Chagas disease (American trypanosomiasis) in Mexico: An update ...

Acta Tropica 127 (2013) 126–135

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Chagas disease (American trypanosomiasis) in Mexico: An update Alejandro Carabarin-Lima a , María Cristina González-Vázquez b , Olivia Rodríguez-Morales a , Lidia Baylón-Pacheco c , José Luis Rosales-Encina c , Pedro Antonio Reyes-López a , Minerva Arce-Fonseca a,∗ a b c

Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico Department of Cellular Biology, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City 07360, Mexico Department of Infectomics and Molecular Pathogenesis, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City 07360, Mexico

a r t i c l e

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Article history: Received 5 December 2012 Received in revised form 11 April 2013 Accepted 17 April 2013 Available online xxx Keywords: Trypanosoma cruzi Chagas disease Vectors Mexico

a b s t r a c t Chagas disease is a parasitic infection caused by the protozoan Trypanosoma cruzi, a flagellated organism that is transmitted mainly to humans through the infected feces of triatomine kissing bugs (vector transmission in endemic areas) or by transfusion of infected blood, donations of infected organ, or transmission from an infected mother to her child at birth. Chagas disease was first described in 1909 by the Brazilian physician Carlos Chagas, and due to the parasite’s distribution throughout North, Central and South America, the disease is commonly known as American trypanosomiasis. However, this disease is now present in non-endemic countries such as Canada, the United States of America, and several countries in Europe (principally Spain). Moreover, Chagas disease was recently designated by the World Health Organization as one of the main neglected tropical diseases. The aim of this review is to summarize the research efforts recently described in studies conducted in Mexico on Chagas disease. In this country, there are no existing vector control programs. In addition, there is no consensus on the diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and trypanocidal therapy is not administered to chronic patients. The actual prevalence of the disease is unknown because no official reporting of cases is performed. Therefore, the number of people infected by different routes of transmission (vector, congenital, blood transfusion, organ transplantation, or oral) is unknown. We believe that by promoting education about Chagas disease in schools starting at the basic elementary level and including reinforcement at higher education levels will ensure that the Mexican population would be aware of this health problem and that the control measures adopted will have more acceptance and success. We hope that this review sensitizes the relevant authorities and that the appropriate measures to reduce the risk of infection by T. cruzi are undertaken to provide the Mexican people a better quality of life. © 2013 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4. 5. 6. 7. 8. 9.

Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-vector transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Phases of disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Domestic animals as reservoirs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Development of vaccines against Chagas disease: the news . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

127 127 127 128 129 130 131 133 133 133 133 133

∗ Corresponding author at: Department of Molecular Biology, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico. Tel.: +52 55 55 73 29 11x1461; fax: +52 55 55 73 09 94. E-mail address: mini [email protected] (M. Arce-Fonseca). 0001-706X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.actatropica.2013.04.007

A. Carabarin-Lima et al. / Acta Tropica 127 (2013) 126–135

1. Methods The aim of this review was to summarize the research efforts described recently in studies in Mexico about Chagas disease. For this purpose, a thorough literature review was conducted to obtain basic demographic information on the Mexican population, information on host and vector species, and the epidemiological parameters for which direct estimates were possible. Reports were obtained by searching PubMed (from January 2011 to February 2013) using the terms “Chagas disease,” “American trypanosomiasis,” “vectors,” “seroprevalence,” “reservoirs,” “congenital transmission,” and “blood transfusion” together with “Mexico.” From the over 500 articles retrieved, approximately 80 papers were selected. Most discarded papers were focused exclusively on genetics or were published before the year 2000, so only those papers with unique data or clinical cases in which no update was available were selected. In addition, reports and journals that were not cited in PubMed were identified. Publications in both English and Spanish were reviewed.

2. Introduction Currently, the neglected tropical diseases (NTDs) are the principal infections of the world’s poorest people living in Africa, Asia, and the Americas (Hotez et al., 2007). The NTDs represent a group of chronic parasitic, bacterial, and viral infections that actually promote poverty in people because they affect child development, pregnancy outcome, and worker productivity (Hotez et al., 2009). Chagas disease is an NTD and a serious threat to human health in Latin America. The disease is one of the most important emerging health problems in Europe and the United States of America (USA) (Gascon et al., 2010). According to a World Health Organization (WHO) report released in 2010, approximately 10 million people are infected, and more than 25 million people are at risk of infection in endemic countries (WHO, 2010). It has been assessed that more than 300,000 infected patients live in the USA (Bern and Montgomery, 2009). Recently, a study documented the burden of vector-borne autochthonous Trypanosoma cruzi infection in United States blood donors. This report adds 16 new autochthonous cases to the list of seven documented cases, 5.5% of seropositive donors are expected to have acquired the infection from the vector in the United States, which would represent one case per 485,000 donations. T. cruzi vectors in the United States live predominantly in a sylvatic cycle, and the presence of mammalian reservoir species on the donor’s property would suggest that these individuals lived in areas with the potential for the establishment of a sylvatic or peridomestic cycle. The vectors capable of transmitting the parasite and infected reservoir mammals have been identified in 28 and 17 states, respectively (Cantey et al., 2012). Up to 40% of chronically infected individuals develop cardiac alterations, and up to 10% develop digestive and/or neurological alterations that result in considerable morbidity and mortality (WHO, 2006). Currently, nifurtimox and benznidazole are the only licensed drugs with proven efficacy against Chagas disease. Both drugs have significant activity during the acute phase of the disease, causing parasitological cure in up to 80% of patients if treated early; however, it appears that the efficacy of the antiparasitic treatment is inversely related to the chronicity of the disease. A longitudinal study demonstrated a significant decrease in the progression of cardiomyopathy and increased negative seroconversion among benznidazole-treated patients compared with untreated individuals (Viotti et al., 2006). Moreover, some studies have shown that after treatment, congenitally infected infants were observed to be

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cured, demonstrating the efficacy of the treatment in newborns (Schijman et al., 2003; Oliveira et al., 2010). Other recent data suggest that although the treatment of chronically infected women does not guarantee cure, the risk of congenital transmission is decreased by treating infected women before pregnancy. These findings demonstrate that the treatment of women before pregnancy prevents congenital Chagas disease transmission (Murcia et al., 2013). Considering these data, we believe that treatment in fertile women, newborns and children should be a priority in Mexico to control the spread of the disease; however, it will be necessary to promote diagnosis and treatment programs in maternity wards, nurseries and elementary schools. These programs should be promoted by the Ministry of Health in conjunction with research groups and assisted by international institutions such as the WHO and the Pan American Health Organization to ensure operation. Consensus documents from the WHO, the United States, and Brazil strongly recommend antitrypanosomal treatment for acute, congenital, and reactivated T. cruzi infection and for children (up to 12 or up to 18 years of age, depending on the publication) with chronic infection. The recommendations for adults with longstanding infection carry a lower evidence grade and strength because of the lack of data from randomized clinical trials. Nevertheless, most recommendations published since 2000 include provisions to offer treatment for this group of patients (Bern, 2011). Importantly, parasites naturally resistant to chemotherapy have been reported in several regions of Latin America (Camandaroba et al., 2003), and no vaccine is currently available. The economic impact of Chagas disease is significant and includes the high social cost attributable to chronic infections. It is important to highlight that the damage caused by the parasite is irreversible, leaving consequences that often make it impossible for the patients to perform their daily activities, and many people still of productive age die prematurely (Silveira, 2011; Silveira and Dias, 2011).

3. Non-vector transmission Vector transmission of T. cruzi has been the most important mechanism through which humans become infected with the parasite. Natural transmission of the disease occurs through feces of the vector (haematophagous triatomine kissing bugs, family Reduviidae) deposited near a skin lesion or a mucous membrane (80–90%). In non-endemic areas, transmission may occur via organ transplantation, blood transfusion, congenital transmission or as a result of a laboratory accident (Dias, 2000; Gutierrez et al., 2009). In non-vector transmission, blood transfusion and congenital Chagas disease have re-emerged as two very important factors for transmission in non-endemic areas. These non-vector transmission methods are most troubling in urbanized areas. In Spain, Chagas disease is considered an emerging infection because of the increasing number of immigrants from Latin America. A study was conducted to estimate the prevalence of T. cruzi infection in blood donors in Catalonia, and an overall seroprevalence of 0.62%, with 11 confirmed donors positive among the 1770 at-risk donors studied was observed. The highest rate (10.2%) was observed in Bolivian donors. Interestingly, the countries of origin of positive donors were Bolivia, Argentina, Ecuador, and Paraguay, and there was one Spaniard who had been living in Venezuela for 27 years (Piron et al., 2008). Another study assessing the risk of vertical transmission found a 3.4% seroprevalence of T. cruzi infection in Latin American pregnant women and demonstrated that 7.3% of the newborns of these mothers were infected. Of the participants that were seroreactive to T. cruzi, 91% of these women were from ˜ et al., 2009). Bolivia (Munoz Studies conducted in blood donors in the USA have demonstrated that T. cruzi seropositive donors have persistent infection

