ARTÍCULO SOBRE MAL DE CHAGAS EN CARACAS

PARA MIS ESTUDIANTES: ARTÍCULO PUBLICADO EN REVISTA INGLESA SOBRE INFECCIONES. TRATA DE MAL DE CHAGAS ORAL EN CARACAS. LEÁNLO, APRENDAN MEDICINA Y PRACTIQUEN EL INGLÉS.

Orally Acquired Chagas Disease: Lessons from an Urban
School Outbreak
Michael A. Miles
Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
(See the article by de Noya et al, on pages 1308–1315.)
Received 19 January 2010; accepted 19 January 2010;
electronically published 22 March 2010.
Potential conflicts of interest: none reported.
Financial support: Wellcome Trust and EC contract 223034
(ChagasEpiNet).
Reprints or correspondence: Prof Michael A. Miles, Pathogen
Molecular Biology Unit, Dept of Infectious and Tropical Diseases,
London School of Hygiene and Tropical Medicine, Keppel St,
London WC1E 7HT, UK (michael.miles@lshtm.ac.uk).
The Journal of Infectious Diseases 2010;201(9):1282–
1284
_ 2010 by the Infectious Diseases Society of America. All
rights reserved.
0022-1899/2010/20109-0002$15.00
DOI: 10.1086/651609

The protozoan pathogen Trypanosoma
cruzi causes Chagas disease, one of the
most important parasitic infections in
Latin America. Without effective treatment,
infection is usually for life. A likely
outcome of infection is heart disease, with
electrocardiogram abnormalities and cardiomyopathy.
In some geographical areas,
this may be complicated by megasyndromes,
particularly megaesophagus and
megacolon [1].
The insect vectors are blood-sucking
triatomines. Transmission occurs when
insects feed, but the route is precarious
and indirect, by contamination of mucous
membranes or abraded skin with T. cruzi–
infected triatomine feces. The main culprit
vectors are a few triatomine species that
colonize poor rural dwellings and feed
from the inhabitants and from their domestic
animals. Despite the recent success
of international programs to control such
domestic triatomines (notably, Triatoma
infestans in the Southern Cone countries
of South America), wide regions of domestic
transmission remain. Furthermore,
T. cruzi is a zoonosis; there are many
mammal reservoir hosts (such as opossums,
armadillos, and rodents), and many
triatomine species act as vectors in sylvatic
habitats. Such sylvatic bugs pose a threat
by replenishing household colonies or by
new adaptations to domestic habitats, as
well as by occasional incursion of adult
insects that fly into houses and may cause
sporadic cases of Chagas disease.
T. cruzi is not confined to transmission
by contamination of the host as the vector
feeds, and it has several secondary routes
of dissemination. Potential transfusion of
contaminated blood demands that all
blood donors in areas of endemicity
should be screened with serological testing.
Similarly, transplant of organs and
other tissues may require screening of
both donors and recipients, who, if they
carry T. cruzi, are liable to experience relapse
to an acute infection when immunosuppressed.
Ideally, the possibility of
congenital transmission requires followup
of infants born to seropositive mothers. T.
cruzi can travel with Latin American migrants,
and these secondary routes allow
transmission beyond the established
regions of endemic Chagas disease. Thus,
T. cruzi infection has been demonstrated
among potential blood donors in North
America and in Europe, where occasional
autochthonous transmission has occurred.
As if that were not enough, there is at
least 1 more increasingly apparent and important
means of T. cruzi dissemination,
and that is transmission by the oral route,
which is the focus of the report by deNoya
et al [2] that appears in this issue of the
Journal. Consumption of infective forms
of T. cruzi may occur as the result of eating
raw or undercooked blood and meat of
reservoir hosts or by contamination of
food with the anal gland secretions of the
common opossum, Didelphis (which, extraordinarily,
may contain forms equivalent
to the infective forms in the hindgut
of the triatomine). However, by far the
most likely source of orally acquired T.
cruzi infection is food contaminated by an
entire infected triatomine or by infected
insect feces. Not only are the adult triatomine
winged, but several species are attracted
to artificial lights, bringing them
into houses or to other sites where food
is produced locally or commercially. In experimental
animals, infection by ingestion
and gastric invasion can readily occur and
is believed to be an important mechanism
of propagation among omnivorous or insectivorous
mammal reservoirs of infection.
