Review TRENDS in Parasitology
12
The future of Chagas disease control
Chris J. Schofield1, Jean Jannin2 and Roberto Salvatella3
1
London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK
2
Neglected Tropical Diseases Department, World Health Organization (WHO), 1211 Geneva 27, Switzerland
3
Pan American Health Organization (PAHO), Montevideo CP 11300, Uruguay
In the past 15 years, there have been major advances in
the control of Chagas disease in most of the countries
endemic for this infection. Attention now turns to
the future continuity of surveillance and control interven-
tions – especially in regions where control has been so
successful that the epidemiological significance of Cha-
gas disease is in steep decline. The effort and expenditure
of the recent past cannot continue indefinitely, but a
degree of surveillance and selective intervention will be
required because of the risk of new infestations and
infections resulting from adventitious silvatic vectors
accidentally entering houses. In this review, we summar-
ize the progress of multinational control initiatives
against Chagas disease. In addition, we suggest that
the most sustainable approach to future surveillance
involves both the primary healthcare system and univer-
sity-based teams, with progressively greater attention
given to case detection and treatment. Such an idea is
not new, but we believe that it merits extensive discus-
sion because of the different ways that research and
health interventions are financed and because of the need
to establish clearer reporting links between the research
communities and the national health authorities.
Is Chagas disease conquered?
On 9 June 2006, at their 15th annual meeting, the
Intergovernment Commission of the Southern Cone Initia-
tive against Chagas disease formally declared Brazil to be
free of Chagas disease transmission due to Triatoma infes-
tans. This represents a remarkable achievement considering
that this species had been the primary domestic vector
infesting rural houses in >700 municipalities of the 12 most
populated states of Brazil, in addition to vast areas of
neighbouring countries of the Southern Cone (Figure 1).
Throughout Latin America, the transmission of Trypano-
soma cruzi, the causative agent of Chagas disease (American
trypanosomiasis), has been steadily reduced through a ser-
ies of multinational initiatives coordinated by the Pan Amer-
ican Health Organization (PAHO: http://www.paho.org). In
addition to Brazil, transmission has been effectively elimi-
nated in Uruguay (1997), Chile (1999), substantial areas of
Argentina, Bolivia and Paraguay, and parts of Central
America. Global disease prevalence has been reduced from
the 1990 estimates of 16–18 million people infected to
9 million (Box 1) and can be expected to decline further
through demographic changes and as a result of current
control interventions. But the health advances come at a
Corresponding author: Schofield, C.J. (cj.schofield@lshtm.ac.uk).
Available online 16 October 2006.
www.sciencedirect.com 1471-4922/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2006.09.011
Vol.22 No.
price – sometimes known as ‘el castigo del éxito’ (lit.
punishment of success) – whereby success in reducing the
epidemiological burden invariably also reduces political
interest and operational budgets.
Yet it is premature to believe that Chagas disease is
conquered. Experience from the programmes and cam-
paigns against Triatominae throughout the Americas
demonstrates that all domestic populations of this subfam-
ily can and should be eliminated. It is less clear whether
peridomestic populations of Triatominae can be so readily
eliminated [1] and whether interventions should be contem-
plated against silvatic populations [2]. Because available
techniques sometimes fail to eliminate all bugs inhabiting
peridomestic habitats and because silvatic populations of
Triatominae are widespread in the Americas, even the
successful elimination of domestic populations might not
be sustained against occasional reinfestation from perido-
mestic or silvatic habitats. Even without re-establishment of
the main domestic vectors such as T. infestans and Rhodnius
prolixus, a low level of accidental transmission can be
expected because of silvatic or peridomestic species entering
houses. The resulting transmission risks might be substan-
tially lower than those attributed to the original domestic
vectors – as shown by comparing human prevalence in areas
with Triatoma dimidiata, which was almost four times
lower than in areas with R. prolixus [3] – but are not
insignificant. Moreover, when an adventitious silvatic tria-
tomine contaminates comestibles in a house, the consequent
oral transmission can result in a localized ‘microepidemic’ of
acute cases of Chagas disease – as has occurred frequently in
the Amazon region and elsewhere in Brazil [4–6]. In such
situations, in which transmission occurs without the estab-
lishment of domestic vector populations, vector control
becomes of questionable priority compared with prompt
diagnosis and specific treatment.
