American Trypanosomiasis

Aka: American Trypanosomiasis, Chagas Disease, Trypanosoma cruzi, Rowana's Sign

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II. Epidemiology

  1. Endemic Regions (tropical Americas)
    1. Mexico
    2. Central America
    3. South America
    4. Southern Texas
  2. Prevalence (estimated)
    1. Endemic regions: 8-11 Million infected
    2. United States: 300,000 infected
      1. Most cases are via immigration and travel
      2. However vector-borne transmission has occurred in Southern U.S.
      3. Bern (2011) Clin Microbiol Rev 24(4): 655-81 [PubMed]

III. Pathophysiology

  1. Organism
    1. Protozoa: Trypanosoma cruzi
    2. African Trypanosomiasis (African Sleeping Sickness) is also caused by a Trypanosome
      1. However, African Trypanosomiasis differs greatly in its manifestations from American Trypanosomiasis
  2. Wild animal reservoirs (in addition to humans)
    1. Rodents
    2. Opossums
    3. Armadillos
  3. Transmission: Vector borne (primary source)
    1. Triatomine bug (reduviid bug, assassin bug or kissing bug) is an Insect that feeds on blood
      1. Triatomine bugs nest in the crevices of mud and clay houses
      2. Triatomine bugs are nocturnal and feed on humans as they sleep
      3. Acquires T. cruzi via ingested blood containing the Parasite as trypomastigote
      4. Trypomastigotes differentiate inside the Insect midgut into epimastigotes which further multiply
      5. Epimastigotes differentiate into the infective form, metacyclic trypomastigotes
    2. Insect carrying the Parasite defecates into a human wound site or mucous membranes (e.g. Conjunctiva)
      1. Parasite is initially transmitted from Insect to human via Insect feces as metacyclic trypomastigote
      2. Metacyclic trypomastigotes differentiate into amastigotes on human cell penetration
        1. Metacyclic trypomastigotes are motile with a flagellum and undulating membrane
        2. Amastigotes are rounded forms, without flagella
      3. Amastigotes multiply via binary fission
        1. Releases trypomastigotes to infect other human cells (Macrophages, Lymph Nodes)
        2. Spreads via blood to distant organs
  4. Transmission: Other mechanisms
    1. Congenital (vertical transmission)
      1. U.S. congenital infections per year: 300
    2. Blood Transfusion
      1. U.S. Blood supply is screened for Trypanosoma cruzi since 2007
    3. Organ transplant
    4. Contaminated food
    5. Lab exposure

IV. Findings: Acute Phase

  1. Often asymptomatic
  2. Duration: 4-8 weeks after infection
  3. Chagoma
    1. Forms at skin Parasite entry site
    2. Hard, red, firm skin with Localized Edema
  4. Rowana's Sign (20-50% of acute cases)
    1. Painless unilateral eye swelling
  5. Non-specific febrile illness (variably present)
    1. Fever
    2. Malaise
    3. Headache
    4. Anorexia
    5. Lymphadenopathy
    6. Non-pruritic rash
  6. Severe manifestations
    1. Persistent Sinus Tachycardia or other Arrhythmia
    2. Severe meningoencephalitis (esp. young patients)

V. Findings: Chronic Phase

  1. Onset weeks to months after infection
    1. Follows an asymptomatic intermediate phase (low level Parasitemia and Antibody formation)
  2. Life-long infection until treated
  3. Asymptomatic in 70-80% of cases
  4. Serious chronic manifestations occur in 20-30% of cases
    1. See Complications below

VI. Complications

  1. Cardiac
    1. Conduction abnormalities
      1. Heart Block risks
      2. Ventricular Tachycardia risk
    2. Apical aneurysm
    3. Dilated Cardiomyopathy or Congestive Heart Failure (late finding)
    4. Thromboembolism
    5. Pericardial Effusion
  2. Gastrointestinal
    1. Megaesophagus
    2. Toxic Megacolon
  3. Neurologic
    1. Cerebrovascular Accident risk
  4. Infants with congenital infection (vertical transmission from mother)
    1. Often asymptomatic
    2. IUGR with low birth weight in some cases
    3. Low APGAR Scores at birth
    4. Anemia
    5. Thrombocytopenia
    6. Hepatomegaly
    7. Splenomegaly
    8. Myocarditis (rare)
    9. Meningoencephalitis (rare)

