WHO , 2020. Chagas Disease (Also Known as American Trypanosomiasis). Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis). Accessed November 18, 2020.
Gourbiere S , Dorn P , Tripet F , Dumonteil E , 2012. Genetics and evolution of triatomines: from phylogeny to vector control. Heredity 108: 190–202.
Angheben A , Boix L , Buonfrate D , Gobbi F , Bisoffi Z , Pupella S , Gandini G , Aprili G , 2015. Chagas disease and transfusion medicine: a perspective from non-endemic countries. Blood Transfus 13: 540–550.
Echeverria LE , Morillo CA , 2019. American trypanosomiasis (Chagas disease). Infect Dis Clin North Am 33: 119–134.
Garcia MN et al., 2016. One health interactions of Chagas disease vectors, canid hosts, and human residents along the Texas-Mexico border. PLoS Negl Trop Dis 10: e0005074.
Lynn MK , Bossak BH , Sandifer PA , Watson A , Nolan MS , 2020. Contemporary autochthonous human Chagas disease in the USA. Acta Trop 205: 105361.
Stanaway JD , Roth G , 2015. The burden of Chagas disease: estimates and challenges. Glob Heart 10: 139–144.
Garcia MN et al., 2015. Development of chagas cardiac manifestations among Texas blood donors. Am J Cardiol 115: 113–117.
Perez-Molina JA , Molina I , 2018. Chagas disease. Lancet 391: 82–94.
Nolan M , Aguilar D , Misra A , Gunter S , Erickson T , Gorchakov R , Rivera H , Montgomery S , Murray K , 2021. Trypanosoma cruzi in nonischemic cardiomyopathy patients, Houston, Texas, USA. Emerg Infect Dis J 27: 1958.
Blumental S , Lambermont M , Heijmans C , Rodenbach MP , El Kenz H , Sondag D , Bottieau E , Truyens C , 2015. First documented transmission of Trypanosoma cruzi infection through blood transfusion in a child with sickle-cell disease in Belgium. PLoS Negl Trop Dis 9: e0003986.
Ries J , Komarek A , Gottschalk J , Brand B , Amsler L , Jutzi M , Frey BM , 2016. A case of possible Chagas transmission by blood transfusion in Switzerland. Transfus Med Hemother 43: 415–417.
Cura CI , Lattes R , Nagel C , Gimenez MJ , Blanes M , Calabuig E , Iranzo A , Barcan LA , Anders M , Schijman AG , 2013. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors. Am J Transplant 13: 3253–3261.
Salvador F et al., 2018. Prevalence of Chagas disease among solid organ-transplanted patients in a nonendemic country. Am J Trop Med Hyg 98: 742–746.
Jackson Y , Myers C , Diana A , Marti HP , Wolff H , Chappuis F , Loutan L , Gervaix A , 2009. Congenital transmission of Chagas disease in Latin American immigrants in Switzerland. Emerg Infect Dis 15: 601–603.
Barona-Vilar C et al., 2012. Prevalence of Trypanosoma cruzi infection in pregnant Latin American women and congenital transmission rate in a non-endemic area: the experience of the Valencian Health Programme (Spain). Epidemiol Infect 140: 1896–1903.
Forsyth CJ , Stigler Granados P , Pacheco GJ , Betancourt JA , Meymandi SK , 2019. Current gaps and needs for increasing access to healthcare for people with Chagas disease in the USA. Curr Trop Med Rep 6: 13–22.
Dumonteil E , Herrera C , 2017. Ten years of Chagas disease research: looking back to achievements, looking ahead to challenges. PLoS Negl Trop Dis 11: e0005422.
Moure Z , Sulleiro E , Iniesta L , Guillen C , Molina I , Alcover MM , Riera C , Pumarola T , Fisa R , 2018. The challenge of discordant serology in Chagas disease: the role of two confirmatory techniques in inconclusive cases. Acta Trop 185: 144–148.
Edwards MS , Stimpert KK , Montgomery SP , 2017. Addressing the challenges of Chagas disease: an emerging health concern in the United States. Infect Dis Clin Pract 25: 118–125.
Hochberg NS , Wheelock A , Hamer DH , Marcus R , Nolan MS , Meymandi S , Gilman RH , 2021. Chagas disease in the United States: a perspective on diagnostic testing limitations and next steps. Am J Trop Med Hyg 104: 800–804.
CDC , 2019. DPDx - Laboratory Identification of Parasites of Public Health Concern - American Trypanosomiasis. Available at: https://www.cdc.gov/dpdx/trypanosomiasisAmerican/index.html. Accessed May 26, 2021.