The future scenario seems likely to involve a diverse
range of peridomestic and silvatic populations of Triato-
minae, some of which might colonize houses and some of
which might mediate the transmission of T. cruzi without
establishing domestic colonies. Such risks cannot be
ignored and will require adequate approaches to surveil-
lance, selective vector control, and treatment of new
human infections. However, this must be organized within
the anticipated framework of reduced political interest and
reduced operational budgets.
The balance of success
The Southern Cone Initiative against Chagas disease
followed a resolution by the Ministers of Health of
584 Review TRENDS in Parasitology Vol.22 No.12
Figure 1. Apparent distribution of Triatoma infestans. (a) The maximum predicted
distribution (in the absence of control interventions) from a geographic
information system (GIS) thematic analysis, which reveals a few points outside
the Southern Cone region (and in southern Chile and around the Peru–Bolivia–
Brazil border) that might be suitable for T. infestans but from where this species
has never been recorded. The predicted maximum distribution of T. infestans
covers 6 278 081 km2 [38]. (b) An estimate of current distribution based on reports
from the Intergovernment Commission for the Southern Cone Initiative, from
which the estimated distribution of T. infestans has been reduced to 913 485 km2.
Part (a) provided by David E. Gorla.
Argentina, Bolivia, Brazil, Chile, Paraguay and Uruguay,
meeting in Brasilia (Brazil) in 1991. It focused on the
interruption of T. cruzi transmission by eliminating
domestic vectors (particularly T. infestans), together with
extended screening of blood donors to reduce the risk of
transfusional transmission, and the promotion of maternal
screening for infection followed by specific treatment of
infected newborns. Similar initiatives were agreed in 1997
for the Central American and Andean Pact countries, and
in 2004 a surveillance initiative was announced for the
nine countries of the Amazon basin.
The progress of these initiatives has been widely
reviewed [7–12]. Extensive screening of blood donors for
T. cruzi infection is now carried out in most countries of the
Americas (Table 1), and the distribution of domestic
vectors has been markedly reduced, with transmission
interrupted over vast areas. Because the rate of new
infection has declined to zero over such substantial areas,
estimates of prevalence have been progressively reduced to
a current figure of 9.8 million people infected (Box 1). Of the
100 million people thought to be at risk from Chagas
disease in 1990, 60 million now sleep without the risk
of infection and without the nuisance and chronic blood loss
previously caused by domestic colonies of Triatominae.
The medical benefits of the control initiatives are
reflected in the progressive decline of hospitalizations
for Chagas disease [9]. This is primarily because of the
reduced numbers of new acute infections but also seems to
reflect a declining severity of chronic disease. This decline
in severity might be a result of halting reinfection, an idea
recently endorsed by studies of chronically infected mice in
which rates of severe cardiac lesions were significantly
lower in mice infected only once compared with mice that
were repeatedly reinfected [13]. A similar effect might
be reducing the likelihood of congenital infection because
the apparent rate of transplacental transmission from
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Box 1. The rise and fall of Chagas disease
Carlos Chagas first published his report of ‘a new human
trypanosomiasis’ in 1909 [39]. In the following years, there was
extensive argument about whether the discovery was important, or
even real [40,41], with the unnecessary polemic continuing even to
the end of the 20th century [42]. The arguments were trivial, at times
scurrilous, but probably contributed to the successive negation of a
well-deserved Nobel Laureate in recognition of Chagas’ outstanding
and detailed studies [41,43]*.
By 1960, Chagas disease had been reported from all countries of
Latin America, and the first WHO Expert Committee meeting on
Chagas disease estimated global prevalence of the infection to be 7
million people, with perhaps another 35 million at risk [44].
Successive reports revised these estimates steadily upwards to a
peak of 24 million people thought to be infected in the mid-1980s
[45]. By the end of the 1980s, data from wide-ranging serological
surveys provided more detailed estimates for most countries,
leading to the oft-quoted figures of 16–18 million people infected
with Chagas disease, with a further 90–100 million at risk [46,47].
