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Successful treatment of niclosamide- 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 b
Department of Zoology, University of Kashmir, Srinigar, India 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 Taenia saginata; Prevalence; Niclosamide; Praziquantel; Drug resistance; Nitazoxanide
Summary Background: Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately cooked beef that contains the larvae or cysticerci of T. saginata. Niclosamide and praziquantel have proved effective for its treatment but treatment failures are well known. We report herein the results of nitazoxanide therapy. Methods: A prospective study was conducted in 18 children and 34 adults to assess the efficacy 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. Posttreatment 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 Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately cooked beef that contains the larvae or * Corresponding author. Tel.: +91 194 2312092; fax: +91 194 2403470. E-mail address: [email protected] (S.A. Zargar).
cysticerci of T. saginata. It is found worldwide and about 45 million suffer from this disease. Its greatest economic impact, however, is within tropical and sub-tropical cattle rearing countries: Africa, the Middle East, Central and South America, Europe, and Asia. Although many antimicrobial drugs are used to treat T. saginata infections, niclosamide and praziquantel have 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
81
Treatment of beef tapeworm infection with nitazoxanide failures are well known.1—4 In Kashmir, India, with a 95% Muslim population and absence of pigs, T. saginata is endemic but Taenia solium infection is almost unknown. We report herein the results of nitazoxanide therapy in 52 patients, identified in a population-based epidemiological survey, infected with T. saginata resistant to multiple courses of niclosamide, praziquantel, or both.
Materials and methods Between 2004 and 2005, an epidemiological survey for taeniasis was conducted in Sonawari tehsil in the district of Baramulla, Kashmir, India involving 8894 persons from semiurban and urban villages. During this survey 55 persons with confirmed T. saginata infection resistant to multiple courses of niclosamide or praziquantel or both were identified. Three patients were excluded because one was pregnant and two were lactating. The remaining 52 gave written informed consent to participate in the study. There were 18 children, 24 men, and 10 women. They ranged in age from 5 to 65 years, with a mean of 26.2 16.1 years. The duration of infection ranged from 8 months to 15 years with a mean of 3.7 3.1 years. All patients had received two to seven courses (median three) of niclosamide and 10 had received one to three courses of praziquantel (median two) but had continued to pass proglottides with stools. All had demonstrated a relapse 3—6 weeks after initiation of treatment. Symptoms included passage of proglottides in stools and/or trousers while bending, running or washing (n = 52), increased appetite (n = 33), abdominal discomfort (n = 23), nausea (n = 15), and diarrhea (n = 3). Nitazoxanide was administered twice daily for 3 days in 500-mg doses for those aged over 14 years and 20 mg/kg body weight/day in children aged 5—14 years without prior fasting or laxative use. All patients underwent physical examination including analysis of hemogram, serum chemistry (liver function tests, glucose, urea, sodium and potassium), and urine, and electrocardiogram before and 7 days after treatment. Stool specimens were collected for routine examination. Egg viability was tested by staining with methylene blue, and egg count by Stoll’s method. Patients were followed at 1, 2, 4, 8, and 12 weeks for the passage of proglottides, and fecal samples were examined for the presence, number, and viability of Taenia eggs. Overall 51 of 52 patients (98.1%) responded and passed worms ranging from 1 to 6 meters in length, but no worm contained scolex. All responders stopped passing proglottides at a median of 3 days (range 1—5) days. Of the 41 patients who provided stool specimens in the first week, 38 (92.7%) had negative stool examinations for proglottides and eggs. The 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 and eggs with a cure rate of 98.1% (51 of 52 patients). Thirty-two patients (15 children and 17 adolescents and adults) were positive for another parasite in stool at study enrollment. These included Ascaris lumbricoides (n = 19), Trichuris trichiura (n = 6), Giardia lamblia (n = 4), and mixed infections (n = 3). Nitazoxanide cured 89.5% (17/19), 100% (6/6), 75% (3/4), and 66.7% (2/3) of the cases of ascariasis, trichuriasis, giardiasis, and mixed infections, respectively. Eleven adverse events occurred in seven patients including diarrhea (n = 3), mild abdominal pain (n = 3), headache
(n = 2), nausea (n = 2), and giddiness (n = 1). All adverse events were mild and transitory in nature and resolved spontaneously without discontinuation of treatment. No abnormality was observed in hemogram, blood chemistry values, or urine analysis.
