Efficacy of Nitazoxanide, Nitazoxanide-Garlic Combination and Tinidazole in Treatment of Giardia duodenalis and Blastocystis hominis: Coproscopic Assessment
,
Abstract
Background: Giardia duodenalis and Blastocystis hominis are among the most common intestinal protozoa worldwide. Treatment of infection by metronidazole (MTZ) has some limitations. The objective of this study was to detect the prevalence of Blastocystis and giardiasis among school-age children from December 2021 till March 2022 from Motoubes, Kafrelsheikh, Egypt, and determine the efficacy of nitazoxanide (NTZ), NTZ plus garlic and tinidazole (TIN) on Blastocystis and giardiasis infection.
Methods: Stool samples were collected from 390 children and microscopically examined using formalin-ethyl acetate concentration and culturing on Jones' medium for B. hominis. Those who tested positive for giardiasis (120 children, 30.7%) (Group I) or Blastocystis (180 children, 46.1%) (Group II) were equally divided into four subgroups. The first subgroup received NTZ orally, every 12 hours for three successive days. The second subgroup received NTZ in the same dose as the first subgroup plus dry garlic powder every 12 hours for three successive days. The third subgroup received TIN as a single oral dose, and a fourth control subgroup. Successful cure was considered if no Blastocystis or giardiasis stages were found in post-treatment faecal specimens.
Results: Cure rate was significantly higher in TIN treated groups (75.5% and 96.6%) than NTZ (57.7% and 40% ) or NTZ plus garlic treated groups ( 55.5% and 43%) in both Blastocystis and giardiasis, respectively (P<0.05).
Conclusion: TIN, once, is more efficacious than NTZ or NTZ plus garlic in the treatment of Blastocystis and giardiasis in children.
1. Deng L, Wojciech L, Gascoigne NR, Peng G, Tan KS. New insights into the interac-tions between Blastocystis, the gut microbio-ta, and host immunity. PLoS Pathog. 2021; 17(2):e1009253.
2. Naguib D, El-Gohary AH, Roellig D, et al. Molecular characterization of Cryptosporidi-um spp. and Giardia duodenalis in children in Egypt. Parasit Vectors. 2018; 11(1):403. https://doi.org/10.1186/s13071-018-2981-7.
3. Youssef AI, Uga S. Review of parasitic zoonoses in Egypt. Trop Med Health. 2013; 42:3-14. https://doi.org/10.10.2149/tmh.2013-23
4. de Lucio A, Amor-Aramendía A, Bailo B, et al. Prevalence and Genetic Diversity of Giardia duodenalis and Cryptosporidium spp. among School Children in a Rural Area of the Amhara Region, North-West Ethiopia. PLOS One. 2016; 11(7):e015999. https://doi.org/10.1371/journal.pone.0159992
5. Eassa SM, Ali HS, El Masry SA, Abd El-Fattah AH. Blastocystis hominis among im-munocompromised and immunocompe-tent children in Alexandria, Egypt. Ann Clin Lab Res. 2016; 4:92-8.
6. Sánchez A, Munoz M, Gómez N, et al. Molecular Epidemiology of Giardia, Blasto-cystis and Cryptosporidium among Indigenous Children from the Colombian Amazon Basin. Front Microbiol. 2017; 8:248. https://doi.org/10.3389/fmicb.2017.00248.
7. Abdo SM, El-Adawy H, Farag HF, El-Taweel HA, Elhadad H, El-Badry AA. De-tection and molecular identification of Blas-tocystis isolates from humans and cattle in northern Egypt. J Parasit Dis. 2021; 45:738-745. https://doi.org/10.1007/s12639-021-01354-5
8. Elhadad H, Abdo S, Tolba M, et al. Detec-tion of Giardia intestinalis assemblages A and B among children from three villages in the West Delta region, Egypt using as-semblage specific primers. J Parasit Dis. 2121; 45:655-663. https://doi.org/10.1007/s12639-020-01338-x.
