CONICET | Buscador de Institutos y Recursos Humanos

Chagas disease or American trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi). Although more than 110 years have elapsed since the first description of a clinical case of Chagas disease1, it still constitutes a major public health problem in Latin America due to its prevalence, morbidity, and mortality. A minimum of 7 million people is estimated to be infected worldwide, mostly in Latin America countries where the parasite is transmitted mostly by triatomine bug vectors to humans by contact with infected faeces or urine. Additionally, as a consequence of immigration Chagas disease has emerged outside of its typical endemic regions, affecting countries such as the United States of America (USA), Canada and many European and Western Pacific countries, where disease transmission channels moved towards non vectorial routes, such as blood transfusion, congenital transmission and organ transplants. Nevertheless, autochthonous T. cruzi infection via vectorial transmission has been recently reported in the southern parts of the USA2.Cardiac involvement represents the most frequent and severe complication of Chagas disease, affecting about 30-40% of infected individuals. Consequently, Chagas myocarditis is the most common form of non-ischemic cardiomyopathy worldwide. The 10-year mortality rate may range from 80%, depending on the cardiac damage. According to recent computational models, Chagas disease imposes on the world an economic burden of approximately $7 billion a year, similar or substantially higher than the global burden of many cancers (uterine, cervical, and oral) and infections (cholera and rotavirus) of recognized global incidence. Several reasons account for these numbers: i) underutilized therapies and lack of effective2prophylactic vaccines, ii) long duration (up to 2 months) of current treatment, which is frequently associated to possible adverse reactions, iii) the vast majority of infected individuals (~99%) do not have access to treatment, either because they have not been diagnosed positive for T. cruzi infection or they do not know that treatments exist, iv) the parasite is transmitted to human and domestic animals by triatomine bug vectors that dwell in structures closely associated with social constructions (chicken coops, goat corrals, and grain storage bins) or inside the houses in rural areas, v) chemical control of the vector has been successfully implemented, but these programs were only temporarily effective or interrupted. As such, Chagas disease control is multifactorial and needs the urgent attention of several and different areas of action that afford the interruption of disease progression and propagation.Last year the World Health Organization (WHO) in the 72nd World Health Assembly approved the 14th April as the ?World Chagas Disease Day? namely to raise global public awareness against a disease that has been neglected for more than one century. Indeed, the 14th April of 1909, the physician Carlos Chagas found, for the first time, the parasite in the blood of a two years old Brazilian girl named Berenice1. The discovery was completed with the description of most clinical aspects of the disease between 1909 and 1917 by Dr. Chagas and his colleagues and with relevant observations made by Dr. Mazza3 and contemporaries4 in Argentina. However, academic rivalries and the possible association of clinical aspects with goiter postulated by Dr. Chagas made have overlooked the importance of Chagas-Mazza observations, even though their work ?had and still has a direct socio-economic impact affecting the lives of millions?. In the present Special Issue, C Vigliano and collaborators describe with an engaging literary resource, the historical aspect of Chagas disease from the pre-Columbus evidence and Darwin observations to the current vision of the pathophysiology. They investigate Chagas disease´s history through the ?Contact Zone? concept to refer to ?the space in which geographically and historically separated people come into contact with each other and establish long-lasting relationships?.Since the discovery of Chagas disease, the ?education? has been considered as one fundamental pillar to face the pathology and related social issues. Recently, the IEC (Information, Education, and Communication) component has been included in some Chagas´ Programs as an essential and complementary tool of other related actions. In this sense, in 2017, the ?WHO Chagas Disease Control Program? has3incorporated a new Technical Group to the five previously existing, to afford ?Information, Education, and Communication? aspects. From the perspective that education act as a promoter of changes that favor dynamics of formation and information in the communities, M. Sanmartino and collaborators performed a critical review study to characterize how the link education-Chagas was considered in scientific publications from the last 15 years.This disease that disproportionately affects poor and remote populations with