Chagas disease is infection with Trypanosoma cruzi, transmitted by Triatominae bug bites or, less commonly, via ingestion of sugar cane juice or foods contaminated with infected Triatominae bugs or their feces, transplacentally from an infected mother to her fetus, or via blood transfusion or an organ transplant from an infected donor. 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 patients develop chronic cardiomyopathy, megaesophagus, or megacolon. Many who are infected never develop disease. In patients with AIDS, 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.
T. cruzi is transmitted by Triatominae (reduviid, kissing, or assassin) bugs in South and Central America, Mexico, and very rarely in the US. Nonhuman reservoirs include domestic dogs, opossums, armadillos, rats, raccoons, and many other animals. Less commonly, T. cruzi is transmitted via ingestion of sugar cane juice or food contaminated with infected Triatominae bugs or their feces, transplacentally from an infected mother to her fetus, or via blood transfusion or an organ transplant from an infected donor.
Worldwide, an estimated 8 million people are chronically infected with T. cruzi. Most reside in Latin America, but about 300,000 of those infected in Latin America now live in the US; others live in Europe or elsewhere. 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.
Chagas disease is spread when a kissing bug bites an infected person or animal, 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. 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.
Chagas disease can occur in 3 stages:
Acute infection is followed by a latent (indeterminate) period, which may remain asymptomatic or progress to chronic disease. Immunosuppression may reactivate latent infection, with high parasitemia and a 2nd acute stage, skin lesions, or brain abscesses.
About 1 to 5% of infected pregnant women transmit the infection transplacentally, resulting in abortion, stillbirth, or chronic neonatal disease with high mortality.
Acute infection in endemic areas usually occurs in childhood and can be asymptomatic. When present, symptoms start 1 to 2 wk 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.
Acute Chagas disease is fatal in a small percentage of patients; death results from acute myocarditis with heart failure or meningoencephalitis. In the remainder, symptoms subside without treatment.
Primary acute Chagas disease in immunocompromised patients, such as those with AIDS, may be severe and atypical, with skin lesions and, rarely, brain abscesses.
Patients with indeterminate infection have parasitologic and/or serologic evidence of T. cruzi infection but have neither symptoms, abnormal physical findings, nor evidence of cardiac or GI involvement as assessed by ECG and rhythm strip, cardiac ultrasonography, chest x-ray, or other studies.
Many infected patients are identified by screening enzyme-linked immunosorbent blood assay (ELISA) and confirmatory radioimmunoprecipitation assay (RIPA) when they donate blood.
Chronic disease develops in 20 to 40% after a latent phase that may last years or decades. The main effects are
Chronic cardiomyopathy leads to flaccid enlargement of all chambers, apical aneurysms, and localized degenerative 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.
The number of trypanosomes in peripheral blood is large during the acute phase of Chagas disease and can be readily detected by examining thin or thick smears. In contrast, few parasites are present in blood during latent infection or chronic disease. Definitive diagnosis of acute-stage Chagas disease may also be made by examining tissue from lymph nodes or heart.
In immunocompetent patients with chronic Chagas disease, serologic tests, such as indirect fluorescent antibody (IFA), enzyme immunoassays (EIA), or enzyme-linked immunosorbent assay (ELISA), are often done to detect antibodies to T. cruzi. Serologic tests are sensitive but may yield false-positive results in patients with leishmaniasis or other diseases. Thus, an initial positive test is followed by one or more different tests (typically, radioimmunoprecipitation assay [RIPA] in the US) or sometimes light microscopy of blood smears or a tissue sample to confirm the diagnosis. Serologic tests are also used to screen blood donors for T. cruzi in endemic areas and the US.
PCR-based tests are used when the level of parasitemia is likely to be high, as occurs in acute Chagas disease, in transplacentally transmitted (congenital) Chagas disease, or after transmission via blood transfusion, transplantation, or laboratory exposure. In endemic areas, xenodiagnosis has been used; it involves examining the intestinal contents of Triatominae bugs raised in a laboratory after they took a blood meal from a person thought to have Chagas disease.
After Chagas disease is diagnosed, the following tests should be done, depending on findings:
Treatment of acute-stage Chagas disease with antiparasitic drugs does the following:
Treatment is indicated for all cases of acute, congenital, or reactivated Chagas disease and for indeterminate infection in children up to age 18 yr. The younger the patient and the earlier treatment is started, the more likely that treatment will result in parasitologic cure.
For indeterminate infections, treatment of adults up to age 50 yr has been recommended. For patients > 50 yr, treatment is individualized based on potential risks and benefits.
Once signs of cardiac or GI manifestations of chronic Chagas disease appear, antiparasitic drugs are not thought to be helpful.
Supportive measures include treatment for heart failure, pacemakers for heart block, antiarrhythmic drugs, cardiac transplantation, esophageal dilation, botulinum toxin injection into the lower esophageal sphincter, and GI tract surgery for megacolon.
The only effective drugs are
Benznidazole: For adults and children > 12 yr, 2.5 to 3.5 mg/kg po bid for 60 days
For children ≤ 12 yr, 2.5 to 3.75 mg/kg bid for 60 days
Nifurtimox: For patients ≥ 17 yr, 2 to 2.5 mg/kg po qid for 90 days
For children aged 11 to 16 yr, 3 to 3.75 mg/kg qid for 90 days
For children aged 1 to 10 yr, 4 to 5 mg/kg qid for 90 days
Both drugs are available through the CDC. They have substantial toxicity, which increases with age. Contraindications for treatment include severe liver or kidney disease.
Common adverse effects of benznidazole include allergic dermatitis, peripheral neuropathy, anorexia, weight loss, and insomnia.
Common adverse effects of nifurtimox are anorexia, weight loss, polyneuropathy, nausea, vomiting, headache, dizziness, vertigo.
It is recommended that these drugs not be used in pregnant women or in breastfeeding mothers.
Plastering walls and replacing thatched roofs or repeated spraying of houses with residual insecticides (those that have prolonged duration of action) can control Triatominae bugs. Infection in travelers is rare and can be avoided by not sleeping in adobe dwellings or by using bed nets if sleeping in such dwellings is unavoidable.
Blood and organ donors are screened in many endemic areas and, since 2006, in the US to prevent transfusion- and organ transplant–related Chagas disease.
Chagas disease is caused by Trypanosoma cruzi, which is transmitted by Triatominae (reduviid, kissing, or assassin) bugs.
Infection is endemic in South and Central America and Mexico; an estimated 8 million people worldwide, including an estimated 300,000 people in the US (primarily immigrants), are infected.
Acute infection is followed by a latent (indeterminate) period, which may remain asymptomatic, but in 20 to 40%, it progresses to chronic disease, which particularly affects the heart and GI tract.
Diagnose acute Chagas using light microscopy of blood smears (thin or thick) or a tissue sample.
Diagnose chronic T. cruzi infection by screening enzyme-linked immunosorbent blood assay (ELISA) with confirmatory radioimmunoprecipitation assay (RIPA) or other assay for antibodies.
Use PCR-based tests to evaluate cases potentially transmitted transplacentally or via transfusion, transplantation, or laboratory exposure.
To detect chronic Chagas disease, do echocardiography if patients have symptoms suggesting heart disease or potential cardiac abnormalities on a chest x-ray, ECG, or rhythm strip; do GI contrast studies or endoscopy if they have dysphagia or other GI symptoms.
Treat patients in the acute stage and many in the indeterminate stage with benznidazole or nifurtimox.
Antiparasitic drugs are not effective in chronic Chagas 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.