondii in a patient with acquired toxoplasmosis.

Specific cellular and humoral response to Toxoplasma were evaluated during a 2 yr follow up in a patient with acquired infection. Antibodies were titrated using conventional serological tests and analyzed by western blot technique. Analysis of the patterns obtained with IgA, IgG and IgM antibodies allowed a clear differentiation between acute and chronic stages of infection. Determination of lymphocyte subsets showed an important increase in the number of CD8 suppressive cells at the acute phase whereas CD4 cells remained within the normal range. Lymphocyte proliferation to Toxoplasma antigen was detectable one month after the onset of clinical symptoms and remained constantly positive. These results indicate that western blot analysis of antigens recognized by antibodies and determination of lymphocyte subsets may be helpful in the characterization of the infectious stage of acquired toxoplasmosis.

Adult↗
PubMed1988

Early prenatal diagnosis of congenital toxoplasmosis using amniotic fluid samples and tissue culture.

The presence of Toxoplasma gondii in amniotic fluid was demonstrated using tissue culture in four of nine cases of congenital toxoplasmosis, whereas Toxoplasma gondii antigen was undetectable using a sensitive enzyme immunoassay technique. Parasites were identified in monolayers four days after inoculation using an indirect immunofluorescence assay. Since tissue culture may provide evidence of infection within a few days, this method is proposed for early prenatal diagnosis of congenital toxoplasmosis.

Amniotic Fluid↗
PubMed1988

Enzyme immunoassay to assess effect of antimicrobial agents on Toxoplasma gondii in tissue culture.

Toxoplasma gondii grown on MRC5 fibroblasts in 96-well tissue culture plates was tested for susceptibility to five antimicrobial agents. T. gondii growth was quantitated by an enzyme-linked immunosorbent assay, which was performed directly on the fixed cultures, using a rabbit anti-T. gondii immunoglobulin G as the first antibody and a phosphatase-labeled anti-rabbit immunoglobulin G as the second antibody. Optical density values were highly correlated with the number of T. gondii organisms in the Giemsa-stained cultures (r = 0.89), and an enzyme-linked immunosorbent assay was used to assess the effect of antimicrobial agents at various concentrations. For each drug, regression models were used to quantify the relationship between optical density values and antimicrobial agent concentrations in the cultures. A significant inhibitory effect was found with pyrimethamine and sulfadoxine for concentrations greater than or equal to 0.05 and 30 micrograms/ml, respectively. With spiramycin, a progressive increase in inhibition of T. gondii was observed for increasing concentrations from 1 to 100 micrograms/ml. Ornidyl (difluoromethylornithine) and (2R,5R)-6-heptyne-2,5-diamine, which are ornithine decarboxylase inhibitors, were found to have a marked inhibitory effect for concentrations greater than or equal to 25 and 2 mM, respectively. This proposed method was sensitive and easy to perform and does not require the use of radiolabeled compounds; since it allows experimental design on replicate cultures and can be partially automated, it thus may prove useful for the systematic screening of the activity of new compounds against T. gondii.

Animals↗
PubMed1988

[In vitro measurement of the inhibitory effect of macrolides, lincosamides and synergestines on the growth of Toxoplasma gondii].

The in vitro inhibitory effect of macrolides, synergestines and lincosamides on Toxoplasma gondii was evaluated using an enzyme immunoassay performed directly on the infected cultures. Antimicrobial agents were tested at various concentrations, and regression models were used to quantify the relationship between optical density values (correlated to Toxoplasma count in the cultures) and drug concentrations in the cultures. A significant inhibitory effect was observed with the macrolides (erythromycin, roxithromycin, midecamycin, spiramycin, josamycin and oleandomycin) for concentration of 0.1 to 4 micrograms/ml. This effect progressively increased with increasing concentration of drug in the cultures and reached its maximum value for concentrations of 40 to 250 micrograms/ml. Similarly, clindamycin was found to have a significant inhibitory effect for concentration ranging from 0.5 ng/ml to 100 micrograms/ml. Only a partial inhibitory effect was noted with virginiamycin, pristinamycin and lincomycin. The concentrations giving a 50% inhibition of Toxoplasma growth in the culture were determined from regression models and ranged between 0.15 and 12 micrograms/ml according to the drug. This results confirm that macrolides, lincosamides are effective against Toxoplasma gondii in vitro, and can be proposed for treatment of toxoplasmosis because of their large diffusion, their good tolerance and their concentration in tissues such as lung and placenta.

Animals↗
PubMed1987

Detection of circulating antigens in immunocompromised patients during reactivation of chronic toxoplasmosis.

