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Antimicrobial Agents and Chemotherapy, January 2000, p. 167-168, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Successful Treatment with Nitazoxanide of Enterocytozoon
bieneusi Microsporidiosis in a Patient with AIDS
Alain
Bicart-Sée,1,*
Patrice
Massip,1
Marie-Denise
Linas,2 and
Annick
Datry3
Department of Infectious and Tropical
Diseases, Purpan Hospital,1 and
Parasitology-Mycology Laboratory, Rangueil
Hospital,2 Toulouse, and
Parasitology-Mycology Laboratory, Pitie-Salpetriere Hospital,
Paris,3 France
Received 11 March 1999/Returned for modification 23 August
1999/Accepted 13 October 1999
 |
ABSTRACT |
A patient with AIDS and chronic diarrhea caused by
Enterocytozoon bieneusi was successfully treated with
nitazoxanide, producing a complete clinical and parasitological
response, while off of antiviral therapy. This suggests that
nitazoxanide may be effective in treating microsporidiosis caused by
E. bieneusi, a disease for which there is no established treatment.
| |
TEXT |
Microsporidiosis can be responsible
for a severe diarrheal syndrome in AIDS patients, the severity of which
is related to the degree of immunosuppression of the patient. Clinical
trials have shown partial effectiveness of albendazole in treating
microsporidiosis caused by Encephalitozoon intestinalis
(8), but there is no established treatment for infection
caused by Enterocytozoon bieneusi, the most prevalent
microsporidian pathogen. We report a case of E. bieneusi
diarrheal syndrome associated with AIDS and successfully treated with nitazoxanide.
Nitazoxanide is a new broad-spectrum antiparasitic drug effective
against a broad range of protozoa, nematodes, cestodes, and trematodes
(10, 12). It has been used for the treatment of
cryptosporidiosis in AIDS patients (4, 11).
A 37-year-old formerly intravenous-drug-addicted male, infected with
both human immunodeficiency virus (HIV) and hepatitis C, presented in
early April 1997 in the day care HIV clinic of the Purpan Hospital in
Toulouse with mild diarrhea consisting of four pasty stools per day
without weight loss. Examinations of three pretreatment fecal samples
over approximately 90 days by the Weber trichrome stain technique and
with a fluorescence assay (Uvitex 2B, Ciba-Geigy, Basel, Switzerland),
later confirmed by PCR (9), showed that this patient was
infected by E. bieneusi, his first opportunistic infection.
The number of spores observed in fecal samples by Weber trichrome stain
and fluorescence assay increased significantly between the time of the
initial diagnosis in April and later examinations in June and just
before treatment in July. A full workup did not reveal any other
protozoal or bacterial pathogens (7). The source of
microsporidial infection could not be identified. His travel in the
previous 12 months had been limited to southern Europe and North
America. He had been HIV positive since 1986, and at the time of
consultation, his CD4 count was 126/mm3 (14%), with a
viral load of 5.2 log (156,000) copies/ml. He had previously received
several antiviral combination therapies, beginning in October 1989 with
zidovudine alone, and he was currently taking stavudine, lamivudine,
and indinavir. Approximately 1 month after the initial diagnosis of
E. bieneusi infection, the patient was hospitalized with
mixed hepatitis consistent with his hepatitis C, probably worsened by
his antiretroviral therapy (1, 5, 6) (alkaline phosphatase,
498 IU/liter [normal, <280 IU/liter]; 
-glutamyltransferase,
141 IU/liter [normal, <25 IU/liter]; serum glutamic
oxaloacetic transaminase, 340 IU/liter [normal, <34 IU/liter]; serum glutamic pyruvic transaminase, 185 IU/liter [normal, <37 IU/liter]; total bilirubin, 213 µM/liter [normal, <17
µM/liter]). Triple therapy was discontinued, and his hepatitis
symptoms improved, but the diarrhea worsened, with 5 to 10 episodes of
liquid stool per day and with night awakening. An attempt was made to
treat the condition with albendazole at a dose of 1,200 mg/day for a total of 15 days (30 April to 14 May 1997). The patient did not respond. This is not surprising, because albendazole is known to be
weakly effective against E. bieneusi (2). While
he was in the hospital in May 1997, he experienced pain at the profound palpation of the right hypochondrium. His weight remained stable at
approximately 70 kg, and he was still negative for other protozoal or
bacterial pathogens.
Nitazoxanide therapy was initiated on 1 July 1997 at a dose of 1,000 mg
twice a day for 60 consecutive days. Informed consent was obtained from
the patient prior to initiation of treatment. The drug was supplied by
Romark Laboratories, Tampa, Fla., for compassionate use in France. At
the time of treatment, the patient was not receiving any antiretroviral
therapy. When treatment with nitazoxanide was initiated, his CD4 count
was 85/mm3 (13%), and his viral load was 5.5 log (330,000)
copies/ml. The diarrhea resolved during treatment, with pasty stools on
day 10 of treatment and normal bowel movements by the end of the 60 days of treatment with nitazoxanide. Fecal examination by the
techniques described above showed a few spores on day 7 of therapy and
negative stools on days 11, 19, and 60 of treatment. Clinical and
biological tolerance were good. Liver function tests conducted during
and after treatment showed no significant changes compared to baseline values. Three posttreatment fecal examinations, including PCR, conducted over 2 months following the end of the treatment with nitazoxanide did not reveal any microsporidial spores, and the patient
continued normal bowel movements.
After it was evident that the patient's microsporidial diarrhea had
resolved in August 1997, antiviral therapy was reinitiated with
dianosine and lamivudine. At the end of the treatment with nitazoxanide, his CD4 count was 53/mm3 (10%), and his
viral load was 5.2 log (170,000) copies/ml. The patient remained
without any symptoms of microsporidiosis until he died in December 1997 due to chronic cirrhosis of the liver secondary to hepatitis C.
Nitazoxanide has been reported to be effective in cell culture
against E. intestinalis and Vittaforma
corneae (3). This case study suggests that
nitazoxanide is effective clinically and that prospective trials should
be performed to evaluate its possible role in treating microsporidiosis
in patients with AIDS.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Service des
Maladies Infectieuses, Hôpital Purpan, 31059 Toulouse Cedex,
France. Phone: 33 561 77 20 92. Fax: 33 561 77 34 73. E-mail:
bicart{at}club-internet.fr.
| |
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Antimicrobial Agents and Chemotherapy, January 2000, p. 167-168, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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