Top

Published in:

Open Access 01-12-2013 | Research article

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

Authors: Amanda Farage Frade, Cristina Wide Pissetti, Barbara Maria Ianni, Bruno Saba, Hui Tzu Lin-Wang, Luciana Gabriel Nogueira, Ariana de Melo Borges, Paula Buck, Fabrício Dias, Monique Baron, Ludmila Rodrigues Pinto Ferreira, Andre Schmidt, José Antonio Marin-Neto, Mario Hirata, Marcelo Sampaio, Abílio Fragata, Alexandre Costa Pereira, Eduardo Donadi, Jorge Kalil, Virmondes Rodrigues, Edecio Cunha-Neto, Christophe Chevillard

Published in: BMC Infectious Diseases | Issue 1/2013

Abstract

Background

Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage.

Methods

Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects.

Results

The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%.

Conclusions

Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.

Schofield CJ, Jannin J, Salvatella R: The future of Chagas disease control. Trends Parasitol. 2006, 22 (12): 583-588. 10.1016/j.pt.2006.09.011.CrossRefPubMed

Coura JR: Chagas disease: what is known and what is needed–a background article. Mem Inst Oswaldo Cruz. 2007, 102 (Suppl 1): 113-122.PubMed

Kirchhoff LV, Weiss LM, Wittner M, Tanowitz HB: Parasitic diseases of the heart. Front Biosci. 2004, 9: 706-723. 10.2741/1255.CrossRefPubMed

Barbosa AP, Cardinalli Neto A, Otaviano AP, Rocha BF, Bestetti RB: Comparison of outcome between Chagas cardiomyopathy and idiopathic dilated cardiomyopathy. Arq Bras Cardiol. 2011, 97 (6): 517-525. 10.1590/S0066-782X2011005000112.CrossRefPubMed

Bestetti RB, Muccillo G: Clinical course of Chagas’ heart disease: a comparison with dilated cardiomyopathy. Int J Cardiol. 1997, 60 (2): 187-193. 10.1016/S0167-5273(97)00083-1.CrossRefPubMed

Bafica A, Santiago HC, Goldszmid R, Ropert C, Gazzinelli RT, Sher A: Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J Immunol. 2006, 177 (6): 3515-3519.CrossRefPubMed

Reis MM, Higuchi Mde L, Benvenuti LA, Aiello VD, Gutierrez PS, Bellotti G, Pileggi F: An in situ quantitative immunohistochemical study of cytokines and IL-2R + in chronic human chagasic myocarditis: correlation with the presence of myocardial Trypanosoma cruzi antigens. Clin Immunol Immunopathol. 1997, 83 (2): 165-172. 10.1006/clin.1997.4335.CrossRefPubMed

Bilate AM, Cunha-Neto E: Chagas disease cardiomyopathy: current concepts of an old disease. Rev Inst Med Trop Sao Paulo. 2008, 50 (2): 67-74. 10.1590/S0036-46652008007500001.CrossRefPubMed

Muller U, Kohler G, Mossmann H, Schaub GA, Alber G, Di Santo JP, Brombacher F, Holscher C: IL-12-independent IFN-gamma production by T cells in experimental Chagas’ disease is mediated by IL-18. J Immunol. 2001, 167 (6): 3346-3353.CrossRefPubMed

10.

Rocha Rodrigues DB, dos Reis MA, Romano A, Pereira SA, Teixeira Vde P, Tostes S, Rodrigues V: In situ expression of regulatory cytokines by heart inflammatory cells in Chagas’ disease patients with heart failure. Clin Dev Immunol. 2013, 2012: 361730-

11.

Ribeirao M, Pereira-Chioccola VL, Renia L, Augusto Fragata Filho A, Schenkman S, Rodrigues MM: Chagasic patients develop a type 1 immune response to Trypanosoma cruzi trans-sialidase. Parasite Immunol. 2000, 22 (1): 49-53. 10.1046/j.1365-3024.2000.00260.x.CrossRefPubMed

12.

