01Approach to the Critical Patient/attcp40

Immediate priorities

›Life-threatening presentations

›Acute myocarditis or cardiogenic shock

›Chest pain with tachycardia out of proportion to fever

›Hypotension with signs of low cardiac output

›Occurs in fewer than 5% of acute cases but carries significant mortality

›Meningoencephalitis

›Altered mental status, seizures, or focal neurologic deficits

›Approximately 1% of acute cases; higher mortality in infants and immunocompromised

›Pericardial effusion with tamponade physiology

›Muffled heart sounds

›Pulsus paradoxus

›If hemodynamically unstable, immediate resuscitation bay activation

›IV access x2 large bore

›Continuous cardiac monitoring and 12-lead ECG

Hemodynamic goals and monitoring

›Stabilization targets

›MAP >= 65 mmHg

›IV fluid resuscitation for hypotension

›Norepinephrine if vasopressor required

›SpO2 >= 92% on supplemental oxygen

›HFNC or mechanical ventilation if respiratory compromise from cardiogenic pulmonary edema

›Continuous telemetry

›AV block, RBBB, or ventricular arrhythmia triggers escalation

›Atrial fibrillation management per ACLS protocol

›Escalation triggers

›Worsening cardiac function on bedside echo

›Cardiology and cardiac ICU consultation

02History/hx60

Exposure and travel history

›Geographic exposure

›Prolonged stay (more than 6 months) in Mexico, Central America, or South America

›Single most important screening question for Chagas disease

›21 endemic countries, primarily rural areas

›Rural dwelling in adobe or thatch-walled housing

›Triatomine kissing bug habitat

›Sub-peridomestic infestation patterns

›Immigration history from endemic region

›Country of origin and housing conditions

Transmission route

›Vector-borne exposure

›Triatomine bug bite during sleep

›Bug defecates near bite; scratching inoculates wound

›Symptoms appear 1 to 2 weeks after exposure

›Oral transmission

›Contaminated fresh fruit juices (acai, sugarcane, guava)

›Associated with more severe disease and higher case-fatality rates

›Outbreak setting consideration

›Non-vector transmission

›Blood transfusion from endemic-area donor

›Symptoms up to 3 to 4 months after transfusion

›Organ transplant from seropositive donor

›Congenital transmission

›Maternal history of T. cruzi infection

›1 to 10% vertical transmission rate in seropositive mothers

›Laboratory accident (rare, occupational exposure)

03Physical Exam/exam53

Vital signs

›Hemodynamic status

›Temperature (often low-grade fever)

›High fever may indicate oral-route transmission (more severe disease)

›Heart rate

›Tachycardia out of proportion to fever suggests cardiac involvement

›Bradycardia or irregular rhythm suggests conduction disease

›Blood pressure

›SBP below 90 mmHg indicates hemodynamic compromise

›MAP below 65 mmHg triggers resuscitation

›Respiratory rate

›Elevated rate in cardiogenic pulmonary edema or meningoencephalitis

Head and neck exam

›Pathognomonic signs

›Romaña sign

›Unilateral painless periorbital edema

›Conjunctival injection with regional lymphadenopathy

›Present in approximately 50% of recognized vector-borne acute cases

›Chagoma at inoculation site

›Erythematous indurated subcutaneous nodule

›Any skin surface; often extremities

›Lymphadenopathy

›Generalized lymphadenopathy

›Mononucleosis-like clinical syndrome

›Absence of posterior cervical lymphadenopathy distinguishes from African trypanosomiasis

Cardiovascular exam

›Cardiac findings

›Tachycardia or irregular rhythm

04Differential Diagnosis/ddx52

Life-threatening mimics

›Acute viral myocarditis

›ICD-10 I40.9

›Travel history and blood smear or PCR differentiates

›Endomyocardial biopsy may be needed if diagnosis unclear

›Bacterial meningitis

›ICD-10 G00.9

›CSF analysis with differential cell count and culture distinguishes

›Chagas meningoencephalitis CSF may show predominantly mononuclear pleocytosis

›Septic shock from bacteremia

›ICD-10 A41.9

›Blood cultures and response to antibiotics differentiating

Infectious disease mimics

›Malaria

›ICD-10 B54

›Febrile illness in returning traveler; thick and thin smear shows Plasmodium not trypomastigotes

