Chagas disease (Portuguese: doença de Chagas, Spanish: enfermedad de Chagas-Mazza, mal de Chagas in both languages; also called American trypanosomiasis) is a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector, the blood-sucking assassin bugs of the subfamily Triatominae (family Reduviidae) most commonly species belonging to the Triatoma, Rhodnius, and Panstrongylus genera.[1] 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.[2]
The symptoms of Chagas disease vary over the course of an infection. In the early, acute stage, symptoms are mild and usually produce no more than local swelling at the site of infection. The initial acute phase is responsive to antiparasitic 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.[3][4][5]
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 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.[4] Control strategies have mostly focused on eliminating the triatomine insect vector and preventing transmission from other sources.[1]
Signs and symptoms
The human disease occurs in two stages: an acute 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).[6] The acute phase also can be severe in people with weakened immune systems.[1]
If symptoms develop during the acute phase, they usually resolve spontaneously within 3–8 weeks in approximately 90% of individuals.[3][4] Although the symptoms resolve, even with treatment the infection persists and enters a chronic phase. Of individuals with chronic Chagas disease, 60-80% will never develop symptoms (called indeterminate chronic Chagas disease), while the remaining 20-40% will develop life-threatening heart and/or digestive disorders during their lifetime (called determinate chronic Chagas disease). In 10% of individuals the disease progresses directly from the acute form to a symptomatic clinical form of chronic Chagas disease.[3][4]
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 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.[2] Twenty to fifty percent of individuals with intestinal involvement also exhibit cardiac involvement.[2] 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.[7]
The clinical manifestations of Chagas disease are due to cell death in the target tissues that occurs during the infective cycle, by sequentially inducing an inflammatory response, cellular lesions, and fibrosis. For example, intracellular amastigotes destroy the intramural neurons of the autonomic nervous system in the intestine and heart, leading to megaintestine and heart aneurysms, respectively. If left untreated, Chagas disease can be fatal, in most cases due to heart muscle damage.[2]
Transmission
In Chagas-endemic areas, the main mode of transmission is through an insect vector called a triatomine bug.[1] A triatomine becomes infected with T. cruzi by feeding on the blood of an infected person or animal. During the day, triatomines hide in crevices in the walls and roofs. The bugs emerge at night, when the inhabitants are sleeping. Because they tend to feed on people’s faces, triatomine bugs are also known as “kissing bugs.” After they bite and ingest blood, they defecate on the person. Triatomines pass T. cruzi parasites (called trypomastigotes) in feces left near the site of the bite wound. Scratching the site of the bite causes the trypomastigotes to enter the host through the wound, or through intact mucous membranes, such as the conjunctiva. Once inside the host, the trypomastigotes invade cells, where they differentiate into intracellular amastigotes. The amastigotes multiply by binary fission and differentiate into trypomastigotes, which are then released into the bloodstream. This cycle is repeated in each newly infected cell. Replication resumes only when the parasites enter another cell or are ingested by another vector.[1] (See also: Life cycle and transmission of T. Cruzi)
Dense vegetation (such as that of tropical rainforests) and urban habitats are not ideal for the establishment of the human transmission cycle. However, in regions where the sylvatic habitat and its fauna are thinned by economical exploitation and human habitation, such as in newly deforested areas, piassava palm culture areas, and some parts of the Amazon region, a human transmission cycle may develop as the insects search for new food sources.[8]
T. cruzi can also be transmitted through blood transfusions. With the exception of blood derivatives (such as fractionated antibodies), all blood components are infective. The parasite remains viable at 4°C for at least 18 days or up to 250 days when kept at room temperature. It is unclear whether T. cruzi can be transmitted through frozen-thawed blood components.[9]
Other modes of transmission include organ transplantation, through breast milk,[10] and by accidental laboratory exposure. Chagas disease can also be spread congenitally (from a pregnant woman to her baby) through the placenta, and accounts for approximately 13% of stillborn deaths in parts of Brazil.[11]
In 1991, farm workers in the state of Paraíba, Brazil, were infected by eating contaminated food; transmission has also occurred via contaminated açaí palm fruit juice and sugar cane juice.[12][13][14] A 2007 outbreak in 103 Venezuelan school children was attributed to contaminated guava juice.[15]
Diagnosis
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 (e.g., NNN, LIT); and by xenodiagnosis,[16] where uninfected Reduviidae bugs are fed on the patient's blood, and their gut contents examined for parasites.[2]
Various immunoassays 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, radioimmunoassays, and ELISA. Alternatively, diagnosis and strain identification can be made using polymerase chain reaction (PCR).[2]
Prevention
There is currently no vaccine against Chagas disease[17] and prevention is generally focused on fighting the vector Triatoma by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in rural areas.[18] 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 yeast trap tested for monitoring infestations of certain species of triatomine bugs (Triatoma sordida, Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus).[19]
- Promising results were gained with the treatment of vector habitats with the fungus Beauveria bassiana.[20]
- Targeting the symbionts of Triatominae through paratransgenesis.[21]
A number of potential vaccines are currently being tested. Vaccination with Trypanosoma rangeli has produced positive results in animal models.[22] More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas disease is being tested by several research groups.[23]
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 donations 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.[24][25] In Spain, donors are evaluated with a questionnaire to identify individuals at risk of Chagas exposure for screening tests.[25] The US FDA has approved two Chagas tests including one recently approved in April of 2010, and has published guidelines that recommend testing of all donated blood and tissue products.[25][26] While these tests are not required in U.S., it is estimated that 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.[26][27] 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.[28]