Cunha-Neto E, Dzau VJ, Allen PD, Stamatiou D, Benvenutti L, Higuchi ML, Koyama NS, Silva JS, Kalil J, Liew CC: Cardiac gene expression profiling provides evidence for cytokinopathy as a molecular mechanism in Chagas’ disease cardiomyopathy. Am J Pathol. 2005, 167 (2): 305-313. 10.1016/S0002-9440(10)62976-8.CrossRefPubMedPubMedCentral

13.

Cunha-Neto E, Kalil J: Heart-infiltrating and peripheral T cells in the pathogenesis of human Chagas’ disease cardiomyopathy. Autoimmunity. 2001, 34 (3): 187-192. 10.3109/08916930109007383.CrossRefPubMed

14.

Talvani A, Rocha MO, Barcelos LS, Gomes YM, Ribeiro AL, Teixeira MM: Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy. Clin Infect Dis. 2004, 38 (7): 943-950. 10.1086/381892.CrossRefPubMed

15.

Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R: Evidence that development of severe cardiomyopathy in human Chagas’ disease is due to a Th1-specific immune response. Infect Immun. 2003, 71 (3): 1185-1193. 10.1128/IAI.71.3.1185-1193.2003.CrossRefPubMedPubMedCentral

16.

Talvani A, Rocha MO, Ribeiro AL, Correa-Oliveira R, Teixeira MM: Chemokine receptor expression on the surface of peripheral blood mononuclear cells in Chagas disease. J Infect Dis. 2004, 189 (2): 214-220. 10.1086/380803.CrossRefPubMed

17.

Araujo FF, Gomes JA, Rocha MO, Williams-Blangero S, Pinheiro VM, Morato MJ, Correa-Oliveira R: Potential role of CD4 + CD25HIGH regulatory T cells in morbidity in Chagas disease. Front Biosci. 2007, 12: 2797-2806. 10.2741/2273.CrossRefPubMed

18.

Guedes PM, Gutierrez FR, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ, Bendhack LM, Rassi A, Rassi A, Schmidt A, Maciel BC, et al: Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas’ disease. PLoS Negl Trop Dis. 2012, 6 (4): e1630-10.1371/journal.pntd.0001630.CrossRefPubMedPubMedCentral

19.

Magalhaes LM, Villani FN, Nunes Mdo C, Gollob KJ, Rocha MO, Dutra WO: High interleukin 17 expression is correlated with better cardiac function in human Chagas disease. J Infect Dis. 2013, 207 (4): 661-665. 10.1093/infdis/jis724.CrossRefPubMed

20.

Abel LC, Rizzo LV, Ianni B, Albuquerque F, Bacal F, Carrara D, Bocchi EA, Teixeira HC, Mady C, Kalil J, et al: Chronic Chagas’ disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection. J Autoimmun. 2001, 17 (1): 99-107. 10.1006/jaut.2001.0523.CrossRefPubMed

21.

Reis DD, Jones EM, Tostes S, Lopes ER, Chapadeiro E, Gazzinelli G, Colley DG, McCurley TL: Expression of major histocompatibility complex antigens and adhesion molecules in hearts of patients with chronic Chagas’ disease. Am J Trop Med Hyg. 1993, 49 (2): 192-200.PubMed

22.

Nogueira LG, Santos RH, Ianni BM, Fiorelli AI, Mairena EC, Benvenuti LA, Frade A, Donadi E, Dias F, Saba B, et al: Myocardial Chemokine expression and intensity of myocarditis in Chagas cardiomyopathy Are controlled by polymorphisms in CXCL9 and CXCL10. PLoS Negl Trop Dis. 2012, 6 (10): e1867-10.1371/journal.pntd.0001867.CrossRefPubMedPubMedCentral

23.