›Cyclic fever pattern more prominent; no periorbital edema

›Dengue fever

›ICD-10 A90

›Rash and arthralgias more prominent; thrombocytopenia common

›No trypomastigotes on smear; dengue NS1 antigen or PCR positive

›Infectious mononucleosis (EBV)

›ICD-10 B27.00

›Mononucleosis-like syndrome overlap; atypical lymphocytes on smear

›Monospot or EBV serology positive; no trypomastigotes

›Visceral leishmaniasis (Kala-azar)

›ICD-10 B55.0

›Fever, hepatosplenomegaly, pancytopenia; different vector (sandfly) and geography

05Laboratory Tests/lt58

Diagnostic parasitology

›Blood smear microscopy

›Giemsa-stained thick and thin blood smear

›Standard first-line test in acute phase

›Look for trypomastigotes with large posterior kinetoplast and C-shaped morphology

›High sensitivity in acute phase when parasitemia is high

›IDSA/ASM 2024 guideline recommended (Class I)

›Buffy coat preparation

›Concentrates parasites; increases sensitivity

›Useful when smear is negative in symptomatic patient

›Fresh wet mount of anticoagulated blood

›May show motile trypomastigotes

›Not routinely available in US labs

Molecular diagnostics

›PCR for T. cruzi DNA

›Higher sensitivity than microscopy as adjunct

›Useful when parasitemia low (congenital, reactivation, chronic)

›IDSA/ASM 2024 guideline recommended

›Quantitative PCR useful for monitoring treatment response

›Parasitemia should clear within weeks of effective treatment

›Reference laboratory testing required in most US institutions

›CDC can facilitate

Serologic testing

›Acute phase serology

›Not reliable in acute phase (antibodies may be absent for 4 to 8 weeks)

›IgM anti-T. cruzi may be detectable earlier but not widely available

›Two-test algorithm required for chronic infection diagnosis

›Two different antigen or format tests required; one positive is insufficient

06Diagnostic Tests/dt92

Scoring Systems

›Chagas disease severity staging

›WHO/PAHO staging classification

›Acute phase: parasitemia detectable, nonspecific febrile illness

›Indeterminate chronic phase: seropositive, normal ECG and imaging

›Chronic cardiac phase: ECG abnormalities, cardiomegaly, arrhythmia

›Chronic digestive phase: megaesophagus or megacolon

›Rassi score (chronic cardiomyopathy risk stratification)

›Not for acute phase; used for chronic phase prognosis

›Variables include NYHA class, cardiomegaly, LV dysfunction, non-sustained VT, QRS low voltage, male sex

›Sepsis screening tools

›qSOFA

›RR >= 22 per minute

›SBP <= 100 mmHg

›Altered mental status

›Screening tool; clinical judgment required

›SOFA score

›Full organ dysfunction assessment for ICU disposition

›Limitations of scoring systems

›No validated acute Chagas-specific score

›Clinical trajectory and cardiac involvement supersede scoring

MRI

›Cardiac MRI

›Role in acute Chagas myocarditis

›Late gadolinium enhancement identifies myocardial inflammation and fibrosis

›Characteristic pattern: subepicardial and midmyocardial enhancement, often involving lateral and inferior walls

›Superior tissue characterization compared to echocardiography alone

›Indications in acute setting

›Myocarditis with normal or borderline echo but ongoing clinical concern

›Differentiating Chagas myocarditis from other cardiomyopathies

›Pericardial disease characterization

›Contraindications and limitations

›Hemodynamically unstable patient — echocardiography preferred

›Non-MRI-compatible implants or pacemakers

›Availability constraint in emergency setting

›Brain MRI for meningoencephalitis

›Indications

›CNS symptoms in confirmed or suspected acute Chagas

›Immunocompromised patient with focal neurologic signs

›Expected findings

›Brain chagomas: ring-enhancing lesions, typically larger than toxoplasmosis

›Diffuse meningoencephalitic changes

›FLAIR signal abnormalities in white matter

›Differentiating from toxoplasmosis

›Chagas CNS lesions often larger and fewer

›T. cruzi PCR on CSF distinguishes

CT

›CT chest

›Indications in acute Chagas

›Cardiomegaly evaluation when CXR equivocal

›Pericardial effusion size quantification

›Pulmonary edema assessment in acute myocarditis

›Findings

›Cardiomegaly with globular cardiac silhouette (pericardial effusion or dilated cardiomyopathy)

