Chagas disease (Portuguese Portuguese ( português or língua portuguesa) is a Romance language that grew from the Latin descended Galician-Portuguese language that was spoken in the mediaeval Kingdom of Galicia, whose territory is now divided between northern Portugal, Galicia and Asturias. It also absorbed influences from the Romance and Arabic languages spoken in the: doença de Chagas, Spanish Countries where Spanish has official status. States of the U.S. where Spanish has no official status but is spoken by 25% or more of the population. States of the U.S. where Spanish has no official status but is spoken by 10-20% of the population. States of the U.S. where Spanish has no official status but is spoken by 5-9.9% of the population: enfermedad de Chagas-Mazza, mal de Chagas in both languages; also called American trypanosomiasis) is a tropical Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions. The diseases are less prevalent in temperate climates, due in part to the occurrence of a cold season, which controls the insect population by forcing hibernation. Insects such as mosquitoes and flies are by far the most common disease carrier, or parasitic disease A parasitic disease is an infectious disease caused or transmitted by a parasite. Many parasites do not cause diseases. Parasitic diseases can affect practically all living organisms, from plants to mammals. The study of parasitic diseases is called parasitology caused by the flagellate Flagellates are organisms with one or more whip-like organelles called flagella. Some cells in animals may be flagellate, for instance the spermatozoa of most phyla. Higher plants and fungi do not produce flagellate cells, but the closely related green algae and chytrids do. Many protists take the form of single-celled flagellates protozoan Protozoa is a subkingdom of microorganisms that are classified generally as unicellular non-fungal eukaryotes. Protozoans are a major component of the ecosystem.[clarification needed] Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector In epidemiology, a vector is an insect or any living carrier that transmits an infectious agent.[page needed] Vectors are vehicles by which infections are transmitted from one host to another. Most commonly known vectors consist of arthropods, domestic animals, or mammals that assist in transmitting parasitic organisms to humans or other mammals, the blood-sucking Hematophagy is the habit of certain animals of feeding on blood (from the Greek words, haima "blood" and phagein "to eat"). Since blood is a fluid tissue rich in nutritious proteins and lipids that can be taken without enormous effort, hematophagy has evolved as a preferred form of feeding in many small animals such as worms assassin bugs of the subfamily Triatominae (family Reduviidae) most commonly species belonging to the Triatoma, Rhodnius Rhodnius is a genus of bugs in the subfamily Triatominae, important vectors of Chagas disease, and Panstrongylus genera.^[1] The disease may also be spread through blood transfusion Blood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery. Blood transfusions may also be used to treat a severe anaemia and organ transplantation An organ transplant is the moving of an organ from one body to another, or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of Regenerative medicine is allowing scientists to engineer organs to be re-grown from the patient's own cells , ingestion of food contaminated with parasites Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the host, and from a mother to her fetus Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission. The concept of vertical transmission is also used in population.^[2]

The symptoms of Chagas disease vary over the course of an infection. In the early, acute stage, symptoms are mild and usually produce no more than local swelling at the site of infection. The initial acute phase is responsive to antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases such as nematodes, cestodes, trematodes, infectious protozoa, and amoebas treatments, with 60-90% cure rates. After 4-8 weeks, individuals with active infections enter the chronic phase of Chagas disease that is asymptomatic for 60-80% of chronically infected individuals throught their lifetime. The antiparasitic treatments also appear to delay or prevent the development of disease symptoms during the chronic phase of the disease, but 20-40% of chronically infected individuals will still eventually develop life-threatening heart and digestive system disorders. The currently available antiparasitic treatments for Chagas disease are benznidazole and nifurtimox Nifurtimox is a 5-nitrofuran and is used to treat diseases caused by trypanosomes . It is given by mouth and not by injection, which can cause temporary side effects in many patients including skin disorders, brain toxicity, and digestive system irritation.^[3][4][5]

