Chagas' Disease
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Chagas disease, also known as American trypanosomiasis, is a
tropical The tropics are the regions of Earth surrounding the equator, where the sun may shine directly overhead. This contrasts with the temperate or polar regions of Earth, where the Sun can never be directly overhead. This is because of Earth's ax ...
parasitic disease A parasitic disease, also known as parasitosis, is an infectious disease caused by parasites. Parasites are organisms which derive sustenance from its host while causing it harm. The study of parasites and parasitic diseases is known as parasitol ...
caused by ''
Trypanosoma cruzi ''Trypanosoma cruzi'' is a species of parasitic euglenoids. Among the protozoa, the trypanosomes characteristically bore tissue in another organism and feed on blood (primarily) and also lymph. This behaviour causes disease or the likelihood ...
''. It is spread mostly by insects in the
subfamily In biological classification, a subfamily (Latin: ', plural ') is an auxiliary (intermediate) taxonomic rank, next below family but more inclusive than genus. Standard nomenclature rules end botanical subfamily names with "-oideae", and zo ...
Triatominae The members of the Triatominae , a subfamily of the Reduviidae, are also known as conenose bugs, kissing bugs (so-called from their habit of feeding from around the mouths of people), or vampire bugs. Other local names for them used in the Amer ...
, 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 A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s, headaches, or swelling at the site of the
bite Biting is an action involving a set of teeth closing down on an object. It is a common zoological behavior, being found in toothed animals such as mammals, reptiles, amphibians, fishes, and arthropods. Biting is also an action humans participate ...
. After four to eight weeks, untreated individuals enter the chronic phase of disease, which in most cases does not result in further symptoms. Up to 45% of people with chronic infections develop
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
10–30 years after the initial illness, which can lead to
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
. Digestive complications, including an enlarged esophagus or an enlarged colon, may also occur in up to 21% of people, and up to 10% of people may experience nerve damage. is commonly spread to humans and other mammals by the kissing bug's bite wound and the bug's infected feces. The disease may also be spread through
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
,
organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be trans ...
, consuming food or drink contaminated with the parasites, and
vertical transmission Vertical transmission of symbionts is the transfer of a microbial symbiont from the parent directly to the offspring.  Many metazoan species carry symbiotic bacteria which play a mutualistic, commensal, or parasitic role.  A symbiont is acq ...
(from a mother to her baby). Diagnosis of early disease is by finding the parasite in the blood using a microscope or detecting its
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
by
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
. Chronic disease is diagnosed by finding
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
for in the blood. Prevention focuses on eliminating kissing bugs and avoiding their bites. This may involve the use of
insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, i ...
s or
bed-nets A mosquito net is a type of meshed curtain or cloth that is circumferentially draped over a bed or a sleeping area to offer the sleeper barrier protection against bites and stings from mosquitos, flies, and other pest insects, and thus ag ...
. Other preventive efforts include screening blood used for transfusions. Early infections are treatable with the medications
benznidazole Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its mod ...
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 In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...
s, including skin disorders, digestive system irritation, and neurological symptoms, which can result in treatment being discontinued. New drugs for Chagas disease are under development, and while experimental vaccines have been studied in animal models, a human
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...
has not been developed. It is estimated that 6.5 million people, mostly in
Mexico Mexico, officially the United Mexican States, is a country in North America. It is the northernmost country in Latin America, and borders the United States to the north, and Guatemala and Belize to the southeast; while having maritime boundar ...
,
Central America Central America is a subregion of North America. Its political boundaries are defined as bordering Mexico to the north, Colombia to the southeast, the Caribbean to the east, and the Pacific Ocean to the southwest. Central America is usually ...
and
South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a considerably smaller portion in the Northern Hemisphere. It can also be described as the southern Subregion#Americas, subregion o ...
, have Chagas disease as of 2019, resulting in approximately 9,490 annual deaths. Most people with the disease are poor, and most do not realize they are infected. Large-scale population migrations have carried Chagas disease to new regions, which include the United States and many European countries. The disease affects more than 150 types of animals. The disease was first described in 1909 by Brazilian physician
Carlos Chagas Carlos Justiniano Ribeiro Chagas, or Carlos Chagas (; July 9, 1879 – November 8, 1934), was a Brazilian sanitary physician, scientist, and microbiologist who worked as a clinician and researcher. Most well known for the discovery of an eponym ...
, after whom it is named. Chagas disease is classified as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bacteri ...
.


