Close
Close

Chagas disease

American trypanosomiasis, South American trypanosomiasis, New world trypanosomiasis

Overview

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi. It is spread mostly by insects known as Triatominae or kissing bugs. The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild, and may include fever, swollen lymph nodes, headaches, or local swelling at the site of the bite. After 8–12 weeks, individuals enter the chronic phase of disease and in 60–70% it never produces further symptoms. The other 30 to 40% of people develop further symptoms 10 to 30 years after the initial infection, including enlargement of the ventricles of the heart in 20 to 30%, leading to heart failure. An enlarged esophagus or an enlarged colon may also occur in 10% of people.

T. cruzi is commonly spread to humans and other mammals by the blood-sucking "kissing bugs" of the subfamily Triatominae. These insects are known by a number of local names, including: vinchuca in Argentina, Bolivia, Chile and Paraguay, barbeiro (the barber) in Brazil, pito in Colombia, chinche in Central America, and chipo in Venezuela. The disease may also be spread through blood transfusion, organ transplantation, eating food contaminated with the parasites, and by vertical transmission (from a mother to her fetus). Diagnosis of early disease is by finding the parasite in the blood using a microscope. Chronic disease is diagnosed by finding antibodies for T. cruzi in the blood.

Prevention mostly involves eliminating kissing bugs and avoiding their bites. Other preventative efforts include screening blood used for transfusions. A vaccine has not been developed as of 2013. Early infections are treatable with the medication benznidazole or nifurtimox. Medication nearly always results in a cure if given early, but becomes less effective the longer a person has had Chagas disease. When used in chronic disease, medication may delay or prevent the development of end–stage symptoms. Benznidazole and nifurtimox cause temporary side effects in up to 40% of people including skin disorders, brain toxicity, and digestive system irritation.

It is estimated that 7 to 8 million people, mostly in Mexico, Central America and South America, have Chagas disease as of 2013. In 2006, Chagas was estimated to result in 12,500 deaths per year. Most people with the disease are poor, and most people with the disease do not realize they are infected. Large-scale population movements have increased the areas where Chagas disease is found and these include many European countries and the United States. These areas have also seen an increase in the years up to 2014. The disease was first described in 1909 by Carlos Chagas after whom it is named. It affects more than 150 other animals.

Symptoms - Chagas disease

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, muscle pain, headache, rash, loss of appetite, diarrhea, nausea, 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 sensory 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 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.

Causes - Chagas disease

The cause of Chagas disease is the parasite Trypanosoma cruzi, which is transmitted to humans from a bite from an insect known as the triatomine bug. These insects can become infected by T. cruzi when they ingest blood from an animal already infected with the parasite.

Triatomine bugs live primarily in mud, thatch or adobe huts in Mexico, South America and Central America. They hide in crevices in the walls or roof during the day, then come out at night — often feeding on sleeping humans.

Infected bugs defecate after feeding, leaving behind T. cruzi parasites on the skin. The parasites can then enter your body through your eyes, mouth, a cut or scratch, or the wound from the bug's bite.

Scratching or rubbing the bite site helps the parasites enter your body. Once in your body, the parasites multiply and spread.

You may also become infected by:

  • Eating uncooked food contaminated with feces from T. cruzi-infected bugs
  • Being born to a woman infected with T. cruzi
  • Having a blood transfusion containing infected blood
  • Getting an organ transplant containing viable T. cruzi
  • Working in a laboratory where there's an accidental exposure to the parasite
  • Spending time in a forest that contains infected wild animals, such as raccoons and opossums
  • Being around an infected pet

Prevention - Chagas disease

There is currently no vaccine against Chagas disease. Prevention is generally focused on decreasing the numbers of the insect that spreads it (Triatoma) and decreasing their contact with humans. This is done by using sprays and paints containing insecticides (synthetic pyrethroids), 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 measures 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 bassiana.
  • Targeting the symbionts of Triatominae through paratransgenesis can be done.

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 21st century. 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. 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 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 US, 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.

Diagnosis - Chagas disease

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 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).

Prognosis - Chagas disease

The 'prognosis' of Chagas disease usually refers to the likely outcome of Chagas disease. The prognosis of Chagas disease may include the duration of Chagas disease, chances of complications of Chagas disease, probable outcomes, prospects for recovery, recovery period for Chagas disease, survival rates, death rates, and other outcome possibilities in the overall prognosis of Chagas disease. Naturally, such forecast issues are by their nature unpredictable.

Treatment - Chagas disease

There are two approaches to treating Chagas disease: antiparasitic treatment, to kill the parasite; and symptomatic treatment, to manage the symptoms and signs of the infection. Management uniquely involves addressing selective incremental failure of the parasympathetic nervous system. Autonomic disease imparted by Chagas may eventually result in megaesophagus, megacolon and accelerated dilated cardiomyopathy. The mechanisms that explain why Chagas targets the parasympathetic autonomic nervous system and spares the sympathetic autonomic nervous system remain poorly understood.

Medication

The two drugs used to treat Chagas disease are nifurtimox and benznidazole. On August 30, 2017, the FDA approved benznidazole to treat Chagas disease in children between the ages of 2 to 12 years old. Nifurtimox may also used to treat Chagas disease. Although not FDA approved, nifurtimox can be obtained for the treatment of Chagas disease in the United States through special CDC studies. Similarly, benznidazole is also available through special CDC studies for those with Chagas disease whose treatment is deemed necessary by their doctor but whose age falls outside FDA approval.

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 azole or nitro derivatives, such as benznidazole or nifurtimox. Both agents are limited in their capacity to completely eliminate T. cruzi from the body (parasitologic cure), especially in chronically infected patients, and resistance to these drugs has been reported.

Studies suggest antiparasitic treatment leads to parasitological cure in more than 90% of infants but only about 60–85% of adults 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, pacemakers 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.

Resources - Chagas disease

  • NIH
Orphan Therapies
Videos
by Birgit Bramlage
1,463 views