Using Albendazole to Treat Microsporidiosis in AIDS Patients
abstract & commentary
Synopsis: Albendazole was effective in the treatment and secondary prophylaxis of intestinal infection due to E. intestinalis in patients with AIDS.
Source: Molina JM, et al. Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS. J Infect Dis 1998; 177:1373-1377.
Encephalitozoon intestinalis (formerly Septata intestinalis) is a microsporidial species that is an opportunistic pathogen in patients with AIDS. Diverse clinical manifestations of this infection include chronic diarrhea and cachexia that can be associated with cholangitis, sinusitis, bronchitis, conjunctivitis, and interstitial nephritis. Molina and associates conducted this randomized study of albendazole for treatment and prophylaxis of E. intestinalis infections in two hospitals in France in conjunction with SmithKline Beecham Pharmaceuticals. Given the results of the first interim analysis, enrollment of additional patients into this study was discontinued.
This study is unique in that all eligible patients underwent upper gastroduodenal endoscopy with duodenal biopsy to confirm the infection and to identify by electron microscopy the species involved. PCR was used to specify E. intestinalis. Molina et al intended to study an initial group of 10 patients. Patients were recruited between September 1994 and November 1996. However, two patients were excluded because electron microscopy analysis of their duodenal biopsies and PCR results from stool and intestinal biopsies showed that they were not infected with E. intestinalis but with Enterocytozoon bieneusi and Encephalitozoon hellem. Therefore, there were eight patients for evaluation. Only one patient did not have E. intestinalis detected in their duodenal biopsy by electron microscopy. However, this patient had E. intestinalis DNA by PCR as well as parasitologic findings confirming E. intestinalis infection in stool, urine, and bile samples. Microspordial spores could be found in urine in seven of eight patients. One patient had concomitant cytomegalovirus duodenitis and Clostridium difficile in his stools.
All patients were homosexual men with a history of chronic intermittent diarrhea and CD4 counts below 55 cells/cubic mm. Four patients were randomized to receive albendazole and four to receive placebo for a 21-day course. Premature discontinuation of therapy occurred exclusively in the placebo group. Microspordial spores were always detected in follow-up stool and urine specimens from patients randomized to receive placebo with no change in the semi-quantitative number of spores. By contrast, clearance of microsporidial spores was observed in follow-up stool specimens from the four patients randomized to receive albendazole. Urine specimens from two of these four patients still yielded microsporidia although the spores appeared to be altered.
These four patients underwent a second duodenal endoscopy with biopsies that failed to yield microsporidia when examined by histopathology and electron microscopy in three of four patients. In the fourth patient, electron microscopy revealed only what seemed to be remnants of microsporidial spore. All patients randomized to receive albendazole gained weight during the three-week study (mean, 4.1 kg; range 2.0-7.5 kg). All patients in the albendazole group had formed stools at the end of the treatment compared with none in the placebo group. Also, decreases in alkaline phosphatase and creatinine levels were noted in the albendazole group associated with disappearance of leukocyturia.
In the next phase of the study, the four patients without cure completed a 21-day course of open-labelled albendazole and cleared E. intestinalis from follow-up stools and intestinal biopsies. Thus, the overall cure rate of the albendazole regimen in their study was 100% (8 out of 8; 95% confidence interval 0.64-1.0%). Urinalysis still yielded microsporidial spores in three of these patients at the end of the treatment.
The prophylaxis phase of the study randomized the eight patients to receive maintenance therapy with albendazole 400 mg twice daily or no treatment. During the study period, none of the three patients receiving maintenance therapy had a recurrence of E. intestinalis infection (mean follow-up 7.7 months; range 6-9). Microsporidial spores were no longer detected in the urine samples of these patients. Three relapses were recorded among the five patients receiving no prophylaxis. Two of the relapses occurred in patients with persistent asymptomatic shedding of microsporidial spores in urine. Death occurred in four patients during follow-up (in three receiving no prophylaxis and in one receiving albendazole). By log rank analysis, albendazole had no significant effect on mortality during follow-up. There were no serious adverse effects reported during the double-blind study related to albendazole. Adverse events reported included headache and gastrointestinal events that were not different from placebo.
Comment by Geza Ruszka, MD
Even though the numbers are small, based on these studies, it appears that albendazole is safe and effective for treatment and long-term prophylaxis for E. intestinalis infection in AIDS patients. It also appears that albendazole is probably effective for Encephalitozoon species other than intestinalis so that the strict diagnostic criteria observed during this study may not be necessary for clinical treatment of patients. Persistent shedding of spores in the urine might be associated with relapse because two of the three relapses occurred among the three patients who had microspordial spores in the urine of two patients detected at randomization who received no treatment. The issue of urinary shedding requires further study.
In the useful chapter by Carolyn Peterson on microsporidiosis available on the Internet (http://hivinsite.ucsf.edu/akb/1997/06mispor/index.html), it is noted that albendazole is an inhibitor of tublin polymerization and has a chemical structure related to metronidazole. Nevertheless, albendazole has been associated with C. difficile colitis in an AIDS patient under treatment for microsporidiosis. Because severe pancytopenia has been associated with albendazole therapy for Echinococcus infection, WBC counts need to be monitored in HIV-positive persons treated with albendazole. (Dr. Ruszka is Clinical Assistant Professor of Medicine, Robert Wood Johnson Medical School-UMDNJ, New Brunswick, NJ.)