Comparative parasitological and electron microscopic studies on the effects of Nitazoxanide and Praziquantel in Schistosoma mansoni-infected mice

  • Authors

    • Hend A. El-Taweel Department of Medical Parasitology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
    • Mona H. El-Sayad
    • Sahar A. Abu Helw
    • Mohammad A. Al-Kazzaz
  • Antischistosomal, Electronmicroscopy, Nitazoxanide, Parasitological, Praziquantel, Schistosoma.
  • This study was designed to evaluate antischistosomal activity of Nitazoxanide (NTZ) in Schistosoma mansoni-infected mice compared to Praziquantel (PZQ). Fifty four infected mice were recruited into 3 groups, each of 18 mice. Group 1 was infected non-treated control. Group 2 was infected and then treated with PZQ 500 mg for two days, and group 3 was infected and treated with NTZ 100 mg/kg for seven days. Efficacy of drugs was assessed by Parasitological, and scanning electron microscopic studies. PZQ reduced (4.9%, 22.5% and 50.7%) of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs, (20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load whereas, NTZ reduced (4.9%, 22.5% and 50.7%),of faecal eggs, (22%, 22.6% and 55.1%) of intestinal eggs ,(20.4%, 44.3% and 46.7%) of hepatic egg counts and (27%, 45.1% and 64.9%) of total worm load at 1, 2 and 4 WPT, respectively. The percentages of dead eggs were more than 80% after PZQ treatment and only 30% after NTZ at 4 WPT. PZQ showed extensive tegumental damages in male and female worms more than NTZ at 2 WPT. Our findings concluded that Nitazoxanide showed weaker antischistosomal activity in animal models than praziquantel.

  • References

    1. [1] Abaza H, El-Zayadi A, Kabil SM, Rizk H (1998) Nitazoxanide in the treatment of patients with intestinal protozoan and helminthic infections: a report on 546 patients in Egypt. Curr Ther Res 59:116–121.

      [2] Abdulla MH, Ruelas DS, Wolff B, Snedecor J, Lim KC, Xu F, et al. (2009) Drug Discovery for Schistosomiasis: Hit and Lead Compounds Identified in a Library of Known Drugs by Medium-Throughput Phenotypic Screening. PLoS Negl Trop Dis 3(7): e478.

      [3] Abou-El-Maatti DM, Atteya FM, Ghattas MH (2006) Oxidative stress and vascular endothelial growth factor in an experimental animal model of Schistosoma mansoni treated with myrrh or praziquantel. Egypt J Biochem Mol Biol 24(1):25-39.

      [4] Aires AL, Ximenes ECPA, Silva RAR, Barbosa VX, Góes AS, Peixoto CA, et al. (2014) Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms. Exp Parasitol 142: 83–90.

      [5] Aly AMN (2010) A diagnostic approach to detect murine Schistosoma mansoni infection using a polymerase chain reaction (PCR) technique. MSc.Thesis, Department of applied chemistry, Medical Research Institute, University of Alexandria, Alexandria; Egypt.

      [6] Araújo N, Kohn A, Katz N (1991) Activity of the artemether in experimental schistosomiasis mansoni. Mem Inst Oswaldo Cruz 86 (Suppl 2):185-8.

      [7] Bakr M, El-Sobky M, Harba N, Hassb El-Nabi S (2009) Study of in vivo and in vitro effects of Mirazid on murine schistosomiasis mansoni. J schistosomiasis Infect Endem Dis 31:35-49.

      [8] Barakat RMR (2013) Epidemiology of Schistosomiasis in Egypt: Travel through Time: Review. J Adv Res 4:425–432.

      [9] Botros SS, Mahmoud MR, Moussa MM, Nosseir MM (2007) Immuno- histopathological and biochemical changes in Schistosoma mansoni-infected mice treated with artemether. J Infect 55: 470-7.

      [10] Botros S, William S, Ebeid F, Cioli D, Katz N, Day T , et al . (2004) Lack of evidence for an antischistosomal activity of myrrh in experimental animals. Am J Trop Med Hyg 71: 206-10.

      [11] Bricker CS, Depenbusch A, Bennett JL, Thompson P (1983) The relationship between tegumental disruption and muscle contraction in Schistosoma mansoni worms exposed to various compounds. Z Parasitenkd 69:61-71.

      [12] Chaiworaporn R, Maneerat Y, Rojekittikhun,W, Ramasoota P, Janecharut T, Matsuda H, et al. (2005) Therapeutic effect of subcurative dose praziquantel on Schistosoma mansoni infected mice and resistance to challenge infection after treatment. Southeast Asian J Trop Med Public Health 36(4):846-852.