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with demonstrable parasitemia long after acquisition of infection (Leiby et al., 2008). These studies have reported prevalence rates of 0.19% in Los Angeles, 0.08% in Miami (Leiby et al., 2002), and 0.052% in New York (Zaniello et al., 2012). The prevalence of Chagas disease in blood banks has been observed in several countries in Latin America, such as Argentina (4.9–17.6%), Bolivia (51%), Brazil (2.9–14.6%), Chile (3.7–14.5%), Honduras (11.6%), Paraguay (11.3%), Uruguay (4.7–7.7%), Venezuela (1.3%), Colombia (2.5–7.5%), Costa Rica (1.6%), Ecuador (3.2%), and Peru (12.9%) (Moncayo, 2003). Recent reports indicated a 0.47% prevalence for T. cruzi in blood donors in Brazil (Araújo et al., 2008) and an 18% prevalence in Chaco province, an area of Argentina with highly endemic T. cruzi infection (Remesar et al., 2009). Fortunately, the coverage in screening tests for T. cruzi antibodies in blood donors is increasing, reaching almost 100% in Uruguay and parts of Brazil, and coverage has also reached high levels in Argentina and some endemic regions of Chile, Venezuela, Honduras and Paraguay (Schmunis et al., 2001). Some estimates indicate there are 69,000 new infections annually, and only 30% of donated blood is screened before transfusion in Mexico (Petherick, 2010). In the state of Puebla, prevalences of 7.7% in 2001 (Sánchez-Guillen et al., 2002) and 1.24% in 2005 (Monteón et al., 2005) in blood donors were demonstrated, and for Mexico City in 2004 (Cabrera et al., 2004) and 2005 (Hernandez-Becerril et al., 2005) a prevalence was 6.8% and 0.37%, respectively, was reported. These discrepancies may be a result of differences in laboratory procedures, variations in immunologic testing techniques, or disparate cutoff values. Some efforts to control the spread of Chagas disease via blood transfusion are ongoing. In accordance with the official blood donation regulations, the testing of blood donors for Chagas disease is mandatory, and this requirement is included in the Norma Oficial Mexicana (NOM-003-SSA2-1993) “for the disposition of human blood and its components with therapeutic aims”; however, this test is only performed in blood donors with a history of residence or origin in T. cruzi endemic areas. This concept should be changed, and every donor should be tested for Chagas disease. A new Mexican regulation for the prevention, diagnostic, treatment and all activities involved with the control of Chagas disease is necessary. The congenital transmission of Chagas disease currently has epidemiological importance because it is partially responsible for the spread of the disease in non-endemic areas worldwide. Epidemiological data estimate >15,000 cases per year of congenital infection by T. cruzi in Latin America (PAHO, 2006). Prevalences of infection in pregnant women between 2% and 51% have been reported in several Latin American countries in both rural and urban regions (Carlier et al., 2011). Recently, a study performed in the Choapa province in Chile demonstrated a 3.4% seroprevalence of T. cruzi infection in pregnant women and 4.7% congenital transmission (Apt et al., 2013). Likewise, a study conducted in Colombia reported a 2.7–3.5% prevalence in pregnant women and a 20% congenital transmission prevalence (Manrique-Abril et al., 2009). More recently in the same country, Cucunubá et al. (2012) reported a 4% T. cruzi infection prevalence in pregnant women. Chagas disease represents one of the major health problems in Bolivia, where T. cruzi infection prevalence in pregnant women is 23.6%, and the prevalence is 3.4% for congenital transmission (Salas Clavijo et al., 2012). Finally, studies performed by Gurtler et al. (2003) in Argentina indicated that the probability of congenital transmission from pregnant women varies between 2.6% and 6.7% in accordance with the geographical areas of the country (endemic or non-endemic regions). The WHO reported that approximately 243,000 women in Mexico are fertile and infected with Chagas disease and estimated that 1100 newborns are at risk of infection each year (WHO, 2005).

Recently, one study demonstrated that the prevalence of infection among pregnant women was 4.4% in Oaxaca, 12.02% in Jalisco and 4.12% in Mexico City. Likewise, the rate of maternal-fetal transmission has been reported to be 4.08% in Oaxaca and 9.1% in Jalisco, demonstrating the high prevalence of the congenital transmission in the country (Cardoso et al., 2012). In Mexico, there is routine screening of pregnant women; however, a Chagas disease test is not included in that screening. In this case, the Ministry of Health and clinical laboratories must study and evaluate the incorporation of a Chagas disease test. These studies confirm the potential risk of Chagas disease transmission by non-vector forms in non-endemic areas, demonstrating that congenital transmission and blood transfusion are important forms of Chagas disease spread, which represents a serious health problem.

4. Phases of disease Chagas disease has two differentiated phases: acute and chronic. The acute phase is usually subclinical, most likely because the parasite load is fairly small. Most acute cases are asymptomatic, last for 6–12 weeks and occur in childhood (Carod-Artal and Gascon, 2010). When symptoms occur they include the following: inflammation at the inoculation site (chagoma), unilateral ˜ sign) in the particular case of vector palpebral edema (Romana transmission, and other symptoms include fever, headache, joint and muscle pain, anorexia, vomiting, diarrhea, drowsiness, apathy, lymphadenopathy, hepatosplenomegaly, edema, and convulsions. This phase usually resolves spontaneously in 2–4 months; however, some acute cases (2–6%) can lead to death, which is mainly due to myocarditis and meningoencephalitis (Dumonteil, 1999; Rassi et al., 2010). The clinical diagnosis of this phase is difficult due to the heterogeneous and non-specific clinical findings, suggesting that most acute cases are not diagnosed and are only sporadically reported (Coll-Cárdenas et al., 2004; Salazar Schettino et al., 2011). In 1986, nine cases in the acute stage of the disease were diagnosed in the Hospital Civil de Guadalajara in the state of Jalisco, Mexico (Hernandez-Matheson et al., 1987). In the same year, the first deaths of two children (siblings) who suffered multiple bites by triatomines at their home in the Sayula Township in the state of Jalisco were reported; the patients had fever and died of acute Chagas heart disease (Delgadillo-Jaime et al., 1988). Later, in 1999, a proven case of acute chagasic cardiopathy was reported in a 9-month-old infant with suspected transfusional infection during the neonatal period in the Hospital General in Guadalajara, Jalisco (GonzálezZambrano et al., 1999). Chronic phase: Two major forms of disease are observed in the chronic phase, an indeterminate (also named latent) form and a symptomatic form. A high percentage of patients with Chagas disease remain in the indeterminate form for 10 or 30 years or even for life. These patients usually remain asymptomatic, with no clinical or physical signs of disease, but with positive serology. Sometimes, the heart and gastrointestinal tract reveal no pathological findings when electrocardiographical, echocardiographical, and/or radiological examinations are used, but in other patients, the early cardiac form of the chronic phase appears as changes in the electrocardiogram. Asymptomatic patients are only diagnosed by screening for T. cruzi circulating antibodies. Approximately 30–40% of the infected individuals, several years after initial exposure, develop clinical symptoms. In Mexico, asymptomatic chronic cases (indeterminate form) are mainly detected in epidemiological studies, particularly when these studies are conducted in Chagas endemic areas, so it is possible to identify people at this stage of the disease. In a study

