What is Chagas disease?

Chagas disease (also termed American trypanosomiasis) is an infection caused by a protozoan parasite (Trypanosoma cruzi) that can result in acute inflammatory skin changes (chagomas) and eventually may cause infection and inflammation of many other body tissues, especially those of the heart and intestinal tract. The disease may have three phases in an individual: acute, with mild or no symptoms that may last weeks to about two months; intermediate or indeterminate phase that has few if any symptoms and may last 10-20 years or longer; and chronic, with the more severe symptoms appearing from gradual chronic organ damage (especially heart and intestinal although other organs may be affected) with symptoms that usually remain for life. People with Chagas disease seen in the U.S. usually have acquired it while living in a country where the disease is endemic (Mexico, Central and South America). The CDC estimates about 8-11 million people are infected in countries where the disease is endemic.

American trypanosomiasis (Chagas disease) is distinguished from African trypanosomiasis (sleeping sickness) by the part of the world where they occur, their vectors, their different symptoms and different treatments (see Table 1).

Table 1

Comparison of American (Chagas disease) and African trypanosomiasis (sleeping sickness)

	American trypanosomiasis	African trypanosomiasis
Cause	T. cruzi	T. brucei (subspecies)
Main vector	Triatominae bugs (kissing bugs)	Tsetse fly
Main symptoms	Chagomas, heart, gastrointestinal	Chancres, nighttime insomnia, seizures
Treatment	Benznidazole, nifurtimox; symptomatic treatments in chronic phase	Suramin, melarsoprol, pentamidine, eflornithine

What is the history of Chagas disease?

Chagas disease was named after Carlos Chagas, who first described Trypanosoma cruzi in infected humans in 1909 while working for the Oswaldo Cruz Institute in Brazil. Chagas discovered that the parasites are transmitted to humans by entering breaks in the skin after they are deposited on the skin in insect feces. Chagas was the first scientist to discover all aspects of a new infectious disease; its pathogen (T. cruzi), main insect vector (Triatominae or kissing bugs), hosts (humans, mammals), clinical manifestations, and epidemiology. The parasite species was named cruzi to honor his employer and scientific mentor, Oswaldo Cruz. Chagas disease is also known as American trypanosomiasis because it mainly occurs in the Americas where the triatomine insects (kissing bugs) usually are found. These bugs and the mammals they infect range from states along the U.S. border with Mexico through Central America to the South American countries (for example, Argentina, Bolivia), where the disease is endemic. Almost all cases diagnosed in the U.S. are in immigrants from other countries in the Americas.

What causes Chagas disease?

Chagas disease is caused by a protozoan parasite named Trypanosoma cruzi. Infection of humans occurs when an insect vector (mainly Triatominae or kissing bugs, a member of the family Reduviidae and sometimes referred to as reduviid bugs) deposits feces that contains the parasites on human skin. The parasites then enter the mammalian (human) host through the bug bite, or breaks in the skin or conjunctiva. Occasionally, the parasites enter through mucosal cells when ingested or inhaled. The bugs often deposit feces near the eyes and lips; when the parasites enter the skin, swelling and redness (a chagoma) often develop. The term "kissing bugs" comes from the appearance of these symptoms that resemble skin changes that occur with prolonged kissing. In some individuals, the parasites eventually go into the bloodstream and lodge in various organs, multiply, and eventually cause chronic symptoms such as cardiac arrhythmias, poor gastrointestinal motility, or death.

Humans who live in poor or primitive housing conditions that border or invade the habitats of Triatominae bugs cause a break in the normal life cycle of the insect vectors (bugs) and their usual hosts (over 100 types of animals), termed the sylvatic cycle. The bugs then enter the world of humans and their domesticated animals (cats, dogs) and transmit T. cruzi to them. When T. cruzi is transmitted from bugs to humans or human pets and back to the bugs, the life cycle is referred to as the domiciliary cycle. The life cycle of T. cruzi is complex; it has multiple developmental stages in both the insect vector (Triatominae bugs and also termed triatomine bugs) and mammalian (human and animal) hosts. The figure below from the CDC shows the developmental stages that occur in both the sylvatic and domiciliary cycles.