From the same dataset of seroprevalence, annual incidence could
be calculated at 450 000 new infections per year in the absence of
control interventions, and the World Bank (http://www.worldbank.
com) ranked Chagas disease as the most important parasitic disease
of the Americas in terms of its socioeconomic impact, estimated as
disability-adjusted life years (DALYs) lost because of the infection
[48].
With the success of the Southern Cone Initiative, launched in
1991, and similar initiatives launched in 1997 for Central America
and the Andean Pact countries, prevalence estimates have been
steadily declining. As early as 1994, from reports of reduced
incidence in Argentina and Brazil, overall prevalence was estimated
to be 14 615 000 [49]. Estimates for these two countries, and Chile
and Venezuela were then further reduced, although prevalence
estimates for Ecuador and Mexico were revised upwards as a result
of more-extensive serological surveys, leading to an overall
estimated prevalence of 11 253 375 in 1998 [50]. The most recent
estimate, from the Disease Control Priorities Project of the NIH
(http://www.nih.gov) and World Bank, indicates an overall preva-
lence of 9.8 million people [51].
*
Carlos Chagas was formally nominated twice for the Nobel Prize in Medicine,
in 1913 and 1921.
chronically infected mothers seems to be declining in areas
where vectorial transmission has been interrupted.
The Chagas disease control interventions also seem to
have been extremely beneficial in financial terms. In
Brazil, for example, annual treatment costs for Chagas
disease were estimated to be approximately US$200
million per year in 1996, compared with the annual invest-
ment in control of approximately US$20 million; in Chile,
annual treatment costs were estimated to be US$14–19
million, compared with annual intervention costs of
approximately US$300 000. For the Southern Cone
countries as a whole, aggregate costs since 1991 have been
approximately US$320 million [9], which is within the
initial estimates of US$190–350 million [14]. The internal
rate of return on this investment was initially predicted at
just over 14% [11] but point studies show actual rates of
return of 30% in Brazil [15] and >60% for the province of
Salta in Argentina [16].
But, against the social, medical and financial successes
of the Chagas disease control initiatives, some difficulties
must be acknowledged. Although 60 million people no
longer share their homes with blood-sucking Triatominae,
40 million people remain at risk. Although 5 million
new infections of Chagas disease have probably been
 Review TRENDS in Parasitology Vol.22 No.12 585

Table 1. Screening of blood donors for Trypanosoma cruzi in R. prolixus from Central America, which seems to have
Latin Americaa been accidentally imported from a Venezuelan origin early
Coverage (%) Seropositive (%) in the 20th century [23,24]. Such arguments might also be
Southern Cone countries
applicable to populations of T. dimidiata in Ecuador and
Argentina 100 4.50
Bolivia 86 9.90 northern Peru, which seem to have been accidentally
Brazil 100 0.61 imported in pre-Columbian times [25,26], and to Rhodnius
Chile 75 b 0.47 ecuadoriensis in parts of northern Peru, which might
Paraguay 99 2.80 have been imported within the past 50 years [27]. To a
Uruguay 100 0.47
large extent, however, much of what seemed possible in
Andean Pact countries
Colombia 99 0.98
these elimination concepts has already been achieved. T.
Ecuador 100 0.15 infestans does seem to have been eliminated over much of
Peru 99 0.26 its range, R. prolixus is disappearing from Central Amer-
Venezuela 100 0.67 ica, and the recently launched national programme in
Central America Ecuador will probably have substantial success against
Belize 100 0.40
100 0.34
domestic T. dimidiata.
Costa Rica
El Salvador 100 2.46 The imperative to eliminate all domestic populations of
Guatemala 100 0.79 Triatominae derives not only from their capacity to trans-
Honduras 100 1.40 mit T. cruzi but also from their high nuisance value and
Nicaragua 100 0.49 contribution to chronic blood loss [28,29]. Although this
Panama 98 0.90
a
must remain central to future programmes, the underlying
Table based on data from Ref. [26], with revisions from 2006 Intergovernment
Commission reports.
