Paschalis Vergidis
Matthew E. Falagas
DESCRIPTION 
Trypanosomiasis is a zoonotic protozoal disease transmitted to humans by blood-sucking insect vectors. It produces various acute and chronic diseases in humans.
EPIDEMIOLOGY
Incidence
- The estimated global annual infection rate with Trypanosoma cruzi is 300,000.
- In 1999, 45,000 cases of African trypanosomiasis were reported to WHO.
Prevalence
- An estimated 16–18 million people are infected with Trypanosoma cruzi.
- T. cruzi is present in South and Central America, Mexico, and the southern US. The majority of cases are reported from Brazil. Autochthonous disease is extremely rare in the US.
- It is estimated that at least 300,000 to 500,000 people have African trypanosomiasis. The disease is endemic in Sub-Saharan Africa. Approximately 80% of cases occur in Congo.
RISK FACTORS
- Chagas disease is prevalent in poor rural areas where the reduviid bug takes to houses made of clay or mud brick.
- Chagas disease may reactivate in immunosuppressed patients, such as those with organ transplantation or HIV.
GENERAL PREVENTION
- Adequate housing and avoidance of infestations of the insect vectors, especially in bedrooms, are needed in Latin America, primarily in the poor rural areas.
- Insect repellents for travelers. No vaccine is available.
- Blood for transfusion should be screened for T. cruzi in high-risk areas. Blood donors are currently screened in the US.
PATHOPHYSIOLOGY
- T. cruzi is transmitted by blood-sucking insects (kissing bugs), in the insects´ feces. From there, the infectious trypomastigotes enter the human body through breaks in the skin and are transformed into amastigotes.
- T. cruzi also can be transmitted by blood transfusions or organ transplantation.
- T. cruzi has been transmitted in utero, and is associated with fetal demise and fetal abnormalities.
- Oral transmission has been reported after ingestion of contaminated food.
- Human African trypanosomiasis is caused by trypanosomes transmitted by the tsetse fly.
ETIOLOGY
- T. cruzi causes Chagas disease in 10–30% of those infected.
- Trypanosoma brucei gambiense causes West African disease.
- T. brucei rhodesiense causes East African disease.
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HISTORY
- Acute symptoms of Chagas disease occur 1 week after contact with the parasite. Usually a mild illness occurring in young children.
- Chronic Chagas disease takes years to decades to cause significant illness.
- Symptoms suggestive of heart disease:
- Symptoms of West African trypanosomiasis occur 1 to 2 weeks following the insect bite.
- Symptoms of East African trypanosomiasis occur a few days following the insect bite.
PHYSICAL EXAM
ACUTE CHAGAS DISEASE
- A small, indurated papule with erythema and local lymphadenopathy occurs at the site of invasion by the organism (chagoma).
- When contact is made from the organism to the conjunctiva, periocular or palpebral edema occurs (Romaña sign). This is a classic sign of acute Chagas disease.
- Fevers, constitutional symptoms, lymphadenopathy, and splenomegaly can occur and usually resolve within weeks.
- Central nervous system symptoms and myocarditis are rare complications at this stage.
CHRONIC CHAGAS DISEASE
- Develops years after the initial infection. Most commonly it involves the heart.
- Cardiomyopathy develops and is associated with heart failure and/or arrhythmias, which are often fatal.
- Patients develop megaesophagus and dysphagia.
- Aspiration is common.
- Colonic dysfunction with megacolon occurs.
WEST AFRICAN TRYPANOSOMIASIS
Stage I (hemolymphatic)
- A painful, indurated chancre develops within 1 to 2 weeks following the tsetse fly bite. The chancre may ulcerate.
- Several weeks to several months after the initial infection, patients develop fevers associated with nontender lymphadenopathy.
- Marked constitutional signs occur at this stage, along with pruritus, arthralgias, transient edema of the face and extremities, and round erythematous rashes with internal clearing.
Stage II (meningoencephalitic)
- Several months to years after the initial infections, patients can develop CNS signs of lethargy, somnolence, and personality changes. Severe headache, ataxia, fasciculations, and choreiform movements occur at this stage.
- Neurologic signs progress slowly to stupor, coma, and death.
EAST AFRICAN TRYPANOSOMIASIS
- Acute disease with early CNS involvement and duration of less than 9 months.
- Patients develop fevers, malaise, headache and rash within weeks, as opposed to months, after the tsetse fly bite.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Initial lab tests
ACUTE CHAGAS DISEASE
- Finding circulating parasites in the blood confirms the diagnosis.
- Wet preparations and Giemsa stains of anticoagulated blood or buffy coat (thin and thick smears) should be obtained.
- The organisms are motile. Detection occurs 50% of the time.
- IgM serology not useful for diagnosing acute disease.
- PCR assays have been developed. These have variable sensitivity and are not commercially available.