Life cycle of T. cruzi. Image courtesy of the CDC.

For humans, the disease process slowly advances when the amastigotes forms replicate in host cells and eventually transform into trypomastigotes that leave the cell and enter the bloodstream. These forms then can be transferred to a triatomine bug if it gets a blood meal from an infected human, thereby entering the cycle of development in the bugs. Unfortunately in some humans, many trypomastigotes can go on to reinfect other organs in the human, transform into amastigotes and repeat this cycle of infection so that T. cruzi forms continue to spread in the body.

In addition, T. cruzi has been reported to be transferred to humans from blood transfusions, organ transplantation, transplacental or congenital, by ingestion, inhalation, and by laboratory accidents. Fortunately, these forms of transmission occur very infrequently.

Pictures, photos, and diagrams related to Chagas disease and its parasites can be found in the first two references listed below, while the last three references provide maps of the disease in the Americas.

What are the symptoms and signs of Chagas disease?

The symptoms of Chagas disease can be quite variable and range from no symptoms to severe. The first symptoms, when present in the acute phase, may include some of the following:

• Swelling and/or redness at the skin infection site (termed chagoma)



• Rash



• Swollen lymph nodes



• Fever



• Head and body aches



• Fatigue



• Nausea, vomiting, and/or diarrhea



• Liver and/or spleen enlargement



• Romaña sign (unilateral painless edema of tissues around the eye)

Most individuals who get the above acute-phase symptoms have them resolve spontaneously in about three to eight weeks. Occasionally, acute infections show chronic symptoms (listed below) if the patient is severely immunocompromised..

Most investigators suggest that the intermediate or indeterminate phase has no symptoms. This stage may last throughout the person's life and the individuals may never know they have Chagas disease, especially if they had mild or no symptoms in the acute phase. However, this stage may only last about 10-20 years before the chronic symptoms develop in about 10%-30% of those infected.

Symptoms of chronic Chagas disease vary according to the organs most affected; in most cases, the heart or the gastrointestinal tract (or both) show the most serious symptoms. Chronic Chagas disease symptoms may include the following:

• Irregular heartbeats



• Palpitations



• Fainting (syncope)



• Cardiomyopathy



• Congestive heart failure



• Shortness of breath (dyspnea)



• Emphysema



• Stroke



• Sudden death



• Chronic abdominal pain



• Chronic constipation



• Dilated colon



• Difficulty swallowing

These symptoms are due to organ damage caused by the chronic presence of the parasites within the tissues of these organs. Chronic inflammation develops as the body reacts to the parasites; it affects the neurons in these tissues, causing electrical changes in the heart and poor muscle tone in the intestines.

How is Chagas disease diagnosed?

Unless the person lives in an area where the chagomas associated with Chagas disease are well recognized, the acute phase is not often diagnosed. The majority of acute-phase infections are not diagnosed because many people develop nonspecific symptoms and the people who get the infection usually are very poor, have primitive living conditions, and no access to medical care.

There are multiple types of blood tests available to test for Chagas disease. Most are based on the host (human) production of antibodies directed against the infecting parasites, although direct microscopic examination of blood smears may visualize the parasites. However, microscopic visualization of the parasites usually needs confirmation by immunological studies because visually, the parasites may be confused with those seen in people with malaria, leishmaniasis, or African sleeping sickness. Microscopic preparation and examination is recommended to be done by experienced lab technicians or experts in parasitology.

In the U.S., the FDA approved an ELISA test by Ortho-Clinical Diagnostics in 2006. It detects antibodies formed against T. cruzi with high sensitivity and specificity and currently is the only FDA-approved test. Since 2007, about 800 blood-donor samples have been detected as Chagas-positive across the U.S. (see map, reference five). Other tests used in other countries (indirect immunofluoresence, hemagglutination) are less sensitive and specific but are still used. A Chagas Radioimmune Precipitation assay (Chagas RIPA) is used in research and with FDA permission in some clinical testing but is not widely available.

