Chagas disease
Encyclopedia
Chagas disease is a tropical
parasitic disease
caused by the flagellate
protozoa
n Trypanosoma cruzi
. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking
insects of the subfamily Triatominae
(family Reduviidae
) most commonly species belonging to the Triatoma
, Rhodnius
, and Panstrongylus
genera.
The disease may also be spread through blood transfusion
and organ transplantation, ingestion of food contaminated with parasites, and from a mother to her fetus
.
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 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 through 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
, which can cause temporary side effects in many patients including skin disorders, brain toxicity, and digestive system irritation.
Chagas disease is contracted primarily in the Americas, particularly in poor, rural areas of Mexico
, Central America, and South America; very rarely, the disease has originated in the Southern United States. The insects that spread the disease are known by various local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber
) in Brazil, pito in Colombia, chinche in Central America, chipo in Venezuela, 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. Control strategies have mostly focused on eliminating the triatomine insect vector and preventing transmission from other sources.
The human disease occurs in two stages: an acute
stage, which occurs shortly after an initial infection
, and a chronic
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
) or brain (meningoencephalitis
). The acute phase also can be severe in people with weakened immune systems.
If symptoms develop during the acute phase, they usually resolve spontaneously within three to eight weeks in approximately 90% of individuals. 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.
The symptomatic (determinate) chronic stage affects the nervous system
, digestive system and heart
. About two-thirds of people with chronic symptoms have cardiac damage, including dilated cardiomyopathy
, which causes heart rhythm abnormalities and may result in sudden death. About one-third of patients go on to develop digestive system damage, resulting in dilation of the digestive tract (megacolon
and megaesophagus
), accompanied by severe weight loss
. Swallowing
difficulties (secondary achalasia
) may be the first symptom of digestive disturbances and may lead to malnutrition
. 20% to 50% of individuals with intestinal involvement also exhibit cardiac involvement. Up to 10% of chronically infected individuals develop neuritis that results in altered tendon reflexes and sensory impairment. Isolated cases exhibit central nervous system involvement, including dementia
, confusion, chronic encephalopathy
and sensitivity
and motor
deficits.
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, cellular lesions, and fibrosis
. For example, intracellular amastigote
s destroy the intramural neurons of the autonomic nervous system
in the intestine and heart, leading to megaintestine and heart aneurysm
s, respectively. If left untreated, Chagas disease can be fatal, in most cases due to heart muscle damage.
In Chagas-endemic areas, the main mode of transmission is through an insect vector called a triatomine bug. 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, such as the conjunctiva
. Once inside the host, the trypomastigotes invade cells, where they differentiate into intracellular amastigote
s. 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. (See also: Life cycle and transmission of T. cruzi)
Dense vegetation (such as that of tropical rainforest
s) 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 economic 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.
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.
Other modes of transmission include organ transplant
ation, through breast milk
, 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.
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
. A 2007 outbreak in 103 Venezuelan school children was attributed to contaminated guava
juice.
The presence of T. cruzi is diagnostic of Chagas disease. It can be detected by microscopic
examination of fresh anticoagulated blood, or its buffy coat
, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa
, for direct visualization of parasites
. Microscopically, T. cruzi can be confused with Trypanosoma rangeli
, which is not known to be pathogenic in humans. Isolation of T. cruzi can occur by inoculation into mice
, by culture in specialized media (for example,, NNN, LIT); and by xenodiagnosis
, where uninfected Reduviidae
bugs are fed on the patient's blood, and their gut contents examined for parasites.
Various immunoassay
s for T. cruzi are available and can be used to distinguish among strains
(zymodemes of T.cruzi with divergent pathogenicities). These tests include: detecting complement fixation, indirect hemagglutination
, indirect fluorescence
assays, radioimmunoassay
s, and ELISA
. Alternatively, diagnosis and strain identification can be made using polymerase chain reaction
(PCR).
There is currently no vaccine against Chagas disease and prevention is generally focused on fighting the vector Triatoma
by using sprays and paints containing insecticide
s (synthetic pyrethroid
s), and improving housing and sanitary conditions in rural areas. For urban dwellers, spending vacations and camping
out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous; a mosquito net
is recommended. Some stepstones of vector control include:
A number of potential vaccines are currently being tested. Vaccination with Trypanosoma rangeli
has produced positive results in animal models. More recently, the potential of DNA vaccines for immunotherapy
of acute and chronic Chagas disease is being tested by several research groups.
Blood transfusion
was formerly the second-most common mode of transmission for Chagas disease, but the development and implementation of blood bank
screening tests has dramatically reduced this risk in the last decade. Blood donation
s in all endemic Latin American countries undergo Chagas screening, and testing is expanding in countries, such as France, Spain and the United States, that have significant or growing populations of immigrants from endemic areas. In Spain, donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests. The US FDA has approved two Chagas tests, including one recently approved in April 2010, and has published guidelines that recommend testing of all donated blood and tissue products. While these tests are not required in U.S., an estimated 75–90% of the blood supply is currently tested for Chagas, including all units collected by the American Red Cross
, which accounts for 40% of the U.S. blood supply. The Chagas Biovigilance Network reports current incidents of Chagas-positive blood products in the United States, as reported by labs using the screening test approved by the FDA in 2007.
or nitro
derivatives, such as benznidazole
or nifurtimox
. Both agents are limited in their capacity to effect parasitologic cure (a complete elimination of T. cruzi from the body), especially in chronically infected patients, and resistance to these drugs has been reported. Studies suggest antiparasitic treatment leads to parasitological cure in about 60–85% of adults and more than 90% of infants treated in the first year of acute phase Chagas disease. Children (aged six to 12 years) with chronic disease have a cure rate of about 60% with benznidazole. While the rate of cure declines the longer an adult has been infected with Chagas, treatment with benznidazole has been shown to slow the onset of heart disease in adults with chronic Chagas infections.
