• View in gallery
    Figure 1.

    T1-weighted, gadolinium-enhanced MRI scans 3 months before surgery. The arrows in A indicate hydatid invasion of lumbar vertebra L4. The arrows in B indicate hydatid invasion of the left os ileum (R, right; L, left).

  • View in gallery
    Figure 2.

    T2-weighted MRI scans 12 months postoperatively. The arrows in A indicate extension of the paravertebral hydatid cyst cranially toward thoracic vertebra Th12, subcutaneously and around the spondylodesis material. The dotted arrows indicate the spondylodesis material in lumbar vertebrae L5 and L3 (A, anterior; P, posterior). The arrows in B indicate progression of the hydatid invasion into the left os ileum (R, right; L, left).

  • View in gallery
    Figure 3.

    Computed tomography scan of the patient 3.5 years postoperatively. Arrows in A and B indicate the parapelvic hydatid cyst complex invading into the fractured left os ileum and extending into the fractured hip joint (acetabulum).

  • 1

    Winning A, Braslins P, McCarthy JS, 2009. Case report: nitazoxanide for treatment of refractory bony hydatid disease. Am J Trop Med Hyg 80 :176–178.

    • Search Google Scholar
    • Export Citation
  • 2

    Wen H, Zhang HW, Muhmut M, Zou PF, New RR, Craig PS, 1994. Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. Ann Trop Med Parasitol 88 :49–52.

    • Search Google Scholar
    • Export Citation
  • 3

    Stettler M, Fink R, Walker M, Gottstein B, Geary TG, Rossignol JF, Hemphill A, 2003. In vitro parasiticidal effect of nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrob Agents Chemother 47 :467–474.

    • Search Google Scholar
    • Export Citation
  • 4

    Stettler M, Rossignol JF, Fink R, Walker M, Gottstein B, Merli M, Theurillat R, Thormann W, Dricot E, Segers R, Hemphill A, 2004. Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. Int J Parasitol 34 :615–624.

    • Search Google Scholar
    • Export Citation
  • 5

    Walker M, Rossignol JF, Torgerson P, Hemphill A, 2004. In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes. J Antimicrob Chemother 54 :609–616.

    • Search Google Scholar
    • Export Citation
  • 6

    Schipper HG, Koopmans RP, Nagy J, Butter JJ, Kager PA, Van Boxtel CJ, 2000. Effect of dose increase or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 63 :270–273.

    • Search Google Scholar
    • Export Citation
  • 7

    Nagy J, Schipper HG, Koopmans RP, Butter JJ, Van Boxtel CJ, Kager PA, 2002. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 66 :260–263.

    • Search Google Scholar
    • Export Citation
  • 8

    WHO Informal Working Group, 2003. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 85 :253–261.

    • Search Google Scholar
    • Export Citation
  • 9

    Filice C, Brunetti E, Bruno R, Crippa FG, WHO-Informal Working Group on Echinococcosis-PAIR Network, 2000. Percutaneous drainage of echinococcal cysts (PAIR-puncture, aspiration, injection, reaspiration): results of a worldwide survey for assessment of its safety and efficacy. Gut 47 :156–157.

    • Search Google Scholar
    • Export Citation
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Bone Hydatid Disease Refractory to Nitazoxanide Treatment

Hans G. SchipperDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, The Netherlands; Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Suat SimsekDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, The Netherlands; Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Michiel A. van AgtmaelDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, The Netherlands; Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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Krijn P. van LiendenDepartment of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Amsterdam, The Netherlands; Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

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We report a patient with bone hydatid disease that was refractory to both long-term daily treatment with albendazole, combined with cimetidine or administered as monotherapy (~15 years) and a relatively short course of nitazoxanide combined with albendazole (3 months). Despite continuous daily medical treatment, bone invasion and destruction proceeded. His pain and disability progressively increased.

Unlike the case report described by Winning and others,1 we report a patient with bone hydatid disease that was refractory to treatment with nitazoxanide combined with albendazole.

