Chagas disease is infection with protozoa of the species Trypanosoma cruzi, which is most commonly transmitted by Triatominae (kissing bug) bites or, less commonly, via ingestion of sugar cane juice or foods contaminated with infected Triatominae or their feces, via blood transfusion or an organ transplant from an infected donor, or via maternal-fetal transmission. Symptoms after a Triatominae bite typically begin with a skin lesion or unilateral periorbital edema then progress to fever, malaise, generalized lymphadenopathy, and hepatosplenomegaly; years later, some infected patients develop arrhythmias, chronic cardiomyopathy, or, less commonly, megaesophagus or megacolon. In patients with advanced HIV infection, the skin or brain may be affected. Diagnosis is by detecting trypanosomes in peripheral blood or aspirates from infected organs. Antibody tests are sensitive and can be helpful. Treatment is with nifurtimox or benznidazole; however, antiparasitic drugs do not reverse the course of cardiac or intestinal disease that has developed., which is most commonly transmitted by Triatominae (kissing bug) bites or, less commonly, via ingestion of sugar cane juice or foods contaminated with infected Triatominae or their feces, via blood transfusion or an organ transplant from an infected donor, or via maternal-fetal transmission. Symptoms after a Triatominae bite typically begin with a skin lesion or unilateral periorbital edema then progress to fever, malaise, generalized lymphadenopathy, and hepatosplenomegaly; years later, some infected patients develop arrhythmias, chronic cardiomyopathy, or, less commonly, megaesophagus or megacolon. In patients with advanced HIV infection, the skin or brain may be affected. Diagnosis is by detecting trypanosomes in peripheral blood or aspirates from infected organs. Antibody tests are sensitive and can be helpful. Treatment is with nifurtimox or benznidazole; however, antiparasitic drugs do not reverse the course of cardiac or intestinal disease that has developed.
Chagas disease is caused by Trypanosoma cruzi. Infection is mainly transmitted to humans when bitten by Triatominae (also called reduviids, kissing bugs, or assassin bugs).
Less commonly, T. cruzi is transmitted via ingestion of sugar cane juice or food contaminated with infected Triatominae or their feces, transplacentally from infected mother to fetus, or via blood transfusion or an organ transplant from an infected donor.
Nonhuman reservoirs include domestic dogs, opossums, armadillos, rats, raccoons, and many other animals. (See also Trypanosomiasis in Animals.)
Triatominae are found throughout North America, Central America, and South America.
Worldwide, an estimated 6 to 8 million people are chronically infected with T. cruzi. The majority of infections are in people in continental Latin America where T. cruzi remains endemic in 21 countries (1). However, the incidence of T. cruzi infection has been decreasing in Latin America because of improved housing, screening of blood and organ donors, and other control measures.
In 2010, an estimated 1.13 million women of childbearing age in Latin America were infected with T. cruzi. It is estimated that 1 to 5% of their children were born with congenital infection. At least 15,000 cases of congenital infection occur annually in Latin America (1).
Approximately 288,000 people in the United States were infected with T. cruzi between 2014 and 2018 (1). Most infections were acquired by people who have lived endemic regions. Although rare, local vector-borne transmission has been increasingly recognized in the United States, and autochthonous (ie, indigenous) cases have been documented in Arizona, Arkansas, California, Louisiana, Mississippi, Missouri, Tennessee, and Texas (2). Approximately 40,000 women of childbearing age in the United States have Chagas disease (3). (See also Centers for Disease Control and Prevention: Trypanosomiasis, American/Chagas Disease.)
General references
1. Cucunubá ZM, Gutiérrez-Romero SA, Ramírez JD, et al. The epidemiology of Chagas disease in the Americas. Lancet Reg Health Am. 2024;37:100881. Published 2024 Sep 13. doi:10.1016/j.lana.2024.100881
2. Beatty NL, Klotz SA. Autochthonous Chagas Disease in the United States: How Are People Getting Infected?. Am J Trop Med Hyg. 2020;103(3):967-969. doi:10.4269/ajtmh.19-0733
3. Centers for Disease Control and Prevention (CDC): Clinical Considerations for Congenital Chagas Disease. Accessed March 21, 2025.