Treatment of chronic infection in women prior to or during pregnancy does not appear to reduce the probability the disease will be passed on to the infant. Likewise, it is unclear whether prophylactic treatment of chronic infection is beneficial in persons who will undergo immunosuppression (for example, organ transplant recipients) or in persons who are already immunosuppressed (for example, those with HIV infection).
s and medications for irregular heartbeats, such as the anti-arrhythmia drug amiodarone
, may be life saving for some patients with chronic cardiac disease, while surgery may be required for megaintestine. The disease cannot be cured in this phase, however. Chronic heart disease caused by Chagas disease is now a common reason for heart transplantation
surgery. Until recently, however, Chagas disease was considered a contraindication
for the procedure, since the heart damage could recur as the parasite was expected to seize the opportunity provided by the immunosuppression
that follows surgery. It was noted that survival rates in Chagas patients could be significantly improved by using lower dosages of the immunosuppressant drug ciclosporin
. Recently, direct stem cell therapy of the heart muscle using bone marrow cell transplantation has been shown to dramatically reduce risks of heart failure in Chagas patients.
Chagas disease affects eight to 10 million people living in endemic Latin American countries, with an additional 300,000–400,000 living in nonendemic countries, including Spain and the United States. An estimated 41,200 new cases occur annually in endemic countries, and 14,400 infants are born with congenital Chagas disease annually. About 20,000 deaths are attributed to it each year.
The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina
. Chagas exists in two different ecological zones. In the Southern Cone
region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where triatomines breed and feed on the over 150 species from 24 families of domestic and wild mammals, as well as humans, that are the natural reservoir
s of T.cruzi. Although Triatominae bugs feed on them, birds appear to be immune to infection and therefore are not considered to be a T. cruzi reservoir. Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters, they can re-emerge from plants or animals that are part of the ancient, sylvatic
(referring to wild animals) infection cycle. This is especially likely in zones with mixed open savannah, with clumps of trees interspersed by human habitation.
The primary wildlife reservoirs for Trypanosoma cruzi in the United States include opossums, raccoon
s, armadillo
s, squirrel
s, woodrats and mice
. Opossums are particularly important as reservoirs, because the parasite can complete its life cycle in the anal glands of the animal without having to re-enter the insect vector. Recorded prevalence of the disease in opossums in the U.S. ranges from 8.3% to 37.5%. Studies on raccoons in the Southeast have yielded infection rates ranging from 47% to as low as 15.5%. Armadillo prevalence studies have been described in Louisiana, and range from a low of 1.1% to 28.8%. Additionally, small rodents, including squirrels, mice and rats, are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors. A Texas study revealed 17.3% percent T. cruzi prevalence in 75 specimens representing four separate small rodent species.
Chronic Chagas disease remains a major health problem in many Latin American countries, despite the effectiveness of hygienic and preventive measures, such as eliminating the transmitting insects. However, several landmarks have been achieved in the fight against it in Latin America, including a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Southern Cone
Initiative, and at least three countries (Uruguay
, in 1997, and Chile
, in 1999, and Brazil in 2006) have been certified free of vectorial and transfusional transmission. In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces. and major progress toward this goal has also been made in both Paraguay and Bolivia.
Screening of donated blood, blood components, and solid organ donors, as well as donors of cells, tissues and cell and tissue products for T. cruzi is mandated in all Chagas-endemic countries and has been implemented. Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries. With increased population movements, the possibility of transmission by blood transfusion became more substantial in the United States. Transfusion blood and tissue products are now actively screened in the U.S., thus addressing and minimizing this risk.
ian physician and infectologist Carlos Chagas
, who first described it in 1909, but the disease was not seen as a major public health
problem in humans until the 1960s (the outbreak of Chagas disease in Brazil in the 1920s went widely ignored). He discovered that the intestines of Triatomidae (now Reduviidae
: Triatominae
) harbored a flagellate protozoan, a new species of the Trypanosoma
genus, and was able to prove experimentally that it could be transmitted to marmoset
monkeys that were bitten by the infected bug. Later studies showed squirrel monkey
s were also vulnerable to infection.
Chagas named the pathogen
ic parasite as Trypanosoma cruzi and later that year as Schizotrypanum cruzi, both honoring Oswaldo Cruz
, the noted Brazilian physician and epidemiologist who successfully fought epidemics of yellow fever
, smallpox
, and bubonic plague
in Rio de Janeiro
and other cities in the beginning of the 20th century. Chagas’ work is unique in the history of medicine
because he was the only researcher so far to describe solely and completely a new infectious disease
: its pathogen
, vector, host
, clinical manifestations, and epidemiology.
Nevertheless, he believed (falsely) until 1925 that the main infection route was by the bite of the insect, not by its feces
, as was proposed by his colleague Emile Brumpt
in 1915 and assured by Silveira Dias in 1932, Cardoso in 1938, and Brumpt himself in 1939. Chagas was also the first to unknowingly discover and illustrate the parasitic fungal genus Pneumocystis
, later infamously to be linked to PCP (Pneumocystis pneumonia]] in AIDS victims). Confusion between the two pathogens' life-cycles led him to briefly recognize his genus Schizotrypanum, but following the description of Pneumocystis by others as an independent genus, Chagas returned to the use of the name Trypanosoma cruzi.
In Argentina
, the disease is known as mal de Chagas-Mazza, in honor of Salvador Mazza
, the Argentine
physician who in 1926 began investigating the disease and over the years became the principal researcher of this disease in the country. Mazza produced the first scientific confirmation of the existence of Trypanosoma cruzi
in Argentina in 1927, eventually leading to support from local and European medical schools and Argentine government policy makers.