9. Hamdy DA, Abd El Wahab WM, Senosy SA, Mabrouk AG. Blastocystis spp. and Giar-dia intestinalis co-infection profile in children suffering from acute diarrhea. J Parasit Dis. 2020; 44:88-98. https://doi.org/10.1007/s12639-019-01165-9
10. Dixon BR. Giardia duodenalis in humans and animals–Transmission and disease. Res Vet Sci. 2121;135:283-9. https://doi.org/10.1016/j.rvsc.2020.09.034
11. Rossignol JF. Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol. 2010; 124:45-53. https://doi.org/10.1016/j.exppara.2009.07.005
12. Pasupuleti V, Escobedo AA, Deshpande A, Thota P, Roman Y, Hernandez AV. Ef-ficacy of 5-nitroimidazoles for the treat-ment of giardiasis: a systematic review of randomized controlled trials. PLoS Negl Tropl Dis. 2014; 8:e2733. https://doi.org/10.1371/journal.pntd.0002733
13. Sekar U, Shanthi M. Blastocystis: Consensus of treatment and controversies. Trop Par-asitol. 2013; 3:35. https://doi.org/10.4103/2229-5070.113901
14. Lalle M, Hanevik K. Treatment-refractory giardiasis: challenges and solutions. Infect Drug Resist. 2018; 11:1921. https://doi.org/10.2147/IDR.S141468
15. Nigam P, Kapoor K, Kumar A, Sarkari N, Gupta A. Clinical profile of giardiasis and comparison of its therapeutic response to metronidazole and tinidazole. J Assoc Physicians India. 1991; 39:613-5.
16. Cedillo‐Rivera R, Chávez B, Gonzá-lez‐Robles A, Tapia A, Yépez‐Mulia L. In vitro effect of nitazoxanide against Enta-moeba histolytica, Giardia intestinalis and Trichomonas vaginalis trophozoites. J Eukary-ot Microbiol. 2002; 49:201-8. https://doi.org/10.1111/j.1550-7408.2002.tb00523.x.
17. Mendoza D, Núñez FÁ, Escobedo ÁA, et al. Utilidad de 2 métodos coproparasito-lógicos y su empleo en un ensayo terapéu-tico antigiardiásico. Rev Cubana Med Trop. 2003; 55:174-8.
18. Roberts T, Ellis J, Harkness J, Marriott D, Stark D. Treatment failure in patients with chronic Blastocystis infection. J medl Micro-biol. 2014;63:252-7. https://doi.org/10.1099/jmm.0.065508-0
19. Gilles HM, Hoffman PS. Treatment of intestinal parasitic infections: a review of nitazoxanide. Trends Parasitol. 2002; 18:95-7. https://doi.org/10.1016/s1471-4922(01)02205-x
20. Galeh TM, Kazemi A, Mahami-Oskouei M, et al. Introducing nitazoxanide as a promising alternative treatment for symp-tomatic to metronidazole-resistant giardia-sis in clinical isolates. Asian Pac J Trop Med. 2016; 9:887-92. https://doi.org/10.1016/j.apjtm.2016.07.013.
21. Ibrahim AN. Comparison of in vitro ac-tivity of metronidazole and garlic-based product (Tomex®) on Trichomonas vaginalis. Parasitol Res. 2013; 112(5):2063-7. doi: 10.1007/s00436-013-3367-6. Epub 2013 Mar 2. PMID: 2345594
22. Yakoob J, Abbas Z, Beg MA, et al. In vitro sensitivity of Blastocystis hominis to gar-lic, ginger, white cumin, and black pepper used in diet. Parasitol Res. 2011; 109:379-85. https://doi.org/10.1007/s00436-011-2265-z.
23. Argüello-García R, de la Vega-Arnaud M, Loredo-Rodríguez IJ, EA, et al. Activity of thioallyl compounds from garlic against Giardia duodenalis trophozoites and in ex-perimental giardiasis. Front Cell Infect Mi-crobiol. 2018; 8:353. https://doi.org/10.3389/fcimb.2018.00353
24. Soffar SA, Mokhtar GM. Evaluation of the antiparasitic effect of aqueous garlic (Allium sativum) extract in hymenolepiasis nana and giardiasis. J Egypt Soc Parasitol. 1991; 21:497-502.
25. Coyle CM, Varughese J, Weiss LM, Tan-owitz HB. Blastocystis: to treat or not to treat. Clin Infect Dis. 2012; 54:105-10. https://doi.org/10.1093/cid/cir810
26. Escobedo A, Alvarez G, González M, et al. The treatment of giardiasis in children: single-dose tinidazole compared with 3 days of nitazoxanide. Ann Trop Med Par-asitol. 2008; 102:199-207. https://doi.org/10.1179/136485908X267894
27. Nagel R, Bielefeldt-Ohmann H, Traub R. Clinical pilot study: efficacy of triple antibi-otic therapy in Blastocystis positive irritable bowel syndrome patients. Gut Pathog. 2014; 6:1-9. https://doi.org/10.1186/s13099-014-0034-0
28. Dunn LA, Boreham PF. The in-vitro activ-ity of drugs against Blastocystis hominis. J An-timicrob Chemother. Apr. 1991; 27:507-16. doi: https://doi.org/10.1093/jac/27.4.507.
