Chagas Disease (American Trypanosomiasis) Treatment & Management

Updated: Sep 07, 2018
  • Author: Louis V Kirchhoff, MD, MPH; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Treatment

Medical Care

The goals of therapy in persons with T cruzi infection are to eliminate the parasites with specific drug treatment and to manage the signs and symptoms that result from the largely irreversible lesions associated with the disease. In 2017, benznidazole was approved by the FDA for the treatment of Chagas disease caused by T cruzi in children aged 2-12 years. Nifurtimox (see Medication), is available through the CDC Drug Service (phone number: 404‑639‑3670) for specific treatment of T cruzi infection. For the most part, both benznidazole and nifurtimox are limited in their capacity to effect parasitologic cure, especially in chronically infected patients. Moreover, it has not been established in properly structured trials that treatment of chronically infected persons with either benznidazole or nifurtimox improves outcomes. [140, 141, 142] Thus, the use of these drugs in such patients continues to be controversial.

The safety and efficacy of benznidazole were established in 2 placebo-controlled clinical trials in children aged 6-12 years. In the trials, antibody test results changed from positive to negative in approximately 55%-60% of children treated with benznidazole, compared with approximately 5%-14% who received placebo. An additional study of the safety and pharmacokinetics of benznidazole provided information for dosing recommendations in children as young as 2 years. [143]

The CDC recommends antiparasitic treatment for all cases of acute (ie, congenital) or reactivated Chagas disease and for chronic T cruzi in children up to age 18 years. The CDC also strongly recommends treatment for adults aged 50 years or younger with chronic infection who do not already have advanced Chagas cardiomyopathy. [144]

Acute Chagas disease

All patients with acute Chagas disease, including infants with congenital infection and persons with reactivation of chronic infections due to immunosuppression, should be treated with either benznidazole or nifurtimox.

In general, the younger the patient and the closer to acquisition of the infection, the higher the probability of parasitologic cure. Babies with congenital Chagas disease have the greatest chance for cure. Data from Argentina show that the cure rate exceeds 90% if treatment is given within the first year of life. [145] Some sources have stated that the overall parasitologic cure rate in persons with acute Chagas disease is 70%, although the author is unaware of specific data that support this estimate.

The usefulness of corticosteroids or interferon-γ in patients with acute Chagasic myocarditis or meningoencephalitis has not been established. 

Indeterminate-phase Chagas disease

The current evidence‑based consensus concerning treatment of chronic T cruzi infection is that chronically infected children and adolescents aged 18 years or younger should be treated with either benznidazole or nifurtimox. Convincing data from trials in Argentina and Brazil indicate that a major proportion of these patients will be cured parasitologically. [38, 140, 146]

In contrast, the probability of parasitologic cure with a full course of either drug in adults with long-standing T cruzi infection, including persons in the indeterminate phase, as well as those with manifest chagasic symptoms, most of whom presumably were infected while quite young, is less than 10%. [147, 148, 149, 150, 151, 152, 153] Moreover, determining which treated patients are cured is challenging, since treatment suppresses parasitemias, as reflected in reduced rates of positivity in posttreatment PCR assays, as well as in xenodiagnosis and hemoculture, and levels of anti–T cruzi antibodies can remain positive for years. [132, 154]

Until recently, data from properly structured randomized clinical trials (RCTs) that assess the effect of specific treatment outcomes in chronically infected adults have been lacking. A segment of this void was recently filled by the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. [141, 155] In this blinded, placebo‑controlled trial of benznidazole versus placebo performed in Brazil, Argentina, and Colombia, a total of 2,854 T cruzi–infected patients with mild cardiac disease were followed for a mean of 5.4 years. As expected, parasite detection as shown on PCR assay was suppressed; however, benznidazole did not significantly reduce cardiac clinical deterioration. In view of these results, specific treatment of adults with longstanding T cruzi infection and demonstrable cardiac disease cannot be recommended.

Importantly, no patients in the indeterminate phase of chronic T cruzi infection were included in the BENEFIT trial, so data from proper comparative trials that address the question of the usefulness of treating persons in this group are still lacking. [142] A detailed discussion of this issue took place in 2006 at a two-day meeting convened by the CDC of an expert panel from several endemic countries and the United States, in which the author of this article was a participant. In the publication that resulted from that meeting, [140] the panel recommended that treatment be offered to chronically infected adults (the BENEFIT data were not available then) and that, after discussion of the risks and possible benefits, treatment decisions be shared by patients and caregivers. This recommendation was driven by data from several nonrandomized controlled trials that had suggested that treatment of chronically infected persons might be useful and by the assumption that the suppression of parasitemias was a marker for better clinical outcomes. The BENEFIT results clearly indicate that the latter is not the case, since such suppression was clearly documented in the patients in the benznidazole arm but no clinical benefit was observed. Thus, the assumption regarding suppression of parasitemias can no longer be held out as a reason to treat chronically infected persons.