It has been hypothesized that Charles Darwin
might have suffered from Chagas disease as a result of a bite of the so-called great black bug of the Pampas (vinchuca) (see Charles Darwin's illness
). The episode was reported by Darwin in his diaries of the Voyage of the Beagle
as occurring in March 1835 to the east of the Andes
near Mendoza
. Darwin was young and generally in good health, though six months previously he had been ill for a month near Valparaiso
, but in 1837, almost a year after he returned to England, he began to suffer intermittently from a strange group of symptom
s, becoming incapacitated for much of the rest of his life. Attempts to test Darwin's remains at the Westminster Abbey
by using modern PCR techniques were met with a refusal by the Abbey's curator
.
cyclase
and squalene synthase, cysteine protease
inhibitors, dermaseptin
s collected from frogs in the genus Phyllomedusa
(P. oreades
and P. distincta
), the sesquiterpene lactone
dehydroleucodine (DhL), which affects the growth of cultured epimastigote–phase Trypanosoma cruzi, inhibitors of purine
uptake, and inhibitors of enzymes involved in trypanothione
metabolism. Hopefully, new drug targets may be revealed following the sequencing of the T. cruzi genome
.
A 2004 in vitro
study suggests components of green tea
(catechins) may be effective against T. cruzi.
Tropical disease
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...
parasitic disease
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, including plants and mammals...
caused by the flagellate
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. Flowering plants do not produce flagellate cells, but ferns, mosses, green algae, some gymnosperms and other closely related plants...
protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
n Trypanosoma cruzi
Trypanosoma cruzi
Trypanosoma cruzi is a species of parasitic euglenoid trypanosomes. This species causes the trypanosomiasis diseases in humans and animals in America...
. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking
Hematophagy
Hematophagy is the practice of certain animals of feeding on blood...
insects of the subfamily Triatominae
Triatominae
The members of Triatominae , a subfamily of Reduviidae, are also known as conenose bugs, kissing bugs, assassin bugs or triatomines. Most of the 130 or more species of this subfamily are haematophagous, i.e. feed on vertebrate blood; a very few species feed on other invertebrates...
(family Reduviidae
Reduviidae
Reduviidae is a large, cosmopolitan family of predatory insects in the suborder Heteroptera...
) most commonly species belonging to the Triatoma
Triatoma
Triatoma is a genus of assassin bug in the subfamily Triatominae The members of Triatoma are blood-sucking insects that can transmit serious diseases, such as Chagas disease....
, Rhodnius
Rhodnius
Rhodnius is a genus of bugs in the subfamily Triatominae, important vectors of Chagas disease. They were important models for Sir Vincent Wigglesworth's studies of insect physiology, specifically growth and development.-Species:...
, and Panstrongylus
Panstrongylus
The Genus Panstrongylus Berg, 1879 belongs to the subfamily Triatominae.-Species:Panstrongylus chinai Panstrongylus diasi Pinto & Lent, 1946Panstrongylus geniculatus...
genera.
The disease may also be spread through blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
and organ transplantation, ingestion of food contaminated with parasites, and from a mother to her fetus
Vertical transmission
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 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 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 through 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
Benznidazole
Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. Its mechanism of action is thought to be inhibition of protein and ribonucleic acid synthesis...
and nifurtimox
Nifurtimox
Nifurtimox is a 5-nitrofuran and is used to treat diseases caused by trypanosomes including Chagas disease and sleeping sickness. It is given by mouth and not by injection.-Indications:...
, which can cause temporary side effects in many patients including skin disorders, brain toxicity, and digestive system irritation.
Chagas disease is contracted primarily in the Americas, particularly in poor, rural areas of Mexico
Mexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...
, Central America, and South America; very rarely, the disease has originated in the Southern United States. The insects that spread the disease are known by various local names, including vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber
Barber surgeon
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 Brazil, pito in Colombia, chinche in Central America, chipo in Venezuela, 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. Control strategies have mostly focused on eliminating the triatomine insect vector and preventing transmission from other sources.
Signs and symptoms
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
stage, which occurs shortly after an initial infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, and a chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
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
Myocarditis
Myocarditis is inflammation of heart muscle . It resembles a heart attack but coronary arteries are not blocked.Myocarditis is most often due to infection by common viruses, such as parvovirus B19, less commonly non-viral pathogens such as Borrelia burgdorferi or Trypanosoma cruzi, or as a...
) or brain (meningoencephalitis
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.-Causes:...
). The acute phase also can be severe in people with weakened immune systems.
If symptoms develop during the acute phase, they usually resolve spontaneously within three to eight weeks in approximately 90% of individuals. 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.
The symptomatic (determinate) chronic stage affects the nervous system
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...
, digestive system and heart
Human heart
The human heart is a muscular organ that provides a continuous blood circulation through the cardiac cycle and is one of the most vital organs in the human body...
. About two-thirds of people with chronic symptoms have cardiac damage, including dilated cardiomyopathy
Dilated cardiomyopathy
Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems....
, which causes heart rhythm abnormalities and may result in sudden death. About one-third of patients go on to develop digestive system damage, resulting in dilation of the digestive tract (megacolon
Megacolon
Megacolon is an abnormal dilation of the colon . The dilatation is often accompanied by a paralysis of the peristaltic movements of the bowel...
and megaesophagus
Megaesophagus
Megaesophagus is a condition in humans, cats 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...
), accompanied by severe weight loss
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...
. Swallowing
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, and into the esophagus, while shutting the epiglottis. If this fails and the object goes through the trachea, then choking or pulmonary aspiration...
difficulties (secondary achalasia
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...
) may be the first symptom of digestive disturbances and may lead to malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....
. 20% to 50% of individuals with intestinal involvement also exhibit cardiac involvement. Up to 10% of chronically infected individuals develop neuritis that results in altered tendon reflexes and sensory impairment. Isolated cases exhibit central nervous system involvement, including dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, confusion, chronic encephalopathy
Encephalopathy
Encephalopathy 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.-Terminology:...
and sensitivity
Stimulus (physiology)
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....
and motor
Motor skill
A motor skill is a learned sequence of movements that combine to produce a smooth, efficient action in order to master a particular task. The development of motor skill occurs in the motor cortex, the region of the cerebral cortex that controls voluntary muscle groups.- Development of motor skills...
deficits.
