 = Chagas disease = 
 
 Chagas disease , also known as American trypanosomiasis , is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi . It is spread mostly by insects known as Triatominae or kissing bugs . The symptoms change over the course of the infection . In the early stage , symptoms are typically either not present or mild , and may include fever , swollen lymph nodes , headaches , or local swelling at the site of the bite . After 8 – 12 weeks , individuals enter the chronic phase of disease and in 60 – 70 % it never produces further symptoms . The other 30 to 40 % of people develop further symptoms 10 to 30 years after the initial infection , including enlargement of the ventricles of the heart in 20 to 30 % , leading to heart failure . An enlarged esophagus or an enlarged colon may also occur in 10 % of people . 
 T. cruzi is commonly spread to humans and other mammals by the blood @-@ sucking " kissing bugs " of the subfamily Triatominae . These insects are known by a number of local names , including : vinchuca in Argentina , Bolivia , Chile and Paraguay , barbeiro ( the barber ) in Brazil , pito in Colombia , chinche in Central America , and chipo in Venezuela . The disease may also be spread through blood transfusion , organ transplantation , eating food contaminated with the parasites , and by vertical transmission ( from a mother to her fetus ) . Diagnosis of early disease is by finding the parasite in the blood using a microscope . Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood . 
 Prevention mostly involves eliminating kissing bugs and avoiding their bites . Other preventative efforts include screening blood used for transfusions . A vaccine has not been developed as of 2013 . Early infections are treatable with the medication benznidazole or nifurtimox . Medication nearly always results in a cure if given early , but becomes less effective the longer a person has had Chagas disease . When used in chronic disease , medication may delay or prevent the development of end – stage symptoms . Benznidazole and nifurtimox cause temporary side effects in up to 40 % of people including skin disorders , brain toxicity , and digestive system irritation . 
 It is estimated that 7 to 8 million people , mostly in Mexico , Central America and South America , have Chagas disease as of 2013 . In 2006 , Chagas was estimated to result in 12 @,@ 500 deaths per year . Most people with the disease are poor , and most people with the disease do not realize they are infected . Large @-@ scale population movements have increased the areas where Chagas disease is found and these include many European countries and the United States . These areas have also seen an increase in the years up to 2014 . The disease was first described in 1909 by Carlos Chagas after whom it is named . It affects more than 150 other animals . 
 
 = = Signs and symptoms = = 
 
 The human disease occurs in two stages : an acute stage , which occurs shortly after an initial infection , and a chronic stage that develops over many years . 
 The acute phase lasts for the first few weeks or months of infection . It usually occurs unnoticed because it is symptom @-@ free or exhibits only mild symptoms that are not unique to Chagas disease . These can include fever , fatigue , body aches , muscle pain , headache , rash , loss of appetite , diarrhea , nausea , and vomiting . The signs on physical examination can include mild enlargement of the liver or spleen , swollen glands , and local swelling ( a chagoma ) where the parasite entered the body . 
 The most recognized marker of acute Chagas disease is called Romaña 's sign , which includes swelling of the eyelids on the side of the face near the bite wound or where the bug feces were deposited or accidentally rubbed into the eye . Rarely , young children , or adults may die from the acute disease due to severe inflammation / infection of the heart muscle ( myocarditis ) or brain ( meningoencephalitis ) . The acute phase also can be severe in people with weakened immune systems . 
 If symptoms develop during the acute phase , they usually resolve spontaneously within three to eight weeks in approximately 90 % of individuals . Although the symptoms resolve , even with treatment the infection persists and enters a chronic phase . Of individuals with chronic Chagas disease , 60 – 80 % will never develop symptoms ( called indeterminate chronic Chagas disease ) , while the remaining 20 – 40 % will develop life @-@ threatening heart and / or digestive disorders during their lifetime ( called determinate chronic Chagas disease ) . In 10 % of individuals , the disease progresses directly from the acute form to a symptomatic clinical form of chronic Chagas disease . 
 The symptomatic ( determinate ) chronic stage affects the nervous system , digestive system and heart . About two @-@ thirds of people with chronic symptoms have cardiac damage , including dilated cardiomyopathy , which causes heart rhythm abnormalities and may result in sudden death . About one @-@ third of patients go on to develop digestive system damage , resulting in dilation of the digestive tract ( megacolon and megaesophagus ) , accompanied by severe weight loss . Swallowing difficulties ( secondary achalasia ) may be the first symptom of digestive disturbances and may lead to malnutrition . 
 20 % to 50 % of individuals with intestinal involvement also exhibit cardiac involvement . Up to 10 % of chronically infected individuals develop neuritis that results in altered tendon reflexes and sensory impairment . Isolated cases exhibit central nervous system involvement , including dementia , confusion , chronic encephalopathy and sensory and motor deficits . 
 The clinical manifestations of Chagas disease are due to cell death in the target tissues that occurs during the infective cycle , by sequentially inducing an inflammatory response , cellular lesions , and fibrosis . For example , intracellular amastigotes destroy the intramural neurons of the autonomic nervous system in the intestine and heart , leading to megaintestine and heart aneurysms , respectively . If left untreated , Chagas disease can be fatal , in most cases due to heart muscle damage . 
 
