Table 18.1 Nomenclature of bone tumors
Chagas disease
Chagas disease

Chagas disease is a infection caused by the protozoan parasite Trypanosoma cruzi. The disease is characterized by an acute nonspecific febrile illness that may be followed, after a variable latency period, by chronic cardiac, GI, and neurologic sequelae.
American trypanosomiasis

• Four cases of autochthonous transmission in California and Texas
• In the last two decades, six cases of laboratory-acquired infection, three cases of transfusion-associated transmission, and nine cases of imported disease reported to the Centers for Disease Control and Prevention (none of the imported cases involving returning tourists)
PREVALENCE (IN U.S.): Based on regional seroprevalence studies in Hispanic blood donors, it is estimated that between 50,000 and 100,000 persons infected with T. cruzi are currently residing in the U.S.
PREDOMINANT SEX: Male = female
• In highly endemic areas, mean age of acute infection: approximately 4 years old
• Variable age distribution for both types of chronic disease, depending on geography
• Mean age of onset: usually between 35 and 45 years
Congenital Infection: Congenital transmission has been documented with attendant high fetal mortality and morbidity in surviving infants.
Neonatal Infection: In rural areas, within substandard housing, transmission is likely to occur.
Chagas disease
• Inflammatory lesion that develops about 1 week after contamination of a break in the skin with infected insect feces (chagoma)
1. Area of induration and erythema
2. Usually accompanied by local lymphadenopathy
• Presence of Romaña’s sign, which consists of unilateral painless palpebral and periocular edema, when conjunctiva is portal of entry
• Constitutional symptoms of fever, fatigue, and anorexia, along with edema of the face and lower extremities, generalized lymphadenopathy, and mild hepatosplenomegaly after the appearance of local signs of disease
• Myocarditis in a small portion of patients, sometimes with resultant CHF
• Uncommonly, CNS disease, such as meningoencephalitis, which carries a poor prognosis
• Symptoms and signs of disease persisting for weeks to months, followed by spontaneous resolution of the acute illness; patient then in the indeterminate phase of the disease (asymptomatic with attendant subpatent parasitemia and reactive antibodies to T. cruzi antigens)
• Chronic disease may become manifest years to decades after the initial infection:
1. Most common organ involved: heart, followed by GI tract, and to a much lesser extent the CNS
a. Cardiac involvement takes the form of arrhythmias or cardiomyopathy, but rarely both.
b. Cardiomyopathy is bilateral but predominantly affects the right ventricle and is often accompanied by apical aneurysms and mural thrombi.
c. Arrhythmias are a consequence of involvement of the bundle of His and have been implicated as the leading cause of sudden death in adults in highly endemic areas.
d. Right-sided heart failure, thromboembolization, and rhythm disturbances associated with symptoms of dizziness and syncope are characteristic.
2. Patients with megasophagus: dysphasia, odynophagia, chronic cough, and regurgitation, frequently resulting in aspiration pneumonitis
3. Megacolon: abdominal pain and chronic constipation, which, when severe, may lead to obstruction and perforation
4. CNS symptoms: most often secondary to embolization from the heart or varying degrees of peripheral neuropathy
• T. cruzi
1. Found only in the Americas, ranging from the southern half of the U.S. to southern Argentina
2. Transmitted to humans by various species of bloodsucking reduviid (“kissing”) insects, primarily those of the genera Triatoma, Panstrongylus, and Rhodnius
3. Usually found in burrows and trees where infected insects transmit the parasite to nonhuman mammals (e.g., opossums and armadillos), which constitute the natural reservoir
4. Intrusion into enzootic areas for farmland, allowing insects to take up residence in rural dwellings, thus including humans and domestic animals in the cycle of transmission
5. Initial infection of insects by ingesting blood from animals or humans that have circulating flagellated trypanosomes (trypomastigotes)
6. Multiplication of ingested parasites in the insect midgut as epimastigotes, then differentiation into infective metacyclic trypomastigotes in the hindgut whereby the parasites are discharged with the feces during subsequent blood meals
7. Transmission to the second mammalian host through contamination of mucous membranes, conjunctivae, or wounds with insect feces containing infected forms.
• In the vertebrate host
1. Movement of parasites into various cell types, intracellular transformation and multiplication in the cytoplasm as amastigotes, and thereafter differentiation into trypomastigotes
2. Following rupture of the cell membrane, parasitic invasion of local tissues or hematogenous spread to distant sites, maintaining a parasitemia infective for vectors
• In addition to insect vectors, T. cruzi is transmitted through blood transfusions, transplacentally, and, occasionally, secondary to laboratory accidents.

