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Chagas Disease

(American Trypanosomiasis)

by Richard D. Pearson, MD

Chagas disease is infection with Trypanosoma cruzi, transmitted by Triatominae bug bites. Symptoms 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. 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.

Pathophysiology

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.

Infection can also be transmitted by blood transfusion, organ transplantation, or ingestion of uncooked food or drink (eg, drinks made from sugar cane juice) contaminated by infected reduviid bugs or their feces. Transplacental transmission is also possible.

Etiology

Infected Triatominae bugs are present in North, Central, and South America. Between 8 and 11 million people in the Americas are infected with T. cruzi; > 300,000 infected immigrants are estimated to be living in the US. Worldwide prevalence has been decreasing because of control measures. Nonhuman reservoirs include dogs, cats, opossums, rats, and many other animals.

Vector-borne disease is rare in the US, but infected Latin American immigrants are potential sources of infection transmitted transplacentally or via donated blood or organs.

Symptoms and Signs

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

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.

Indeterminate

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

Chronic disease develops in 20 to 40% after a latent phase that may last years or decades. The main effects are

  • Cardiac

  • GI

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.

GI disease causes 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.

Diagnosis

  • Light microscopy of blood smears (thin or thick) or another fluid sample

The number of trypanosomes in peripheral blood is large during the acute phase and readily detected by examining thin or thick smears. In contrast, few parasites are present in blood during latent infection or chronic disease. Definitive diagnosis may be made by examining aspirates from organs such as lymph nodes.

Serologic tests including indirect fluorescent antibody (IFA) and enzyme immunoassays (EIA) are sensitive but may yield false-positive results in patients with leishmaniasis or other diseases. The diagnosis is typically confirmed by RIPA for T. cruzi. Other diagnostic approaches include xenodiagnosis (examination of the intestinal contents of laboratory-raised bugs after they take a blood meal from a patient suspected of having Chagas disease) and detection of PCR-amplified parasite DNA in blood or tissue fluids using investigational assays.

Testing for chronic Chagas disease

Asymptomatic patients with documented T. cruzi infection should have a screening ECG and rhythm strip and a chest x-ray. Patients who have potential cardiac abnormalities on a screening test or symptoms should have echocardiography. Those with dysphagia or other GI symptoms or findings should have GI contrast studies and/or endoscopy.

Treatment

  • Nifurtimox or benznidazole

  • Supportive care

Treatment in the acute stage rapidly reduces parasitemia, shortens the clinical illness, reduces risk of mortality, and decreases the likelihood of chronic disease.

For indeterminate infections, treatment of children and adults up to age 50 yr has been recommended. For patients > 50 yr, treatment is controversial and individualized based on potential risks and benefits.

Once the signs of chronic Chagas disease appear, antiparasitic drugs are not 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

  • 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

  • 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

Both drugs have substantial toxicity. The long treatment courses are often associated with GI adverse effects, peripheral neuropathy, poor tolerance, and low compliance.

Prevention

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.

Key Points

  • Chagas disease is caused by Trypanosoma cruzi, which is transmitted by Triatominae (reduviid, kissing, or assassin) bugs.

  • Infection is endemic in Central and South America, where 8 to 11 million are infected; an estimated 300,000 immigrants to the US 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 occasionally by light microscopy of blood smears or a tissue sample.

  • To detect chronic Chagas disease, do echocardiography if patients have symptoms suggesting cardiac 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 nifurtimox or benznidazole.

  • Antiparasitic drugs are not effective in the chronic stage, 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.

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