J. K. M. Eeftinck Schattenkerk

Diagnosis of intestinal and disseminated microsporidial infections in patients with HIV by a new rapid fluorescence technique.

AIMS--To assess the value of a new rapid fluorescence method for the diagnosis of microsporidiosis in HIV seropositive patients. METHODS--Microsporidian spores in stools were demonstrated by using the fluorochrome stain Uvitex 2B. The new technique was evaluated in three groups of HIV seropositive patients with diarrhoea. Group 1: 19 patients with biopsy confirmed E bieneusi infection (186 stool samples); group 2: 143 consecutive patients from whom faeces were submitted for routine investigation of diarrhoea (318 samples); group 3: 16 patients with small intestinal biopsy specimens negative for microsporidia (55 samples). The new method was used to monitor spore shedding during experimental treatment with paromomycin and albendazole in four patients. RESULTS--Brightly fluorescent spores were detected in all stool samples of patients in group 1. In group 2 16 (11%) patients had spores in their stool samples. E bieneusi was found in 11 patients; in the other five another genus of microsporidia, Encephalitozoon, was recognised. Encephalitozoon spores were also found in the urine of three of these patients and in the maxillary sinus aspirate of two of them, suggesting disseminated infection. The results were confirmed by electron microscopic examination. In group 3 negative biopsy specimens were confirmed by negative stool samples in all cases. Treatment with albendazole and paromomycin did not affect the spore shedding in three patients with E bieneusi infection. By contrast, in a patient with Encephalitozoon sp infection albendazole treatment resulted in clinical improvement together with complete cessation of spore excretion in the stool. CONCLUSION--The Uvitex 2B fluorescence method combines speed, sensitivity, and specificity for the diagnosis and treatment evaluation of intestinal and disseminated microsporidiosis.

Itraconazole compared with amphotericin B plus flucytosine in Aids patients with cryptococcal meningitis

ObjectiveWe conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. DesignThe trial was a prospective, randomized, and non-blinded study.Setting: The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. Patients, participantsTwenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. InterventionsOral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. Main outcome measuresOutcome measures were a complete or partial response, recrudescence and relapse. ResultsA complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). ConclusionItraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.

Septata intestinalis frequently isolated from stool of AIDS patients with a new cultivation method

Two species of microsporidia, Enterocytozoon bieneusi and Septata intestinalis have been reported as intestinal parasites of AIDS patients. In attempts to establish E. bieneusi in vitro, spores were concentrated from stool samples from 4 AIDS patients with biopsy-proven E. bieneusi infections. After sterilization of the concentrate in antibiotic solution, the spores were added to monolayers of RK13 cells grown on the membranes of Transwells. Cultures were established from 7 stool samples from the 4 patients but in every case the species established was S. intestinalis not E. bieneusi. On retrospective examination of the stools, a very small number of spores of a size comparable to that of S. intestinalis was found but this species was not detected in biopsies. Typical septate vacuoles containing Type I tubules were observed in vitro but in contrast to the original description, meronts were intravacuolar and sporogony was mainly disporoblastic. The cultivation system, used for the first time for microsporidia, revealed the presence of unsuspected S. intestinalis infections and indicates that this species may be much more common than hitherto suspected. S. intestinalis has not previously been cultured.

Combined zidovudine and interferon‐alpha treatment in patients with AIDS‐associated Kaposi's sarcoma

Abstract. The effectiveness of addition of interferon‐alpha (IFN‐alpha) to zidovudine in patients with AIDS‐associated Kaposis sarcoma was assessed in a non‐randomized, phase II clinical trial. Twenty‐one patients were treated with oral zidovudine (600 mg daily) and IFN‐alpha (9 MU subcutaneously daily) for 8 weeks. In patients with progressive disease, IFN‐alpha was increased to 18 MU daily for another 4 weeks. Only one of the 20 evaluable patients achieved a partial response at 8 weeks, that lasted for 3 months. Despite IFN‐alpha dose escalation in six patients, no further responses were seen. While myelotoxicity was mild, fatigue was the dose‐limiting side‐effect that prevented dose escalation in seven eligible patients. The combined treatment did not result in a decrease in HIV‐Ag. In summary, our results indicate that the addition of IFN‐alpha to zidovudine in patients with AIDS‐associated Kaposis sarcoma is not an efficacious treatment.

Otorhinolaryngological findings in AIDS patients: a study of 63 cases

SummaryPatients with acquired immunodeficiency syndrome (AIDS) frequently show signs and symptoms involving the head and neck. We reviewed the clinical histories of 63 cases with AIDS, with patients treated from 1982 to December 1985, in our hospital. Findings referable to the head and neck were seen in 43 patients. Comparison with a previous study in San Francisco revealed remarkable differences. We found otolaryngological manifestations in 68% of the patients in contrast to 41% in this latter study. We saw more rapidly increasing neck masses, a greater incidence of shortness of breath and chronic cough, and an increased occurrence of candidiasis. The number of cases with Kaposis sarcoma lesions was equal in both studies.

Can the course of high dose cotrimoxazole for Pneumocystis carinii pneumonia in AIDS be shorter? A possible solution to the problem of cotrimoxazole toxicity

Abstract. Fifty consecutive patients with confirmed PCP received a high dose of cotrimoxazole for 14 d, or until development of intolerance, directly followed by reduced dose maintenance therapy. Seven individuals died during the high dose course. Twenty (47%) of the 43 survivors showed toxicity reactions that necessitated dose reduction to maintenance level on average after 9.6 d. Thirteen of these 20 individuals tolerated the reduced dose, and seven did not. No further cases of toxicity were observed. In 43 survivors only one early relapse (day 17) was observed in a patient who had received full dose treatment for 14 d.