View source for Chagas disease

{{Short description|Mammal parasitic disease}}
{{Use dmy dates|date=March 2020}}
{{Featured article}}
{{Infobox medical condition (new)
| name            = Chagas disease
| synonyms        = American trypanosomiasis
| image           = Trypanosoma cruzi in a blood smear.jpg
| alt             = Crescent-shaped Trypanosoma cruzi parasites surrounded by red blood cells
| caption         = Photomicrograph of [[Giemsa]]-stained ''Trypanosoma cruzi'' trypomastigotes in human blood
| pronounce       = {{IPAc-en|ˈ|tʃ|ɑː|ɡ|ə|s}}, {{IPA|pt|size=97%|ˈʃaɡɐs}}
| field           = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms        = Fever, large lymph nodes, headache<ref name=WHO2019/>
| complications   = [[Heart failure]], [[megaesophagus|enlarged esophagus]], [[megacolon|enlarged colon]]<ref name=WHO2019/>
| onset           = 
| duration        =  
| causes          = ''[[Trypanosoma cruzi]]'' spread by [[kissing bugs]]<ref name=WHO2019/>
| risks           = 
| diagnosis       = Finding the parasite, its DNA, or [[Antibody|antibodies]] in the blood<ref name="Molina2018"/>
| differential    = 
| prevention      = Eliminating kissing bugs and avoiding their bites<ref name=WHO2019/>
| treatment       = 
| medication      = [[Benznidazole]], [[nifurtimox]]<ref name=WHO2019/>
| frequency       = 6.5 million (2019)<ref name=GBD2019/>
| deaths          = 9,490 (2019)<ref name=GBD2019/>
}}
<!-- Definition and symptoms -->

'''Chagas disease''', also known as '''American trypanosomiasis''', is a [[tropical disease|tropical]] [[parasitic disease]] caused by ''[[Trypanosoma cruzi]]''. It is spread mostly by insects in the [[subfamily]] [[Triatominae]], known as "kissing bugs". The symptoms change throughout the infection. In the early stage, symptoms are typically either not present or mild and may include fever, swollen [[lymph node]]s, headaches, or swelling at the site of the [[Insect bites and stings|bite]].<ref name=WHO2019>{{cite web|title=Chagas disease (American trypanosomiasis)|url=https://www.who.int/en/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)|date=17 April 2019|website=World Health Organization|access-date=9 March 2020|archive-url=https://web.archive.org/web/20200120210150/https://www.who.int/en/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)|archive-date=20 January 2020}}</ref> After four to eight weeks, untreated individuals enter the [[chronic condition|chronic phase]] of disease, which in most cases does not result in further symptoms.<ref name=Molina2018/><ref name=Bern2015/> Up to 45% of people with chronic infections develop [[heart disease]] 10–30 years after the initial illness, which can lead to [[heart failure]]. Digestive complications, including an [[megaesophagus|enlarged esophagus]] or an [[megacolon|enlarged colon]], may also occur in up to 21% of people, and up to 10% of people may experience nerve damage.<ref name=Molina2018/>

<!-- Cause and diagnosis-->{{nowrap|''T. cruzi''}} is commonly spread to humans and other mammals by the kissing bug's bite wound and the bug's infected feces.<ref name=CDC>{{cite web |publisher=Centers for Disease Control (CDC) |url=https://www.cdc.gov/dpdx/trypanosomiasisAmerican/ |title=DPDx&nbsp;– Trypanosomiasis, American. Fact Sheet |date=30 April 2019| access-date=10 March 2020 |url-status=live |archive-url=https://web.archive.org/web/20190905010437/https://www.cdc.gov/dpdx/trypanosomiasisAmerican/ |archive-date=5 September 2019}}</ref> The disease may also be spread through [[blood transfusion]], [[organ transplantation]], consuming food or drink contaminated with the parasites, and [[vertical transmission]] (from a mother to her baby).<ref name=WHO2019/> Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its [[Deoxyribonucleic acid|DNA]] by [[polymerase chain reaction]].<ref name=Bern2015/> Chronic disease is diagnosed by finding [[Antibody|antibodies]] for {{nowrap|''T. cruzi''}} in the blood.<ref name=Gua2019>{{cite journal |vauthors= Guarner J |title=Chagas disease as example of a reemerging parasite |journal=Seminars in Diagnostic Pathology |date=May 2019 |volume=36 |issue=3 |pages=164–9 |doi=10.1053/j.semdp.2019.04.008 |pmid=31006555|doi-access=free }}</ref>

<!-- Prevention and treatment -->
Prevention focuses on eliminating kissing bugs and avoiding their bites.<ref name=WHO2019/> This may involve the use of [[insecticide]]s or [[bed-nets]].<ref>{{cite web|title=Prevention of Chagas disease|url=https://www.who.int/chagas/disease/prevention/en/|website=World Health Organization|access-date=24 February 2018|archive-url=https://web.archive.org/web/20180211034545/http://www.who.int/chagas/disease/prevention/en/|archive-date=11 February 2018}}</ref> Other preventive efforts include screening blood used for transfusions. Early infections are treatable with the medications [[benznidazole]] or [[nifurtimox]], which usually cure the disease if given shortly after the person is infected, but become 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 often cause [[side effect]]s, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued.<ref name=Molina2018/><ref name=Santi2022>{{cite journal |vauthors= Santi AM, Murta SM|title=Antioxidant defence system as a rational target for Chagas disease and Leishmaniasis chemotherapy |journal=[[Memórias do Instituto Oswaldo Cruz]] |date=2022 |volume= 117|article-number=e210401|doi=10.1590/0074-02760210401|pmid= 35239945|pmc=8896756 |doi-access=free}}</ref> New drugs for Chagas disease are under development,<ref name=Porta2023>{{cite journal |vauthors=Porta EO, Kalesh K, Steel PG |title=Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities |journal=Front Pharmacol |volume=14 |issue= |article-number=1233253 |date=2023 |pmid=37576826 |pmc=10416112 |doi=10.3389/fphar.2023.1233253 |doi-access=free |url=}}</ref> and while experimental vaccines have been studied in animal models,<ref name=Rios2019/><ref name=Vermelho2019/> a human [[vaccine]] has not been developed. 

<!-- History and epidemiology -->
It is estimated that 6.5 million people, mostly in [[Mexico]], [[Central America]] and [[South America]], have Chagas disease as of 2019,<ref name="WHO2019"/><ref name="GBD2019"/> resulting in approximately 9,490 annual deaths.<ref name="GBD2019"/> Most people with the disease [[Diseases of poverty|are poor]],<ref name=Rassi2012>{{cite journal|vauthors=Rassi Jr A, Rassi A, Marcondes de Rezende J|title=American trypanosomiasis (Chagas disease)|journal=Infectious Disease Clinics of North America|date=June 2012|volume=26|issue=2|pages=275–91|pmid=22632639|doi=10.1016/j.idc.2012.03.002|s2cid=34941921 }}</ref> and most do not realize they are infected.<ref>{{cite book|editor= Capinera JL |title=Encyclopedia of entomology |year=2008|publisher=Springer|location=Dordrecht|isbn=978-1-4020-6242-1|page=[https://books.google.com/books?id=i9ITMiiohVQC&pg=PA824 824] |edition=2nd}}</ref> Large-scale population migrations have carried Chagas disease to new regions, which include the United States and many European countries.<ref name=WHO2019/> The disease affects more than 150 types of animals.<ref name=Rassi2010>{{cite journal |vauthors=Rassi A, Rassi A, Marin-Neto JA |title=Chagas disease |journal=Lancet |volume=375 |issue=9723 |pages=1388–402 |date=April 2010 |pmid=20399979 |doi=10.1016/S0140-6736(10)60061-X|s2cid=5068417 }}</ref> From 2000–2018, 29 confirmed locally-acquired cases of Chagas disease were reported in eight US states, leading to calls to reclassify Chagas as endemic to the US.<ref name="Beatty" />