›Pulmonary vascular congestion pattern

›Pleural effusions in heart failure

›Contrast considerations

›Renal function assessment before contrast administration

›Allergy history

›CT brain

›Indications

›Altered mental status or new focal deficit

›Seizure in febrile patient with suspected Chagas

›Before lumbar puncture to exclude mass effect

›Findings with CNS Chagas

›Hypodense lesions corresponding to chagomas

›Ring-enhancing lesions with contrast (may mimic toxoplasmosis)

›Mass effect with large chagomas

›Evidence

›CT brain recommended before LP when focal deficits or papilledema present

›ACEP Level C recommendation for neuroimaging before LP in this setting

Ultrasound

›Echocardiography

›Indications in acute Chagas

›Any suspicion of cardiac involvement

›All patients with ECG abnormalities, chest pain, or dyspnea

›American Society of Echocardiography recommends multimodality cardiac imaging in Chagas disease (2018 Guideline)

›Key echocardiographic findings in acute myocarditis

›Regional or global wall motion abnormalities

›Reduced LV ejection fraction (below 50%)

›Pericardial effusion

›Intracardiac thrombus (risk of embolism)

›ASE/ECOSIAC guideline recommendations

›Baseline echo for all confirmed Chagas cases

›Repeat echo at 6 months to assess for progression to chronic cardiomyopathy

›Point-of-care ultrasound (POCUS)

›Cardiac POCUS in ED

›Pericardial effusion rapid identification

›Gross LV function assessment

›IVC size for fluid responsiveness guidance

›Abdominal POCUS

›Hepatosplenomegaly confirmation

›Ascites detection if severe disease

›Lung POCUS

›B-lines for pulmonary edema from myocarditis

›Pleural effusion detection

07Disposition/dispo51

Admission indications

›Cardiac involvement

›ECG abnormalities

›AV block (any degree)

›Right bundle branch block (RBBB)

›Ventricular arrhythmias or non-sustained VT

›Atrial fibrillation or flutter

›ST changes or QTc prolongation

›Clinical myocarditis

›Elevated troponin with symptoms

›LV dysfunction on echo

›Pericardial effusion (any size with tamponade physiology; moderate or large)

›Hemodynamic instability

›SBP below 90 mmHg

›MAP below 65 mmHg despite initial resuscitation

›Neurologic involvement

›Meningoencephalitis or altered mental status

›Seizures

›Focal neurologic deficits

›High-risk host

›Immunocompromised with suspected reactivation

›HIV with low CD4 count

›Transplant recipient

›Neonates with symptomatic congenital infection

›Infants with acute disease (higher mortality risk)

›Inability to initiate outpatient treatment

›Severe nausea or vomiting precluding oral antiparasitic therapy

›No access to infectious disease follow-up

08Treatment/t104

Antiparasitic therapy — first-line

›Benznidazole

›Mechanism

›Nitroreductase-mediated formation of toxic metabolites

›Direct trypanocidal activity

›First-line preference due to better tolerability and tissue penetration

›Dosing — adults

›5 to 8 mg/kg/day PO divided in 2 doses (BID)

›Maximum 300 mg/day per expert recommendation

›Duration 60 days

›Take with food to reduce GI side effects

›Dosing — children 2 to 12 years (FDA-approved)

›Same weight-based dosing: 5 to 8 mg/kg/day divided BID

›Duration 60 days

›Meningoencephalitis dosing

›Up to 15 mg/kg/day recommended

›Specialist guidance required

›Cure rate in acute phase

›76 to 100% when initiated early

›Near 100% in congenital Chagas when treated in first year of life

›Adverse effects

›Dermatitis and photosensitivity rash (approximately 30% of patients)

›Peripheral neuropathy (approximately 30% with prolonged use)

›GI intolerance (nausea, anorexia)

›Bone marrow suppression (rare)

›Management of adverse effects

›Mild rash: antihistamines or short-course corticosteroids

›Discontinue immediately for severe or exfoliative dermatitis

›Discontinue for dermatitis with fever and lymphadenopathy

›Contraindications

›Pregnancy (teratogenic)

