231.1 🎓 醫孞生版

231.1.0.1 📌 䞀頁重點

231.1.0.1.1 Microbiology + Vector
  • Pathogen: Trypanosoma cruzi (single species, multiple discrete typing units DTU I-VI)
  • Vector: Triatomine bug (“kissing bug”, “vinchuca”); Triatoma infestans in Southern Cone (main); T. dimidiata, Rhodnius prolixus others
  • Reservoir: dogs, opossums, armadillos, raccoons, etc. (many sylvatic + domestic mammals)
231.1.0.1.2 Transmission
  • Vectorial: triatomine bug feces (NOT bite directly — bug bites and defecates near; rubbing feces into bite wound or mucous membrane transmits)
  • Transfusion: major in Latin America historic; now screened
  • Vertical: 5-10% of pregnancies in chronically infected mothers
  • Oral: contaminated food/juice with bug feces (açaí outbreaks)
  • Organ transplant from infected donor
  • Lab exposure: rare
231.1.0.1.3 Epidemiology
  • 6-7 million chronic infections globally (WHO)
  • Endemic Latin America: Bolivia (highest), Argentina, Brazil, Mexico, others
  • Increasing in non-endemic (migration): USA (300,000+), Spain, Italy, Japan, Australia
  • 30% of chronic develop cardiomyopathy + GI complications
231.1.0.1.4 Clinical Stages
231.1.0.1.4.1 Acute (Weeks-Months Post-Exposure)
  • 1-2 weeks incubation
  • Usually mild / asymptomatic (75-95%)
  • Sometimes:
    • Romaña sign: unilateral painless periorbital edema + conjunctivitis (eye inoculation)
    • Chagoma: erythematous nodule at skin inoculation site
    • Fever, malaise, lymphadenopathy, hepatosplenomegaly
    • Rare: myocarditis, meningoencephalitis (especially pediatric / immunocompromise)
  • High parasitemia
  • Self-limited; 100% become chronic without treatment
231.1.0.1.4.2 Indeterminate (Chronic Asymptomatic)
  • Years to decades
  • ~ 60-70% of chronic patients remain in this stage
  • Antibodies + low parasitemia
  • ECG + echo normal
231.1.0.1.4.3 Chronic Cardiomyopathy (30%)
  • Decades after acute
  • Conduction abnormalities (RBBB + LAFB + bradyarrhythmias) — earliest
  • Dilated cardiomyopathy + congestive heart failure
  • Apical aneurysms of LV (characteristic)
  • Mural thrombus + embolic stroke
  • Sudden cardiac death (ventricular tachycardia / fibrillation)
  • Mortality: leading cause of death in endemic areas
231.1.0.1.4.4 Chronic Digestive (Megacolon / Megaesophagus)
  • 10-20% chronic in Brazil + Southern Cone (geographic variation)
  • Less common Mexico + Central America (different DTU)
  • Megaesophagus: dysphagia → progressive
  • Megacolon: chronic constipation → fecal impaction → volvulus
  • Mechanism: autonomic ganglia destruction
  • Surgical management often required
231.1.0.1.5 Diagnosis
231.1.0.1.5.1 Acute
  • Blood smear (Giemsa) — trypomastigotes visible
  • PCR — most sensitive in acute
  • Serology (IgM) — may be delayed
  • Buffy coat
231.1.0.1.5.2 Chronic
  • Serology (2 different assays required for confirmation):
    • IFA
    • ELISA
    • Recombinant antigen tests
    • Discordant results → 3rd test
  • PCR sensitivity variable in chronic (low parasitemia)
231.1.0.1.5.3 Imaging
  • ECG: RBBB + LAFB suggestive; advanced AV block, sustained VT
  • Echo: LV dysfunction, apical aneurysm, mural thrombus
  • MRI: fibrosis pattern (subepicardial inferolateral)
  • Esophagram, colonoscopy for digestive forms
231.1.0.1.6 Treatment
231.1.0.1.6.1 Drugs
  • Benznidazole — first-line, ~ 60 days oral
  • Nifurtimox — alternative, ~ 90 days oral
  • Both target T. cruzi; less effective in chronic late disease
231.1.0.1.6.2 Indications for Treatment
  • Acute infection: all (high cure rate ~ 80-100%)
  • Recent infection including vertical (newborns): all
  • Chronic indeterminate < 18 yr: all
  • Chronic indeterminate 18-50 yr: shared decision (efficacy ~ 60-70%)
  • Chronic with mild-moderate cardiomyopathy 18-50 yr: shared decision
  • Chronic with advanced cardiomyopathy or > 50 yr: less benefit on outcomes (limited evidence — BENEFIT trial)
  • Pre-transplant chronic chagas patient
  • Pre-immunosuppression to reduce reactivation risk
  • HIV/immunosuppression with reactivation — treat
231.1.0.1.6.3 Side Effects
  • Benznidazole: dermatologic (rash 20-30%), peripheral neuropathy, marrow suppression
  • Nifurtimox: GI, weight loss, peripheral neuropathy, psychiatric
231.1.0.1.6.4 Reactivation Risk
  • HIV + low CD4
  • Transplant immunosuppression
  • Anti-TNF
  • Chemotherapy
  • Severe reactivation can cause myocarditis, meningoencephalitis — high mortality
  • Pre-treatment screening + monitoring required
231.1.0.1.7 Prevention
  • Vector control (insecticide spraying + housing improvements + bed nets)
  • Blood donor screening (Latin America + USA + Spain + others)
  • Maternal screening + treatment of infected mothers (prevent vertical)
  • Newborn screening + treatment (high cure if treated promptly)
  • No vaccine yet
231.1.0.1.8 Special
  • Chagas heart disease = leading cause of cardiomyopathy + heart transplant indication in Latin America
  • Transplant from Chagas donor — possible but PCR + treat recipient
  • Pre-immunosuppression screening in patients from endemic areas

