Different treatment schemes and dynamizations of Trypanosoma cruzi biotherapies: what information do they transfer to the organism in infected mice?

Background: The use of biotherapies in Trypanosoma cruzi infection can provide an understanding about effects of these highly diluted medications.

Objectives: To evaluate different treatment schemes and dynamizations of biotherapies prepared from blood trypomastigotes (buffy coat) in mice infected with T. cruzi.

Methods: Swiss mice infected with Y strain of T. cruzi were divided into two experiments. Experiment 1, all treated groups received biotherapy 7dH (10 μL/mL ad libitum) in different treatment schemes: TB_7dH – treated 3 days before infection; TBA_7dH – treated 3 days before and after infection; TBAe.d._7dH – treated 3 days before infection and every day after infection and IC – infection control. Experiment 2, all treated groups received medication in different dynamizations 3 days before and after infection (10 μL/mL ad libitum): TBA_15dH – treated with biotherapy 15dH; TBA_16dH – treated with biotherapy 16dH; TBA_17dH – treated with biotherapy 17dH; TBA_p.chords – treated with biotherapy ‘potency chords’ and IC – infection control. We evaluated parasitological and clinical parameters.

Results: Experiment 1 showed that different treatment schemes with biotherapy 7dH produced different effects on infection evolution. TBA_7dH group had the best outcome, with lower parasitemia, higher survival, and better clinical evolution compared to IC. Experiment 2 showed that biotherapy ‘potency chords’ had effects different from the individual dynamizations that it contained (15dH, 16dH, and 17dH). Animals that had patent parasitemia had delayed emergence of parasites in blood and subsequent increase in parasitemia, but had better clinical evolution compared to IC.

Conclusions: The effects of T. cruzi biotherapies depend on frequency at which they are administered, dynamization, and host–parasite relationship/individual susceptibility of treated organism. Biotherapy appeared to transfer to infected organism ‘antigenic information’ related to parasite and ‘disease information’ related to molecules produced by host's immune response and contained in the buffy coat used to prepare the medication.

Keywords

Homeopathy - Biotherapy - Trypanosoma cruzi - Animal model - Parasitological evaluation - Clinical evaluation

