And Praziquantel-Resistant Beef Tapeworm Infection with Nitazoxanide

International Journal of Infectious Diseases (2008) 12, 80—82

http://intl.elsevierhealth.com/journals/ijid

Successful treatment of niclosamide- and praziquantel-resistant beef tapeworm infection with nitazoxanide

Mohammad Lateef a, Showkat Ali Zargar b,*, Abdul Rashid Khan a, Muzzaffar Nazir b, Abid Shoukat b a Department of Zoology, University of Kashmir, Srinigar, India b Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India

Received 31 October 2006; received in revised form 22 January 2007; accepted 21 April 2007 Corresponding Editor: William Cameron, Ottawa, Canada

KEYWORDS Summary Taenia saginata; Background: Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately Prevalence; cooked beef that contains the larvae or cysticerci of T. saginata. Niclosamide and praziquantel Niclosamide; have proved effective for its treatment but treatment failures are well known. We report herein Praziquantel; the results of nitazoxanide therapy. Drug resistance; Methods: A prospective study was conducted in 18 children and 34 adults to assess the efﬁcacy Nitazoxanide and safety of nitazoxanide in the treatment of niclosamide- and praziquantel-resistant T. saginata infection. Nitazoxanide was administered twice daily for 3 days in 500-mg doses for those aged over 14 years and at 20 mg/kg body weight/day in children aged 5—14 years. Post- treatment follow-up was undertaken at 1, 2, 4, 8, and 12 weeks for fecal samples for proglottides, and to check the presence, number, and viability of Taenia eggs. Results: Nitazoxanide cured 51 of 52 (98.1%) patients. Mild side effects occurred in seven patients, which resolved spontaneously. There were no abnormalities in laboratory parameters. Conclusions: Nitazoxanide is a safe, effective, inexpensive, and well-tolerated drug for the treatment of niclosamide- and praziquantel-resistant beef tapeworm infection. # 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Introduction cysticerci of T. saginata. It is found worldwide and about 45 million suffer from this disease. Its greatest economic Beef tapeworm (Taenia saginata) infection is acquired by impact, however, is within tropical and sub-tropical cattle eating inadequately cooked beef that contains the larvae or rearing countries: Africa, the Middle East, Central and South America, Europe, and Asia. * Corresponding author. Tel.: +91 194 2312092; Although many antimicrobial drugs are used to treat T. fax: +91 194 2403470. saginata infections, niclosamide and praziquantel have E-mail address: [email protected] (S.A. Zargar). proved effective for its treatment; however treatment