The disease was first described in 1909 by Brazilian physician [[Carlos Chagas]], after whom it is named.<ref name=WHO2019/> Chagas disease is classified as a [[neglected tropical disease]].<ref name=NTD2017>{{cite web|title=Neglected Tropical Diseases |url=https://www.cdc.gov/globalhealth/ntd/diseases/index.html|website=cdc.gov|access-date=28 November 2014|date=6 June 2011|url-status=live|archive-url= https://web.archive.org/web/20141204084219/http://www.cdc.gov/globalhealth/ntd/diseases/index.html |archive-date= 4 December 2014}}</ref>

==Signs and symptoms==
[[File:Chagoma.jpg|thumb|alt=Black and white photo of a young boy with a swollen right eye|An acute Chagas disease infection with swelling of the right eye (Romaña's sign)]]
Chagas disease occurs in two stages: an [[acute (medicine)|acute]] stage, which develops one to two weeks after the insect bite, and a [[chronic condition|chronic]] stage, which develops over many years.<ref name="Molina2018"/><ref name="Bern2015"/><ref name=PD7/> The acute stage is often symptom-free.<ref name="Molina2018"/> When present, the symptoms are typically minor and not specific to any particular disease.<ref name=Bern2015>{{cite journal |vauthors=Bern C |title=Chagas' disease |journal=N. Engl. J. Med. |volume=373 |issue=5 |pages=456–66 |date=July 2015 |pmid=26222561 |doi=10.1056/NEJMra1410150 |type= Review}}</ref> Signs and symptoms include fever, [[malaise]], headache, and [[Hepatomegaly|enlargement of the liver]], [[splenomegaly|spleen]], and [[lymphadenopathy|lymph nodes]].<ref name="WHO2019"/><ref name="Molina2018"/><ref name="Bern2015"/> Sometimes, people develop a swollen nodule at the site of infection, which is called "[[Cecilio Romaña|Romaña]]'s sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin.<ref name="Bern2015"/><ref>{{Cite web|url=https://www.cdc.gov/parasites/chagas/gen_info/detailed.html|title=Chagas Disease – Detailed Fact Sheet|publisher=CDC-Centers for Disease Control and Prevention|website=www.cdc.gov|access-date=15 April 2020|archive-url=https://web.archive.org/web/20190816154641/https://www.cdc.gov/parasites/chagas/gen_info/detailed.html|archive-date=16 August 2019|url-status=live}}</ref> In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve [[myocarditis|inflammation of the heart muscle]], [[Pericardial effusion|fluid accumulation around the heart]], and [[meningoencephalitis|inflammation of the brain and surrounding tissues]], and may be life-threatening. The acute phase typically lasts four to eight weeks and resolves without treatment.<ref name="Molina2018"/>

Unless treated with [[antiparasitic drug]]s, individuals remain infected with {{nowrap|''T. cruzi''}} after recovering from the acute phase. Most chronic infections are asymptomatic, which is referred to as ''indeterminate'' chronic Chagas disease. However, over decades with the disease, approximately 30–40% of people develop organ dysfunction (''determinate'' chronic Chagas disease), which most often affects the [[Human heart|heart]] or [[digestive system]].<ref name="Molina2018"/><ref name="Bern2015"/>

The most common long-term manifestation is [[Cardiomyopathy|heart disease]], which occurs in 14–45% of people with chronic Chagas disease.<ref name="Molina2018"/> People with Chagas heart disease often experience [[palpitations|heart palpitations]], and sometimes [[Syncope (medicine)|fainting]], due to irregular heart function. By [[electrocardiogram]], people with Chagas heart disease most frequently have [[arrhythmia]]s. As the disease progresses, the heart's [[Ventricle (heart)|ventricles]] become enlarged ([[dilated cardiomyopathy]]), which reduces its ability to pump blood. In many cases, the first sign of Chagas heart disease is [[heart failure]], [[thromboembolism]], or chest pain associated with abnormalities in the [[microvasculature]].<ref name="Nunes2018"/>

Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people.<ref name="Molina2018"/> Enlargement of the [[esophagus]] or [[Colon (organ)|colon]] are the most common digestive issues.<ref name="PD7"/> Those with [[Megaesophagus|enlarged esophagus]] often experience pain ([[odynophagia]]) or trouble swallowing ([[dysphagia]]), [[acid reflux]], [[cough]], and weight loss. Individuals with [[megacolon|enlarged colon]] often experience [[constipation]], and may develop severe [[Intestinal obstruction|blockage of the intestine]] or its [[bowel ischaemia|blood supply]]. Up to 10% of chronically infected individuals develop [[Polyneuropathy|nerve damage]] that can result in numbness and altered [[reflex]]es or movement.<ref name="Molina2018"/> While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease.<ref name="Nunes2018">{{cite journal |vauthors=Nunes MC, Beaton A, Acquatella H, et al |title=Chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American Heart Association |journal=Circulation |volume=138 |issue=12 |pages=e169–e209 |date=September 2018 |pmid=30354432 |doi=10.1161/CIR.0000000000000599 |doi-access=free |type= Review}}</ref>

Signs and symptoms differ for people infected with {{nowrap|''T. cruzi''}} through less common routes. People infected through ingestion of parasites tend to develop severe disease within three weeks of consumption, with symptoms including fever, [[vomiting]], [[shortness of breath]], cough, and pain in the chest, [[Abdominal pain|abdomen]], and [[myalgia|muscles]].<ref name="Molina2018"/> Those infected [[congenital]]ly typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as [[jaundice]], [[respiratory distress]], and heart problems.<ref name="Molina2018"/> People infected through organ transplant or [[blood transfusion]] tend to have symptoms similar to those of [[vector (epidemiology)|vector]]-borne disease, but the symptoms may not manifest for anywhere from a week to five months.<ref name="Molina2018"/> Chronically infected individuals who become [[immunosuppression|immunosuppressed]] due to [[HIV]] infection can have particularly severe and distinct disease, most commonly characterized by [[Encephalitis|inflammation in the brain]] and surrounding tissue or [[brain abscess]]es.<ref name="Bern2015"/> Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or [[Focal neurologic signs|other neurological issues]] that indicate particular sites of nervous system damage.<ref>{{cite journal|title=American Trypanosomiasis (Chagas Disease) |vauthors=Echeverria LE, Morillo CA |journal=Infectious Disease Clinics of North America |volume=33 |issue=1 |date=February 2019 |pages=119–134 |doi=10.1016/j.idc.2018.10.015|pmid=30712757 |s2cid=73446292 }}</ref> Occasionally, these individuals also experience acute heart inflammation, [[Skin condition#Lesions|skin lesions]], and disease of the stomach, intestine, or [[peritoneum]].<ref name="Bern2015"/>

==Cause==
[[File:Trypanosoma cruzi LifeCycle.gif|thumb|upright=1.4|alt=See "Cause" section.|Life cycle and transmission of ''T. cruzi'']]
Chagas disease is caused by infection with the [[protozoa]]n parasite {{nowrap|''T. cruzi''}}, which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs".<ref name="Bern2015"/> When the insect defecates at the bite site, motile {{nowrap|''T. cruzi''}} forms called trypomastigotes enter the bloodstream and invade various host cells.<ref name=CDC/> Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication.<ref name=CDC/> The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream.<ref name="Molina2018"/> Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate.<ref name="Molina2018"/> Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.<ref name="Molina2018"/>