Gomes JA, Bahia-Oliveira LM, Rocha MO, Busek SC, Teixeira MM, Silva JS, Correa-Oliveira R: Type 1 chemokine receptor expression in Chagas’ disease correlates with morbidity in cardiac patients. Infect Immun. 2005, 73 (12): 7960-7966. 10.1128/IAI.73.12.7960-7966.2005.CrossRefPubMedPubMedCentral

24.

Zicker F, Smith PG, Netto JC, Oliveira RM, Zicker EM: Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas’ cardiopathy. Am J Trop Med Hyg. 1990, 43 (5): 498-505.PubMed

25.

Llop E, Rothhammer F, Acuna M, Apt W: HLA antigens in cardiomyopathic Chilean chagasics. Am J Hum Genet. 1988, 43 (5): 770-773.PubMedPubMedCentral

26.

Llop E, Rothhammer F, Acuna M, Apt W, Arribada A: HLA antigens in Chagas cardiomyopathy: new evidence based on a case–control study. Rev Med Chil. 1991, 119 (6): 633-636.PubMed

27.

Fernandez-Mestre MT, Layrisse Z, Montagnani S, Acquatella H, Catalioti F, Matos M, Balbas O, Makhatadze N, Dominguez E, Herrera F, et al: Influence of the HLA class II polymorphism in chronic Chagas’ disease. Parasite Immunol. 1998, 20 (4): 197-203.PubMed

28.

Layrisse Z, Fernandez MT, Montagnani S, Matos M, Balbas O, Herrera F, Colorado IA, Catalioti F, Acquatella H: HLA-C(*)03 is a risk factor for cardiomyopathy in Chagas disease. Hum Immunol. 2000, 61 (9): 925-929. 10.1016/S0198-8859(00)00161-0.CrossRefPubMed

29.

Deghaide NH, Dantas RO, Donadi EA: HLA class I and II profiles of patients presenting with Chagas’ disease. Dig Dis Sci. 1998, 43 (2): 246-252. 10.1023/A:1018829600200.CrossRefPubMed

30.

Colorado IA, Acquatella H, Catalioti F, Fernandez MT, Layrisse Z: HLA class II DRB1, DQB1, DPB1 polymorphism and cardiomyopathy due to Trypanosoma cruzi chronic infection. Hum Immunol. 2000, 61 (3): 320-325. 10.1016/S0198-8859(99)00177-9.CrossRefPubMed

31.

Rodriguez-Perez JM, Cruz-Robles D, Hernandez-Pacheco G, Perez-Hernandez N, Murguia LE, Granados J, Reyes PA, Vargas-Alarcon G: Tumor necrosis factor-alpha promoter polymorphism in Mexican patients with Chagas’ disease. Immunol Lett. 2005, 98 (1): 97-102. 10.1016/j.imlet.2004.10.017.CrossRefPubMed

32.

Campelo V, Dantas RO, Simoes RT, Mendes-Junior CT, Sousa SM, Simoes AL, Donadi EA: TNF microsatellite alleles in Brazilian Chagasic patients. Dig Dis Sci. 2007, 52 (12): 3334-3339. 10.1007/s10620-006-9699-7.CrossRefPubMed

33.

Drigo SA, Cunha-Neto E, Ianni B, Mady C, Fae KC, Buck P, Kalil J, Goldberg AC: Lack of association of tumor necrosis factor-alpha polymorphisms with Chagas disease in Brazilian patients. Immunol Lett. 2007, 108 (1): 109-111. 10.1016/j.imlet.2006.10.008.CrossRefPubMed

34.

Beraun Y, Nieto A, Collado MD, Gonzalez A, Martin J: Polymorphisms at tumor necrosis factor (TNF) loci are not associated with Chagas’ disease. Tissue Antigens. 1998, 52 (1): 81-83. 10.1111/j.1399-0039.1998.tb03028.x.CrossRefPubMed

35.