29. Rossignol JF, Kabil SM, Said M, Samir H, Younis AM. Effect of nitazoxanide in per-sistent diarrhea and enteritis associated with Blastocystis hominis. Clin Gastroenterol Hepatol. 2005;3:987-91. https://doi.org/10.1016/s1542-3565(05)00427-1.
30. Ibrahim HS, Salem AI, Ahmed NMAE-R, El-Taweel HA. Pre-and post-treatment evaluation of intestinal inflammation in Gi-ardia and Blastocystis infected children: a community-based study. J Parasit Dis. 2021; 45:1026-1033. https://doi.org/10.1007/s12639-021-01398-7
31. Rossignol JF, Ayoub A, Ayers MS. Treat-ment of diarrhea caused by Giardia intesti-nalis and Entamoeba histolytica or E. dispar: A randomized, double‐blind, place-bo‐controlled study of nitazoxanide. J In-fect Dis. 2001; 184:381-4. https://doi.org/10.1086/322038
32. Diaz E, Mondragon J, Ramirez E, Bernal R. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. 2003; 68:384-5.
33. Tejman-Yarden N, Millman M, Lauwaet T, et al. Impaired parasite attachment as fit-ness cost of metronidazole resistance in Giardia lamblia. Antimicrob Agents Chemother. 2011; 55:4643-51. https://doi.org/10.1128/AAC.00384-11
34. Bhagyalakshmi N, Thimmaraju R, Venka-tachalam L, Murthy KC, Sreedhar R. Nutraceutical applications of garlic and the intervention of biotechnology. Crit Rev Food Sci Nutr. 2005; 45:607-21. https://doi.org/10.1080/10408390500455508.
35. Harris JC, Plummer S, Turner MP, Lloyd D. The microaerophilic flagellate Giardia in-testinalis: Allium sativum (garlic) is an effec-tive antigiardial. Microbiology. 2000; 146:3119-27. https://doi.org/10.1099/00221287-146-12-3119
36. Pengsaa K, Sirivichayakul C, Pojjaroen-Anant C, Nimnual S, Wisetsing P. Albend-azole treatment for Giardia intestinalis infec-tions in school children. Southeast Asian J Trop Med Public Health. 1999; 30:78-83.
37. Cañete R, Escobedo AA, Elena González M, Almirall P, Cantelar N. A randomized, controlled, open-label trial of a single day of mebendazole versus a single dose of tinidazole in the treatment of giardiasis in children. Curr Med Res Opin. 2006; 22:2131-6.
38. Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duode-nalis infections. World J Gastroenterol. 2013; 19: 8974-8985.
39. Mørch K, Hanevik K. Giardiasis treat-ment: an update with a focus on refractory disease. Curr Opin Infect Dis. 2020; 33: 355-364.
2. Naguib D, El-Gohary AH, Roellig D, et al. Molecular characterization of Cryptosporidi-um spp. and Giardia duodenalis in children in Egypt. Parasit Vectors. 2018; 11(1):403. https://doi.org/10.1186/s13071-018-2981-7.
3. Youssef AI, Uga S. Review of parasitic zoonoses in Egypt. Trop Med Health. 2013; 42:3-14. https://doi.org/10.10.2149/tmh.2013-23
4. de Lucio A, Amor-Aramendía A, Bailo B, et al. Prevalence and Genetic Diversity of Giardia duodenalis and Cryptosporidium spp. among School Children in a Rural Area of the Amhara Region, North-West Ethiopia. PLOS One. 2016; 11(7):e015999. https://doi.org/10.1371/journal.pone.0159992
5. Eassa SM, Ali HS, El Masry SA, Abd El-Fattah AH. Blastocystis hominis among im-munocompromised and immunocompe-tent children in Alexandria, Egypt. Ann Clin Lab Res. 2016; 4:92-8.
6. Sánchez A, Munoz M, Gómez N, et al. Molecular Epidemiology of Giardia, Blasto-cystis and Cryptosporidium among Indigenous Children from the Colombian Amazon Basin. Front Microbiol. 2017; 8:248. https://doi.org/10.3389/fmicb.2017.00248.