Pathophysiology of Chagas Disease
Chagas disease is most commonly spread when a Triatominae or kissing bug bites an infected person or animal and then bites another person. While biting, infected bugs deposit feces containing metacyclic trypomastigotes on the skin. These infective forms enter through the bite wound or penetrate the conjunctivae or mucous membranes.
In addition to humans, a number of other mammals serve as reservoir hosts for T. cruzi (eg, armadillos, opossums, raccoons, woodrats, some other rodents, domestic dogs). Common Triatominae vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus.
CDC/DPDx
The parasites invade macrophages at the site of entry and transform into amastigotes that multiply by binary fission; the amastigotes develop into trypomastigotes, enter the bloodstream and tissue spaces, and infect other cells. Cells of the reticuloendothelial system, myocardium, muscles, and nervous system are most commonly involved in infection.
Image from the Centers for Disease Control and Prevention, Global Health, Division of Parasitic Diseases and Malaria.
Symptoms and Signs of Chagas Disease
T. cruzi infection has 3 stages:
Acute
Chronic indeterminate
Chronic
Acute infection is followed by a chronic indeterminate (latent) period, in which people may remain asymptomatic or progress to chronic disease. Immunosuppression may reactivate infection, causing high parasitemia and, in some people, skin or brain lesions.
Acute stage
Acute T. cruzi infection in endemic areas usually occurs in childhood and can be asymptomatic.
When present, symptoms start 1 to 2 weeks after exposure. An indurated, erythematous skin lesion (a chagoma) appears at the site of parasite entry. When the inoculation site is the conjunctiva, unilateral periocular and palpebral edema with conjunctivitis and preauricular lymphadenopathy are collectively called the Romaña sign.
CDC image courtesy of the WHO/TDR Image Library.
Acute Chagas disease is fatal in a small percentage of patients; T. cruzi is cardiotropic, and death results from acute myocarditis with heart failure or sometimes from meningoencephalitis. In the remainder, symptoms subside without treatment.
Primary acute Chagas disease in immunocompromised patients, such as those with advanced HIV infection, may be severe and manifest atypically, with skin lesions and, rarely, ring-enhancing brain lesions.
Congenital infections are mostly asymptomatic, but in 10 to 30% of neonates, nonspecific manifestations can occur, including prematurity, low birth weight, fever, hepatosplenomegaly, anemia, and thrombocytopenia (1). Rarely, death can result from fulminant disease. Signs of acute infection resolve even without therapy in the majority of congenital infections.
Chronic indeterminate stage
Patients with chronic indeterminate infection have parasitologic and/or serologic evidence of T. cruzi infection but do not have symptoms, abnormal physical findings, or evidence of cardiac or gastrointestinal involvement as assessed by ECG and rhythm strip, echocardiogram, chest radiograph, or other studies.
Many infected patients are identified by screening enzyme-linked immunosorbent assay (ELISA) and confirmatory radioimmunoprecipitation assay (RIPA) when they donate blood. Most patients remain in this asymptomatic stage for the rest of their life.
Chronic stage with cardiac or gastrointestinal involvement
Chronic Chagas disease develops in 20 to 30% of patients after the chronic indeterminate stage, which may last years or decades (2). The parasites are probably present in chronic disease; an autoimmune reaction also may contribute to organ damage. The main effects are:
Cardiac
Gastrointestinal
Cardiac disease usually manifests with conduction abnormalities including right bundle branch block or left anterior fascicular block. Chronic cardiomyopathy often follows with flaccid enlargement of all chambers, apical aneurysms, and progression of lesions in the conduction system. Patients may present with heart failure, syncope, sudden death due to heart block or ventricular arrhythmia, or thromboembolism. ECG may show right bundle branch or complete heart block.
Gastrointestinal disease manifests with symptoms resembling achalasia or Hirschsprung disease. Chagas megaesophagus manifests as dysphagia and may lead to pulmonary infections caused by aspiration or to severe undernutrition. Megacolon may result in long periods of obstipation and intestinal volvulus.
