distinguish it from other species of trypanosomes that infect humans. alternatively, t. cruzi dna can be detected by polymerase chain reaction (pcr). in acute and congenital chagas disease, pcr is more sensitive than microscopy, and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by transfer of antibodies against t. cruzi from a mother to her baby (passive immunity). pcr is also used to monitor t. cruzi levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage. in chronic chagas disease, the concentration of parasites in the blood is too low to be reliably detected by microscopy or pcr, so the diagnosis is usually made using serological tests, which detect immunoglobulin g antibodies against t. cruzi in the blood. two positive serology results, using different test methods, are required to confirm the diagnosis. if the test results are inconclusive, additional testing methods such as western blot can be used. various rapid diagnostic tests for chagas disease are available. these tests are easily transported and can be performed by people without special training. they are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result. t. cruzi parasites can be grown from blood samples by blood culture, xenodiagnosis, or by inoculating animals with the person's blood. in the blood culture method, the person's red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. it can take up to six months to obtain the result. xenodiagnosis involves feeding the blood to triatomine insects, then examining their feces for the parasite 30 to 60 days later. these methods are not routinely used, as they are slow and have low sensitivity. prevention bed nets can be used in endemic areas to prevent bites from triatomine bugs. efforts to prevent chagas disease have largely focused on vector control to limit exposure to triatomine bugs. insecticide-spraying programs have been the mainstay of vector control, consisting of spraying homes and the surrounding areas with residual insecticides. this was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. these programs have drastically reduced transmission in brazil and chile, and eliminated major vectors from certain regions: triatoma infestans from brazil, chile, uruguay, and parts of peru and paraguay, as well as rhodnius prolixus from central america. vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. in response, vector control programs have implemented alternative insecticides (e.g. fenitrothion and bendiocarb in argentina and bolivia), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. in areas with triatomine bugs, transmission of t. cruzi can be prevented by sleeping under bed nets and by housing improvements that prevent triatomine bugs from colonizing houses. blood transfusion was formerly the second-most common mode of transmission for chagas disease. t. cruzi can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood, packed red blood cells, granulocytes, cryoprecipitate, and platelets. the development and implementation of blood bank screening tests has dramatically reduced the risk of infection during blood transfusion. nearly all blood donations in latin american countries undergo chagas screening. widespread screening is also common in non-endemic nations with significant populations of immigrants from endemic areas, including the united kingdom (implemented in 1999), spain (2005), the united states (2007), france and sweden (2009), switzerland (2012), and belgium (2013). serological tests, typically elisas, are used to detect antibodies against t. cruzi proteins in donor blood. other modes of transmission have been targeted by chagas disease prevention programs. treating t. cruzi-infected mothers during pregnancy reduces the risk of congenital transmission of the infection. to this end, many countries in latin america have implemented routine screening of pregnant women and infants for t. cruzi infection, and the world health organization recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. similarly to blood transfusions, many countries with endemic chagas disease screen organs for transplantation with serological tests. there is no vaccine against chagas disease. several experimental vaccines have been tested in animals infected with t. cruzi and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone clinical trials in humans as of 2016. management a bottle of nifurtimox tablets chagas disease is managed using antiparasitic drugs to eliminate t. cruzi from the body, and symptomatic treatment to address the effects of the infection. as of 2018, benznidazole and nifurtimox were the antiparasitic drugs of choice for treating chagas disease, though benznidazole is the only drug available in most of latin america. for either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. antiparasitic treatment is most effective early in the course of infection: it eliminates t. cruzi from 50 to 80% of people in the acute phase (who: "nearly 100 %"), but only 20–60% of those in the chronic phase. treatment of chronic disease is more effective in children than in adults, and the cure rate for congenital disease approaches 100% if treated in the first year of life. antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. elimination of t. cruzi does not cure the cardiac and gastrointestinal damage caused by chronic chagas disease, so these conditions must be treated separately. antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy. benznidazole is usually considered the first-line treatment because it has milder adverse effects than nifurtimox, and its efficacy is better understood. both benznidazole and nifurtimox have common side effects that can result in treatment being discontinued. the most common side effects of benznidazole are skin rash, digestive problems, decreased appetite, weakness, headache, and sleeping problems. these side effects can sometimes be treated with antihistamines or corticosteroids, and are generally reversed when treatment is stopped. however, benznidazole is discontinued in up to 29% of cases. nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. the