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, cellular lesions, and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. For example, intracellular amastigote
Amastigote
An amastigote is a cell that does not have a visible external flagella or cilia. The term is used mainly to describe a certain phase in the life-cycle of trypanosome protozoans. It is also called the leishmanial stage, since in Leishmania it is the form the parasite takes in the vertebrate host,...
s destroy the intramural neurons of the autonomic nervous system
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,...
in the intestine and heart, leading to megaintestine and heart aneurysm
Aneurysm
An aneurysm or aneurism is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain and an aortic aneurysm occurs in the main artery carrying blood from the left ventricle of the heart...
s, respectively. If left untreated, Chagas disease can be fatal, in most cases due to heart muscle damage.
Transmission
Conjunctiva
The conjunctiva covers the sclera and lines the inside of the eyelids. It is composed of rare stratified columnar epithelium.-Function:...
. Once inside the host, the trypomastigotes invade cells, where they differentiate into intracellular amastigote
Amastigote
An amastigote is a cell that does not have a visible external flagella or cilia. The term is used mainly to describe a certain phase in the life-cycle of trypanosome protozoans. It is also called the leishmanial stage, since in Leishmania it is the form the parasite takes in the vertebrate host,...
s. 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. (See also: Life cycle and transmission of T. cruzi)
Dense vegetation (such as that of tropical rainforest
Rainforest
Rainforests are forests characterized by high rainfall, with definitions based on a minimum normal annual rainfall of 1750-2000 mm...
s) and urban habitats are not ideal for the establishment of the human transmission cycle. However, in regions where the sylvatic
Sylvatic
Sylvatic is a scientific term referring to diseases or pathogens affecting only wild animals. In the context of animal research, its opposite is domestic, which refers to pets, farm animals or other animals which do not dwell in the wild.*Examples: sylvatic rabies; sylvatic and domestic bacterial...
habitat
Habitat (ecology)
A habitat is an ecological or environmental area that is inhabited by a particular species of animal, plant or other type of organism...
and its fauna are thinned by economic exploitation and human habitation, such as in newly deforested
Deforestation
Deforestation is the removal of a forest or stand of trees where the land is thereafter converted to a nonforest use. Examples of deforestation include conversion of forestland to farms, ranches, or urban use....
areas, piassava palm culture areas, and some parts of the Amazon
Amazon River
The Amazon of South America is the second longest river in the world and by far the largest by waterflow with an average discharge greater than the next seven largest rivers combined...
region, a human transmission cycle may develop as the insects search for new food sources.
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.
Other modes of transmission include organ transplant
Organ transplant
Organ transplantation 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 and engineers to create organs to be...
ation, through breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
, and by accidental laboratory exposure. Chagas disease can also be spread congenitally (from a pregnant woman to her baby) through the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
, and accounts for approximately 13% of stillborn deaths in parts of Brazil.
In 1991, farm workers in the state of Paraíba
Paraíba
Paraíba Paraíba Paraíba (Tupi: pa'ra a'íba: "bad to navigation"; Brazilian Portuguese pronunciation: is a state of Brazil. It is located in the Brazilian Northeast, and is bordered by Rio Grande do Norte to the north, Ceará to the west, Pernambuco to the south and the Atlantic Ocean to the east...
, Brazil, were infected by eating contaminated food; transmission has also occurred via contaminated açaí palm
Açaí Palm
The açaí palm is a species of palm tree in the genus Euterpe cultivated for their fruit and superior hearts of palm. Its name comes from the Portuguese adaptation of the Tupian word ïwasa'i, '[fruit that] cries or expels water'. Global demand for the fruit has expanded rapidly in recent years,...
fruit juice and sugar cane juice
Garapa
Garapa or Caldo de cana is the Brazilian Portuguese term for the juice of raw sugar cane. Sugar cane juice is consumed as a beverage worldwide, and especially in regions where sugarcane is commercially grown such as Southeast Asia, South Asia, and Latin America...
. A 2007 outbreak in 103 Venezuelan school children was attributed to contaminated guava
Guava
Guavas are plants in the myrtle family genus Psidium , which contains about 100 species of tropical shrubs and small trees. They are native to Mexico, Central America, and northern South America...
juice.
Diagnosis
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
examination of fresh anticoagulated blood, or its buffy coat
Buffy coat
The buffy coat is the fraction of an anticoagulated blood sample after density gradient centrifugation that contains most of the white blood cells and platelets.-Description:...
, for motile parasites; or by preparation of thin and thick blood smears stained with Giemsa
Giemsa stain
Giemsa stain, named after Gustav Giemsa, an early German microbiologist, is used in cytogenetics and for the histopathological diagnosis of malaria and other parasites.-Uses:...
, for direct visualization of parasites
Parasitism
Parasitism is a type of symbiotic relationship between organisms of different species where one organism, the parasite, benefits at the expense of the other, the host. Traditionally parasite referred to organisms with lifestages that needed more than one host . These are now called macroparasites...
. Microscopically, T. cruzi can be confused with Trypanosoma rangeli
Trypanosoma rangeli
Trypanosoma rangeli is a species of Trypanosoma.It is considered nonpathogenic in humans.It has been proposed for use in the prevention of Chagas disease....
, which is not known to be pathogenic in humans. Isolation of T. cruzi can occur by inoculation into mice
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
, by culture in specialized media (for example,, NNN, LIT); and by xenodiagnosis
Xenodiagnosis
Xenodiagnosis is a process to diagnose an infectious disease by exposing tissue to a vector and then examining the vector for the presence of a microorganism or pathogen.- Uses :...
, where uninfected Reduviidae
Reduviidae
Reduviidae is a large, cosmopolitan family of predatory insects in the suborder Heteroptera...
bugs are fed on the patient's blood, and their gut contents examined for parasites.