Chagas disease is contracted primarily in the Americas, particularly in poor, rural areas of Mexico In Pre-Columbian Mesoamerica many cultures matured into advanced civilizations such as the Olmec, the Toltec, the Teotihuacan, the Zapotec, the Maya and the Aztec before the first contact with Europeans. In 1521, Spain conquered and colonized the territory, which was administered as the viceroyalty of New Spain which would eventually become Mexico, Central America Central America is the central geographic region of the Americas. It is the southernmost, isthmian portion of the North American continent, which connects with South America on the southeast. Central America is considered to be part of the Mesoamerican biodiversity hotspot, excluding the southern portions of Panama, and South America South America is the southern continent of America, situated in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere. It is bordered on the west by the Pacific Ocean and on the north and east by the Atlantic Ocean; North America and the Caribbean Sea lie to the northwest; very rarely, the disease has originated in the Southern United States The Southern United States—commonly referred to as the American South, Dixie, Down South, or simply the South—constitutes a large distinctive region in the southeastern and south-central United States. Because of the region's unique cultural and historic heritage, including Native Americans, early European settlements of English, Ulster Scots,. The insects that spread the disease are known by various local names, including vinchuca in Argentina, Bolivia and Paraguay, barbeiro (the barber The barber surgeon was one of the most common medical practitioners of medieval Europe - generally charged with looking after soldiers during or after a battle. In this era, surgery was not generally conducted by physicians, but by barbers) in Brazil, pito in Colombia, chinche in Central America, chipo, chupança, chinchorro, and "the kissing bug". It is estimated that as many as 8 to 11 million people in Mexico, Central America, and South America have Chagas disease, most of whom do not know they are infected. Large-scale population movements from rural to urban areas of Latin America and to other regions of the world have increased the geographic distribution of Chagas disease, and cases have been noted in many countries, particularly in Europe.^[4] Control strategies have mostly focused on eliminating the triatomine insect vector and preventing transmission from other sources.^[1]

Signs and symptoms

The human disease occurs in two stages: an acute This adjective is part of the definition of several diseases and is, therefore, incorporated in their name, for instance, severe acute respiratory syndrome, acute leukemia stage, which occurs shortly after an initial infection An infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the host and can lead to chronic wounds, gangrene, loss, and a chronic In medicine, a chronic disease is a disease that is long-lasting or recurrent. The term chronic describes the course of the disease, or its rate of onset and development. A chronic course is distinguished from a recurrent course; recurrent diseases relapse repeatedly, with periods of remission in between. As an adjective, chronic can refer to a 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, headache, rash, loss of appetite, diarrhea, 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 In medicine , myocarditis is inflammation of heart muscle (myocardium). It resembles a heart attack but coronary arteries are not blocked) or brain (meningoencephalitis Meningoencephalitis is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain).^[6] The acute phase also can be severe in people with weakened immune systems.^[1]

If symptoms develop during the acute phase, they usually resolve spontaneously within 3–8 weeks in approximately 90% of individuals.^[3][4] 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.^[4][3]