      [13] Cheever AW, Anderson LA (1971) Rate of destruction of Schistosoma mansoni eggs in the tissues of mice. Am J Trop Med Hyg 20:62-8.

      [14] Cheever AW (1968) Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting S.mansoni eggs in tissues. Bull WHO 39:328-331.

      [15] Cheever AW, Macedonia JG, Deb S, Cheever EA, Mosimann JR (1992) Persistence of eggs and hepatic fibrosis after treatment of Schistosoma mansoni-infected mice. Am J Trop Med Hyg 46: 752-758.

      [16] Cheever AW, Mosimann JE, Deb S, Cheever EA, Duvall AH (1994) Natural history of Schistosoma mansoni infection in mice: egg production, egg passage in the feces, and contribution of host and parasite death to changes in worm numbers. Am J Trop Med Hyg 50(3):269-80.

      [17] Conceiço MJ, Lenzi HL, Coura JR (2008) Human study and experimental behavior of Schistosoma mansoni isolates from patients with different clinical forms of schistosomiasis. Acta Trop 108: 98-103.

      [18] Cowan N, Keiser J (2015) Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni. Parasites & Vectors 8:417.

      [19] De Oliveira RN, Rehder VLG, Oliveira ASSO, Jeraldo VDS, Linhares AX, Allegretti SM (2014) Anthelmintic activity in vitro and in vivo of Baccharis trimera (Less) DC against immature and adult worms of Schistosoma mansoni. Exp Parasitol 139: 63-72.

      [20] Diaz E, Mondragon J, Ramirez E, Bernal R (2003) Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg 68: 384-385.

      [21] Ebeid FA, Metwally AA,Botros S, Bennet JL (1994) Treatment of experimental schistosomiasis mansoni with praziquantel alone and combined with cimetidine. Arzneimittelforschung 44: 1268-70.

      [22] Elbaz T, Esmat G (2013) Hepatic and intestinal schistosomiasis: review.J Adv Res 4:445–452.

      [23] El Ridi RAF, Tallima HAM (2013) Novel Therapeutic and Prevention Approaches for Schistosomiasis: Review. J Adv Res 4:467–478.

      [24] El-Shafei MMA, Mattar MA, Afify HA (2002) Parasitological and immunological changes in murine hepatic schistosomiasis before and after praziquantel treatment. J Egypt Soc Para 32(2):551-560.

      [25] Emam MH, Abd El-Rahman M, Gamil IS, Muselhy MA (2009) Studies on the effect of antioxidant Selenium-ACE after treatment with Praziquantel and Mirazid in Schistosoma mansoni infected mice. Egypt J Hosp Med 37: 709-25.

      [26] Farag HF, Youssef M, Hammouda NA, Awadalla HN (1978) Oogram studies with Bilarcil in S.mansoni and S.haematobium infected mice. J Egypt Soc Parasitol 8(1):1-7.

      [27] Favennec L, Ortiz J, Gargala G, Lopez N, Ayoub A, Rossignol JF (2003) Double-blind, randomized, placebo-controlled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru. Aliment Pharmacol Ther 17: 265–270.

      [28] FDA (2005) Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers.

      [29] Fitzsimmons CM, Joseph S, Jones FM, Reimert CM, Hoffmann KF et al. (2004) Chemotherapy of schistosomiasis in Ugandan fisher men: Treatment can cause a rapid increase in Interleukin-5 levels in plasma but decreased level of eosinophilia and worm specific immunoglobulin E. Infect Immun 72(7):4023-30.

      [30] Fox LM, Saravolatz LD (2005) Nitazoxanide: A New Thiazolide Antiparasitic Agent. Clin Infect Dis 40 (8): 1173-1180.

      [31] Gonnert R, Andrews P (1977) Praziquantel, a new broad spectrum schistosomicidal agent. Z Parasitenk 52: 129-150.

      [32] Hamza RS, Metwaly AS,Abo El-Maaty DA (2012) Effects of Artemether Treatment on Prepatent and Patent Schistosoma mansoni Infection in Experimentally Infected Mice. PUJ 5(2): 147-154.

      [33] Harnett W, Kusel JR (1986) Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro. Parasitol 93:401-5.

      [34] Hassan M, El-Motaiem M, Afify H, Abaza B, El-Shafei M, Massoud AM (2003) In vitro effect of Mirazid on Schistosoma mansoni worms. J Egypt Soc Parasitol 33(3):999-1008.

