Chagas disease

Chagas disease (American trypanosomiasis) is an infectious disease caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), which is typically transmitted by triatomine bugs of the Reduviid family. Chagas disease is endemic to Central and South America and most cases that occur in the US are reported in immigrants from endemic regions. Patients present initially with fever, swelling at the site of inoculation of triatomine feces, and generalized lymphadenopathy. These symptoms resolve within a few weeks, and the patient enters an asymptomatic latent phase, which may last for 10–20 years. Eventually, 10–30% of all infected patients enter a chronic phase and develop symptoms of Chagas cardiomyopathy and/or gastrointestinal disease characterized by achalasia and progressive dilation of the colon. The disease is diagnosed by thin and thick peripheral smears in the acute phase and by serological tests in the chronic phase. Chagas disease patients are treated with the antitrypanosomal drugs benznidazole and nifurtimox. Supportive therapy is required for Chagas cardiomyopathy and gastrointestinal disease. Treatment of Chagas disease is most effective when initiated early (in the acute phase).

• Global statistics
  • Prevalence: 8–10 million infected individuals; endemic in Central and South America
• Prevalence in the US: > 300,000 infected individuals

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: : Trypanosoma cruzi
• Route of infections
  • Vector transmission
    • Numerous triatomine species of the Reduviidae family (also called kissing bug because it typically bites around the mouth)
    • T. cruzi is shed in the feces of the reduviid bug; feces is then rubbed into the bite site while scratching.
  • Contaminated food and drinks ^[1][2]
  • Transplacental transmission from the mother to the fetus
  • Blood transfusion, solid organ transplantation

• Life cycle of T. cruzi in the triatomine insect
  1. Ingestion of the trypomastigote form of T. cruzi by the triatomine insect occurs during a blood meal.
  2. Transformation of the trypomastigotes into epimastigotes in the midgut and transformation of epimastigotes into metacyclic trypomastigotes in the hindgut occurs after 8–10 days.
  3. Metacyclic trypomastigotes are shed in feces.
• Life cycle of T. cruzi in the human host
  1. Metacyclic trypomastigotes enter cells that are located in the vicinity of the wound site and/or mucosal membranes (e.g. conjunctiva).
  2. Within the cells, the metacyclic trypomastigote is converted into an amastigote, which then multiplies within the infected cell by binary fission.
  3. Intracellular amastigotes transform into trypomastigotes
  4. Both trypomastigotes and amastigotes are released into the blood stream by lysis of the infected cell.
  5. Trypomastigotes can reinfect host cells and perpetuate the cycle within the host.
     • The parasite causes immune-mediated tissue damage as a result of cross-reaction with T. cruzi antigens.

• Incubation period: 1–2 weeks
• Acute phase (acute American trypanosomiasis): lasts ∼ 8–12 weeks
  • Fever, malaise, loss of appetite
  • Cutaneous manifestations
    • Chagoma: inflammatory edema at the bite site (usually in the face)
    • Romana sign: unilateral painless edema of the eyelids and periocular tissue
  • Generalized lymphadenopathy and hepatosplenomegaly
  • Rarely (∼ 1% of cases): myocarditis, meningoencephalitis
• Indeterminate phase
  • Patient enters an asymptomatic latent phase.
  • Patients in the indeterminate phase are serologically positive but do not develop signs and symptoms associated with the chronic phase.
• Chronic phase (chronic American trypanosomiasis): develops after ∼ 10–20 years
  • Chagas cardiomyopathy
    • Conduction disorders: right bundle branch block (RBBB)
    • Biventricular dilative cardiomyopathy → heart failure
    • Atrophy of the apex, which may lead to ventricular aneurysm
    • Mural thrombi → stroke
  • Gastrointestinal tract
    • Damage to the submucosal and myenteric plexus → inability to relax lower esophageal sphincter and impaired gut motility → progressive dilation of the esophagus and colon
      • Megaesophagus and achalasia: dysphagia, weight loss, regurgitation
      • Megacolon: abdominal pain, chronic constipation

• Confirmatory tests
  • Acute phase
    • Best initial test: direct visualization of T. cruzi trypomastigotes in thin and thick peripheral blood smears using a Giemsa stain
    • PCR to detect T. cruzi DNA
  • Indeterminate and chronic phase: serological assays to detect IgG antibodies against T. cruzi
• Additional tests
  • Regular ECG monitoring
    • Patients with symptoms or ECG signs of Chagas cardiomyopathy → see “Diagnostics of dilated cardiomyopathy”
  • Patient with symptoms of GI involvement: barium radiography, endoscopy, and manometry (also see “Diagnostics” in achalasia)

Chagas disease should be suspected in immigrants from endemic regions.

Antitrypanosomal therapy

Treatment against Chagas disease is most effective when initiated early (in the acute phase).

• First-line: benznidazole (generates free radicals that cause DNA damage in the parasite)
• Second-line: nifurtimox

Chagas disease is caused by the kissing bug and treated with nifurtimox or Benznidazole: “I'm blowing charming kisses from my nifty Benz.”

Supportive therapy

• Chagas cardiomyopathy
  • See “Therapy of dilated cardiomyopathy.”
  • Patients with severe cardiomyopathy: heart transplantation

• Gastrointestinal disease
  • Megaesophagus: see “Therapy” in achalasia
  • Megacolon
    • High fiber diet with adequate fluid intake, laxatives, and/or rectal enemas to treat constipation
    • Patients with persistent constipation, fecalomas, sigmoid volvulus: rectosigmoidectomy (with either retrocecal interpositioning or end-to-side low colorectal anastomosis)

• Instructions for people traveling to or working in endemic regions
  • Use insect repellents and insecticide-treated bed nets.
  • Avoid sleeping in poorly constructed houses with thatched roofs and cracked walls.
• Public health measures
  • Screening of blood donors
  • Screening of neonates born to infected mothers
  • Vector control methods such as insecticide spraying and reduviid-proof housing
  • Food hygiene

No vaccination against T. cruzi is available and chemoprophylaxis is not recommended!