The symptomatic (determinate) chronic stage affects the nervous system The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous system contains the brain, spinal cord, and retina, digestive system Digestion is the mechanical and chemical breaking down of food into smaller components that can be absorbed into a blood stream, for instance. Digestion is a form of catabolism: a break-down of larger food molecules to smaller ones and heart The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions. The term cardiac (as in cardiology) means "related to the heart" and comes from the Greek καρδιά, kardia, for "heart". About two thirds of people with chronic symptoms have cardiac damage, including cardiomyopathy Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both, which causes heart rhythm abnormalities and may result in sudden death. About one third of patients go on to develop digestive system Digestion is the mechanical and chemical breaking down of food into smaller components that can be absorbed into a blood stream, for instance. Digestion is a form of catabolism: a break-down of larger food molecules to smaller ones damage, resulting in dilation of the digestive tract The Human gastrointestinal tract is the system by which ingested food is acted upon by physical and chemical means to provide the body with nutrients it can absorb and to excrete waste products; in mammals the system includes the alimentary canal extending from the mouth to the anus, and the hormones and enzymes assisting in digestion (megacolon Megacolon is an abnormal dilatation of the colon that is not caused by mechanical obstruction. The dilatation is often accompanied by a paralysis of the peristaltic movements of the bowel. In more extreme cases, the feces consolidate into hard masses inside the colon, called fecalomas (literally, fecal tumor), which can require surgery to be and megaesophagus Megaesophagus is a condition in humans and dogs where peristalsis fails to occur properly and the esophagus is enlarged. Normally, when the dog's esophagus is functioning properly, it acts as a muscle and pushes the food down the esophagus into the stomach. However, when a dog has megaesophagus, the esophagus stays enlarged and does not push the), accompanied by severe weight loss Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue. It can occur unintentionally due to an underlying disease or can arise from a conscious. Swallowing Swallowing, known scientifically as deglutition, is the process in the human or animal body that makes something pass from the mouth, to the pharynx, into the esophagus, with the shutting of the epiglottis. If this fails and the object goes through the trachea, then choking or pulmonary aspiration can occur. In the human body it is controlled by difficulties (secondary achalasia Achalasia, also known as esophageal achalasia, achalasia cardiae, cardiospasm, and esophageal aperistalsis, is an esophageal motility disorder involving the smooth muscle layer of the esophagus and the lower esophageal sphincter (LES). It is characterized by incomplete LES relaxation, increased LES tone, and aperistalsis of the esophagus () may be the first symptom of digestive disturbances and may lead to malnutrition Malnutrition is the insufficient, excessive or imbalanced consumption of nutrients. A number of different nutrition disorders may arise, depending on which nutrients are under or overabundant in the diet.^[2] Twenty to fifty percent of individuals with intestinal involvement also exhibit cardiac involvement.^[2] Up to 10% of chronically infected individuals develop neuritis Symptoms depend on the nerves involved, but may include pain, paresthesia, paresis, hypoesthesia , anesthesia, paralysis, wasting, and disappearance of the reflexes that results in altered tendon reflexes and sensory impairment. Isolated cases exhibit central nervous system involvement, including dementia Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging. It may be static, the result of a unique global brain injury, or progressive, resulting in long-term decline due to damage or disease in the body. Although dementia is far more common in the geriatric population, it, confusion, chronic encephalopathy Encephalopathy /ɛnˌsɛfəˈlɒpəθi/ literally means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses and sensitivity In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity. When a stimulus is applied to a sensory receptor, it elicits or influences a reflex via stimulus transduction. A stimulus is often the first component of a homeostatic and motor Motor skill dysfunction has many causes, e.g. demyelination of motor neurons. While fatigue or weariness may lead to temporary short-term deterioration of fine motor skills , serious nervous disorders may result in a loss of both gross and fine motor skills due to the hampering of muscular control. A defect in muscle is also a symptom of motor deficits.^[7]

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 Inflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a synonym for infection. Even in cases where, cellular lesions Because the definition of lesion is so broad, the varieties of lesions are virtually endless. They are subsequently classified by their features. If a lesion is caused by a tumor it will be classified as malignant versus benign. Lesions may be classified by the shape they form, as is the case with many ulcers, which can have a bullseye or 'target', and fibrosis Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue. Scarring is confluent fibrosis that obliterates the architecture of the underlying organ or tissue. For example, intracellular amastigotes destroy the intramural neurons of the autonomic nervous system The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils, micturition (urination), and sexual arousal in the intestine and heart, leading to megaintestine and heart aneurysms An aneurysm or aneurism , is a localized, blood-filled dilation (balloon-like bulge) of a blood vessel caused by disease or weakening of the vessel wall, respectively. If left untreated, Chagas disease can be fatal, in most cases due to heart muscle damage.^[2]

Transmission

In Chagas-endemic areas, the main mode of transmission is through an insect vector In epidemiology, a vector is an insect or any living carrier that transmits an infectious agent.[page needed] Vectors are vehicles by which infections are transmitted from one host to another. Most commonly known vectors consist of arthropods, domestic animals, or mammals that assist in transmitting parasitic organisms to humans or other mammals called a triatomine bug.^[1] 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 The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line various body cavities that are exposed to the external environment and internal organs. They are at several places continuous with skin: at the nostrils, the mouth, the lips, the eyelids, the ears, the, such as the conjunctiva The conjunctiva is a clear mucous membrane consisting of cells and underlying basement membrane that covers the sclera (white part of the eye) and lines the inside of the eyelids. It is made up of rare stratified columnar epithelium. 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.^[1] (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 economical 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.^[8]

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.^[9]

Other modes of transmission include organ transplantation, through breast milk,^[10] 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.^[11]

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 sugar cane juice.^[12][13][14] A 2007 outbreak in 103 Venezuelan school children was attributed to contaminated guava juice.^[15]

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