===Transmission===
[[File:Triatoma infestans - ZSM.jpg|thumb|left|upright=0.35|alt=A brown winged insect|''[[Triatoma infestans]]'', a common vector of ''T. cruzi''<ref name="AlbaSoto2019"/>]]
''T. cruzi'' can be transmitted by various triatomine bugs in the genera ''[[Triatoma]]'', ''[[Panstrongylus]]'', and ''[[Rhodnius]]''.<ref name="Molina2018"/> The primary [[vector (epidemiology)|vectors]] for human infection are the species of triatomine bugs that inhabit human dwellings, namely ''[[Triatoma infestans]]'', ''[[Rhodnius prolixus]]'', ''[[Triatoma dimidiata]]'' and ''[[Panstrongylus megistus]]''.<ref name="AlbaSoto2019"/> These insects are known by a number of local names, including ''vinchuca'' in Argentina, Bolivia, Chile and Paraguay, ''barbeiro'' (the [[barber surgeon|barber]]) in Brazil, ''pito'' in Colombia, ''chinche'' in Central America, and ''chipo'' in Venezuela.<ref>{{cite book|veditors=Maudlin I, Holmes PH, Miles MA|title=The Trypanosomiases|date=2004|publisher=CAB International|location=Wallingford|isbn=978-0-85199-034-7|page= [https://books.google.com/books?id=6Z1zUWY9LroC&pg=PA184 184]}}</ref> The bugs tend to [[Nocturnality|feed at night]], preferring moist surfaces near the eyes or mouth.<ref name=PD7/><ref name="AlbaSoto2019">{{cite book|vauthors=Alba Soto CD, González Cappa SM|title=Chagas Disease |chapter=Trypanosoma cruzi Journey from the Insect Vector to the Host Cell |veditors=Marcelo Altcheh J, Freilij H|url=https://books.google.com/books?id=WpyuDwAAQBAJ|series=Birkhäuser Advances in Infectious Diseases|date=9 September 2019|publisher=Springer Nature|location=Switzerland|isbn=978-3-030-00054-7|pages=25–59|issn=2504-3811|doi=10.1007/978-3-030-00054-7_2|s2cid=203357705}}</ref> A triatomine bug can become infected with {{nowrap|''T. cruzi''}} when it feeds on an infected host.<ref name=PD7/> {{nowrap|''T. cruzi''}} replicates in the insect's intestinal tract and is shed in the bug's feces.<ref name=PD7/> When an infected triatomine feeds, it pierces the skin and takes in a [[Hematophagy|blood meal]], defecating at the same time to make room for the new meal.<ref name=PD7>{{cite book|chapter=American Trypanosomiasis |pages=71–84 |title=Parasitic Diseases |edition=7 |vauthors=Despommier DD, Griffin DO, Gwadz RW, Hotez PJ, Knirsch CA |publisher=Parasites Without Borders |location=New York |date=2019 |url=https://parasiteswithoutborders.com/books/ |access-date=26 March 2020}}</ref> The bite is typically painless, but causes itching.<ref name=PD7/> Scratching at the bite introduces the {{nowrap|''T. cruzi''}}-laden feces into the bite wound, initiating infection.<ref name=PD7/>

In addition to classical vector spread, Chagas disease can be transmitted through the consumption of food or drink contaminated with triatomine insects or their feces.<ref name=Robertson2016>{{cite journal|title=Trypanosoma cruzi: Time for International Recognition as Foodborne Parasite |vauthors=Robertson LJ, Deveesschauwer B, de Noya BA, Gozalez ON, Togerson PR |date=June 2016 |journal=PLOS Neglected Tropical Diseases |volume=10 |issue=6 |doi=10.1371/journal.pntd.0004656 |article-number=e0004656|pmid=27253136 |pmc=4890754 |doi-access=free }}</ref> Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection.<ref name=Robertson2016/> This oral route of transmission has been implicated in several outbreaks, where it led to unusually severe symptoms, likely due to infection with a higher parasite load than from the bite of a triatomine bug—<ref name=Gua2019/><ref name=Robertson2016/>a single crushed triatomine in a food or beverage harboring ''T cruzi'' can contain about 600,000 metacyclic trypomastigotes, while triatomine fecal matter contains 3,000-4,000 per μL.<ref>{{cite web | title=Oral Transmission of Chagas Disease Has Severe Effects (with section 'Seven Things to Know About Orally Transmitted Chagas Disease')| website=Medscape | date=1 March 2024 | url=https://www.medscape.com/viewarticle/oral-transmission-chagas-disease-has-severe-effects-2024a100042f?ecd=wnl_tp10_daily_240304_MSCPEDIT_etid6352192&uac=88149SY&impID=6352192}}</ref>

''T. cruzi'' can be transmitted independently of the triatomine bug during blood transfusion, following organ transplantation, or across the [[placenta]] during pregnancy.<ref name="Molina2018"/> Transfusion with the blood of an infected donor infects the recipient 10–25% of the time.<ref name="Molina2018"/> To prevent this, blood donations are screened for {{nowrap|''T. cruzi''}} in many countries with endemic Chagas disease, as well as the United States.<ref name=Gua2019/> Similarly, transplantation of solid organs from an infected donor can transmit {{nowrap|''T. cruzi''}} to the recipient.<ref name="Molina2018"/> This is especially true for [[Heart transplantation|heart transplant]], which transmits ''T. cruzi'' 75–100% of the time, and less so for transplantation of the [[Liver transplantation|liver]] (0–29%) or a [[Kidney transplantation|kidney]] (0–19%).<ref name="Molina2018"/> An infected mother can pass {{nowrap|''T. cruzi''}} to her child through the placenta; this occurs in up to 15% of births by infected mothers.<ref name=Messenger2018>{{cite journal|title=Congenital Chagas disease: current diagnostics, limitations, and future perspectives |journal=Current Opinion in Infectious Diseases |volume=31 |issue=5 |pages=415–21 |doi=10.1097/QCO.0000000000000478 |vauthors=Messenger LA, Bern C |date=2018|pmid=30095485 |s2cid=51955023 |url=https://researchonline.lshtm.ac.uk/id/eprint/4650860/1/Messenger-Bern-Congenital-Chagas-Disease.pdf |archive-url=https://web.archive.org/web/20200305151311/https://researchonline.lshtm.ac.uk/id/eprint/4650860/1/Messenger-Bern-Congenital-Chagas-Disease.pdf |archive-date=2020-03-05 |url-status=live }}</ref> As of 2019, 22.5% of new infections occurred through congenital transmission.<ref name="Bern2019">{{cite journal|vauthors=Bern C, Messenger LA, Whitman JD, Maguire JH|title=Chagas Disease in the United States: a Public Health Approach|journal=Clinical Microbiology Reviews|volume=33|issue=1|year=2019|article-number=e00023-19 |issn=0893-8512|doi=10.1128/CMR.00023-19|pmid=31776135|pmc=6927308|type=Review}}</ref>

==Pathophysiology==
[[File:Heart pathology Chagas disease.JPG|thumb|upright=0.7|alt=Photograph of a heart showing perforation of the walls|Large scale anatomy of a heart damaged by chronic Chagas disease]]
In the acute phase of the disease, signs and symptoms are caused directly by the replication of {{nowrap|''T. cruzi''}} and the [[immune system]]'s response to it.<ref name="Molina2018"/> During this phase, {{nowrap|''T. cruzi''}} can be found in various tissues throughout the body and circulating in the blood.<ref name="Molina2018"/> During the initial weeks of infection, parasite replication is brought under control by the production of [[antibody|antibodies]] and activation of the host's [[Inflammation|inflammatory response]], particularly cells that target [[intracellular pathogen]]s such as [[NK cell]]s and [[macrophage]]s, driven by [[cytokine|inflammation-signaling molecules]] like [[Tumor necrosis factor alpha|TNF-α]] and [[IFN-γ]].<ref name="Molina2018"/>