Signs and symptoms

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. The acute stage is often symptom-free. When present, the symptoms are typically minor and not specific to any particular disease. Signs and symptoms include fever,
malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...
, headache, and enlargement of the liver,
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
, and
lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...
. Sometimes, people develop a swollen nodule at the site of infection, which is called "
Romaña Romaña is a Spanish-language surname. Notable people with the name include: * Romaña (guerrilla leader), Henry Castellanos Garzón, a Colombian guerrilla leader * Alberto Rey de Castro y Romaña (1869–1961), a Peruvian politician and diploma ...
's sign" if it is on the eyelid, or a "chagoma" if it is elsewhere on the skin. 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. Unless treated with antiparasitic drugs, individuals remain infected with 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
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
or
digestive system The human digestive system consists of the gastrointestinal tract plus the accessory organs of digestion (the tongue, salivary glands, pancreas, liver, and gallbladder). Digestion involves the breakdown of food into smaller and smaller compone ...
. The most common long-term manifestation is
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
, which occurs in 14–45% of people with chronic Chagas disease. People with Chagas heart disease often experience heart palpitations, and sometimes
fainting Syncope , commonly known as fainting or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...
, due to irregular heart function. By electrocardiogram, people with Chagas heart disease most frequently have
arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...
s. As the disease progresses, the heart's ventricles become enlarged (
dilated cardiomyopathy Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. C ...
), which reduces its ability to pump blood. In many cases, the first sign of Chagas heart disease is
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
,
thromboembolism Thromboembolism is a condition in which a blood clot (thrombus) breaks off from its original site and travels through the bloodstream (as an embolus) to obstruct a blood vessel, causing tissue ischemia and organ damage. Thromboembolism can affe ...
, or chest pain associated with abnormalities in the microvasculature. Also common in chronic Chagas disease is damage to the digestive system, which affects 10–21% of people. Enlargement of the
esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...
or colon are the most common digestive issues. Those with enlarged esophagus often experience pain (
odynophagia Odynophagia is pain when swallowing. The pain may be felt in the mouth or throat and can occur with or without difficulty swallowing. The pain may be described as an ache, burning sensation, or occasionally a stabbing pain that radiates to the ...
) or trouble swallowing (
dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...
), acid reflux,
cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...
, and weight loss. Individuals with enlarged colon often experience
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
, and may develop severe blockage of the intestine or its blood supply. Up to 10% of chronically infected individuals develop nerve damage that can result in numbness and altered
reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...
es or movement. While chronic disease typically develops over decades, some individuals with Chagas disease (less than 10%) progress to heart damage directly after acute disease. 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 Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
,
shortness of breath Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that con ...
, cough, and pain in the chest,
abdomen The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
, and
muscles Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
. Those infected
congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...
ly typically have few to no symptoms, but can have mild non-specific symptoms, or severe symptoms such as
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
,
respiratory distress Shortness of breath (SOB), known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that c ...
, and heart problems. People infected through organ transplant or
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
tend to have symptoms similar to those of
vector Vector most often refers to: * Euclidean vector, a quantity with a magnitude and a direction * Disease vector, an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematics a ...
-borne disease, but the symptoms may not manifest for anywhere from a week to five months. Chronically infected individuals who become immunosuppressed due to
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
infection can have particularly severe and distinct disease, most commonly characterized by inflammation in the brain and surrounding tissue or
brain abscess The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special sense ...
es. Symptoms vary widely based on the size and location of brain abscesses, but typically include fever, headaches, seizures, loss of sensation, or other neurological issues that indicate particular sites of nervous system damage. Occasionally, these individuals also experience acute heart inflammation, skin lesions, and disease of the stomach, intestine, or
peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...
.


Cause

Chagas disease is caused by infection with the
protozoa Protozoa (: protozoan or protozoon; alternative plural: protozoans) are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically ...
n parasite , which is typically introduced into humans through the bite of triatomine bugs, also called "kissing bugs". When the insect defecates at the bite site, motile forms called trypomastigotes enter the bloodstream and invade various host cells. Inside a host cell, the parasite transforms into a replicative form called an amastigote, which undergoes several rounds of replication. The replicated amastigotes transform back into trypomastigotes, which burst the host cell and are released into the bloodstream. Trypomastigotes then disseminate throughout the body to various tissues, where they invade cells and replicate. Over many years, cycles of parasite replication and immune response can severely damage these tissues, particularly the heart and digestive tract.


