Abstract
In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.
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References
Baker DG (1998) Natural pathogens of laboratory mice, rats, and rabbits and their effects on research. Clin Microbiol Rev 11:231–266
Bendesky A, Menéndez D, Ostrosky-Wegman P (2002) Is metronidazole carcinogenic? Mutat Res 511:133–144
Besirbellioglu BA, Ulcay A, Can M, Erdem H, Tanyuksel M, Avci IY, Araz E, Pahsa A (2006) Saccharomyces boulardii and infection due to Giardia lamblia. Scand J Infect Dis 38:479–481
Beyhan YE, Hökelek M (2014) Giardia muris infection in laboratory rats (Rattus norvegicus) and treatment with metronidazole. Turkiye Parazitol Derg 38:181–184
Brener Z (1962) Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi. Rev Inst Med Trop Sao Paulo 4:389–396
Cotton JA, Beatty JK, Buret AG (2011) Host parasite interactions and pathophysiology in Giardia infections. Int J Parasitol 41:925–933
Cruz CCP, Ferrari L, Sogayar R (1997) Ensaio terapêutico na infecção por Giardia muris em camundongo com metronidazole, tinidazole, secnidazole e furazolidone. Rev Soc Bras Med Trop 30:223–228
Dobiáš L, Černá M, Rössner P, Srám R (1994) Genotoxicity and carcinogenicity of metronidazole. Mutat Res 317:177–194
Dreesen L, De Bosscher K, Grit G, Staels B, Lubberts E, Bauge E, Geldhof P (2014) Giardia muris infection in mice is associated with a protective interleukin 17A response and induction of peroxisome proliferator-activated receptor alpha. Infect Immun 82:3333–3340
Faust EC, D’Antoni JS, Odom V, Miller MJ, Peres C, Sawitz W, Thomen LF, Tobie J, Walker H (1938) A critical study of clinical laboratory technics for the diagnosis of protozoan cysts and helminth eggs in feces. AmJTrop Med Hyg 18:169–183
Feng Y, Xiao L (2011) Zoonotic potential and molecular epidemiology of Giardia species and giardiasis. Clin Microbiol Rev 24:110–140
Gardner TB, Hill DR (2001) Treatment of giardiasis. Clin Microbiol Rev 14:114–128
Geurden T, Vandenhoute E, Pohle H, Casaert S, De Wilde N, Vercruysse J, Claerebout E (2010) The effect of a fenbendazole treatment on cyst excretion and weight gain in calves experimentally infected with Giardia duodenalis. Vet Parasitol 169:18–23
Gilioli R, Andrade LAG, Passos LAC, Silva FA, Rodrigues DM, Guaraldo AMA (2000) Parasite survey in mouse and rat colonies of Brazilian laboratory animal houses kept under differents sanitary barrier conditions. Arq Bras Med Vet Zootec 52:33–37
Goyal N, Tiwari RP, Shukla G (2011) Lactobacillus rhamnosus GG as an effective probiotic for murine giardiasis. Interdiscip Perspect Infect Dis 2011:1–4
Keith CL, Radecki SV, Lappin MR (2003) Evaluation of fenbendazole for treatment of Giardia infection in cats concurrently infected with Cryptosporidium parvum. Am J Vet Res 64:1027–1029
Kelesidis T, Pothoulakis C (2012) Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therap Adv Gastroenterol 5:111–125
Leitsch D (2015) Drug resistance in the microaerophilic parasite Giardia lamblia. Curr Trop Med Rep 2:128–135
Marques MAP (2002) Controle parasitológico. In: Andrade A, Pinto SC, Oliveira RS (eds) Animais de Laboratório: criação e experimentação. Editora Fiocruz, Rio de Janeiro, pp 303–315
O'Handley RM, Buret AG, McAllister TA, Jelinski M, Olson ME (2001) Giardiasis in dairy calves: effects of fenbendazole treatment on intestinal structure and function. Int J Parasitol 31:73–79
O’Handley RM, Cockwill C, Jelinski M, McAllister TA, Olson ME (2000) Effects of repeat fenbendazole treatment in dairy calves with giardiosis on cyst excretion, clinical signs and production. Vet Parasitol 89:209–218
Oliveira-Sequeira TCG, Ribeiro CM, Gomes MIFV (2008) Potencial bioterapêutico dos probióticos nas parasitoses intestinais. Cienc Rural 38:2670–2679
Pereira AM (2002) Principais doenças dos camundongos, ratos e hamsters. In: Andrade A, Pinto SC, Oliveira RS (eds) Animais de Laboratório: criação e experimentação. Editora Fiocruz, Rio de Janeiro, pp 127–137
Scott KG, Logan MR, Klammer GM, Teoh DA, Buret AG (2000) Jejunal brush border microvillous alterations in Giardia muris-infected mice: role of T lymphocytes and interleukin-6. Infect Immun 68:3412–3418
Shukla G, Devi P, Sehgal R (2008) Effect of Lactobacillus casei as a probiotic on modulation of giardiasis. Dig Dis Sci 53:2671–2679
Travers MA, Florent I, Kohl L, Grellier P (2011) Probiotics for the control of parasites: an overview. J Parasitol Res 2011:1–11
Uda-Shimoda CF, Colli CM, Pavanelli MF, Falavigna-Guilherme AL, Gomes ML (2014) Simplified protocol for DNA extraction and amplification of 2 molecular markers to detect and type Giardia duodenalis. Diagn Microbiol Infect Dis 78:53–58
Venkatesan P, Finch RG, Wakelin D (1997) A comparison of mucosal inflammatory responses to Giardia muris in resistant B10 and susceptible BALB/c mice. Parasite Immunol 19:137–143
Younas M, Shah S, Talaat A (2008) Frequency of Giardia lamblia infection in children with recurrent abdominal pain. J Pak Med Assoc 58:171–174
Acknowledgements
We are grateful to Programa de Apoio à Pós-Graduação—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (PROAP-CAPES) for financial support, and R. C. Bezagio has benefited from CAPES by the study scholarship.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethics Committee in the Use of Animals in Experimentation (CEAE) at the Universidade Estadual de Maringá—Brazil (Registration No. 9375170816).
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Bezagio, R.C., Colli, C.M., Romera, L.I.L. et al. Synergistic effects of fenbendazole and metronidazole against Giardia muris in Swiss mice naturally infected. Parasitol Res 116, 939–944 (2017). https://doi.org/10.1007/s00436-016-5367-9
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DOI: https://doi.org/10.1007/s00436-016-5367-9