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ABSTRACT |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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CASE REPORT |
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Gastro-duodenal aspiration was started and a steroid bolus (methylprednisolone, 120 mg/day) was given for seven days. At day 7, his condition worsened and he was admitted to the Oncology Department of the Hôpital Européen Georges Pompidou. Physical examination showed fever, intestinal ileus, headache, confusion, and dyspnea. The white blood cell count was 11.3 x 109/L with 10.5 x 109/L neutrophils and 0.5 x 109/L eosinophils. The C-reactive protein level was 66 mg/L. Microbiologic findings showed Klebsiella pneumoniae in a peripheral blood culture and Escherichia coli meningitis. He was then treated with intravenous cefotaxime (2 grams every 4 hours for 48 hours, then 2 grams every 6 hours for 8 or more days) ciprofloxacine (200 mg twice a day for 10 days). Demonstration of numerous S. stercoralis rhabditiform and filariform larvae in the gastric fluid confirmed Strongyloides hyperinfection syndrome. Oral ivermectin (12 mg/day) plus oral albendazole (400 mg/day) were given in a nasogastric catheter. Steroids were decreased rapidly during four days and then discontinued. Two days after initiation of the anthelminthic therapy, the patient showed acute respiratory failure due to interstitial pneumonitis. He was referred to the intensive care unit.
Bronchoalveolar lavage fluid, gastric fluid, and stool specimens showed persistent numerous S. stercoralis rhabditiform and filariform larvae. The eosinophil count increased to 1.79 x 109/L. Due to the persistence of the intestinal ileus, the absorption and efficacy of the oral treatment were uncertain. As a life-saving therapy, after informed consent of the patient’s family and agreement of the French drug administration (Agence Française de Sécurité Sanitaires des Produits de Santé) were obtained, a veterinary formulation of parenteral ivermectin (Ivomec®; Merial, Lyon, France) was given (6 mg twice a day) by subcutaneous injections in the thighs or abdomen wall. Treatment with oral albendazole was continued. The patient’s condition improved rapidly and the amount of living larva in the stools decreased dramatically 48 hours after the initiation of parenteral ivermectin. Four days later, no larva could be demonstrated in the stool, gastric fluid, or sputum. Parenteral ivermectin was administered for six days (6 mg twice a day) and was then replaced by the oral route (12 mg/day) for six additional days. The tolerance of the injections was good, except for transient pain at the injection site in the abdomen. The eosinophil count remained high (1.0 x 109/L) for two weeks after the beginning of oral treatment and then decreased to a stable count of 0.2 x 109/L. The patient did not have any relapse of the S. stercoralis infection after discontinuation of treatment, but he died five weeks later of progressive lymphoma, despite a new regimen of interferon-
and zidovudine.
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DISCUSSION |
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Currently available regimens for treatment of strongyloidiasis in humans include only oral agents. Ivermectin is now recognized as the drug of choice because it showed comparable and better rates of larval clearance than thiabendazole and albendazole, respectively, and fewer and comparable side effects than thiabendazole and albendazole, respectively.7,8 Albendazole has been used successfully in treating S. hyperinfection syndrome.9 However, since the clinical features of S. stercoralis hyperinfection include intestinal ileus, oral absorption of the drugs may be impaired. Only a few reports of non-oral therapy for hyperinfection syndrome have been published. One patient with bowel obstruction was successfully treated by rectal administration of thiabendazole.10 Tarr and others reported the use of rectal ivermectin enemas concurrently to oral albendazole and ivermectin in a patient with ileus but without diarrhea.11 Only two previous reports described the successful subcutaneous administration of ivermectin to human patients with S. stercoralis hyperinfection syndrome12 (Turner SA and others, unpublished data). In two of the three patients, as in our patient, the hyperinfection syndrome was associated with an HTLV-I infection. Since these studies reported a daily dose of 200 µg/kg/day, up to 14 consecutive days in the patient described by Turner and others (unpublished data), we chose the same daily regimen.12 No significant accumulation of ivermectin was seen in the patient described by Turner and others (unpublished data). In our patient, the subcutaneous treatment was replaced by the oral route after six days because no larva could be detected in the specimen collected and the condition of the patient improved.