During chronic Chagas disease, long-term organ damage develops over the years due to continued replication of the parasite and damage from the immune system. Early in the course of the disease, {{nowrap|''T. cruzi''}} is found frequently in the [[Striated muscle tissue#Cardiac muscle|striated muscle fibers]] of the heart.<ref name="Bonney2019">{{cite journal |vauthors=Bonney KM, Luthringer DJ, Kim SA, Garg NJ, Engman DM |title=Pathology and Pathogenesis of Chagas Heart Disease |journal=Annu Rev Pathol |volume=14 |pages=421–47 |date=January 2019 |pmid=30355152 |doi=10.1146/annurev-pathol-020117-043711 |pmc=7373119 |type= Review}}</ref> As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by [[Scar|scar tissue]] and [[fat]].<ref name="Bonney2019"/> Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically [[macrophage]]s and [[T cell]]s.<ref name="Bonney2019"/> Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels.<ref name="Bonney2019"/>

In the heart, colon, and esophagus, chronic disease leads to a massive [[Denervation|loss of nerve endings]].<ref name="Nunes2018"/> In the heart, this may contribute to arrhythmias and other cardiac dysfunction.<ref name="Nunes2018"/> In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction.<ref name="Nunes2018"/> Loss of nerves impairs the movement of food through the digestive tract, which can lead to blockage of the esophagus or colon and restriction of their blood supply.<ref name="Nunes2018"/>

The parasite can insert kinetoplast DNA into host cells, an example of [[horizontal gene transfer]]. Vertical inheritance of the inserted kDNA has been demonstrated in rabbits and birds. In chickens, offspring carrying inserted kDNA show symptoms of disease despite carrying no live trypanosomes.<ref name=Texeira>{{cite journal |vauthors=Teixeira AR, Nitz N, Guimaro MC, Gomes C, Santos-Buch CA |title=Chagas disease |journal=Postgrad Med J |volume=82 |issue=974 |pages=788–98 |date=December 2006 |pmid=17148699 |pmc=2653922 |doi=10.1136/pgmj.2006.047357 |url=}}</ref> In 2010, integrated kDNA was found to be vertically transmitted in five human families.<ref name=Hecht>{{cite journal |vauthors=Hecht MM, Nitz N, Araujo PF, et al |title=Inheritance of DNA transferred from American trypanosomes to human hosts |journal=PLOS ONE |volume=5 |issue=2 |article-number=e9181 |date=February 2010 |pmid=20169193 |pmc=2820539 |doi=10.1371/journal.pone.0009181 |bibcode=2010PLoSO...5.9181H |doi-access=free |url=}}</ref>

==Diagnosis==
[[File:T. cruzi trypomastigotes in peripheral blood smear.jpg|thumb|left|alt=Four T. cruzi parasites surrounded by red blood cells. Undulating membranes, flagella, and kinetoplasts are visible.|''T. cruzi'' trypomastigotes seen in a [[blood smear]]]]
The presence of ''T. cruzi'' in the blood is diagnostic of Chagas disease. During the acute phase of infection, it can be detected by [[microscope|microscopic]] examination of fresh [[anticoagulant|anticoagulate]]d blood, or its [[buffy coat]], for motile parasites; or by preparation of thin and thick [[blood smear]]s stained with [[Giemsa stain|Giemsa]], for direct visualization of parasites.<ref name="Bern2015"/><ref name=Gua2019/> Blood smear examination detects parasites in 34–85% of cases. The [[Sensitivity (statistics)|sensitivity]] increases if techniques such as [[microhematocrit|microhematocrit centrifugation]] are used to concentrate the blood.<ref name="Molina2018"/> On microscopic examination of stained blood smears, {{nowrap|''T. cruzi''}} trypomastigotes appear as S or U-shaped organisms with a [[flagellum]] connected to the body by an undulating membrane. A [[Cell nucleus|nucleus]] and a smaller structure called a [[kinetoplast]] are visible inside the parasite's body; the kinetoplast of {{nowrap|''T. cruzi''}} is relatively large, which helps to distinguish it from other species of trypanosomes that infect humans.<ref name="Bain2015">{{cite book| vauthors= Bain BJ| title= Blood Cells: A Practical Guide|url= https://books.google.com/books?id=dckoCQAAQBAJ |date= 20 January 2015 |publisher= John Wiley & Sons |isbn= 978-1-118-81733-9 |pages= 165–7}}</ref>

Alternatively, ''T. cruzi'' DNA can be detected by [[polymerase chain reaction]] (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy,<ref name="Bern2019"/> and it is more reliable than antibody-based tests for the diagnosis of congenital disease because it is not affected by the transfer of antibodies against {{nowrap|''T. cruzi''}} from a mother to her baby ([[Passive immunity#Naturally acquired|passive immunity]]).<ref>{{Cite journal|vauthors= Schijman AG |date= August 2018 |title= Molecular diagnosis of Trypanosoma cruzi | journal= Acta Tropica | volume=184 |pages=59–66|doi= 10.1016/j.actatropica.2018.02.019|pmid= 29476727|hdl= 11336/79861|s2cid= 3513900 |hdl-access= free }}</ref> PCR is also used to monitor {{nowrap|''T. cruzi''}} levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage.<ref name="Molina2018"/><ref name="Bern2015"/><ref name="Bern2019"/>

In chronic Chagas disease, the [[Parasitemia|concentration of parasites in the blood]] is too low to be reliably detected by microscopy or PCR,<ref name="Molina2018"/> so the diagnosis is usually made using [[Serology|serological]] tests, which detect [[immunoglobulin G]] antibodies against {{nowrap|''T. cruzi''}} in the blood.<ref name=Gua2019/> Two positive serology results, using different test methods, are required to confirm the diagnosis.<ref name="Bern2015"/> If the test results are inconclusive, additional testing methods such as [[Western blot]] can be used.<ref name="Molina2018"/>

Various [[rapid diagnostic test]]s for Chagas disease are available. These tests are easily transported and can be performed by people without special training.<ref name="Luquetti2019">{{cite book|vauthors=Luquetti AO, Schijman AG|title=Chagas Disease |chapter=Diagnosis of Chagas Disease |editor=Marcelo Altcheh J, Freilij H|url=https://books.google.com/books?id=WpyuDwAAQBAJ|series=Birkhäuser Advances in Infectious Diseases|date=9 September 2019|publisher=Springer Nature|location=Switzerland|isbn=978-3-030-00054-7|pages=141–58|doi=10.1007/978-3-030-00054-7_7|s2cid=203376369|issn=2504-3811}}</ref> They are useful for [[Screening (medicine)|screening]] large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low,<ref name="Molina2018"/> and it is recommended that a second method is used to confirm a positive result.<ref name="Luquetti2019"/><ref name="Gurtler2019">{{cite journal | vauthors = Angheben A, Buonfrate D, Cruciani M, et al| title = Rapid immunochromatographic tests for the diagnosis of chronic Chagas disease in at-risk populations: A systematic review and meta-analysis | journal = PLOS Neglected Tropical Diseases | volume = 13 | issue = 5 | article-number = e0007271 | date = May 2019 | pmid = 31150377 | doi = 10.1371/journal.pntd.0007271 | pmc = 6561601 | doi-access = free }}</ref>

''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 cell]]s are separated from the [[Blood plasma|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, and then examining their feces for the parasite 30 to 60 days later.<ref name="Luquetti2019"/> These methods are not routinely used, as they are slow and have low sensitivity.<ref name=emed>{{cite web |url=http://emedicine.medscape.com/article/214581-overview |title=Chagas disease (American Trypanosomiasis) |vauthors= Kirchhoff OV|date=26 April 2019 |publisher=[[eMedicine]] |access-date=8 April 2020 |url-status=live |archive-url=https://web.archive.org/web/20200312071301/https://emedicine.medscape.com/article/214581-overview|archive-date=12 March 2020}}</ref><ref name="Luquetti2019"/>

==Prevention==
[[File:Bungalow_at_Bird_of_Paradise.jpg|thumb|alt=A net hanging over a bed|[[Bed net]]s can be used in endemic areas to prevent bites from triatomine bugs.<ref name="PD7"/>]]