Pane S et al., 2018. Serological evaluation for Chagas disease in migrants from Latin American countries resident in Rome, Italy. BMC Infect Dis 18: 212.
Silva ED et al., 2020. Development of a new lateral flow assay based on IBMP-8.1 and IBMP-8.4 chimeric antigens to diagnose Chagas disease. BioMed Res Int 2020: 1803515.
Luquetti AO et al., 2003. Chagas’ disease diagnosis: a multicentric evaluation of Chagas Stat-Pak, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi. Diagn Microbiol Infect Dis 46: 265–271.
Ponce C et al., 2005. Validation of a rapid and reliable test for diagnosis of Chagas’ disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America. J Clin Microbiol 43: 5065–5068.
nanoComposix, 2017. Increased Sensitivity of Lateral Flow Assays Using Gold Nanoshells. Available at: https://cdn.shopify.com/s/files/1/0257/8237/files/Nanoshells_for_Increased_Sensitivty_in_Lateral_Flow_-_nanoComposix_-_v1.1.pdf?13398085647345355955. Accessed May 20, 2021.
Oldenburg SJ , Averitt RD , Westcott SL , Halas NJ , 1998. Nanoengineering of optical resonances. Chem Phys Lett 288: 243–247.
Hirsch LR , Gobin AM , Lowery AR , Tam F , Drezek RA , Halas NJ , West JL , 2006. Metal nanoshells. Ann Biomed Eng 34: 15–22.
Averitt RD , Westcott SL , Halas NJ , 1999. Linear optical properties of gold nanoshells. J Opt Soc Am B 16: 1824–1832.
Gonzalez-Moa MJ , Van Dorst B , Lagatie O , Verheyen A , Stuyver L , Biamonte MA , 2018. Proof-of-concept rapid diagnostic test for onchocerciasis: exploring peptide biomarkers and the use of gold nanoshells as reporter nanoparticles. ACS Infect Dis 4: 912–917.
Hirsch LR , Jackson JB , Lee A , Halas NJ , West JL , 2003. A whole blood immunoassay using gold nanoshells. Anal Chem 75: 2377–2381.
Rastinehad AR et al., 2019. Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study. Proc Natl Acad Sci USA 116: 18590–18596.
Sershen SR , Westcott SL , Halas NJ , West JL , 2000. Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery. J Biomed Mater Res 51: 293–298.
Afonso AM , Ebell MH , Tarleton RL , 2012. A systematic review of high quality diagnostic tests for Chagas disease. PLoS Negl Trop Dis 6: e1881.
Santos FL , de Souza WV , Barros Mda S , Nakazawa M , Krieger MA , Gomes Yde M , 2016. Chronic Chagas disease diagnosis: a comparative performance of commercial enzyme immunoassay tests. Am J Trop Med Hyg 94: 1034–1039.
Verani JR et al., 2009. Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection. Am J Trop Med Hyg 80: 410–415.
Santos FLN , Celedon PAF , Zanchin NIT , Brasil TdAC , Foti L , Souza WVd , Silva ED , Gomes YdM , Krieger MA , 2016. Performance assessment of four chimeric Trypanosoma cruzi antigens based on antigen-antibody detection for diagnosis of chronic Chagas disease. PLoS One 11: e0161100.
Camussone C , Gonzalez V , Belluzo MS , Pujato N , Ribone ME , Lagier CM , Marcipar IS , 2009. Comparison of recombinant Trypanosoma cruzi peptide mixtures versus multiepitope chimeric proteins as sensitizing antigens for immunodiagnosis. Clin Vaccine Immunol 16: 899–905.
da Silveira JF , Umezawa ES , Luquetti AO , 2001. Chagas disease: recombinant Trypanosoma cruzi antigens for serological diagnosis. Trends Parasitol 17: 286–291.
Houghton RL , Benson DR , Reynolds L , McNeill P , Sleath P , Lodes M , Skeiky YA , Badaro R , Krettli AU , Reed SG , 2000. Multiepitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in patients with treated or untreated Chagas’ disease. J Infect Dis 181: 325–330.
Houghton RL , Benson DR , Reynolds LD , McNeill PD , Sleath PR , Lodes MJ , Skeiky YA , Leiby DA , Badaro R , Reed SG , 1999. A multi-epitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in radioimmunoprecipitation-confirmed and consensus-positive sera. J Infect Dis 179: 1226–1234.
Granjon E , Dichtel-Danjoy ML , Saba E , Sabino E , Campos de Oliveira L , Zrein M , 2016. Development of a novel multiplex immunoassay multi-cruzi for the serological confirmation of Chagas disease. PLoS Negl Trop Dis 10: e0004596.
