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      Drugs & Diseases > Infectious Diseases

      Chagas Disease (American Trypanosomiasis) Treatment & Management

      Updated: Jul 06, 2023
      • 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 Trypanosoma 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. Its safety and efficacy were established in two placebo-controlled clinical trials in children aged 6-12 years. In these 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. [158, 159]

      Nifurtimox gained FDA approval in 2020 for pediatric patients (birth to younger than 18 years who weigh at least 2.5 kg) for the treatment of T cruzi infection. Approval for nifurtimox was based on the number of treated patients who became IgG antibody negative or who showed an at least 20% decrease in optical density on 2 different IgG antibody tests against antigens of T cruzi. [160]  No other drugs, either alone or in combination with nifurtimox or benznidazole, have been approved for treating T cruzi infection. [161, 162, 163]

      For the most part, both benznidazole and nifurtimox are limited in their capacity to effect parasitologic cure, especially in chronically infected patients (see below). It merits mention that prescribing benznidazole or nifurtimox for patients who do not fall within the age ranges specified in their corresponding FDA approvals constitutes off‑label use.

      Acute Chagas disease

      Consistent with WHO 2022 and current CDC recommendations, 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. Responses to treatment of patients with reactivation is best monitored by PCR assay. [164]

      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. [165]  Some sources have stated that the overall parasitologic cure rate in persons with acute Chagas disease is 70%, but 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 T cruzi infection is that chronically infected children and adolescents up to 18 years of age should be treated with either benznidazole or nifurtimox. Convincing data from trials in Argentina and Brazil indicate that a substantial proportion of these patients will be cured parasitologically. [36, 166, 167]

      In addition, there is broad agreement that all women of child‑bearing age should be given a full course of treatment. This recommendation is based on convincing evidence that has accumulated over the last decade indicating that the treatment of girls and women of child‑bearing age infected with T cruzi markedly reduces the probability of congenital transmission to their babies conceived after treatment. [168, 169, 170, 171, 172, 173, 174]

      It is noteworthy that a substantial proportion of the girls and women in these trials treated prior to pregnancy likely were not cured parasitologically, and in some instances many years had gone by between the treatment and the pregnancies. These data indicate clearly that specific pre-pregnancy treatment of chronic T cruzi infection has a marked suppressive effect on the likelihood of subsequent congenital transmission, and it seems likely that treating all infected women of child-bearing age who are not pregnant will become the standard of care. In view of the potential fetal toxicity of benznidazole and nifurtimox, care must be taken to establish that chronically infected women are not pregnant when treatment is started and that they do not become pregnant during treatment.

      In contrast to the largely good news related to the utility of treating children, adolescents, and women of child bearing age, 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 and those with manifest chagasic symptoms, most of whom presumably were infected while quite young, actually may be less than 10%. [175, 176, 177, 178, 179, 180, 181]  Moreover, determining which treated patients are cured is challenging, since treatment suppresses parasitemias, as reflected in reduced rates of positivity in post‑treatment PCR assays, [182]  as well as in xenodiagnosis and hemoculture. To further complicate this issue, levels of anti–T cruzi antibodies can remain positive for years even in cured patients. [149, 183]

      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 detailed discussion of this issue took place in 2006 at a 2-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 guidance document that resulted from that meeting, [166]  the panel recommended that treatment be offered to chronically infected adults with at most mild clinical disease, and that, after discussion of the risks and possible benefits, treatment decisions be shared by patients and caregivers. This tepid recommendation was accompanied by references to a review that summarized data suggestive of treatment efficacy from several studies [184]  and to the then recent report of a nonrandomized and unblinded benznidazole treatment trial that showed a hint of efficacy. [185]  An important background issue that was considered in the discussion of treatment efficacy at the meeting was the well-established observation that treatment of chronically infected persons generally suppressed parasitemias and prompted the hopeful assumption that this might lead to better clinical outcomes.

      A major step forward in assessing the effect of specific treatment was taken in 2015 by the publication of the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial. [186, 187]  In this blinded, placebo‑controlled trial of benznidazole versus placebo performed in Brazil, Argentina, Bolivia, and Colombia, 2,854 T cruzi–infected patients with mild cardiac disease were followed for a mean of 5.4 years. As expected, parasite detection as indicated by PCR assay was suppressed; however, benznidazole did not significantly reduce cardiac clinical deterioration or death rates. In view of these results and others published more recently, [188, 189]  specific treatment of adults with chronic T cruzi infection and mild cardiac disease cannot be recommended. Moreover, the BENEFIT results clearly showed that, at least in persons with mild cardiac disease associated with chronic T cruzi infection, suppression of parasitemias, which was clearly documented in the benznidazole arm, was not a marker for better clinical outcomes. In summary, a variety of heterogeneous trials that addressed the thorny issue of whether to treat patients with indeterminate T cruzi infection have been conducted both before and after BENEFIT, but unfortunately the question remains largely unresolved. [190]  Importantly, for technical reasons related to study design, no patients in the indeterminate phase of chronic T cruzi infection were included in the BENEFIT trial, and in the years since the report of the trial was published no convincing data from other RCTs have been published that address the question of the usefulness of treating indeterminate phase persons. [191]

      To summarize the current institutional positions regarding the treatment of adults with indeterminate phase T cruzi infection, the recommendations of WHO 2022 [192]  and PAHO 2023, [193]  are largely similar to those published following the 2006 CDC meeting. [166]  The lack of certainty of benefit, the long course of treatment, and the frequent and sometimes serious adverse reactions to benznidazole and nifurtimox all should be weighed carefully in the process of deciding to recommend treatment or not. A substantial proportion of patients treated with nifurtimox have bothersome side effects. [194]  Although nifurtimox lowers parasitemias and anti‑T cruzi antibody levels in a considerable proportion of treated patients, its long-term benefits have not been clearly established. [195, 196]  Finally, it merits recalling here that the FDA approvals of benznidazole and nifurtimox are limited to children and adolescents. This situation likely reflects the reality that the data suggesting that the treatment of adults with chronic T cruzi infection might be beneficial are of low quality, making any recommendations favoring treatment controversial. [197]

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

      Chronic symptomatic Chagas disease

      There is a general consensus among Chagas experts that 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. However, the benefits and risks of implantable cardioverter devices (ICDs) in patients with advanced Chagas heart disease is controversial and requires further study in properly structured trials. [107, 198, 199, 200, 201, 202, 203, 204, 205]  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 such patients have undergone this procedure in Argentina, Brazil, and the United States. [206, 207, 208]  Not surprisingly, T cruzi has been found in endomyocardial biopsies of transplant recipients, thus raising the possibility of early failure of the transplanted hearts due to invasion of parasites. [209]  It is notable that the survival rate among patients with Chagas disease who have undergone cardiac transplantation is comparable to that in the general group of patients who have undergone cardiac transplantation for other reasons. [210, 211]

      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. [58, 212, 213]  Laparoscopic myotomy is being used increasingly to manage severe megaesophagus. Partial esophageal resection with reconstruction with esophagogastroplasty has been used in extreme cases. [214, 215]

      Megacolon

      Patients with severe chagasic megacolon may benefit from the Duhamel-Haddad operation typically used in the treatment of idiopathic congenital megacolon. [216]

      In some cases, patients with sigmoid volvulus awaiting the Duhamel-Haddad procedure have undergone anterior sigmoidostomy with an eventual resection of the necrosed segment. [217]

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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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