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performed on 654 serum samples obtained in the municipality of Tezonapa, state of Veracruz, a 16.8% seroprevalence for T. cruzi infection was observed. Furthermore, reproductive-age women had a 34.3% seroprevalence of T. cruzi infection in this population, which suggests that congenital transmission could be occurring and contributing to the infection rate in children (Ramos-Ligonio et al., 2010). Chronic cardiac form and chronic digestive form: Signs of chronic infection can usually occur 25–30 years after the acquisition of the acute infection. Among chagasic patients with clinical manifestations, chronic chagasic cardiomyopathy (CCC) is the most frequent and severe clinical manifestation. The first signs of CCC are usually conduction system abnormalities (right bundle branch block or left anterior fascicular block) followed by complex ventricular extrasystoles, ventricular tachycardia, sinus bradycardia, high degree heart block, thromboembolism, and progressive dilated cardiomyopathy with congestive heart failure. These symptoms include fibrosis, necrosis, vasculopathy, autonomic dysfunction, diffuse myocarditis, progressive and cumulative injury in which the focal inflammatory reaction can be observed by the presence of lymphocytes and extensive fibrotic degeneration in the surrounding regions. Microvascular changes are also observed that gradually disrupt cell myocardial contractile response (myocytolysis) (James et al., 2005; Bern et al., 2007). In patients with severe heart damage, ventricular aneurysm can be produced, a pathognomonic characteristic of cardiac Chagas disease (Punukollu et al., 2007); approximately one-third of these chagasic patients die suddenly, and a greater percentage will succumb due to heart failure. A direct progression from the acute phase to a chronic clinical form of Chagas disease has been recorded in few patients (Prata, 2001). The remaining chagasic patients who do not present a heart disorder may develop other alterations in the digestive system such as megacolon, megaesophagus, megastomach, megaduodenum, megajejunum, megagallbladder, megacholedochus and gastrointestinal motor disorders, such as achalasia of the cardia, disturbances of gastric emptying, altered intestinal transit and colon and gallbladder motor disorders (Villanova et al., 1987; Oliveira et al., 1998; Troncon et al., 2000; Prata, 2001; Meneghelli, 2004; Bern et al., 2007). These gastrointestinal tract disorders are usually associated with dysphagia, weight loss, and characteristic radiological findings. These patients may also undergo chronic aspiration. Patients with megacolon due to denervation of the colon may suffer constipation, which can be severe and unremitting (Matsuda et al., 2009). The chronic gastrointestinal manifestations are mainly a result of enteric nervous system injury (Iantorno et al., 2007; da Silveira et al., 2007a,b). Chagas disease is known to cause both central nervous system and enteric nervous system injury (Bern et al., 2007). The reactivation of Chagas disease can also occur in chronically infected patients who became immunologically compromised, such as those who are co-infected with the Human Immunodeficiency Virus (HIV) or those who are receiving immunosuppressive drugs as a consequence of heart transplantation (Braz et al., 2008). In Mexico, there are a large number of reports of patients in the chronic symptomatic phase of the disease, and cardiomyopathy is usually the main observed effect. According to a report from the Instituto Nacional de Cardiología, Ignacio Chávez in Mexico City (Monteón-Padilla et al., 2002), in the country, there are 5000 persons suffering from severe CCC. Moreover, in a two-year period in which 540 cardiac patients were examined in Oaxaca, 16 (2.4% cases) were diagnosed with primary dilated cardiomyopathy, and 13 (81%) of these patients were seropositive for anti-T. cruzi antibodies, thus fulfilling the epidemiological and clinical criteria for chronic chagasic cardiomyopathy (Moreno López et al., 2001). A study performed in the cardiology service at the Hospital General in the state of Veracruz indicated that 14 (29%) cases of 49 of

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dilated cardiomyopathy were attributable to CCC. This case series highlights that Chagas disease is a regional public health problem in northern Veracruz (Olivera-Mar et al., 2006). Furthermore, T. cruzi serologic testing conducted on 67 patients with cardiomyopathy in a small rural hospital in the state of Chiapas, in the period 2000–2002, demonstrated that 82.5% of patients were positive for Chagas disease (Capps and Abad, 2004). These results indicate that the symptomatic chronic form of the disease continues to be a major cause of heart failure in some rural and urban areas of Mexico.

5. Epidemiology There are a total of 18 endemic areas in Mexico, located in the southeast, and these areas include the states of Oaxaca, Jalisco, Yucatán, Chiapas, Veracruz, Puebla, Guerrero, Hidalgo, and Morelos, all of them with rural areas (Dumonteil, 1999). Nevertheless, the highest prevalence was observed in the northeastern region of the country, which corresponds to the central area of a tropical region that includes the states of Hidalgo, San Luis Potosí, Veracruz, and Tamaulipas named La Huasteca (Guzman-Bracho, 2001). In this region, the prevalence has increased in recent years (GalavizSilva et al., 2009). T. cruzi is increasingly transmitted through blood transfusions partly due to recent migration from rural areas toward Mexico City (Monteón-Padilla et al., 1999). A national serological survey conducted from 1987 to 1989 reported a T. cruzi seroprevalence of 1.6%, corresponding to at least 1–2 million persons exposed to the parasite in the country, with approximately 70,000 new cases per year and a mortality of 5–6% (25,000 cases) of the total burden in Mexico (Guzman et al., 1998; Guzman-Bracho, 2001; Ramsey et al., 2003b; Velasco-Castrejón et al., 1992). However, other studies have identified much higher seroprevalence levels of up to 5.9% in specific regions (Cruz-Reyes and Pickering-Lopez, 2006). A crosssectional epidemiological study in a population under 18 years of age, who lived in different municipalities of the state of Veracruz, Mexico, from 2000 to 2001, indicated that the seroprevalence of antibodies against T. cruzi was 0.91%; however, the clinical data of patients positive for T. cruzi were not reported in this study. In addition, in this study, active vector transmission was confirmed in this Mexican state (Salazar et al., 2007). Chiapas, Oaxaca, Puebla, Veracruz, and Yucatán are among the most affected states (where the prevalence may exceed 10%), although cases have been reported in most areas of the country (Cruz-Reyes and Pickering-Lopez, 2006; Dumonteil, 1999). The 2010 national census (Instituto Nacional de Estadistica Geografía e informática, 2010) reported 112.3 million people living in Mexico and based on the percent of seropositivity published by Cruz-Reyes and Pickering-Lopez (2006), an estimate of the number of T. cruzi infections by state in the country can be made (Table 1) that indicates that the calculated number of potentially affected people in Mexico is 5.5 million. People from endemic areas of Chagas disease tend to migrate to industrialized cities of the country, mainly Mexico City, in search of jobs. In accordance with this movement, one report showed that infected children under 5 years of age are frequently distributed in urban rather than in rural areas, indicating that the disease is becoming urbanized in Mexico (Guzman-Bracho, 2001). Nonetheless, the disease is still severely underreported in Mexico and, in fact, to date, no data are available on the burden and distribution of Chagas disease. Indeed, the data officially reported by the Mexican Ministry of Health (Centro Nacional de Vigilancia Epidemiológica y Control de Enfermedades (CENAVECE), 2010) are underestimates because the total cumulative number of new cases identified in the 2000–2010 period (Fig. 1) is very low compared to data reported in different seroprevalence research articles about Chagas disease (Cruz-Reyes and PickeringLopez, 2006; Ramos-Ligonio et al., 2010). In accordance with the

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Table 1 Estimated population at-risk for Trypanosoma cruzi infection in Mexico in accordance with the prevalence (%) of anti-T. cruzi antibodies in 2006 by serological surveys, clinical manifestations, and blood bank reports (Cruz-Reyes and Pickering-Lopez, 2006). Prevalence of Chagas disease State Quéretaro Oaxaca Chiapas Nayarit Jalisco Morelos Guerrero Hidalgo Veracruz Zacatecas Sinaloa Tabasco Distrito Federal Puebla Yucatán Baja California San Luis Potosí Quintana Roo Michoacán Durango Nuevo León Aguascalientes Tamaulipas Sonora Campeche Tlaxcala Colima Baja California Sur Guanajuato Estado de México Coahuila Chihuahua Total a b

Estimated population in Mexico by state 2010a (× 106 )

Estimated number of infected individuals (cases)

1.82 3.80 4.79 1.08 7.35 1.77 3.38 2.66 7.64 1.49 2.76 2.23 8.85 5.77 1.95 3.15 2.58 1.32 4.35 1.63 4.65 1.18 3.26 2.66 0.82 1.16 0.65 0.63 5.48 15.17 2.74 3.4

347,125 672,947 611,564 132,259 890,168 203,315 383,947 164,698 438,719 83,776 154,441 84,171 331,916 205,184 61,992 87,711 66,965 31,946 96,158 35,598 90,277 21,685 54,912 43,132 12,830 15,560 7481 6625 44,988 95,608 16,765 15,329

112.17

5,509,794

Prevalence (%)b 18.99 17.70 12.75 12.19 12.11 11.44 11.33 6.18 5.74 5.62 5.58 3.76 3.75 3.55 3.17 2.78 2.59 2.41 2.21 2.18 1.94 1.83 1.68 1.62 1.56 1.33 1.15 1.04 0.82 0.63 0.61 0.45

Instituto Nacional de Estadistica Geografía e informática (2010). http://www.inegi.gob.mx. Cruz-Reyes and Pickering-Lopez (2006).

estimation of infected persons in this work, Jalisco, Oaxaca and Chiapas have the highest cases of Chagas disease followed by Veracruz, Guerrero, Queretaro, Mexico City, Puebla, Morelos, Hidalgo, Sinaloa and Nayarit (Table 1 and Fig. 2). These statements must be analyzed in depth by the Ministry of Health to establish appropriate and effective control measures to control the disease. This analysis stands out in that the high number of cases that could be present in the Distrito Federal (Mexico City), which is an urban area where there are no reports of the presence of vectors; therefore, other transmission methods are occurring. It is necessary to elucidate these routes to reduce the risk of Chagas disease transmission.