rationale will be different. The idea of large-scale elimina-
b
98% in endemic regions. tion was justified as a strategy to prevent future reinfesta-
tions by that species. However, where reinfestation is
expected to be less frequent and probably due to local
prevented, transmission is still apparent in several coun- silvatic species, the more appropriate strategy will be of
tries and might even be increasing in parts of Argentina periodic intervention when householders report new infes-
[17], Venezuela [18] and the Amazon region [4]. Mexico, tations. The effectiveness of such an idea depends on three
Peru, Colombia and Costa Rica still have no national features: (i) a system to receive and acknowledge house-
programme for the control of Chagas disease vectors, holder reports; (ii) a system to collate such reports with
and programmes for screening blood donors remain below other information of operational and epidemiological rele-
targets in Bolivia and Mexico. But perhaps the greatest vance; and (iii) capacity to implement selective interven-
difficulty lies in the premature idea that Chagas disease tions in response to reports of individual and/or clustered
has been conquered, and the consequent dismemberment infestations. Such a design has already been proposed and
of executive services responsible for surveillance and con- tested for the control of Chagas disease in areas of Central
trol. Today, only four countries in the Americas – Nicar- America where the main vector is T. dimidiata (Box 2).
agua, Ecuador, Paraguay and Panama – retain an This species retains silvatic and peridomestic populations
executive structure with national responsibility for the in many areas, from which it can gradually recolonize
control of Chagas and other vector-borne diseases. In the houses from which the original domestic population has
other countries, responsibility has been devolved to state, been eliminated. The proposed strategy involves an initial
provincial and municipal authorities, with – at best – a programme to eliminate all existing domestic populations,
centralized authority retained only for statistics and leg- followed by an annual cycle of accumulating reinfestation
islation. Such decentralization risks heterogeneity of reports and an annual round of selective interventions in
action (and inaction), discontinuity of programme imple- response. In parallel, progressively greater emphasis is
mentation (especially of surveillance) and inefficiencies given to active case detection and treatment, especially
due to duplication of administrative effort – precisely among school-age children.
the problems that the multinational initiatives, with all
countries working simultaneously within a coordinated Case detection and treatment
framework, were designed to avoid. The change from an elimination strategy to one of
continual selective intervention carries implicit acceptance
Vector control strategy that occasional accidental transmission might occur –
When the Southern Cone programme was launched in chiefly due to adventitious silvatic vectors entering houses.
1991, it was believed that the main vector in the countries In the past, such an idea was seen to be problematic
affected, T. infestans, could be eliminated over most of its because of the belief that treatment of human cases would
range. This idea was based on historical reconstruction [19] be satisfactory only if administered within the early acute
progressively supported by genetic studies [20–22] indicat- phase of infection, although accumulating experience
ing that, in most Southern Cone countries, T. infestans had begins to indicate otherwise.
been accidentally imported in relatively recent times, par- The two drugs available for specific treatment of T.
ticularly during the past 100 years. The control interven- cruzi infection are nifurtimox (Lampit1), launched by
tions could be seen as correcting a historical accident and Bayer (http://www.bayer.com) in 1967, and benznidazole
restoring the vector distribution to its origins. Similar (Rochagan1, Radanil1), launched by Roche (http://
arguments were implicit in the idea of eliminating www.roche.com) in 1972. Initially shown to be effective
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586 Review TRENDS in Parasitology Vol.22 No.12
Box 2. Steps in the proposed operational strategy for the
control of Triatoma dimidiata in Central America
The following information was adapted from Ref. [52].
1. In each school in the endemic areas, serological testing of a
random sample of 30 schoolchildren using the Chagas
Stat-Pak1 and a questionnaire for possible recognition of
Triatominae.
(a) If all tests are negative and no child reports having seen T.
dimidiata in their house, the school catchment area apparently
has no active transmission.
(b) If three or fewer children are positive for Chagas disease, the
school catchment area is considered a medium priority for
entomological survey and control interventions. All positive
children given quantitative ELISA for confirmation, followed by
specific treatment with benznidazole or nifurtimox.
(c) If more than three children are positive, the school catchment
area is considered a high priority for entomological survey and
control interventions. All children in school are tested by Chagas
Stat-Pak1, with all positives given quantitative ELISA for
confirmation, followed by specific treatment with benznidazole
or nifurtimox.
2. School catchment areas can now be ranked in terms of
apparently active transmission. In this order, they can be visited
for entomological surveys in each house, followed by residual
spraying of all houses confirmed to be infested; all houses are
identified by their geographical coordinates, and all house-
holders are informed about T. dimidiata and asked to report all
such insects to the local health centre.