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.<ref name=Cueto2015>{{cite journal|journal=Acta Tropica |volume=149 |date=September 2015 |pages=70–85 |title=Insecticide resistance in vector Chagas disease: Evolution, machanisms, and management |vauthors=Mougabure-Cueto G, Picollo MI |doi=10.1016/j.actatropica.2015.05.014|pmid=26003952 |hdl=11336/61521 |hdl-access=free }}</ref> This was originally done with [[organochlorine]], [[organophosphate]], and [[carbamate]] insecticides, which were supplanted in the 1980s with [[pyrethroid]]s.<ref name=Cueto2015/> These programs have drastically reduced transmission in [[Brazil]] and [[Chile]],<ref name=PD7/> 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]].<ref name="Nunes2018"/> Vector control in some regions has been hindered by the development of [[insecticide resistance]] among triatomine bugs.<ref name=Cueto2015/> 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.<ref name=Cueto2015/> In areas with triatomine bugs, transmission of {{nowrap|''T. cruzi''}} can be prevented by sleeping under [[bed net]]s and by housing improvements that prevent triatomine bugs from colonizing houses.<ref name=PD7/>

Blood transfusion was formerly the second-most common mode of transmission for Chagas disease.<ref name=Angheben2015/> {{nowrap|''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]], [[granulocyte]]s, [[cryoprecipitate]], and [[platelet]]s.<ref name=Angheben2015/> The development and implementation of [[blood bank]] screening tests have dramatically reduced the risk of infection during a blood transfusion.<ref name=Angheben2015>{{cite journal|journal=Blood Transfusion |date=October 2015 |volume=13 |issue=4 |pages=540–50 |doi=10.2450/2015.0040-15 |vauthors=Angheben A, Boix L, Buonfrate D, et al. |title=Chagas disease and transfusion medicine: a perspective from non-endemic countries|pmid=26513769 |pmc=4624528 }}</ref> Nearly all [[blood donation]]s in Latin American countries undergo Chagas screening.<ref name=Angheben2015/> 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).<ref name=Lidani2019>{{cite journal|journal=Frontiers in Public Health |date=July 2019 |volume=7 |article-number=166 |doi=10.3389/fpubh.2019.00166 |title=Chagas disease: from discovery to a worldwide health problem |vauthors=((Lidani KCF)), Andrade FA, Bavia L, et al.|pmid=31312626 |pmc=6614205 |bibcode=2019FrPH....7..166L |doi-access=free }}</ref> Serological tests, typically [[ELISA]]s, are used to detect antibodies against {{nowrap|''T. cruzi''}} proteins in donor blood.<ref name=Angheben2015/>

Other modes of transmission have been targeted by Chagas disease prevention programs. Treating {{nowrap|''T. cruzi''}}-infected mothers during pregnancy reduces the risk of congenital transmission of the infection.<ref name=Messenger2018/> To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for {{nowrap|''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.<ref name=WHO2019/><ref name=Bonney2014>{{cite journal|journal=Parasite |date=March 2014 |volume=21 |issue=11 |doi=10.1051/parasite/2014012 |title=Chagas disease in the 21st century: a public health success or an emerging threat |vauthors=Bonney KM|page=11 |pmid=24626257 |pmc=3952655 }}</ref> Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests.<ref name="Molina2018"/>

There is no vaccine against Chagas disease.<ref name=Santi2022/> Several experimental vaccines have been [[Animal testing|tested in animals]] infected with {{nowrap|''T. cruzi''}} and were able to reduce parasite numbers in the blood and heart,<ref>{{cite journal |journal=PLOS Neglected Tropical Diseases |date=January 2019 |volume=13 |issue=1 |article-number=e0006985 |doi=10.1371/journal.pntd.0006985 |pmid=30703092 |title=A therapeutic preconceptional vaccine against Chagas disease: A novel indication that could reduce congenital transmission and accelerate vaccine development |vauthors=Dumonteil E, Herrera C, Buekens P |pmc=6354953 |doi-access=free }}</ref> but no vaccine candidates had undergone [[clinical trial]]s in humans as of 2016.<ref>{{cite journal|title=Status of vaccine research and development of vaccines for Chagas disease |vauthors=Beaumier CM, Gillespie PM, Strych U, et al. |journal=Vaccine |volume=34 |issue=26 |date=June 2016 |pages=2996–3000 |doi=10.1016/j.vaccine.2016.03.074|pmid=27026146 |doi-access=free }}</ref>

==Management==
[[File:NECT treatment (cropped).jpg|thumb|upright=0.7|alt=A brown glass bottle of pills, labeled "Lampit (nifurtimox)"|A bottle of [[nifurtimox]] tablets]]
Chagas disease is managed using [[antiparasitic drug]]s to eliminate ''T. cruzi'' from the body, and symptomatic treatment to address the effects of the infection.<ref name=Gua2019/> As of 2018, [[benznidazole]] and [[nifurtimox]] were the antiparasitic drugs of choice for treating Chagas disease,<ref name="Molina2018"/> though benznidazole is the only drug available in most of Latin America.<ref name="Ribeiro2019"/> For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days.<ref name="Molina2018"/> Antiparasitic treatment is most effective early in the course of infection: it eliminates {{nowrap|''T. cruzi''}} from 50 to 80% of people in the acute phase (WHO: "nearly 100 %"),<ref>WHO. (13 April 2022). [https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis) "Chagas disease (also known as American trypanosomiasis"]. ''Fact sheets''.</ref> but only 20–60% of those in the chronic phase.<ref name=Gua2019/> 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.<ref name="Molina2018"/> Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission.<ref name="WHO2019"/> Elimination of {{nowrap|''T. cruzi''}} does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately.<ref name=Gua2019/> Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy.<ref name="Nunes2018"/>

Benznidazole is usually considered the [[first-line treatment]] because it has milder [[adverse effect]]s than nifurtimox, and its efficacy is better understood.<ref name="Molina2018"/><ref name="Bern2019"/> Both benznidazole and nifurtimox have common [[side effect]]s that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems, [[anorexia (symptom)|decreased appetite]], weakness, headache, and [[sleep disorder|sleeping problems]]. These side effects can sometimes be treated with [[antihistamine]]s or [[corticosteroid]]s, and are generally reversed when treatment is stopped.<ref name="Molina2018"/> However, benznidazole is discontinued in up to 29% of cases.<ref name="Molina2018"/> Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug.<ref name="Molina2018"/> The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various [[neurological disorder]]s including mood changes, [[insomnia]], [[paresthesia]] and [[peripheral neuropathy]].<ref name="Molina2018"/> Treatment is discontinued in up to 75% of cases.<ref name="Molina2018"/><ref name="Bern2019"/> Both drugs are contraindicated for use in pregnant women and people with [[liver failure|liver]] or [[kidney failure]].<ref name="WHO2019"/> As of 2019, resistance to these drugs has been reported.<ref name="Ribeiro2019">{{cite journal |vauthors=Ribeiro V, Dias N, Paiva T, et al |title=Current trends in the pharmacological management of Chagas disease |journal=Int J Parasitol Drugs Drug Resist |volume=12 |pages=7–17 |date=December 2019 |pmid=31862616 |pmc=6928327 |doi=10.1016/j.ijpddr.2019.11.004 |type= Review}}</ref>

===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.<ref name="Molina2018"/> [[Beta blocker]]s and [[ACE inhibitor]]s 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]].<ref name="Molina2018"/><ref name="Nunes2018"/> To manage irregular heartbeats, people may be prescribed [[anti-arrhythmic drug]]s such as [[amiodarone]], or have a [[pacemaker]] implanted.<ref name="Bern2015"/> [[Blood thinner]]s may be used to prevent [[thrombosis|thromboembolism]] and [[stroke]].<ref name="Nunes2018"/> Chronic heart disease caused by untreated ''T. cruzi''  infection is a common reason for [[heart transplantation]] surgery.<ref name="PD7"/> Because transplant recipients take [[immunosuppressive drug]]s 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.<ref name="Nunes2018"/>

