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From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

The prevalence of intestinal microsporidiosis among human immunodefiency virus (HIV)-infected persons with chronic diarrhea varies from 7% to 50%; thus, microsporidia are a significant source of morbidity and, occasionally, mortality among these patients. Anecdotal reports suggest that intestinal microsporidiosis is also an important infection in patients with AIDS in Germany. To determine the prevalence of microsporidiosis among HIV-infected patients in Germany, we performed a prospective coprodiagnostic study of 97 consecutive HIV-infected patients. Microsporidia were the most common enteropathogen identified in 18 (36.0%) of 50 patients with diarrhea and 2 (4.3%) of 47 patients without diarrhea (P < .001; chi2 test). Microsporidia were present in 60% of patients with chronic diarrhea and 5.9% of patients with acute diarrhea. The etiologic agent was Enterocytozoon bieneusi in 18 patients and Encephalitozoon intestinalis in two patients. The prevalence of intestinal microsporidiosis in this cohort of German patients with AIDS and diarrhea is one of the highest to be reported anywhere in the world. Microsporidiosis seems to represent one of the most important causes of diarrhea in HIV-infected patients in Germany and thus must be considered in the differential diagnosis for all AIDS patients presenting with diarrhea.

Diarrhea is an important clinical problem in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS). There are numerous classical as well as emerging enteric pathogens that can produce diarrhea; however, these agents can be missed when only one method, such as microbiological examination of stool, is used for diagnosis. The endoscopic biopsy is a sensitive method for diagnosis of many viral, fungal, and parasitic infections of the gastrointestinal tract. Although only one agent is often identified in mucosal biopsies from these immunosuppressed patients, coinfection with multiple microbial agents is being increasingly recognized. Giardia infection is not as prevalent as other pathogens in patients with AIDS, but it remains an important diarrheal agent that is potentially curable. However, there have been only rare reports of coinfections with giardiasis and other infectious agents. This report describes a patient with AIDS and chronic diarrhea who had repeated negative stool examinations for ova and parasites. Light and electron microscopic examination of subsequent endoscopically obtained small intestinal biopsies revealed coinfection with two parasites, Enterocytozoon bieneusi and Giardia lamblia. Following treatment with metronidazole for giardiasis, the diarrhea persisted, but was less severe. This report also describes the diagnostic features of Giardia and Enterocytozoon infections in biopsy tissues and emphasizes the importance of identifying enteric coinfections in patients with AIDS to ensure timely and specific modes of therapy.

Although Candida esophagitis is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), there has been no systematic study of the endoscopic and pathologic manifestations of this disease. During a 53-month period, 141 patients with AIDS and Candida esophagitis were studied. All patients had the severity of esophagitis graded prospectively and esophageal mucosal biopsies performed. Tissue biopsies were evaluated for histologic evidence of ulceration, extent of candidiasis, and presence of viral cytopathic effect. Follow-up was obtained. There appeared to be a uniform endoscopic appearance; with increasing severity, the scattered mucosal plaques coalesced, resulting in circumferential disease and luminal impingement. The pathologic pattern of Candida esophagitis was homogenous. Plaque material was composed primarily of desquamated superficial hyperplastic hyperkeratotic squamous epithelium and inflammatory cells, with infiltration by fungal elements and bacteria consistent with superinfection. Although endoscopic and histopathologic ulcer was commonly seen in these patients (32%), only four patients had ulcer believed secondary to Candida esophagitis alone. In conclusion, in patients with AIDS, Candida esophagitis is a superficial mucosal infection resulting in characteristic endoscopic and histopathologic patterns.

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.

Recent studies suggest human immunodeficiency virus (HIV) may be the cause of HIV-associated idiopathic esophageal ulcer (IEU). However, other causes of esophageal disease in HIV-infected patients have not been evaluated for appropriate comparison. Over a 14-month period 13 patients with IEU as determined by clinical, endoscopic, and pathologic criteria were identified. During the same period nine HIV-infected patients with cytomegalovirus (CMV) esophagitis and one HIV-infected patient each with herpes simplex virus esophagitis and gastroesophageal reflux disease (GERD) were also identified. Polymerase chain reaction (PCR) and in situ DNA hybridization (ISH) were performed on paraffin-embedded tissue formed on paraffin-embedded tissue of endoscopic biopsies of ulcer tissue using standard techniques. Eleven of 13 IEU patients (85%) as compared to seven of nine patients (78%) with CMV had HIV detected by PCR (P = 0.38). HIV was also detected in ulcer tissue from biopsy material from the patient with GERD but not herpes simplex virus esophagitis. In PCR-positive patients, ISH confirmed the presence of HIV in four patients (57%) with CMV and eight (73%) with IEU (p = 0.31). HIV was found only in inflammatory cells and not squamous epithelial cells. Given the similar prevalence of detection of HIV by PCR and ISH in ulcer tissue from both groups of HIV-infected patients as well as the location in rare inflammatory cells, we conclude that HIV infection of squamous mucosa does not appear to be the primary cause of IEU.

