Trypanosoma cruzi/Chagas disease

Chagas disease is an infection caused by the American trypanosome Trypanosoma cruzi. This parasitic protozoan is transmitted in the feces of reduviid bugs in South and Central America. Acute infection may present with inflammation at the inoculation site (chagoma), fever, and lymphadenopathy. Untreated, chronic infection can progress to severe complications, including megacolon, megaesophagus, and cardiomyopathy. The diagnosis can be confirmed with identification of organisms on blood smear, serology, or PCR. Treatment with benznidazole or nifurtimox is effective only in the acute phase.

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General Characteristics and Epidemiology

Basic features of Trypanosoma cruzi

  • Parasitic protozoan
  • Taxonomy:
    • Family: Trypanosomatidae
    • Genus: Trypanosoma
  • General characteristics:
    • Thin, irregularly shaped
    • Single, polar flagellum
    • Undulating membrane
  • Morphologic forms:
    • Epimastigote (extracellular, noninfectious form)
    • Trypomastigote (infectious form)
    • Amastigote (intracellular form that replicates)

Associated disease

American trypanosomiasis is called Chagas disease.

Epidemiology

  • Geographic distribution:
    • South America
    • Central America
  • Prevalence: Approximately 8 million people are infected.
    • Previously, more prevalent in rural communities
    • Infections are becoming more widespread because of migration.
  • Morbidity is higher in children.

Pathogenesis

Reservoir

  • Humans
  • Domesticated and wild mammals

Transmission

  • Primarily vector-borne: triatomine bugs (reduviid bug or “kissing bug”)
  • Less common:
    • Blood transfusion
    • Organ transplantation
    • Ingestion of contaminated food or drink
    • Vertical
    • Laboratory exposure
A species of Triatoma Trypanosoma cruzi Chagas disease

A species of Triatoma, or kissing bug:
The kissing bug serves as a vector to transmit the protozoan pathogen Trypanosoma cruzi, which causes Chagas disease.

Image: “A species of Triatoma, or kissing bug” by CDC. License: Public Domain

Host risk factors

  • Living in an endemic region
  • Poor housing conditions
  • Prolonged exposure to vectors

Life cycle and pathophysiology

  • Reduviid bug feeds on an infected human or mammal host → bug becomes infected with trypomastigotes
  • Transform into epimastigotes in the midgut → replicate 
  • Differentiate into trypomastigotes in the hindgut
  • During a blood meal on a human host, bug defecates
  • Trypomastigote entry into the host occurs through contact of infected feces with:
    • Bug bite wound
    • Conjunctiva
    • Mucous membranes
  • Invasion of cells at the site of inoculation → become intracellular amastigotes → asexual replication (binary fission)
  • Differentiation into trypomastigotes → disseminate through the bloodstream to other organs
  • Immune reaction → tissue damage
  • Chronic dissemination of T. cruzi is associated with:
    • Fibrosis of cardiac tissue → cardiomyopathy
    • Fibrosis involving cardiac conduction pathways → arrhythmias
    • Invasion of nerve plexuses (often GI tract) → megaesophagus and megacolon
Life cycle American trypanosome Trypanosoma cruzi Chagas disease

Life cycle of the American trypanosome Trypanosoma cruzi:
During a blood meal, the reduviid bug will defecate. Scratching the area allows entry of parasites through the bite wound or conjunctiva.
Once inside the body, replication and dissemination occurs. There is particular preference for myocardium and myenteric plexus.
With chronic infection, tissue damage can lead to cardiomyopathy, megacolon, and megaesophagus.

Image by Lecturio.

Clinical Presentation

Acute infection

The incubation period is approximately 1–2 weeks, and the infection lasts 8–12 weeks.

  • Many patients are asymptomatic.
  • Inflammation and pruritus may occur at the site of inoculation
    • Chagoma: 
      • Subcutaneous inflammatory nodule
      • Typically on the face or extremities
    • Romaña’s sign: 
      • Unilateral swelling of the eyelid secondary to chagoma
      • Occurs when the conjunctiva is the site of inoculation
  • Nonspecific signs and symptoms:
    • Fever
    • Malaise
    • Anorexia
    • Lymphadenopathy
  • Severe disease (↑ risk of mortality):
    • Myocarditis
    • Pericardial effusion
    • Meningoencephalitis
Chagas disease infection with swelling of the right eye Trypanosomes

Photograph of a patient with acute Chagas disease infection with swelling of the right eye (Romaña’s sign).