 = = Transmission = = 
 
 In Chagas @-@ endemic areas , the main mode of transmission is through an insect vector called a triatomine bug . A triatomine becomes infected with T. cruzi by feeding on the blood of an infected person or animal . During the day , triatomines hide in crevices in the walls and roofs . 
 The bugs emerge at night , when the inhabitants are sleeping . Because they tend to feed on people 's faces , triatomine bugs are also known as " kissing bugs " . After they bite and ingest blood , they defecate on the person . Triatomines pass T. cruzi parasites ( called trypomastigotes ) in feces left near the site of the bite wound . 
 Scratching the site of the bite causes the trypomastigotes to enter the host through the wound , or through intact mucous membranes , such as the conjunctiva . Once inside the host , the trypomastigotes invade cells , where they differentiate into intracellular amastigotes . The amastigotes multiply by binary fission and differentiate into trypomastigotes , which are then released into the bloodstream . This cycle is repeated in each newly infected cell . Replication resumes only when the parasites enter another cell or are ingested by another vector . ( See also : Life cycle and transmission of T. cruzi ) 
 Dense vegetation ( such as that of tropical rainforests ) and urban habitats are not ideal for the establishment of the human transmission cycle . However , in regions where the sylvatic habitat and its fauna are thinned by economic exploitation and human habitation , such as in newly deforested areas , piassava palm culture areas , and some parts of the Amazon region , a human transmission cycle may develop as the insects search for new food sources . 
 T. cruzi can also be transmitted through blood transfusions . With the exception of blood derivatives ( such as fractionated antibodies ) , all blood components are infective . The parasite remains viable at 4 ° C for at least 18 days or up to 250 days when kept at room temperature . It is unclear whether T. cruzi can be transmitted through frozen @-@ thawed blood components . 
 Other modes of transmission include organ transplantation , through breast milk , and by accidental laboratory exposure . Chagas disease can also be spread congenitally ( from a pregnant woman to her baby ) through the placenta , and accounts for approximately 13 % of stillborn deaths in parts of Brazil . 
 Oral transmission is an unusual route of infection , but has been described . In 1991 , farm workers in the state of Paraíba , Brazil , were infected by eating contaminated food ; transmission has also occurred via contaminated açaí palm fruit juice and garapa . A 2007 outbreak in 103 Venezuelan school children was attributed to contaminated guava juice . 
 Chagas disease is a growing problem in Europe , because the majority of cases with chronic infection are asymptomatic and because of migration from Latin America . 
 
