Correspondence
Fumagillin for Intestinal Microsporidiosis
N Engl J Med 2002; 347:1381October 24, 2002
- Article
To the Editor:
Molina et al. (June 20 issue)1 report a two-week study confirming the activity of fumagillin against intestinal microsporidiosis in 12 immunosuppressed adults, 10 of them with advanced human immunodeficiency virus (HIV) infection. Ten patients had partial clinical responses after a median of 10 months; histologic improvement was not documented. It is not certain, however, that these prolonged responses were a result of fumagillin therapy. As the authors note, highly active antiretroviral therapy for HIV infection is also effective against intestinal microsporidiosis (and cryptosporidiosis), probably because it improves immune function.2,3 Of five of our patients who had had complete clinical responses after a median of 13 months of highly active antiretroviral therapy, two had no diarrhea for more than 5 years.
Did any HIV-infected patient studied by Molina et al. (three of whom had never received highly active antiretroviral therapy) begin new antiretroviral therapy after week 2? Were the doses of immunosuppressive therapy reduced in the two patients without HIV infection? If so, did the CD4 lymphocyte counts increase? An improved CD4 count in response to either intervention may explain the prolonged responses to fumagillin.
Three opportunistic infections developed during the 10 months of follow-up. These infections might have been avoided with the use of a new regimen of highly active antiretroviral therapy.4,5 Fumagillin is active only against microsporidiosis and is not risk-free, whereas highly active antiretroviral therapy reduces the incidence of almost all HIV-related opportunistic infections, cancers, and dementia. HIV-infected patients with microsporidiosis should therefore probably receive fumagillin in combination with a new regimen of highly active antiretroviral therapy if that option is available.
5 ReferencesAndrew Carr, M.D.
St. Vincent's Hospital, Sydney 2010, Australia
acarr@stvincents.com. au David A. Cooper, M.D., D.Sc.
National Centre in HIV Epidemiology and Clinical Research, Sydney 2010, Australia1
Molina J-M ,Tourneur M ,Sarfati C , et al. Fumagillin treatment of intestinal microsporidiosis. N Engl J Med 2002;346:1963-1969
Full Text | Web of Science | Medline2
Carr A ,Marriott D ,Field A ,Vasak E ,Cooper DA . Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998;351:256-261
CrossRef | Web of Science | Medline3
Foudraine NA ,Weverling GJ ,van Gool T , et al. Improvement of chronic diarrhoea in patients with advanced HIV-1 infection during potent antiretroviral therapy. AIDS 1998;12:35-41
CrossRef | Web of Science | Medline4
Palella FJ Jr ,Delaney KM ,Moorman AC , et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998;338:853-860
Full Text | Web of Science | Medline5
Mocroft A ,Katlama C ,Johnson AM , et al. AIDS across Europe, 1994-98: the EuroSIDA study. Lancet 2000;356:291-296
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree with Drs. Carr and Cooper that it is not certain that the prolonged responses in our patients were the result of fumagillin alone, and we discussed this point in our article. Our study was designed primarily to assess the parasitologic and clinical efficacy of fumagillin after four weeks. Since all patients had clearance of the microsporidial infection with fumagillin, we also wished to assess the long-term parasitologic efficacy of the drug. Among the 10 patients without relapse, 3 patients who had not previously been treated with antiretroviral drugs received highly active antiretroviral therapy that prevented assessment of the long-term efficacy of fumagillin. However, in the seven other patients, the absence of relapse was unexpected and was most likely attributable to fumagillin therapy. The immunosuppressive regimens of the two recipients of organ transplants were not changed during follow-up, and multiple regimens of highly active antiretroviral therapy had failed in the five patients with AIDS. They were all receiving such regimens during the study, but their CD4 cell counts remained low at the end of follow-up (10, 6, 35, 72, and 95 cells per cubic millimeter).
The three opportunistic infections to which Carr and Cooper refer did not occur during follow-up but during the first four weeks of the study. These infections developed in patients with low CD4 counts for whom no effective regimen of highly active antiretroviral therapy was available.
We think our study shows the efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi. Immune reconstitution is probably the best option for controlling microsporidiosis, but if it is not possible, fumagillin should be used.
Jean-Michel Molina, M.D.
Muriel Tourneur, M.D.
Hôpital Saint-Louis, 75010 Paris, France
jean-michel.molina@sls. ap-hop-paris. fr - Citing Articles (2)
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