Symptoms and signs references
1. Matthews S, Tannis A, Puchner KP, et al. Estimation of the morbidity and mortality of congenital Chagas disease: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2022;16(11):e0010376. Published 2022 Nov 7. doi:10.1371/journal.pntd.0010376
2. CDC: Clinical Care of Chagas Disease. Accessed March 21, 2025.
Diagnosis of Chagas Disease
Light microscopy of blood smears (thin or thick) or tissue (acute Chagas disease)
Screening serologic test confirmed by a second test (chronic Chagas disease)
Polymerase chain reaction (PCR)–based tests (acute, chronic with cardiac or gastrointestinal involvement, and congenital Chagas diseases)
In endemic areas, xenodiagnosis (microbiologic examination of intestinal contents of Triatominae bugs)
The number of trypanosomes in peripheral blood is large during the acute stage of Chagas disease and can be readily detected by examining thin or thick smears. In contrast, few parasites are present in blood during the chronic indeterminate or chronic stage. Definitive diagnosis of acute-stage Chagas disease may also be made by examining tissue from lymph nodes or the heart.
PCR tests are used when the level of parasitemia is likely to be high, as occurs in acute Chagas disease, in congenital Chagas disease, or after transmission via blood transfusion, transplantation, or laboratory exposure (1).
In endemic areas, xenodiagnosis has been used; it involves examining the intestinal contents of laboratory raised–Triatominae after they have ingested a blood meal from a person thought to have Chagas disease.
CDC/DPDx
In immunocompetent patients with chronic Chagas disease, serologic tests, such as indirect fluorescent antibody (IFA) and enzyme immunoassays/enzyme-linked immunosorbent assays (EIA/ELISA), are often performed to detect antibodies to T. cruzi. Positive results from at least 2 different serologic tests, ideally using different test methodologies, should be performed to confirm the diagnosis (2). Serologic tests are sensitive but may yield false-positive results in patients with leishmaniasis or other diseases. Thus, an initial positive serologic test is followed by one or more different tests eg, in the United States, an immunoblot to detect trypomastigote excreted-secreted antigens [TESA]), or sometimes light microscopy of blood smears or a tissue sample can be used to confirm the diagnosis. If initial results are discordant, testing should be repeated using a second specimen. Serologic tests are also used to screen blood donors for T. cruzi in endemic areas.
Ancillary testing in patients with chronic Chagas disease
After Chagas disease is diagnosed, the following tests should be performed, depending on findings:
No symptoms but documented T. cruzi infection: A screening ECG and rhythm strip and a chest radiograph
Potential cardiac abnormalities on a screening test or symptoms suggesting heart disease: Echocardiogram
Dysphagia or other gastrointestinal (GI) symptoms or findings: GI contrast studies and/or endoscopy
Diagnosis references
1. Centers for Disease Control and Prevention (CDC): Trypanosomiasis, American/Chagas Disease. CDC Yellow Book 2024.
2. Miller JM, Binnicker MJ, Campbell S, et al. Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Clin Infect Dis. Published online March 5, 2024. doi:10.1093/cid/ciae104
Treatment of Chagas Disease
Benznidazole or nifurtimoxBenznidazole or nifurtimox
Supportive care
Treatment of acute-stage Chagas disease with antiparasitic drugs does the following:
Rapidly reduces parasitemia
Shortens the clinical illness
Reduces risk of mortality
Decreases the likelihood of chronic disease
Antiparasitic treatment is indicated for all cases of acute, congenital, or reactivated Chagas disease and for chronic indeterminate infection in children up to age 18 years. The younger the patient and the earlier treatment is started, the more likely that treatment will result in parasitologic cure.
The efficacy of treatment decreases as the duration of infection lengthens, and adverse effects are more likely in adults. Treatment is also recommended for adults 18 to 50 years old unless they have evidence of advanced cardiac or gastrointestinal (GI) disease. For patients > 50 years old, treatment is individualized based on potential risks and benefits.
Once signs of advanced cardiac or GI disease appear, antiparasitic drugs are not recommended.
Supportive measures include treatment for heart failure, pacemakers for heart block, antiarrhythmic medications, cardiac transplantation, esophageal dilation, botulinum toxin injection into the lower esophageal sphincter, and GI tract surgery for megacolon.
The only effective antiparasitic drugs are benznidazole and nifurtimox (The only effective antiparasitic drugs are benznidazole and nifurtimox (1).