Fig. 1. Reported cases of Chagas disease in Mexico (period 2000–2010). Data from the Centro Nacional de Vigilancia Epidemiológica y Control de Enfermedades (CENAVECE), Secretaría de Salud. Información Epidemiológica de Morbilidad 2010.

6. Vectors Currently, 40 species of triatomes are known to be naturally infected by T. cruzi in North America. Triatomes belonging to the genera Rhodnius (R. prolixus), Triatoma (T. infestans), and Panstrongylus (P. megistus) are the most important from an epidemiological viewpoint (WHO, 1991). Twenty-eight species are found exclusively in Mexico, and 8 are shared with the USA (IbarraCerdena et al., 2009). In Mexico, more than 96% of transmission of the disease is believed to occur via the vector route (Ramsey et al., 2003a). Mexico hosts one of the most diverse triatomine populations, with 39 species documented in the country, at least 21 of which have been observed to be infected by T. cruzi, indicating them as potential vectors of Chagas disease (Bargues et al., 2008; Cruz-Reyes and Pickering-Lopez, 2006). Recently, different reports have revealed information about the major vectors in endemic areas of Mexico. In the state of Veracruz, the main recognized vectors are Triatoma dimidiata and R. prolixus, and only T. dimidiata has been identified in the state of Chiapas. Triatoma phyllosoma has been reported only in the state of Oaxaca and is considered the most important transmission vector of Chagas disease in the southern part of that state (Villalobos et al., 2011; Zárate and Zárate, 1985). There is only one report that demonstrates the presence of Meccus longipennis, Meccus pallidipennis, Triatoma barberi, and T. dimidiata in the state of Michoacán. Surprisingly, the rates of infection with T. cruzi were higher than 50% in all examined species (Martínez-Ibarra et al., 2011). Another study identified two species

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Fig. 2. The estimated number of individuals infected with Trypanosoma cruzi in Mexico. The map was created to show the states with an estimated prevalence of Chagas disease in accordance with the prevalence of anti-T. cruzi antibodies (Cruz-Reyes and Pickering-Lopez, 2006) and using data from Mexican population (Instituto Nacional de Estadistica Geografía e informática, 2010).

of Triatoma in the southern region of state of Estado de México: Triatoma pallidipennis (97.4%) and T. dimidiata (2.6%), and 28.94% of the triatomes were infected with T. cruzi (Medina-Torres et al., 2010). T. barberi, T. dimidiata and Triatoma mexicana were identified in three regions of the state of Hidalgo, with a T. cruzi infection rate ranging between 6% and 10.3% (Becerril-Flores et al., 2007). T. pallidipennis was the only species found in Valle de Iguala in the state of Guerrero, where 38.2% of triatomes collected were infected with T. cruzi. The greatest percentage of infected triatomines was observed in rural areas compared with urban areas (Becerril-Flores and ValleDe La Cruz, 2003). T. mexicana, Triatoma longipennis, T. pallidipennis, and T. barberi were the main species collected between 1998 and 2002 in several communities of the state of Guanajuato, which is not considered an endemic area (López-Cárdenas et al., 2005). T. pallidipennis, T. barberi, Triatoma picturata, and T. dimidiata were identified in the state of Puebla in 2006 with T. cruzi infection rates of 75%, 50%, 41%, and 37%, respectively (Romero-Cabello et al., 2006). M. pallidipennis was the only triatomine captured in the locality of Puente Pantitán, state of Morelos, in a study performed in 2011. That study demonstrated that the triatomines had a 44% T. cruzi infection rate (Portugal-García et al., 2011). No national vector control program has been implemented in Mexico thus far to prevent Chagas disease. The use of insecticides in dwellings and their surroundings has decreased vector transmission of T. cruzi; however, these efforts have not been sufficient because the disease has not been controlled in areas with domiciled cycles (Dias and Schofield, 1999). The disadvantages in applying insecticides include the operating costs resulting from constant application in the houses of endemic areas, and although, insecticide use has reduced the populations of triatomines in homes in some regions, this has not impeded continuous mobility of the vectors between wild and domestic areas with the

consequent re-infestation of the buildings treated with pesticides (Vassena et al., 2000; Ramsey et al., 2003a) or the emergence of chemical-resistant populations of triatomines (Zerba, 1999). Another inconvenience is the damage caused to many other insect species that should be protected by strategies directed specifically against harmful species. In Mexico, the control of vector ˜ transmission is still in the initial stages (Coura and Vinas, 2010). Dichlorodiphenyltrichloroethane (DDT) has been banned in the country since 2006. This has been beneficial for controlling Chagas disease vectors, having encouraged the use of pyrethroids as a replacement (Petherick, 2010). However, the efforts have not been sufficient because vector distribution is poorly documented. There is a need in some areas to monitor the entomological scenario, with selective action undertaken against any vector population that might reinitiate domestic colonization. It is possible to target such regions of risk, using, for example, predictive geographic models of vector and host distribution, overlaid with patterns of human land use (Peterson et al., 2002).

7. Domestic animals as reservoirs Domestic species may play several roles in T. cruzi transmission. They may act as a link between wild and peridomestic or domestic habitats, or they also may be definitive hosts. More than 180 domestic, synanthropic and wild species of mammals, especially nest-building rodents and opossums, are likely to be infected with T. cruzi and to be involved in the transmission cycle of the disease (WHO, 2002). Dogs, cats, and rodents are important domestic reservoirs (Cruz-Reyes and Pickering-Lopez, 2006). Moreover, dogs and cats are very often observed to have a high T. cruzi infection prevalence, and both types of mammals have displayed a 10-fold higher incidence of infection than local children in an area of active

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transmission in Argentina (Gurtler et al., 2005). However, as with all other mammal species, these animals’ role in the transmission cycle of T. cruzi varies, as shown by the patterns of infection in distinct study areas. Some studies in Argentina have reported that both cats and dogs are epidemiologically important and highly infected by triatomines (Gurtler et al., 2007), and the presence of dogs in dwellings increases the risk for human infection approximately 3- to 5-fold (Gurtler et al., 1993). In addition, an active canine T. cruzi transmission cycle with severe symptoms affecting a broad range of dog breeds and age groups was observed in several counties in Texas, USA (Kjos et al., 2008). Several studies describing the seroprevalence in dogs of Mexico have been conducted and importantly demonstrated a direct correlation with the seropositivity in humans. The high seroprevalence observed in dogs in different areas suggests that dogs may be domestic reservoir hosts and help to maintain human transmission of T. cruzi. The anti-T. cruzi prevalence in dogs of the urban area of Mérida in the state of Yucatán was higher (14.4%) than in those sampled in rural communities (9.8%) (Jimenez-Coello et al., 2008). Two years later, the same research group reported a seroprevalence of 34% in dogs and 8% in owners in the southern area of the city of Mérida, Yucatán (Jiménez-Coello et al., 2010). Recently, the anti-T. cruzi antibody prevalence in dogs was determined to be 14.76% in the Yucatán peninsula and determined to be 10.74% and 21.34% in the states of Yucatán and Quintana Roo, respectively (López-Céspedes et al., 2012). A direct correlation of seropositivity between humans and dogs in the southern region of the state of Estado de México has been observed, and a seroprevalence of 7.1% in humans and 21% in dogs

has been reported, emphasizing the importance of dogs acting as sentinels as part of the surveillance measures in the country (Estrada-Franco et al., 2006). This correlation was also noted in Palmar de Bravo, state of Puebla, where a 4% prevalence of T. cruzi antibodies in humans and a 10% prevalence in canine reservoirs were demonstrated (Sosa-Jurado et al., 2004). A high seroprevalence of IgG and IgM T. cruzi antibodies (17.5%) in dogs was observed in Toluca, state of Estado de México, and this study asserted that immigrants who bring their domestic animals with them may inadvertently contribute to the spread of T. cruzi infection (Estrada-Franco et al., 2006). A seroepidemiological study conducted in Puente Pantitán, state of Morelos, reported a seroprevalence of anti-T. cruzi antibodies of 1.2% in humans and 24.2% in dogs (Portugal-García et al., 2011). These results demonstrate that the domestic dog is a risk factor for Chagas disease in Mexico because they can be a source of T. cruzi infection and significantly enhance transmission of the disease in humans, particularly in cohabitation situations. Moreover, dogs have a greater capacity to be infected by triatomine bugs than do humans, and thus they have been used as efficient natural sentinels to assess T. cruzi reinfections in vector surveillance studies (Cardinal et al., 2006; Castanera et al., 1998; Estrada-Franco et al., 2006; Gurtler et al., 1993). The government of Mexico, through the Ministry of Health, provides economic resources each year and conducts campaigns to address the problem of canine overpopulation; however, these efforts have not been sufficient because the last census reported 23 million of dogs, of which only 30% have a fixed home (Instituto Nacional de Estadistica Geografía e informática, 2010). A more thorough study to determine the demographic and epidemiological data of dogs is necessary to develop better population controls

Fig. 3. Current transmission routes of Chagas disease in Mexico. The cartoon shows the risks for transmission in Mexico, which include not only the vector in endemic areas but also other different routes in non-endemic and urbanized areas, such as blood transfusion, organ transplantation, vertical transmission, and close coexistence with domestic reservoirs. Competent authorities should establish some measures for care health and Chagas disease control such as performing screening for T. cruzi in all blood and organ donors, establishing a Chagas disease test diagnosis in every pregnant woman, and reducing the overpopulation of homeless dogs to properly diagnose infection cases and provide an appropriate and timely treatment.