      [35] Helmy MMF, Mahmoud SS, Fahmy ZH (2009) Schistosoma mansoni: Effect of dietary zinc supplement on egg granuloma in Swiss mice treated with praziquantel. Exp Parasitol 122: 310–17.

      [36] Hoffman PS, Sisson G, Croxen MA, Welch K, Harman DW,Cremades N, et al (2007) Antiparasitic Drug Nitazoxanide Inhibits the Pyruvate Oxidoreductases of Helicobacter pylori, Selected Anaerobic Bacteria and Parasites, and Campylobacter jejuni. Antimicrob agent chemother 51(3):868-876.

      [37] Holtfreter MC, Stachs O, Reichard M, Loebermann M, Guthoff RF, Reisinger EC (2011) Confocal laser scanning microscopy for detection of Schistosoma mansoni eggs in the gut of mice. PLoS One 6: e18799.

      [38] Hotez PJ (2014) Could Nitazoxanide be added to other essential medicines for integrated neglected tropical disease control and elimination? PLoS Negl Trop Dis 8(3): e2758.

      [39] Inobaya M T,Olveda R M, Chau T N. P, Olveda D U, Ross A G (2014) Prevention and control of schistosomiasis: a current perspective. Res Rep Trop Med 5:65-75.

      [40] Issa RM (2007) Schistosoma mansoni: The prophylactic and curative effects of propolis in experimentally infected mice. Raw Med J 32(2): 94-8.

      [41] Katz N, Chaves A, Pellegrino J (1972)A simple device for quantitative stool thick-smear technique in schistosomiasis mansoni. Revist Inst Med Trop Sao Paulo 14: 397-400.

      [42] Khalil SS (2000) On the schistosomicidal effect of Triclabendazole an experimental study. J Egypt Soc Parasitol 30(3):799-808.

      [43] Liang. YS, Bruce JI, Boyd DA (1987) Laboratory cultivation of schistosome vector snails and maintenance of schistosome life cycles. Proc.1stSino-American Symp.USA 1: 34-48.

      [44] Nessim NG, Demerdash Z (2000) Correlation between infection intensity, serum immunoglobulin profile, cellular immunity and the efficacy of treatment with praziquantel in murine schistosomiasis mansoni. Arzneimittelforschung 50 (2):173-177.

      [45] N’Goran EK, Gnaka HN, Tanner M, Utzinger J (2003) Efficacy and side effects of two praziquantel treatments against Schistosoma hamatobium infection, among schoolchildren from Côte d’Ivoire. Ann Trop Med Parasitol 97: 37-51.

      [46] NRC 2011. Guide for the Care and Use of Laboratory Animals: 8th Ed., in: Guide for the Care and Use of Laboratory Animals. National Research Council. p.118.

      [47] Othman AA, Soliman RH (2015) Schistosomiasis in Egypt: a never-ending story? Acta Trop 148: 179-190.

      [48] Panic G, Vargas M, Scandale I, Keiser J (2015) Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. PLoS Negl Trop Dis 9(7): e0003962.

      [49] Pellegrino J, Faria J (1965) the oogram method for the screening of drugs in schistosomiasis mansoni. Am J Trop Med Hyg 14:363-369.

      [50] Pellegrino J, Oliveira CA, Faria J, Cunah AS (1962) New approach to the screening of drugs in experimental schistosomiasis mansoni in mice. Am J Trop Med Hyg 11(2):201-15.

      [51] Pinto-Almeida A, Mendes T, de Oliveira RN, Corrêa SAP, Allegretti SM, Belo S, et al. (2016) Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel. Front Microbiol 7: 594.

      [52] Popiel I, Irving DL, Basch PF (1985) Wound healing in the trematode Schistosoma. Tissue Cell 17: 69-77.

      [53] Rossignol JF, Abaza H, Friedman H (1998) Successful treatment of human fascioliasis with Nitazoxanide. Trans R Soc Trop Med Hyg 92: 103-104.

      [54] Rossignol JF, Maisonneuve H (1984) Nitazoxanide in the treatment of Taenia saginata and Hymenolepis nana infections. Am J Trop Med Hyg 33: 511-512.

      [55] Sadhu PS,Kumar SNK,Chandrasekharam M, Pica-Mattoccia L, Cioli D, Rao VJ (2012) Synthesis of new praziquantel analogues: Potential candidates for the treatment of schistosomiasis. Bioorg Med Chem Lett 22:1103-1106.