Most cases of Chagas disease are diagnosed when individuals donate blood; most people are not aware they have been infected with T. cruzi. However, since blood and organ donation can pass the disease to other people, most labs now test donated blood and organs for Chagas disease with the approved ELISA assay. If the donors are positive, they are notified (diagnosed). The prevalence of Chagas-positive blood donors is estimated by various investigations to widely range between about one positive per 2,000- 29,000 donors.

Chronic-phase Chagas disease is diagnosed also with the above-mentioned blood tests, but these patients also often have physical findings that indicate the patient has chronic disease. Physical findings may include peripheral edema, ascites, pulmonary congestion, and arrhythmias in patients with heart involvement. Patients with mainly chronic gastrointestinal involvement may have weight loss, severe reflux, esophageal erosions, inability to swallow normally, or an enlarged colon (megacolon) with an enlarged abdomen. Many different diseases can cause these physical findings so it is important to know that the patient has a positive blood test for T. cruzi before concluding the person has Chagas disease. Conversely, if such physical findings and history of possible contact with Chagas vectors is present, then the blood tests could be done to either prove or rule out the diagnosis of Chagas disease in chronic phase.

Other tests such as electrocardiography and Holter or heart-event monitoring, endoscopy, esophageal manometry (pressure measurements), or motility studies are used to help determine the functionality of heart or gastrointestinal tissues in patients with chronic-phase Chagas disease.

What is the treatment for Chagas disease?

Treatment for Chagas disease often depends on the phase of the disease and the age of the patient. Acute-phase treatment centers on killing the T. cruzi parasites with antiparasitic drugs. The prescription medications benznidazole (Rochagan, Ragonil) and nifurtimox (Lampit) may eliminate or reduce the number of infecting parasites. Some investigators suggest that drug-resistant parasites occur and others suggest these drugs of choice never eliminate all of the parasites. However, the CDC recommends drug treatment for "all people diagnosed with an acute (Chagas) infection, congenital infection, and for those with suppressed immune systems, and for all children with chronic infection. Adults with chronic infection may also benefit from treatment." The CDC advises caution about treating adults over the 50 years of age and recommends that treatment for older adults be individualized. Both drugs are available in Central and South America. In the United States, however, the drugs can be obtained only through the CDC (Centers for Disease Control and Prevention).

During the intermediate or indeterminate phase, the vast majority of adult patients obtain no antiparasitic treatments; however, children in this stage of disease should continue drug therapy. The situation with adults may change as new investigations with antiparasitic drug treatments are being done in South America.

Antiparasitic drug therapy of the chronic phase in adults is controversial. As quoted above, the CDC says adults with chronic infection may benefit from drug treatment but most experts suggest there is no benefit to adults with chronic phase Chagas disease. However, treatment of the symptoms of chronic Chagas disease is often necessary and can be life-prolonging or life-saving. For example, pacemaker

placement or even cardiac transplantation can be life-saving to some patients who develop arrhythmias or cardiomyopathy. Surgical resection of the gastrointestinal tract may help alleviate some gastrointestinal problems. In addition, there are many medications available to treat specific arrhythmias and other bowel problems that may be seen in chronic Chagas disease; cardiac and gastrointestinal consultants often can help manage chronic-phase Chagas.

Can transmission of Chagas disease be prevented with a vaccine?

Currently, there is no vaccine available for humans to prevent Chagas disease. However, there are other ways available to humans to reduce or even prevent the disease. Most experts in Chagas disease agree that a majority of infections can be prevented by improving poor or primitive housing. Judicious use of insecticides and education of people about home cleanliness for populations at risk for Chagas disease can augment good-housing design. The principle goal is to prevent the vector (bugs) from establishing a domiciliary cycle in the home by making a home difficult for the bugs to invade or live in. For example, plaster-sealed walls in a home with a metal or shingle roof are far less likely to be populated by bug vectors than a mud-walled structure covered with a thatch roof and a well-cleaned home is far less likely to have areas for bugs to hide and replicate than an unclean home. Several studies suggest this is an effective way to prevent Chagas disease.