1201-9712/$32.00 # 2007 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2007.04.017 Treatment of beef tapeworm infection with nitazoxanide 81 failures are well known.1—4 In Kashmir, India, with a 95% (n = 2), nausea (n = 2), and giddiness (n = 1). All adverse Muslim population and absence of pigs, T. s a g i n a t a is ende- events were mild and transitory in nature and resolved mic but Taenia solium infection is almost unknown. We spontaneously without discontinuation of treatment. No report herein the results of nitazoxanide therapy in 52 abnormality was observed in hemogram, blood chemistry patients, identified in a population-based epidemiological values, or urine analysis. survey, infected with T. s a g i n a t a resistant to multiple courses of niclosamide, praziquantel, or both. Discussion Materials and methods The present study demonstrated that a 3-day course of nitazoxanide cured 98.1% of patients infected with T. sagi- Between 2004 and 2005, an epidemiological survey for tae- nata unresponsive to niclosamide, praziquantel, or both. niasis was conducted in Sonawari tehsil in the district of Nitazoxanide was safe and well tolerated. Adverse events Baramulla, Kashmir, India involving 8894 persons from semi- reported by patients were mild and resolved easily without urban and urban villages. During this survey 55 persons with any treatment. In two previous clinical studies in patients confirmed T. saginata infection resistant to multiple courses infected with T. saginata, nitazoxanide cured 21 of 22 of niclosamide or praziquantel or both were identified. Three patients (95.5%) and five of five patients (100%).5,6 Taenia patients were excluded because one was pregnant and two saginata infections are endemic in Kashmir, India. Niclosa- were lactating. The remaining 52 gave written informed mide or praziquantel are safe and effective drugs for its consent to participate in the study. There were 18 children, treatment but therapeutic failures with these drugs are 24 men, and 10 women. They ranged in age from 5 to 65 encountered. years, with a mean of 26.2 Æ 16.1 years. The duration of Taeniasis is not only a significant public health problem but infection ranged from 8 months to 15 years with a mean of also an important economic problem in endemic areas. It is 3.7 Æ 3.1 years. All patients had received two to seven becoming increasingly clear that it should be given greater courses (median three) of niclosamide and 10 had received priority because of its economic impact, particularly in one to three courses of praziquantel (median two) but had resource-poor countries. Most patients are asymptomatic continued to pass proglottides with stools. All had demon- and become aware of the infection when they notice proglot- strated a relapse 3—6 weeks after initiation of treatment. tides or segments of tapeworm in stools or motile proglot- Symptoms included passage of proglottides in stools and/or tides emerging from the anus, in trousers, on bedding, while trousers while bending, running or washing (n = 52), bending, walking, and running, and this can cause huge increased appetite (n = 33), abdominal discomfort (n = 23), psychological distress. Rarely, migration of motile proglot- nausea (n = 15), and diarrhea (n = 3). Nitazoxanide was admi- tides or worm to ectopic sites such as the appendix, biliary nistered twice daily for 3 days in 500-mg doses for those aged tree, or pancreatic duct can cause morbidity. over 14 years and 20 mg/kg body weight/day in children aged Nitazoxanide (2-acetyloxy-N-(5-nitro-2-thiazolyl)benza- 5—14 years without prior fasting or laxative use. mide) is a new thiazolide antiparasitic agent that shows All patients underwent physical examination including ana- excellent activity against a wide variety of protozoa and lysis of hemogram, serum chemistry (liver function tests, helminths. Although developed in 1980, the literature on glucose, urea, sodium and potassium), and urine, and electro- its use is scanty because it only received approval by the US cardiogram before and 7 days after treatment. Stool speci- FDA in November 2002 for the treatment of diarrhea caused mens were collected for routine examination. Egg viability was by Cryptosporidium parvum and Giardia lamblia in children tested by staining with methylene blue, and egg count by and adults. It became available in India in June 2004. It is also Stoll’s method. Patients were followed at 1, 2, 4, 8, and 12 effective against a broad range of other parasitic infections weeks for the passage of proglottides, and fecal samples were including Hymenolepis nana, Trichuris trichiura, Ascaris lum- examined for the presence, number, and viability of Taenia bricoides, Fasciola hepatica, Entamoeba histolytica, and eggs. Overall 51 of 52 patients (98.1%) responded and passed Taenia solium/saginata.7 worms ranging from 1 to 6 meters in length, but no worm In conclusion nitazoxanide is a safe, effective, and inex- contained scolex. All responders stopped passing proglottides pensive drug for the treatment of niclosamide- and prazi- at a median of 3 days (range 1—5) days. Of the 41 patients who quantel-resistant T. saginata infections. It represents a provided stool specimens in the first week, 38 (92.7%) had significant addition to the antiparasitic arsenal in the treat- negative stool examinations for proglottides and eggs. The ment of intestinal parasitic infections. reduction was in excess of 98% in egg count and from a median of 100% to 0% in viability at 1 week. Subsequent stool examinations at 2, 4, 8, and 12 weeks were negative for proglottides Acknowledgments and eggs with a cure rate of 98.1% (51 of 52 patients). Thirty-two patients (15 children and 17 adolescents and Financial support for this study was provided by Sher-i-Kash- adults) were positive for another parasite in stool at study mir Institute of Medical sciences. enrollment. These included Ascaris lumbricoides (n = 19), Conflict of interest: No conflict of interest to declare. Trichuris trichiura (n = 6), Giardia lamblia (n = 4), and mixed infections (n = 3). 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