7. Abdo SM, El-Adawy H, Farag HF, El-Taweel HA, Elhadad H, El-Badry AA. De-tection and molecular identification of Blas-tocystis isolates from humans and cattle in northern Egypt. J Parasit Dis. 2021; 45:738-745. https://doi.org/10.1007/s12639-021-01354-5
8. Elhadad H, Abdo S, Tolba M, et al. Detec-tion of Giardia intestinalis assemblages A and B among children from three villages in the West Delta region, Egypt using as-semblage specific primers. J Parasit Dis. 2121; 45:655-663. https://doi.org/10.1007/s12639-020-01338-x.
9. Hamdy DA, Abd El Wahab WM, Senosy SA, Mabrouk AG. Blastocystis spp. and Giar-dia intestinalis co-infection profile in children suffering from acute diarrhea. J Parasit Dis. 2020; 44:88-98. https://doi.org/10.1007/s12639-019-01165-9
10. Dixon BR. Giardia duodenalis in humans and animals–Transmission and disease. Res Vet Sci. 2121;135:283-9. https://doi.org/10.1016/j.rvsc.2020.09.034
11. Rossignol JF. Cryptosporidium and Giardia: treatment options and prospects for new drugs. Exp Parasitol. 2010; 124:45-53. https://doi.org/10.1016/j.exppara.2009.07.005
12. Pasupuleti V, Escobedo AA, Deshpande A, Thota P, Roman Y, Hernandez AV. Ef-ficacy of 5-nitroimidazoles for the treat-ment of giardiasis: a systematic review of randomized controlled trials. PLoS Negl Tropl Dis. 2014; 8:e2733. https://doi.org/10.1371/journal.pntd.0002733
13. Sekar U, Shanthi M. Blastocystis: Consensus of treatment and controversies. Trop Par-asitol. 2013; 3:35. https://doi.org/10.4103/2229-5070.113901
14. Lalle M, Hanevik K. Treatment-refractory giardiasis: challenges and solutions. Infect Drug Resist. 2018; 11:1921. https://doi.org/10.2147/IDR.S141468
15. Nigam P, Kapoor K, Kumar A, Sarkari N, Gupta A. Clinical profile of giardiasis and comparison of its therapeutic response to metronidazole and tinidazole. J Assoc Physicians India. 1991; 39:613-5.
16. Cedillo‐Rivera R, Chávez B, Gonzá-lez‐Robles A, Tapia A, Yépez‐Mulia L. In vitro effect of nitazoxanide against Enta-moeba histolytica, Giardia intestinalis and Trichomonas vaginalis trophozoites. J Eukary-ot Microbiol. 2002; 49:201-8. https://doi.org/10.1111/j.1550-7408.2002.tb00523.x.
17. Mendoza D, Núñez FÁ, Escobedo ÁA, et al. Utilidad de 2 métodos coproparasito-lógicos y su empleo en un ensayo terapéu-tico antigiardiásico. Rev Cubana Med Trop. 2003; 55:174-8.
18. Roberts T, Ellis J, Harkness J, Marriott D, Stark D. Treatment failure in patients with chronic Blastocystis infection. J medl Micro-biol. 2014;63:252-7. https://doi.org/10.1099/jmm.0.065508-0
19. Gilles HM, Hoffman PS. Treatment of intestinal parasitic infections: a review of nitazoxanide. Trends Parasitol. 2002; 18:95-7. https://doi.org/10.1016/s1471-4922(01)02205-x
20. Galeh TM, Kazemi A, Mahami-Oskouei M, et al. Introducing nitazoxanide as a promising alternative treatment for symp-tomatic to metronidazole-resistant giardia-sis in clinical isolates. Asian Pac J Trop Med. 2016; 9:887-92. https://doi.org/10.1016/j.apjtm.2016.07.013.
21. Ibrahim AN. Comparison of in vitro ac-tivity of metronidazole and garlic-based product (Tomex®) on Trichomonas vaginalis. Parasitol Res. 2013; 112(5):2063-7. doi: 10.1007/s00436-013-3367-6. Epub 2013 Mar 2. PMID: 2345594
22. Yakoob J, Abbas Z, Beg MA, et al. In vitro sensitivity of Blastocystis hominis to gar-lic, ginger, white cumin, and black pepper used in diet. Parasitol Res. 2011; 109:379-85. https://doi.org/10.1007/s00436-011-2265-z.
23. Argüello-García R, de la Vega-Arnaud M, Loredo-Rodríguez IJ, EA, et al. Activity of thioallyl compounds from garlic against Giardia duodenalis trophozoites and in ex-perimental giardiasis. Front Cell Infect Mi-crobiol. 2018; 8:353. https://doi.org/10.3389/fcimb.2018.00353
24. Soffar SA, Mokhtar GM. Evaluation of the antiparasitic effect of aqueous garlic (Allium sativum) extract in hymenolepiasis nana and giardiasis. J Egypt Soc Parasitol. 1991; 21:497-502.
