Editing Chagas disease (section)

==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 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 |pages=e9181 |date=February 2010 |pmid=20169193 |pmc=2820539 |doi=10.1371/journal.pone.0009181 |doi-access=free |url=}}</ref>