Acute disease
• Early African trypanosomiasis
• New World cutaneous and mucocutaneous leishmaniasis
Chronic disease
• Idiopathic cardiomyopathy
• Idiopathic achalasia
• Congenital or acquired megacolon
Principal considerations in diagnosis:
• A history of residence where transmission is known to occur
• Recent receipt of a blood product while in an endemic area
• Occupational exposure in a laboratory
For acute diagnosis:
• Demonstration of T. cruzi in wet preparations of blood, buffy coat, or Giemsa-stained smears
• Xenodiagnosis, a technique involving laboratory-reared insect vectors fed on subjects with suspected infection thereafter examined for parasites, and culture of body fluids in liquid media to establish diagnosis
1. Hampered by the length of time required for completion
2. Of limited use in clinical decision making with regard to drug therapy
3. Although xenodiagnosis and broth culture are considered to be more sensitive than microscopic examination of body fluids, sensitivities may not exceed 50%.
• Recent advances in serologic testing, including immunoblot assay, in situ indirect fluorescent antibody, and PCR-based techniques
1. Show increased sensitivity and specificity for T. cruzi in acute and chronic infections
2. Not widely available, limiting their usefulness in the diagnosis of acute disease
For chronic T. cruzi infection:
• Traditional serologic tests including: complement fixation (CF), indirect immunofluorescence (IIF), indirect hemagglutination, enzyme-linked immunosorbent assay (ELISA), and radioimmune precipitation assay
• Persistent problem with these tests: in addition to sensitivity and specificity, false-positive results
• Saliva ELISA may be useful as a screening diagnostic test in epidemilogic studies of chronic trypanosomiasis infection in endemic areas.

• Chronic chagasic heart disease: mainly supportive
• Megaesophagus: symptoms usually amenable to dietary measures or pneumonic dilation of the esophagogastric junction
• Chagasic megacolon: in its early stages responsive to a high-fiber diet, laxatives, and enemas
Nifurtimox (Lampit, Bayer 2502):
• Only drug available in the U.S. for the treatment of acute, congenital, or laboratory-acquired infection
• Recommended oral dosage for adults: 8 to 10 mg/kg/day given in four divided daily doses and continued for 90 to 120 days
• Parasitologic cure in approximately 53% of those treated; should be begun as early as possible
Benznidazole, a nitroimidazole derivative:
• Has demonstrated similar efficacy as nifurtimox in limited trials
• Recommended oral dosage: 5 mg/kg/day for 60 days
• In patients with indeterminate phase or chronic disease: no evidence of benefit with pharmacologic therapy
• In patients exhibiting bradyarrhythmias: pacemakers
• In individuals with congestive heart failure:
1. Treat with modalities appropriate for dilated, especially right-sided, cardiomyopathic disease.
2. Cardiac transplant is a controversial alternative for end-stage cardiomyopathy; however, reactivation rate found to be low and amenable to therapy without subsequent infection of the allograft in one study.
3. Myotomy or esophageal resection is reserved for patients with advanced disease.
• In advanced chagasic megacolon associated with chronic fecal impaction, perforation, or, less commonly, volvulus: surgical resection
Based on few prospective studies, most patients infected with T. cruzi will not develop symptomatic Chagas disease.
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