      [56] Sarvel AK, Kusel JR, Araujo N, Coelho PMZ, Katz N (2006) Comparison between morphological and staining characteristics of live and dead eggs of Schistosoma mansoni. Mem Inst Oswaldo Cruz 101(1):289-292.

      [57] Seif El-Din SH, Sabra AA, Hammam OA, El-Lakkany NM (2013) Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice. Korean J Parasitol 51(2):165-175.

      [58] Shaohong L, Kumagai T, Qinghua A, Xiaolan Y, Ohmae H, Yabu Y, et al. (2006) Evaluation of the anthelmintic effects of artesunate against experimental Schistosoma mansoni infection in mice using different treatment protocols. Parasitol Int 5, 63-8.

      [59] Shaw MK, Erasmus DA (1987) Schistosoma mansoni: Structural damage and tegumental repair after in vivo treatment with praziquantel. Parasitology 94: 243-54.

      [60] Shaw MK (1990) Schistosoma mansoni: stage dependent damage after in vitro treatment with praziquantel. Parasitology 100: 65.

      [61] Siddiqui AA, Phillips T , Charest H , Podesta RB , Quinlin ML, Pinkston JR, et al. (2003) Induction of Protective Immunity against Schistosoma mansoni via DNA Priming and Boosting with the Large Subunit of Calpain (Sm-p80): Adjuvant Effects of Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-4. Infect Immun 71(7): 3844–3851.

      [62] Smithers SR, Terry RJ (1965) the infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitolology 55(4):695-700.

      [63] Soliman M (2012) Evaluation of avocado/soybean unsaponifiable alone or concurrently with praziquantel in murine schistosomiasis. Acta Trop 122:261-266.

      [64] Stettler M, Fink R,Walker M, Gottstein B, Geary TG, Rossignol JF, et al. (2003) In Vitro Parasiticidal Effect of Nitazoxanide against Echinococcus multilocularis Metacestodes. Antimicrob Agents Chemother 47(2): 467–474.

      [65] Stockis A, Allemon AM, DeBruyn S, Gengler C (2002) Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral doses.Int J Clin Pharmacol Ther 40:213–20.

      [66] Sweify MM (2009) Study of some plant essential oil compounds against Schistosoma mansoni infection in experimental animals. Msc. Thesis, Department of Parasitology and medical entomology, Medical Research Institute, University of Alexandria, Alexandria; Egypt.

      [67] Tchuenté LAT, Momo SC, Stothard JR, Rollinson D (2013) Efficacy of praziquantel and reinfection patterns in single and mixed infection foci for intestinal and urogenital schistosomiasis in Cameroon. Acta Trop 128: 275–283.

      [68] Thibaut JPB, Monteiro LM, Leite LCC, Menezes CMS, Lima LM, Noël F (2009) The effects of 3-methylclonazepamon Schistosoma mansoni musculature are not mediated by benzodiazepine receptors. Eur J Pharmacol 606: 9–16.

      [69] Tran MH, Pearson MS, Bethony JM, Smyth DJ, Jones MK, Duke-Don TA, et al. (2006) Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nat Med 12: 835-840.

      [70] Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH (2003) Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemother 47(5): 1487-1495.

      [71] Voge M, Bueding E (1980) Schistosoma mansoni: Tegumental surface alterations induced by subcurative doses of the schistosomicide Amoscanate. Exp Parasitol 50:257-9.

      [72] Wang W,Wang L, Liang Y (2012) Susceptibility or resistance of praziquantel in human schistosomiasis: a review. Parasitol Res 111:1871–1877.

      [73] WHO (1998) Basic OECD principles of GLP. Geneva, Switzerland: World Health Organization. http://www.who/int/tdr/publications 02-01-2008.

      [74] WHO (2015) Schistosomiasis: number of people treated worldwide in 2013. Wkly Epidemiol Rec 5 (90):25-32.

      [75] Xiao SH, Catto BA, Webster LT (1985) Effects of praziquantel on different developmental stages of Schistosoma mansoni in vitro and in vivo. J Infect Dis 151:1130-1137.

      [76] Xiao SH, Mei JY, Jiao PY (2011) Effect of mefloquine administrated orally at single, multiple or combined with artmether, artesunate or praziquantel in treatment of mice infected with Schistosoma japonicum. Parasitol Res 108: 399-406.

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    A. El-Taweel, H., H. El-Sayad, M., A. Abu Helw, S., & A. Al-Kazzaz, M. (2016). Comparative parasitological and electron microscopic studies on the effects of Nitazoxanide and Praziquantel in Schistosoma mansoni-infected mice. International Journal of Pharmacology and Toxicology, 4(2), 228-234.