3. Health centre reports are collated and mapped during the year.
Isolated reports of infestation can be checked, with the houses
sprayed if infestation is confirmed; if several reports indicate a
cluster of infested houses, all houses in the apparent cluster can
be checked and sprayed.
4. If, during a reporting year, no reports are received from houses
in what was a previous infestation cluster, the cluster can be
checked to make sure that the absence of reports is not due to a
breakdown of the reporting system.
5. Steps 1 and 2 can be repeated in accordance with epidemio-
logical assessment and available resources.
at curing acute infections, these drugs were largely
discarded for treatment of chronic T. cruzi infections
because of a high likelihood of serious side-effects com-
bined with an apparently low likelihood of radical cure
[30]. Such ideas are being challenged by evidence that
serious side-effects are much less frequent in younger
age-groups and that reversion to seronegativity after
treatment can occur in a large proportion of patients –
especially children – although this might not occur for
several years [31,32]. National policy in several countries
is now to offer specific treatment to all cases that occur in
patients under 14–15 years of age, whether acute or
chronic, and current research on adults in Argentina
indicates that this policy could be extended to a much
wider range of patients [33–35].
The World Health Organization (WHO: http://
www.who.int) is working in partnership with industry to
ensure adequate supplies of both drugs. Nifurtimox is now
manufactured by Bayer in El Salvador and can be made
available free of charge through WHO and PAHO; the
supply of benznidazole has been guaranteed by Roche until
adequate production can be sustained by the Brazilian
laboratory Laboratório Farmacêutico do Estado de
Pernambuco (LAFEPE) – although neither the cost of
the drug nor procedures for its distribution outside Brazil
have been finalized. A further issue to be resolved concerns
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the feasibility and the most appropriate techniques for
active case detection of asymptomatic Chagas disease; this
is actively pursued in Central America, using the Chagas
Stat-Pak1 for a rapid assessment of schoolchildren [36],
followed by quantitative ELISA to confirm positivity and
monitor changes in serological titres after treatment (Box
2). In some countries, however, treatment is discouraged
for non-acute cases, and may be authorized only after
residual house spraying to remove vectors.
Outline for the future
The future scenario for Chagas disease control must
continue to be based on the idea of eliminating all existing
domestic populations of Triatominae but then accepting
that reinfestation might occur or that adventitious silvatic
Triatominae might enter a house and cause disease trans-
mission without establishing a new domestic colony – as in
Amazonia. In such a scenario, large-scale vector control
campaigns of the style of the multinational initiatives
would become progressively less relevant as existing
domestic infestations are eliminated. However, surveil-
lance and focal interventions against newly established
domestic colonies of Triatominae would be required. In
addition, improved parasitological surveillance would be
warranted, with the idea of offering specific treatment to
all new cases of infection and probably to asymptomatic
chronic cases. The key issue is how to maintain entomo-
logical and parasitological surveillance, especially as the
incidence of new infestation and infection declines. Much is
written about the importance of community participation,
and it is indeed a key component both of the initial inter-
ventions and of the subsequent surveillance, but commu-
nity interest wanes when there is little to report, so an
additional approach is required. This could be provided by
university-based research teams [37] but would be of little
relevance without a clear reporting structure so that data
can be collated and selective interventions undertaken
where necessary.
Perhaps one of the greatest achievements of the
multinational initiatives against Chagas disease is that
surveillance and control of the disease and its vectors are
currently on the agenda of all endemic countries, even
those such as Belize, Guyana and Suriname, where the
problem has been minimal. This means that a degree of
vector and disease surveillance will be carried out in all of
these countries so that, with adequate data collation, it
should be possible to detect epidemiological trends and
potential new outbreaks of transmission. But such an idea
must emphasize the need for adequate collation of avail-
able data at national and regional levels, which at present
is often lost between official reports and formal publication.
There is currently no international system – beyond review
articles – that can monitor and collate epidemiological data
over a continental scale.