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because dogs could be transmitting several diseases, including Chagas disease. Dogs are important reservoirs and hosts of the parasite, as well as a good animal model to evaluate the process of disease development following T. cruzi infection (Andrade, 1999; de Lana et al., 1992; Guedes et al., 2007). Dogs infected with Mexican isolates of T. cruzi exhibit electrocardiographic alterations, left- and rightventricle dilation and hydropericardium (Barbabosa-Pliego et al., 2009) and left ventricular enlargement, right bundle branch block and ventricular premature complexes (Rodríguez-Morales et al., 2012). More recently, a report demonstrated the first case of experimental perinatal transmission in dogs in Mexico, providing new insights into this particular method of transmission (RodríguezMorales et al., 2011). Altogether, these observations confirm the relevance of the dog as an excellent model to study the pathogenesis of Chagas disease.

8. Development of vaccines against Chagas disease: the news The development of an effective vaccine against Chagas disease has been a concern of several research groups in Mexico. The search for antigens that could be used at a DNA or recombinant protein level as a vaccine for Chagas disease is a subject of interest. There are excellent reports that describe the antigens that have been tested and the levels of protection conferred to animals experimentally infected with T. cruzi (Aparicio-Burgos et al., 2011; Arce-Fonseca et al., 2013; Dumonteil et al., 2012; Quijano-Hernandez et al., 2008; Rodríguez-Morales et al., 2012; Vázquez-Chagoyán et al., 2011). Recently, the Carlos Slim Health Institute proposed an important initiative aimed at accelerating the development of the new vaccine against Chagas disease in Mexico, forming an integrative consortium, including the Centro de Investigación y de Estudios Avanzados of the I.P.N. (CINVESTAV-IPN), Laboratorios de Biológicos y Reactivos de México, S. A. de C. V. (BIRMEX) in Mexico City, and the Centro de Investigaciones Regionales “Dr. Hideyo Noguchi” in Mérida, state of Yucatán. This initiative will work together with a focus on developing an optimal vaccine in the least possible time (Bottazzi et al., 2011).

9. Conclusions Chagas disease, caused by the parasite T. cruzi, is still active in several countries of Latin America, including Mexico, and affects a great number of individuals. Chagas disease had been confined to the population living in rural and extreme poverty; however, due to recent migrations of infected people from rural to urban areas, the disease has begun to spread in different non-endemic regions. Even in non-endemic areas, the transmission of T. cruzi is possible through blood transfusion, organ transplants and vertical (motherto-child) transmission (Fig. 3). Although there has been significant progress in understanding the biological and genetic diversity of the parasite, as well as the triatomine vectors, many other aspects such as host–parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism require further elucidation. In Mexico, there are no established vector control programs. Moreover, there is no consensus on appropriate diagnostic methods for acute and chronic Chagas disease in maternity wards and blood banks, and chronic patients do not receive trypanocidal therapy. The actual prevalence of the disease is unknown because there is minimal official case reporting. Therefore, the number of people infected by different routes of transmission is also unknown. Thus, in the coming years, it will be crucial to recognize and properly document the existence of several Chagas disease epidemiological

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situations in Mexico and to affirm the need to implement suitable reference schemes and medical care accordingly. Encouraging teaching about and research on Chagas disease in the curricula of health personnel (physicians, nurses, veterinarians, environmental technicians, biologists, and chemists) would be a good beginning in strengthen the recognition of the disease by the general population as a growing health problem and also encouraging the acceptance and successful adoption of appropriate measures to treat the disease. Conflict of interests None of the authors has any potential financial conflict of interest related to this manuscript. Acknowledgments This work was in part supported by a grant from the Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF), Mexico (Grant no. 236/2010) and a grant from the Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico (Grant no. 69081 FONSEC SSA/IMSS/ISSSTE) to M.A.-F. A.C.-L. is recipient of a postdoctoral fellowship from the ICyTDF, Mexico. References Andrade, Z.A., 1999. Immunopathology of Chagas disease. Mem. Inst. Oswaldo Cruz 94 (Suppl. 1), 71–80. Aparicio-Burgos, J.E., Ochoa-García, L., Zepeda-Escobar, J.A., Gupta, S., Dhiman, M., Martínez, J.S., et al., 2011. Testing the efficacy of a multi-component DNAprime/DNA-boost vaccine against Trypanosoma cruzi infection in dogs. PLoS Negl. Trop. Dis. 5, e1050, http://dx.doi.org/10.1371/journal.pntd.0001050. Apt, W., Zulantay, I., Arnello, M., Oddó, D., González, S., Rodríguez, J., 2013. Congenital infection by Trypanosoma cruzi in an endemic área of Chile: a multidisciplinary study. Trans. R. Soc. Trop. Med. Hyg. 207, 98–104. Araújo, A.B., Vianna, E.E., Berne, M.E., 2008. Anti-Trypanosoma cruzi antibody detection in blood donors in the Southern Brazil. Braz. J. Infect. Dis. 12, 480–482. Arce-Fonseca, M., Ballinas-Verdugo, M.A., Abreu-Zenteno, E.R., Suárez-Flores, D., Carrillo-Sánchez, S.C., Alejandre-Aguilar, R., et al., 2013. Specific humoral and cellular immunity induced by Trypanosoma cruzi DNA immunization in a canine model. Vet. Res. 44, 15. Barbabosa-Pliego, A., Diaz-Albiter, H.M., Ochoa-Garcia, L., Aparicio-Burgos, E., LopezHeydeck, S.M., Velasquez-Ordonez, V., et al., 2009. Trypanosoma cruzi circulating in the southern region of the State of Mexico (Zumpahuacan) are pathogenic: a dog model. Am. J. Trop. Med. Hyg. 81, 390–395. Bargues, M.D., Klisiowicz, D.R., Gonzalez-Candelas, F., Ramsey, J.M., Monroy, C., Ponce, C., et al., 2008. Phylogeography and genetic variation of Triatoma dimidiata, the main Chagas disease vector in Central America, and its position within the genus Triatoma. PLoS Negl. Trop. Dis. 2, e233. Becerril-Flores, M.A., Rangel-Flores, E., Imbert-Palafox, J.L., Gomez-Gomez, J.V., Figueroa-Gutierrez, A.H., 2007. Human infection and risk of transmission of Chagas disease in Hidalgo State, Mexico. Am. J. Trop. Med. Hyg. 76, 318–323. Becerril-Flores, M.A., Valle-De La Cruz, A., 2003. Description of Chagas disease in the Valle de Iguala, Guerrero state, Mexico-Marco. Gac. Med. Mex. 139, 539–544. Bern, C., 2011. Antitrypanosomal therapy for chronic Chagas’ disease. N. Engl. J. Med. 364, 2527–2534. Bern, C., Montgomery, S.P., 2009. An estimate of the burden of Chagas disease in the United States. Clin. Infect. Dis. 49, e52–e54. Bern, C., Montgomery, S.P., Herwaldt, B.L., Rassi Jr., A., Marin-Neto, J.A., Dantas, R.O., et al., 2007. Evaluation and treatment of Chagas disease in the United States: a systematic review. J. Am. Med. Assoc. 298, 2171–2181. Bottazzi, M.E., Dumonteil, E., Valenzuela, J.G., Betancourt-Cravioto, M., Tapia-Conyer, R., Hotez, P.J., 2011. Bridging the innovation gap for neglected tropical diseases in Mexico: capacity building for the development of a new generation of antipoverty vaccines. Bol. Méd. Hosp. Infant. Méx. 68, 138–146. Braz, L.M., Amato Neto, V., Okay, T.S., 2008. Reactivation of Trypanosoma cruzi infection in immunosuppressed patients: contributions for the laboratorial diagnosis standardization. Rev. Inst. Med. Trop. São Paulo 50, 65–66. Cabrera, M., Bucio, M., Rojo, J., Bonifaz, R., Guevara, Y., Salazar-Schettino, P.M., 2004. Detection of antibodies against Trypanosoma cruzi in blood donors in the General Hospital of México City. Rev. Patol. Trop. 33, 71–80. Camandaroba, E.L., Reis, E.A., Goncalves, M.S., Reis, M.G., Andrade, S.G., 2003. Trypanosoma cruzi: susceptibility to chemotherapy with benznidazole of clones isolated from the highly resistant Colombian strain. Rev. Soc. Bras. Med. Trop. 36, 201–209. Cantey, P.T., Stramer, S.L., Townsend, R.L., Kamel, H., Ofafa, K., Todd, C.W., et al., 2012. The United States Trypanosoma cruzi infection study: evidence for vector-borne