• References

• 1 Chagas C. Nova tripanozomiase humana. Estudos sobre a morfologia e o ciclo evolutivo do Schizortypanum cruzi n.gen., s.sp. agente etiológico de uma entidade mórbida do homem. Mem Inst Oswaldo Cruz 1909; 1: 159-218.
• 2 World Health Organization, Chagas disease (American trypanosomiasis), Fact sheet N°340, 2015. Available: http://www.who.int/mediacentre/factsheets/fs340/en/ Accessed: April 14, 2015.
• 3 Hasslocher-Moreno A.M., de Sousa A.S., do Brasil P.E.A.A., Sperandio da Silva G.M., Xavier S.S., Chambela M.C. Safety of benznidazole use in the treatment of chronic Chagas' disease. J Antimicrob Chemother 2012; 67: 1261-1266.
• 4 Coura J.R., Castro S.L. A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz 2002; 97: 3-24.
• 5 Guedes P.M., Silva G.K., Gutierrez F.R., Silva J.S. Current status of Chagas disease chemotherapy. Expert Rev Anti Infect Ther 2011; 9: 609-620.
• 6 Coura J.R. Present situation and new strategies for Chagas disease chemotherapy: a proposal. Mem Inst Oswaldo Cruz 2009; 104: 549-554.
• 7 Queiroz A.O., Xavier S.C.C., Faria K.G., Bernardo R.R., Leitão T.C.A. Avaliação do bioterápico Trypanosoma cruzi 30 DH: Um Estudo In Vivo . Cult Homeopática 2006; 17: 9-13.
• 8 Almeida R.L., Campos M.C.O., Herrera L.V.B., Bonamin L.V., Fonseca A.H. Effects of homeopathy in mice experimentally infected with Trypanosoma cruzi . Homeopathy 2008; 97: 65-69.
• 9 Ferraz F.N., Simoni G.K., do Nascimento A. et al. Different forms of administration of biotherapy 7dH in mice experimentally infected by Trypanosoma cruzi produce different effects. Homeopathy 2011; 100: 237-243.
• 10 Aleixo D.L., Ferraz F.N., Ferreira E.C. et al. Highly diluted medication reduces parasitemia and improves experimental infection evolution by Trypanosoma cruzi . BMC Res Notes 2012; 5: 352-367.
• 11 Ferraz F.N., Bilotti C.C., Aleixo D.L., Martinichen-Herrero J.C., Nascimento Junior A.D., de Araújo S.M. Hematological and parasitological changes in mice experimentally infected by Trypanosoma cruzi and treated with biotherapy 7dH. Eur J Integr Med 2014; 6: 664-671.
• 12 Sandri P., Aleixo D.L., Falkowski G.J.S. et al. Trypanosoma cruzi: biotherapy made from trypomastigote modulates the inflammatory response. Homeopathy 2015; 104: 48-56.
• 13 Mutlu O., Ulak G., Kokturk S., Celikyurt I.K., Akar F., Erden F. Effects of homeopathic Anax imperator on behavioural and pain models in mice. Homeopathy 2015; 104: 15-23.
• 14 Rodrigues de Santana F., Coelho C.P., Cardoso T.N., Laurenti M.D., Perez Hurtado E.C., Bonamin L.V. Modulation of inflammation response to murine cutaneous Leishmaniosis by homeopathic medicines: thymulin 5cH. Homeopathy 2014; 103: 275-284.
• 15 Brasil. Farmacopeia Homeopática Brasileira. ANVISA. 3rd edn Brasília DF: Agência Nacional de Vigilância Sanitária; 2011
• 16 Frase W. La eficacia de las diluiciones homeopáticas en forma de acordes de potencias. Med Biol – Int J Biomed Res Ther 1999; 12: 59-61.
• 17 Reckeweg H.H. Homotoxicologia, enfermedad y curación con Terapias Antihomotóxicas. 2nd edn Baden-Baden: Aurelia–Verlog; 1992.
• 18 Pedalino C.M., Perazzo F.F., Carvalho J.C., Martinho K.S., Massoco C.O., Bonamin L.V. Effect of Atropa belladonna and Echinacea angustifolia in homeopathic dilution on experimental peritonitis. Homeopathy 2004; 93: 193-198.
• 19 Brasil, Presidência da República. Lei n.11.794, de 8 de outubro de 2008, Estabelece procedimento para o uso científico de animais Available: http://www.planalto.gov.br/ccivil_03/_ato2007-2010/2008/lei/l11794.htm Accessed: April 14, 2015.
• 20 Silva L.H.P., Nussenzweig V. Sobre uma cepa de Trypanosoma cruzi altamente virulenta para camundongo branco. Folia Clin Biol 1953; 20: 191-208.
• 21 Ferraz F.N., da Veiga F.K., Moreira N.M. et al. Evaluation of effect of succussed and unsuccussed homeopathic vehicle on murine infection by Trypanosoma cruzi . Int J High Dilution Res 2013; 12: 91-92. Proceedings of the XXVII GIRI Symposium, 2013 Sep 03–04, Bern (Switzerland).
• 22 Brener Z. Therapeutic activity and criterion of cure on mice experimentally infected with Trypanosoma cruzi . Rev Inst Med Trop São Paulo 1962; 4: 389-396.
• 23 Wincker P., Britto C., Pereira J.B., Cardoso M.A., Oelemann W., Morel C.M. Use of a simplified polymerase chain reaction procedure to detect Trypanosoma cruzi in blood samples patients in a rural endemic area. Am J Trop Med Hyg 1994; 51: 771-777.
• 24 Gomes M.L., Macedo A.M., Vago R., Pena S.D.J., Galvão L.M.C., Chiari E. Trypanosoma cruzi: optimization of polymerase chain reaction for detection in human blood. Exp Parasitol 1998; 88: 28-33.
• 25 Falkowski G.J.S., Sandri P.F., Tiyo R., Aleixo D.L., de Araújo S.M. Parameters for evaluation of clinical trial in mice infected with Trypanosoma cruzi . Arq Bras Med Vet Zootec 2012; 64: 1539-1546.
• 26 Moreira N.M., Zanoni J.N., de Oliveira Dalálio M.M., de Almeida Araújo E.J., Braga C.F., de Araújo S.M. Physical exercise protects myenteric neurons and reduces parasitemia in Trypanosoma cruzi infection. Exp Parasitol 2014; 141: 68-74.
• 27 Lindenau J.D.R., Guimarães L.S.P. Calculando o tamanho de efeito no SPSS. Rev HCPA 2012; 32: 363-381.
• 28 Araújo Jorge T.C., Castro S.L. Doença de Chagas: manual para experimentação animal. 1st edn Rio de Janeiro: Editora FioCruz; 2000.
• 29 Ortega P.S. Introducción a la medicina homeopática: teoria y técnica. 1st edn México D.F.: Biblioteca de Homopatía de México; 1992.
• 30 Bonamin L.V. Signals and images: contributions and contradictions about high dilution research. 1st edn Heidelberg (Deutschland): Springer; 2008.
• 31 Pedalino C.M.V. Medicamentos homeopáticos em acordes de potência. Cult Homeopática 2006; 16: 18-21.
• 32 Gomez D., Jorge M. Aportación al estudio de la eficacia de diluciones homeopáticas de Phosphorus . Med Biológica 1992; 5: 4-14.
• 33 Ferraz F.N., Veiga F.K., Aleixo D.L., da Silva S.S., Pavanelli W.R., de Araújo S.M. Biotherapy of mice's serum 13cH modifies parasitological and immunological parameters of Trypanosoma cruzi infection. Int J High Dilution Res 2014; 13: 105-107. Proceedings of the XXVIII GIRI Symposium, 2014 Jun 20–22, Sighisoara (Romania).
• 34 Hahnemann S. Doenças crônicas – Sua natureza peculiar e sua cura homeopática, 6ª ed brasileira (tradução). São Paulo: GEHSP Benoit Mure; 2010.
• 35 Marzotto M., Conforti A., Magnani P., Zanolin M.E., Bellavite P. Effects of Ignatia amara in mouse behavioural models. Homeopathy 2012; 101: 57-67.
• 36 Cavalca P.A.M., Lolis M.I.G.A., Reis B., Bonato C.M. Homeopathic and larvicide effect of Eucalyptus cinerea essential oil against Aedes aegypti . Braz Arch Biol Technol 2010; 53: 835-843.
• 37 Bracho G., Varela E., Fernández R. et al. Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control. Homeopathy 2010; 99: 156-166.
• 38 Siqueira C.M., Homsani F., Veiga V.F. et al. Homeopathic medicines for prevention of influenza and acute respiratory tract infections in children: blind, randomized, placebo-controlled clinical trial. Homeopathy 2016; 105: 71-77.