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Chapter 158 Hematologic Aspects of Parasitic Diseases 2297

although occasionally acute myocarditis with focal hemorrhage and
inflammation may lead to heart failure. As the disease progresses, the
inflammatory response is increased and is associated with increased
tissue damage. There may be an autoimmune component to this
inflammatory response, but the precise pathogenesis is poorly under-
220
stood. In the heart, chronic myocarditis leads to a decline in cardiac
function. In late-stage disease, amastigotes can be found in almost all
organs. Acute myocarditis with focal hemorrhage and inflammation
may also lead to heart failure. Involvement of the brain, meninges,
liver, lymph nodes, and spleen is common. Damage to the muscle
walls and intramural nerve plexus in the esophagus and colon leads
to dilation of these structures in the later phases of the disease.

Clinical Features

In about half the patients, a granuloma (or chagoma) occurs where
Fig. 158.14 TRYPANOSOMA RANGELI. T. rangeli is a long, slender try- parasites have been inoculated. The tender erythematous papule
panosome also transmitted by reduviid bugs from wild animals to humans. becomes keratotic and later heals, forming a hyperpigmented scar.
It is readily distinguished by its shape from Trypanosoma cruzi in blood films When the conjunctiva are inoculated, the extensive unilateral perior-
and appears to be nonpathogenic to humans. bital edema may be prolonged (Romaña sign).
The severity of the acute illness is variable and ranges from
asymptomatic infection or a mild febrile illness to a severe, potentially
trypomastigotes, adherent to the epithelium of the rectum. These fatal illness with cardiac failure and meningoencephalitis in a minor-
infective forms are excreted into the feces, and people are infected by ity of cases. Myalgia, generalized lymphadenopathy, hepatospleno-
rubbing this infected material from the bug into the skin or conjunc- megaly, headaches, facial or generalized edema, vomiting, diarrhea,
tival membranes. In the human host, multiplication into macrophages and anorexia are common features of the acute disease. The disease
is followed by rapid dissemination of trypomastigotes into the blood may be worse in children. The acute illness typically resolves in 4 to
and hence to tissues. The genome sequence of T. cruzi has stimulated 8 weeks. Chagas disease must be distinguished from typhoid fever,
a plethora of comparative and genomic approaches to the study of VL, brucellosis, toxoplasmosis, and malaria in cases of chronic, febrile
the parasite. 216,217 illness in endemic areas.

Trypanosoma rangeli Infections Chronic Disease

The nonpathogenic trypanosomes can be transmitted directly to The acute phase of T. cruzi infection is followed by a variable latent
people by the bite of the triatomine bugs, and they exist only as or indeterminate phase with no clinical symptoms. Indeed, patients
circulating trypomastigotes. No tissue amastigotes exist. Circulating may never present with signs of end-organ damage. However, up to
organisms are sparse, but sometimes diagnosis can be made by careful one-third of clinically infected patients may develop cardiac involve-
microscopic examination of the distinctive morphology of these ment and show right bundle branch block, atrioventricular conduc-
organisms in blood smears. The anterior position of the nucleus and tion abnormalities, and/or abnormal T and Q waves. The patient may
small kinetoplast distinguish it from T. cruzi (Fig. 158.14). The experience palpitations, chest pain, edema, and dizziness or syncope
antibodies produced to T. rangeli cross-react with those from T. cruzi or dyspnea. The heart is enlarged, and intramural thrombus may
and hence cause false-positive serologic test results for T. cruzi. cause sudden death.
However, the species may be differentiated by xenodiagnosis or In a further minority of chronically infected patients, the gastro-
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molecular genetics in specialized laboratories. The importance of intestinal tract is infected with abnormal motility of the esophagus
recognizing this nonpathogenic infection is to avoid unnecessary and colon, leading to dysphagia and/or severe constipation. Occa-
treatment for T. cruzi. sionally, other hollow organ systems may be affected.

Pathology Pregnancy and Congenital Infection
There is a wide variation in the pathogenicity of isolates and some In pregnant women, Chagas disease can cause spontaneous abortion,
regional variation in the clinical spectrum of acute and chronic illness. premature birth, intrauterine growth retardation, and stillbirth.
Molecular typing has demonstrated considerable heterogeneity of T. Congenital infection occurs in 1% to 2% of women with chronic
cruzi isolates, although the association between strains of parasite and infection. Prompt diagnosis of circulating parasites in neonates at risk
the outcome of infection are unclear. Clearly the organism must have for congenital Chagas disease is essential to beginning early treat-
many mechanisms of the immune evasion to cause chronic infections ment. It is recognized that infection can also be transmitted by
in a high proportion of individuals. Some of these have been elegantly breastfeeding. Most children are asymptomatic, but 10% to 20% of
defined, including resistance to activation of the alternate pathway of children have a mild systemic illness with hepatosplenomegaly. More
complement, specific mechanisms of entering the host cells, and severely affected newborn children have pneumonitis, meningoen-
evasion of intracellular killing by the oxidative burst and lysozymes. cephalitis, and diffuse dermal granulomas. Petechiae, purpura, and a
+
+
Both CD4 and CD8 T cells are important for killing T. cruzi– generalized bleeding tendency may occur. 221
infected cells, and IFN-γ has shown to be important to controlling
disease, whereas transforming growth factor-β and IL-10 enhance
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parasite replication (for review, see Dutra et al ). Immunocompromised Patients
End-organ damage occurs after tissues have been infected by T.
cruzi amastigotes, but the mechanisms leading to extensive cell The disease may recrudesce after chemotherapy for malignant disease,
damage are not clear. After multiplication, tissue amastigotes form immunosuppressive therapy, or after organ transplant. The clinical
pseudocysts in the heart with little or no inflammatory reaction, disease may be fulminating with obvious parasitemia. Irregular