Transmission

''T. cruzi'' can be transmitted by various triatomine bugs in the genera '' Triatoma'', '' Panstrongylus'', and ''
Rhodnius ''Rhodnius'' is a genus of assassin bugs in the subfamily Triatominae (the kissing bugs), and is an important vector in the spread of Chagas disease. The ''Rhodnius'' species were important models for Sir Vincent Wigglesworth's studies of insect ...
''. The primary vectors for human infection are the species of triatomine bugs that inhabit human dwellings, namely '' Triatoma infestans'', '' Rhodnius prolixus'', '' Triatoma dimidiata'' and '' Panstrongylus megistus''. These insects are known by a number of local names, including ''vinchuca'' in Argentina, Bolivia, Chile and Paraguay, ''barbeiro'' (the
barber A barber is a person whose occupation is mainly to cut, dress, groom, style and shave hair or beards. A barber's place of work is known as a barbershop or the barber's. Barbershops have been noted places of social interaction and public discourse ...
) in Brazil, ''pito'' in Colombia, ''chinche'' in Central America, and ''chipo'' in Venezuela. 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. replicates in the insect's intestinal tract and is shed in the bug's feces. When an infected triatomine feeds, it pierces the skin and takes in a
blood meal Blood meal is a dry, inert powder made from blood, used as a high-nitrogen organic fertilizer and a high protein animal feed. By weight, it is generally 12% nitrogen with trace amounts (≤1%) of phosphorus and potassium. It is one of the hig ...
, defecating at the same time to make room for the new meal. The bite is typically painless, but causes itching. Scratching at the bite introduces the -laden feces into the bite wound, initiating infection. 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. Since heating or drying kills the parasites, drinks and especially fruit juices are the most frequent source of infection. 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—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. ''T. cruzi'' can be transmitted independently of the triatomine bug during blood transfusion, following organ transplantation, or across the
placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...
during pregnancy. Transfusion with the blood of an infected donor infects the recipient 10–25% of the time. To prevent this, blood donations are screened for in many countries with endemic Chagas disease, as well as the United States. Similarly, transplantation of solid organs from an infected donor can transmit to the recipient. This is especially true for
heart transplant A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure when other medical or surgical treatments have failed. , the most common procedure is to take a functioning heart ...
, which transmits ''T. cruzi'' 75–100% of the time, and less so for transplantation of the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
(0–29%) or a
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
(0–19%). An infected mother can pass to her child through the placenta; this occurs in up to 15% of births by infected mothers. 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 The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
's response to it. During this phase, can be found in various tissues throughout the body and circulating in the blood. During the initial weeks of infection, parasite replication is brought under control by the production of
antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
and activation of the host's
inflammatory response Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, particularly cells that target intracellular pathogens such as
NK cell Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...
s and
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s, driven by inflammation-signaling molecules like TNF-α and IFN-γ. 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, is found frequently in the striated muscle fibers of the heart. As disease progresses, the heart becomes generally enlarged, with substantial regions of cardiac muscle fiber replaced by scar tissue and
fat In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food. The term often refers specif ...
. Areas of active inflammation are scattered throughout the heart, with each housing inflammatory immune cells, typically
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s and
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s. Late in the disease, parasites are rarely detected in the heart, and may be present at only very low levels. In the heart, colon, and esophagus, chronic disease leads to a massive loss of nerve endings. In the heart, this may contribute to arrhythmias and other cardiac dysfunction. In the colon and esophagus, loss of nervous system control is the major driver of organ dysfunction. 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. The parasite can insert kinetoplast DNA into host cells, an example of
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HGT is an important factor in the e ...
. 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. 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 The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale betwe ...
examination of fresh anticoagulated blood, or its buffy coat, for motile parasites; or by preparation of thin and thick
blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the i ...
s stained with
Giemsa Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...
, for direct visualization of parasites. Blood smear examination detects parasites in 34–85% of cases. The sensitivity increases if techniques such as microhematocrit centrifugation are used to concentrate the blood. On microscopic examination of stained blood smears, trypomastigotes appear as S or U-shaped organisms with a
flagellum A flagellum (; : flagella) (Latin for 'whip' or 'scourge') is a hair-like appendage that protrudes from certain plant and animal sperm cells, from fungal spores ( zoospores), and from a wide range of microorganisms to provide motility. Many pr ...
connected to the body by an undulating membrane. A nucleus and a smaller structure called a
kinetoplast A kinetoplast is a network of circular DNA (called kDNA) inside a mitochondrion that contains many copies of the mitochondrial genome. The most common kinetoplast structure is a disk, but they have been observed in other arrangements. Kinetoplasts ...
are visible inside the parasite's body; the kinetoplast of is relatively large, which helps to distinguish it from other species of trypanosomes that infect humans. Alternatively, ''T. cruzi'' DNA can be detected by
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR). In acute and congenital Chagas disease, PCR is more sensitive than microscopy, 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 from a mother to her baby (
passive immunity In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced arti ...
). 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. In chronic Chagas disease, the concentration of parasites in the blood is too low to be reliably detected by microscopy or PCR, so the diagnosis is usually made using
serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
tests, which detect
immunoglobulin G Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
antibodies against in the blood. Two positive serology results, using different test methods, are required to confirm the diagnosis. If the test results are inconclusive, additional testing methods such as
Western blot The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
can be used. Various
rapid diagnostic test A rapid diagnostic test (RDT) is a medical diagnostic test that is quick and easy to perform. RDTs are suitable for preliminary or emergency Screening (medicine), medical screening and for use in medical facilities with limited resources. They als ...
s for Chagas disease are available. These tests are easily transported and can be performed by people without special training. They are useful for screening large numbers of people and testing people who cannot access healthcare facilities, but their sensitivity is relatively low, and it is recommended that a second method is used to confirm a positive result. ''T. cruzi'' parasites can be grown from blood samples by
blood culture A blood culture is a medical laboratory test used to detect bacteria or fungi in a person's blood. Under normal conditions, the blood does not contain microorganisms: their presence can indicate a bloodstream infection such as bacteremia or ...
, xenodiagnosis, or by inoculating animals with the person's blood. In the blood culture method, the person's
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s are separated from the plasma and added to a specialized
growth medium A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Differe ...
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. These methods are not routinely used, as they are slow and have low sensitivity.