most common side effects are loss of appetite, weight loss, nausea and vomiting, and various neurological disorders including mood changes, insomnia, paresthesia and peripheral neuropathy. treatment is discontinued in up to 75% of cases. both drugs are contraindicated for use in pregnant women and people with liver or kidney failure. as of 2019, resistance to these drugs has been reported. complications in the chronic stage, treatment involves managing the clinical manifestations of the disease. the treatment of chagas cardiomyopathy is similar to that of other forms of heart disease. beta blockers and ace inhibitors may be prescribed, but some people with chagas disease may not be able to take the standard dose of these drugs because they have low blood pressure or a low heart rate. to manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as amiodarone, or have a pacemaker implanted. blood thinners may be used to prevent thromboembolism and stroke. chronic heart disease caused by chagas is a common reason for heart transplantation surgery. because transplant recipients take immunosuppressive drugs to prevent organ rejection, they are monitored using pcr to detect reactivation of the disease. people with chagas disease who undergo heart transplantation have higher survival rates than the average heart transplant recipient. mild gastrointestinal disease may be treated symptomatically, such as by using laxatives for constipation, or taking a prokinetic drug like metoclopramide before meals to relieve esophageal symptoms. surgery to sever the muscles of the lower esophageal sphincter (cardiomyotomy) may be performed in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus. epidemiology epidemiology of chagas disease circa 2011: red is endemic countries where spread is through vectors; yellow is endemic countries where spread is occasionally through vectors; blue is non-endemic countries where spread is through blood transfusions and migration. disability-adjusted life years due to chagas disease in 2016. grey indicates no data. otherwise, colors get increasingly dark red for each order of magnitude increase in daly burden: 0, white. up to 1,000 dalys, yellow. 1,001 to 10,000 dalys, orange. 10,001 to 100,000 dalys, light red. greater than 100,000 dalys, dark red. in 2019, an estimated 6.5 million people worldwide had chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. the disease resulted in a global annual economic burden estimated at us$7.2 billion in 2013, 86% of which is borne by endemic countries. chagas disease results in the loss of over 800,000 disability-adjusted life years each year. the endemic area of chagas disease stretches from the southern united states to northern chile and argentina, with bolivia (6.1%), argentina (3.6%), and paraguay (2.1%) exhibiting the highest prevalence of the disease. within continental latin america, chagas disease is endemic to 21 countries: argentina, belize, bolivia, brazil, chile, colombia, costa rica, ecuador, el salvador, french guiana, guatemala, guyana, honduras, mexico, nicaragua, panama, paraguay, peru, suriname, uruguay, and venezuela. in endemic areas, due largely to vector control efforts and screening of blood donations, annual infections and deaths have fallen by 67% and more than 73% respectively from their peaks in the 1980s to 2010. transmission by insect vector and blood transfusion has been completely interrupted in uruguay (1997), chile (1999), and brazil (2006), and in argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. during venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and chagas disease seroprevalence rates have increased. transmission rates have also risen in the gran chaco region due to insecticide resistance and in the amazon basin due to oral transmission. while the rate of vector-transmitted chagas disease has declined throughout most of latin america, the rate of orally transmitted disease has risen, possibly due to increasing urbanization and deforestation bringing people into closer contact with triatomines and altering the distribution of triatomine species. orally transmitted chagas disease is of particular concern in venezuela, where 16 outbreaks have been recorded between 2007 and 2018. chagas exists in two different ecological zones: in the southern cone region, the main vector lives in and around human homes. in central america and mexico, the main vector species lives both inside dwellings and in uninhabited areas. in both zones, chagas occurs almost exclusively in rural areas, where t. cruzi also circulates in wild and domestic animals. t. cruzi commonly infects more than 100 species of mammals across latin america including opossums (didelphis spp.), armadillos, marmosets, bats, various rodents and dogs all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. for entomophagous animals this is a common mode. didelphis spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. veterinary transmission also occurs through vertical transmission through the placenta, blood transfusion and organ transplants. non-endemic countries though chagas is traditionally considered a disease of rural latin america, international migration has dispersed those with the disease to numerous non-endemic countries, primarily in north america and europe. as of 2020, approximately 300,000 infected people are living in the united states, and in 2018 it was estimated that 30,000 to 40,000 americans had chagas cardiomyopathy. the vast majority of cases in the united states occur in immigrants from latin america, but local transmission is possible. eleven triatomine species are native to the united states, and some southern states have persistent cycles of disease transmission between insect vectors and animal reservoirs, which include woodrats, possums, raccoons, armadillos and skunks. however, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. as of 2013, the cost of treatment in the united states was estimated to be us$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers. chagas disease affects approximately