›Breastfeeding

›Severe hepatic or renal insufficiency

›Advanced chagasic cardiomyopathy

Antiparasitic therapy — alternative

›Nifurtimox

›Role

›Alternative when benznidazole not tolerated or contraindicated

›FDA-approved for children birth to under 18 years (weight >= 2.5 kg)

›Adult use off-label but standard practice

›Dosing — adults

›8 to 10 mg/kg/day PO divided in 3 doses (TID)

›Duration 60 days

›Take with food

›Dosing — pediatric (per kg)

›Children 1 to 10 years: 15 to 20 mg/kg/day in 4 divided doses

›Adolescents 11 to 16 years: 12.5 to 15 mg/kg/day in 4 divided doses

›Duration 60 to 90 days

›Adverse effects

›Anorexia and weight loss

›Neuropsychiatric symptoms: irritability, insomnia, restlessness

›Nausea and vomiting

›Peripheral neuropathy with prolonged use

›Discontinuation rates reported 14.5 to 75%

›Contraindications

›Pregnancy

›Severe neuropsychiatric disease

›Severe hepatic or renal insufficiency

Cardiac management

›Acute myocarditis

›Standard heart failure therapy as needed

›Diuretics (furosemide IV 40 mg initially; titrate to urine output)

›ACE inhibitor or ARB initiation with cardiologist guidance

›Vasodilators for afterload reduction

›Arrhythmia management

›Continuous telemetry

›ACLS protocol for ventricular tachycardia or fibrillation

›Amiodarone for refractory ventricular arrhythmia

›Temporary pacing for high-degree AV block

›Transcutaneous pacing as bridge

›Transvenous pacing if persistent

›Anticoagulation

›Anticoagulation for LV thrombus detected on echo

›Anticoagulation for atrial fibrillation per CHA2DS2-VASc score

›Pericardial effusion

›Pericardiocentesis if tamponade physiology present

›Emergent if hemodynamic compromise

›Echocardiography-guided preferred

›Cardiology consultation for all pericardial effusions

Meningoencephalitis management

›Antiparasitic at higher dose

›Benznidazole up to 15 mg/kg/day

›Duration extended to 60 days minimum; specialist guidance

›Supportive CNS care

›Seizure management: lorazepam IV 0.1 mg/kg (max 4 mg) for active seizure

›Levetiracetam for seizure prophylaxis consideration

›Dexamethasone 0.15 mg/kg IV q6h for vasogenic edema (specialist guidance)

›Neurology and infectious disease co-management required

Immunocompromised and HIV management

›HIV-coinfected patients

›Initiate or optimize antiretroviral therapy (ART)

›Same antiparasitic regimen as immunocompetent

›Mortality remains high even with treatment in fulminant reactivation

›Screen for CNS involvement aggressively

›Transplant recipients with reactivation

›Reduction in immunosuppression if feasible (discuss with transplant team)

›Antiparasitic therapy initiated immediately

›Monitoring with PCR during treatment

Supportive care

›Fever management

›Antipyretics (acetaminophen preferred)

›IV hydration for dehydration from fever and poor oral intake

›Drug monitoring during treatment

›CBC every 2 weeks during therapy

›Monitor for bone marrow suppression (benznidazole)

›LFTs every 2 weeks during therapy

›Monitor for hepatotoxicity

›Renal function at baseline and monthly

›Prevention of oral transmission reinfection

›Counsel on avoiding raw or untreated fruit juices from endemic areas

09Special Populations/sp67

Pregnancy

›Treatment considerations

›Benznidazole and nifurtimox both contraindicated in pregnancy

›Teratogenic in animal studies

›Antiparasitic treatment deferred until after delivery and cessation of breastfeeding

›Supportive therapy for acute illness

›Antipyretics (acetaminophen; avoid NSAIDs in third trimester)

›IV hydration for severe dehydration

›Congenital transmission risk

›Occurs in 1 to 10% of pregnancies in seropositive mothers

›Screening of all neonates born to seropositive mothers

›PCR or microscopy at birth and 4 to 8 weeks

›Serology not valid before 9 months of age (maternal antibody interference)

