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1 Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Lee BY, Bacon KM, Bottazzi ME, Hotez PJ. Global economic burden of Chagas disease: a computational simulation model. Lancet Infect Dis 2013; published online Feb 8.

2 Appendix Table 1. Model Inputs Acute Disease Parameter State Country Income Quartile Value Reference Low Middle Income $785 A High Middle Income $2613 Low Income $257 High Income $4829 Low Income $72 Indeterminate Disease Low Middle Income $221 A High Middle Income $1,603 High Income $3280 ** B Low Income $612 Low Middle Income $805 C (Cardiomyopathy) High Middle Income $4463 D High Income $6006 E Diagnosis, Treatment, and Monitoring Costs ($US) * Duration of Absenteeism (Days) Probabilities Risk (Given T cruzi infection) Seeking Treatment Mortality Low Income $1,609 Low Middle Income $2701 *** F (Congestive Heart Failure, CHF) High Middle Income $5224 G High Income $9495 H Low Income $705 Low Middle Income $1044 A (Megaviscera) High Middle Income $2217 High Income $3640 B Low Income $36 Low Middle Income $111 A (Surgery for Megacolon) High Middle Income $1,204 High Income $2,527 I Low Income $649 Low Middle Income $1986 (Pacemaker Implant) High Middle Income $6608 J High Income $ **** K Acute Disease - 11 A Indeterminate Disease - 5 A (Cardiomyopathy or CHF) - 15 A (Megaviscera) - 11 A Megacolon Surgery A Abbreviation Acute Disease pacute 5 0% L (Cardiomyopathy, annual, pcardiomyopathy 2 0% M endemic) (CHF, annual) pchf 4 0% N (Megaviscera, annual) pmegaviscera % O Acute Disease % P Indeterminate Disease % Q (Cardiomyopathy or CHF) % P - assumed same as 78 0% (Megaviscera) cardiac disease Megaviscera Surgery ( 2 surgeries) - 5 0% O 1 st Pacemaker Implant - 3 5% R 2 nd Pacemaker Implant % ***** R Cure, Acute Disease pcure Acute 65 0% S Cure, Indeterminate Disease pcure Indeterminate 8 0% T Treatment Side Effects - 5 0% U Acute Disease (annual) pmortality Acute 5 0% V Indeterminate Disease (annual) pmortality Indeterminate 0 18% W (Cardiomyopathy, annual) pmortality Cardiomyopathy 4 2% N 1

3 (CHF, annual) Megaviscera Surgery pmortality CHF 30 0% N pmortality Megaviscera Surgery 2 25% O * Treatment costs do not include productivity losses Included initial consult, general and specific diagnostic tests in addition to treatment Included periodic medical checkups involving laboratory tests and x-rays Countries reporting T cruzi infections were divided into quartiles according to their GDP/capita. Annual treatment costs (by disease phase) from the literature were converted into 2012 US dollars using a 3% discount rate (ref X) and then extrapolated to country quartiles where no treatment data was found, assuming a linear relationship between GDP/capita and medical costs. This was concluded to be a reasonable assumption, as the GDP/capita demonstrated good predictive ability (R 2 >0.9) for treatment in all disease states with costs for >2 income quartiles. ** Gamma distribution (SD: 1230) Gamma distribution (SD: 75) Gamma distribution (SD: 3162) Gamma distribution (SD: 9238) *** Gamma distribution (SD: 2561) Gamma distribution (SD: 3073) Gamma distribution (SD: ) Gamma distribution (SD: 2610) **** Gamma distribution (SD: ) Uniform distribution (7 15) Uniform distribution (7 15) Triangular distribution ( %) ***** Triangular distribution ( %) Uniform distribution (50 80%) Uniform distribution (6 10%) Uniform distribution ( %) 2