Drigo SA, Cunha-Neto E, Ianni B, Cardoso MR, Braga PE, Fae KC, Nunes VL, Buck P, Mady C, Kalil J, et al: TNF gene polymorphisms are associated with reduced survival in severe Chagas’ disease cardiomyopathy patients. Microbes Infect. 2006, 8 (3): 598-603. 10.1016/j.micinf.2005.08.009.CrossRefPubMed

36.

Florez O, Martin J, Gonzalez CI: Interleukin 4, interleukin 4 receptor-alpha and interleukin 10 gene polymorphisms in Chagas disease. Parasite Immunol. 2011, 33 (9): 506-511. 10.1111/j.1365-3024.2011.01314.x.CrossRefPubMed

37.

Cruz-Robles D, Chavez-Gonzalez JP, Cavazos-Quero MM, Perez-Mendez O, Reyes PA, Vargas-Alarcon G: Association between IL-1B and IL-1RN gene polymorphisms and Chagas’ disease development susceptibility. Immunol Invest. 2009, 38 (3–4): 231-239.CrossRefPubMed

38.

Costa GC, da Costa Rocha MO, Moreira PR, Menezes CA, Silva MR, Gollob KJ, Dutra WO: Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy. J Infect Dis. 2009, 199 (3): 451-454. 10.1086/596061.CrossRefPubMed

39.

Moreno M, Silva EL, Ramirez LE, Palacio LG, Rivera D, Arcos-Burgos M: Chagas’ disease susceptibility/resistance: linkage disequilibrium analysis suggests epistasis between major histocompatibility complex and interleukin-10. Tissue Antigens. 2004, 64 (1): 18-24. 10.1111/j.1399-0039.2004.00260.x.CrossRefPubMed

40.

Zafra G, Morillo C, Martin J, Gonzalez A, Gonzalez CI: Polymorphism in the 3′ UTR of the IL12B gene is associated with Chagas’ disease cardiomyopathy. Microbes Infect. 2007, 9 (9): 1049-1052. 10.1016/j.micinf.2007.04.010.CrossRefPubMed

41.

Ramasawmy R, Cunha-Neto E, Fae KC, Borba SC, Teixeira PC, Ferreira SC, Goldberg AC, Ianni B, Mady C, Kalil J: Heterozygosity for the S180L variant of MAL/TIRAP, a gene expressing an adaptor protein in the Toll-like receptor pathway, is associated with lower risk of developing chronic Chagas cardiomyopathy. J Infect Dis. 2009, 199 (12): 1838-1845. 10.1086/599212.CrossRefPubMed

42.

Ramasawmy R, Cunha-Neto E, Fae KC, Martello FG, Muller NG, Cavalcanti VL, Ianni B, Mady C, Kalil J, Goldberg AC: The monocyte chemoattractant protein-1 gene polymorphism is associated with cardiomyopathy in human chagas disease. Clin Infect Dis. 2006, 43 (3): 305-311. 10.1086/505395.CrossRefPubMed

43.

Ramasawmy R, Cunha-Neto E, Fae KC, Muller NG, Cavalcanti VL, Drigo SA, Ianni B, Mady C, Kalil J, Goldberg AC: BAT1, a putative anti-inflammatory gene, is associated with chronic Chagas cardiomyopathy. J Infect Dis. 2006, 193 (10): 1394-1399. 10.1086/503368.CrossRefPubMed

44.

Ramasawmy R, Fae KC, Cunha-Neto E, Muller NG, Cavalcanti VL, Ferreira RC, Drigo SA, Ianni B, Mady C, Goldberg AC, et al: Polymorphisms in the gene for lymphotoxin-alpha predispose to chronic Chagas cardiomyopathy. J Infect Dis. 2007, 196 (12): 1836-1843. 10.1086/523653.CrossRefPubMed

45.