 = = Diagnosis = = 
 
 The presence of T. cruzi is diagnostic of Chagas disease . It can be detected by microscopic examination of fresh anticoagulated blood , or its buffy coat , for motile parasites ; or by preparation of thin and thick blood smears stained with Giemsa , for direct visualization of parasites . Microscopically , T. cruzi can be confused with Trypanosoma rangeli , which is not known to be pathogenic in humans . Isolation of T. cruzi can occur by inoculation into mice , by culture in specialized media ( for example , NNN , LIT ) ; and by xenodiagnosis , where uninfected Reduviidae bugs are fed on the patient 's blood , and their gut contents examined for parasites . 
 Various immunoassays for T. cruzi are available and can be used to distinguish among strains ( zymodemes of T.cruzi with divergent pathogenicities ) . These tests include : detecting complement fixation , indirect hemagglutination , indirect fluorescence assays , radioimmunoassays , and ELISA . Alternatively , diagnosis and strain identification can be made using polymerase chain reaction ( PCR ) . 
 
 = = Prevention = = 
 
 There is currently no vaccine against Chagas disease . Prevention is generally focused on decreasing the numbers of the insect that spreads it ( Triatoma ) and decreasing their contact with humans . This is done by using sprays and paints containing insecticides ( synthetic pyrethroids ) , and improving housing and sanitary conditions in rural areas . For urban dwellers , spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous ; a mosquito net is recommended . Some measures of vector control include : 
 A yeast trap can be used for monitoring infestations of certain species of triatomine bugs ( Triatoma sordida , Triatoma brasiliensis , Triatoma pseudomaculata , and Panstrongylus megistus ) . 
 Promising results were gained with the treatment of vector habitats with the fungus Beauveria bassiana . 
 Targeting the symbionts of Triatominae through paratransgenesis can be done . 
 A number of potential vaccines are currently being tested . Vaccination with Trypanosoma rangeli has produced positive results in animal models . More recently , the potential of DNA vaccines for immunotherapy of acute and chronic Chagas disease is being tested by several research groups . 
 Blood transfusion was formerly the second @-@ most common mode of transmission for Chagas disease , but the development and implementation of blood bank screening tests has dramatically reduced this risk in the 21st century . Blood donations in all endemic Latin American countries undergo Chagas screening , and testing is expanding in countries , such as France , Spain and the United States , that have significant or growing populations of immigrants from endemic areas . In Spain , donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests . 
 The US FDA has approved two Chagas tests , including one approved in April 2010 , and has published guidelines that recommend testing of all donated blood and tissue products . While these tests are not required in US , an estimated 75 – 90 % of the blood supply is currently tested for Chagas , including all units collected by the American Red Cross , which accounts for 40 % of the U.S. blood supply . The Chagas Biovigilance Network reports current incidents of Chagas @-@ positive blood products in the United States , as reported by labs using the screening test approved by the FDA in 2007 . 
 
 = = Management = = 
 
 There are two approaches to treating Chagas disease : antiparasitic treatment , to kill the parasite ; and symptomatic treatment , to manage the symptoms and signs of the infection . Management uniquely involves addressing selective incremental failure of the parasympathetic nervous system . Autonomic disease imparted by Chagas may eventually result in megaesophagus , megacolon and accelerated dilated cardiomyopathy . The mechanisms that explain why Chagas targets the parasympathetic autonomic nervous system and spares the sympathetic autonomic nervous system remain poorly understood . 
 
 = = = Medication = = = 
 
 Antiparasitic treatment is most effective early in the course of infection , but is not limited to cases in the acute phase . Drugs of choice include azole or nitro derivatives , such as benznidazole or nifurtimox . Both agents are limited in their capacity to completely eliminate T. cruzi from the body ( parasitologic cure ) , especially in chronically infected patients , and resistance to these drugs has been reported . 
 Studies suggest antiparasitic treatment leads to parasitological cure in more than 90 % of infants but only about 60 – 85 % of adults treated in the first year of acute phase Chagas disease . Children aged six to 12 years with chronic disease have a cure rate of about 60 % with benznidazole . While the rate of cure declines the longer an adult has been infected with Chagas , treatment with benznidazole has been shown to slow the onset of heart disease in adults with chronic Chagas infections . 
 Treatment of chronic infection in women prior to or during pregnancy does not appear to reduce the probability the disease will be passed on to the infant . Likewise , it is unclear whether prophylactic treatment of chronic infection is beneficial in persons who will undergo immunosuppression ( for example , organ transplant recipients ) or in persons who are already immunosuppressed ( for example , those with HIV infection ) . 
 