4 Table 2. Country Income Classification and Reported Chagas Cases Country GDP per capita (US$) (Y) No. Chagas Cases Ref. Low Income (<$5053) Nicaragua Z Bolivia Z Honduras Z Paraguay Z Guatemala Z El Salvador Z Ecuador Z Belize Z Guyana Z Low Middle Income ($ ) Peru Z Colombia Z Panama Z Costa Rica Z Argentina Z Mexico Z Brazil Z Venezuela Z High Middle Income ($ ) Uruguay ,700 Z Chile ,200 Z Portugal AA Spain AA - ( ) AC Italy AA, 7671 AD - ( ) AF United Kingdom AA France AA High Income (>$39 615) Germany AA Belgium AA Canada AB United States ( ) Z, AB Sweden AA Australia AB Switzerland AG Austria ( ) AE Netherlands AA Worldwide ( ) 3

5 Table 3. References for Model Inputs A B C D E F References Basombrio MA, Schofield CJ, Rojas CL, del Rey EC. A cost-benefit analysis of Chagas disease control in north-western Argentina. Trans R Soc Trop Med Hyg Mar-Apr;92(2): Basombrio MA, Schofield CJ, Rojas CL, del Rey EC. A cost-benefit analysis of Chagas disease control in north-western Argentina. Trans R Soc Trop Med Hyg Mar-Apr;92(2): Castillo-Riquelme M, Guhl F, Turriago B, Pinto N, Rosas F, Martinez MF, et al. The costs of preventing and treating chagas disease in Colombia. PLoS Negl Trop Dis. 2008;2(11):e336. * This reference provided costs of a cardiomyopathy case --- a complication of diabetes. * This reference provided costs of a cardiomyopathy case --- a complication of diabetes. Basombrio MA, Schofield CJ, Rojas CL, del Rey EC. A cost-benefit analysis of Chagas disease control in north-western Argentina. Trans R Soc Trop Med Hyg Mar-Apr;92(2): Castillo-Riquelme M, Guhl F, Turriago B, Pinto N, Rosas F, Martinez MF, et al. The costs of preventing and treating chagas disease in Colombia. PLoS Negl Trop Dis. 2008;2(11):e336. Araujo DV, Tavares LR, Verissimo R, Ferraz MB, Mesquita ET. [Cost of heart failure in the Unified Health System]. Arq Bras Cardiol May;84(5): G Hart WM, Rubio-Terres C, Pajuelo F, Gonzalez Juanatey JR. Cost-effectiveness of the treatment of heart failure with ramipril: a Spanish analysis of the AIRE study. Eur J Heart Fail Aug;4(4): H Cline CM, Israelsson BY, Willenheimer RB, Broms K, Erhardt LR. Cost effective management programme for heart failure reduces hospitalisation. Heart Nov;80(5): I J K Agapova M, Busch MP, Custer B. Cost-effectiveness of screening the US blood supply for Trypanosoma cruzi. Transfusion Oct;50(10): American Medical Association. CPT Code/Relative Value Search. American Medical Association; American Medical Association. CPT Code/Relative Value Search. American Medical Association; Heerey A, Lauer M, Alsolaiman F, Czerr J, James K. Cost effectiveness of biventricular pacemakers in heart failure patients. Am J Cardiovasc Drugs. 2006;6(2): Nichol G, Kaul P, Huszti E, Bridges JF. Cost-effectiveness of cardiac resynchronization therapy in patients with symptomatic heart failure. Ann Intern Med Sep 7;141(5): Rinfret S, Cohen DJ, Lamas GA, Fleischmann KE, Weinstein MC, Orav J, et al. Cost-effectiveness of dual-chamber pacing compared with ventricular pacing for sinus node dysfunction. Circulation Jan 18;111(2): L Teixeira AR, Nitz N, Guimaro MC, Gomes C, Santos-Buch CA. Chagas disease. Postgrad Med J Dec;82(974): M Punukollu G, Gowda RM, Khan IA, Navarro VS, Vasavada BC. Clinical aspects of the Chagas' heart disease. Int J Cardiol

