Approach

Although there are differences regarding the cure rates in the treatment of Chagas disease, there is consensus about the utility of treatment, depending on several factors, such as the clinical phase and form of Chagas disease, age of the patient, and other associated clinical conditions.[34][166][167]​ Despite the public health importance of Chagas disease, few rigorous clinical trials have been conducted. The objectives of the clinical treatment for Trypanosoma cruzi infection are to eliminate the parasites in the human hosts with antiparasitic treatment, and to manage the clinical syndrome that results from the irreversible lesions associated with the disease. Surgical interventions may be necessary for the management of Chagas disease complications, mostly in advanced-stage disease (e.g., megaesophagus, volvulus, or cardiac function failure).

The phase of T. cruzi infection will determine the type of consultations (family medicine, internal medicine, infectious diseases, cardiology and cardiac surgery, gastroenterology, or general surgery) required. In all cases, a multiprofessional approach is needed.

Antiparasitic treatment: general principles

Antiparasitic drugs should be given as soon as possible after infection in order to achieve the best chance of cure.[134] At present, there are only two antiparasitic drugs available with established efficacy for the treatment of Chagas disease: benznidazole and nifurtimox.[34][138][168][169][170]​ The same treatments are recommended in patients with HIV.[7]​ Benznidazole is recommended as the first-line treatment as it is more widely available, is better tolerated, and has more efficacy data available. Nifurtimox may be used if the patient is unable to tolerate benznidazole, or if it is not available.[2][134]

Adverse effects are common with both drugs and tend to be more frequent and severe with increasing age. Benznidazole is associated with allergic dermatitis, peripheral neuropathy, weight loss, and insomnia. Leukopenia can occur; therefore, a complete blood count is recommended approximately 21 days after starting treatment. Mild-to-moderate dermatitis can be controlled with the use of an oral corticosteroid. Nifurtimox is associated with polyneuropathy, nausea/vomiting, headache, dizziness/vertigo, and weight loss.[2] CDC: Chagas disease: antiparasitic treatment Opens in new window Treatment may need to be stopped temporarily and reintroduced, stopped permanently, or the dose reduced and then uptitrated according to tolerance if the patient reports adverse effects, depending on the severity of the effects.

Antiparasitic drugs are not recommended in pregnancy or in patients with severe renal or hepatic impairment; however, they may be used after birth or if the hepatic/renal impairment is corrected. A negative pregnancy test result is required before starting treatment in women of childbearing potential.[2] Breast-feeding is generally not contraindicated in women with chronic disease; however, it is not recommended in the acute phase or reactivated disease, or if the mother has perimamillar fissures or bleeding mamillae.[171]

Availability of these drugs varies across different countries and a local formulary should be consulted. In the US, benznidazole is approved for use in children 2-12 years of age and is commercially available from the manufacturer after completing a fast access order. Exeltis: benznidazole tablet Opens in new window Nifurtimox is now also commercially available in the US, and no longer needs to be obtained from the Centers for Disease Control and Prevention (CDC).[172] In other countries, the drugs are available from local health regulatory agencies such as the World Health Organization.[173]

Antiparasitic treatment: indications for treatment

Parasite elimination and cure is achieved in 60% to 90% of patients with acute infection, and more than 90% of infants treated during the first year of life achieve cure.[2] According to recent studies, the cure rate for the etiologic treatment of acute Chagas disease is lower in cases of oral transmission with contaminated food compared to traditional vector transmission.[174] Therefore, antiparasitic treatment is indicated in the following patient groups once the diagnosis has been confirmed, provided there are no contraindications:[2][134][175]

  • Acute phase of infection (regardless of mode of transmission)

  • Infants with congenital infection

  • Women of childbearing age (to prevent vertical transmission)

  • All cases of reactivation in immunocompromised patients

  • Accidental high-risk contaminations (e.g., contact with living parasites or cultures through skin breaks or mucosal membranes in laboratory/clinical/necroscopy settings).

Treatment is not recommended in low-risk exposures (e.g., contact with the blood of a chronically infected patient); however, serologic monitoring is recommended. Monitoring is also recommended in patients with high-risk exposures who cannot take antiparasitic drugs.

