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Biomedical subjects

B Beauvais

Publications and source records attributed to B Beauvais.

At least 19 recordsLinked to original sources

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

[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

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

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

Toxoplasmosis in bone marrow-transplant recipients: report of seven cases and review.

We report seven cases of cerebral or disseminated toxoplasmosis that occurred following bone marrow transplantation (BMT) and review the other 24 cases described in the literature. For all the cases, toxoplasmosis occurred within 6 months of BMT, with the highest incidence in the second and third months. Twenty-four of 26 recipients tested serologically before BMT were positive for Toxoplasma gondii, a finding that supports the view that such cases result from reactivation of latent infection. At the onset of clinical symptoms, IgG antibody titers were unchanged or decreased in 23 of 25 documented cases, and IgM antibodies were detected in two cases. Antemortem diagnosis was made in 16 cases and was based on the response to specific therapy in six cases and/or the demonstration of the parasite in body fluids or tissues in 10 cases. Autopsy was performed in 19 cases and revealed that infection was not restricted to the brain but either involved lung or heart tissue or was disseminated in 14 cases.

Adult

Olfactory threshold shift following controlled 7-hour exposure to toluene and/or xylene.

The present study was undertaken to examine olfactory perception threshold (OPT) shift following exposure of healthy subjects to toluene and/or xylene in an inhalation chamber. Five volunteers were exposed to 50 ppm toluene, 40 ppm xylene or an additive mixture of the two, for a period of 7 consecutive hr in an inhalation chamber. A Latin square design was used and subjects were exposed over 3 consecutive days/week, with an 11-day interval between each 3-day session. Olfactory perception thresholds, measured in decismels (ds), were ascertained for both toluene and PM-carbinol, contained in 100 ml bottles with serially increasing concentrations (Olfacto-Lab Kits # 191 & 11). Test administration was based on the forced choice method. Analysis of variance of pre-exposure OPTs indicated that for both toluene and PM-carbinol, significant differences were observed between individuals (p less than 0.05), but not between days or weeks. Measurements, made immediately following exposures revealed a significant six-fold increase in OPT for toluene (median: 15 ds), while PM-carbinol OPT remained stable. Individual differences were observed, but there was no effect of type of exposure, day, week, or interactions. OPT for toluene, determined at intervals following cessation of exposure, indicated a return to pre-exposure values at a mean rate of 6.8 ds/hr. The findings of this study suggest that there is a substantial olfactory threshold shift during a 7-hr period, specific to a particular solvent or family of solvents. Receptor-specific saturation is proposed as the underlying mechanism.

Administration, Inhalation

[Techniques applicable to broncho-alveolar lavage fluid in hospital laboratory for the diagnosis of parasitic and fungal pneumopathies in immunosuppressed patients].

Parasitic and fungal organisms which are likely to cause pulmonary infections in immunosuppressed patients can be detected in broncho-alveolar fluid (BAL fluid). Single and standard methods, such as direct examination of the pellet, eosine-methylene blue fast (RAL 555), cultures in usual mediums of mycology must be systematically applied to this sample and may help detect these organisms without further exploration. If the results are negative, more recent techniques can be used if they present a real asset: an easier reading and mostly an improved sensitivity. Such is the case of immuno-fluorescence assay with monoclonal antibodies for detection of Pneumocystis carinii, and inoculation of MRC5 fibroblast cell line in tissue culture for isolation of Toxoplasma. Fungal pulmonary infections diagnosis has not yet succeeded in benefiting from modern findings: latex tests proposed for the detection of circulating antigens are nor sensitive nor specific, except the "Crypto LA test". Considering the relatively frequent association with other infectious agents, the detection of a parasitic or fungal organism in the BAL fluid should not interrupt investigation of this sample; neither should it lead to hasty conclusions regarding the responsibility of this agent in acute pneumopathy. This role will have to be evaluated according to criteria which are different for each isolated organism.

Bronchoalveolar Lavage Fluid

Opportunistic agents in bronchoalveolar lavage in 99 HIV seropositive patients.

During a ten month period, 117 fibreoptic bronchoscopies and bronchoalveolar lavages (BAL) were performed in human immunodeficiency virus (HIV) infected patients suspected of having opportunistic pulmonary infections. The BAL were classified into 3 groups, according to clinical manifestations related to HIV infection at the time of fibreoptic bronchoscopy: pre-acquired immunodeficiency syndrome (AIDS) (n = 54), AIDS with Kaposi's sarcoma (n = 37), AIDS without Kaposi's sarcoma (n = 26). On chest X-ray, diffuse infiltrates were most common (54%), followed by normal X-rays (24%) and localized infiltrates (18%). Amongst the 117 BAL, 68 (58%) yielded at least one opportunistic agent. In 28 BAL performed for pulmonary signs or unexplained fever with normal chest X-rays, one or several opportunistic agents were isolated in 17 samples of BAL fluid. The most frequently identified opportunistic agents were Pneumocystis carinii (in 38% of BAL) and cytomegalovirus (35%); these were associated in 17% of BAL. There was no statistically significant difference in opportunistic agents among the 3 groups of BAL (pre-AIDS, AIDS with Kaposi's sarcoma, AIDS without Kaposi's sarcoma). In particular, cytomegalovirus was found in BAL with the same frequency in these 3 groups.

Acquired Immunodeficiency Syndrome

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

[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

[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

[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

[Comparative study of 2 classical technics of coloration and an indirect immunofluorescent assay applied to research on Pneumocystis carinii in the bronchoalveolar lavage fluid and induced sputum in HIV+ patients].

Two histochemical staining methods, eosine-methylene blue fast (RAL 555) and silver methenamine (modified Grocott's technique), and indirect immunofluorescence assay with an anticyst monoclonal antibody were used to detect Pneumocystis carinii in the broncho-alveolar lavage fluid and induced sputum from 58 HIV+ patients. Immunofluorescence disclosed the largest number of carriers (35 p. cent of examined patients). However, the histochemical staining techniques remain of interest and are the initial method of choice. They are inexpansive and rapid to achieve; less sensitive than immunofluorescence, positive results argue a high enough level of parasitism which leads to clinical manifestations. The increased sensitivity of immunofluorescence has considerably improved the ability to detect Pneumocystis in induced sputum. It allowed us to disclose 18 out 20 carriers (90 p. cent). However when a Pneumocystis is suspected, it is preferable to sample bronchoalveolar lavage fluid. Its examination is quick, easy and quantitative appreciation of results bring important diagnostic arguments. Other parasites, such as toxoplasmas, may also be detected. On the other hand, the examination of expectoration is time consuming and difficult to read and interpret. Therefore, sputum induction for the diagnosis of Pneumocystosis should be reserved to unequiped centers or insufficiently equiped centers (i.e., devoid of intensive care units).

Acquired Immunodeficiency Syndrome