The patient was born in 1966 in Aksaray, a rural area in Turkey. He had been in frequent contact with dogs owned by his father who was a sheep farmer. At the age of 25, he emigrated to the Netherlands. Hydatid disease of the lumbar spine was diagnosed in 1993 when he had low-energy back trauma. Since then, he was treated with albendazole 400 mg twice a day combined with cimetidine 400 mg twice a day, administered daily without interruption.2 From 1993 to 2005, he had several surgical interventions of his lumbar spine in an attempt to eradicate the bone-invasive hydatid disease and to relieve his low back pain. Finally, in 2005, a vertebral stabilization procedure of the lumbar spine was performed (spondylodesis of vertebrae L3–L5) together with a laminectomy of lumbar vertebra L4, a resection of the left pedicle of vertebra L4, removal of the hydatid cyst from vertebra L4, and cementation of the vertebral defect. This procedure significantly relieved his low back pain. During the 3 months preceding this surgical intervention, he was treated with nitazoxanide 500 mg twice a day combined with albendazole 800 mg twice a day. We reasoned that the higher albendazole sulfoxide plasma levels that may occur when albendazole is combined with nitazoxanide, plus the individual mechanism of action of both albendazole and nitazoxanide against protoscoleces, might be more effective than albendazole alone.35 Postoperatively, albendazole 800 mg twice a day combined with cimetidine 400 mg twice a day was continued on a daily basis without interruption. When the patient was referred to our hospital, cimetidine co-administration was stopped because pharmacokinetic studies had shown that albendazole sulfoxide levels substantially decreased by combining albendazole with cimetidine. 6,7 Magnetic resonance imaging (MRI) scanning was performed before the combined course of nitazoxanide and albendazole and after surgery. The most prominent findings of the preoperative MRI scan were hydatid invasion of the lumbar vertebra L4 and its left pedicle; impression of the spinal channel and dural pouch; and extension of hydatid cysts toward the sacral vertebrae S1 and S2, the left sacroiliac (SI) joint, the left os ileum, and into the gluteus muscle. The left hemipelvis was invaded by hydatid cysts (Figure 1).

Despite continuous daily treatment of albendazole, combined with cimetidine or administered as monotherapy, the MRI scans made 12 months postoperatively showed significant growth of the paravertebral hydatid cyst, extending cranially toward the thoracic vertebra Th12; around the spondylodesis material; toward the skin; inside the osseous spinal channel with protrusion of the dural sac anteriorly; caudally toward the sacrum; and into the left os ileum with significant pelvic invasion and destruction (Figure 2).

Three years later, the patient developed progressive pain in his left hemipelvis and left hip joint, despite continuous daily treatment with albendazole combined with cimetidine. Radiography showed extensive sclerosis of the sacrum, the right sacroiliac joint, and the fractured left hemipelvis. Pelvic destruction was extending into the left hip joint (Figure 3).

Several hydatid cysts were identified. Ultrasonography showed a large (9 × 2.6 cm) paravertebral hydatid cyst in a transitional state (type CE3), encasing the osteosynthesis material in the lower lumbar spine.8 Another large hydatid cyst complex, some cysts in an active state (type CE1) and others in a transitional stage (type CE3a), was extending from the left iliac wing toward the left gluteus muscle.

Both the paravertebral and the parailiacal hydatid cysts were treated percutaneously. The paravertebral hydatid cysts contained ochre colored turbid fluid and were considered non-viable. At microscopy, no protoscoleces or hooklets could be identified in the cyst fluid. From two parailiacal hydatid cysts, small amounts of almost clear fluid were aspirated, and from another parailiacal cyst crystal, clear fluid was aspirated. All three parailiacal hydatid cysts were considered as viable and were treated with the so-called PAIR method (echo-guided puncture, aspiration, injection, and re-aspiration of a scolecidal).9 However, in the native cyst fluid of these parailiacal hydatid cysts, no protoscoleces or hooklets could be identified at microscopy.