Mild gastrointestinal disease may be treated symptomatically, such as by using [[laxative]]s for constipation or taking a [[prokinetic]] drug like [[metoclopramide]] before meals to relieve esophageal symptoms.<ref name="Bern2015"/><ref name="Oliveira2019"/> Surgery to sever the muscles of the lower esophageal sphincter ([[cardiomyotomy]]) may be performed in more severe cases of esophageal disease,<ref name="Oliveira2019">{{cite book|vauthors=de Oliveira EC, ((da Silveira ABM)), Luquetti AO|title=Chagas Disease |veditors=Marcelo Altcheh J, Freilij H|url=https://books.google.com/books?id=WpyuDwAAQBAJ|series=Birkhäuser Advances in Infectious Diseases|date=9 September 2019|publisher=Springer Nature|location=Switzerland|isbn=978-3-030-00054-7|pages=243–62|chapter=Gastrointestinal Chagas Disease|doi=10.1007/978-3-030-00054-7_12|s2cid=203457516|issn=2504-3811}}</ref> and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.<ref name="Bern2015"/><ref name="emed"/>

==Epidemiology==
[[File:Chagas2011Map.jpg|thumb|upright=1.4|alt=A world map. South America and Mexico are red, the United States is yellow, and Canada, Japan, Australia, the United Kingdom, Scandinavia, Romania, and most of Western Europe is blue.|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.<ref>{{cite journal | vauthors = Liu Q, Zhou XN | title = Preventing the transmission of American trypanosomiasis and its spread into non-endemic countries | journal = Infectious Diseases of Poverty | volume = 4 | article-number = 60 | date = December 2015 | pmid = 26715535 | doi = 10.1186/s40249-015-0092-7 | pmc = 4693433 | doi-access = free }}</ref>]]
[[File:2016 Chagas Disease DALYs.svg|thumb|upright=1.4|alt=See description.|[[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.<ref name="WHO2016">{{cite web|author=World Health Organization|title=Disease burden and mortality estimates|url=https://www.who.int/healthinfo/global_burden_disease/estimates/en/index1.html|access-date=27 April 2020|archive-url=https://web.archive.org/web/20200210135939/https://www.who.int/healthinfo/global_burden_disease/estimates/en/index1.html|archive-date=10 February 2020}}</ref>]]
<!--Impact-->
In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year.<ref name="GBD2019">{{cite web|date=2020|title=Global Health Metrics: Chagas disease—Level 3 cause|work=[[The Lancet]]|url=https://www.thelancet.com/pb-assets/Lancet/gbd/summaries/diseases/chagas-disease.pdf|archive-url=https://web.archive.org/web/20220318033609/https://www.thelancet.com/pb-assets/Lancet/gbd/summaries/diseases/chagas-disease.pdf |archive-date=18 March 2022|url-status=live}}</ref> 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.<ref name=Lidani2019/><ref name=econ/> Chagas disease results in the loss of over 800,000 [[disability-adjusted life years]] each year.<ref name="Molina2018"/>

<!--Endemic areas-->
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.<ref name="Molina2018">{{cite journal|vauthors=Pérez-Molina JA, Molina I|title=Chagas disease|journal=The Lancet|volume=391|issue=10115|year=2018|pages=82–94|issn=0140-6736|doi=10.1016/S0140-6736(17)31612-4|pmid=28673423|s2cid=4514617}}</ref> 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.<ref name="WHO2019"/><ref name="Molina2018"/> 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.<ref name="Molina2018"/><ref name=Moncayo2017>{{cite book|title=American Trypanosomiasis – Chagas Disease |edition=2 |date=2017 |chapter=Current epidemiological trends of Chagas disease in Latin America and future challenges: epidemiology, surveillance, and health policies |vauthors=Moncayo A, Silveria AC |doi=10.1016/B978-0-12-801029-7.00004-6 |publisher=Elsevier |pages=59–88}}</ref> Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006),<ref name=Moncayo2017/> and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001.<ref name=TDR1>{{cite press release|url=https://www.who.int/tdrold/publications/tdrnews/news65/chagas.htm |title=The Southern Cone Initiative: an update |work=Special Programme for Research and Training in Tropical Diseases (TDR) |publisher=WHO |year=2004 |access-date=29 August 2008 |archive-url=https://web.archive.org/web/20090922232932/http://www.who.int/tdrold/publications/tdrnews/news65/chagas.htm |archive-date=22 September 2009 }}</ref> During Venezuela's [[Crisis in Venezuela|humanitarian crisis]], vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease [[seroprevalence]] rates have increased.<ref name=Grillet2019>{{cite journal |vauthors=Grillet ME, Hernández-Villena JV, Llewellyn MS, et al |title=Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region |journal=Lancet Infect Dis |volume=19 |issue=5 |pages=e149–e161 |date=May 2019 |pmid=30799251 |doi=10.1016/S1473-3099(18)30757-6 |s2cid=73475841 |type= Review|url=http://eprints.gla.ac.uk/180750/7/180750.pdf }}</ref> Transmission rates have also risen in the [[Gran Chaco]] region due to insecticide resistance and in the [[Amazon basin]] due to oral transmission.<ref name="Molina2018"/>

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.<ref name="Robertson2016"/><ref name="Alarcon2019">{{cite book|vauthors=Alarcón de Noya B, Noya Gonzáles O|title=Chagas Disease |editor=Marcelo Altcheh J, Freilij H|series=Birkhäuser Advances in Infectious Diseases|date=9 September 2019|publisher=Springer Nature|location=Switzerland|isbn=978-3-030-00054-7|pages=[https://books.google.com/books?id=WpyuDwAAQBAJ&q=Orally+Transmitted+Chagas+Disease 225–241]|chapter=Orally Transmitted Chagas Disease: Biology, Epidemiology, and Clinical Aspects of a Foodborne Infection|doi=10.1007/978-3-030-00054-7_11|s2cid=239445211|issn=2504-3811}}</ref><ref name="Hotez2017">{{cite journal|vauthors=Hotez PJ, Basáñez MG, Acosta-Serrano A, Grillet ME|title=Venezuela and its rising vector-borne neglected diseases|journal=PLOS Neglected Tropical Diseases|volume=11|issue=6|year=2017|article-number=e0005423|issn=1935-2735|doi=10.1371/journal.pntd.0005423|pmid=28662038|pmc=5490936 |doi-access=free }}</ref> Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018.<ref name="Grillet2019">{{cite journal |vauthors=Grillet ME, Hernández-Villena JV, Llewellyn MS, et al |title=Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region |journal=Lancet Infect Dis |volume=19 |issue=5 |pages=e149–e161 |date=May 2019 |pmid=30799251 |doi=10.1016/S1473-3099(18)30757-6 |s2cid=73475841 |type= Review|url=http://eprints.gla.ac.uk/180750/7/180750.pdf }}</ref>