Pissetti CW, de Oliveira RF, Correia D, Nascentes GA, Llaguno MM, Rodrigues V: Association between the lymphotoxin-alpha gene polymorphism and chagasic cardiopathy. J Interferon Cytokine Res. 2013, 33 (3): 130-135. 10.1089/jir.2012.0024.CrossRefPubMed

46.

Ramasawmy R, Fae KC, Cunha-Neto E, Borba SC, Ianni B, Mady C, Goldberg AC, Kalil J: Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas’ cardiomyopathy among Trypanosoma cruzi-infected individuals. Mol Immunol. 2008, 45 (1): 283-288. 10.1016/j.molimm.2007.04.015.CrossRefPubMed

47.

Calzada JE, Nieto A, Beraun Y, Martin J: Chemokine receptor CCR5 polymorphisms and Chagas’ disease cardiomyopathy. Tissue Antigens. 2001, 58 (3): 154-158. 10.1034/j.1399-0039.2001.580302.x.CrossRefPubMed

48.

Fernandez-Mestre MT, Montagnani S, Layrisse Z: Is the CCR5-59029-G/G genotype a protective factor for cardiomyopathy in Chagas disease?. Hum Immunol. 2004, 65 (7): 725-728. 10.1016/j.humimm.2004.05.002.CrossRefPubMed

49.

Torres OA, Calzada JE, Beraun Y, Morillo CA, Gonzalez CI, Gonzalez A, Martin J: Association of the macrophage migration inhibitory factor -173G/C polymorphism with Chagas disease. Hum Immunol. 2009, 70 (7): 543-546. 10.1016/j.humimm.2009.04.022.CrossRefPubMed

50.

Torres OA, Calzada JE, Beraun Y, Morillo CA, Gonzalez A, Gonzalez CI, Martin J: Role of the IFNG +874 T/A polymorphism in Chagas disease in a Colombian population. Infect Genet Evol. 2010, 10 (5): 682-685. 10.1016/j.meegid.2010.03.009.CrossRefPubMed

51.

Cunha-Neto E, Kalil J: Autoimmunity in Chagas’ heart disease. Sao Paulo Med J. 1995, 113 (2): 757-766.PubMed

52.

Teixeira PC, Frade AF, Nogueira LG, Kalil J, Chevillard C, Cunha-Neto E: Pathogenesis of Chagas disease cardiomyopathy. World J Clin Infect Dis. 2012, 2 (3): 39-53. 10.5495/wjcid.v2.i3.39.CrossRef

53.

Vasconcelos RH, Montenegro SM, Azevedo EA, Gomes YM, Morais CN: Genetic susceptibility to chronic Chagas disease: an overview of single nucleotide polymorphisms of cytokine genes. Cytokine. 2012, 59 (2): 203-208. 10.1016/j.cyto.2012.04.035.CrossRefPubMed

54.

Fae KC, Drigo SA, Cunha-Neto E, Ianni B, Mady C, Kalil J, Goldberg AC: HLA and beta-myosin heavy chain do not influence susceptibility to Chagas disease cardiomyopathy. Microbes Infect. 2000, 2 (7): 745-751. 10.1016/S1286-4579(00)00501-3.CrossRefPubMed

55.

Weitzel T, Zulantay I, Danquah I, Hamann L, Schumann RR, Apt W, Mockenhaupt FP: Mannose-binding lectin and Toll-like receptor polymorphisms and Chagas disease in Chile. Am J Trop Med Hyg. 2012, 86 (2): 229-232. 10.4269/ajtmh.2012.11-0539.CrossRefPubMedPubMedCentral

56.

Jorge MT, Macedo TA, Janones RS, Carizzi DP, Heredia RA, Acha RE: Types of arrhythmia among cases of American trypanosomiasis, compared with those in other cardiology patients. Ann Trop Med Parasitol. 2003, 97 (2): 139-148. 10.1179/000349803235001561.CrossRefPubMed

57.

van Veldhuisen DJ, Linssen GC, Jaarsma T, van Gilst WH, Hoes AW, Tijssen JG, Paulus WJ, Voors AA, Hillege HL: B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol. 2013, 61 (14): 1498-1506. 10.1016/j.jacc.2012.12.044.CrossRefPubMed

58.