Purpose: Although cytomegalovirus (CMV) esophagitis is an important complication of acquired immunodeficiency syndrome, there has been little study specifically addressing the response to currently available antiviral therapy, relapse rate without maintenance therapy, and long-term outcome., Patients and Methods: Over a 45-month period, 44 patients with CMV esophagitis established endoscopically and histopathologically were prospectively identified from among all human immunodeficiency virus (HIV)-infected patients undergoing endoscopy. Induction therapy consisted of intravenous ganciclovir at 10 mg/kg per day for approximately 14 days. Foscarnet was given at 60 mg/kg every 8 hours for nonresponders to ganciclovir., Results: Of these patients, 35 completed induction ganciclovir therapy, resulting in a complete response in 17 (49%) and a partial response in 10 (29%), yielding a 77% overall response rate. Seven of 8 nonresponders were subsequently treated with foscarnet, with a clinical response seen in 5 patients. In the 18 eventual complete responders to ganciclovir or foscarnet followed up without maintenance therapy, 7 (39%) relapsed at a median of 4 months (range 2 to 18 months). In all cases, relapse was manifested by recurrent odynophagia. Reinduction ganciclovir therapy yielded a complete response in 1 patient and a partial response in 2, and induction foscarnet treatment resulted in a complete response in the other treated patients. During long-term follow-up, 1 complete responder developed CMV colitis with concurrent retinitis, and 4 other patients developed retinitis. The median survival after diagnosis was 8.2 months, although survival for greater than 1 year was seen in 4 patients. No patient died as a direct result of esophageal disease, although ulcer-related bleeding may have contributed to death in 2 patients with end-stage liver diseases and hepatic encephalopathy., Conclusions: CMV esophagitis has a favorable response to induction ganciclovir therapy, and a long-term remission may occur after induction therapy alone. Despite the favorable response to ganciclovir therapy, the long-term survival is poor, reflecting the severe immunodeficiency of these patients.

In conclusion, at the current time the most important task of the laboratory for proper clinical management of the patient with microsporidiosis is to perform genus-level diagnosis of the agent, i.e. distinguishing Encephalitozoon sp. infection from other microsporidial agents including Septata, Enterocytozoon, Nosema, and Pleistophora. This can be performed in any well-equipped pathology department with access to electron microscopy. If species identification is desired, we currently recommend consultation with one of several laboratories specializing in this area until diagnostic reagents become more widely available.

Cytomegalovirus (CMV) esophagitis is an important cause of esophageal ulceration in patients with the acquired immunodeficiency syndrome. However, the endoscopic appearance of these lesions has not been well characterized. During a 3-year period, we identified 141 CMV esophageal ulcerations endoscopically in 33 patients. CMV esophagitis was the index diagnosis of human immunodeficiency virus (HIV) infection in 8 patients. Odynophagia was almost uniformly present, although gastrointestinal bleeding was the initial manifestation in 5 patients. Multiple ulcers were identified in 58% of patients. Giant ulcers were seen in 28%, whereas 43% of the lesions were less than 1 cm in greatest dimension. The majority of the lesions were located in the middle to distal section of the esophagus. The ulcers were characterized as either shallow or of intermediate depth in 74% of patients; deep ulcers were seen in 8%; diffuse erosive disease was found in 6%; and the ulcers had a "heaped up" appearance in 12%. In contrast to reports from previous studies, CMV esophageal disease appeared highly variable endoscopically. Multiple, well-circumscribed ulcerations were the most common endoscopic findings, although lesions could vary in number, size, and appearance. As this lack of uniformity may cause CMV esophagitis to be confused with other conditions characterized by esophageal ulceration, all HIV-infected patients with esophageal ulceration should undergo endoscopy with biopsy so that a definitive diagnosis can be obtained.

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.

Four genera of microsporidia have been associated with disease in humans, which predominantly affects immunocompromised persons. Systemic infection with a newly characterized microsporidian species, Encephalitozoon hellem, was recently reported in a patient with AIDS. This article describes a second patient with AIDS and disseminated E. hellem infection. In this case the parasite was detected in sputum, urine, and conjunctival swab specimens. Apart from recurrent mild conjunctivitis and asymptomatic microhematuria, the patient had no findings or symptoms that could be related to this parasite. Specifically, no microsporidian-associated pulmonary pathology was documented. Detection of E. hellem in the patient's sputum may have epidemiological implications in that this finding suggests transmission of microsporidia by the aerosol route. Because the patient died of unrelated complications, it remains unknown whether he was an asymptomatic carrier of microsporidia or whether microhematuria heralded early microsporidian disease, with the onset of cellular damage in the urinary tract.

There recently have been several reports of microsporidial keratoconjunctivitis caused by the organism Encephalitozoon hellem. However, treatment of this infection has been largely ineffective. We report a case of a 35-year-old Hispanic woman with AIDS and E. hellem keratoconjunctivitis confirmed with light, electron, and immunofluorescence microscopy that resolved promptly with topical fumagillin, a crystalline antibiotic with proven efficacy against Encephalitozoon species. No corneal or systemic toxicities were noted using the dosage and preparation employed (10 mg/ml suspension in balanced salt solution). An easily prepared, topical fumagillin suspension appears to be a safe, effective treatment for E. hellem keratoconjunctivitis.

We studied the clinicopathologic features of seven patients with acquired immunodeficiency syndrome (AIDS) and ocular microsporidiosis. All patients had decreased levels of CD4-positive cells (mean, 26/ml3) and ocular symptoms; five had bilateral punctate epithelial keratopathy, one had intermittent red eyes with conjunctivitis, and one had red eyes only. Light and electron microscopy of corneal and conjunctival biopsy and cytologic specimens and intact globes disclosed microsporidia belonging to the genus Encephalitozoon. Because E. cuniculi and E. hellem, the two species of the Encephalitozoon genus, are morphologically identical, an immunofluorescent antibody technique was used for species identification. In all seven patients, the agent was identified as E. hellem. Pathologic examination of globes obtained after autopsy disclosed E. hellem infection to be restricted to the corneal and conjunctival epithelium. We studied methods for the routine diagnosis of ocular microsporidiosis in patients with AIDS, including the role of immunofluorescent antibody staining.