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 {{nowrap|''T. cruzi''}} also circulates in wild and domestic animals.<ref name=NatRev>{{cite journal |vauthors=Morel CM, Lazdins J |title=Chagas disease |journal=Nat Rev Microbiol |volume=1 |issue=1 |pages=14–5 |date=October 2003 |pmid=15040175 |doi=10.1038/nrmicro735|s2cid=29869370 |doi-access=free }}</ref> {{nowrap|''T. cruzi''}} commonly infects more than 100 species of mammals across Latin America including [[opossum]]s (''Didelphis'' spp.),<ref name="Wilkowsky-2022">{{cite web | vauthors=Wilkowsky SE| title=Trypanosomiasis in Animals - Circulatory System | website=[[Merck Veterinary Manual]] | date=2022-03-09 | url=http://www.merckvetmanual.com/circulatory-system/blood-parasites/trypanosomiasis-in-animals?autoredirectid=17926 | access-date=28 March 2022|archive-url=https://web.archive.org/web/20220328212043/https://www.merckvetmanual.com/circulatory-system/blood-parasites/trypanosomiasis-in-animals?autoredirectid=17926|archive-date=28 March 2022|url-status=live}}</ref> [[armadillo]]s, [[marmoset]]s, [[bat]]s, various [[rodent]]s<ref name="Telleria-Tibayrenc-2010">{{cite book|veditors=Telleria J, Tibayrenc M|title=American Trypanosomiasis |url=https://archive.org/details/americantrypanos00tiba|url-access=limited|chapter=11 - Domestic and Wild Mammalian Reservoirs |vauthors=Jansen AM, ((Roque ALR)) |publisher=Elsevier |doi=10.1016/B978-0-12-384876-5.00011-3 |date=2010 |pages=249–276 |isbn=978-0-123-84876-5}}</ref> and [[dog]]s<ref name="Wilkowsky-2022" /> all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals.<ref name="Telleria-Tibayrenc-2010" /><ref name="Wilkowsky-2022" /> For [[entomophagy|entomophagous]] animals this is a common mode.<ref name="Wilkowsky-2022" /> ''Didelphis'' spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces.<ref name="Wilkowsky-2022" /> Veterinary transmission also occurs through [[vertical transmission]] through the placenta, [[veterinary blood transfusion|blood transfusion]] and [[veterinary organ transplant|organ transplant]]s.<ref name="Wilkowsky-2022" />

===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.<ref name="WHO2019"/><ref name=Lidani2019/> As of 2020, approximately 300,000 infected people are living in the United States,<ref name="mmwr">{{Cite journal |vauthors=Turabelidze G, Vasudevan A, Rojas-Moreno C, et al |date=2020 |title=Autochthonous Chagas Disease — Missouri, 2018 |journal=MMWR. Morbidity and Mortality Weekly Report |volume=69 |issue=7 |doi=10.15585/mmwr.mm6907a4 |issn=0149-2195 |pages=193–195 |pmid=32078594 |pmc=7043387 }}</ref> and in 2018 it was estimated that 30,000 to 40,000 people in the United States had Chagas cardiomyopathy.<ref name="Nunes2018"/> The vast majority of cases in the United States occur in [[Immigration to the United States#Contemporary immigration|immigrants from Latin America]],<ref name="Nunes2018"/><ref name="Bern2019"/> 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,<ref name="Molina2018"/><ref name="Bern2019"/> which include woodrats, possums, [[raccoon]]s, armadillos and [[skunk]]s.<ref name="Montgomery2014">{{cite journal|vauthors=Montgomery SP, Starr MC, Cantey PT, Edwards MS, Meymandi SK|title=Neglected Parasitic Infections in the United States: Chagas Disease|journal=Am J Trop Med Hyg|volume=90|issue=5|year=2014|pages=814–818|doi=10.4269/ajtmh.13-0726|pmid=24808250|pmc=4015570}}</ref> However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015.<ref name="Molina2018"/><ref name="mmwr"/> Taking into account the local reservoir and transmission to humans, some scientists have proposed reclassifying Chagas disease as endemic to the US, specifically "hypoendemic" to reflect the low transmission.<ref name="Beatty">{{cite journal |last1=Beatty |first1=Norman L. |last2=Hamer |first2=Gabriel L. |last3=Moreno-Peniche |first3=Bernardo |last4=Mayes |first4=Bonny |last5=Hamer |first5=Sarah A. |title=Chagas Disease, an Endemic Disease in the United States |journal=Emerging Infectious Diseases |date=September 2025 |volume=31 |issue=9 |doi=10.3201/eid3109.241700|doi-access=free |pmc=12407112 }}</ref> 

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.<ref name=econ>{{cite journal|vauthors=Lee BY, Bacon KM, Bottazzi ME, Hotez PJ |title=Global economic burden of Chagas disease: a computational simulation model|journal=The Lancet Infectious Diseases|date=April 2013|volume=13|issue=4|pages=342–8|doi=10.1016/S1473-3099(13)70002-1|pmc=3763184 |pmid=23395248}}</ref>

Chagas disease affected approximately 68,000 to 123,000 people in Europe as of 2019.<ref name="Alonso2019">{{cite book|vauthors=Alonso-Padilla J, Pinazo MJ, Gascón J|title=Chagas Disease |editor=Marcelo Altcheh J, Freilij H|url=https://books.google.com/books?id=WpyuDwAAQBAJ|series=Birkhäuser Advances in Infectious Diseases|date=9 September 2019|publisher=Springer Nature|location=Switzerland|isbn=978-3-030-00054-7|pages=111–123|chapter=Chagas Disease in Europe|issn=2504-3811|doi=10.1007/978-3-030-00054-7_5|s2cid=203406723}}</ref> 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 people in Spain are living with Chagas disease, accounting for the majority of European cases.<ref name="Velasco2020"/> The prevalence varies widely within European countries due to differing immigration patterns.<ref name="Alonso2019"/> Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.<ref name="Velasco2020">{{cite journal |vauthors=Velasco M, Gimeno-Feliú LA, Molina I, et al |title=Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology |journal=Euro Surveill. |volume=25 |issue=8 |date=February 2020 |pmid=32127121 |doi=10.2807/1560-7917.ES.2020.25.8.1900393 |type= Review|pmc=7055039 }}</ref>

==History==
[[File:Carlos Chagas.png|thumb|alt=Black and white photo of Charlos Chagas, in his lab coat, sitting next to his microscope and surrounded by flasks and jars|[[Carlos Chagas]], in his laboratory at [[Oswaldo Cruz Foundation|Instituto Oswaldo Cruz]]]]

''T. cruzi'' likely circulated in South American mammals long before the arrival of humans on the continent.<ref name="Steverding2014"/> {{nowrap|''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]].<ref name="Steverding2014">{{cite journal | vauthors = Steverding D | title = The history of Chagas disease | journal = Parasites & Vectors | volume = 7 | page = 317 | date = July 2014 | pmid = 25011546 | pmc = 4105117 | doi = 10.1186/1756-3305-7-317 | doi-access = free }}</ref> Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to [[Miguel Diaz Pimenta]] (1707), {{ill|Luís Gomes Ferreira|pt}} (1735), and [[Theodoro J. H. Langgaard]] (1842).<ref name = "Steverding2014" />

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.<ref name="Steverding2014"/> 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]].<ref name="Steverding2014"/> He sent infected triatomine bugs to Cruz in [[Rio de Janeiro]], who showed the bite of the infected triatomine could transmit {{nowrap|''T. cruzi''}} to [[marmoset monkey]]s as well.<ref name="Steverding2014"/> 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.<ref name=Kropf2009>{{cite journal |journal=Hist Cienc Saude Manguinhos |date=July 2009 |volume=16 |issue=Suppl 1 |pages=13–34 |title=The discovery of ''Trypanosoma cruzi'' and Chagas disease (1908–1909): tropical medicine in Brazil |vauthors=Kropf SP, Sá MR |pmid=20027916 |doi=10.1590/s0104-59702009000500002|s2cid=36106351 |doi-access=free }}</ref><ref name="Chagas_1909">{{cite journal |vauthors=Chagas C | title=Neue Trypanosomen |journal=Vorläufige Mitteilung Arch Schiff Tropenhyg |year=1909 |volume=13 |pages = 120–2 }}</ref><ref name="Chagas_1909b">{{cite journal |vauthors=Chagas C |title=Nova tripanozomiase humana: Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem [New human trypanosomiasis. Studies about the morphology and life-cycle of ''Schizotripanum cruzi'', etiological agent of a new morbid entity of man] |journal=Mem Inst Oswaldo Cruz |year=1909 |volume=1 |issue=2 |pages=159–218 |issn=0074-0276 |doi=10.1590/S0074-02761909000200008 |url=https://www.biodiversitylibrary.org/part/150058 |doi-access=free }} (in Portuguese with German full translation as "Ueber eine neue Trypanosomiasis des Menschen.")</ref> Almost immediately thereafter, at the suggestion of [[Miguel Couto]], then professor of the {{ill|Faculdade de Medicina do Rio de Janeiro|pt}}, the disease was widely referred to as "Chagas disease".<ref name=Kropf2009/> 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 [[Nobel Prize controversies#Physiology or medicine|frustrating his nomination]] for the [[Nobel Prize in Physiology or Medicine|Nobel Prize]] in 1921.<ref name=Kropf2009/><ref>{{cite journal|title=Justice where justice is due: A posthumous Nobel Prize to Carlos Chagas (1879–1934), the discoverer of American Trypanosomiasis (Chagas' disease) |vauthors=Bestetti RB, Martins CA, Cardinalli-Neto A |journal=International Journal of Cardiology |volume=134 |issue=1 |date=May 2009 |pages=9–16 |doi=10.1016/j.ijcard.2008.12.197|pmid=19185367 }}</ref>