Januzzi JL: Natriuretic peptides, ejection fraction, and prognosis: parsing the phenotypes of heart failure. J Am Coll Cardiol. 2013, 61 (14): 1507-1509. 10.1016/j.jacc.2013.01.039.CrossRefPubMed

59.

Barretto AC, Arteaga E, Mady C, Ianni BM, Bellotti G, Pileggi F: Male sex. Prognostic factor in Chagas’ disease. Arq Bras Cardiol. 1993, 60 (4): 225-227.PubMed

60.

Basquiera AL, Sembaj A, Aguerri AM, Omelianiuk M, Guzman S, Moreno Barral J, Caeiro TF, Madoery RJ, Salomone OA: Risk progression to chronic Chagas cardiomyopathy: influence of male sex and of parasitaemia detected by polymerase chain reaction. Heart. 2003, 89 (10): 1186-1190. 10.1136/heart.89.10.1186.CrossRefPubMedPubMedCentral

61.

Florez O, Martin J, Gonzalez CI: Genetic variants in the chemokines and chemokine receptors in Chagas disease. Hum Immunol. 2012, 73 (8): 852-858. 10.1016/j.humimm.2012.04.005.CrossRefPubMed

62.

Marino AP, da Silva A, dos Santos P, Pinto LM, Gazzinelli RT, Teixeira MM, Lannes-Vieira J: Regulated on activation, normal T cell expressed and secreted (RANTES) antagonist (Met-RANTES) controls the early phase of Trypanosoma cruzi-elicited myocarditis. Circulation. 2004, 110 (11): 1443-1449. 10.1161/01.CIR.0000141561.15939.EC.CrossRefPubMed

63.

Medeiros GA, Silverio JC, Marino AP, Roffe E, Vieira V, Kroll-Palhares K, Carvalho CE, Silva AA, Teixeira MM, Lannes-Vieira J: Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage. Microbes Infect. 2009, 11 (2): 264-273. 10.1016/j.micinf.2008.11.012.CrossRefPubMed

64.

Marino AP, Silva AA, Santos PV, Pinto LM, Gazinelli RT, Teixeira MM, Lannes-Vieira J: CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis. Mem Inst Oswaldo Cruz. 2005, 100 (Suppl 1): 93-96.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/587/prepub

Title: Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways
Authors: Amanda Farage Frade
Cristina Wide Pissetti
Barbara Maria Ianni
Bruno Saba
Hui Tzu Lin-Wang
Luciana Gabriel Nogueira
Ariana de Melo Borges
Paula Buck
Fabrício Dias
Monique Baron
Ludmila Rodrigues Pinto Ferreira
Andre Schmidt
José Antonio Marin-Neto
Mario Hirata
Marcelo Sampaio
Abílio Fragata
Alexandre Costa Pereira
Eduardo Donadi
Jorge Kalil
Virmondes Rodrigues
Edecio Cunha-Neto
Christophe Chevillard
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2013
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/1471-2334-13-587

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Establishment and application of real-time quantitative PCR for diagnosing invasive Aspergillosis via the blood in hematological patients: targeting a specific sequence of Aspergillus 28S-ITS2

Maternal anaemia and duration of zidovudine in antiretroviral regimens for preventing mother-to-child transmission: a randomized trial in three African countries

Antibiograms from community-acquired uropathogens in Gulu, northern Uganda - a cross-sectional study

Prevalence of rotavirus and adenovirus associated with diarrhea among displaced communities in Khartoum, Sudan

Age-related differences in symptoms, diagnosis and prognosis of bacteremia

Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali district (Bihar), India

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials