REVIEW ARTICLE

Chagas disease: An underrecognized diagnosis

Dan M. Tzizik, MPAS, PA-C; Roy A. Borchardt, PA-C, PhD

ABSTRACT
Chagas disease is a parasite infection primarily transmitted
to humans via the bite of triatomine insect vectors. Up to 8
million people are estimated to be infected with Chagas dis-
ease in the Americas. Patients who do not receive treatment
can develop severe cardiac debility, gastrointestinal organ
Downloaded from http://journals.lww.com/jaapa by BhDMf5ePHKbH4TTImqenVBaqevB2sTM0e1wRXdcBxc3tKoIkM3d83ETCm8TpO/Lm on 01/06/2019

dysfunction, and may die. The changing demographics of

the United States, a consequence of changing immigration
patterns, means that healthcare providers are more likely to
encounter patients with Chagas disease, and must under-
stand its cause, pathogenesis, diagnosis, and treatment.
Keywords: Chagas disease, cardiomyopathy, megacolon,

PHOTOGRAPH COURTESY OF THE CDC/DR. MAE MELVIN

triatomine, Trypanosoma cruzi, tropical

C
hagas disease, also called American trypanoso-
miasis, is an infectious illness caused by the pro-
tozoan parasite Trypanosoma cruzi. Without
treatment, patients with Chagas disease can progress to
severe cardiac debility, gastrointestinal (GI) organ dys-
function, and death.1 The World Health Organization
(WHO) has recognized Chagas disease as one of 17
neglected tropical diseases.2 Once confined to tropical
rural areas of Latin America (primarily Mexico, Central
America, and South America), Chagas disease now is
found in Europe, the Pacific, the United States, and FIGURE 1.
Canada.3 Up to 8 million people in the Americas, includ- Romaña sign on the right eye of a boy with Chagas disease
ing up to 300,000 in the United States, are thought to be
infected with Chagas disease.3 Many patients with Chagas encounter patients with Chagas disease. Having a better
disease are immigrants from endemic areas of Latin understanding of the cause, pathogenesis, diagnosis, and
America and are unaware of their infection because the treatment of Chagas disease can improve outcomes for
disease often is asymptomatic.3 infected patients.
Chagas disease is poorly recognized and undertreated
by healthcare providers in nonendemic regions such as the EPIDEMIOLOGY
United States.4 The changing demographics of the United T. cruzi is transmitted to humans via the bite of a triatomine
States, a consequence of changing immigration patterns, insect vector as it obtains a blood meal.5 Nymphs and adult
increases the likelihood that healthcare providers will triatomines of both sexes serve as vectors.6 Patients typi-
cally are infected at night while sleeping. Sleeping or
Dan M. Tzizik practices in the ED at Portsmouth (N.H.) Regional unsuspecting human hosts may scratch or rub infected
Hospital. Roy A. Borchardt is supervisor of advanced practice triatomine feces into the bite wound or into the mucous
providers at M.D. Anderson Cancer Center’s Department of Infectious
Diseases, Infection Control and Employee Health, in Houston, Tex. The membranes of the eyes or mouth.6 Once inside the human
authors have disclosed no potential conflicts of interest, financial or host, the T. cruzi trypomastigotes infect surrounding cells,
otherwise. multiply intracellularly, and enter the bloodstream.1 Unlike
DOI:10.1097/01.JAA.0000547749.92933.6a African trypanosomes, T. cruzi trypanosomes do not rep-
Copyright © 2018 American Academy of Physician Assistants licate in the blood.1 Other routes of transmission of T. cruzi

