In most cases, the acute phase of Chagas disease is asymptomatic and goes undiagnosed. When symptomatic, the findings are typically non-specific and can easily be attributed to other etiologies.  Typical findings include:

• Asymptomatic
• Fever
• Malaise
• Localized nodule at the inoculation site (chagoma)
• Unilateral palpebral edema (Romana sign)
• Lymphadenopathy 
• Hepatosplenomegaly 

These findings usually occur over four to eight weeks. If infected by oral transmission, symptoms may also include nausea, vomiting, diarrhea, abdominal pain, or gastrointestinal hemorrhage. In most cases, the acute infection resolves spontaneously. Severe but rare acute organ-specific manifestations can include myocarditis or meningoencephalitis.[6]  Congenital infections may cause premature birth, low birth weight, fever, anemia, and hypotonicity.[1][2]

A small subset of patients will experience an anaphylactic reaction to the kissing bug bite. Presenting signs and symptoms can include acute onset urticarial rash, flushing, difficulty breathing, wheezing, nausea, vomiting, diarrhea, tachycardia, and edema.[8][19]

Approximately 30% to 40% will develop a chronic infection with subsequent organ damage.[2] Most individuals with chronic infection will develop heart disease or less commonly have gastrointestinal involvement.[1][2] The manifesting symptoms will depend on the location and degree of organ dysfunction.  Cardiac manifestations can include heart block, bundle branch block, syncope.  With more severe disease, including dilated cardiomyopathy or dysrhythmia, symptoms may include shortness of breath, dyspnea, orthopnea, chest pain, or sudden cardiac death.[7] Gastrointestinal manifestations may include problems with motility and include dysphagia, nausea, vomiting, abdominal distention, and abdominal pain.[6]

Clinical manifestations of Chagas reactivation often occur in the setting of immunosuppression and results in an acute illness that may include chagoma, panniculitis, myocarditis, or meningoencephalitis.[18] 

During the acute phase, parasitemia is high, and the diagnosis of Chagas disease is made by visualizing the parasite under microscopy.[7] This is typically done on a blood smear, but occasionally, other body fluids such as cerebrospinal fluid are options. Blood smears can detect parasites; however, polymerase chain reaction (PCR) is a more sensitive test.[6]  Quantitative PCR may also be used for periodic monitoring or suspected reactivation.[12]  For suspected congenital exposure that is not identified at birth, serology can be obtained at approximately nine months.[6]

With the chronic phase, there is minimal parasitemia; therefore, T. cruzi PCR is less reliable, and the detection of serum antibodies is necessary.  These tests are typically enzyme-linked immunosorbent assays (ELISA) or immunofluorescent antibody tests (IFAT) and rely on the detection of IgG antibodies against T. cruzi.[7][12] Due to limitations of assay sensitivity, a two-test regimen using different antigens is recommended.[6][12] In some circumstances, serologic tests can be unreliable. Examples include the diagnosis of early congenital infections and the diagnosis of infection from an organ transplant. In these cases, molecular testing targeted to identify specific DNA sequences is recommended.[1][2]

In patients diagnosed with Chagas disease, evaluation for visceral organ involvement should be performed. This is mainly done with a thorough history to identify early symptoms. Cardiac assessment for those with a history of Chagas disease includes electrocardiogram and echocardiogram.  Common electrocardiographic findings are right bundle branch block, left anterior fascicular block, first degree AV node block, atrial flutter/ fibrillation.[20] Ancillary testing depending on the clinical circumstances could include event monitoring and cardiac MRI.[16] In those with gastrointestinal symptoms, ancillary testing may consist of a barium swallow and barium enema.  

Antitrypanosomal treatment should be considered for acute infections, congenital, reactivation, indeterminate form, women of childbearing age, accidental high-risk exposures, and chronic phase in the pediatric population (less than 18 years).[7] Treatment may also be indicated for immunosuppressed patients.[12] Treatment decisionmaking for adults with chronic phase or Chagas cardiomyopathy is less clear. There are only two medications currently used to treat Chagas disease. Benznidazole and nifurtimox are the only two approved antitrypanosomal drugs available. Based on the 2018 Pan American Health Organization guideline, there is no strict evidence to suggest which medication should be used as first-line; however, in the United States, benznidazole will be more often used due to availability.[12] In the United States, benznidazole was approved by the Food and Drug Administration (FDA) in 2017. Dosing is 5 to 10 mg/kg/day divided every 12 hours for 30-60 days.[6][12] Pediatric dosing also includes a 60-day weight-based regimen. A common side-effect is dermatitis; more serious side effects include myelosuppression and peripheral neuropathy.[17] The presence of myelosuppression or neuropathy is an indication to discontinue treatment immediately. Nifurtimox is the other antitrypanosomal therapy and is not currently FDA approved but can be obtained through the Centers for Disease Control and Prevention (CDC) under an investigational protocol. Dosing is 8 to 10 mg/kg/day divided into three doses for 60 to 120 days. Pediatric dosing also includes a weight-based regimen.[12] Gastrointestinal side-effects are very common with nifurtimox and may include nausea and vomiting.[6]  More serious side-effects can include neurotoxicity, including neurocognitive effects or neuropathy.[17][6]

