Trypanosoma cruzi

Microbiology

• Protozoan parasite that causes Chagas disease (South American trypanosomiasis)

Life Cycle

T. cruzi Lifecycle

Epidemiology

• Endemic throughout the Americas from the southern half of the United States to Argentina
  • Particularly in rural, impoverished areas
  • A small number of autochthonous cases of Chagas disease in the US
• Reservoirs include armadillos, opossums, raccoons, woodrats, some other rodents, and domestic dogs
• Triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus
  • Bugs live in substandard dwellings (especially wood, mud, or stone houses)
  • Vector is present from southern US to southern Argentina
  • Transmission is via feces, either in direct contact with mucous membranes (especially conjunctivae), breaks in the skin, or contaminating the bite of the insect
• Can also be transmitted via blood transfusion or vertically from mother to child or via ingestion of contaminated food and drink

Pathophysiology

• Infective metacyclic trypomastigotes from feces enter the skin or mucosa
• Multiply in host cells as amastigotes, developing into trypomastigotes intracellularly and rupturing the cell, releasing more trypomastigotes
  • Chagoma develops at site of inoculation
  • Intracellular amastigotes visible as characteristic pseudocysts on histopathology
• Hematogenous spread to distant sites, especially muscles, with the cycle repeating
  • Especially tropic for myocardium, where it causes biventricular enlargement, thinning of ventricular walls, apical aneurysms, and mural thrombi
• Parasitemia maintained for years

Clinical Presentation

Acute disease

• Often asymptomatic
• Incubation period of about 1 week
• Usually mild febrile illness, sometimes with hepatosplenomegaly, rash, edema, local inflammation
  • Incurs in 20% of infections
  • More common in children
• Nodular lesions ("chagomas") may develop at site of inoculation
  • Romaña sign if periorbital, often with ipsilateral lymphadenopathy
  • Often 1-2 weeks after exposure
• Acute myocarditis, pericardial effusion, and meningoencephalitis in 1-5%

Indeterminate phase

• Following acute infection, may enter a latent phase

Chronic disease

• Following acute infection can remain asymptomatic (indeterminate form)
• Cardiac complications in 25-30% (1.5-5% per year)
  • Non-ischemic dilated biventricular (right more than left) cardiomyopathy with heart failure
  • Apical aneurysms and mural thrombi
  • Conduction defects, with heart blocks, bundle branch blocks, sinus node dysfunction, bradycardia, and ventricular arrhythmias
  • Can cause sudden cardiac death
• GI involvement in 10-15%
  • Megaesophagus, with dysphagia, odynophagia, chest pain, cough, and regurgitation
    • May result in aspiration and recurrent pneumonias
  • Megacolon, with constipation and abdominal pain
• Meningoencephalitis
• Other: polyneuropathy, stroke syndrome

Immunocompromised patients

• May have reactivation following immune suppression or HIV
• Severe acute infection; may have skin lesions and cerebral masses/abscesses
• Meningoencephalitis

Diagnosis

Acute disease

• Direct microscopy blood film or tissue biopsy (e.g. lymph node, bone marrow, pericardial fluid, CSF)
  • In immunocompromised, these other samples are even more important
• Hemoculture is only 50% sensitive and takes several weeks
• Serology for IgM is useless
• PCR is sensitive and specific
• Xenodiagnosis

Indeterminate and chronic disease

• No gold standard
• Serology for IgG is most useful
  • Detectable after 6 to 9 months following infection
  • Many assays (ELISA, indirect hemagglutination, chemiluminescence, and IFA)
• PCR (of blood) less sensitive

Management

Acute

• Treatment is most useful in acute disease, congenital Chagas, and children with chronic infection up to 18 years
  • It can decrease illness severity and mortality
  • Start ASAP before infection can become established
  • However, treatment may not result in parasitologic cure
• Treatment options
  • Nifurtimox: 90-120 day treatment course; AEs include anorexia, weightloss, neurologic symptoms
  • Benznidazole: 60 day treatment course; AEs include hypersensitivity, GI upset, rare polyneuropathy and agranulocytosis
• Adverse events are common during treatment

Chronic

• Less clear benefit to antiparasitic treatment
• Cardiac disease
  • May benefit from pacemaker in patients with conduction disease
    • Monitor with ECG q6mo
  • May need heart transplantation, though this can become complicated by ongoing chronic infection or recrudescence
• Megaesophagus: balloon dilatation or surgical management
• Megacolon may need surgical management

Prevention

• Screening immigrants and then following up with regular cardiac screening, if positive
• Avoid sleeping in dilapidated dwellings in endemic countries, use insect repellent and bed nets
• Improve housing in endemic areas

Canadian Blood Services

• Samples are only tested for antibodies when increased risk is present, determined by the donor screening questions
• No reported cases since screening began in 2010