Hernandez P , Heimann M , Riera C , Solano M , Santalla J , Luquetti AO , Beck E , 2010. Highly effective serodiagnosis for Chagas’ disease. Clin Vaccine Immunol 17: 1598–1604.
Kelly EA , Bulman CA , Gunderson EL , Irish AM , Townsend RL , Sakanari JA , Stramer SL , Bern C , Whitman JD , 2021. Comparative performance of latest-generation and FDA-cleared serology tests for the diagnosis of Chagas disease. J Clin Microbiol 59: e00158–21.
Whitman JD , Bulman CA , Gunderson EL , Irish AM , Townsend RL , Stramer SL , Sakanari JA , Bern C , 2019. Chagas disease serological test performance in U.S. blood donor specimens. J Clin Microbiol 57: e01217–19.
Eguez KE , Alonso-Padilla J , Teran C , Chipana Z , Garcia W , Torrico F , Gascon J , Lozano-Beltran DF , Pinazo MJ , 2017. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis. PLoS Negl Trop Dis 11: e0005501.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1932 | 1021 | 61 |
Full Text Views | 205 | 70 | 0 |
PDF Downloads | 161 | 28 | 0 |
Chagas disease is a neglected parasitic infection and a major public health problem in the Americas. It remains underdiagnosed in the United States and internationally due to the lack of affordable testing and disparities in healthcare, particularly for those most at risk. We describe a proof-of-concept lateral flow immunoassay employing a recombinant Chagas multiantigen conjugated to gold nanoshells (AuNS) to detect circulating human anti-Chagas IgG antibodies. This is one of the first lateral flow immunoassays to capitalize on the larger surface area of AuNS compared with nanoparticles that can help amplify low-magnitude signals. Results were compared with 42 positive and negative Chagas serum samples, of which a subset of 27 samples was validated against an ELISA (Hemagen®). The sensitivity and specificity of our assay were 83% and 95%, respectively. These results suggest that an AuNS-based rapid testing for Chagas disease could facilitate in-field screening/diagnosis with a performance comparable to commercial methods.
Financial support: Primary support for this research was granted by the National Institute of Biomedical Imaging and Bioengineering from the National Institutes of Health (Grant no. R01 EB021331). M. M. R. acknowledges the funding support by the National Center for Advancing Translational Sciences from the National Institutes of Health (Grant no. TL1-TR-002386). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors’ addresses: Melisa Medina-Rivera and Saurabh Mehta, Division of Nutritional Sciences, Cornell University, Ithaca, NY, and Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, E-mails: mm2463@cornell.edu and smehta@cornell.edu. Washington B. Cárdenas, Laboratorio para Investigaciones Biomédicas, Escuela Superior Politécnica del Litoral, Guayaquil, Guayas, Ecuador, E-mail: wbcarden@espol.edu.ec. David Erickson, Division of Nutritional Sciences, Cornell University, Ithaca, NY, Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, and Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, E-mail: de54@cornell.edu.
WHO , 2020. Chagas Disease (Also Known as American Trypanosomiasis). Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis). Accessed November 18, 2020.
Gourbiere S , Dorn P , Tripet F , Dumonteil E , 2012. Genetics and evolution of triatomines: from phylogeny to vector control. Heredity 108: 190–202.
Angheben A , Boix L , Buonfrate D , Gobbi F , Bisoffi Z , Pupella S , Gandini G , Aprili G , 2015. Chagas disease and transfusion medicine: a perspective from non-endemic countries. Blood Transfus 13: 540–550.
Echeverria LE , Morillo CA , 2019. American trypanosomiasis (Chagas disease). Infect Dis Clin North Am 33: 119–134.
Garcia MN et al., 2016. One health interactions of Chagas disease vectors, canid hosts, and human residents along the Texas-Mexico border. PLoS Negl Trop Dis 10: e0005074.
Lynn MK , Bossak BH , Sandifer PA , Watson A , Nolan MS , 2020. Contemporary autochthonous human Chagas disease in the USA. Acta Trop 205: 105361.
Stanaway JD , Roth G , 2015. The burden of Chagas disease: estimates and challenges. Glob Heart 10: 139–144.
Garcia MN et al., 2015. Development of chagas cardiac manifestations among Texas blood donors. Am J Cardiol 115: 113–117.
Perez-Molina JA , Molina I , 2018. Chagas disease. Lancet 391: 82–94.