Unfortunately, in our patient, bone-invasive hydatid disease was refractory to both long-term daily treatment with albendazole, combined with cimetidine or administered as monotherapy (~15 years), and a relatively short course of nitazoxanide combined with albendazole (3 months). Despite continuous daily medical treatment, bone invasion and destruction proceeded. His pain and disability have progressively increased. This observation confirms the clinical experience that bone-invasive hydatidosis is very difficult to eradicate with medical treatment.

Figure 1.
Figure 1.

T1-weighted, gadolinium-enhanced MRI scans 3 months before surgery. The arrows in A indicate hydatid invasion of lumbar vertebra L4. The arrows in B indicate hydatid invasion of the left os ileum (R, right; L, left).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 81, 3; 10.4269/ajtmh.2009.81.446

Figure 2.
Figure 2.

T2-weighted MRI scans 12 months postoperatively. The arrows in A indicate extension of the paravertebral hydatid cyst cranially toward thoracic vertebra Th12, subcutaneously and around the spondylodesis material. The dotted arrows indicate the spondylodesis material in lumbar vertebrae L5 and L3 (A, anterior; P, posterior). The arrows in B indicate progression of the hydatid invasion into the left os ileum (R, right; L, left).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 81, 3; 10.4269/ajtmh.2009.81.446

Figure 3.
Figure 3.

Computed tomography scan of the patient 3.5 years postoperatively. Arrows in A and B indicate the parapelvic hydatid cyst complex invading into the fractured left os ileum and extending into the fractured hip joint (acetabulum).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 81, 3; 10.4269/ajtmh.2009.81.446

*

Address correspondence to Hans G. Schipper, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail: H.G.Schipper@amc.uva.nl

Authors’ addresses: Hans G. Schipper, Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands, E-mail: H.G.Schipper@amc.uva.nl. Suat Simsek and Michiel A. van Agtmael, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. Krijn P. van Lienden, Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands.

REFERENCES

  • 1

    Winning A, Braslins P, McCarthy JS, 2009. Case report: nitazoxanide for treatment of refractory bony hydatid disease. Am J Trop Med Hyg 80 :176–178.

    • Search Google Scholar
    • Export Citation
  • 2

    Wen H, Zhang HW, Muhmut M, Zou PF, New RR, Craig PS, 1994. Initial observation on albendazole in combination with cimetidine for the treatment of human cystic echinococcosis. Ann Trop Med Parasitol 88 :49–52.

    • Search Google Scholar
    • Export Citation
  • 3

    Stettler M, Fink R, Walker M, Gottstein B, Geary TG, Rossignol JF, Hemphill A, 2003. In vitro parasiticidal effect of nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrob Agents Chemother 47 :467–474.

    • Search Google Scholar
    • Export Citation
  • 4

    Stettler M, Rossignol JF, Fink R, Walker M, Gottstein B, Merli M, Theurillat R, Thormann W, Dricot E, Segers R, Hemphill A, 2004. Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. Int J Parasitol 34 :615–624.

    • Search Google Scholar
    • Export Citation
  • 5

    Walker M, Rossignol JF, Torgerson P, Hemphill A, 2004. In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes. J Antimicrob Chemother 54 :609–616.

    • Search Google Scholar
    • Export Citation
  • 6

    Schipper HG, Koopmans RP, Nagy J, Butter JJ, Kager PA, Van Boxtel CJ, 2000. Effect of dose increase or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 63 :270–273.

    • Search Google Scholar
    • Export Citation
  • 7

    Nagy J, Schipper HG, Koopmans RP, Butter JJ, Van Boxtel CJ, Kager PA, 2002. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 66 :260–263.

    • Search Google Scholar
    • Export Citation
  • 8

    WHO Informal Working Group, 2003. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 85 :253–261.

    • Search Google Scholar
    • Export Citation
  • 9

    Filice C, Brunetti E, Bruno R, Crippa FG, WHO-Informal Working Group on Echinococcosis-PAIR Network, 2000. Percutaneous drainage of echinococcal cysts (PAIR-puncture, aspiration, injection, reaspiration): results of a worldwide survey for assessment of its safety and efficacy. Gut 47 :156–157.

    • Search Google Scholar
    • Export Citation
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