Ca nine Chagas’

Dis eas e ( Americ a n

Tr ypanosomiasis )
in Nor th America
Stephen C. Barr, BVSc, PhD

KEYWORDS
 Dog  Trypanosomiasis  Chagas disease
 North America  Zoonosis

Chagas disease, or American trypanosomiasis, is caused by the hemoflagellated

protozoan, Trypanosoma cruzi (class Zoomastigophorea and family Trypanosomati-
dae). The disease was first described by the Brazilian doctor and scientist Carlos Cha-
gas in 1909.1 The parasite is a zoonosis in the Americas, particularly in South and parts
of Central America, and is the leading cause of dilated cardiomyopathy in man.2 In
dogs in North America, disease usually manifests as cardiac disease typified by
arrhythmias or myocarditis (acute and chronic), and rarely, neurologic disease.3–8
However, many infected dogs remain asymptomatic for life. Although the parasite
usually requires a reduviid vector for transmission, there is evidence that some
dogs may become infected without being bitten by vectors; they may eat infected
vectors instead. Canine Chagas disease is of importance to veterinary practitioners
because it can be difficult to diagnose and is a serious zoonosis, and there is a lack
of therapeutic options.

ETIOLOGY AND LIFE CYCLE

The organism exists in three morphologic forms. The blood-form found in circulation in
the host, the trypomastigote, is 15 to 20 mm long, with a flattened spindle-shaped body
and a centrally placed vesicular nucleus. A single flagellum originates near the large
subterminal kinetoplast (situated posterior to the nucleus) and passes along the
body to project anteriorly (Fig. 1). The host intracellular or amastigote form is approx-
imately 1.5 to 4.0 mm in diameter, roughly spheroid, and contains both nucleus and
rodlike kinetoplast. With regular cytological staining, these structures have similar
staining properties although the kinetoplast stains more densely. The small flagellum
is rarely obvious under light microscopy. Epimastigotes, the third morphologic form,
are found in the reduviid vector (subfamily Triatomae). In South America, these large

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY

14853, USA
E-mail address: scb6@cornell.edu

Vet Clin Small Anim 39 (2009) 1055–1064

doi:10.1016/j.cvsm.2009.06.004 vetsmall.theclinics.com
0195-5616/09/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.
1056 Barr

Fig. 1. Trypomastigotes of T cruzi in a blood smear of a dog (Wright-Giemsa stain, original

magnification 1000).

insects (adults can reach an inch in length) are commonly known as ‘‘kissing bugs.’’
Epimastigotes are flagellated and spindle shaped with the kinetoplast situated anterior
to the nucleus.
When the vector is involved, infection occurs when trypomastigotes are deposited
in the insect vector’s feces at the vector bite site, as occurs in human infections in
South America, but this may not be the main route of infection for dogs in North Amer-
ica. Ingestion of infected insect vectors causing the parasite to be released into the
mouth of the dog is probably more likely; certainly, opossums9 and armadillos10 fed
infected vectors will become infected by this route. Blood transfusion and transpla-
cental transmission can also occur, and transmission by ingestion of milk from in-
fected lactating bitches has been proposed.7 Ingestion of meat from infected
reservoir hosts has also been suggested to occur in dogs, but transmission did not
occur when infected meat was fed to armadillos.10 After infection, trypomastigotes
may enter macrophages, transform into amastigotes, which multiply by binary fission,
or remain free in circulation to spread from the local site of infection. After hematog-
enous spread, myocardiocytes become infected with trypomastigotes which, after
transforming into amastigotes, multiply and transform back into trypomastigotes
before rupture of and release from the cell back into circulation. Parasitemia in dogs
first appears as early as 3 days post infection (DPI), peaks at 17 DPI, and is usually
subpatent by 30 DPI.3 Clinical signs of acute myocarditis, should they occur, develop
about 14 DPI with recovery occurring around 28 DPI.3 Rapid intracellular multiplication
cycles ensure a rapid rise in parasitemia before effective immunity develops. The
vector becomes infected by ingesting circulating trypomastigotes, which transform
to epimastigotes and multiply by binary fission. Transformation of the epimastigotes
back into trypomastigotes occurs in the vector’s hindgut before the trypomastigotes
are passed in the feces.