Cure rates are variable and dependent on several factors such as the age of the patient, stage of the disease, and duration of infection. During the acute phase, cure rates range from 80% to 90% and 20% to 60% in chronic disease.[17][6]  Children generally respond better to therapy; earlier screening and treatment leads to a higher rate of negative seroconversion.[6][7] Transplant patients with prior infection should undergo monitoring at intervals similar to monitoring for rejection and if there are concerns for an acute infection or reactivation.[17]

Treatment for organ-specific sequelae, such as Chagas rhythm disturbances and cardiomyopathy, should follow current recommended treatment for that particular disease (e.g., dilated cardiomyopathy).  Conduction or rhythm disturbances may be treated with an implantable pacemaker and/or cardioverter-defibrillator. Amiodarone is recommended for recurrent ventricular dysrhythmias.[16]  For those with end-stage cardiomyopathy, heart transplantation is a viable option.[6] Trypanocidal therapy for established Chagas cardiomyopathy is controversial.  In a randomized trial, trypanocidal treatment for patients with Chagas cardiomyopathy resulted in a higher negative seroconversion rate but did not appear to improve clinical outcomes.[21]  Despite largely negative results, some authors continue to advocate for treating Chagas cardiomyopathy with trypanocidal therapy.[22]

Differential diagnosis may be broad since signs and symptoms of Chagas disease are non-specific and may include dysfunction of multiple organ systems. During the acute phase, symptoms of fever and malaise can mimic many other febrile illnesses. Unilateral palpebral edema could be mistaken for periorbital cellulitis. A chagoma could be mistaken for another arthropod bite or other dermatologic conditions of localized inflammation.

• Achalasia
• Acute colonic pseudo-obstruction
• Angina pectoris
• Atrioventricular block
• Atrioventricular dissociation
• Chronic megacolon
• Colonic Obstruction
• Constipation
• Coronary artery atherosclerosis
• Dilated cardiomyopathy
• Esophageal motility disorders
• Esophagitis
• Gastroesophageal reflux disease
• Hypertrophic cardiomyopathy
• Leishmaniasis
• Malaria
• Meningitis
• Myocardial rupture
• Myocarditis
• Pulmonary regurgitation 
• Syncope
• Third-degree atrioventricular block
• Toxic megacolon
• Toxoplasmosis

There are three stages of the disease:

• Acute infection
• Indeterminate phase
• Chronic infection

The indeterminate phase occurs after an acute infection resolves, but there remains serologic evidence of an infection. This phase can last for years or even decades. During this time, a person will remain asymptomatic with normal organ function. Approximately 70% of these patients will stay in the indeterminate phase for the remainder of their life, while the remaining 30% will develop chronic disease.[1][2]

In the acute phase, 1% to 5% of patients will develop severe disease, with a mortality rate of 0.2% to 0.5%.[2] Of those who develop chronic infection, approximately 10% develop symptomatic organ dysfunction, and 20% develop asymptomatic organ involvement.[4] It is estimated that approximately 12,000 people per year die from Chagas disease. There is significant variability in morbidity and mortality based on the route of infection.[2] 

During the acute phase of infection, serious complications include:

• Myocarditis 
• Pericardial effusion
• Encephalitis 
• Meningoencephalitis 

During the chronic phase complications include:

• Heart failure
• Arrhythmias
• Thromboembolic disease
• Megaesophagus
• Megacolon
• Neuropathy 

The main form of deterrence is vector control. This can be achieved with measures such as insecticides. There is also a large emphasis placed on improved housing. Protective strategies include the elimination of mud dwellings in developing countries and the use of bed nets. Other methods include screening blood products, organ donors, and pregnant patients.[1][2] 

Chagas disease is one of the neglected tropical diseases outlined by the World Health Organization. If left untreated, it can lead to significant morbidity and mortality.[4][2] With the concern of climate change, it is possible this disease could spread.[23] Additionally, with increasing human migration patterns, there may be an increased spread of Chagas disease in non-endemic areas such as Europe and the United States.[5][13]

An interprofessional team can enhance the care of patients with Chagas disease. Primary care and emergency department personnel need to have a high level of suspicion for those at risk for the disease. Pharmacists review prescribed medications and counsel patients and their families about the importance of compliance and potential side effect. A board-certified infectious disease pharmacist may also help with agent selection and help guide the treatment plan. Nurses are involved in initial evaluation, facilitate communication among the interdisciplinary team, and provide patient information. [Level 5]