 = = = Complications = = = 
 
 In the chronic stage , treatment involves managing the clinical manifestations of the disease . For example , pacemakers and medications for irregular heartbeats , such as the anti @-@ arrhythmia drug amiodarone , may be life saving for some patients with chronic cardiac disease , while surgery may be required for megaintestine . The disease cannot be cured in this phase , however . Chronic heart disease caused by Chagas disease is now a common reason for heart transplantation surgery . Until recently , however , Chagas disease was considered a contraindication for the procedure , since the heart damage could recur as the parasite was expected to seize the opportunity provided by the immunosuppression that follows surgery . 
 
 = = Epidemiology = = 
 
 Chagas disease affects 8 to 10 million people living in endemic Latin American countries , with an additional 300 @,@ 000 – 400 @,@ 000 living in nonendemic countries , including Spain and the United States . An estimated 41 @,@ 200 new cases occur annually in endemic countries , and 14 @,@ 400 infants are born with congenital Chagas disease annually. in 2010 it resulted in approximately 10 @,@ 300 deaths up from 9 @,@ 300 in 1990 . 
 The disease is present in 18 countries on the American continents , ranging from the southern United States to northern Argentina . 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 triatomines breed and feed on the more than 150 species from 24 families of domestic and wild mammals , as well as humans , that are the natural reservoirs of T. cruzi . 
 Although Triatominae bugs feed on them , birds appear to be immune to infection and therefore are not considered to be a T. cruzi reservoir . Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters , they can re @-@ emerge from plants or animals that are part of the ancient , sylvatic ( referring to wild animals ) infection cycle . This is especially likely in zones with mixed open savannah , with clumps of trees interspersed by human habitation . 
 The primary wildlife reservoirs for Trypanosoma cruzi in the United States include opossums , raccoons , armadillos , squirrels , woodrats , and mice . Opossums are particularly important as reservoirs , because the parasite can complete its life cycle in the anal glands of this animal without having to re @-@ enter the insect vector . Recorded prevalence of the disease in opossums in the U.S. ranges from 8 @.@ 3 % to 37 @.@ 5 % . 
 Studies on raccoons in the Southeast have yielded infection rates ranging from 47 % to as low as 15 @.@ 5 % . Armadillo prevalence studies have been described in Louisiana , and range from a low of 1 @.@ 1 % to 28 @.@ 8 % . Additionally , small rodents , including squirrels , mice , and rats , are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors . A Texas study revealed 17 @.@ 3 % percent T. cruzi prevalence in 75 specimens representing four separate small rodent species . 
 Chronic Chagas disease remains a major health problem in many Latin American countries , despite the effectiveness of hygienic and preventive measures , such as eliminating the transmitting insects . However , several landmarks have been achieved in the fight against it in Latin America , including a reduction by 72 % of the incidence of human infection in children and young adults in the countries of the Southern Cone Initiative , and at least three countries ( Uruguay , in 1997 , and Chile , in 1999 , and Brazil in 2006 ) have been certified free of vectorial and transfusional transmission . In Argentina , vectorial transmission has been interrupted in 13 of the 19 endemic provinces , and major progress toward this goal has also been made in both Paraguay and Bolivia . 
 Screening of donated blood , blood components , and solid organ donors , as well as donors of cells , tissues , and cell and tissue products for T. cruzi is mandated in all Chagas @-@ endemic countries and has been implemented . Approximately 300 @,@ 000 infected people live in the United States , which is likely the result of immigration from Latin American countries , and there have been only 23 human cases of domestically acquired vector @-@ borne Chagas disease reported between 1955 and 2014 . With increased population movements , the possibility of transmission by blood transfusion became more substantial in the United States . Transfusion blood and tissue products are now actively screened in the U.S. , thus addressing and minimizing this risk . 
 