Benznidazole is generally better tolerated, and the duration of treatment is shorter. Both Benznidazole is generally better tolerated, and the duration of treatment is shorter. Bothbenznidazole and nifurtimox have substantial toxicity, which increases with age. Contraindications for treatment include severe liver or kidney disease. Young children usually tolerate treatment better than adults. and nifurtimox have substantial toxicity, which increases with age. Contraindications for treatment include severe liver or kidney disease. Young children usually tolerate treatment better than adults.
When pregnant patients are diagnosed with Chagas, treatment is typically delayed until after delivery, and the infant is then treated if infected. These medications are not recommended for use in patients who are pregnant or breastfeeding.
Common adverse effects of benznidazole include allergic dermatitis, anorexia, weight loss, peripheral neuropathy, and insomnia.
Common adverse effects of nifurtimox are anorexia, nausea, vomiting, weight loss, polyneuropathy, headache, dizziness, and vertigo.
Treatment reference
1. Bern C, Montgomery SP, Herwaldt BL, et al. Evaluation and treatment of Chagas disease in the United States: a systematic review. JAMA. 2007;298(18):2171-2181. doi:10.1001/jama.298.18.2171
Prevention of Chagas Disease
Plastering walls and replacing thatched roofs or repeatedly spraying houses with residual insecticides (those that have prolonged duration of action) can control Triatominae.
Infection in travelers is rare and can be avoided by not sleeping in adobe dwellings or, if sleeping in such dwellings is unavoidable, by using bed nets.
Another preventive measure is avoiding fresh sugar cane juice or other foods that might be contaminated.
Screening at-risk patients of childbearing age and treating before pregnancy decrease the likelihood of congenital infection.
Blood and organ donors are screened in many endemic areas. Since 2006 in the United States, blood and organ donors are also screened to prevent transfusion- and organ transplant–related Chagas disease.
Key Points
Chagas disease is caused by Trypanosoma cruzi, which is transmitted by Triatominae (reduviids, kissing bugs, or assassin bugs).
Infection is endemic in Latin America; an estimated 6 to 8 million people worldwide, including an estimated 288,000 people in the United States (primarily people who have lived in endemic areas), are infected.
The acute stage is followed by the chronic indeterminate stage, in which patients may remain asymptomatic, but in 20 to 30% of patients, the chronic indeterminate stage progresses to the chronic stage, which particularly affects the heart and/or gastrointestinal tract.
Diagnose acute Chagas using light microscopy of blood smears (thin or thick) or a tissue sample, or polymerase chain reaction (PCR)–based assays.
Diagnose chronic T. cruzi infection by serologic tests with confirmatory trypomastigote excreted-secreted antigens (TESA) immunoblot or other assay for antibodies.
Use PCR-based tests to evaluate cases potentially transmitted transplacentally or via transfusion, transplantation, or laboratory exposure.
After Chagas disease is diagnosed, perform echocardiography if patients have potential cardiac abnormalities on a screening test or symptoms suggesting heart disease; perform a chest radiograph, screening ECG, and rhythm strip if patients have no symptoms but confirmed T. cruzi infection; and perform GI contrast studies or endoscopy if patients have dysphagia or other GI symptoms.
Give benznidazole or nifurtimox to patients with acute, congenital, or reactivated Chagas disease, to children up to age 18 years with chronic infection, and to adults 18 to 50 who do not have advanced cardiac or GI disease; these medications should not be given to pregnant or breastfeeding patients. Give benznidazole or nifurtimox to patients with acute, congenital, or reactivated Chagas disease, to children up to age 18 years with chronic infection, and to adults 18 to 50 who do not have advanced cardiac or GI disease; these medications should not be given to pregnant or breastfeeding patients.
For patients > 50 years with chronic infection, treatment is individualized based on balance of risks and benefits.
Antiparasitic drugs are not effective in patients with advanced Chagas with cardiac or gastrointestinal disease, but supportive measures (eg, treatment of heart failure, pacemakers for heart block, antiarrhythmic drugs, cardiac transplantation, esophageal dilation, botulinum toxin injection into the lower esophageal sphincter, GI tract surgery) are often helpful.
More Information
The following English-language resources may be useful. Please note that The Manual is not responsible for the content of these resources.
Centers for Disease Control and Prevention (CDC): Clinical Care of Chagas Disease
MSD Veterinary Manual: Trypanosomiasis in Animals
Drugs Mentioned In This Article