134

A. Carabarin-Lima et al. / Acta Tropica 127 (2013) 126–135

transmission of the parasite that causes Chagas disease among United States blood donors. Transfusion (Paris) 52, 1922–1930. Capps, L., Abad, B., 2004. Chagas cardiomyopathy and serologic testing in a small rural hospital in Chiapas, Mexico. Rev. Panam. Salud Pública 15, 337–340. Cardinal, M.V., Castanera, M.B., Lauricella, M.A., Cecere, M.C., Ceballos, L.A., VazquezProkopec, G.M., et al., 2006. A prospective study of the effects of sustained vector surveillance following community-wide insecticide application on Trypanosoma cruzi infection of dogs and cats in rural Northwestern Argentina. Am. J. Trop. Med. Hyg. 75, 753–761. Cardoso, E.J., Valdez, G.C., Campos, A.C., de la Luz, S.R., Mendoza, C.R., Hernandez, A.P., et al., 2012. Maternal fetal transmission of Trypanosoma cruzi: a problem of public health little studied in Mexico. Exp. Parasitol. 131, 425–432. Carlier, Y., Truyens, C., Deloron, P., Peyron, F., 2011. Congenital parasitic infections: a review. Acta Trop. 121, 55–70. Carod-Artal, F.J., Gascon, J., 2010. Chagas disease and stroke. Lancet Neurol. 9, 533–542. Castanera, M.B., Lauricella, M.A., Chuit, R., Gurtler, R.E., 1998. Evaluation of dogs as sentinels of the transmission of Trypanosoma cruzi in a rural area of northwestern Argentina. Ann. Trop. Med. Parasitol. 92, 671–683. Centro Nacional de Vigilancia Epidemiológica y Control de Enfermedades (CENAVECE). Sistema Nacional de Vigilancia Epidemiológica, 2010. Información Epidemiológica de Morbilidad. Secretaría de Salud México, D.F. Available from: http://www.dgepi.salud.gob.mx/anuario/html/anuarios.html (accessed June 2012). Coll-Cárdenas, R., Espinoza-Gómez, F., Maldonado-Rodríguez, A., Reyes-López, P.A., Huerta-Viera, M., Rojas-Larios, F., 2004. Active transmission of human Chagas disease in Colima Mexico. Mem. Inst. Oswaldo Cruz 99, 363–368. ˜ Coura, J.R., Vinas, P.A., 2010. Chagas disease: a new worldwide challenge. Nature 465, S6–S7. Cruz-Reyes, A., Pickering-Lopez, J.M., 2006. Chagas disease in Mexico: an analysis of geographical distribution during the past 76 years—a review. Mem. Inst. Oswaldo Cruz 101, 345–354. Cucunubá, Z.M., Flórez, A.C., Cárdenas, A., Pavía, P., Montilla, M., Aldana, R., 2012. Prevalence and risk factors for Chagas disease in pregnant women in Casanare, Colombia. Am. J. Trop. Med. Hyg. 87, 837–842. da Silveira, A.B., D’Avila Reis, D., Oliveira, E.C., Neto, S.G., Luquetti, A.O., Poole, D., et al., 2007a. Neurochemical coding of the enteric nervous system in chagasic patients with megacolon. Dig. Dis. Sci. 52, 2877–2883. da Silveira, A.B., Lemos, E.M., Adad, S.J., Correa-Oliveira, R., Furness, J.B., D’Avila Reis, D., 2007b. Megacolon in Chagas disease: a study of inflammatory cells, enteric nerves, and glial cells. Hum. Pathol. 38, 1256–1264. de Lana, M., Chiari, E., Tafuri, W.L., 1992. Experimental Chagas’ disease in dogs. Mem. Inst. Oswaldo Cruz 87, 59–71. Delgadillo-Jaime, C., Paredes-Casillas, P., Velasco-Rodríguez, F., Gómez-Salcedo, H., Estrada-Espinoza, M., Paredes-Espinoza, M., 1988. Brote de enfermedad de Chagas aguda en Jalisco: Reporte preliminar. UNED/Gobierno de Jalisco/Secretaría general Unidad editorial Guadalajara, Guadalajara. Dias, J., Schofield, C., 1999. The evolution of Chagas disease (American trypanosomiasis) control after 90 years since Carlos Chagas discovery. Mem. Inst. Oswaldo Cruz 94 (Suppl. 1), 103–121. Dias, J.C., 2000. Epidemiological surveillance of Chagas disease. Cad. Saude Publica 16 (Suppl. 2), 43–59. Dumonteil, E., 1999. Update on Chagas’ disease in Mexico. Salud Pública Mex. 41, 322–327. Dumonteil, E., Bottazzi, M.E., Zhan, B., Heffernan, M.J., Jones, K., Valenzuela, J.G., et al., 2012. Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects. Exp. Rev. Vaccines 11, 1043–1055. Estrada-Franco, J.G., Bhatia, V., Diaz-Albiter, H., Ochoa-Garcia, L., Barbabosa, A., Vazquez-Chagoyan, J.C., et al., 2006. Human Trypanosoma cruzi infection and seropositivity in dogs, Mexico. Emerg. Infect. Dis. 12, 624–630. Galaviz-Silva, L., Molina-Garza, D.P., Gonzalez-Santos, M.A., Mercado-Hernandez, R., Gonzalez-Galaviz, J.R., Rosales-Encina, J.L., et al., 2009. Update on seroprevalence of anti-Trypanosoma cruzi antibodies among blood donors in northeast Mexico. Am. J. Trop. Med. Hyg. 81, 404–406. Gascon, J., Bern, C., Pinazo, M.J., 2010. Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop. 115, 22–27. González-Zambrano, H., Amador Mena, J.E., Delgadillo Jaime, C.B., 1999. Regression of acute Chagas cardiopathy in an infant with a suspected transfusion infection. Arch. Inst. Cardiol. Mex. 69, 363–366. Guedes, P.M., Veloso, V.M., Caliari, M.V., Carneiro, C.M., Souza, S.M., De Lana, M., et al., 2007. Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagle dogs. Mem. Inst. Oswaldo Cruz 102, 141–147. Gurtler, R.E., Cecere, M.C., Lauricella, M.A., Cardinal, M.V., Kitron, U., Cohen, J.E., 2007. Domestic dogs and cats as sources of Trypanosoma cruzi infection in rural northwestern Argentina. Parasitology 134, 69–82. Gurtler, R.E., Cecere, M.C., Lauricella, M.A., Petersen, R.M., Chuit, R., Segura, E.L., et al., 2005. Incidence of Trypanosoma cruzi infection among children following domestic reinfestation after insecticide spraying in rural northwestern Argentina. Am. J. Trop. Med. Hyg. 73, 95–103. Gurtler, R.E., Cecere, M.C., Petersen, R.M., Rubel, D.N., Schweigmann, N.J., 1993. Chagas disease in north-west Argentina: association between Trypanosoma cruzi parasitaemia in dogs and cats and infection rates in domestic Triatoma infestans. Trans. R. Soc. Trop. Med. Hyg. 87, 12–15. Gurtler, R.E., Segura, E.L., Cohen, J.E., 2003. Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerg. Infect. Dis. 9, 29–32.