T. cruzi is destroyed in dry triatomine
feces and by high temperatures, so the
food that is contaminated must remain
EDITORIAL COMMENTARY • JID 2010:201 (1 May) • 1283
moist or be partially liquid and be kept at
not much more than ambient temperature.
In such foods, T. cruzi may survive
for hours or days and might even multiply
in some foodstuffs. Cooling does not kill
T. cruzi and may prolong survival, although
freezing without chemical protection
can destroy the organism. Palm, sugar
cane, and fruit juices are therefore ideal
contaminated sources for oral outbreaks,
because they are often grown, harvested,
and pressed locally, with the aid of artificial
light, in rural or periurban areas where
sylvatic triatomines may be abundant.
Orally acquired human infection with
T. cruzi has been known since the 1930s
but has risen to more recent prominence
as a result of the series of outbreaks that
has occurred in the Amazon region, which
have been associated with preparation and
consumption of popular juice from the
fruit of the ac¸ai palm (Euterpe oleracea)
[3]. These outbreaks are especially notable
because, although T. cruzi is enzootic and
abundant among Amazonian sylvatic vectors
and reservoirs, there are as yet no
commonly established domestic triatomine
species, and orally acquired Chagas
disease therefore accounts for approximately
one-half of the known Amazonian
cases. South of the Amazon region in Brazil,
several outbreaks have been associated
with consumption of sugar cane juice.
The report by de Noya et al [2] in this
issue is unique and extraordinary in several
respects. First, it describes by far the
largest known outbreak of orally acquired
Chagas disease. Second, it is urban and
occurred in a school. Third, it indicates a
new type of contaminated food, guava
fruit juice. Furthermore, the study incorporates
considerable detail on the clinical
presentation and uses an interesting combination
of epidemiological methods. Several
important conclusions are derived
from or reinforced by the investigation.
A crucial initial observation was the detection
by microscopy of trypomastigotes
in blood smears obtained from the 9-yearold
index case patient, which triggered follow-
up in other students who were hospitalized
with fever of unknown origin. A
combination of parasitology, serological
testing, and polymerase chain reaction
amplification of T. cruzi kinetoplast DNA
led to the confirmation of 103 cases
among the 1000 individuals exposed. As
expected, cardiovascular symptoms were
commonplace, whereas some clinical features
were considered to be unusual and
possibly related to the oral transmission
route. Because the school was in a relatively
well-developed urban area with no
evidence of vector infestation, it was presumed
that contaminated food must be
the source.
A traditional investigative epidemiological
approach was then used, with a
within-cohort, case-control approach for
all students, staff, at-risk contacts, and external
food producers. Questionnaires,
odds ratios, and multivariate analysis revealed
that guava juice, prepared and
cooled over night in a Caracas suburb, was
the likely source. Infection was most common
among the morning shift of children,
who were the first to consume the juice.
Peridomestic rodents and T. cruzi–infected
Panstrongylus geniculatus were found in
the suburb where the juice was prepared;
P. geniculatus has previously shown signs
of adapting to peridomestic habitats in
both Brazil and Venezuela [4]. Commendably,
de Noya et al [2] then married
this traditional approach with molecular
characterization of the T. cruzi genetic lineage
that was involved in the outbreak. A
provisional comparison of 3 isolates from
patients with 1 isolate from P. geniculatus
found no differences, which supported the
identification of the source.