Several veterinary avermectins (including ivermectin) are now available. These drugs are frequently used for the treatment and prophylaxis of gastrointestinal strongyloidiases in cattle at a dosage of 200 µg/kg. However, the approval process for drugs for veterinary use is different from those for human use. Many parenteral formulations are licensed for use in cattle because these formulations are much more convenient to use than oral formulations and the dosage is not variable. The present case confirms the efficacy and safety for the salvage therapy of humans of a parenteral administration of veterinary ivermectin that is not currently licensed for human use. However, oral albendazole was concurrently given to our patient and could have provided a partial and late positive effect.
An association between HTLV-I infection and S. stercoralis increased prevalence, treatment failure, recurrent strongyloidiasis, and hyperinfection syndrome has been reported.2 However, this association remains controversial.13 Conversely, it has been suggested that S. stercoralis might be a cofactor in the pathogenesis of HTLV-I-induced T cell lymphomas.2,14 As observed in our patient before treatment, the lack of eosinophilia is typical in patients infected with HTLV-1 infection; this retrovirus enhances the production of interferon-
, and decreases the production of interleukin-5 and the IgE response.15 In our patient, corticosteroid therapy could have contributed to the lack of eosinophilia.
This report confirms that the subcutaneous use of a veterinary ivermectin preparation is a safe salvage therapy in patients with S. stercoralis hyperinfection syndrome unresponsive to oral therapy. Further studies assessing on a larger scale the pharmacokinetics parameters and tolerance of parenteral ivermectin are urgently needed.
Received September 28, 2004. Accepted for publication January 19, 2005.
* Address correspondence to Muriel Cornet, Laboratoire de Microbiologe, Hôtel-Dieu, 1, Place du Parvis Notre-Dame, 75181, Paris Cedex 04, France. E-mail: mucornet{at}aol.com 
Authors’ addresses: Jerome Pacanowski, Service de Maladies Infectieuses, Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine, 75012 Paris, France. Marie Dos Santos and Veronique Lavarde, Laboratoire de Microbiologie, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France. Antoine Roux, Service de Pneumologie, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France. Christine Le Maignan, Service d’Oncologie Médicale, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, 75015 Paris, France. Jacques Guillot, Département de Parasitologie-Mycologie, Ecole Vétérinaire d’Alfort, 7 Avenue du Général de Gaulle, 94700 Maisons-Alfort, France. Muriel Cornet, Laboratoire de Microbiologie, Hôtel-Dieu, 1, Place du Parvis Notre-Dame, 75181, Paris Cedex 04, France, Telephone: 33-1-42-34-82-73, Fax: 33-1-42-34-87-19, E-mail: mucornet{at}aol.com.
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This article has been cited by other articles:
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  V. Leung, G. N. Al-Rawahi, J. Grant, L. Fleckenstein, and W. Bowie Failure of Subcutaneous Ivermectin in Treating Strongyloides Hyperinfection Am J Trop Med Hyg, December 1, 2008; 79(6): 853 - 855. [Abstract] [Full Text] [PDF]
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 M. Segarra-Newnham Manifestations, Diagnosis, and Treatment of Strongyloides stercoralis Infection Ann. Pharmacother., December 1, 2007; 41(12): 1992 - 2001. [Abstract] [Full Text] [PDF]
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 M. Boscolo, M. Gobbo, W. Mantovani, M. Degani, M. Anselmi, G. B. Monteiro, S. Marocco, A. Angheben, M. Mistretta, M. Santacatterina, et al. Evaluation of an Indirect Immunofluorescence Assay for Strongyloidiasis as a Tool for Diagnosis and Follow-Up Clin. Vaccine Immunol., February 1, 2007; 14(2): 129 - 133. [Abstract] [Full Text] [PDF]
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