Discussion The present study demonstrated that a 3-day course of nitazoxanide cured 98.1% of patients infected with T. saginata unresponsive to niclosamide, praziquantel, or both. Nitazoxanide was safe and well tolerated. Adverse events reported by patients were mild and resolved easily without any treatment. In two previous clinical studies in patients infected with T. saginata, nitazoxanide cured 21 of 22 patients (95.5%) and five of five patients (100%).5,6 Taenia saginata infections are endemic in Kashmir, India. Niclosamide or praziquantel are safe and effective drugs for its treatment but therapeutic failures with these drugs are encountered. Taeniasis is not only a significant public health problem but also an important economic problem in endemic areas. It is becoming increasingly clear that it should be given greater priority because of its economic impact, particularly in resource-poor countries. Most patients are asymptomatic and become aware of the infection when they notice proglottides or segments of tapeworm in stools or motile proglottides emerging from the anus, in trousers, on bedding, while bending, walking, and running, and this can cause huge psychological distress. Rarely, migration of motile proglottides or worm to ectopic sites such as the appendix, biliary tree, or pancreatic duct can cause morbidity. Nitazoxanide (2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide) is a new thiazolide antiparasitic agent that shows excellent activity against a wide variety of protozoa and helminths. Although developed in 1980, the literature on its use is scanty because it only received approval by the US FDA in November 2002 for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia in children and adults. It became available in India in June 2004. It is also effective against a broad range of other parasitic infections including Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Fasciola hepatica, Entamoeba histolytica, and Taenia solium/saginata.7 In conclusion nitazoxanide is a safe, effective, and inexpensive drug for the treatment of niclosamide- and praziquantel-resistant T. saginata infections. It represents a significant addition to the antiparasitic arsenal in the treatment of intestinal parasitic infections.
Acknowledgments Financial support for this study was provided by Sher-i-Kashmir Institute of Medical sciences. Conflict of interest: No conflict of interest to declare.
References 1. Perera DR, Western KA, Schultz MG. Niclosamide treatment of cestodiasis: clinical trials in the United States. Am J Trop Med Hyg 1970;19:610—2.
82 2. Vermund SH, MacLeod S, Goldstein RG. Taeniasis unresponsive to a single dose of niclosamide: case report of persistent infection with Taenia saginata and a review of therapy. Rev Infect Dis 1986;8:423—6. 3. Esteves FM, Silva-Vergara ML, Carvalho AC. Epidemiologic survey of taeniasis in Health and Family Program in Uberaba, MG. Rev Soc Bras Med Trop 2005;38:530—1. 4. Koul PA, Waheed A, Hayat M, Sofi BA. Praziquantel in niclosamideresistant Taenia saginata infection. Scand J Infect Dis 1999;31:603—4.
M. Lateef et al. 5. Rossignol JF, Maisonneuve H. Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana infections. Am J Trop Med Hyg 1984;33:511—2. 6. Romero Cabello R, Guerrero LR, Munoz Garcia MR, Geyne Cruz A. Nitazoxanide for the treatment of intestinal protozoan and helminthic infections in Mexico. Trans R Soc Trop Med Hyg 1997;91:701—3. 7. Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 2005;40:1173—80.
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 b
Department of Zoology, University of Kashmir, Srinigar, India 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 Taenia saginata; Prevalence; Niclosamide; Praziquantel; Drug resistance; Nitazoxanide
Summary Background: Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately cooked beef that contains the larvae or cysticerci of T. saginata. Niclosamide and praziquantel have proved effective for its treatment but treatment failures are well known. We report herein the results of nitazoxanide therapy. Methods: A prospective study was conducted in 18 children and 34 adults to assess the efficacy 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. Posttreatment 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 Beef tapeworm (Taenia saginata) infection is acquired by eating inadequately cooked beef that contains the larvae or * Corresponding author. Tel.: +91 194 2312092; fax: +91 194 2403470. E-mail address: [email protected] (S.A. Zargar).
cysticerci of T. saginata. It is found worldwide and about 45 million suffer from this disease. Its greatest economic impact, however, is within tropical and sub-tropical cattle rearing countries: Africa, the Middle East, Central and South America, Europe, and Asia. Although many antimicrobial drugs are used to treat T. saginata infections, niclosamide and praziquantel have 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
81
Treatment of beef tapeworm infection with nitazoxanide failures are well known.1—4 In Kashmir, India, with a 95% Muslim population and absence of pigs, T. saginata is endemic but Taenia solium infection is almost unknown. We report herein the results of nitazoxanide therapy in 52 patients, identified in a population-based epidemiological survey, infected with T. saginata resistant to multiple courses of niclosamide, praziquantel, or both.