Prevention

Efforts to prevent Chagas disease have largely focused on
vector control Vector control is any method to limit or eradicate the mammals, birds, insects or other arthropods (here collectively called " vectors") which transmit disease pathogens. The most frequent type of vector control is mosquito control using a varie ...
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. This was originally done with
organochlorine Organochlorine chemistry is concerned with the properties of organochlorine compounds, or organochlorides, organic compounds that contain one or more carbon–chlorine bonds. The chloroalkane class (alkanes with one or more hydrogens substituted ...
,
organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...
, and
carbamate In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...
insecticides, which were supplanted in the 1980s with
pyrethroid A pyrethroid is an organic compound similar to the natural pyrethrins, which are produced by the flowers of pyrethrums (''Chrysanthemum cinerariaefolium'' and ''Chrysanthemum coccineum, C. coccineum''). Pyrethroids are used as commercial and hou ...
s. These programs have drastically reduced transmission in
Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...
and
Chile Chile, officially the Republic of Chile, is a country in western South America. It is the southernmost country in the world and the closest to Antarctica, stretching along a narrow strip of land between the Andes, Andes Mountains and the Paci ...
, and eliminated major vectors from certain regions: ''Triatoma infestans'' from Brazil, Chile,
Uruguay Uruguay, officially the Oriental Republic of Uruguay, is a country in South America. It shares borders with Argentina to its west and southwest and Brazil to its north and northeast, while bordering the Río de la Plata to the south and the A ...
, and parts of
Peru Peru, officially the Republic of Peru, is a country in western South America. It is bordered in the north by Ecuador and Colombia, in the east by Brazil, in the southeast by Bolivia, in the south by Chile, and in the south and west by the Pac ...
and
Paraguay Paraguay, officially the Republic of Paraguay, is a landlocked country in South America. It is bordered by Argentina to the Argentina–Paraguay border, south and southwest, Brazil to the Brazil–Paraguay border, east and northeast, and Boli ...
, as well as ''Rhodnius prolixus'' from
Central America Central America is a subregion of North America. Its political boundaries are defined as bordering Mexico to the north, Colombia to the southeast, the Caribbean to the east, and the Pacific Ocean to the southwest. Central America is usually ...
. Vector control in some regions has been hindered by the development of insecticide resistance among triatomine bugs. In response, vector control programs have implemented alternative insecticides (e.g.
fenitrothion Fenitrothion (IUPAC name: ''O'',''O''-dimethyl ''O''-(3-methyl-4-nitrophenyl) phosphorothioate) is a phosphorothioate (organophosphate) insecticide that is inexpensive and widely used worldwide. Trade names include ''Sumithion'', a 94.2% solutio ...
and bendiocarb in
Argentina Argentina, officially the Argentine Republic, is a country in the southern half of South America. It covers an area of , making it the List of South American countries by area, second-largest country in South America after Brazil, the fourt ...
and
Bolivia Bolivia, officially the Plurinational State of Bolivia, is a landlocked country located in central South America. The country features diverse geography, including vast Amazonian plains, tropical lowlands, mountains, the Gran Chaco Province, w ...
), treatment of domesticated animals (which are also fed on by triatomine bugs) with pesticides, pesticide-impregnated paints, and other experimental approaches. In areas with triatomine bugs, transmission of can be prevented by sleeping under
bed net A mosquito net is a type of meshed curtain or cloth that is circumferentially draped over a bed or a sleeping area to offer the sleeper barrier protection against bites and stings from mosquitos, flies, and other pest insects, and thus ag ...
s and by housing improvements that prevent triatomine bugs from colonizing houses. Blood transfusion was formerly the second-most common mode of transmission for Chagas disease. can survive in refrigerated stored blood, and can survive freezing and thawing, allowing it to persist in whole blood,
packed red blood cells Red blood cell concentrates, also known as red cell concentrates or packed red blood cells, are red blood cells that have been separated for blood transfusion. A red blood cell concentrate typically has a haematocrit of 0.50 – 0.70 L/L and ...
,
granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that i ...
s,
cryoprecipitate Cryoprecipitate, also called cryo for short, or Cryoprecipitate Antihemophilic factor (AHF), is a frozen blood product prepared from blood plasma. To create cryoprecipitate, plasma is slowly thawed to 1–6 °C. A cold-insoluble precipita ...
, and
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s. The development and implementation of
blood bank A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a department of a hospital usually within a clinical pathology labora ...
screening tests have dramatically reduced the risk of infection during a blood transfusion. Nearly all
blood donation A 'blood donation'' occurs when a person voluntarily has blood drawn and used for transfusions and/or made into biopharmaceutical medications by a process called fractionation (separation of whole blood components). A donation may be of wh ...
s in Latin American countries undergo Chagas screening. 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). Serological tests, typically
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
s, are used to detect antibodies against proteins in donor blood. Other modes of transmission have been targeted by Chagas disease prevention programs. Treating -infected mothers during pregnancy reduces the risk of congenital transmission of the infection. To this end, many countries in Latin America have implemented routine screening of pregnant women and infants for infection, and the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
recommends screening all children born to infected mothers to prevent congenital infection from developing into chronic disease. Similarly to blood transfusions, many countries with endemic Chagas disease screen organs for transplantation with serological tests. There is no vaccine against Chagas disease. Several experimental vaccines have been tested in animals infected with and were able to reduce parasite numbers in the blood and heart, but no vaccine candidates had undergone
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s in humans as of 2016.