EPIDEMIOLOGY

American trypanosomiasis is a major human health problem in South and Central

America, and is becoming more recognized in Mexico2,11 To date, there have been
six human cases involving transmission by vectors reported in the United States.
The last reported human case was detected in June 2006 in a 74-year-old woman
residing in rural New Orleans, Louisiana, who experienced a large influx of vectors
 American Trypanosomiasis 1057

(Triatoma sanguisuga) into her house after hurricane Katrina.12 Of the 33 vectors found
in her dwelling, 56% were found to contain T cruzi. However, by far the largest number
of people (estimated to be 50,000 to 100,000) infected in the United States have
emigrated from endemic regions. Consequently, reports of cases associated with
transfusion transmission continue to increase in number,13,14 and blood is now tested
for T cruzi at blood banks. Most canine cases in the United States occur in Texas,
especially within the southeastern quadrant.15–17 Isolated canine cases have been re-
ported in other southern states,6,18–20 but also as far north in the east as Virginia.7
Transmission of T cruzi in endemic countries depends on the confluence of vectors,
reservoirs, parasites, and hosts (both people and animals) in a single habitat. Only
three Triatomae species (Triatoma infestans, Triatoma dimidiata, and Rhodnius pro-
lixus) of the many that feed on humans in endemic regions in South America display
the appropriate behavior that enables them to transmit T cruzi effectively. These para-
sites feed on blood from both people and domestic reservoir mammals (dog, cat,
guinea pigs), reproduce prolifically while cohabiting close to people, and defecate
soon after taking a blood meal, meaning that they are usually still on the host near
the bite wound when they defecate.21 Infection rates in these vectors can be as
high as 100% south of the equator. By contrast, domestic transmission cycles prob-
ably do not occur in the United States, except in areas of southeastern Texas where
there is evidence to suggest that the dog can be involved in domestic transmission
cycles involving vectors and humans,22 similar to what has been suggested across
the boarder in Mexico11 and endemic regions in South America.21 In general, however,
the two principal vectors in the United States (Triatoma protracta and Triatoma sangui-
suga) have low infection rates (20%), display different feeding habits, and defecate
about 20 minutes after feeding, often when they have long fled the host.23 These
factors and higher standards of housing in the United States are suggested to have
contributed to a much lower rate of autochthonous transmission.
The principal sylvan reservoir hosts of T cruzi in the eastern seaboard states from Mary-
land south and most other southern states (Texas, Louisiana, Oklahoma, to name a few)
are opossums and raccoons. Armadillos are also infected wherever they range.24–31
Various mouse, squirrel, and rat species are the main sylvan hosts in New Mexico and
California.32 Isolates of T cruzi from infected vectors and animal reservoirs in North Amer-
ica are less pathogenic in mice than South American isolates despite showing similar in
vitro characteristics.24,33 Because inoculation of T cruzi isolates from opossums and ar-
madillos into dogs experimentally produces a similar disease described in naturally
acquired cases of acute and chronic canine trypanosomiasis, it is likely that dogs in
nature are infected with the same isolates as these sylvan hosts.3–7

