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Biomedical subjects

R T Bryan

Publications and source records attributed to R T Bryan.

At least 37 records · Page 2Linked to original sources

Atovaquone is effective treatment for the symptoms of gastrointestinal microsporidiosis in HIV-1-infected patients.

OBJECTIVE: To report the clinical response to atovaquone in HIV-1-infected patients with symptomatic intestinal microsporidiosis. DESIGN: A retrospective review of a cohort of AIDS patients with symptomatic intestinal microsporidiosis who received atovaquone. SETTING: Infectious Disease Program of the Grady Memorial Hospital, Veterans Affairs Medical Center and private physicians' offices in Atlanta, Georgia. PATIENTS AND METHODS: HIV-1-infected patients (n = 371) were offered a complete stool evaluation and monthly follow-up. Among them, 22 were diagnosed with intestinal microsporidial infection using stool smears stained with modified trichrome stain. Species confirmation was made by light microscopy or electron microscopy on small intestinal biopsy specimens in some patients. MAIN OUTCOME MEASURE: Differences in symptoms, number of stools, and body weight were compared before and after a minimum of 1 month of atovaquone therapy. RESULTS: Eight patients received atovaquone treatment. The mean onset of clinical improvement after beginning treatment was 13 days (SEM, +/- 2). The mean number of stools per day decreased from 10 +/- 2.5 to 2 +/- 1 (P = 0.02, paired t test). The mean weight gain was 3 +/- 2 kg. The parasite was continuously present in the repeated stool specimens. However, semiquantitative analysis performed on two patients' stool specimens showed a decreased parasite burden. Four patients underwent small intestinal endoscopy was consistent with Enterocytozoon bieneusi in all four patients. Only one out of these four patients demonstrated a decrease in parasite burden in the biopsy specimen. Ultrastructural analysis performed in another of these four patients following treatment demonstrated the presence of electron-dense granules in spores, suggestive of toxic effects. CONCLUSION: Atovaquone demonstrates promise as a symptomatic treatment for intestinal microsporidiosis. A double-blind and placebo-controlled clinical trial is currently in progress.

AIDS-Related Opportunistic Infections↗

An outbreak of acute fascioliasis among Aymara Indians in the Bolivian Altiplano.

Fasciola hepatica is a common and important parasite of sheep, cattle, and other ruminants. In May 1991, 30 persons with possible acute fascioliasis were identified by health care providers at a district hospital in the Bolivian Altiplano, and two deaths were associated with this illness. A cross-sectional survey of a random sample of 30 (20%) of the 148 households in the community and a case-control study were performed to determine the extent of the outbreak and the vehicle of transmission. Ninety-one members from 23 of the 30 selected families participated in the cross-sectional survey. Twenty-one of the 91 members met the case definition for acute fascioliasis (illness since 16 February 1991 that was characterized by fever and abdominal pain plus serum IgG antibodies to F. hepatica), and 38 (49%) of 78 members had serum IgG antibodies to F. hepatica. If this rate is extrapolated to the entire community, an estimated 116 individuals (23% of 504) would have acute fascioliasis and 247 individuals (49% of 504) would have evidence of current or previous infection. Case-control analysis indicated that the only factor associated with illness was eating kjosco (an aquatic plant) while tending animals in the fields; 27 (52%) of the 52 case-patients vs. 9 (14%) of the 66 controls ate kjosco (OR = 6.84; 95% CI = 2.60, 18.44). The cause of the two deaths attributed to fascioliasis could not be firmly established. Fascioliasis is a significant human health problem and is highly endemic in the Aymara Indian community in the Bolivian Altiplano. Efforts to prevent fascioliasis should include educating people to avoid eating uncooked aquatic plants such as kjosco.

Acute Disease↗

Microsporidiosis as an AIDS-related opportunistic infection.

The clinical manifestations of AIDS-related microsporidiosis range from mild or asymptomatic infections to debilitating illness involving the gastrointestinal, respiratory, or urogenital tracts or the eyes. Intestinobiliary infections with Enterocytozoon bieneusi are the most common microsporidial diseases, but disseminated infections with Encephalitozoon hellem, Encephalitozoon cuniculi, and Septata intestinalis are being increasingly recognized. The isolation of infective microsporidial spores from urine and respiratory secretions and the presence of spores in stool and duodenal aspirates suggest that person-to-person transmission may occur. Primary infection may also occur by inhalation or ingestion of spores from environmental sources or by zoonotic transmission. Development of guidelines for prevention of microsporidiosis will require that sources of infection and modes of transmission be more clearly elucidated. The presence of infective spores in bodily fluids, however, suggests that precautions when handling body fluids in clinical settings and personal hygiene measures such as hand washing may help to prevent primary infections.