Management

Chagas disease is managed using antiparasitic drugs to eliminate ''T. cruzi'' from the body, and symptomatic treatment to address the effects of the infection. As of 2018,
benznidazole Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its mod ...
and nifurtimox were the antiparasitic drugs of choice for treating Chagas disease, though benznidazole is the only drug available in most of Latin America. For either drug, treatment typically consists of two to three oral doses per day for 60 to 90 days. Antiparasitic treatment is most effective early in the course of infection: it eliminates from 50 to 80% of people in the acute phase (WHO: "nearly 100 %"), but only 20–60% of those in the chronic phase. 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. Antiparasitic treatment can also slow the progression of the disease and reduce the possibility of congenital transmission. Elimination of does not cure the cardiac and gastrointestinal damage caused by chronic Chagas disease, so these conditions must be treated separately. Antiparasitic treatment is not recommended for people who have already developed dilated cardiomyopathy. Benznidazole is usually considered the
first-line treatment A therapy or medical treatment is the attempted remediation of a health problem, usually following a medical diagnosis. Both words, ''treatment'' and ''therapy'', are often abbreviated tx, Tx, or Tx. As a rule, each therapy has indications an ...
because it has milder
adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...
s than nifurtimox, and its efficacy is better understood. Both benznidazole and nifurtimox have common
side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...
s that can result in treatment being discontinued. The most common side effects of benznidazole are skin rash, digestive problems,
decreased appetite Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...
, weakness, headache, and
sleeping problems Dyssomnias are a broad classification of sleep disorder, sleeping disorders involving difficulty getting to sleep, remaining asleep, or of excessive sleepiness. Dyssomnias are primary disorders of initiating or maintaining sleep or of excessive sl ...
. These side effects can sometimes be treated with
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...
s or
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s, and are generally reversed when treatment is stopped. However, benznidazole is discontinued in up to 29% of cases. Nifurtimox has more frequent side effects, affecting up to 97.5% of individuals taking the drug. The most common side effects are loss of appetite, weight loss, nausea and vomiting, and various
neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...
s including mood changes,
insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
,
paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...
and
peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
. Treatment is discontinued in up to 75% of cases. Both drugs are contraindicated for use in pregnant women and people with
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
or
kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
. As of 2019, resistance to these drugs has been reported.