CLINICAL SIGNS AND PATHOGENESIS

As in humans, there are three distinct phases of Chagas myocarditis in dogs; acute,
indeterminate (or latent), and chronic.3–7 After infection, trypomastigotes enter cells
(mainly macrophages) where they evade the immune system and spread throughout
the body. Some do enter the circulation and can be detected cytologically as early
as 3 DPI. The parasitemia steadily rises as more and more intracellular multiplication
cycles add to the number of circulating trypomastigotes. Peak parasitemia occurs at
about 17 DPI, roughly at about the time that clinical signs of generalized lymphade-
nopathy and acute myocarditis appear. The cause of the myocarditis is thought to
be due to cell damage and the resulting inflammation as trypomastigotes rupture
from myocardiocytes. Lethargy, generalized lymphadenopathy, slow capillary refill
time with pale mucous membranes, and in some cases splenomegaly and
1058 Barr

hepatomegaly, are the main presenting signs in young puppies. In dogs older than 6
months, clinical signs are often much less severe and sometimes not apparent at all.
Serum troponin I levels slowly increase in infected dogs to spike at 10 to 30 mg/mL at
21 DPI. Serum alanine aminotransferase, aspartate aminotransferase, creatinine, and
urea nitrogen can be elevated, especially in dogs that are at risk of death from severe
acute myocarditis. Dogs infected after 6 months of age may show no signs of acute
disease other than slight depression and low-rising parasitemia. Serum troponin I
levels are elevated in these dogs but usually not to high levels. The electrocardiogram
(ECG) of dogs with severe myocarditis may show sinus tachycardia, decreased
R-wave amplitude, prolonged P-R interval, axis shifts, T-wave inversion, and conduc-
tion abnormalities, including first- and second-degree atrioventricular block and right
bundle branch block (Fig. 2). ECGs are usually within normal limits. Sudden death,
presumably from cardiac muscle failure or conduction system failures leading to
malignant arrhythmias, is not a common occurrence. Histopathologic findings include
a severe diffuse granulomatous myocarditis, large numbers of parasitic pseudocysts,
and minimal fibrosis (Fig. 3). Although less common than signs referable to cardiac
abnormalities, neurologic signs referable to meningoencephalitis (as a direct result
of parasitic invasion of the neurologic system) may also occur, and include weakness,
pelvic limb ataxia, and hyperreflexive spinal reflexes suggestive of distemper.
Dogs that survive the acute phase enter the prolonged indeterminate phase typified
by the lack of clinical signs. The parasitemia becomes subpatent at about 30 DPI and
can only be demonstrated by blood culture or xenodiagnosis. The ECG is usually
normal during this phase although ventricular-based arrhythmias can be induced by
exercise.4 Although not all dogs progress to develop chronic disease, some develop
chronic myocarditis with cardiac dilatation over the next 8 to 36 months.3,4 With the
progressive development of cardiac dilation, ECG abnormalities become more prev-
alent and may even result in sudden death. Clinical signs referable to right-sided and
eventually, in some, left-sided chamber failure occurs, and can include pulse deficits,
ascites, pleural effusion, hepatomegaly, and jugular venous congestion.3 Dogs

Fig. 2. Electrocardiogram showing second-degree heart block and depressed QRS complexes
often present in dogs with acute Chagas disease.
 American Trypanosomiasis 1059

Fig. 3. Pseudocyst of T cruzi within a myocardiocyte of an infected dog (hematoxylin-eosin

stain, original magnification 1000).

diagnosed at an older age (mean of 9 years) survived between 30 to 60 months

whereas dogs diagnosed at a younger age (mean of 4.5 years) survived only up to 5
months after diagnosis.17 These cases are indistinguishable from chronic dilative
cardiomyopathy seen in large breeds of dogs, and often are diagnosed as such until
histology or immunohistochemistry findings are available.5–7 Echocardiographic
abnormalities include right ventricular dilation with progression to include a loss of
left ventricular function with decreased fractional shortening, reduced ejection frac-
tion, reduced left ventricular free wall thickness, and increase in end-systolic volume.
The pathogenesis of the biventricular dilative cardiomyopathy is unknown, but
possible mechanisms include immune-mediated mechanisms or toxic parasitic
products directed against the myocardiocytes or autonomic nervous system, or
microvascular disease coupled with platelet dysfunction.34,35 Histopathology of the
myocardium is characterized by multifocal interstitial mononuclear cellular infiltrates,
perivasculitis, and marked fibrosis, and the rare presence, if any, of parasitic pseudo-
cysts.5,34 Cardiac dilatation occurs when fibrosis no longer permits efficient compen-
satory hypertrophy.34,36 Some T cruzi isolates that infect dogs in the United States are
not pathogenic but can produce a marked serologic response and a low parasitemia
during times of stress or immunosuppression.3,37

