Chagas disease

Chagas disease occurs in two stages: an acute stage, which develops one to two weeks after the insect bite, and a chronic stage, which develops over many years. Signs and symptoms include fever, malaise, headache, and enlargement of the liver, spleen, and lymph nodes. In rare cases (less than 1–5%), infected individuals develop severe acute disease, which can involve inflammation of the heart muscle, fluid accumulation around the heart, and 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. Signs and symptoms differ for people infected with 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, abdomen, and muscles. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or peritoneum. ==Cause==

Chagas disease is caused by infection with the protozoan parasite , which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". The bugs tend to feed at night, preferring moist surfaces near the eyes or mouth. A triatomine bug can become infected with when it feeds on an infected host. The bite is typically painless, but causes itching. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. T. cruzi can be transmitted independently of the triatomine bug during blood transfusion, following organ transplantation, or across the placenta during pregnancy. As of 2019, 22.5% of new infections occurred through congenital transmission. ==Pathophysiology==

In the acute phase of the disease, signs and symptoms are caused directly by the replication of and the immune system's response to it. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and fat. In 2010, integrated kDNA was found to be vertically transmitted in five human families. ==Diagnosis==

The presence of T. cruzi in the blood is diagnostic of Chagas disease. During the acute phase of infection, 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. Alternatively, T. cruzi DNA can be detected by polymerase chain reaction (PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, PCR is also used to monitor levels in organ transplant recipients and immunosuppressed people, which allows infection or reactivation to be detected at an early stage. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, T. cruzi parasites can be grown from blood samples by blood culture, xenodiagnosis, or by inoculating animals with the person's blood. In the blood culture method, the person's red blood cells are separated from the plasma and added to a specialized growth medium to encourage multiplication of the parasite. It can take up to six months to obtain the result. Xenodiagnosis involves feeding the blood to triatomine insects, and then examining their feces for the parasite 30 to 60 days later. ==Prevention==

s can be used in endemic areas to prevent bites from triatomine bugs. This was originally done with organochlorine, organophosphate, and carbamate insecticides, which were supplanted in the 1980s with pyrethroids. Nearly all blood donations in Latin American countries undergo Chagas screening. Serological tests, typically ELISAs, are used to detect antibodies against proteins in donor blood. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests. but no vaccine candidates had undergone clinical trials in humans as of 2016. ==Management==

tablets Chagas disease is managed using antiparasitic drugs to eliminate T. cruzi from the body, and symptomatic treatment to address the effects of the infection. but only 20–60% of those in the chronic phase. 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. and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus. ==Epidemiology==

due to Chagas disease in 2016. Grey indicates no data. Otherwise, colors get increasingly dark red for each order of magnitude increase in DALY burden: 0, white. Up to 1,000 DALYs, yellow. 1,001 to 10,000 DALYs, orange. 10,001 to 100,000 DALYs, light red. Greater than 100,000 DALYs, dark red. In 2019, an estimated 6.5 million people worldwide had Chagas disease, with approximately 173,000 new infections and 9,490 deaths each year. The disease resulted in a global annual economic burden estimated at US$7.2 billion in 2013, 86% of which is borne by endemic countries. 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. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), During Venezuela's humanitarian crisis, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease seroprevalence rates have increased. Transmission rates have also risen in the Gran Chaco region due to insecticide resistance and in the Amazon basin due to oral transmission. Orally transmitted Chagas disease is of particular concern in Venezuela, where 16 outbreaks have been recorded between 2007 and 2018. Chagas exists in two different ecological zones. In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where also circulates in wild and domestic animals. commonly infects more than 100 species of mammals across Latin America including opossums (Didelphis spp.), armadillos, marmosets, bats, various rodents and dogs 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. and in 2018 it was estimated that 30,000 to 40,000 people in the United States had Chagas cardiomyopathy. However, locally acquired infection is very rare: only 28 cases were documented from 1955 to 2015. As of 2013, the cost of treatment in the United States was estimated to be US$900 million annually (global cost $7 billion), which included hospitalization and medical devices such as pacemakers. Chagas disease affected approximately 68,000 to 123,000 people in Europe as of 2019. Spain, which has a high rate of immigration from Latin America, has the highest prevalence of the disease. It is estimated that 50,000 to 70,000 people in Spain are living with Chagas disease, accounting for the majority of European cases. ==History==

, in his laboratory at Instituto Oswaldo Cruz T. cruzi likely circulated in South American mammals long before the arrival of humans on the continent. Many early written accounts describe symptoms consistent with Chagas disease, with early descriptions of the disease sometimes attributed to Miguel Diaz Pimenta (1707), (1735), and Theodoro J. H. Langgaard (1842). Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the , the disease was widely referred to as "Chagas disease". In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentina's Chaco Province. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with was widespread across Latin America. These programs received a major boost in the 1980s with the introduction of pyrethroid insecticides, which did not leave stains or odors after application and were longer-lasting and more cost-effective. Regional bodies dedicated to controlling Chagas disease arose through support of the Pan American Health Organization, with the Initiative of the Southern Cone for the Elimination of Chagas Diseases launching in 1991, followed by the Initiative of the Andean countries (1997), Initiative of the Central American countries (1997), and the Initiative of the Amazon countries (2004). ==Research==

Treatments Fexinidazole, an antiparasitic drug approved for treating African trypanosomiasis, has shown activity against Chagas disease in animal models. As of 2019, it is undergoing phase II clinical trials for chronic Chagas disease in Spain. Other drug candidates include GNF6702, a proteasome inhibitor that is effective against Chagas disease in mice and is undergoing preliminary toxicity studies, and AN4169, which has had promising results in animal models. More recently, has been tested AVN-944, an IMPDH inhibitor currently in Phase II clinical trials, has been shown to be active against Trypanosoma cruzi amastigotes in an in vitro cardiomyoblast infection model. Pointing out IMPDH as a novel target to treat Chagas disease. Several experimental vaccines have been tested in animals. In addition to subunit vaccines, some approaches have involved vaccination with attenuated parasites or organisms that express some of the same antigens as but do not cause human disease, such as Trypanosoma rangeli or Phytomonas serpens. DNA vaccination has also been explored. As of 2019, vaccine research has mainly been limited to small animal models. Diagnostic tests As of 2018, standard diagnostic tests for Chagas disease were limited in their ability to measure the effectiveness of antiparasitic treatment, as serological tests may remain positive for years after is eliminated from the body, and PCR may give false-negative results when the parasite concentration in the blood is low. Several potential biomarkers of treatment response are under investigation, such as immunoassays against specific antigens, flow cytometry testing to detect antibodies against different life stages of , and markers of physiological changes caused by the parasite, such as alterations in coagulation and lipid metabolism. An assay for antigens in urine has been developed to diagnose congenital disease. ==See also==