Current CDC guidance states that treatment is strongly recommended for adults aged 50 years or younger with chronic infection who do not already have advanced Chagas cardiomyopathy. [144] The current recommendations of the Ministries of Health in Brazil [156] and Argentina [157] are consistent with those from the 2006 CDC meeting as published. [140] However, since these recommendations are not evidence‑based, the results from the BENEFIT trial, and the appearance of bothersome side effects in a substantial proportion of treated patients, the author of this article does not support benznidazole or nifurtimox treatment in adults with chronic T cruzi infection, regardless of their clinical status. It merits mention that the CDC guidance and the recommendations of the Ministries of Health in Brazil and Argentina have not been updated since the results of the BENEFIT trial have been published.

Little information has been published that sheds light on the question of whether the rate of congenital transmission can be reduced by prophylactically treating women of child‑bearing age with either nifurtimox or benznidazole before they become pregnant. In the one investigation relevant to this question, [158] only a small number of women in the study group received treatment as adults. No data regarding the suppression of parasitemias or parasitological cure were included in the report. None of the infants born to the women in the study had congenital Chagas disease, suggesting that treatment of women with chronic T cruzi infection prior to pregnancy may be effective in reducing congenital transmission. This question needs to be addressed in a larger study.

No information is available on which to base guidance for prophylactic treatment of chronic infection in persons who will undergo immunosuppression (eg, pretransplant) or in persons who are already immunosuppressed (eg, those with HIV infection). 

Chronic symptomatic Chagas disease

Persons who have already developed cardiac or gastrointestinal symptoms should not be given antiparasitic treatment. 

General medical treatment

As with diagnostic procedures, the medical treatment of cardiac and gastrointestinal signs and symptoms attributable to Chagas disease is similar to that instituted for similar problems caused by other etiologies. Such patients should be referred to appropriate subspecialists for evaluation and management. 

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Surgical Care

Cardiopathy

Atrial and ventricular rhythm disturbances may require pacemaker placement. Ablation procedures for tachyarrhythmias, as well as implanted defibrillators, have been used in some patients with Chagas disease.

The usefulness of implantable cardioverter devices in patients with advanced Chagas heart disease is controversial. [106, 159, 160, 161, 162]

The usefulness of resection of the left ventricular apical aneurysms that develop in some patients with Chagas cardiomyopathy has not been established.

Cardiac transplantation is an option for some patients with end-stage Chagas heart disease, and hundreds of patients have undergone this procedure in Argentina, Brazil, and the United States. [163, 164, 165] Interestingly, the survival rate among patients with Chagas disease who have undergone cardiac transplantation is better than that in the general group of patients who have undergone cardiac transplantation for other reasons, [166] probably because the pathogenic process that results in cardiomyopathy in Chagas disease is not systemic, as is the case in diabetes mellitus, for example. Reactivation of the underlying T cruzi infection was a severe problem when the first such transplantations were performed in the late 1980s in Brazil; however, this is less of a problem now with the reduced dosing of immunosuppressives. [167, 168, 169]  

Megaesophagus

Patients with chagasic megaesophagus in whom esophageal dilatation is inadequate often undergo wide esophagocardiomyectomy of the anterior gastroesophageal junction, combined with valvuloplasty to reduce reflux. [67, 170, 171] Laparoscopic myotomy is being used increasingly to manage severe megaesophagus. Partial esophageal resection with reconstruction with esophagogastroplasty has been used in extreme cases. [172]

Megacolon

Patients with severe chagasic megacolon may benefit from the Duhamel-Haddad operation typically used in the treatment of idiopathic congenital megacolon. [173]

In some cases, patients with sigmoid volvulus awaiting the Duhamel-Haddad procedure have undergone anterior sigmoidostomy with an eventual resection of the necrosed segment. [174]

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Consultations

Depending on the phase of T cruzi infection, the following consultations may be appropriate:

  • Infectious diseases specialist
  • Cardiologist and cardiac surgeon
  • Gastroenterologist and general surgeon
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Diet

A diet appropriate for patients with congestive heart failure should be recommended as appropriate.

Ingestion of warm and pasty food, in small volumes with water, is recommended in patients with megaesophagus. Such patients should not eat in the hours before bedtime to reduce the likelihood of regurgitation and aspiration.

A high-fiber diet is recommended in patients with chagasic megacolon.

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Activity

Activity should be as tolerated.

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