Materials and methods Between 2004 and 2005, an epidemiological survey for taeniasis was conducted in Sonawari tehsil in the district of Baramulla, Kashmir, India involving 8894 persons from semiurban and urban villages. During this survey 55 persons with confirmed T. saginata infection resistant to multiple courses of niclosamide or praziquantel or both were identified. Three patients were excluded because one was pregnant and two were lactating. The remaining 52 gave written informed consent to participate in the study. There were 18 children, 24 men, and 10 women. They ranged in age from 5 to 65 years, with a mean of 26.2 16.1 years. The duration of infection ranged from 8 months to 15 years with a mean of 3.7 3.1 years. All patients had received two to seven courses (median three) of niclosamide and 10 had received one to three courses of praziquantel (median two) but had continued to pass proglottides with stools. All had demonstrated a relapse 3—6 weeks after initiation of treatment. Symptoms included passage of proglottides in stools and/or trousers while bending, running or washing (n = 52), increased appetite (n = 33), abdominal discomfort (n = 23), nausea (n = 15), and diarrhea (n = 3). Nitazoxanide was administered twice daily for 3 days in 500-mg doses for those aged over 14 years and 20 mg/kg body weight/day in children aged 5—14 years without prior fasting or laxative use. All patients underwent physical examination including analysis of hemogram, serum chemistry (liver function tests, glucose, urea, sodium and potassium), and urine, and electrocardiogram before and 7 days after treatment. Stool specimens were collected for routine examination. Egg viability was tested by staining with methylene blue, and egg count by Stoll’s method. Patients were followed at 1, 2, 4, 8, and 12 weeks for the passage of proglottides, and fecal samples were examined for the presence, number, and viability of Taenia eggs. Overall 51 of 52 patients (98.1%) responded and passed worms ranging from 1 to 6 meters in length, but no worm contained scolex. All responders stopped passing proglottides at a median of 3 days (range 1—5) days. Of the 41 patients who provided stool specimens in the first week, 38 (92.7%) had negative stool examinations for proglottides and eggs. The 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 and eggs with a cure rate of 98.1% (51 of 52 patients). Thirty-two patients (15 children and 17 adolescents and adults) were positive for another parasite in stool at study enrollment. These included Ascaris lumbricoides (n = 19), Trichuris trichiura (n = 6), Giardia lamblia (n = 4), and mixed infections (n = 3). Nitazoxanide cured 89.5% (17/19), 100% (6/6), 75% (3/4), and 66.7% (2/3) of the cases of ascariasis, trichuriasis, giardiasis, and mixed infections, respectively. Eleven adverse events occurred in seven patients including diarrhea (n = 3), mild abdominal pain (n = 3), headache
(n = 2), nausea (n = 2), and giddiness (n = 1). All adverse events were mild and transitory in nature and resolved spontaneously without discontinuation of treatment. No abnormality was observed in hemogram, blood chemistry values, or urine analysis.
Discussion The present study demonstrated that a 3-day course of nitazoxanide cured 98.1% of patients infected with T. saginata unresponsive to niclosamide, praziquantel, or both. Nitazoxanide was safe and well tolerated. Adverse events reported by patients were mild and resolved easily without any treatment. In two previous clinical studies in patients infected with T. saginata, nitazoxanide cured 21 of 22 patients (95.5%) and five of five patients (100%).5,6 Taenia saginata infections are endemic in Kashmir, India. Niclosamide or praziquantel are safe and effective drugs for its treatment but therapeutic failures with these drugs are encountered. Taeniasis is not only a significant public health problem but also an important economic problem in endemic areas. It is becoming increasingly clear that it should be given greater priority because of its economic impact, particularly in resource-poor countries. Most patients are asymptomatic and become aware of the infection when they notice proglottides or segments of tapeworm in stools or motile proglottides emerging from the anus, in trousers, on bedding, while bending, walking, and running, and this can cause huge psychological distress. Rarely, migration of motile proglottides or worm to ectopic sites such as the appendix, biliary tree, or pancreatic duct can cause morbidity. Nitazoxanide (2-acetyloxy-N-(5-nitro-2-thiazolyl)benzamide) is a new thiazolide antiparasitic agent that shows excellent activity against a wide variety of protozoa and helminths. Although developed in 1980, the literature on its use is scanty because it only received approval by the US FDA in November 2002 for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia in children and adults. It became available in India in June 2004. It is also effective against a broad range of other parasitic infections including Hymenolepis nana, Trichuris trichiura, Ascaris lumbricoides, Fasciola hepatica, Entamoeba histolytica, and Taenia solium/saginata.7 In conclusion nitazoxanide is a safe, effective, and inexpensive drug for the treatment of niclosamide- and praziquantel-resistant T. saginata infections. It represents a significant addition to the antiparasitic arsenal in the treatment of intestinal parasitic infections.
Acknowledgments Financial support for this study was provided by Sher-i-Kashmir Institute of Medical sciences. Conflict of interest: No conflict of interest to declare.
References 1. Perera DR, Western KA, Schultz MG. Niclosamide treatment of cestodiasis: clinical trials in the United States. Am J Trop Med Hyg 1970;19:610—2.
82 2. Vermund SH, MacLeod S, Goldstein RG. Taeniasis unresponsive to a single dose of niclosamide: case report of persistent infection with Taenia saginata and a review of therapy. Rev Infect Dis 1986;8:423—6. 3. Esteves FM, Silva-Vergara ML, Carvalho AC. Epidemiologic survey of taeniasis in Health and Family Program in Uberaba, MG. Rev Soc Bras Med Trop 2005;38:530—1. 4. Koul PA, Waheed A, Hayat M, Sofi BA. Praziquantel in niclosamideresistant Taenia saginata infection. Scand J Infect Dis 1999;31:603—4.
M. Lateef et al. 5. Rossignol JF, Maisonneuve H. Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana infections. Am J Trop Med Hyg 1984;33:511—2. 6. Romero Cabello R, Guerrero LR, Munoz Garcia MR, Geyne Cruz A. Nitazoxanide for the treatment of intestinal protozoan and helminthic infections in Mexico. Trans R Soc Trop Med Hyg 1997;91:701—3. 7. Fox LM, Saravolatz LD. Nitazoxanide: a new thiazolide antiparasitic agent. Clin Infect Dis 2005;40:1173—80.