In the 1930s, [[Salvador Mazza]] rekindled Chagas disease research, describing over a thousand cases in Argentina's [[Chaco Province]].<ref name="Steverding2014"/> In Argentina, the disease is known as ''mal de Chagas-Mazza'' in his honor.<ref>{{cite web|url=http://www.drwebsa.com.ar/alcha/hist4.htm |publisher=Asociación Lucha Contra el Mal de Chagas |title=Enfermedad de Chagas&nbsp;– Mazza |language=es |access-date=15 September 2011 |archive-url=https://web.archive.org/web/20110916130857/http://www.drwebsa.com.ar/alcha/hist4.htm |archive-date=16 September 2011}}</ref> Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with {{nowrap|''T. cruzi''}} was widespread across Latin America.<ref name="Steverding2014"/> 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.<ref name=Cueto2015/><ref name="Steverding2014"/> 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.<ref name="Steverding2014"/> 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.<ref name=Dias2015>{{cite journal|title=Evolution of Chagas disease screening programs and control programs |vauthors=((Dias JCP)) |journal=Global Heart |volume=10 |issue=3 |date=September 2015 |pages=193–202 |doi=10.1016/j.gheart.2015.06.003|pmid=26407516 |doi-access=free }}</ref> 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.<ref name=Steverding2014/><ref name=Dias2015/> 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).<ref name=Cueto2015/>

==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 trial]]s for chronic Chagas disease in Spain.<ref name="Ribeiro2019">{{cite journal |vauthors=Ribeiro V, Dias N, Paiva T, et al |title=Current trends in the pharmacological management of Chagas disease |journal=Int J Parasitol Drugs Drug Resist |volume=12 |pages=7–17 |date=December 2019 |pmid=31862616 |pmc=6928327 |doi=10.1016/j.ijpddr.2019.11.004 |type= Review}}</ref><ref name="Deeks2019">{{cite journal|vauthors= Deeks ED|title=Fexinidazole: First Global Approval|journal=Drugs|volume=79|issue=2|year=2019|pages=215–220|issn=0012-6667|doi=10.1007/s40265-019-1051-6|pmid=30635838|s2cid=57772417|type=Review}}</ref> 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.<ref name="Vermelho2019">{{cite journal|vauthors=Vermelho AB, Rodrigues GC, Supuran CT|title=Why hasn't there been more progress in new Chagas disease drug discovery?|journal=Expert Opinion on Drug Discovery|volume=15|issue=2|year=2019|pages=145–158|issn=1746-0441|doi=10.1080/17460441.2020.1681394|pmid=31670987|s2cid=207815975}}</ref><ref name="Kratz2019">{{cite journal|vauthors=Kratz JM|title=Drug discovery for Chagas disease: A viewpoint|journal=Acta Tropica|volume=198|year=2019|article-number=105107|issn=0001-706X|doi=10.1016/j.actatropica.2019.105107|pmid=31351074|type=Review|doi-access=free}}</ref>

Several experimental vaccines have been tested in animals. In addition to [[subunit vaccine]]s, some approaches have involved vaccination with [[Attenuated vaccine|attenuated]] {{nowrap|''T. cruzi''}} parasites or organisms that express some of the same antigens as {{nowrap|''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.<ref name="Rios2019">{{cite journal|vauthors=Rios LE, Vázquez-Chagoyán JC, Pacheco AO, Zago MP, Garg NJ|title=Immunity and vaccine development efforts against Trypanosoma cruzi|journal=Acta Tropica|volume=200|year=2019|article-number=105168|issn=0001-706X|doi=10.1016/j.actatropica.2019.105168|pmid=31513763|pmc=7409534|doi-access=free}}</ref>

===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 {{nowrap|''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 [[biomarker]]s of treatment response are under investigation, such as [[immunoassay]]s against specific {{nowrap|''T. cruzi''}} antigens, [[flow cytometry]] testing to detect antibodies against different life stages of {{nowrap|''T. cruzi''}}, and markers of physiological changes caused by the parasite, such as alterations in [[coagulation]] and [[lipid metabolism]].<ref name="Nunes2018"/>

Another research area is the use of biomarkers to predict the progression of chronic disease. Serum levels of [[Tumor necrosis factor|tumor necrosis factor alpha]], [[Ventricular natriuretic peptide|brain]] and [[atrial natriuretic peptide]], and [[angiotensin-converting enzyme 2]] have been studied as indicators of the prognosis of Chagas cardiomyopathy.<ref name="Balouz2017"/>

''T. cruzi'' shed acute-phase antigen (SAPA), which can be detected in blood using [[ELISA]] or Western blot,<ref name="Messenger2018"/> has been used as an indicator of early acute and congenital infection.<ref name="Balouz2017">{{cite journal |vauthors=Balouz V, Agüero F, Buscaglia CA |title=Chagas disease diagnostic applications: present knowledge and future steps |journal=Adv. Parasitol. |volume=97 |pages=1–45 |date=2017 |pmid=28325368 |pmc=5363286 |doi=10.1016/bs.apar.2016.10.001 |type= Review}}</ref> An assay for {{nowrap|''T. cruzi''}} antigens in urine has been developed to diagnose congenital disease.<ref name="Messenger2018"/>

==See also==
* [[Drugs for Neglected Diseases Initiative]]
* [[Chagas: Time to Treat campaign]]

==References==
{{Reflist}}

==External links==
{{Commons category}}
{{offline|med}}
* [https://www.cdc.gov/chagas/ Chagas information] at the U.S. [[Centers for Disease Control]]
* [https://www.dndi.org/?s=chagas Chagas information] from the [[Drugs for Neglected Diseases initiative]]
* [https://www.iamat.org/risks/chagas-disease Chagas disease information] for travellers from the International Association for Medical Assistance to Travellers

{{Medical condition classification and resources
| DiseasesDB     = 13415
| ICD11          = {{ICD11|1F53}}
| ICD10          = {{ICD10|B57}}
| ICD9           = {{ICD9|086}}
| ICDO           = 
| OMIM           = 
| MedlinePlus    = 001372
| eMedicineSubj  = med
| eMedicineTopic = 327
| MeshID         = D014355
| Scholia        = Q649558
}}
{{Diseases of Poverty}}
{{Protozoal diseases}}
{{Authority control}}

{{DEFAULTSORT:Chagas Disease}}
[[Category:Chagas disease| ]]
[[Category:Parasitic infestations, stings, and bites of the skin]]
[[Category:Insect-borne diseases]]
[[Category:Protozoal diseases]]
[[Category:Tropical diseases]]
[[Category:Zoonoses]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia infectious disease articles ready to translate]]