The role of antiparasitic therapy in the chronic phase of disease is less certain.[134]

  • Pediatric patients: treatment is recommended in all pediatric patients <18 years of age.[2][166][176]

  • Adults: treatment may be considered in patients >18 years of age with indeterminate disease (i.e., positive serology with no evidence of end-organ damage), mild-to-moderate cardiomyopathy (i.e., without congestive cardiac failure), and gastrointestinal disease.[2][34][177][178][179] The CDC strongly recommend treatment in adults ≤50 years of age who do not have advanced Chagas cardiomyopathy, but due to the increased risk of drug toxicity they only recommend treatment in adults >50 years after weighing the risks and benefits of treatment, taking into consideration factors such as age, clinical status, overall health, and patient preference. CDC: Chagas disease: antiparasitic treatment Opens in new window

  • Women of childbearing potential: treatment should generally be offered (once pregnancy has been excluded) in order to reduce the risk of vertical transmission.[180]

In a study with long-term follow-up, benznidazole was associated with reduced occurrence of progression from the indeterminate form to the cardiac form and was also linked to a decreased risk of cardiovascular events, compared with no treatment.[181] However, data show that treatment is unlikely to change clinical outcomes in patients with established cardiac disease.[134][182]​​​ Therefore, antiparasitic treatment is not recommended in patients with established dilated cardiomyopathy. It is also not recommended in patients with advanced gastrointestinal disease (e.g., megaesophagus or megacolon).[34]

There is insufficient evidence to support the efficacy of both benznidazole and nifurtimox for late-stage symptomatic disease.[183]

Supportive treatment

Supportive therapy is indicated for all patients with acute, chronic, or reactivated forms of the disease. Supportive therapy is the only treatment indicated in patients who cannot take antiparasitic treatment (e.g., pregnant and breast-feeding women, severe hepatic/renal insufficiency) or in those with advanced disease.

Patients with cardiac manifestations require obesity correction and maintenance at optimal weight; control of salt consumption, water intake restriction (for the most severe cases), elimination of complicating factors; avoidance of alcohol, individualized physical activity program (in accordance with cardiopathy grade and patient age), influenza and pneumococcal vaccination (if cardiopathy is advanced). It may be necessary to limit professional, school, or sport activities.

Patients with esophageal manifestations should be advised to chew food well; ingest liquid and semi-solid food if necessary; avoid food consumption before sleep; and avoid ingestion of tablets at night. Patients with colonic manifestations require habitual diet; restriction of constipating foods (e.g., banana, guava, jaboticaba); abundant ingestion of water (≥2 L/day if there is no heart failure); increased ingestion of food that favors intestinal transit (e.g., pawpaw, plum, orange, high-fiber food); systematic attention to the wish to evacuate; osmotic laxatives or mineral oil (avoid administration at night, due to risk of aspiration); enemas twice a week; avoidance of constipating medications (e.g., opioids, diuretics, antidepressants, antihistamines, anticonvulsants, antacids with aluminum hydroxide) if possible.

Exercise is an important aspect of cardiovascular rehabilitation because it increases both functional capacity and quality of life; however, there are few trials regarding this subject in the literature.[184] Individualized cardiovascular rehabilitation based on simple, supervised aerobic training can be safely performed in patients with chronic Chagas disease.[185][186][187][188]

Pharmacologic treatment of heart failure

Recommendations for the medical management of Chagas cardiomyopathy are based on extrapolated data from other forms of heart failure, and the safety and efficacy of these drugs in patients with Chagas disease has not been established. Drugs such as ACE inhibitors or angiotensin-II receptor antagonists, beta-blockers, aldosterone receptor antagonists, diuretics, digoxin, anticoagulants, antiplatelet agents, and amiodarone are recommended depending on the presentation (e.g., heart failure, arrhythmias, stroke). Detailed discussion of the medical management of Chagas cardiomyopathy is beyond the scope of this topic.[2] One Cochrane review found very low quality evidence for the use of pharmacologic interventions, such as rosuvastatin and carvedilol, in patients with Chagas disease and heart failure.[189]

Surgical intervention

Patients with cardiopathy may require pacemaker placement for atrial and ventricular rhythm disturbances; ablation procedures for tachyarrhythmias; implanted defibrillators; resection of left ventricular apical aneurysms, or heart transplant.[4]​​[26]​​[143][144][176][190]​ 

Patients with megaesophagus may require esophagocardiomyectomy of the anterior gastroesophageal junction (combined with valvuloplasty) to reduce reflux in cases with no response to esophageal dilation; laparoscopic myotomy to manage severe megaesophagus; or partial esophageal resection with reconstruction by esophagogastroplasty, in severe cases. Patients with megacolon may require the Duhamel-Haddad operation, and patients with sigmoid volvulus may require anterior sigmoidostomy with resection of the necrosed segment.[4]​​[26][158]

End-stage organ failure

Patients with Chagasic end-stage organ failure may require organ transplantation.[191][192][193][194][195] In these situations, the serologic status of donor and receiver should be checked, as the risk of infection transmission and Chagas reactivation needs to be considered for both.[13][97][165][176][196] The surgical transplant team will be able to decide which parties require antiparasitic pharmacotherapy.

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