Concluding remarks: towards a sustainable end-point
The most consistently successful programme against
Chagas disease has been that of the Brazilian state of
Sao Paulo – a programme initiated with a state-wide ‘attack
phase’ in 1964–1967 and continued through a series of
strategic adjustments in accordance with the changing
 Review TRENDS in Parasitology
Box 3. Current and future phases in Chagas disease control
Phase 1
1.1 Elimination of all existing domestic populations of Triatominae;
this requires one or two spray rounds, designed to treat all
houses in infested localities in the case of Triatoma infestans or
Rhodnius prolixus, or targeting only those confirmed to be
infested with other vectors.
1.2 Organization of community-based surveillance networks. These
report the presence of residual (or new) domestic infestations to
a local voluntary post (posto de informacion sobre triatomi-
neos), with adequate reporting to the local health authorities,
entomological confirmation and written acknowledgement of
householder reports, followed by selective intervention where
required or requested.
1.3 Improved and standardized screening of blood donors (with
clinical follow-up and psychological counselling for those found
to be infected).
Phase 2
2.1 Continuation and support for community-based surveillance
networks, with selective interventions carried out by local health
authorities.
2.2 Development of the community networks as general health
surveillance systems linked to the primary healthcare system of
that locality.
2.3 Routine blood-slide microscopy from all febrile cases (com-
bined with haemoconcentration techniques where possible) to
diagnose new infections and offer prompt specific treatment as
necessary.
2.4 Encouragement of university-based field teams to carry out
investigative projects designed to evaluate the progress of
Chagas disease control and study the biology of non-dom-
iciliated vectors in specific regions (this could involve logistic
support from the local health authorities and financial support
from the national research councils).
Phase 3
3.1 Development of a national database for epidemiological
surveillance of Chagas disease using GIS techniques, with
mandatory reporting of all new cases of infection and all
findings of domestic, peridomestic and silvatic populations of
Triatominae (such reporting could be a condition of research
council support for academic research teams and of national
support to local health centres).
3.2 Development of the Chagas database and reporting system for
other pathologies, ideally linked to a small ‘rapid deployment
force’ of highly trained professionals able to support emergency
vector control or public health interventions in all parts of the
country.
Phase 1 is well advanced in most countries, and a small number –
notably Brazil and some Central American countries – is advancing
with phase 2. None, however, has yet advanced to phase 3.
epidemiological circumstances (D. Wanderley, PhD thesis,
Universidade de Sao Paulo, Brazil, 1994). Although
T. infestans was probably eliminated from Sao Paulo by
1990, a system of community-based surveillance is main-
tained for secondary vectors (e.g. Triatoma sordida and
Panstrongylus megistus), together with centralized data
assimilation and selective interventions where necessary.
Sao Paulo has been effectively free of Chagas disease trans-
mission since the early 1990s and offers a model for the
various phases in Chagas disease control. This includes the
essential idea that, although domestic vector populations
can and should be eliminated, there will be a perennial need
for surveillance, data assimilation and selective interven-
tions. In addition, a primary healthcare approach is
required to detect and treat new cases of Chagas disease
(Box 3) – although this will require a consensus about the
most appropriate diagnostics and treatment regime.
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Vol.22 No.12 587
At national and regional levels, however, the focus in
recent decades has been on eliminating the primary
domestic vectors. Less thought has been given to the design
of an institutionally stable end-point to maintain the
advances, prevent recrudescence of transmission and
respond adequately to new cases that might occur. Such
a system will depend crucially on a capacity to seek and
assimilate georeferenced epidemiological data – from
whatever source – and to organize serological screening,
and treatment of new cases, together with selective vector
control interventions where necessary. Medical profes-
sionals and the primary healthcare system, together with
schools (Box 2), would have a fundamental role but only
with adequate training and clear reporting lines to the
epidemiological surveillance centre. In many countries,
academic research teams also have a significant role in
the surveillance and control of Chagas disease, and this
should be encouraged as an important complement to the
health surveillance structure. It is a way to accord national
relevance to research, improve interactions between
health and education authorities, and might come to
represent the primary source of specific epidemiological
information.
Acknowledgements
This review has benefited from international collaboration through the
Latin American Network for Research on the Biology and Control of
Triatominae (ECLAT). We also thank Sergio Sosa-Estani for additional
information about current trials of specific treatment for Chagas disease
in chronically infected adults, and David E. Gorla for access to
unpublished geographic information systems (GIS) studies of Triatoma
infestans distribution.
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