VII. Labs

  1. Acute infection
    1. Peripheral Smear (Light Microscopy)
      1. Peripheral blood (or anticoagulated cord blood) for trypomastigotes
    2. Polymerase chain reaction (PCR)
      1. Highly specific and may be positive before Peripheral Smear demonstrates organisms
  2. Chronic infection
    1. Organism counts too low in chronic disease to be detectable by Peripheral Smear or PCR
    2. Serology tests for T. cruzi
      1. Positive on at least two different Serologic Tests (insufficient efficacy of any individual test)
      2. Enzyme-linked immunosorbent assay (ELISA)
      3. Immunofluorescent Antibody assay
    3. Adjunctive diagnostic modalities
      1. Echocardiogram (for Heart Failure)
      2. Electrocardiogram (for Arrhythmia)
      3. Upper endoscopy (for megaesophagus)

VIII. Diagnostics

  1. Electrocardiogram
    1. Obtain at time of diagnosis and as needed

IX. Management: Antiparasitic

  1. Protocol
    1. Treat immediately if not contraindicated
    2. Course of Antiparasitic Agent treatment is 60-90 days
    3. Perform physical exam to evaluate for end-organ involvement
    4. Electrocardiogram
  2. Contraindications to Antiparasitic therapy
    1. Pregnancy
    2. Severe hepatic insufficiency
    3. Severe Renal Insufficiency
  3. Indications: Acute Chagas Disease
    1. Treat all acute Chagas Disease cases (if not contraindicated)
    2. Treat congenitally acquired Chagas Disease
    3. Treat Immunocompromised patients with reactivated Chagas Disease
  4. Indications: Chronic Chagas Disease
    1. Chronic Chagas Disease is far less responsive to treatment than acute Chagas Disease
    2. All patients under age 18 years old with chronic Chagas Disease
    3. Patients under age 50 years old with chronic Chagas Disease and no advanced Cardiomyopathy
    4. Patients over age 50 years have had longterm infection that is unlikely to be cured with medication
    5. Consult CDC or infectious disease for management recommendations regarding specific case management
  5. Medications (available in U.S. through CDC)
    1. Contraindications (see above)
      1. Pregnancy and Lactation
      2. Severe renal dysfunction
      3. Severe liver dysfunction
    2. Only two agents have proven efficacy
      1. Benznidazole
        1. FDA approved for ages 2-12 years old
      2. Nifurtimox (Lampit)
        1. FDA approved from birth to 18 years (weight >5 lb 8 oz or 2.5 kg)
  6. Adverse effects from treatment agents
    1. Weight loss
    2. Anorexia
    3. Polyneuropathy or Peripheral Neuropathy
    4. Rash
    5. Nausea

X. Management: Complications

  1. Congestive Heart Failure
    1. See Congestive Heart Failure Exacerbation Management
    2. Exercise caution with Beta Blockers (higher risk of Bradycardia)
  2. Atrial Arrythmias
    1. Cardiac Pacemaker (Heart Block, Sick Sinus Syndrome)
  3. Ventricular Arrhythmias (e.g. Ventricular Tachycardia)
    1. Amiodarone
    2. Catheter ablation and placement of IACD
  4. Thromboembolism risk
    1. Consider antithrombotic therapy

XI. Screening

  1. U.S. Immigrants from Mexico, Central America or South America
  2. Children of mothers with Chagas Disease
  3. Blood donors in U.S.

XII. Prevention

  1. Blood donors in the United States are screened for T cruzi (since 2007)
    1. Not allowed to donate blood if positive
  2. Endemic area strategies
    1. Clean rooms
    2. Mosquito nets
    3. Insecticides

XIII. Resources

  1. CDC Trypanosomiasis
    1. http://www.cdc.gov/parasites/chagas/

XIV. References

  1. Gladwin, Trattler and Mahan (2014) Clinical Microbiology, Medmaster, Fl, p. 349-51
  2. Wang and Nguyen (2017) Crit Dec Emerg Med 31(9):13-8
  3. Bern (2007) JAMA 298(18): 2171-81 [PubMed]
  4. Cantey (2021) Am Fam Physician 104(3): 277-87 [PubMed]
  5. Rassi (2010) Lancet 375(9723): 1388-1402 [PubMed]
  6. Woodhall (2014) Am Fam Physician 89(10): 803-11 [PubMed]

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