Various immunoassay
Immunoassay
An immunoassay is a biochemical test that measures the presence or concentration of a substance in solutions that frequently contain a complex mixture of substances. Analytes in biological liquids such as serum or urine are frequently assayed using immunoassay methods...
s for T. cruzi are available and can be used to distinguish among strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
(zymodemes of T.cruzi with divergent pathogenicities). These tests include: detecting complement fixation, indirect hemagglutination
Hemagglutination
Hemagglutination, or haemagglutination, is a specific form of agglutination that involves red blood cells . It has two common uses in the laboratory: blood typing and the quantification of virus dilutions.-Blood Typing:...
, indirect fluorescence
Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...
assays, radioimmunoassay
Radioimmunoassay
Radioimmunoassay is a very sensitive in vitro assay technique used to measure concentrations of antigens by use of antibodies...
s, and ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
. Alternatively, diagnosis and strain identification can be made using polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
(PCR).
Prevention
Triatoma
Triatoma is a genus of assassin bug in the subfamily Triatominae The members of Triatoma are blood-sucking insects that can transmit serious diseases, such as Chagas disease....
by using sprays and paints containing insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s (synthetic pyrethroid
Pyrethroid
A pyrethroid is an organic compound similar to the natural pyrethrins produced by the flowers of pyrethrums . Pyrethroids now constitute a major commercial household insecticides...
s), and improving housing and sanitary conditions in rural areas. For urban dwellers, spending vacations and camping
Camping
Camping is an outdoor recreational activity. The participants leave urban areas, their home region, or civilization and enjoy nature while spending one or several nights outdoors, usually at a campsite. Camping may involve the use of a tent, caravan, motorhome, cabin, a primitive structure, or no...
out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous; a mosquito net
Mosquito net
A mosquito net offers protection against mosquitos, flies, and other insects, and thus against diseases such as malaria, dengue fever, yellow fever, and various forms of encephalitis, including the West Nile virus, if used properly and especially if treated with an insecticide, which can double...
is recommended. Some stepstones of vector control include:
- A yeast trap can be used for monitoring infestations of certain species of triatomine bugs (Triatoma sordida, Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus).
- Promising results were gained with the treatment of vector habitats with the fungus Beauveria bassianaBeauveria bassianaBeauveria bassiana is a fungus that grows naturally in soils throughout the world and acts as a parasite on various arthropod species, causing white muscardine disease; it thus belongs to the entomopathogenic fungi. It is being used as a biological insecticide to control a number of pests such as...
. - Targeting the symbionts of TriatominaeTriatominaeThe members of Triatominae , a subfamily of Reduviidae, are also known as conenose bugs, kissing bugs, assassin bugs or triatomines. Most of the 130 or more species of this subfamily are haematophagous, i.e. feed on vertebrate blood; a very few species feed on other invertebrates...
through paratransgenesisParatransgenesisParatransgenesis is a technique that attempts to eliminate a pathogen from vector populations through transgenesis of a symbiont of the vector. The goal of this technique is to control vector-borne diseases. The first step is to identify proteins that prevent the vector species from transmitting...
can be done.
A number of potential vaccines are currently being tested. Vaccination with Trypanosoma rangeli
Trypanosoma rangeli
Trypanosoma rangeli is a species of Trypanosoma.It is considered nonpathogenic in humans.It has been proposed for use in the prevention of Chagas disease....
has produced positive results in animal models. More recently, the potential of DNA vaccines for immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
of acute and chronic Chagas disease is being tested by several research groups.
Blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
was formerly the second-most common mode of transmission for Chagas disease, but the development and implementation of blood bank
Blood bank
A blood bank is a cache or bank of blood or blood components, gathered as a result of blood donation, stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a division of a hospital laboratory where the storage of blood product occurs and where proper...
screening tests has dramatically reduced this risk in the last decade. Blood donation
Blood donation
A blood donation occurs when a person voluntarily has blood drawn and used for transfusions or made into medications by a process called fractionation....
s in all endemic Latin American countries undergo Chagas screening, and testing is expanding in countries, such as France, Spain and the United States, that have significant or growing populations of immigrants from endemic areas. In Spain, donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests. The US FDA has approved two Chagas tests, including one recently approved in April 2010, and has published guidelines that recommend testing of all donated blood and tissue products. While these tests are not required in U.S., an estimated 75–90% of the blood supply is currently tested for Chagas, including all units collected by the American Red Cross
American Red Cross
The American Red Cross , also known as the American National Red Cross, is a volunteer-led, humanitarian organization that provides emergency assistance, disaster relief and education inside the United States. It is the designated U.S...
, which accounts for 40% of the U.S. blood supply. The Chagas Biovigilance Network reports current incidents of Chagas-positive blood products in the United States, as reported by labs using the screening test approved by the FDA in 2007.
Management
There are two approaches to treating Chagas disease, antiparasitic treatment, to kill the parasite; and symptomatic treatment, to manage the symptoms and signs of infection.Medication
Antiparasitic treatment is most effective early in the course of infection, but is not limited to cases in the acute phase. Drugs of choice include azoleAzole
An azole is a class of five-membered nitrogen heterocyclic ring compounds containing at least one other non-carbon atom of either nitrogen, sulfur, or oxygen. The parent compounds are aromatic and have two double bonds; there are successively reduced analogs with fewer...
or nitro
Nitro
-Chemistry:*Nitroglycerin, an explosive chemical compound*Nitromethane, the simplest organic nitro compound; also used to fuel high-performance internal-combustion engines*Nitrous oxide, "laughing gas", used in some dental procedures as an anaesthetic...
derivatives, such as benznidazole
Benznidazole
Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. Its mechanism of action is thought to be inhibition of protein and ribonucleic acid synthesis...
or nifurtimox
Nifurtimox
Nifurtimox is a 5-nitrofuran and is used to treat diseases caused by trypanosomes including Chagas disease and sleeping sickness. It is given by mouth and not by injection.-Indications:...