One hundred and fifteen sera from nineteen patients undergoing bone marrow transplant and four recipients of kidney transplant who showed serological or clinical reactivation of chronic toxoplasmosis were tested for Toxoplasma gondii circulating antigen (TCA) by enzyme-linked immunosorbent assay using antitoxoplasma IgG antibody coupled to alkaline phosphatase. Seven bone marrow transplant patients and one kidney transplant recipient were TCA positive either before or at the time of antitoxoplasma IgG antibody increase. TCA continued to be detected in one patient with neurological toxoplasmosis until his death. In the other patients, TCA disappeared when IgG antibodies rose, probably due to the formation of immunocomplexes consisting of TCA and immunoglobulins. In the TCA seronegative patients, the presence of circulating immunocomplexes or TCA kinetics of short duration may explain these results. Patients receiving immunosuppressive therapy should be tested for TCA.

Antigens, Protozoan↗
PubMed1987

Toxoplasma antibody titers in renal transplant recipients. Pretransplant evaluation and posttransplant follow-up of 73 patients.

In 73 consecutive kidney transplant recipients, anti-Toxoplasma antibodies were determined before transplantation and during a 3-year follow-up after transplantation. In 9 patients, antibody titers increased significantly after transplantation. Antibody titers to various viral antigens determined in parallel remained unchanged, suggesting that the anti-Toxoplasma antibody increase was not due to polyclonal nonspecific stimulation. In 2 of the 24 pretransplant seronegative patients, acquired toxoplasmosis was diagnosed serologically after transplantation, with the observation of a strong IgM and IgG antibody response. The incidence of toxoplasmosis in this group of patients was not found to be significantly different from that in a normal population, suggesting that transmission of Toxoplasma from the transplanted kidney may not be a significant mode of contamination. Among the 49 patients who were seropositive before transplantation, reactivation of toxoplasmosis was suspected in 7 cases on the basis of a significant increase in IgG antibodies. Reactivation occurred more frequently in patients treated with azathioprine and antithymocyte globulin, and a direct relationship between administration of steroids and antibody increase was demonstrated in three patients. Although toxoplasmosis has occasionally been reported as a major infectious problem in kidney transplant recipients, our clinical and serological data show that the potential risk of developing Toxoplasma infection is low since none of the patients with either acquired or reactivated toxoplasmosis developed clinical disease.

Adolescent↗
PubMed1987

Comparative study of tissue culture and mouse inoculation methods for demonstration of Toxoplasma gondii.

Two methods for the isolation of Toxoplasma gondii were analyzed and compared. Bradyzoites or tachyzoites of three strains of T. gondii were injected into mice and introduced in parallel onto MRC5 fibroblasts cultured on cover slips. In the cultures, the parasites were more readily identified by an indirect immunofluorescence assay than by examination of unstained or Giemsa-stained cultures. With the RH strain, the tachyzoites replicated actively, and large foci of parasites were observed in 24 h. The bradyzoites or tachyzoites of the other strains could also be cultivated, but grew rather slowly; 2 days after inoculation, early stages of multiplication could be observed: from day +4, Toxoplasma clusters or foci were easily identified at a x100 magnification. The course of infection in mice was greatly dependent on the virulence of the strain and on the parasitic stage inoculated. In the chronically infected mice, evidence of Toxoplasma infection was only detected 45 days after inoculation through the demonstration of cysts in the brain or the presence of specific antibodies in the serum. The mean ratio of infected mice and positive cultures was compared in relation to the inoculum size. The tissue culture method was found to be at least as sensitive as mouse inoculation. Since Toxoplasma organisms may be isolated within a few days in tissue culture, it is proposed that this method should be used when early isolation of the parasite is crucial for the diagnosis of toxoplasmosis.

Animals↗
PubMed1987

[Ivermectin in the treatment and prevention of human onchocerciasis].

Ivermectin is a synthetic derivative of a macrocyclic lactone produced by an actinomycete Streptomyces avermitilis. It has a broad spectrum antiparasitic activity against nematodes and certain acarians in animals. The microfilaricide action of this product against horse and cattle onchocercosis led to the study of its effects in human onchocercosis against O. volvulus. Several trials performed mainly in endemic zones of Africa showed that this drug was more effective than the reference microfilaricide, diethylcarbamazine. A single oral dose of 200 micrograms/kg of Ivermectin reduces the dermal microfilaria population to nearly zero within a few days and the effect is maintained for at least 6 months. Secondary ocular or systemic effects are rare, negligible and transitory. The prolonged elimination of dermal microfilariasis caused by sequestration followed by degeneration of the microfilaria in the uterus of females raises the hope that Ivermectin used in a single annual or bi-annual dose will contribute to the interruption of the transmission of this serious parasitic disease.

Administration, Oral↗