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.
Beta blocker Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms ( arrhythmia), and to protect the heart from a second heart attack after a first heart attack ( secondary prevention ...
s and
ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...
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. To manage irregular heartbeats, people may be prescribed anti-arrhythmic drugs such as
amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...
, or have a
pacemaker A pacemaker, also known as an artificial cardiac pacemaker, is an implanted medical device that generates electrical pulses delivered by electrodes to one or more of the chambers of the heart. Each pulse causes the targeted chamber(s) to co ...
implanted. Blood thinners may be used to prevent
thromboembolism Thromboembolism is a condition in which a blood clot (thrombus) breaks off from its original site and travels through the bloodstream (as an embolus) to obstruct a blood vessel, causing tissue ischemia and organ damage. Thromboembolism can affe ...
and
stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
. Chronic heart disease caused by untreated ''T. cruzi'' infection is a common reason for
heart transplantation A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure when other medical or surgical treatments have failed. , the most common procedure is to take a functioning heart ...
surgery. Because transplant recipients take
immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classifie ...
s to prevent
organ rejection Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...
, 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. Mild gastrointestinal disease may be treated symptomatically, such as by using
laxative Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubri ...
s for constipation or taking a prokinetic drug like
metoclopramide Metoclopramide is a medication used to treat nausea, vomiting, gastroparesis, and gastroesophageal reflux disease. It is also used to treat migraine headaches. Common side effects include feeling tired, diarrhea, akathisia, and tardive dyski ...
before meals to relieve esophageal symptoms. Surgery to sever the muscles of the lower esophageal sphincter ( cardiomyotomy) may be performed in more severe cases of esophageal disease, and surgical removal of the affected part of the organ may be required for advanced megacolon and megaesophagus.


Epidemiology

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. Chagas disease results in the loss of over 800,000
disability-adjusted life years A disability-adjusted life year (DALY) is a measure of overall disease burden, representing a year lost due to ill-health, disability, or early death. It was developed in the 1990s as a way of comparing the overall health and life expectancy of ...
each year. 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. 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. 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. Transmission by insect vector and blood transfusion has been completely interrupted in Uruguay (1997), Chile (1999), and Brazil (2006), and in Argentina, vectorial transmission had been interrupted in 13 of the 19 endemic provinces as of 2001. During Venezuela's
humanitarian crisis A humanitarian crisis (or sometimes humanitarian disaster) is defined as a singular event or a series of events that are threatening in terms of health, safety or well-being of a community or large group of people. It may be an internal or exter ...
, vectorial transmission has begun occurring in areas where it had previously been interrupted, and Chagas disease
seroprevalence Seroprevalence is the number of persons in a population who test positive for a specific disease based on serology (blood serum) specimens, often presented as a percent of the total specimens tested or as a proportion per 100,000 persons tested. As ...
rates have increased. Transmission rates have also risen in the
Gran Chaco The Gran Chaco or simply Chaco is a sparsely populated, hot and semiarid lowland tropical dry broadleaf forest natural region of the Río de la Plata basin, divided among eastern Bolivia, western Paraguay, northern Argentina, and a portion o ...
region due to insecticide resistance and in the
Amazon basin The Amazon basin is the part of South America drained by the Amazon River and its tributary, tributaries. The Amazon drainage basin covers an area of about , or about 35.5 percent of the South American continent. It is located in the countries ...
due to oral transmission. 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 Deforestation or forest clearance is the removal and destruction of a forest or stand of trees from land that is then converted to non-forest use. Deforestation can involve conversion of forest land to farms, ranches, or urban use. Ab ...
bringing people into closer contact with triatomines and altering the distribution of triatomine species. 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 The Southern Cone (, ) is a geographical and cultural subregion composed of the southernmost areas of South America, mostly south of the Tropic of Capricorn. Traditionally, it covers Argentina, Chile, and Uruguay, bounded on the west by the Pac ...
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
opossum Opossums () are members of the marsupial order Didelphimorphia () endemic to the Americas. The largest order of marsupials in the Western Hemisphere, it comprises 126 species in 18 genera. Opossums originated in South America and entered North A ...
s (''Didelphis'' spp.),
armadillo Armadillos () are New World placental mammals in the order (biology), order Cingulata. They form part of the superorder Xenarthra, along with the anteaters and sloths. 21 extant species of armadillo have been described, some of which are dis ...
s,
marmoset The marmosets (), also known as zaris or sagoin, are twenty-two New World monkey species of the genera '' Callithrix'', '' Cebuella'', '' Callibella'', and ''Mico''. All four genera are part of the biological family Callitrichidae. The term ...
s,
bat Bats are flying mammals of the order Chiroptera (). With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most birds, flying with their very long spread-out ...
s, various
rodent Rodents (from Latin , 'to gnaw') are mammals of the Order (biology), order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and Mandible, lower jaws. About 40% of all mammal specie ...
s and
dog The dog (''Canis familiaris'' or ''Canis lupus familiaris'') is a domesticated descendant of the gray wolf. Also called the domestic dog, it was selectively bred from a population of wolves during the Late Pleistocene by hunter-gatherers. ...
s all of which can be infected by the vectors or orally by eating triatomine bugs and other infected animals. For entomophagous animals this is a common mode. ''Didelphis'' spp. are unique in that they do not require the triatomine for transmission, completing the life cycle through their own urine and feces. Veterinary transmission also occurs through
vertical transmission Vertical transmission of symbionts is the transfer of a microbial symbiont from the parent directly to the offspring.  Many metazoan species carry symbiotic bacteria which play a mutualistic, commensal, or parasitic role.  A symbiont is acq ...
through the placenta,
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
and
organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or org ...
s.


