Microbiology and Pathology

Trypanosoma cruzi causes Chagas disease (American trypanosomiasis) and is transmitted among mammalian hosts by blood-sucking triatomine bugs. Organisms disseminate through the bloodstream, preferentially infecting cardiac, skeletal, and smooth-muscle cells.

Epidemiology

T. cruzi is found exclusively in the Americas and causes disease mostly among the poor in rural areas of Mexico and Central and South America; however, given rapid urbanization and migration, the distribution of cases is extending to cities. An estimated 5.7 million people are infected, including >1 million individuals with chronic cardiomyopathy.

Clinical Manifestations

Acute infection resolves spontaneously-without treatment-in 5-10% of pts infected with T. cruzi; otherwise, pts develop chronic infection, with 30-40% sustaining detectable organ damage of variable severity.

• Acute disease develops 1-2 weeks after a bite by the triatomine bug, with >90% of individuals remaining asymptomatic or having a mild febrile illness. Local swelling develops at the inoculation site and is referred to as a chagoma if on the skin or as Romaña's sign if on the eyelid. Disease resolves spontaneously within 4-8 weeks.
• Chronic disease is indeterminate until there are clinically apparent complications (the determinate form of chronic disease), which generally present as cardiac and/or digestive disorders years to decades after the initial infection. Symptoms include dyspnea, chest pain, palpitations, syncope, sudden death, stroke, dysphagia, regurgitation, constipation, fecaloma, volvulus, and peripheral neuropathy. The 5-year mortality rate is as high as 63% and is typically related to cardiac issues.
• Immunosuppressed pts may develop reactivation of acute disease, which can present as myocarditis, erythema nodosum, panniculitis, Toxoplasma-like focal brain lesion, or meningoencephalitis.

Diagnosis

Microscopic or PCR examination of peripheral blood, CSF, or other body fluids may reveal organisms in cases of acute Chagas disease. Chronic Chagas disease is diagnosed by detection of specific IgG antibodies. Given the frequency of false-positive results, diagnosis requires confirmation by at least two serologic assays.

Microbiology and Epidemiology

Sleeping sickness (human African trypanosomiasis, HAT) is caused by parasites of the T. brucei complex and is transmitted via tsetse flies.

• T. b. rhodesiense causes the East African form and T. b. gambiense the West African form; these two forms are epidemiologically and clinically distinct illnesses.
• Humans are the only reservoir for T. b. gambiense; infection occurs primarily in rural populations and rarely develops in tourists. T. b. rhodesiense has reservoirs in antelope and cattle; tourists can be infected when visiting game parks.
• The incidence of HAT due to either subspecies decreased by ∼90% between 1999 and 2015, with fewer than 3000 cases in 2015.

Pathogenesis and Clinical Manifestations

Following the bite of an infected tsetse fly, a trypanosomal chancre develops; trypanosomes disseminate into the hematolymphatic system; lymphadenopathy develops; and organisms multiply in the skin, skeletal muscles, serous membranes, and heart. The second stage of disease is marked by invasion of the CNS, which occurs weeks to months (T. b. rhodesiense) or months to years (T. b. gambiense) after initial infection.

• T. b. gambiense: After an incubation period of weeks to months, pts develop irregular and remittent fever, fatigue, malaise, myalgia, and painless edema of the face. Serpiginous rashes (trypanids) can occur on the trunk and proximal parts of the extremities.
  • Lymphadenopathy with discrete, rubbery, nontender nodes is prominent in T. b. gambiense disease. Enlargement of nodes of the lateroposterior cervical triangle (Winterbottom's sign) is a classic manifestation.
• T. b. rhodesiense: The incubation period is <3 weeks, after which high fever, headaches, diffuse myalgia, and arthralgia occur. Lymphadenopathy is less common than with T. b. gambiense and occurs in submandibular, axillary, and inguinal regions. Myocarditis and pericarditis influence clinical course and outcome.
• With second-stage disease, pts develop various sleep disturbances (daytime somnolence, nocturnal insomnia), with dysregulation of the daily sleep/wake cycle and fragmented sleep patterns. Other neurologic and psychiatric syndromes (e.g., motor weakness, rigidity, abnormal movements, ataxia, mood disorders, psychosis, apathy) can develop. Disease due to T. b. rhodesiense has a more rapid evolution toward coma and death.

Diagnosis

Examination of fluid from the chancre, thin or thick blood smears, buffy coats, lymph node aspirates, bone marrow biopsy specimens, or CSF can reveal the parasite. Serologic screening tests are available for T. b. gambiense but not T. b. rhodesiense.

• Parasitemia is more likely in stage 1 than in stage 2 disease and in pts infected with T. b. rhodesiense rather than T. b. gambiense.
• CSF should be examined for staging of the disease; >5 leukocytes/μL and/or the presence of trypanosomes confirms second-stage HAT.