30 www.JAAPA.com Volume 31 • Number 12 • December 2018

Copyright © 2018 American Academy of Physician Assistants


Key points
The changing demographics of the United States mean
that healthcare providers are more likely to encounter
patients with Chagas disease.
Up to 8 million people are estimated to be infected with
Chagas disease in the Americas; many patients do not
know they are infected.
Patients who do not receive treatment can develop severe
cardiac debility, GI organ dysfunction, and may die.
include congenital, infected donor blood transfusions,
organ transplantation from infected donors, and consump-
tion of food contaminated with triatomine insect feces or
urine.6 Vector-borne transmission is the predominant route
in endemic areas.6
Historically, Chagas disease was primarily restricted to
Latin America, with Bolivia, Argentina, El Salvador, and
Honduras having the highest seroprevalence of T. cruzi.3
Chagas disease was much more prevalent in poor, rural
areas.7 Poorly constructed housing with adobe mud and
straw walls and palm-thatched roofs, common to rural
Central and South America, provides an environment that
encourages colonization of triatomine insects, which can
hide during the day in wall and roof crevices.6 Intensive
vector control programs have substantially reduced T. cruzi
transmission in rural areas.8
GI involvement occurs in
15% to 20% of patients
who progress to the chronic
symptomatic phase.
Chagas disease is a zoonotic disease with more than 150
mammalian and marsupial reservoirs for T. cruzi.7 In the
United States, numerous reservoirs support transmission
of T. cruzi; humans are accidental hosts.5,6 Eleven triatomine
species live in the southern half of the United States and
T. cruzi has been isolated in nine of these species.6 However,
documented direct vector-borne transmission in the United
States is rare. The scarcity of indigenous triatomine vector-
borne cases in the United States likely is multifactorial.
Improved housing, compared with that in Central and
South America, probably is the primary contributing fac-
tor.6 Additionally, US healthcare providers have a low index
of suspicion for Chagas disease, so many patients with the
disease are undiagnosed.6 However, five locally transmitted
cases were noted in southeastern Texas.9 Most recently, a
study reported 11 likely autochthonous transmissions of
T. cruzi after serologic screening of blood donor samples
JAAPA Journal of the American Academy of Physician Assistants
Copyright © 2018 American Academy of Physician Assistants
Chagas disease: An underrecognized diagnosis
in south-central Texas.10 The lack of knowledge and dis-
information among healthcare providers of the case patients
in this study was particularly troubling.10
CLINICAL PRESENTATION
Chagas disease has an acute and a chronic phase. The
incubation period generally lasts 1 to 2 weeks before the
onset of the acute phase; however, in transfusion- or
transplant-related infection, the incubation period can be
up to 4 months.11
Acute phase This phase, which lasts 4 to 8 weeks, often
is asymptomatic. Patients may have nonspecific symptoms
such as fever, fatigue, headache, body aches, rash, anorexia,
vomiting, and diarrhea.12 These symptoms generally resolve
spontaneously.7 Patients also may develop lymphade-
nopathy, splenomegaly, leukocytosis, thrombocytopenia,
or anemia.13 In the absence of classic signs and/or a high
index of suspicion, the correct diagnosis may be elusive.
Although uncommon, a chagoma, or local painless edema
and erythema surrounding the inoculation site, may accom-
pany the onset of the acute phase.12 Romaña sign, the
classic sign of Chagas disease, is a specific chagoma char-
acterized by painless unilateral edema of the periocular
region involving the upper and lower eyelids, and indicates
conjunctival invasion by T. cruzi (Figure 1).7
Mortality during the acute phase is relatively rare, occur-
ring in fewer than 5% of cases, and primarily is observed
in young children or immunocompromised patients.7 The
cause of death under these circumstances typically is severe
myocarditis or meningoencephalitis.7
Chronic phase This phase can be subdivided into an
asymptomatic indeterminant phase and a symptomatic
determinant phase.7
• Indeterminate chronic phase. Patients who test positive
serologically but have no clinical evidence (normal 12-lead
ECG, normal radiographs of the chest, and normal esoph-
agus and colon imaging) are in the indeterminate chronic
phase.7 Between 60% and 70% of the patients in this
phase never develop any manifestation of the disease.7
• Determinant chronic phase. The remaining 30% to 40%
of patients progress to the determinant chronic phase,
characterized by cardiac and GI complications.14 Clinical
manifestation of the disease often takes decades to develop.
The most common and severe presentation is cardiac
involvement.14 Cardiomyopathy related to Chagas disease
can range from isolated ECG abnormalities to dilated
cardiomyopathy with left ventricular dysfunction, heart
failure, thromboembolic events, dysrhythmias, and sudden
cardiac death.14 A retrospective cohort study estimated the
annual incidence of T. cruzi-mediated cardiomyopathy of
patients classified as indeterminate at 1.85% per year.15
The cardiac disorders ultimately are caused by a global
chronic myocarditis caused by the infiltration of cardiac
tissue by T. cruzi in combination with immune-mediated
cardiac damage.14
www.JAAPA.com 31
REVIEW ARTICLE
GI involvement occurs in 15% to 20% of patients who
progress to the chronic symptomatic phase, and is more
common in patients in central and southern South Amer-
ica.16 The esophagus and colon are most commonly affected,
resulting in massive dilation referred to as megaesophagus
and megacolon, respectively.16 Patients with megacolon
can present with significant constipation and volvulus.16
However, all sections of the GI system may be affected.16
Treatment of GI manifestations depends on the degree of
dilation and symptoms or comorbidities and can range
from symptomatic care to surgery.16
DIAGNOSTIC TESTING
Diagnostic testing for Chagas disease largely depends on
the patient’s phase at presentation. In the acute phase,
microscopy for parasites in prepared blood samples can
be used to make the diagnosis (Figure 2).12 High circulating
blood levels of parasites can be observed in the acute phase,
but subsequently drop to undetectable levels at 8 to 12
weeks after infection.6 Polymerase chain reaction (PCR) is
a rapid detection method when transfusion, transplant,
and congenital transmission is suspected.17 PCR must be
FIGURE 2.
Life cycle of T. cruzi, the parasite that causes Chagas disease
32 www.JAAPA.com
Copyright © 2018 American Academy of Physician Assistants
used under high parasitemia, such as the acute phase.17
Serologic testing is not useful in acute Chagas disease.12 In
contrast, serologic testing is preferred for diagnostic anal-
ysis in the chronic phase. Serologic tests using either enzyme-
linked immunosorbent assay (ELISA) or immunofluorescence
antibody assay establish the presence of host IgG against
T. cruzi antigens.12 Due to the suboptimal specificity of
these tests, the WHO has recommended the use of at least
two serial serologic tests using different T. cruzi antigens
to reduce the risk for false-positive results.12 Recently, a
novel ELISA test with 12 different T. cruzi antigens has
shown some promise with potentially greater sensitivity
but the validity and reliability has yet to be determined and
the test is not widely available.18
TREATMENT
Two drugs are recommended to treat Chagas disease:
benznidazole (BZL) and nifurtimox (NFX).19 BZL is
approved by the FDA for use in children ages 2 to 12
years and is used off-label in other age groups. NFX has
not been approved by the FDA but may be obtained
through the CDC via a special investigational protocol.20
SCOTT CAMAZINE / ALAMY STOCK PHOTO
Volume 31 • Number 12 • December 2018

