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In 1975, she had recurrent disease; over the next 13 years she had multiple excisions and aspirations of cysts involving the left femur, pelvis, and surrounding soft tissue. She was seen by an infectious diseases physician during this time and received intermittent courses of mebendazole.
In 1988 she began treatment with long-term albendazole at a dose of 400 mg twice a day in a 4-week on 2-week off cycling regimen. Her condition appeared to stabilize for a time with lessening of pain and stable disease as determined by serial computed tomography scans.
She was referred back to the infectious diseases clinic in 2004 with increasing pain and spontaneous discharge from the left hip. Praziquantel was prescribed, to be taken at a dose of 600 mg three times a day on the first day of each albendazole cycle.
When seen again in the infectious diseases clinic in late 2006, she reported worsening hip pain. Examination showed fluctuant masses at the left hip and the right iliac fossa and a discharging sinus at the left hip. Magnetic resonance imaging scans showed new multiloculated cysts in the right rectus abdominis muscle and lateral to the left iliac wing, together with almost complete replacement of the left hemipelvis with disease (Figure 1A and B
).
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After the course of nitazoxanide, repeat imaging demonstrated significant regression of the soft tissue cysts in the abdominal wall and lateral to the left iliac wing, with stable bony disease (Figure 1C and D
). Although the reduction in size of the cysts adjacent to the left iliac wing may have been due in part to aspiration and spontaneous drainage, the right abdominal wall cysts had not been aspirated. She was reviewed in the clinic and reported lessening of hip pain and swelling. She had a persisting sinus over the left hip but the discharge was diminished. An additional one-month course of nitazoxanide was dispensed.
Unfortunately, she was readmitted to hospital after completion of the second course of nitazoxanide with septic shock thought to be caused by a secondary bacterial infection of the hip sinus. She initially responded well to treatment, however, on day 5 of the admission she had a massive left intracerebral hemorrhage and died. Although she had no history of cerebrovascular disease, she had risk factors of hypertension and mild coagulopathy attributed to sepsis, and had received aspirin and heparin for deep venous thrombosis prophylaxis. An autopsy was not conducted.
Nitazoxanide, 2-acetyloxy-N-(5-nitro-2-thiazolyl) benzamide, is the prototype compound of the thiazolide class of drugs. It was initially developed as a veterinary antihelminthic agent against intestinal cestodes but has since been shown to have activity against a wide range of protozoa and helminths in humans. 7,8 It also has activity against a large number of anaerobic and microaerophilic bacteria including Clostridium difficile and Helicobacter pylori, and has recently been found to be active against hepatitis C.7–9 In protozoa and anaerobic bacteria nitazoxanide inhibits pyruvate-ferredoxin oxidoreductase, an enzyme involved in anaerobic energy metabolism. However, its mechanism of action against helminths is unknown. The U.S. Food and Drug Administration has approved the use of nitazoxanide for diarrhea caused by Cryptosporidium spp. and Giardia spp.7
Although use of nitazoxanide for treatment of echinococcosis in humans has not been reported, it has been studied in vitro against E. granulosis5 and E. multilocularis,10,11 and in a mouse model against E. multilocularis.12 The in vitro activity of nitazoxanide against E. granulosus protoscoleces and metacestodes was reported by Walker et al.5 Dose-dependent protoscolex death was seen within a few days of nitazoxanide treatment, with subsequent in vitro culture confirming non-viability. Progressive distortion of nitazoxanide treated metacestodes was seen by electron microscopy, with complete destruction of all parasitic tissue by day 7 of treatment. Metacestodes treated with albendazole showed similar morphologic changes to those treated with nitazoxanide.5 Nitazoxanide therapy against E. multilocularis was studied in an experimental mouse model by Stettler et al. 12 Mice were infected by intraperitoneal injection of metacestodes and treated with nitazoxanide, albendazole, or combined therapy. Combination treatment was the most effective, resulting in the greatest reduction in parasite weight and the most severe ultrastructural changes when viewed by transmission electron microscopy. Nitazoxanide and albendazole alone induced inconsistent ultrastructural changes, with some metacestodes remaining intact and others showing severe destruction. Combination therapy resulted in a 2–4-fold increase in levels of albendazole-sulfoxide, an observation that may have contributed to the improved efficacy of the combined treatment. 12
Nitazoxanide is generally well tolerated and no significant adverse events have been noted in more than 2,000 patients in clinical trials. 7,8 There have been no reports of an increased risk of bleeding with nitazoxanide therapy.
Our patient had a long history of extensive bony and soft tissue pelvic hydatid disease that was progressing while she was taking albendazole and praziquantel. The addition of nitazoxanide in combination with albendazole resulted in a significant improvement in the soft tissue cystic disease, with stable disease in the bony pelvis. Radiologic evidence of response after successful therapy of pyogenic osteomyelitis can be delayed. It is possible that a pharmacokinetic interaction resulting in higher levels of albendazole, as noted in the mouse model, 12 contributed to the response seen in our patient.
Use of nitazoxanide for treatment of cystic echinococcosis has not been previously reported in humans or in animal studies. This case suggests it may represent a treatment option in patients with progressive disease who are receiving conventional therapy.
Received June 11, 2008. Accepted for publication August 13, 2008.
* Address correspondence to Alison Winning, Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Queensland 4006, Australia. E-mail: alison_winning{at}health.qld.gov.au 
Authors’ addresses: Alison Winning and Phillip Braslins, Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Queensland 4006 Australia. James S. McCarthy, Department of Infectious Diseases, Royal Brisbane and Women’s Hospital, Brisbane, Queensland 4006, Australia and Queensland Institute of Medical Research and Australian Centre for International and Tropical Health and Nutrition, Herston, Queensland 4029, Australia.
This article has been cited by other articles:
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  H. G. Schipper, S. Simsek, M. A. van Agtmael, and K. P. van Lienden Bone Hydatid Disease Refractory to Nitazoxanide Treatment Am J Trop Med Hyg, September 1, 2009; 81(3): 446 - 448. [Abstract] [Full Text] [PDF]
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