231.1.0.2 1⃣ Microbiology + Life Cycle

231.1.0.2.1 Trypanosoma cruzi
  • Single species, multiple DTUs (TcI-TcVI) — different geographic + clinical patterns
  • Trypomastigote (extracellular, bloodstream) + amastigote (intracellular, tissue, no flagellum) forms
231.1.0.2.2 Life Cycle
  1. Triatomine bug bites human + defecates near wound
  2. Scratching rubs feces into wound or mucous membrane → trypomastigotes enter
  3. Trypomastigotes invade host cells (cardiac, GI, etc.) → become amastigotes
  4. Amastigotes multiply intracellularly
  5. Cell rupture → trypomastigotes released into bloodstream
  6. Bug takes blood meal → ingests trypomastigotes
  7. Multiply in bug → trypomastigotes in feces
231.1.0.2.3 Tropism
  • Cardiac muscle (key — explains cardiomyopathy)
  • GI smooth muscle + autonomic ganglia (explains megacolon/megaesophagus)
  • Reticuloendothelial system

231.1.0.3 2⃣ Acute Chagas

231.1.0.3.1 Inoculation
  • Site can be skin or eye
  • Most cases asymptomatic
231.1.0.3.2 Clinical Features
231.1.0.3.2.1 Skin Inoculation
  • Chagoma: erythematous nodule at bite site
  • Usually transient
  • May go unnoticed
231.1.0.3.2.2 Eye Inoculation (Romaña Sign)
  • Unilateral painless periorbital edema + conjunctivitis + ipsilateral preauricular LAP
  • Pathognomonic
  • Self-resolves weeks
231.1.0.3.2.3 Systemic
  • Fever (intermittent)
  • Lymphadenopathy
  • Hepatosplenomegaly
  • Mild myocarditis (10%)
  • Rare severe cases: meningoencephalitis, severe myocarditis (especially children, immunocompromise)
231.1.0.3.3 Severity
  • Mostly self-limited
  • Mortality < 5% in acute (typically severe myocarditis or meningoencephalitis)
  • 100% develop chronic without treatment
231.1.0.3.4 Diagnosis Acute
  • Direct microscopy of buffy coat or fresh blood — trypomastigotes
  • PCR — most sensitive
  • IgM serology
231.1.0.3.5 Treatment Acute
  • Benznidazole or nifurtimox × 60-90 days
  • High cure rate (80-100%)
  • Severe: + supportive