BZL is considered first-line therapy for adults and chil-
dren.19 Adverse reactions include rash (photosensitive to
exfoliative), bone marrow suppression, and neuropathy.11
Adverse reactions to NFX include anorexia, nausea,
vomiting, irritability, insomnia, mental status changes,
tremors, and various neuropathies.11 The adverse reaction
profiles of both drugs are better in children than adults.11
Patients treated with antitrypanosomal medication dur-
ing the acute phase usually are cured—about 90% for
patients taking BZL and about 70% for those taking
NFX.7,12 The treatment duration with BZL is 60 days and
60 to 90 days for NFX.19
The treatment of chronic Chagas disease, either in the
indeterminate or chronic symptomatic phases, remains
a subject of much controversy in the literature. The WHO
recommends treatment with BZL for anyone with posi-
tive serology.21 This decision was based on several study
results. First, 60% of schoolchildren classified in the
chronic phase turned serologically negative after treat-
ment with BZL.22 Secondly, fewer children in the inde-
terminate phase developed cardiac complications when
treated with BZL.23 Lastly, clinical severity of chronic
cardiomyopathy decreased in BZL-treated patients rela-
tive to untreated patients.24 Other studies excluded
patients with advanced cardiomyopathy and heart failure,
due to the lack of effect on the existing pathology, and
patients with megaesophagus due to decreased drug
absorption.25 Treatment during pregnancy with BZL or
NFX is contraindicated due to lack of safety data.20 The
drugs also are contraindicated in patients with renal or
hepatic insufficiency.20
CONCLUSION
Up to 300,000 patients in the United States have Chagas
disease, and most are unaware of their infection. Most
infected patients have immigrated from endemic areas of
Central or South America. Because autochthonous trans-
mission is not prevalent in the United States, congenital
transmission from infected mothers to their infants may
play a more significant role. Clinicians in the United States
need to be cognizant of the clinical presentation, risk fac-
tors, and epidemiology of Chagas disease, and include this
parasitic infection on their differential diagnosis when
evaluating patients with consistent symptomatology and
history. JAAPA
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