Image: “An acute Chagas disease infection with swelling of the right eye (Romaña’s sign)” by CDC. License: Public Domain

Chronic infection

A minority of patients develop chronic infection, which presents 10–20 years after the initial inoculation period. 

  • Chronic Chagas cardiomyopathy (primary cause of mortality)
    • Enlargement of all chambers → biventricular heart failure
    • Apical aneurysm → thromboembolism
    • Conduction abnormalities
      • Left anterior fascicular block
      • Right bundle branch block
      • Atrioventricular block
      • Ventricular arrhythmias
  • Megaesophagus 
    • Dysphagia
    • Regurgitation
    • Recurrent aspiration → aspiration pneumonia
    • Malnutrition
  • Megacolon
    • Obstipation
    • Bloating
    • Volvulus → bowel ischemia
    • Malnutrition

Congenital disease

Congenital disease occurs in a minority of infants born to infected mothers.

  • Low birth weight
  • Fever
  • Hepatosplenomegaly
  • Anemia

Diagnosis and Management

Diagnosis

Confirmatory tests:

  • Blood smear visualization of trypomastigotes using Giemsa stain
  • Serology for antibodies
    • ELISA
    • Indirect fluorescent antibody (IFA)
  • PCR for parasitic DNA
  • Xenodiagnosis
    • Uninfected reduviid bugs take a blood meal from the patient.
    • The bug is later examined for the presence of T. cruzi.

Supporting evaluation:

  • ECG showing conduction abnormalities
  • Chest X-ray with cardiomegaly
  • Echocardiography to evaluate for chamber enlargement and ventricular dysfunction
  • Esophageal and colon dilation can be evaluated with:
    • Barium esophagography or colonic enema
    • Esophageal or anorectal manometry
    • Endoscopy or colonoscopy

Management

Acute infection:

  • Benznidazole
  • Nifurtimox

Chronic disease:

  • Effective treatments are limited.
  • Antitrypanosomal drugs are less effective in chronic infections.
  • Focus is on management of irreversible complications:
    • Cardiomyopathy:
      • General heart failure management
      • Consider cardiac transplantation
      • Pacemaker for high-degree atrioventricular block
    • Megaesophagus management is aimed at ↓ the lower esophageal sphincter tone:
      • Nifedipine or isosorbide
      • Pneumatic dilation
      • Surgery
    • Megacolon:
      • High-fiber diet
      • Hydration
      • Laxatives
      • Enemas
      • Suppositories
      • Manual disimpaction, as needed
      • Surgery

Prevention

  • Vector control with insecticides
  • Bug nets
  • Screen blood and organ donors in endemic regions
  • Screen and treat women prior to pregnancy

Comparison of Flagellated Protozoa

Table: Comparison of clinically relevant flagellated protozoa
GiardiaLeishmaniaTrypanosomaTrichomonas
Characteristics
  • 4 pairs of flagella
  • Ovoid shape
  • Adhesive disc
  • Anaerobe
  • Antigenic variation
  • Single, polar flagellum
  • Slender, elongated body
  • Single, polar flagellum
  • Undulating membrane
  • Thin, irregularly shaped
  • Antigenic variation
  • 5 flagella
  • Undulating membrane
  • Ovoid shape
  • Facultative anaerobe
Forms
  • Cyst
  • Trophozoite
  • Promastigote
  • Amastigote
  • Trypomastigote
  • Amastigote
  • Epimastigote
  • Trophozoite
  • No cyst form
Transmission
  • Waterborne
  • Fecal–oral
  • Vector (sandfly)
  • Human to human
  • Zoonotic (rodents, dogs, foxes)
  • Vector (tsetse fly, kissing bug)
  • Blood transfusion
Sexually transmitted
ClinicalGiardiasisLeishmaniasis
  • African sleeping sickness
  • Chagas disease
Trichomoniasis
Diagnosis
  • ELISA
  • Direct fluorescent antibody (DFA)
  • Nuclear acid amplification test (NAAT)
  • Stool microscopy
  • Blood smear
  • Biopsy
  • PCR
  • Leishmanin skin test
  • Antibody titers
  • Blood smear
  • Antibody titers
  • Xenodiagnosis
  • Microscopy of vaginal secretions
  • NAAT
  • Urine or urethral swab culture
Treatment
  • Metronidazole
  • Tinidazole
  • Nitazoxanide
Depends on the clinical syndrome:
  • Amphotericin B
  • Pentavalent antimonials
  • Miltefosine
Depends on the clinical disease:
  • Suramin
  • Pentamidine
  • Melarsoprol
  • Eflornithine
  • Nifurtimox
  • Benznidazole
  • Metronidazole
  • Tinidazole
Prevention
  • Handwashing
  • Water treatment
  • Insecticide
  • Insect repellent
  • Protective clothing
  • Insecticides
  • Insect repellent
  • Bed nets
  • Protective clothing
  • Treatment of sex partners
  • Condoms