DIAGNOSIS

The hallmark of making a diagnosis of Chagas disease is first to suspect the infection.
Chagas disease should be considered in any dog with signs of myocarditis or cardio-
myopathy, particularly if it lives or has lived at any time, even years before presenta-
tion, in an endemic region. During acute disease, trypomastigotes may be detected on
examination of a blood smear during normal hematology examination (see Fig. 1).
However, blood parasite counts may be so low that only a few parasites may be
present on the entire slide, demanding diligent examination; some form of concentra-
tion technique may also be used. High-power (400) examination of the buffy coat-
plasma interface of a centrifuged microhematocrit tube may reveal characteristically
motile parasites. Examination of a thick-film buffy coat smear stained with either
1060 Barr

Wright’s or Giemsa is more sensitive than examination of a blood smear preparation. A

highly effective concentration technique involves pelleting trypomastigotes from
plasma (obtained by centrifugation of 50 mL heparinized blood at 800 g for 10 minutes)
by further centrifugation (8000 g for 15 minutes). The pellet from the final centrifugation
may be examined microscopically after staining, be submitted for polymerase chain
reaction (PCR) analysis, or used to inoculate liver infusion tryptose (LIT) growth media
in which epimastigotes will grow over several weeks. Trypomastigotes may also be
found on cytologic examination of lymph node aspirates and in abdominal effusions.
Serology and PCR may also be extremely useful in the diagnosis of Chagas disease,
especially during the indeterminate and chronic phases when trypomastigotes are
extremely difficult to demonstrate.38 The indirect fluorescent antibody assay,
enzyme-linked immunosorbent assay, and radioimmunoprecipitation assay are
most commonly used.39 These tests confirm the presence of antibodies to T cruzi
but most cross-react with antibodies to Leishmania. Further, in rare cases in dogs,
the clinical signs of Chagas disease and leishmaniasis overlap to such a level that it
is necessary to go to considerable lengths to establish a diagnosis.40 Therefore,
a detailed history of the likelihood of exposure to Leishmania must be known before
an accurate interpretation of serologic results can be made.
A PCR assay, which detects DNA of the organism in various samples (blood,
plasma, lymph node aspirates, or ascitic fluid may all be used), is highly specific for
T cruzi but has low sensitivity unless multiple samples are examined.38 Serology in
association with clinical signs is considered the gold standard for the diagnosis of
Chagas disease in dogs. The serum titer usually becomes positive by 21 DPI at the
time when the parasitemia is declining, and persists for the life span of the animal
irrespective of whether clinical signs develop.37

THERAPY

Treatment of dogs in the acute phase of disease is poorly reported as this phase is
seldom recognized. Nifurtimox (Bayer 2502 or Lampit; Bayer, Leverkusen-Bayerwerk,
Germany), usually in association with corticosteroids,41 and benznidazole (Ragonil;
Roche, Buenos Aires, Argentina) use have been reported in the dog (Table 1).
However, the severe side effects of nifurtimox preclude its use. The drug of choice
currently is benznidazole because it has less side effects, has been reported effective
in treating acute canine infections,42 and is available from the Centers for Disease
Control (CDC) in Atlanta, Georgia. The main side effect of benznidazole is vomiting.
After treatment with benznidazole, serum antibody titers usually remain elevated
although they are reported to drop in people. Ketoconazole, gossypol, allopurinol,
imidazole, and verapamil have shown promise in other species but are all ineffective
in the treatment of Chagas disease in dogs. It is unknown if successful treatment