. Both agents are limited in their capacity to effect parasitologic cure (a complete elimination of T. cruzi from the body), especially in chronically infected patients, and resistance to these drugs has been reported. Studies suggest antiparasitic treatment leads to parasitological cure in about 60–85% of adults and more than 90% of infants treated in the first year of acute phase Chagas disease. Children (aged six to 12 years) with chronic disease have a cure rate of about 60% with benznidazole. While the rate of cure declines the longer an adult has been infected with Chagas, treatment with benznidazole has been shown to slow the onset of heart disease in adults with chronic Chagas infections.
Treatment of chronic infection in women prior to or during pregnancy does not appear to reduce the probability the disease will be passed on to the infant. Likewise, it is unclear whether prophylactic treatment of chronic infection is beneficial in persons who will undergo immunosuppression (for example, organ transplant recipients) or in persons who are already immunosuppressed (for example, those with HIV infection).
Complications
In the chronic stage, treatment involves managing the clinical manifestations of the disease. For example, pacemakerPacemaker
An artificial pacemaker is a medical device that uses electrical impulses to regulate the beating of the heart.Pacemaker may also refer to:-Medicine:...
s and medications for irregular heartbeats, such as the anti-arrhythmia drug amiodarone
Amiodarone
Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
, may be life saving for some patients with chronic cardiac disease, while surgery may be required for megaintestine. The disease cannot be cured in this phase, however. Chronic heart disease caused by Chagas disease is now a common reason for heart transplantation
Heart transplantation
A heart transplant, or a cardiac transplantation, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease. As of 2007 the most common procedure was to take a working heart from a recently deceased organ donor and implant it into the...
surgery. Until recently, however, Chagas disease was considered a contraindication
Contraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
for the procedure, since the heart damage could recur as the parasite was expected to seize the opportunity provided by the immunosuppression
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
that follows surgery. It was noted that survival rates in Chagas patients could be significantly improved by using lower dosages of the immunosuppressant drug ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
. Recently, direct stem cell therapy of the heart muscle using bone marrow cell transplantation has been shown to dramatically reduce risks of heart failure in Chagas patients.
Epidemiology
The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
. Chagas exists in two different ecological zones. In the Southern Cone
Southern Cone
Southern Cone is a geographic region composed of the southernmost areas of South America, south of the Tropic of Capricorn. Although geographically this includes part of Southern and Southeast of Brazil, in terms of political geography the Southern cone has traditionally comprised Argentina,...
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 triatomines breed and feed on the over 150 species from 24 families of domestic and wild mammals, as well as humans, that are the natural reservoir
Natural reservoir
Natural reservoir or nidus, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal...
s of T.cruzi. Although Triatominae bugs feed on them, birds appear to be immune to infection and therefore are not considered to be a T. cruzi reservoir. Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters, they can re-emerge from plants or animals that are part of the ancient, sylvatic
Sylvatic
Sylvatic is a scientific term referring to diseases or pathogens affecting only wild animals. In the context of animal research, its opposite is domestic, which refers to pets, farm animals or other animals which do not dwell in the wild.*Examples: sylvatic rabies; sylvatic and domestic bacterial...
(referring to wild animals) infection cycle. This is especially likely in zones with mixed open savannah, with clumps of trees interspersed by human habitation.
The primary wildlife reservoirs for Trypanosoma cruzi in the United States include opossums, raccoon
Raccoon
Procyon is a genus of nocturnal mammals, comprising three species commonly known as raccoons, in the family Procyonidae. The most familiar species, the common raccoon , is often known simply as "the" raccoon, as the two other raccoon species in the genus are native only to the tropics and are...
s, armadillo
Armadillo
Armadillos are New World placental mammals, known for having a leathery armor shell. Dasypodidae is the only surviving family in the order Cingulata, part of the superorder Xenarthra along with the anteaters and sloths. The word armadillo is Spanish for "little armored one"...
s, squirrel
Squirrel
Squirrels belong to a large family of small or medium-sized rodents called the Sciuridae. The family includes tree squirrels, ground squirrels, chipmunks, marmots , flying squirrels, and prairie dogs. Squirrels are indigenous to the Americas, Eurasia, and Africa and have been introduced to Australia...
s, woodrats and mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
. Opossums are particularly important as reservoirs, because the parasite can complete its life cycle in the anal glands of the animal without having to re-enter the insect vector. Recorded prevalence of the disease in opossums in the U.S. ranges from 8.3% to 37.5%. Studies on raccoons in the Southeast have yielded infection rates ranging from 47% to as low as 15.5%. Armadillo prevalence studies have been described in Louisiana, and range from a low of 1.1% to 28.8%. Additionally, small rodents, including squirrels, mice and rats, are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors. A Texas study revealed 17.3% percent T. cruzi prevalence in 75 specimens representing four separate small rodent species.
Chronic Chagas disease remains a major health problem in many Latin American countries, despite the effectiveness of hygienic and preventive measures, such as eliminating the transmitting insects. However, several landmarks have been achieved in the fight against it in Latin America, including a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Southern Cone
Southern Cone
Southern Cone is a geographic region composed of the southernmost areas of South America, south of the Tropic of Capricorn. Although geographically this includes part of Southern and Southeast of Brazil, in terms of political geography the Southern cone has traditionally comprised Argentina,...
Initiative, and at least three countries (Uruguay
Uruguay
Uruguay ,officially the Oriental Republic of Uruguay,sometimes the Eastern Republic of Uruguay; ) is a country in the southeastern part of South America. It is home to some 3.5 million people, of whom 1.8 million live in the capital Montevideo and its metropolitan area...
, in 1997, and Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
, in 1999, and Brazil in 2006) have been certified free of vectorial and transfusional transmission. In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces. and major progress toward this goal has also been made in both Paraguay and Bolivia.
Screening of donated blood, blood components, and solid organ donors, as well as donors of cells, tissues and cell and tissue products for T. cruzi is mandated in all Chagas-endemic countries and has been implemented. Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries. With increased population movements, the possibility of transmission by blood transfusion became more substantial in the United States. Transfusion blood and tissue products are now actively screened in the U.S., thus addressing and minimizing this risk.