Since blood transfusions can account for a large number of person-to-person transfers of T. cruzi, many blood banks around the world are now testing donated blood for antibodies to the parasite. If a blood sample is positive, the blood is discarded and the donor usually is notified and requested to not donate blood in the future. Similar situations occur with organ donors. Such methods help prevent Chagas disease.

What research is being done for Chagas disease?

Research is progressing on Chagas disease. The BENEFIT study plans to determine if 60 days of treatment with an antiparasitic drug (benznidazole) could prevent the progression of cardiac disease in patients with chronic Chagas disease (18-75 years of age). Another study on benznidazole is in progress to determine how well it performs in children (2-12 years of age) in prevention of deaths and complications in young adults. Researchers continue to search for a vaccine against Chagas disease; one group reports success in protecting mice with inactivated mutant parasites while another group reports development of a vaccine made from parasite DNA. Aggressive research may provide ways to treat and prevent Chagas disease. However, a few researchers say all that is really necessary is to prevent primitive housing that leads to development of the domiciliary cycle.

Chagas Disease At A Glance

• Chagas disease is an infection caused by a protozoan parasite (Trypanosoma cruzi) that can result in acute inflammatory skin changes (chagomas) and may eventually cause infection and inflammation of many other body tissues, especially those of the heart and intestinal tract.
• Chagas disease was first described in 1909 in Brazil.
• Chagas disease is caused by a protozoan parasite named Trypanosoma cruzi that is transmitted to humans from the feces of triatomine bugs (kissing bugs).
• The parasites usually enter the mammalian (human) host through the bug bite, or breaks in the skin or conjunctiva, replicate in mammalian cells, and may eventually reach other organs through the blood.
• Chagas disease may proceed through three phases in an individual: acute, intermediate or indeterminate, and chronic.
• Chagas disease symptoms vary widely from no symptoms to severe in the chronic phase.
• Acute-phase symptoms of Chagas disease may be swelling and/or redness at the skin infection site (termed chagoma), rash, swollen lymph nodes, fever, head and body aches, fatigue, nausea, vomiting and/or diarrhea, liver and/or spleen enlargement, and the Romaña sign.
• Chronic-phase symptoms of Chagas disease may be irregular heartbeats, palpitations, fainting (syncope), cardiomyopathy, congestive heart failure, short of breath (dyspnea), emphysema, stroke, sudden death, chronic abdominal pain, chronic constipation, dilated colon, and difficulty swallowing.
• Patient history, physical exam, direct microscopic visualization of the parasites, and detection of antibodies against the parasites are methods used to diagnose Chagas disease.
• Treatment with antiparasitic drugs benznidazole (Rochagan, Ragonil) and nifurtimox (Lampit) kill or inhibit T. cruzi parasites and are usually in the acute phase of Chagas disease.
• Chronic-phase patients are usually treated symptomatically.
• There is no vaccine against Chagas disease parasites for humans, but many experts suggest that elimination of primitive housing and education may prevent most cases of Chagas disease.

REFERENCES:

Kirchhoff, Louis. "Chagas Disease." eMedicine.com. Dec. 17, 2009. .

United States. "Chagas Disease." Centers for Disease Control and Prevention. Oct. 2, 2009. .

United States. "Trypanosomiasis, American." Centers for Disease Control and Prevention. July 20, 2009. .

"Chagas Disease." MedlinePlus. Jan. 21, 2010. .

United States. "Migration and the Movement of Infectious Diseases: Chagas Disease." Centers for Disease Control and Prevention. June 16, 2009. .

Odero, Randy O., Kerry O. Cleveland, Kitonga P. Kiminyo, and Daniel R. Lucey. "African Trypanosomiasis (Sleeping Sickness): Treatment & Medication." eMedicine.com. Feb. 16, 2009. .

"South America Distribution Map for Chagas' Disease." Insects, Disease, and History. .

"Mexico Distribution Map for Chagas' Disease." Insects, Disease, and History. .

Related Posts Widget