Nolan M , Aguilar D , Misra A , Gunter S , Erickson T , Gorchakov R , Rivera H , Montgomery S , Murray K , 2021. Trypanosoma cruzi in nonischemic cardiomyopathy patients, Houston, Texas, USA. Emerg Infect Dis J 27: 1958.
Blumental S , Lambermont M , Heijmans C , Rodenbach MP , El Kenz H , Sondag D , Bottieau E , Truyens C , 2015. First documented transmission of Trypanosoma cruzi infection through blood transfusion in a child with sickle-cell disease in Belgium. PLoS Negl Trop Dis 9: e0003986.
Ries J , Komarek A , Gottschalk J , Brand B , Amsler L , Jutzi M , Frey BM , 2016. A case of possible Chagas transmission by blood transfusion in Switzerland. Transfus Med Hemother 43: 415–417.
Cura CI , Lattes R , Nagel C , Gimenez MJ , Blanes M , Calabuig E , Iranzo A , Barcan LA , Anders M , Schijman AG , 2013. Early molecular diagnosis of acute Chagas disease after transplantation with organs from Trypanosoma cruzi-infected donors. Am J Transplant 13: 3253–3261.
Salvador F et al., 2018. Prevalence of Chagas disease among solid organ-transplanted patients in a nonendemic country. Am J Trop Med Hyg 98: 742–746.
Jackson Y , Myers C , Diana A , Marti HP , Wolff H , Chappuis F , Loutan L , Gervaix A , 2009. Congenital transmission of Chagas disease in Latin American immigrants in Switzerland. Emerg Infect Dis 15: 601–603.
Barona-Vilar C et al., 2012. Prevalence of Trypanosoma cruzi infection in pregnant Latin American women and congenital transmission rate in a non-endemic area: the experience of the Valencian Health Programme (Spain). Epidemiol Infect 140: 1896–1903.
Forsyth CJ , Stigler Granados P , Pacheco GJ , Betancourt JA , Meymandi SK , 2019. Current gaps and needs for increasing access to healthcare for people with Chagas disease in the USA. Curr Trop Med Rep 6: 13–22.
Dumonteil E , Herrera C , 2017. Ten years of Chagas disease research: looking back to achievements, looking ahead to challenges. PLoS Negl Trop Dis 11: e0005422.
Moure Z , Sulleiro E , Iniesta L , Guillen C , Molina I , Alcover MM , Riera C , Pumarola T , Fisa R , 2018. The challenge of discordant serology in Chagas disease: the role of two confirmatory techniques in inconclusive cases. Acta Trop 185: 144–148.
Edwards MS , Stimpert KK , Montgomery SP , 2017. Addressing the challenges of Chagas disease: an emerging health concern in the United States. Infect Dis Clin Pract 25: 118–125.
Hochberg NS , Wheelock A , Hamer DH , Marcus R , Nolan MS , Meymandi S , Gilman RH , 2021. Chagas disease in the United States: a perspective on diagnostic testing limitations and next steps. Am J Trop Med Hyg 104: 800–804.
CDC , 2019. DPDx - Laboratory Identification of Parasites of Public Health Concern - American Trypanosomiasis. Available at: https://www.cdc.gov/dpdx/trypanosomiasisAmerican/index.html. Accessed May 26, 2021.
Pane S et al., 2018. Serological evaluation for Chagas disease in migrants from Latin American countries resident in Rome, Italy. BMC Infect Dis 18: 212.
Silva ED et al., 2020. Development of a new lateral flow assay based on IBMP-8.1 and IBMP-8.4 chimeric antigens to diagnose Chagas disease. BioMed Res Int 2020: 1803515.
Luquetti AO et al., 2003. Chagas’ disease diagnosis: a multicentric evaluation of Chagas Stat-Pak, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi. Diagn Microbiol Infect Dis 46: 265–271.
Ponce C et al., 2005. Validation of a rapid and reliable test for diagnosis of Chagas’ disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America. J Clin Microbiol 43: 5065–5068.
nanoComposix, 2017. Increased Sensitivity of Lateral Flow Assays Using Gold Nanoshells. Available at: https://cdn.shopify.com/s/files/1/0257/8237/files/Nanoshells_for_Increased_Sensitivty_in_Lateral_Flow_-_nanoComposix_-_v1.1.pdf?13398085647345355955. Accessed May 20, 2021.
Oldenburg SJ , Averitt RD , Westcott SL , Halas NJ , 1998. Nanoengineering of optical resonances. Chem Phys Lett 288: 243–247.
Hirsch LR , Gobin AM , Lowery AR , Tam F , Drezek RA , Halas NJ , West JL , 2006. Metal nanoshells. Ann Biomed Eng 34: 15–22.