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. As of 2020, approximately 300,000 infected people are living in the United States, and in 2018 it was estimated that 30,000 to 40,000 people in the United States had Chagas cardiomyopathy. The vast majority of cases in the United States occur in immigrants from Latin America, 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, which include woodrats, possums,
raccoon The raccoon ( or , ''Procyon lotor''), sometimes called the North American, northern or common raccoon (also spelled racoon) to distinguish it from Procyonina, other species of raccoon, is a mammal native to North America. It is the largest ...
s, armadillos and
skunk Skunks are mammals in the family Mephitidae. They are known for their ability to spray a liquid with a strong, unpleasant scent from their anal glands. Different species of skunk vary in appearance from black-and-white to brown, cream or gi ...
s. 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. The prevalence varies widely within European countries due to differing immigration patterns. Italy has the second highest prevalence, followed by the Netherlands, the United Kingdom, and Germany.


History

''T. cruzi'' likely circulated in South American mammals long before the arrival of humans on the continent. has been detected in ancient human remains across South America, from a 9000-year-old Chinchorro mummy in the
Atacama Desert The Atacama Desert () is a desert plateau located on the Pacific Ocean, Pacific coast of South America, in the north of Chile. Stretching over a strip of land west of the Andes Mountains, it covers an area of , which increases to if the barre ...
, to remains of various ages in
Minas Gerais Minas Gerais () is one of the 27 federative units of Brazil, being the fourth largest state by area and the second largest in number of inhabitants with a population of 20,539,989 according to the 2022 Brazilian census, 2022 census. Located in ...
, to an 1100-year-old mummy as far north as the Chihuahuan Desert near the
Rio Grande The Rio Grande ( or ) in the United States or the Río Bravo (del Norte) in Mexico (), also known as Tó Ba'áadi in Navajo language, Navajo, is one of the principal rivers (along with the Colorado River) in the Southwestern United States a ...
. 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). The formal description of Chagas disease was made by
Carlos Chagas Carlos Justiniano Ribeiro Chagas, or Carlos Chagas (; July 9, 1879 – November 8, 1934), was a Brazilian sanitary physician, scientist, and microbiologist who worked as a clinician and researcher. Most well known for the discovery of an eponym ...
in 1909 after examining a two-year-old girl with fever, swollen lymph nodes, and an enlarged spleen and liver. Upon examination of her blood, Chagas saw trypanosomes identical to those he had recently identified from the
hindgut The hindgut (or epigaster) is the posterior ( caudal) part of the alimentary canal. In mammals, it includes the distal one third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and up to the ano-rectal junct ...
of triatomine bugs and named ''Trypanosoma cruzi'' in honor of his mentor, Brazilian physician
Oswaldo Cruz Oswaldo Gonçalves Cruz (; August 5, 1872 – February 11, 1917), was a Brazilian physician, pioneer bacteriologist, epidemiology, epidemiologist and public health officer and the founder of the Instituto Oswaldo Cruz, Oswaldo Cruz Institute. ...
. He sent infected triatomine bugs to Cruz in
Rio de Janeiro Rio de Janeiro, or simply Rio, is the capital of the Rio de Janeiro (state), state of Rio de Janeiro. It is the List of cities in Brazil by population, second-most-populous city in Brazil (after São Paulo) and the Largest cities in the America ...
, who showed the bite of the infected triatomine could transmit to marmoset monkeys as well. 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. (in Portuguese with German full translation as "Ueber eine neue Trypanosomiasis des Menschen.") Almost immediately thereafter, at the suggestion of Miguel Couto, then professor of the , the disease was widely referred to as "Chagas disease". 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 frustrating his nomination for the
Nobel Prize The Nobel Prizes ( ; ; ) are awards administered by the Nobel Foundation and granted in accordance with the principle of "for the greatest benefit to humankind". The prizes were first awarded in 1901, marking the fifth anniversary of Alfred N ...
in 1921. In the 1930s, Salvador Mazza rekindled Chagas disease research, describing over a thousand cases in Argentina's