231.1.0.4 3⃣ Chronic Chagas

231.1.0.4.1 Indeterminate Stage
  • Years-decades asymptomatic
  • ~ 60-70% of chronic patients remain here lifelong
  • ECG + echo normal
  • Serology persistently positive
  • Low parasitemia (PCR may be negative or low)
231.1.0.4.2 Chronic Cardiomyopathy (~ 30% Develop)
231.1.0.4.2.1 Timeline
  • 10-30 years after acute
  • Progressive over decades
231.1.0.4.2.2 Clinical Stages (Modified Mexican Consensus 2024)
  • Stage A (Indeterminate): serology + only
  • Stage B1: ECG abnormalities (RBBB, LAFB), normal echo
  • Stage B2: echo abnormalities (LVEF preserved), conduction abnormalities
  • Stage C: HF symptoms + reduced LVEF
  • Stage D: refractory HF, advanced
231.1.0.4.2.3 Mechanisms
  • Direct parasite cardiomyocyte damage
  • Microvascular ischemia
  • Autonomic denervation
  • Immune-mediated injury
  • Fibrosis (subepicardial inferolateral pattern on MRI)
231.1.0.4.2.4 Complications
  • Arrhythmias: conduction blocks (often progressing), atrial fibrillation, ventricular tachycardia
  • Apical aneurysms of LV (40-50% of chronic CM)
  • Mural thrombus: stroke risk
  • Sudden cardiac death (VT/VF)
  • Heart failure progression
  • High mortality for advanced HF
231.1.0.4.3 Chronic Digestive (10-20% in Brazil/Southern Cone)
231.1.0.4.3.1 Megaesophagus
  • Loss of myenteric ganglia
  • Progressive dysphagia
  • Aspiration risk
  • Regurgitation, weight loss
  • Esophagitis
  • Squamous cell carcinoma risk increased
231.1.0.4.3.2 Megacolon
  • Chronic constipation
  • Fecal impaction
  • Volvulus (sigmoid)
  • Risk of perforation
231.1.0.4.3.3 Diagnosis
  • Esophagram (barium swallow)
  • Manometry
  • Colonoscopy / barium enema
231.1.0.4.3.4 Treatment
  • Pneumatic dilation (esophagus)
  • Heller myotomy (esophagus)
  • Surgery (megacolon — Hartmann, colectomy)

231.1.0.5 4⃣ Diagnosis Chronic Chagas

231.1.0.5.1 Serology (2 Tests Required)
  • Indirect Hemagglutination (IHA)
  • ELISA
  • IFA
  • Recombinant antigen tests
  • Discordant → 3rd test
  • WHO standard
231.1.0.5.2 PCR
  • Variable sensitivity in chronic (low parasitemia)
  • Useful for:
    • Acute reactivation
    • Vertical transmission monitoring
    • Post-treatment monitoring
231.1.0.5.3 Cardiac Workup (Once Diagnosed)
  • ECG annually + symptom-based
  • Echocardiogram
  • Cardiac MRI (advanced cases — fibrosis pattern)
  • Holter for arrhythmia
  • Exercise testing
  • Cardiopulmonary stress
231.1.0.5.4 GI Workup
  • Esophagram if dysphagia
  • Manometry
  • Colonoscopy / barium enema if constipation