25. Coyle CM, Varughese J, Weiss LM, Tan-owitz HB. Blastocystis: to treat or not to treat. Clin Infect Dis. 2012; 54:105-10. https://doi.org/10.1093/cid/cir810
26. Escobedo A, Alvarez G, González M, et al. The treatment of giardiasis in children: single-dose tinidazole compared with 3 days of nitazoxanide. Ann Trop Med Par-asitol. 2008; 102:199-207. https://doi.org/10.1179/136485908X267894
27. Nagel R, Bielefeldt-Ohmann H, Traub R. Clinical pilot study: efficacy of triple antibi-otic therapy in Blastocystis positive irritable bowel syndrome patients. Gut Pathog. 2014; 6:1-9. https://doi.org/10.1186/s13099-014-0034-0
28. Dunn LA, Boreham PF. The in-vitro activ-ity of drugs against Blastocystis hominis. J An-timicrob Chemother. Apr. 1991; 27:507-16. doi: https://doi.org/10.1093/jac/27.4.507.
29. Rossignol JF, Kabil SM, Said M, Samir H, Younis AM. Effect of nitazoxanide in per-sistent diarrhea and enteritis associated with Blastocystis hominis. Clin Gastroenterol Hepatol. 2005;3:987-91. https://doi.org/10.1016/s1542-3565(05)00427-1.
30. Ibrahim HS, Salem AI, Ahmed NMAE-R, El-Taweel HA. Pre-and post-treatment evaluation of intestinal inflammation in Gi-ardia and Blastocystis infected children: a community-based study. J Parasit Dis. 2021; 45:1026-1033. https://doi.org/10.1007/s12639-021-01398-7
31. Rossignol JF, Ayoub A, Ayers MS. Treat-ment of diarrhea caused by Giardia intesti-nalis and Entamoeba histolytica or E. dispar: A randomized, double‐blind, place-bo‐controlled study of nitazoxanide. J In-fect Dis. 2001; 184:381-4. https://doi.org/10.1086/322038
32. Diaz E, Mondragon J, Ramirez E, Bernal R. Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico. Am J Trop Med Hyg. 2003; 68:384-5.
33. Tejman-Yarden N, Millman M, Lauwaet T, et al. Impaired parasite attachment as fit-ness cost of metronidazole resistance in Giardia lamblia. Antimicrob Agents Chemother. 2011; 55:4643-51. https://doi.org/10.1128/AAC.00384-11
34. Bhagyalakshmi N, Thimmaraju R, Venka-tachalam L, Murthy KC, Sreedhar R. Nutraceutical applications of garlic and the intervention of biotechnology. Crit Rev Food Sci Nutr. 2005; 45:607-21. https://doi.org/10.1080/10408390500455508.
35. Harris JC, Plummer S, Turner MP, Lloyd D. The microaerophilic flagellate Giardia in-testinalis: Allium sativum (garlic) is an effec-tive antigiardial. Microbiology. 2000; 146:3119-27. https://doi.org/10.1099/00221287-146-12-3119
36. Pengsaa K, Sirivichayakul C, Pojjaroen-Anant C, Nimnual S, Wisetsing P. Albend-azole treatment for Giardia intestinalis infec-tions in school children. Southeast Asian J Trop Med Public Health. 1999; 30:78-83.
37. Cañete R, Escobedo AA, Elena González M, Almirall P, Cantelar N. A randomized, controlled, open-label trial of a single day of mebendazole versus a single dose of tinidazole in the treatment of giardiasis in children. Curr Med Res Opin. 2006; 22:2131-6.
38. Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duode-nalis infections. World J Gastroenterol. 2013; 19: 8974-8985.
39. Mørch K, Hanevik K. Giardiasis treat-ment: an update with a focus on refractory disease. Curr Opin Infect Dis. 2020; 33: 355-364.
| Files | ||
| Issue | Vol 18 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v18i1.12379 | |
| Keywords | ||
| Giardia duodenalis Blastocystis hominis Tinidazole Nitazoxanide Garlic | ||
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How to Cite
1.
Abdo S, Ghallab MMIG, Zaghloul MS, Elhadad H. Efficacy of Nitazoxanide, Nitazoxanide-Garlic Combination and Tinidazole in Treatment of Giardia duodenalis and Blastocystis hominis: Coproscopic Assessment. Iran J Parasitol. 2023;18(1):48-55.