T. cruzi is not a single entity but a complex
of at least 6 genetic lineages or discrete
typing units. Until recently, these were divided
into TcI and TcIIa-e, but they have
now, more logically, been redesignated as
6 distinct groups—TcI, TcII, TcIII, TcIV,
TcV, and TcVI—with differences between
ecologies, hosts, vectors, and geographical
and disease distributions [1, 5]. North of
the Amazon, the principal agent of Chagas
disease is TcI, which, consistent with the
Caracas outbreak, causes severe and fatal
cardiomyopathy. In contrast, in the Southern
Cone countries, where megaoesophagus
and megacolon are common, Chagas
disease is predominantly caused by TcII,
TcV, and TcVI. It is of considerable epidemiological
interest that TcV and TcVI
are natural TcII /TcIII hybrids, which have
spread rapidly through the Gran Chaco
and adjacent regions of South America.
Robust and relatively straightforward
methods are now available to identify all
6 T. cruzi genetic lineages [6], and multilocus
microsatellite typing (MLMT) provides
additional high-resolution analysis
for molecular epidemiological tracking
[1]. It would be of great value to deploy
these methods far more widely and routinely
to research groups in areas of endemicity,
to allow more-detailed epidemiological
investigations. Although investigation
of the Caracas outbreak benefited
from the limited molecular comparisons,
under ideal circumstances, far more isolates
would have been available and characterized
in detail by molecular methods.
Both multilocus sequence typing and
MLMT can also be applied to resolve population
structures of closely related and
morphologically similar triatomine species,
clarifying the risk of reinvasion from
sylvatic cycles after vector-control programs
[1].
Several important messages might be
drawn from the landmark study of de
Noya et al [2]. First, the importance of
awareness among clinicians of the presentation
of Chagas disease beyond the usual
epidemiological circumstances, and even
among populations far from areas of vector-
borne transmission. Second, the need
for a rapid response, including standardized,
proven diagnostic procedures and
easy access to chemotherapy. Third, the
importance of the traditional epidemiological
approach and the added value of
molecular methods, which allow precise
epidemiological tracking and should be
1284 • JID 2010:201 (1 May) • EDITORIAL COMMENTARY
more widely deployed. Fourth, the need
for health education to diminish the risk
of orally acquired Chagas disease. Vigilance
or cleaning of crops might exclude
insects. Presses should ideally be covered
to protect against triatomines and should
not be operated directly beneath or adjacent
to artificial light. Commercial ac¸ai
production can be made safe by pasteurization.
Vulnerable juice preparations
should not be left uncovered and open to
contamination. Finally, despite the novelty
and undeniable importance of orally acquired
Chagas disease, it is well to remember
that domestic vectors still colonize
houses across wide areas, and efforts to
eliminate them must be sustained.
References
1. Miles MA, Llewellyn MS, Lewis MD, et al. The
molecular epidemiology and phylogeography
of Trypanosoma cruzi and parallel research on
Leishmania: looking back and to the future.
Parasitology 2009; 136:1509–1528.
2. de Noya BA, Diaz-Bello Z, Colmenares C, et
al. Large urban outbreak of orally acquired
acute Chagas disease at a school in Caracas,
Venezuela. J Infect Dis 2010; 501(9):1308–1315
(in this issue).
3. Pan American Health Organization. Doenc¸a de
Chagas: Guia para vigilancia, prevenc¸a˜o, controle
e manejo clı´nico da doenc¸a de chagas
aguda transmitida por alimentos. PAHO/HS/
CD/539.09. 2009. http://bvs.panalimentos.org.
Accessed 18 March 2010.
4. Feliciangeli MD, Carrasco H, Patterson JS, et
al. Mixed domestic infestation by Rhodnius prolixus
Stal, 1859 and Panstrongylus geniculatus
Latreille, 1811, vector incrimination, and seroprevalence
for Trypanosoma cruzi among inhabitants
in El Guamito, Lara State, Venezuela.
Am J Trop Med Hyg 2004; 71:501–505.
5. Zingales B, Andrade SG, Briones MR, et al. A
new consensus for Trypanosoma cruzi nomenclature:
second revision meeting recommends
TcI to TcVI. Mem Inst Oswaldo Cruz 2009;
104:1051–1054.
6. Lewis MD, Ma J, Yeo M, et al. Genotyping of
Trypansoma cruzi : systematic selection of assays
allowing rapid and accurate discrimination
of all known lineages. Am J Trop Med Hyg
2009; 81:1041–1049.