Table 1
Drug therapy for Chagas disease

Druga Tablet Size (mg) Dose (mg/kg) Route Interval (h) Duration (mos)
Benznidazole (Ragonil) 100 5–10 PO 24 2
Nifurtimox (Lampit) 120 2–7 PO 6 3–5
Prednisone Multiple 0.5 PO 12 1
a
Ragonil and Lampit are available from the Centers for Disease Control, Atlanta, GA.
 American Trypanosomiasis 1061

during the acute phase changes the likelihood of development, or outcome, of chronic
disease in dogs.
Most cases of Chagas disease are diagnosed during the chronic stage. Unfortu-
nately, treatments directed against the parasite at this stage rarely change the
outcome of disease. Treatment should be directed toward the myocardial failure
and ventricular arrhythmias, although the latter seem resistant to drug therapy.39
Unfortunately, medical treatments rarely result in a clinical cure. In severe cases of
acute myocarditis coupled with high parasitemia, prognosis is poor and zoonotic risk
higher (to those handling blood products), so euthanasia should be considered in
these cases. If dogs survive acute disease, progression to the chronic stage tends
to occur more quickly (in about 1 to 2 years) in dogs diagnosed at a younger age
(<2 years) than dogs diagnosed at an older age (>4 years), which survive longer
(3 to 5 years).17

PREVENTION

Limiting contact with vectors and possible reservoir hosts (raccoons, opossums,
armadillos, and skunks) should reduce the risk of infection. Dogs should not be fed
meat from reservoir hosts. Kennels and surrounding structures (chicken houses,
wood piles) should be sprayed monthly with a residual insecticide such as benzene
hexachloride. Dog housing should be upgraded to remove vector nesting sites. Appli-
cations of fipronil on the coats of dogs do not appear to prevent infections in dogs, or
reduce the feeding of vectors,43 but deltamethrin-treated collars do reduce Tri infes-
tans feeding.44,45 Dogs used as blood donors should be serologically screened to
determine previous exposure to T cruzi. In highly endemic regions (southern Texas),
bitches should be screened serologically and positive animals should not be bred.

PUBLIC HEALTH CONSIDERATIONS

Chagas disease is the most common cause of congestive heart failure in the world.
Most cases in humans in the United States are acquired by blood transfusion or labo-
ratory accident. There are probably several reasons why only 6 naturally acquired
cases have been reported in the United States. First, North American vector species
are poorly adapted to living in houses, and do not defecate on the host after a blood
meal. Second, the high standard of housing in North America prevents vectors nesting
in human dwellings. Third, it is possible that some human cases of Chagas disease in
North America have not been identified because of a low level of suspicion.
Although the risk of acquiring infection from an infected dog is extremely low, the
severity and difficulty of treating disease in humans makes this disease of consider-
able public health significance. Veterinarians should be particularly careful in handling
blood samples from infected dogs, and warn laboratory staff of the potential infectivity
of the samples. Accidental needle sticks when administering therapy to or with-
drawing samples from infected dogs should be reported immediately to the CDC.

SUMMARY

Chagas disease mainly occurs in working dogs in southeastern Texas. The protozoan
traditionally is transmitted in the feces of the vector, which defecates in the bite wound
caused by vector feeding. However, it is likely that most dogs become infected by
eating infected vectors, causing the release of the organisms into the mouth of the
host. Soon after infection, an acute myocarditis results from organism multiplication
in and rupture from myocardiocytes. This stage is rarely appreciated clinically. Most
1062 Barr

dogs are diagnosed during the chronic stage of the disease, which is typified by
dilated cardiomyopathy and malignant ventricular-based arrhythmias. Although benz-
nidazole is effective in removing parasites from circulation, supportive therapy to
control the arrhythmias and cardiac dysfunction become the mainstay of treatment.
Chagas disease is considered zoonotic, although infected dogs are of little risk to
humans.

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