 = = History = = 
 
 The disease was named after the Brazilian physician and epidemiologist Carlos Chagas , who first described it in 1909 . The disease was not seen as a major public health problem in humans until the 1960s ( the outbreak of Chagas disease in Brazil in the 1920s went widely ignored ) . Dr Chagas discovered that the intestines of Triatomidae ( now Reduviidae : Triatominae ) harbored a flagellate protozoan , a new species of the Trypanosoma genus , and was able to demonstrate experimentally that it could be transmitted to marmoset monkeys that were bitten by the infected bug . Later studies showed squirrel monkeys were also vulnerable to infection . 
 Chagas named the pathogenic parasite as Trypanosoma cruzi and later that year as Schizotrypanum cruzi , both honoring Oswaldo Cruz , the noted Brazilian physician and epidemiologist who successfully fought epidemics of yellow fever , smallpox , and bubonic plague in Rio de Janeiro and other cities in the beginning of the 20th century . Chagas was also the first to unknowingly discover and illustrate the parasitic fungal genus Pneumocystis , later infamously linked to PCP ( Pneumocystis pneumonia in AIDS victims ) . Confusion between the two pathogens ' life @-@ cycles led him to briefly recognize his genus Schizotrypanum , but following the description of Pneumocystis by others as an independent genus , Chagas returned to the use of the name Trypanosoma cruzi . 
 In Argentina , the disease is known as mal de Chagas @-@ Mazza , in honor of Salvador Mazza , the Argentine physician who in 1926 began investigating the disease and over the years became the principal researcher of this disease in the country . Mazza produced the first scientific confirmation of the existence of Trypanosoma cruzi in Argentina in 1927 , eventually leading to support from local and European medical schools and Argentine government policy makers . 
 It has been hypothesized that Charles Darwin might have suffered from Chagas disease as a result of a bite of the so @-@ called great black bug of the Pampas ( vinchuca ) ( see Charles Darwin 's illness ) . The episode was reported by Darwin in his diaries of the Voyage of the Beagle as occurring in March 1835 to the east of the Andes near Mendoza . Darwin was young and generally in good health , though six months previously he had been ill for a month near Valparaiso , but in 1837 , almost a year after he returned to England , he began to suffer intermittently from a strange group of symptoms , becoming incapacitated for much of the rest of his life . Attempts to test Darwin 's remains at Westminster Abbey by using modern PCR techniques were met with a refusal by the Abbey 's curator . 
 
 = = Research = = 
 
 Several experimental treatments have shown promise in animal models . These include inhibitors of oxidosqualene cyclase and squalene synthase , cysteine protease inhibitors , dermaseptins collected from frogs in the genus Phyllomedusa ( P. oreades and P. distincta ) , the sesquiterpene lactone dehydroleucodine ( DhL ) , which affects the growth of cultured epimastigote @-@ phase Trypanosoma cruzi , inhibitors of purine uptake , and inhibitors of enzymes involved in trypanothione metabolism . Hopefully , new drug targets may be revealed following the sequencing of the T. cruzi genome . 
 Chagas disease has a serious economic impact on the United States and the world . The cost of treatment in the United States alone , where the disease is not indigenous , is estimated to be $ 900 million annually , which includes hospitalization and medical devices such as pacemakers . The global cost is estimated at $ 7 billion . 
 Megazol in a study seems more active against Chagas than benznidazole but has not been studied in humans . Fexinidazole , an old drug rediscovered for this purpose is being tested in phase 2 clinical trials . A Chagas vaccine ( TcVac3 ) has been found to be effective in mice with plans for studies in dogs . It is hoped that it will be commercially available by 2018 . 
 
 