Chaco Province Chaco (; Wichi languages, Wichi: ''To-kós-wet''), officially the Province of Chaco ( ) is one of the 23 provinces of Argentina, provinces of Argentina. Its capital and largest city is Resistencia, Chaco, Resistencia. It is located in the north- ...
. In Argentina, the disease is known as ''mal de Chagas-Mazza'' in his honor. Serological tests for Chagas disease were introduced in the 1940s, demonstrating that infection with was widespread across Latin America. 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. The 1950s saw the discovery that treating blood with
crystal violet Crystal violet or gentian violet, also known as methyl violet 10B or hexamethyl pararosaniline chloride, is a triphenylmethane, triarylmethane dye used as a histological stain and in Gram staining, Gram's method of classifying bacteria. Crystal ...
could eradicate the parasite, leading to its widespread use in transfusion screening programs in Latin America. Large-scale control programs began to take form in the 1960s, first in
São Paulo São Paulo (; ; Portuguese for 'Paul the Apostle, Saint Paul') is the capital of the São Paulo (state), state of São Paulo, as well as the List of cities in Brazil by population, most populous city in Brazil, the List of largest cities in the ...
, then various locations in Argentina, then national-level programs 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 The Pan American Health Organization (PAHO) is a specialized agency of the United Nations (UN) in charge of international health cooperation in the Americas. It fosters technical cooperation among member countries to fight communicable and non ...
, 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 Fexinidazole is a medication used to treat African trypanosomiasis (sleeping sickness) caused by ''Trypanosoma brucei gambiense''. It is effective against both first and second stage disease. It is taken by mouth. Common side effects includ ...
, an antiparasitic drug approved for treating
African trypanosomiasis African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species ''Trypanosoma bru ...
, 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. Several experimental vaccines have been tested in animals. In addition to
subunit vaccine A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expr ...
s, 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
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
s of treatment response are under investigation, such as
immunoassay An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the immunoassay ...
s against specific antigens,
flow cytometry Flow cytometry (FC) is a technique used to detect and measure the physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the ...
testing to detect antibodies against different life stages of , and markers of physiological changes caused by the parasite, such as alterations in
coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of co ...
and
lipid metabolism Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown and storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In ani ...
. Another research area is the use of biomarkers to predict the progression of chronic disease. Serum levels of tumor necrosis factor alpha,
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
and atrial natriuretic peptide, and
angiotensin-converting enzyme 2 Angiotensin-converting enzyme 2 (ACE2) is an enzyme that can be found either attached to the membrane of cells (mACE2) in the intestines, kidney, testis, gallbladder, and heart or in a soluble form (sACE2). Both membrane bound and soluble ACE2 ...
have been studied as indicators of the prognosis of Chagas cardiomyopathy. ''T. cruzi'' shed acute-phase antigen (SAPA), which can be detected in blood using
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay is a solid-phase type of enzyme immunoassay (EIA) to detect the presence of ...
or Western blot, has been used as an indicator of early acute and congenital infection. An assay for antigens in urine has been developed to diagnose congenital disease.


See also

* Drugs for Neglected Diseases Initiative * Chagas: Time to Treat campaign * Association for the Promotion of Independent Disease Control in Developing Countries


References


External links


Chagas information
at the U.S.
Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...

Chagas information
from the Drugs for Neglected Diseases initiative
Chagas disease information
for travellers from the International Association for Medical Assistance to Travellers {{DEFAULTSORT:Chagas Disease Parasitic infestations, stings, and bites of the skin Insect-borne diseases Protozoal diseases Tropical diseases Zoonoses Wikipedia medicine articles ready to translate Wikipedia infectious disease articles ready to translate