CHRONIC CHAGAS DISEASE
- Serology is used to detect IgG antibodies to the organism (ELISA, indirect hemagglutination, indirect immunofluorescence).
- Many false-positive tests occur. Hence, samples should be tested by 2 different assays.
AFRICAN TRYPANOSOMIASIS
- Fluid from chancres or aspirated fluid from lymph nodes should be prepared with Giemsa stains to search for organisms.
- Wet preparations and Giemsa stains of blood may reveal the organism.
- Card agglutination tests for trypanosomes (CATT) can be used for screening purposes. The test takes less than 10 min, can be conducted in the field, and is highly sensitive.
- Lumbar puncture should be performed in all suspected or proven cases. Cerebrospinal fluid analysis shows pleocytosis and elevated protein.
Imaging
- Barium swallow/enema for patients with symptoms suggestive of esophageal/colonic involvement.
- 2-D echocardiography if concern for cardiac disease
Diagnostic Procedures/Other
- Resting electrocardiogram (ECG) with 30-sec lead II rhythm strip.
- If symptoms or abnormal resting ECG findings, proceed to ambulatory 24-hour ECG monitoring, exercise testing, and echocardiography.
- Esophageal manometry
- Upper endoscopy not indicated for diagnosis of megaesophagus. Only if concern for esophageal carcinoma.
Pathological Findings
- In chronic Chagas heart disease, there is marked bilateral ventricular enlargement (more on the right side than the left). There is also thinning of the ventricular walls, apical aneurysms, and mural thrombi.
- Microscopically there is widespread lymphocytic infiltration, diffuse interstitial fibrosis, and atrophy of myocardial cells.
- In megaesophagus/megacolon there is dilation and muscular hypertrophy with marked reduction of neurons in the myenteric plexus.
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MEDICATION
- Indications for antitrypanosomal treatment:
- Acute Chagas disease (AII) (1)
- Early congenital infection (AII)
- Reactivation after immunosuppression (AII)
- Children with chronic Chagas disease (aged
12 years AI, 13–18 years AIII) (2) - For adults 19–50 years without advanced cardiomyopathy treatment should be offered (BII)
- Impending immunosuppression (e.g., before organ transplantation) (BII)
- Younger patients have higher probability of parasitologic cure.
- For adults, data suggest that treatment may prevent progression to cardiomyopathy (3).
- Antitrypanosomal treatment not indicated in patients with cardiomyopathy or megaesophagus.
CHAGAS DISEASE
- Benznidazole 5–7 mg/kg/d orally in 2 divided doses for 60 days. Better tolerated than nifurtimox.
- Nifurtimox 8–10 mg/kg/d orally in 4 divided doses over a 90- to 120-day period.
- Both drugs can be obtained from the Centers for Disease Control.
WEST AFRICAN TRYPANOSOMIASIS
- Stage I
- Pentamidine isoethionate 4 mg/kg/d i.m. or i.v. each day for 10 days. I.m. injections painful. I.v. route preferred
- Stage II
- Eflornithine 400 mg/kg/d i.v. in four divided doses for 14 days. Less toxic than melarsoprol.
EAST AFRICAN TRYPANOSOMIASIS
- Stage I
- Suramin 100 mg i.v. test dose, followed by 1 g i.v. days 1, 3, 7, 14, and 21. Immediate hypersensitivity reaction can occur after injection. Test dose given due to risk of anaphylaxis.
- Stage II
- Melarsoprol 2.0 to 3.6 mg/kg/d i.v. in days 1, 2, 3, followed by 3.6 mg/kg/d in days 11, 12, 13, and days 21, 22, 23. Studies have also shown the effectiveness of a 10-day melarsoprol treatment which decreases treatment duration and drug amount.
FOLLOW-UP RECOMMENDATIONS
- Infected patients who did not receive treatment should be followed closely for signs of cardiac dysfunction, arrhythmias, and signs of achalasia and megacolon.
- Adults should have yearly comprehensive evaluations that include history, physical exam, and ECG.
Patient Monitoring
Offer diagnostic screening to:
- Children of seropositive women
- Family members of patients
- Individuals with a history of potential exposure to the parasite in endemic settings
PATIENT EDUCATION
Persons infected with T. cruzi should be counseled not to donate blood.
PROGNOSIS
- 20–30% of infected persons will progress to heart failure.
- Congestive heart failure and left ventricular ejection fraction <30% have a <30% survival at 2–4 years.
- The presence of an apical aneurysm is associated with a high risk of stroke.
- Cause of death: Sudden death due to ventricular arrhythmias or complete heart block, intractable congestive heart failure, or embolic phenomena.
- Outcome of heart transplantation better in patients with Chagas disease compared to ischemic or idiopathic dilated cardiomyopathy (4).
COMPLICATIONS
- Chronic Chagas disease causes cardiomyopathy and megaesophagus and megacolon.
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