Gutierrez, F.R., Guedes, P.M., Gazzinelli, R.T., Silva, J.S., 2009. The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunol. 31, 673–685. Guzman, B.C., Garcia, G.L., Floriani, V.J., Guerrero, M.S., Torres, C.M., Ramirez, M.C., et al., 1998. Risk of transmission of Trypanosoma cruzi by blood transfusion in Mexico. Rev. Panam. Salud Publica 4, 94–99. Guzman-Bracho, C., 2001. Epidemiology of Chagas disease in Mexico: an update. Trends Parasitol. 17, 372–376. Hernandez-Becerril, N., Mejia, A.M., Ballinas-Verdugo, M.A., Garza-Murillo, V., Manilla-Toquero, E., Lopez, R., et al., 2005. Blood transfusion and iatrogenic risks in Mexico City. Anti-Trypanosoma cruzi seroprevalence in 43,048 blood donors, evaluation of parasitemia, and electrocardiogram findings in seropositive. Mem. Inst. Oswaldo Cruz 100, 111–116. Hernandez-Matheson, I.M., Ericsson, C.D., Delgadillo, J.C., Paredes, C.P., Paredes, E.M., 1987. New focus of Chagas’ disease in Mexico. Lancet 1, 100. Hotez, P.J., Fenwick, A., Savioli, L., Molyneux, D.H., 2009. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373, 1570–1575. Hotez, P.J., Molyneux, D.H., Fenwick, A., Kumaresan, J., Sachs, S.E., Sachs, J.D., et al., 2007. Control of neglected tropical diseases. N. Engl. J. Med. 357, 1018–1027. Iantorno, G., Bassotti, G., Kogan, Z., Lumi, C.M., Cabanne, A.M., Fisogni, S., et al., 2007. The enteric nervous system in chagasic and idiopathic megacolon. Am. J. Surg. Pathol. 31, 460–468. Ibarra-Cerdena, C.N., Sanchez-Cordero, V., Townsend, P.A., Ramsey, J.M., 2009. Ecology of North American triatominae. Acta Trop. 110, 178–186. Instituto Nacional de Estadistica, Geografía e informática, 2010. Censo Nacional de Población y Vivienda México. Available from: http://www.dgepi.salud.gob.mx/ anuario/html/anuarios.html (accessed June 2012). James, T.N., Rossi, M.A., Yamamoto, S., 2005. Postmortem studies of the intertruncal plexus and cardiac conduction system from patients with Chagas disease who died suddenly. Prog. Cardiovasc. Dis. 47, 258–275. Jiménez-Coello, M., Guzmán-Marin, E., Ortega-Pacheco, A., Acosta-Viana, K.Y., 2010. Serological survey of American trypanosomiasis in dogs and their owners from an urban area of Merida Yucatan, Mexico. Transbound. Emerg. Dis. 57, 33–36. Jimenez-Coello, M., Poot-Cob, M., Ortega-Pacheco, A., Guzman-Marin, E., RamosLigonio, A., Sauri-Arceo, C.H., et al., 2008. American trypanosomiasis in dogs from an urban and rural area of Yucatan, Mexico. Vector Borne Zoonotic Dis. 8, 755–761. Kjos, S.A., Snowden, K.F., Craig, T.M., Lewis, B., Ronald, N., Olson, J.K., 2008. Distribution and characterization of canine Chagas disease in Texas. Vet. Parasitol. 152, 249–256. Leiby, D.A., Herron, R.M., Garratty, G., Herwaldt, B.L., 2008. Trypanosoma cruzi parasitemia in US Blood donors with serologic evidence of infection. J. Infect. Dis. 198, 609–613. Leiby, D.A., Herron, R.M., Read, E.J., Lenes, B.A., Stumpf, R.J., 2002. Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion (Paris) 42, 549–555. López-Cárdenas, J., González Bravo, F.E., Salazar Schettino, P.M., Gallaga Solórzano, J.C., Ramírez, B.E., Martínez, M.J., et al., 2005. Fine-scale predictions of distributions of Chagas disease vectors in the state of Guanajuato, Mexico. J. Med. Entomol. 42, 1068–1081. López-Céspedes, A., Longoni, S.S., Sauri-Arceo, C.H., Rodríguez-Vivas, R.I., Villegas, N., Escobedo-Ortegón, J., et al., 2012. Seroprevalence of antibodies against the excreted antigen superoxide dismutase by Trypanosoma cruzi in dogs from the Yucatan Peninsula (Mexico). Zoonoses and Public Health, http://dx.doi.org/10.1111/j.1863-2378.2012.01520.x (Epub ahead of print). Manrique-Abril, F.G., Herrera, G., Ospina, J.M., Pavia, P., Puerta, C.J., Montilla, M., 2009. Prevalencia de enfermedad de Chagas en maternas e incidencia transplacentario en Boyacá. Biomedica 29 (Suppl. 1), 315–316. Martínez-Ibarra, J.A., Valencia-Navarro, I., León-Saucedo, S., Ibanez-Cervantes, G., Bustos-Saldana, R., Montanez-Valdez, O.D., et al., 2011. Distribution and infection of triatomines (Hemiptera: Reduviidae) by Trypanosoma cruzi in the state of Michoacan, Mexico. Mem. Inst. Oswaldo Cruz 106, 445–450. Matsuda, N.M., Miller, S.M., Evora, P.R., 2009. The chronic gastrointestinal manifestations of Chagas disease. Clinics (Sao Paulo) 64, 1219–1224. Medina-Torres, I., Vazquez-Chagoyan, J.C., Rodriguez-Vivas, R.I., de Oca-Jimenez, R.M., 2010. Risk factors associated with triatomines and its infection with Trypanosoma cruzi in rural communities from the southern region of the State of Mexico, Mexico. Am. J. Trop. Med. Hyg. 82, 49–54. Meneghelli, U.G., 2004. Chagasic enteropathy. Rev. Soc. Bras. Med. Trop. 37, 252–260. Moncayo, A., 2003. Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries. Mem. Inst. Oswaldo Cruz 98, 577–591. Monteón, V.M., Reyes-López, P.A., Sosa-Palacio, A., León-Tello, G., Martínez-Murguía, J., Sosa-Jurado, F., 2005. Heterogeneous distribution of the prevalence of antiTrypanosoma cruzi antibodies among blood donors in the State of Puebla, Mexico. Salud Publica Mex. 47, 116–125. Monteón-Padilla, V.M., Hernández-Becerril, N., Guzmán-Bracho, C., Rosales-Encina, J.L., Reyes-López, P.A., 1999. American trypanosomiasis (Chagas’ disease) and blood banking in Mexico City: seroprevalence and its potential transfusional transmission risk. Arch. Med. Res. 30, 393–398. Monteón-Padilla, V.M., Vargas-Alarcón, G., Vallejo-Allende, M., Reyes, P.A., 2002. Specific dilated myocardiopathy. Chronic chagasic cardiopathy at the National