History
The disease was named after the BrazilBrazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
ian physician and infectologist Carlos Chagas
Carlos Chagas
Carlos Justiniano Ribeiro Chagas, or Carlos Chagas , was a Brazilian sanitary physician, scientist and bacteriologist who worked as a clinician and researcher. He discovered Chagas disease, also called American trypanosomiasis in 1909, while working at the Oswaldo Cruz Institute in Rio de Janeiro...
, who first described it in 1909, but the disease was not seen as a major public health
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
problem in humans until the 1960s (the outbreak of Chagas disease in Brazil in the 1920s went widely ignored). He discovered that the intestines of Triatomidae (now Reduviidae
Reduviidae
Reduviidae is a large, cosmopolitan family of predatory insects in the suborder Heteroptera...
: Triatominae
Triatominae
The members of Triatominae , a subfamily of Reduviidae, are also known as conenose bugs, kissing bugs, assassin bugs or triatomines. Most of the 130 or more species of this subfamily are haematophagous, i.e. feed on vertebrate blood; a very few species feed on other invertebrates...
) harbored a flagellate protozoan, a new species of the Trypanosoma
Trypanosoma
Trypanosoma is a genus of kinetoplastids , a monophyletic group of unicellular parasitic flagellate protozoa. The name is derived from the Greek trypano and soma because of their corkscrew-like motion. All trypanosomes are heteroxenous and are transmitted via a vector...
genus, and was able to prove experimentally that it could be transmitted to marmoset
Marmoset
Marmosets are the 22 New World monkey species of the genera Callithrix, Cebuella, Callibella, and Mico. All four genera are part of the biological family Callitrichidae. The term marmoset is also used in reference to the Goeldi's Monkey, Callimico goeldii, which is closely related.Most marmosets...
monkeys that were bitten by the infected bug. Later studies showed squirrel monkey
Squirrel monkey
The squirrel monkeys are the New World monkeys of the genus Saimiri. They are the only genus in the subfamily Saimirinae.Squirrel monkeys live in the tropical forests of Central and South America in the canopy layer. Most species have parapatric or allopatric ranges in the Amazon, while S...
s were also vulnerable to infection.
Chagas named the pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
ic parasite as Trypanosoma cruzi and later that year as Schizotrypanum cruzi, both honoring Oswaldo Cruz
Oswaldo Cruz
Oswaldo Gonçalves Cruz, better known as Oswaldo Cruz |São Paulo]] state, Brazil – February 11, 1917, Petrópolis, Rio de Janeiro state) was a Brazilian physician, bacteriologist, epidemiologist and public health officer and the founder of the Oswaldo Cruz Institute.He also occupied the 5th chair of...
, the noted Brazilian physician and epidemiologist who successfully fought epidemics of yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
, smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
, and bubonic plague
Bubonic plague
Plague is a deadly infectious disease that is caused by the enterobacteria Yersinia pestis, named after the French-Swiss bacteriologist Alexandre Yersin. Primarily carried by rodents and spread to humans via fleas, the disease is notorious throughout history, due to the unrivaled scale of death...
in Rio de Janeiro
Rio de Janeiro
Rio de Janeiro , commonly referred to simply as Rio, is the capital city of the State of Rio de Janeiro, the second largest city of Brazil, and the third largest metropolitan area and agglomeration in South America, boasting approximately 6.3 million people within the city proper, making it the 6th...
and other cities in the beginning of the 20th century. Chagas’ work is unique in the history of medicine
History of medicine
All human societies have medical beliefs that provide explanations for birth, death, and disease. Throughout history, illness has been attributed to witchcraft, demons, astral influence, or the will of the gods...
because he was the only researcher so far to describe solely and completely a new infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
: its pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
, vector, host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
, clinical manifestations, and epidemiology.
Nevertheless, he believed (falsely) until 1925 that the main infection route was by the bite of the insect, not by its feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
, as was proposed by his colleague Emile Brumpt
Emile Brumpt
Alexandre Joseph Emile Brumpt was a French parasitologist who was born in Paris. He studied zoology and parasitology in Paris, obtaining his degree in science in 1901, and his medical doctorate in 1906. In 1919 he became a professor to the Faculté de Médecine, as well as director of the...
in 1915 and assured by Silveira Dias in 1932, Cardoso in 1938, and Brumpt himself in 1939. Chagas was also the first to unknowingly discover and illustrate the parasitic fungal genus Pneumocystis
Pneumocystis pneumonia
Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii...
, later infamously to be linked to PCP (Pneumocystis pneumonia]] in AIDS victims). Confusion between the two pathogens' life-cycles led him to briefly recognize his genus Schizotrypanum, but following the description of Pneumocystis by others as an independent genus, Chagas returned to the use of the name Trypanosoma cruzi.
In Argentina
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
, the disease is known as mal de Chagas-Mazza, in honor of Salvador Mazza
Salvador Mazza
Salvador Mazza was a noted Argentine physician and epidemiologist, best known for his strides in helping control American trypanosomiasisan endemic disease among the rural, poor majority of early 20th century South America....
, the Argentine
Argentina
Argentina , officially the Argentine Republic , is the second largest country in South America by land area, after Brazil. It is constituted as a federation of 23 provinces and an autonomous city, Buenos Aires...
physician who in 1926 began investigating the disease and over the years became the principal researcher of this disease in the country. Mazza produced the first scientific confirmation of the existence of Trypanosoma cruzi
Trypanosoma cruzi
Trypanosoma cruzi is a species of parasitic euglenoid trypanosomes. This species causes the trypanosomiasis diseases in humans and animals in America...
in Argentina in 1927, eventually leading to support from local and European medical schools and Argentine government policy makers.