AIDS-Related Opportunistic Infections↗

Polymerase chain reaction and culture confirmation of disseminated Encephalitozoon cuniculi in a patient with AIDS: successful therapy with albendazole.

Infections due to microsporidia are being recognized increasingly, especially in AIDS patients. A patient with disseminated microsporidiosis with advanced renal failure due to Encephalitozoon cuniculi (confirmed by culture and polymerase chain reaction [PCR]) is described. The organism from urine and sputum was characterized by culture, Weber's chromotrope-based staining, transmission electron microscopy, and indirect immunofluorescence (IIF) tests. PCR was done on DNA extracted from the infected cell cultures. Treatment with albendazole resulted in improvement in serum creatinine levels, complete disappearance of spores from sputum, a negative urine culture, and a 3-log decline in the number of spores in the urine, as evidenced by chromotrope-based staining. IIF and PCR were used to confirm E. cuniculi as the etiologic agent. Our findings indicate that disseminated microsporidiosis with renal failure in AIDS is treatable.

AIDS-Related Opportunistic Infections↗

Pathology and emerging infections--quo vadimus?

There have been dramatic changes in the occurrence of infectious diseases throughout the world in the previous two decades. The emergence of new microbial agents, and the reemergence of infections previously believed to be controlled, threatens the health of all populations. The emergence of these infectious diseases has occurred during a period of breakdown in the capabilities of the public health surveillance systems, prevention programs, and disease control efforts. Expertise in pathology is critical to provide a strong national control program for emerging and reemerging infectious diseases. Despite the many significant achievements made by pathologists in improving understanding of the pathogenesis and diagnosis of infectious diseases, the field of pathology remains largely oriented toward neoplastic diseases, and has not yet identified infectious disease diagnosis as an important component of anatomic pathology training and research, even in the face of the current threats posed by microbial agents. In addition, there is currently a dearth of infectious disease pathologists in the United States and elsewhere in the world, and the use of the autopsy, a prime pathological tool for diagnosis of emerging infections, is on the wane. The most serious problem is that no formal training program for infectious disease pathology currently exists in the United States or elsewhere in the world. As a consequence of this lack of training opportunities, there is a severe deficiency of young, well-educated pathologists with infectious disease expertise. This article explores the historical linkages between the disciplines of infectious diseases and pathology, and suggests that infectious disease pathology as a subspecialty be strengthened and training programs be initiated.

Autopsy↗

The presence of Enterocytozoon bieneusi spores in the lamina propria of small bowel biopsies with no evidence of disseminated microsporidiosis. Enteric Opportunistic Infections Working Group.

Enterocytozoon bieneusi is the most frequently reported microsporidial infection of humans. In patients with the acquired immunodeficiency syndrome, Enterocytozoon infects the lining epithelial cells of the small intestine, hepatobiliary tract, and gallbladder. Because Enterocytozoon has been thought to be limited to infecting lining epithelial cells, the mechanism of spread of E bieneusi within the intestine, to the biliary tract, and, in two case reports, to distant organs remains unknown. This report describes a patient with acquired immunodeficiency syndrome and intestinal microsporidiosis due to E bieneusi. Histopathologic examination of well-oriented biopsies from the duodenum and jejunum revealed both intra- and extracellular spores of Enterocytozoon extending deeply into the lamina propria, where they were located adjacent to capillaries. The patient has not developed disseminated disease 20 months after the initial diagnosis. In this patient, the demonstration of E bieneusi spores in extraepithelial tissues does not appear to be associated with development of subsequent systemic infection.

Acquired Immunodeficiency Syndrome↗

Emerging infectious diseases in the United States, Improved surveillance, a requisite for prevention.

Emerging infectious diseases such as prolonged diarrheal illness due to water-borne Cryptosporidium, hemorrhagic colitis and renal failure from food-borne E. coli O157:H7, and rodent-borne hantavirus pulmonary syndrome as well as reemerging infections such as tuberculosis, pertussis, and cholera vividly illustrate that we remain highly vulnerable to the microorganisms with which we share our environment. Prompt detection of new and resurgent infectious disease threats depends on careful monitoring by modern surveillance systems. This article focuses on five important elements of improved surveillance for emerging infections: 1) strengthening the national notifiable disease system, 2) establishing sentinel surveillance networks, 3) establishing population-based emerging infections programs, 4) developing a system for enhanced global surveillance, and 5) applying new tools and novel approaches to surveillance.

Communicable Disease Control↗

Microsporidial infections in immunodeficient and immunocompetent patients.