231.1.0.6 5⃣ Treatment Chronic Chagas

231.1.0.6.1 Goal
  • Reduce parasite burden
  • Prevent / slow progression
  • BENEFIT trial 2015: benznidazole vs placebo in established cardiomyopathy
    • PCR negativization improved with drug
    • No mortality benefit in advanced chronic CM
  • Most benefit in early chronic before cardiomyopathy develops
231.1.0.6.2 Treatment Indications
Population Treat?
Acute infection Yes (cure ~ 80-100%)
Recent infection (incl vertical newborn) Yes
Chronic indeterminate < 18 yr Yes (efficacy higher in younger)
Chronic indeterminate 18-50 yr Shared decision (efficacy 60-70%)
Chronic mild-moderate cardiomyopathy 18-50 yr Shared decision
Advanced cardiomyopathy or > 50 yr Limited mortality benefit (BENEFIT trial)
HIV / Immunosuppression / Pre-immunosuppression Yes (prevent reactivation)
Pre-organ transplant Yes
Reactivation Yes
Pregnancy + newborn Treat newborn, not pregnant; postpartum mother
231.1.0.6.3 Drugs
231.1.0.6.3.1 Benznidazole
  • 5-7 mg/kg/day PO divided × 60 days
  • First-line in most settings
  • Side effects:
    • Dermatologic (rash 20-30%, sometimes severe Stevens-Johnson)
    • Peripheral neuropathy (dose-dependent)
    • Marrow suppression
    • GI
231.1.0.6.3.2 Nifurtimox
  • 8-10 mg/kg/day PO divided × 90 days
  • Alternative if benznidazole intolerance
  • Side effects:
    • GI (nausea, vomiting, weight loss)
    • Peripheral neuropathy
    • Psychiatric (insomnia, agitation)
231.1.0.6.4 Cardiomyopathy Management
  • ACEi/ARB, beta-blockers, MRA (standard HF)
  • Pacemaker for conduction disease
  • ICD for sudden death prevention
  • Anticoagulation for atrial fibrillation or LV thrombus
  • Heart transplant for refractory HF
  • 通報 in many countries

231.1.0.7 6⃣ Reactivation in Immunocompromise

231.1.0.7.1 Risk Factors
  • HIV + low CD4 (< 200; especially < 100)
  • Organ transplant (immunosuppression)
  • Anti-TNF (rheumatologic, IBD)
  • Chemotherapy
  • Steroid high-dose long-term
231.1.0.7.2 Clinical
  • Severe acute-like presentation
  • Myocarditis (acute)
  • Meningoencephalitis (severe, often fatal)
  • Skin nodules
  • High parasitemia
231.1.0.7.3 Diagnosis
  • PCR in blood (sensitive in reactivation)
  • Direct microscopy (visible parasitemia)
  • Tissue biopsy
231.1.0.7.4 Treatment
  • Benznidazole or nifurtimox
  • Reduce immunosuppression if possible
  • Supportive
231.1.0.7.5 Prevention
  • Pre-immunosuppression screening for Chagas serology in patients from endemic areas
  • Treat seropositive before immunosuppression when possible
  • Monitor on therapy with PCR

231.1.0.8 7⃣ Prevention + Public Health

231.1.0.8.1 Vector Control
  • Insecticide spraying indoor (deltamethrin)
  • Housing improvement (plaster walls, replace thatched roofs)
  • Bed nets in some settings
  • Southern Cone Initiative — eliminated vector transmission in some areas
231.1.0.8.2 Blood Donor Screening
  • Latin America countries since 1990s
  • USA mandatory since 2007
  • Reduces transfusion-transmitted dramatically
231.1.0.8.3 Maternal Screening
  • WHO recommendation: all pregnant women from endemic areas
  • Treat seropositive postpartum (not during pregnancy)
  • Newborn screening + treat if positive
231.1.0.8.4 Newborn Treatment
  • Very high cure rate (90%+ in newborns)
  • Benznidazole 5 mg/kg/d × 60 d
231.1.0.8.5 Travelers
  • Avoid sleeping in adobe/thatched-roof structures in endemic
  • Insecticide treated bedding
231.1.0.8.6 USA + Europe Migration
  • USA: ~ 300,000 chronic Chagas
  • Spain: ~ 70,000 (largest non-endemic country)
  • Italy, Japan, Australia significant populations
  • Surveillance + screening + treatment
231.1.0.8.7 No Vaccine
  • Several candidates in research
  • Not near clinical use
231.1.0.8.8 WHO 2030 Goal
  • Elimination of Chagas as public health problem
  • Vertical transmission elimination