Averitt RD , Westcott SL , Halas NJ , 1999. Linear optical properties of gold nanoshells. J Opt Soc Am B 16: 1824–1832.
Gonzalez-Moa MJ , Van Dorst B , Lagatie O , Verheyen A , Stuyver L , Biamonte MA , 2018. Proof-of-concept rapid diagnostic test for onchocerciasis: exploring peptide biomarkers and the use of gold nanoshells as reporter nanoparticles. ACS Infect Dis 4: 912–917.
Hirsch LR , Jackson JB , Lee A , Halas NJ , West JL , 2003. A whole blood immunoassay using gold nanoshells. Anal Chem 75: 2377–2381.
Rastinehad AR et al., 2019. Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study. Proc Natl Acad Sci USA 116: 18590–18596.
Sershen SR , Westcott SL , Halas NJ , West JL , 2000. Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery. J Biomed Mater Res 51: 293–298.
Afonso AM , Ebell MH , Tarleton RL , 2012. A systematic review of high quality diagnostic tests for Chagas disease. PLoS Negl Trop Dis 6: e1881.
Santos FL , de Souza WV , Barros Mda S , Nakazawa M , Krieger MA , Gomes Yde M , 2016. Chronic Chagas disease diagnosis: a comparative performance of commercial enzyme immunoassay tests. Am J Trop Med Hyg 94: 1034–1039.
Verani JR et al., 2009. Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection. Am J Trop Med Hyg 80: 410–415.
Santos FLN , Celedon PAF , Zanchin NIT , Brasil TdAC , Foti L , Souza WVd , Silva ED , Gomes YdM , Krieger MA , 2016. Performance assessment of four chimeric Trypanosoma cruzi antigens based on antigen-antibody detection for diagnosis of chronic Chagas disease. PLoS One 11: e0161100.
Camussone C , Gonzalez V , Belluzo MS , Pujato N , Ribone ME , Lagier CM , Marcipar IS , 2009. Comparison of recombinant Trypanosoma cruzi peptide mixtures versus multiepitope chimeric proteins as sensitizing antigens for immunodiagnosis. Clin Vaccine Immunol 16: 899–905.
da Silveira JF , Umezawa ES , Luquetti AO , 2001. Chagas disease: recombinant Trypanosoma cruzi antigens for serological diagnosis. Trends Parasitol 17: 286–291.
Houghton RL , Benson DR , Reynolds L , McNeill P , Sleath P , Lodes M , Skeiky YA , Badaro R , Krettli AU , Reed SG , 2000. Multiepitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in patients with treated or untreated Chagas’ disease. J Infect Dis 181: 325–330.
Houghton RL , Benson DR , Reynolds LD , McNeill PD , Sleath PR , Lodes MJ , Skeiky YA , Leiby DA , Badaro R , Reed SG , 1999. A multi-epitope synthetic peptide and recombinant protein for the detection of antibodies to Trypanosoma cruzi in radioimmunoprecipitation-confirmed and consensus-positive sera. J Infect Dis 179: 1226–1234.
Granjon E , Dichtel-Danjoy ML , Saba E , Sabino E , Campos de Oliveira L , Zrein M , 2016. Development of a novel multiplex immunoassay multi-cruzi for the serological confirmation of Chagas disease. PLoS Negl Trop Dis 10: e0004596.
Hernandez P , Heimann M , Riera C , Solano M , Santalla J , Luquetti AO , Beck E , 2010. Highly effective serodiagnosis for Chagas’ disease. Clin Vaccine Immunol 17: 1598–1604.
Kelly EA , Bulman CA , Gunderson EL , Irish AM , Townsend RL , Sakanari JA , Stramer SL , Bern C , Whitman JD , 2021. Comparative performance of latest-generation and FDA-cleared serology tests for the diagnosis of Chagas disease. J Clin Microbiol 59: e00158–21.
Whitman JD , Bulman CA , Gunderson EL , Irish AM , Townsend RL , Stramer SL , Sakanari JA , Bern C , 2019. Chagas disease serological test performance in U.S. blood donor specimens. J Clin Microbiol 57: e01217–19.
Eguez KE , Alonso-Padilla J , Teran C , Chipana Z , Garcia W , Torrico F , Gascon J , Lozano-Beltran DF , Pinazo MJ , 2017. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis. PLoS Negl Trop Dis 11: e0005501.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 1932 | 1021 | 61 |
Full Text Views | 205 | 70 | 0 |
PDF Downloads | 161 | 28 | 0 |