Microsporidia are obligate, intracellular, spore-forming protozoal parasites. Their host range is extensive and includes most invertebrates and all classes of vertebrates. Five microsporidial genera (Enterocytozoon, Encephalitozoon, Septata, Pleistophora, and Nosema) and unclassified microsporidia have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. The majority of microsporidial infections in persons infected with human immunodeficiency virus (HIV) are attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Four cases of microsporidial infection among persons not infected with HIV who had documented or presumed cellular immunodeficiency and four cases of corneal stroma infection due to microsporidia in immunocompetent patients have been described. Furthermore, the first case of traveler's diarrhea due to E. bieneusi in an immunocompetent and otherwise healthy patient is reported in this issue. The sources of human microsporidial infections and modes of transmission are unknown.

Animals↗

Cryptosporidial and microsporidial infections in human immunodeficiency virus-infected patients in northeastern Brazil.

To determine the frequency of the parasitic pathogens in human immunodeficiency virus (HIV)-infected patients in a developing world setting, 295 stool specimens were examined from 166 HIV-positive patients (49% with AIDS) at São José Hospital, Fortaleza, Brazil, from September 1990 to March 1992. Significantly more patients with diarrhea (85%) than without (66%) had AIDS or AIDS-related complex (ARC) (P < .005). Of the potential parasitic causes of diarrhea, only Cryptosporidium parvum and microsporidia were significantly associated with diarrheal disease. Infections with C. parvum, but not microsporidia, were associated with the rainy season (P < .005). Thus, C. parvum and microsporidia are the most common intestinal parasites associated with diarrhea in an HIV-infected population in Brazil and are associated with advanced HIV disease. The association of C. parvum infections with the rainy season suggests that contaminated water may be important in its transmission; however, the source of human microsporidia requires further investigation.

AIDS-Related Opportunistic Infections↗

Human microsporidial infections.

Microsporidia are obligate intracellular spore-forming protozoal parasites belonging to the phylum Microspora. Their host range is extensive, including most invertebrates and all classes of vertebrates. More than 100 microsporidial genera and almost 1,000 species have now been identified. Five genera (Enterocytozoon spp., Encephalitozoon spp., Septata spp., Pleistophora sp., and Nosema spp.) and unclassified microsporidia (referred to by the collective term Microsporidium) have been associated with human disease, which appears to manifest primarily in immunocompromised persons. The clinical manifestations of microsporidiosis are diverse and include intestinal, pulmonary, ocular, muscular, and renal disease. Among persons not infected with human immunodeficiency virus, ten cases of microsporidiosis have been documented. In human immunodeficiency virus-infected patients, on the other hand, over 400 cases of microsporidiosis have been identified, the majority attributed to Enterocytozoon bieneusi, an important cause of chronic diarrhea and wasting. Diagnosis of microsporidiosis currently depends on morphological demonstration of the organisms themselves. Initial detection of microsporidia by light microscopic examination of tissue sections and of more readily obtainable specimens such as stool, duodenal aspirates, urine, sputum, nasal discharge, bronchoalveolar lavage fluid, and conjunctival smears is now becoming routine practice. Definitive species identification is made by using the specific fluorescein-tagged antibody (immunofluorescence) technique or electron microscopy. Treatment options are limited, but symptomatic improvement of Enterocytozoon bieneusi infection may be achieved with the anthelmintic-antiprotozoal drug albendazole. Preliminary observations suggest that Septata intestinalis and Encephalitozoon infections may be cured with albendazole. Progress is being made with respect to in vitro propagation of microsporidia, which is crucial for developing antimicrosporidial drugs. Furthermore, molecular techniques are being developed for diagnostic purposes, taxonomic classification, and analysis of phylogenetic relationships of microsporidia.

Animals↗

Polyclonal and monoclonal antibody and PCR-amplified small-subunit rRNA identification of a microsporidian, Encephalitozoon hellem, isolated from an AIDS patient with disseminated infection.

Microsporidia are primitive, spore-forming, mitochondria-lacking, eukaryotic protozoa that are obligate intracellular parasites. They are known to parasitize almost every group of animals including humans. Recently, microsporidia have increasingly been found to infect patients with AIDS. Five genera (Encephalitozoon, Enterocytozoon, Nosema, Septata, and Pleistophora) of microsporidia are known to infect humans. Enterocytozoon organisms cause gastrointestinal disease in a majority of AIDS patients with microsporidiosis. However, a smaller, but an expanding, number of patients with AIDS are being diagnosed with ocular and disseminated infection with Encephalitozoon hellem. Although microsporidial spores can be identified in clinical samples by a staining technique such as one with Weber's chromotrope stain, identification to the species level is dependent on cumbersome and time-consuming electron microscopy. We have recently isolated and established in continuous culture several strains of E. hellem from urine, bronchoalveolar lavage, and sputum samples from AIDS patients with disseminated microsporidiosis. We developed polyclonal and monoclonal antibodies and PCR primers to a strain of E. hellem that can be used successfully to identify E. hellem from other species of microsporidia either in clinical specimens or in cultures established from clinical specimens. Since patients infected with Encephalitozoon spp. are known to respond favorably to albendazole, identification of the parasite to the species level would be invaluable in the treatment of disseminated microsporidiosis.