limited access to health services, currently demand the establishment of key research priorities, among them, the development of prophylactic or therapeutic vaccines and more efficient and safer therapies to prevent new cases or inhibit disease progression. At this point, it is worthwhile to highlight the current lack of standardized methods to monitor vaccine or treatment efficacy. At the moment, there are no tests-of-cure to follow up infected patients or to search for a safer drug and measure its efficacy. Therefore, the identification and validation of disease progression as well as the development of biomarkers of treatment response that lead to the generation of prognostic test are among research priorities. In this Special Issue J Gascon´s and MC Lopez´s groups give an updated outlook of both parasite- and host-derived markers, respectively. On the other hand, a new generation of immunoassays is being developed to address the clinical necessity for T. cruzi detection and Chagas disease monitoring. These assays focus on specific candidate biomarkers, but the medical need for monitoring the disease status of T. cruzi-infected patients is currently largely unmet (revised by M Zrein and E Chatelain).Over decades, vaccine development against T. cruzi infection was no promoted due to several reports suggesting that parasite antigens would induce autoimmune reactions. However, with the development of more sensitive methods to measure parasite persistence, the scientific paradigm changed, and it became clear that the pathogenesis of chronic Chagas disease relay on parasite presence in target tissues. Considering that current therapies (Benznidazole or Nifurtimox) are associated with several side effects and require long term treatment that frequently leads to low compliance, prophylactic and therapeutic vaccines may improve the etiological treatment. In this Special Issue, EL Malchiodi and collaborators reviewed some aspects of sub-unit vaccines, the advantages, and limitations of DNA-based vaccines and the idea of therapeutic vaccines.4Considering that the parasite exhibits a remarkable tropism for several tissues, including cardiac muscle, T. cruzi infection has been extensively employed to study the innate and adaptive immune responses elicited by the myocardium to an intracellular pathogen in humans and experimental models. Furthermore, it has served as a model to assess cumulative knowledge on the mechanisms triggered during an acute and chronic human infection. As a result, this area of knowledge has experienced an enormous development, and some new insights obtained from these sets of studies are presented by the research groups of MC Paes and MP Aoki and reviewed by EV Acosta Rodriguez; CC Motrán; AR Perezl and O Campetella and their collaborators.One relevant health issue emerged in endemic and non-endemic countries, is the congenital transmission of T. cruzi infection. Considering that the current anti-parasitic drugs are contraindicated during pregnancy, infected expecting mothers afford an important heath challenge. In addition, the diagnosis of congenital transmission is a formidable window of opportunities to interrupt the propagation of T. cruzi and prevent disease progression. In this Special Issue, N. Garg and collaborators discuss the pathogenesis of maternal-fetal parasite transmission and provide a scientific basis that justifies the investment in the development of vaccines against congenital Chagas disease.In summary, in this Special Issue of Biochimica et Biophysical Acta we aim to discuss different aspects of Chagas disease, from an educational and historical point of view to the biological, immunological and therapeutic scientific advances recently achieved. The Special Issue ?Trypanosoma cruzi infection: pathogenesis, diagnosis and therapy? will offer chances to update our current knowledge of the disease and to visualize the actual scenario in order to promote advances toward the interruption of this endemic pathology.We thank Jeffrey Keller, Ronald Oude Elferink and M. Paul Murphy, BBA Executive Editors, for the opportunity to produce this Special Issue and the staff at Elsevier, who have been very friendly and efficient in bringing it all together. We also would like to thanks the authors, who, despite their busy agendas, went out of their way to provide comprehensive and actualized reviews.5References[1] C. Chagas, Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem. Mem. Inst. Oswaldo Cruz 1 (1909) 159-218.[2] C. Bern, S. Kjos, M.J. Yabsley, S.P. Montgomery, Trypanosoma cruzi and Chagas´ disease in the United States, Clin Microbiol Rev 24(4) (2011) 655-81.[3] S. Mazza, Chagas disease in the Argentine Republic, Mem. Inst. Oswaldo Cruz 47 (1949) 289-302.[4] C.Romaña. Acerca de un síntoma inicial de valor para el diagnóstico de forma aguda de la enfermedad de Chagas, la conjuntivitis esquizotripanósica unilateral (hipótesis sobre puerta de entrada conjuntival de la enfermedad) Misión de Estudios de Patología Regional Argentina 22 (1935) 16-28