68,000 to 123,000 people in europe as of 2019. spain, which has a high rate of immigration from latin america, has the highest prevalence of the disease. it is estimated that 50,000 to 70,000 spanish people are living with chagas disease, accounting for the majority of european cases. the prevalence varies widely within european countries due to differing immigration patterns. italy has the second highest prevalence, followed by the netherlands, the united kingdom, and germany. history carlos chagas, in his laboratory at instituto oswaldo cruz t. cruzi likely circulated in south american mammals long before the arrival of humans on the continent. t. cruzi has been detected in ancient human remains across south america, from a 9000-year-old chinchorro mummy in the atacama desert, to remains of various ages in minas gerais, to an 1100-year-old mummy as far north as the chihuahuan desert near the rio grande. many early written accounts describe symptoms consistent with chagas disease, with early descriptions of the disease sometimes attributed to miguel diaz pimenta (1707), luís gomes ferreira (1735), and theodoro j. h. langgaard (1842). the formal description of chagas disease was made by carlos chagas in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. upon examination of her blood, chagas saw trypanosomes identical to those he had recently identified from the hindgut of triatomine bugs and named trypanosoma cruzi in honor of his mentor, brazilian physician oswaldo cruz. he sent infected triatomine bugs to cruz in rio de janeiro, who showed the bite of the infected triatomine could transmit t. cruzi to marmoset monkeys as well. in just two years, 1908 and 1909, chagas published descriptions of the disease, the organism that caused it, and the insect vector required for infection. almost immediately thereafter, at the suggestion of miguel couto, then professor of the faculdade de medicina do rio de janeiro, the disease was widely referred to as "chagas disease". chagas' discovery brought him national and international renown, but in highlighting the inadequacies of the brazilian government's response to the disease, chagas attracted criticism to himself and to the disease that bore his name, stifling research on his discovery and likely frustrating his nomination for the nobel prize in 1921. in the 1930s, salvador mazza rekindled chagas disease research, describing over a thousand cases in argentina's chaco province. in argentina, the disease is known as mal de chagas-mazza in his honor. serological tests for chagas disease were introduced in the 1940s, demonstrating that infection with t. cruzi was widespread across latin america. this, combined with successes eliminating the malaria vector through insecticide use, spurred the creation of public health campaigns focused on treating houses with insecticides to eradicate triatomine bugs. the 1950s saw the discovery that treating blood with crystal violet could eradicate the parasite, leading to its widespread use in transfusion screening programs in latin america. large-scale control programs began to take form in the 1960s, first in são paulo, then various locations in argentina, then national-level programs across latin america. these programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective. regional bodies dedicated to controlling chagas disease arose through support of the pan american health organization, with the initiative of the southern cone for the elimination of chagas diseases launching in 1991, followed by the initiative of the andean countries (1997), initiative of the central american countries (1997), and the initiative of the amazon countries (2004). research treatments fexinidazole, an antiparasitic drug approved for treating african trypanosomiasis, has shown activity against chagas disease in animal models. as of 2019, it is undergoing phase ii clinical trials for chronic chagas disease in spain. other drug candidates include gnf6702, a proteasome inhibitor that is effective against chagas disease in mice and is undergoing preliminary toxicity studies, and an4169, which has had promising results in animal models. a number of experimental vaccines have been tested in animals. in addition to subunit vaccines, some approaches have involved vaccination with attenuated t. cruzi parasites or organisms that express some of the same antigens as t. cruzi but do not cause human disease, such as trypanosoma rangeli or phytomonas serpens. dna vaccination has also been explored. as of 2019, vaccine research has mainly been limited to small animal models. diagnostic tests as of 2018, standard diagnostic tests for chagas disease were limited in their ability to measure the effectiveness of antiparasitic treatment, as serological tests may remain positive for years after t. cruzi is eliminated from the body, and pcr may give false-negative results when the parasite concentration in the blood is low. several potential biomarkers of treatment response are under investigation, such as immunoassays against specific t. cruzi antigens, flow cytometry testing to detect antibodies against different life stages of t. cruzi, and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism. another research area is the use of biomarkers to predict the progression of chronic disease. serum levels of tumor necrosis factor alpha, brain and atrial natriuretic peptide, and angiotensin-converting enzyme 2 have been studied as indicators of the prognosis of chagas cardiomyopathy. t. cruzi shed acute-phase antigen (sapa), which can be detected in blood using elisa or western blot, has been used as an indicator of early acute and congenital infection. an assay for t. cruzi antigens in urine has been developed to diagnose congenital disease.