›Congenital transmission associated with stillbirth, prematurity, and low birth weight

›Delivery and postpartum

›Mode of delivery not changed by Chagas status

›Breastfeeding generally considered safe if no breast wounds or cracked nipples

›Treatment may be initiated after cessation of breastfeeding

›Maternal-fetal medicine and infectious disease co-management

›Cardiac monitoring in pregnancy

›Baseline ECG and echo for seropositive pregnant women

›Increased cardiac demand of pregnancy may unmask latent cardiomyopathy

Geriatric

›Reactivation in older adults

›Immunosenescence increases reactivation risk

›Consider reactivation in older Latin American immigrants with new cardiac symptoms

›Chronic infection may have been acquired decades prior

›Serologic screening in at-risk older adults from endemic regions

10Background/b85

Epidemiology

›Global burden

›Estimated 6 to 7 million people infected worldwide

›GBD 2023 study confirms ongoing high disease burden in Latin America

›21 endemic countries primarily in Central and South America

›Approximately 300,000 to 400,000 people with T. cruzi infection in the United States

›Primarily immigrants from endemic regions

›Congenital transmission occurring in US among seropositive immigrant mothers

›Annual deaths estimated at 7,000 to 10,000 (predominantly from chronic cardiomyopathy)

›Acute phase epidemiology

›More than 98% of acute infections asymptomatic or unrecognized

›Symptomatic acute disease skewed toward children in endemic areas

›Oral transmission outbreaks increasingly recognized

›Higher case-fatality rates than vector-borne infection

›Brazil, Venezuela, and Colombia most reported

›Congenital transmission: 1 to 10% rate in seropositive mothers

›Up to 14,000 infected neonates born annually in Latin America

›Mortality

›Acute phase mortality less than 5% overall

›Higher in infants, young children, and immunocompromised

›Without antiparasitic treatment: 20 to 30% progress to chronic cardiomyopathy over decades

Pathophysiology

›Causative organism

›Trypanosoma cruzi

›Protozoan parasite, Kinetoplastida order

›Discrete typing units (DTUs) TcI through TcVI with geographic and host variation

›Kinetoplast (mitochondrial DNA) is large and posterior; C-shaped morphology on smear

›Transmission cycle

›Vector-borne route (most common historically)

›Triatomine bug (Rhodnius prolixus, Triatoma infestans, others)

›Fecal contamination of bite wound or mucosal surface

›Oral route

›Ingestion of triatomine feces or crushed bugs in fruit juices

›Highly efficient transmission route (higher inoculum)

›Other routes: blood transfusion, organ transplant, congenital, laboratory accident

›Acute phase pathogenesis

›Local inflammation at inoculation site (chagoma or Romaña sign)

›Leishmanoid amastigotes proliferate locally before entering bloodstream

›Parasitemia

›Trypomastigotes circulate and invade multiple cell types

›Cardiac myocytes, macrophages, neurons preferentially parasitized

›Innate and adaptive immune response

›TNF-alpha, IFN-gamma, IL-12 mediate inflammatory myocarditis

›Inflammatory response responsible for much of acute cardiac damage

›Resolution

›Parasitemia controlled by immune response over 4 to 12 weeks

›Parasite persists at low levels in tissue (chronic infection established)

›Acute cardiac pathology

›Myocarditis

›Direct myocardial invasion and inflammatory infiltrate

›Focal necrosis and edema

›Conduction system involvement

›Inflammation of sinus node and AV conduction

›RBBB most common acute ECG abnormality

›Pericarditis

›Inflammatory pericardial involvement

Therapeutic Considerations

›Timing of treatment

›Acute phase antiparasitic treatment has best efficacy

›76 to 100% cure rate in acute phase

›Cure rate declines significantly in chronic phase (less than 30%)

›Treatment in chronic phase (indeterminate or cardiac): reduces seroreversion but evidence for clinical benefit is less established

›BENEFIT trial (Lancet 2015): no significant reduction in cardiac clinical events with benznidazole in chronic cardiomyopathy

›Drug access in the United States

›Benznidazole and nifurtimox not routinely stocked in US pharmacies

›Contact CDC Parasitic Diseases Hotline 404-718-4745

›Investigational drug protocols may apply for adult off-label use

›FDA approved indications

›Benznidazole: ages 2 to 12 years

›Nifurtimox: birth to under 18 years (weight >= 2.5 kg)