Differential Diagnosis

  • African trypanosomiasis: infection caused by Trypanosoma brucei and transmitted by the tsetse fly. Signs and symptoms include a trypanosomal chancre, fever, lymphadenopathy, facial swelling, and erythematous rash. CNS involvement is associated with “sleeping sickness” syndrome. The diagnosis is confirmed with identification of organisms in a fluid sample (e.g., blood, CSF). Management depends on the stage of disease and can include pentamidine, suramin, eflornithine, or melarsoprol.
  • Achalasia: primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. Achalasia results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia with solids and liquids along with regurgitation. Diagnosis is established by high-resolution manometry. Management options include pneumatic balloon dilation, surgical myotomy, and botulinum toxin injection. 
  • Large bowel obstruction: interruption in the normal flow of intestinal contents through the colon and rectum. This obstruction may be mechanical (due to actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis, also known as pseudo-obstruction). Typical symptoms include intermittent lower abdominal pain, abdominal distention, and obstipation. Diagnosis is established with imaging. Mechanical large bowel obstruction requires surgery in most cases.
  • Toxic megacolon: complication of severe colitis, frequently associated with Clostridium difficile, inflammatory bowel disease, or ischemic colitis. Patients with toxic megacolon present with severe abdominal distention and pain with associated systemic toxicity (fever, tachycardia, and altered mental status). The diagnosis is established with the history, physical findings, and imaging. Treatment depends on the cause, but can include supportive care and surgery.
  • Leishmaniasis: infection caused by Leishmania species, which are obligate intracellular parasites transmitted by the sandfly. The mildest form is cutaneous leishmaniasis, characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction and deformities. Visceral leishmaniasis (VL) presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Management is based on clinical severity. Systemic treatment (amphotericin B) is needed for VL.
  • Malaria: mosquito-borne infectious disease caused by Plasmodium species. Malaria often presents with fever, rigors, diaphoresis, jaundice, abdominal pain, hemolytic anemia, hepatosplenomegaly, and renal impairment. A blood smear shows a single pleomorphic ring. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs.

References:

  1. Riedel, S., Jawetz, E., Melnick, J. L., Adelberg, E. A. (2019). Jawetz, Melnick & Adelberg’s Medical Microbiology. New York: McGraw-Hill Education, pp. 730–733.
  2. Bern, C. (2021). Chagas disease: dpidemiology and prevention. UpToDate, Retrieved May 3, 2021, from https://www.uptodate.com/contents/chagas-disease-epidemiology-and-prevention
  3. Bern, C. (2020). Chagas disease: acute and congenital Trypanosoma cruzi infection. In Baron, E.L. (Ed.), UpToDate. Retrieved May 17, 2021, from https://www.uptodate.com/contents/chagas-disease-acute-and-congenital-trypanosoma-cruzi-infection
  4. Bern, C., and Marin-Neto, J.A. (2020). Chagas disease: Chronic Trypanosoma cruzi infection. In Baron, E.L., and Yeon, S.B. (Eds.), UpToDate. Retrieved May 17, 2021, from https://www.uptodate.com/contents/chagas-disease-chronic-trypanosoma-cruzi-infection
  5. Nguyen, T., Waseem, M. (2021). Chagas disease. StatPearls. Retrieved May 17, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK459272/
  6. Le, T., Sochat, M., Chavda, Y., Kalani, M., Kallianos, K., Zureick, A. (2017). First AID for the USMLE Step 1. New York: McGraw-Hill Education, pp. 154, 297, and 360.
  7. Pearson, R.D. (2020). Chagas disease. MSD Manual Professional Version. Retrieved May 17, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/extraintestinal-protozoa/chagas-disease
  8. Centers for Disease Control and Prevention (2019). Parasites—American trypanosomiasis (also known as Chagas disease). Retrieved May 18, 2021, from https://www.cdc.gov/parasites/chagas/

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