It has been hypothesized that Charles Darwin
Charles Darwin
Charles Robert Darwin FRS was an English naturalist. He established that all species of life have descended over time from common ancestry, and proposed the scientific theory that this branching pattern of evolution resulted from a process that he called natural selection.He published his theory...
might have suffered from Chagas disease as a result of a bite of the so-called great black bug of the Pampas (vinchuca) (see Charles Darwin's illness
Charles Darwin's illness
For much of his adult life, Charles Darwin's health was repeatedly compromised by an uncommon combination of symptoms, leaving him severely debilitated for long periods of time...
). The episode was reported by Darwin in his diaries of the Voyage of the Beagle
The Voyage of the Beagle
The Voyage of the Beagle is a title commonly given to the book written by Charles Darwin and published in 1839 as his Journal and Remarks, bringing him considerable fame and respect...
as occurring in March 1835 to the east of the Andes
Andes
The Andes is the world's longest continental mountain range. It is a continual range of highlands along the western coast of South America. This range is about long, about to wide , and of an average height of about .Along its length, the Andes is split into several ranges, which are separated...
near Mendoza
Mendoza Province
The Province of Mendoza is a province of Argentina, located in the western central part of the country in the Cuyo region. It borders to the north with San Juan, the south with La Pampa and Neuquén, the east with San Luis, and to the west with the republic of Chile; the international limit is...
. Darwin was young and generally in good health, though six months previously he had been ill for a month near Valparaiso
Valparaíso
Valparaíso is a city and commune of Chile, center of its third largest conurbation and one of the country's most important seaports and an increasing cultural center in the Southwest Pacific hemisphere. The city is the capital of the Valparaíso Province and the Valparaíso Region...
, but in 1837, almost a year after he returned to England, he began to suffer intermittently from a strange group of symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s, becoming incapacitated for much of the rest of his life. Attempts to test Darwin's remains at the Westminster Abbey
Westminster Abbey
The Collegiate Church of St Peter at Westminster, popularly known as Westminster Abbey, is a large, mainly Gothic church, in the City of Westminster, London, United Kingdom, located just to the west of the Palace of Westminster. It is the traditional place of coronation and burial site for English,...
by using modern PCR techniques were met with a refusal by the Abbey's curator
Curator
A curator is a manager or overseer. Traditionally, a curator or keeper of a cultural heritage institution is a content specialist responsible for an institution's collections and involved with the interpretation of heritage material...
.
Research
Several experimental treatments have shown promise in animal models. These include inhibitors of oxidosqualene2,3-Oxidosqualene
2,3- Oxidosqualene ' is an intermediate in the synthesis of the membrane sterol precursors lanosterol and cycloartenol, as well as saponins. It is formed from squalene by squalene monooxygenase...
cyclase
Cyclase
A cyclase is an enzyme, almost always a lyase, that catalyzes a chemical reaction to form a cyclic compound. Important cyclase enzymes include:* Adenylyl cyclase, which forms cyclic AMP from adenosine triphosphate...
and squalene synthase, cysteine protease
Cysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
inhibitors, dermaseptin
Dermaseptin
Dermaseptins are one of a number of families of peptides that have been identified, isolated and characterised from the Phyllomedusa genus of frogs....
s collected from frogs in the genus Phyllomedusa
Phyllomedusa
Phyllomedusa is a genus of tree frog from Central and South America. It ranges from Costa Rica southward to Argentina. It has around thirty species.-Secretion:...
(P. oreades
Phyllomedusa oreades
Phyllomedusa oreades is a species of frog in the Hylidae family.It is endemic to Brazil.Its natural habitats are subtropical or tropical dry shrubland, subtropical or tropical dry lowland grassland, and rivers.-Source:...
and P. distincta
Phyllomedusa distincta
Phyllomedusa distincta is a species of frog in the Hylidae family.It is endemic to Brazil.Its natural habitats are subtropical or tropical moist lowland forests and freshwater marshes.It is threatened by habitat loss.-References:...
), the sesquiterpene lactone
Sesquiterpene lactone
Sesquiterpene lactones are a class of chemical compounds; they are sesquiterpenoids and contain a lactone ring, hence the name....
dehydroleucodine (DhL), which affects the growth of cultured epimastigote–phase Trypanosoma cruzi, inhibitors of purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
uptake, and inhibitors of enzymes involved in trypanothione
Trypanothione
Trypanothione is an unusual form of glutathione containing two molecules of glutathione joined by a spermidine linker. It is found in parasitic protozoa such as leishmania and trypanosomes. These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease....
metabolism. Hopefully, new drug targets may be revealed following the sequencing of the T. cruzi genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
.
A 2004 in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
study suggests components of green tea
Green tea
Green tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...
(catechins) may be effective against T. cruzi.
See also
- Drugs for Neglected Diseases InitiativeDrugs for Neglected Diseases InitiativeThe Drugs for Neglected Diseases Initiative 501 is a non-profit drug research and development organization that is developing new treatments for neglected diseases....
- Chagas: Time to Treat campaignChagas: Time to Treat campaignThe Chagas: Time to Treat Campaign is an international campaign started by the Drugs for Neglected Diseases initiative to advocate for increased research and development of treatments for Chagas disease. Chagas is a potentially fatal neglected disease that affects between 8 and 13 million people...
- Association for the Promotion of Independent Disease Control in Developing CountriesGEFEKGEFEK, the Association for the Promotion of Independent Disease Control in Developing Countries was created by scientists of the University of Giessen, Germany, in 2004 and is officially registered as a non-profit organisation...
Further reading
A Special issue of the Memórias do Instituto Oswaldo Cruz, covering all aspects of Chagas DiseaseExternal links
- Chagas information at the U.S. Centers for Disease Control
- Chagas information from the Drugs for Neglected Diseases initiativeDrugs for Neglected Diseases InitiativeThe Drugs for Neglected Diseases Initiative 501 is a non-profit drug research and development organization that is developing new treatments for neglected diseases....
- Norma Andrews online iBioSeminar: "Trypanosoma cruzi and Chagas’ Disease"