›Monitoring strategy

›CBC and LFTs every 2 weeks during 60-day treatment course

›Bone marrow suppression and hepatotoxicity surveillance

›Peripheral neuropathy symptom monitoring

›Drug reaction monitoring

›Rash onset typically weeks 2 to 4

›Post-treatment surveillance

›Serologic follow-up to document seroconversion

›May take months to years in adults; faster in children

›PCR negativity as early marker of parasitological cure

›Annual ECG for all confirmed T. cruzi infection even after acute treatment

›Monitor for late cardiac manifestations

›Prevention

›Vector control with insecticide spraying in endemic housing

›Housing improvement (replacing thatch and adobe)

›Blood bank and organ donor screening (now universal in endemic countries and US)

›Avoidance of untreated fresh fruit juices from endemic areas

›No vaccine currently available

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Home care instructions for Chagas disease

›Take your antiparasitic medication exactly as prescribed

›Benznidazole or nifurtimox must be taken with food

›Do not skip doses; full 60-day course is essential

›Contact your doctor if you develop a rash, numbness or tingling in hands or feet, or severe stomach upset

›Rest and hydration

›Drink plenty of fluids during the febrile illness

›Rest as needed until fever resolves

›Sun protection

›Benznidazole can cause photosensitivity rash

›Use sunscreen and avoid prolonged sun exposure during treatment

›Follow-up appointments

›Blood test (CBC and liver tests) every 2 weeks during treatment

›First follow-up appointment within 1 week to check medication tolerance

›Infectious disease specialist appointment arranged

›Cardiology appointment if heart problems were identified

›Warning signs — return to emergency department immediately for

›Chest pain, racing heart, irregular heartbeat, or fainting

›Shortness of breath at rest or waking you from sleep

›Severe rash especially with blistering, peeling, fever, or swollen lymph nodes

›Stop your medication and return immediately

›Numbness, tingling, or weakness in arms or legs (new or worsening)

›Confusion, severe headache, seizures, or difficulty speaking or moving limbs

›Yellowing of skin or eyes (jaundice)

›Fever returning or worsening after initial improvement

›Important information for you and your family

›You cannot donate blood or organs

12References/r31

Guidelines and key sources

›Primary clinical guidelines

›Bern C. Chagas Disease. New England Journal of Medicine 2015

›Comprehensive review of diagnosis and management across all phases

›Nunes MCP et al. Chagas Cardiomyopathy: AHA Scientific Statement. Circulation 2018

›Cardiac management, imaging, and monitoring recommendations

›Perez-Molina JA, Molina I. Chagas Disease. Lancet 2018

›Updated comprehensive clinical review

›Acquatella H et al. ASE Recommendations for Multimodality Cardiac Imaging in Chagas Disease. J Am Soc Echocardiogr 2018

›Echocardiographic surveillance guidelines

›Constance Benson et al. IDSA/OARAC Guidelines for Opportunistic Infections in HIV. 2025

›Chagas reactivation in HIV: management recommendations

›Miller JM et al. IDSA/ASM Guide to Microbiology Laboratory for Infectious Disease Diagnosis. Clinical Infectious Diseases 2024

›Diagnostic testing guidance for T. cruzi

›Cantey PT et al. Neglected Parasitic Infections: CDC Update. American Family Physician 2021

›US-focused management, drug access, and screening

›Key research

›Rassi A et al. Chagas Disease. Lancet 2010

›Natural history and pathophysiology overview

›Bern C et al. Evaluation and Treatment of Chagas Disease in the US. JAMA 2007

›Systematic review of US management and drug access

›GBD 2023 Chagas Disease Collaborators. Global Burden of Chagas Disease 1990-2023. Lancet Infectious Diseases 2026

›Current epidemiologic burden data

›Elkheir N et al. HIV and T. cruzi Co-Infection Systematic Review. PLoS Neglected Tropical Diseases 2026

›Reactivation risk and outcomes in HIV coinfection

›ICD-10 codes

›B57.0 — Acute Chagas disease with heart involvement

›Use for acute myocarditis or cardiac complications

Evidence & Review