6 N O P Q R Feb 14;115(3): Espinosa R, Carrasco HA, Belandria F, Fuenmayor AM, Molina C, Gonzalez R, et al. Life expectancy analysis in patients with Chagas' disease: prognosis after one decade ( ). Int J Cardiol May;8(1): Wilson LS, Strosberg AM, Barrio K. Cost-effectiveness of Chagas disease interventions in latin america and the Caribbean: Markov models. Am J Trop Med Hyg Nov;73(5): Castillo-Riquelme M, Guhl F, Turriago B, Pinto N, Rosas F, Martinez MF, et al. The costs of preventing and treating chagas disease in Colombia. PLoS Negl Trop Dis. 2008;2(11):e336. Lee BY, Bacon KM, Wateska AR, Bottazzi ME, Dumonteil E, Hotez PJ. Modeling the economic value of a Chagas' disease therapeutic vaccine. Hum Vaccin Immunother Sep 1;8(9). Basquiera AL, Sembaj A, Aguerri AM, Omelianiuk M, Guzman S, Moreno Barral J, et al. Risk progression to chronic Chagas cardiomyopathy: influence of male sex and of parasitaemia detected by polymerase chain reaction. Heart Oct;89(10): Rassi A, Jr., Rassi A, Marin-Neto JA. Chagas disease. Lancet Apr 17;375(9723): Coura JR. Present situation and new strategies for Chagas disease chemotherapy: a proposal. Mem Inst Oswaldo Cruz Jul;104(4): S Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Medecins Sans Frontieres. PLoS Negl Trop Dis. 2009;3(7):e488. de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet Nov 23;348(9039): T Ferreira HO. Tratamento da forma indeterminada da doenca de Chagas com Nifurtimox e Benznidazole. Rev Soc Bras Med Trop. 1990;23: Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug safety, and effectiveness of etiological U treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Medecins Sans Frontieres. PLoS Negl Trop Dis. 2009;3(7):e488. Teixeira AR, Teixeira G, Macedo V, Prata A. Acquired cell-mediated immunodepression in acute Chagas' disease. J Clin Invest. V 1978 Dec;62(6): W Rassi A, Jr., Rassi SG, Rassi A. Sudden death in Chagas' disease. Arq Bras Cardiol Jan;76(1): Gold M, Siegel J, Russell L, Weinstein M. Cost-Effectiveness in Health and Medicine. New York; X Y The World Bank. GDP per capita (current US$) ed; Bern C, Kjos S, Yabsley MJ, Montgomery SP. Trypanosoma cruzi and Chagas' Disease in the United States. Clin Microbiol Rev. Z 2011 Oct;24(4): Perez-Molina JA, Perez-Ayala A, Parola P, Jackson Y, Odolini S, Lopez-Velez R, et al. EuroTravNet: imported Chagas disease in AA nine European countries: 2008 to Euro Surveill. 2011;16(37):52-6. Schmunis GA. Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Mem Inst Oswaldo AB Cruz Oct 30;102 Suppl 1: Navarro M, Perez-Ayala A, Guionnet A, Perez-Molina JA, Estevez L, Norman F, et al. Targeted screening and health education for AC Chagas disease tailored to at-risk migrants in Spain, 2007 to Euro Surveill. 2011;16(38):41-5. Schmunis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop AD Jul-Aug;115(1-2): Angheben A, Anselmi M, Gobbi F, Marocco S, Monteiro G, Buonfrate D, et al. Chagas disease in Italy: breaking an AE epidemiological silence. Euro Surveill. 2011;16(37):6-13. AF Control and Prevention of Chagas disease in Europe. Geneva: World Health Organization; AG Jackson Y, Chappuis F. Chagas disease in Switzerland: history and challenges. Euro Surveill. 2011;16(37). Guerri-Guttenberg RA, Grana DR, Ambrosio G, Milei J. Chagas cardiomyopathy: Europe is not spared! Eur Heart J AE Nov;29(21):

The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America

The Potential Economic Value of a Trypanosoma cruzi (Chagas Disease) Vaccine in Latin America Bruce Y. Lee 1,2,3 *, Kristina M. Bacon 1,2,3, Diana L. Connor 1,2,3, Alyssa M. Willig 1,2,3, Rachel R. Bailey