Acquired Immunodeficiency Syndrome↗

Community participation in vector control: lessons from Chagas' disease.

As applied to vector-borne disease control, the term community participation has been broadly interpreted. Community-based vector control projects have been described as having both active and passive components. Recently, community participation in organized efforts to control Chagas' disease has become more dynamic, with increasingly active involvement by local community members. Chagas' disease is a particularly significant vector-borne disease problem in the South American countries of Brazil, Venezuela, and Bolivia, and health officials there are beginning to emphasize horizontal or decentralized approaches to control of triatomine vectors. Experience suggests that vector control programs using community participation have significant and sustainable impact on vector density, appear to be more cost-effective than purely vertically structured programs, are readily integrated with other health or development programs, promote an enduring sense of pride in home and community, and are politically viable vector control strategies. Community participation per se has inherent value because of its positive effect on social relationships and community solidarity. Moreover, it is a dynamic process that results in accrued benefits for public health that exceed most vector control program goals and persist well beyond program termination.

Animals↗

Microsporidiosis in HIV positive patients: current methods for diagnosis using biopsy, cytologic, ultrastructural, immunological, and tissue culture techniques.

Microsporidiosis is an increasingly important opportunistic infection in HIV-positive patients. Five species of microsporidia (Enterocytozoon bieneusi, Encephalitozoon hellem and E. cuniculi, Septata intestinalis, and Pleistophora sp.) have been reported to occur in AIDS, with each agent producing a different clinicopathologic spectrum of disease. This communication reviews routine and specialized methods for diagnosis of these important pathogenic protozoa, including biopsy, cytology, ultrastructural and immunologic examination, and tissue culture, and describes the current knowledge of organ distribution for microsporidia in persons with AIDS.

AIDS-Related Opportunistic Infections↗

Enteric viruses and diarrhea in HIV-infected patients. Enteric Opportunistic Infections Working Group.

BACKGROUND: Diarrhea occurs frequently among persons with the acquired immunodeficiency syndrome, but the cause often remains unknown. We used a group of diagnostic assays to determine which viruses were etiologic agents of diarrhea in a group of persons infected with the human immunodeficiency virus (HIV). METHODS: Stool and serum specimens were obtained from HIV-infected patients enrolled in a longitudinal study in Atlanta. Fecal specimens from patients with diarrhea and from control patients without diarrhea were screened by electron microscopy, polyacrylamide-gel electrophoresis, and enzyme immunoassays for rotaviruses, enteric adenoviruses, caliciviruses, picobirnaviruses, and astroviruses. Paired serum samples were tested for antibody responses to Norwalk virus and picobirnavirus. RESULTS: Viruses were detected in 35 percent of 109 fecal specimens from patients with diarrhea but in only 12 percent of 113 specimens from those without diarrhea (P < 0.001). Specimens from patients with diarrhea were more likely than those from patients without diarrhea to have astrovirus (12 percent vs. 2 percent, P = 0.003); picobirnavirus (9 percent vs. 2 percent, P = 0.017); caliciviruses, including small round structured viruses (6 percent vs. 1 percent, P = 0.062); and adenoviruses (9 percent vs. 3 percent, P = 0.047). They were also more likely to have a mixed viral infection (6 percent vs. 0 percent, P = 0.006). With the use of polyacrylamide-gel electrophoresis to analyze concentrated RNA extracts from stool, picobirnavirus was detected in fecal specimens from 6 of the 65 patients with diarrhea and was associated with prolonged viral shedding and chronic diarrhea. No rotaviruses, enteric adenoviruses, or instances of seroconversion to positivity for Norwalk virus were observed. CONCLUSIONS: Novel enteric viruses such as astrovirus and picobirnavirus may be more important etiologic agents of diarrhea in HIV-infected patients than previously recognized and may be more common than either bacterial or parasitic enteropathogens.

Adenoviruses, Human↗

Treatment of microsporidial keratoconjunctivitis with topical fumagillin.

Encephalitozoon hellem is a newly described cause of microsporidial keratoconjunctivitis, occurring chiefly in patients with significantly diminished CD4+ T-lymphocyte levels. This disorder is symptomatically disabling and generally recalcitrant to topical antimicrobial therapy. Two homosexual men with E. hellem keratoconjunctivitis diagnosed by Gram stain, transmission electron microscopy, and specific indirect immunofluorescent assay were treated with topical fumagillin (Fumidil B). Both patients had marked symptomatic improvement with reduction of clinical findings. Symptoms and signs recurred with temporary discontinuation of the drug. Both patients, however, remained symptom-free on maintenance levels of topical fumagillin with no evidence of toxic side effects.

AIDS-Related Opportunistic Infections↗