A. Carabarin-Lima et al. / Acta Tropica 127 (2013) 126–135 Institute of Cardiology Ignacio Chavez. Arch. Cardiol. Méx. 72 (Suppl. 1), S148–S152. ˜ Moreno López, R.M., Sánchez, P.L., Munoz, J.L., Monteón, V.M., Reyes López, P.A., 2001. Chagasic cardiopathy in Tehuantepec, Preliminary report. Arch. Cardiol. Méx. 71, 43–49. ˜ Munoz, J., Coll, O., Juncosa, T., Vergés, M., del Pino, M., Fumado, V., 2009. Prevalence and vertical transmission of Trypanosoma cruzi infection among pregnant Latin American women attending 2 maternity clinics in Barcelona, Spain. Clin. Infect. Dis. 48, 1736–1740. Murcia, L., Carrilero, B., Munoz-Davila, M.J., Thomas, M.C., López, M.C., Segovia, M., 2013. Risk factors and primary prevention of congenital Chagas disease in a nonendemic country. Clin. Infect. Dis. 56, 496–502. Norma Oficial Mexicana NOM-003-SSA2-1993, 1994. Para la disposición de sangre humana y sus componentes con fines terapéuticos. Diario Oficial de la federación, Secretaría de Salud. ˜ Oliveira, I., Torrico, F., Munoz, J., Gascon, J., 2010. Congenital transmission of Chagas disease: a clinical approach. Expert Rev. Anti-infect. Ther. 8, 945–956. Oliveira, R.B., Troncon, L.E., Dantas, R.O., Menghelli, U.G., 1998. Gastrointestinal manifestations of Chagas disease. Am. J. Gastroenterol. 93, 884–889. Olivera-Mar, A., Hernández-Vicencio, C., Camacho-Marie, M., Hernández-Becerril, N., Monteón-Padilla, V.M., Vallejo, M., et al., 2006. Chronic chagasic cardiomyopathy at the Hospital General de Zona no. 24 IMSS. Poza Rica, Veracruz. Arch. Cardiol. Méx. 76, 269–276. Pan American Health Organization, 2006. Estimación cuantitativa de la enfermedad de Chagas en las Américas (Quantitative Estimation of Chagas Disease in the Americas. OPS/HDM/CD/425-06). Pan American Health Organization, Washington, DC. Peterson, A.T., Sanchez-Cordero, V., Beard, C.B., Ramsey, J.M., 2002. Ecologic niche modeling and potential reservoirs for Chagas disease, Mexico. Emerg. Infect. Dis. 8, 662–667. Petherick, A., 2010. Country by country. Nature 465, S10–S11. ˜ Piron, M., Vergés, M., Munoz, J., Casamitjana, N., Sanz, S., Maymó, R.M., 2008. Seroprevalence of Trypanosoma cruzi infection in at-risk blood donors in Catalonia (Spain). Transfusion (Paris) 48, 1862–1868. Portugal-García, C., García-Vázquez, Z., Monteón-Padilla, V., Chávez-López, V., Olamendi-Portugal, M., Ramos, C., 2011. Trypanosoma cruzi en humanos y perros y presencia del parásito en Meccus pallidipennis en la localidad de Puente Pantitlán, Morelos, México. Rev. Bioméd. 22, 67–75. Prata, A., 2001. Clinical and epidemiological aspects of Chagas disease. Lancet Infect. Dis. 1, 92–100. Punukollu, G., Gowda, R.M., Khan, I.A., Navarro, V.S., Vasavada, B.C., 2007. Clinical aspects of the Chagas’ heart disease. Int. J. Cardiol. 115, 279–283. Quijano-Hernandez, I.A., Bolio-González, M.E., Rodríguez-Buenfil, J.C., RamirezSierra, M.J., Dumonteil, E., 2008. Therapeutic DNA vaccine against Trypanosoma cruzi infection in dogs. Ann. N. Y. Acad. Sci. 1149, 343–346. Ramos-Ligonio, A., López-Monteon, A., Guzmán-Gómez, D., Rosales-Encina, J.L., Limón-Flores, Y., Dumonteil, E., 2010. Identification of a hyperendemic area for Trypanosoma cruzi infection in central Veracruz, Mexico. Am. J. Trop. Med. Hyg. 83, 164–170. Ramsey, J.M., Cruz-Celis, A., Salgado, L., Espinosa, L., Ordonez, R., Lopez, R., 2003a. Efficacy of pyrethroid insecticides against domestic and peridomestic populations of Triatoma pallidipennis and Triatoma barberi (Reduviidae: triatominae) vectors of Chagas’ disease in Mexico. J. Med. Entomol. 40, 912–920. ˜ Ramsey, J.M., Ordónez, R., Tello López, A., Pohls, J.L., Sánchez-Cordero, V., Peterson, A.T., 2003b. VE1 -Chagas disease in Mexico: morbidity, mortality, risk areas and disease burden. Rev. Inst. Med. Trop. São Paulo 45, 198. Rassi Jr., A., Rassi, A., Marin-Neto, J.A., 2010. Chagas disease. Lancet 375, 1388–1402. Remesar, M.C., Gamba, C., Colaianni, I.F., Puppo, M., Sartor, P.A., Murphy, E.L., et al., 2009. Estimation of sensitivity and specificity of several Trypanosoma cruzi antibody assays in blood donors in Argentina. Transfusion (Paris) 49, 2352–2358. Rodríguez-Morales, O., Ballinas-Verdugo, M.A., Alejandre-Aguilar, R., Reyes, P.A., Arce-Fonseca, M., 2011. Trypanosoma cruzi connatal transmission in dogs with Chagas disease: experimental case report. Vector Borne Zoonotic Dis. 11, 1365–1370. Rodríguez-Morales, O., Pérez-Leyva, M.M., Ballinas-Verdugo, M.A., Carrillo-Sánchez, S.C., Rosales-Encina, J.L., Alejandre-Aguilar, R., et al., 2012. Plasmid DNA immunization with Trypanosoma cruzi genes induces cardiac and clinical protection against Chagas disease in the canine model. Vet. Res. 43, 79, http://dx.doi.org/10.1186/1297-9716-43-79.

135

Romero-Cabello, R., Tay-Zavala, J., Sánchez-Vega, J.T., Ruíz-Sánchez, D., CalderónRomero, L., Cruz-López, A., et al., 2006. Enfermedad de Chagas en el estado de Puebla. Reporte de nuevas localidades infectadas. Rev. Fac. Med. UNAM 49, 194–202. Salas Clavijo, N.A., Postigo, J.R., Schneider, D., Santalla, J.A., Brutus, L., Chippaux, J.P., 2012. Prevalence of Chagas disease in pregnant women and incidence of congenital transmission in Santa Cruz de la Sierra, Bolivia. Acta Trop. 124, 87–91. Salazar Schettino, P.M., Bucio, T.M., Cabrera, B.M., Ruiz Hernández, A.L., 2011. Chagas disease in Mexico. Report of two acute cases. Gac. Med. Mex. 147, 63–69. Salazar, P.M., Rojas, G., Bucio, M., Cabrera, M., Garcia, G., Ruiz, A., et al., 2007. Seroprevalence of Trypanosoma cruzi antibodies and associated risk factors among the population under 18 years of age in Veracruz, Mexico. Rev. Panam. Salud Pública 22, 75–82. Sánchez-Guillen, M.C., Barnabe, C., Guegan, J.F., Tibayrenc, M., Velásquez-Rojas, M., Martínez-Munguía, J., et al., 2002. High prevalence anti-Trypanosoma cruzi antibodies, among blood donors in the State of Puebla, a non-endemic area of Mexico. Mem. Inst. Oswaldo Cruz 97, 947–952. Schijman, A.G., Altcheh, J., Burgos, J.M., Biancardi, M., Bisio, M., Levin, M.J., et al., 2003. Aetiological treatment of congenital Chagas’ disease diagnosed and monitored by the polymerase chain reaction. J. Antimicrob. Chemother. 52, 441–449. Schmunis, G.A., Zicker, F., Cruz, J.R., Cuchi, P., 2001. Safety of blood supply for infectious diseases in Latin American countries. Am. J. Trop. Med. Hyg. 65, 924–930. Silveira, A.C., 2011. New challenges and the future of control. Rev. Soc. Bras. Med. Trop. 44 (Suppl. 2), 122–124. Silveira, A.C., Dias, J.C., 2011. The control of vectorial transmission. Rev. Soc. Bras. Med. Trop. 44 (Suppl. 2), 52–63. Sosa-Jurado, F., Zumaquero-Rios, J.L., Reyes, P.A., Cruz-García, A., Guzmán-Bracho, C., Monteón, V.M., 2004. Biotic and abiotic determinants of seroprevalence of antibodies against Trypanosoma cruzi in Palmar de Bravo, Puebla, Mexico. Salud Pública Mex. 46, 39–48. Troncon, L.E., Aprile, L.R., Oliveira, R.B., Iazigi, N., 2000. Abnormally rapid gastric emptying of an isosmotic liquid meal in patients with megaduodenum. Dig. Dis. Sci. 45, 2145–2150. Vassena, C.V., Picollo, M.I., Zerba, E.N., 2000. Insecticide resistance in Brazilian Triatoma infestans and Venezuelan Rhodnius prolixus. Med. Vet. Entomol. 14, 51–55. Vázquez-Chagoyán, J.C., Gupta, S., Garg, N.J., 2011. Vaccine development against Trypanosoma cruzi and Chagas disease. Adv. Parasitol. 75, 121–146. Velasco-Castrejón, O., Valdespino, J.L., Tapia-Conyer, R., Salvatierra, B., GuzmánBracho, C., Magos, C., et al., 1992. Seroepidemiology of Chagas disease in Mexico. Salud Pública Méx. 34, 186–196. Villalobos, G., Martínez-Hernández, F., de la Torre, P., Laclette, J.P., Espinoza, B., 2011. Entomological indices, feeding sources, and molecular identification of Triatoma phyllosoma (Hemiptera: Reduviidae) one of the main vectors of Chagas disease in the Istmo de Tehuantepec, Oaxaca, Mexico. Am. J. Trop. Med. Hyg. 85, 490–497. Villanova, M.G., Meneghelli, U.G., Dantas, R.O., 1987. Gallbladder motor function in chagasic patients with megacolon and/or megaesophagus. Digestion 36, 189–194. Viotti, R., Vigliano, C., Lococo, B., Bertocchi, G., Petti, M., Alvarez, M.G., et al., 2006. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial. Ann. Intern. Med. 144, 724–734. World Health Organization (WHO), 1991. Control of Chagas disease. Report of a WHO Expert Committee. World Health Organ. Tech. Rep. Ser. 811, 1–95. World Health Organization (WHO), 2002. Control of Chagas disease. World Health Organ. Tech. Rep. Ser. 905, i-109, back. World Health Organization (WHO), 2005 Estimación cuantitativa de la enfermedad de Chagas en las Américas. www.bvsops.org.uy/pdf/chagas19.pdf (accessed February 2013). World Health Organization (WHO), 2006. Report of the Scientific Working Group on Chagas Disease. UNDP/World Bank/WHO. World Health Organization (WHO), 2010. Chagas Disease: Control and Elimination. UNDP/World Bank/WHO. Zaniello, B.A., Kessler, D.A., Vine, K.M., Grima, K.M., Weisenberg, S.A., 2012. Seroprevalence of Chagas infection in the donor population. PLoS Negl. Trop. Dis. 6, e1771, http://dx.doi.org/10.1371/journal.pntd.0001771. Zárate, L., Zárate, R.J., 1985. A checklist of the Triatominae (Hemiptera: Reduviidae) of Mexico. Int. J. Entomol. 27, 102–127. Zerba, E.N., 1999. Susceptibility and resistance to insecticides of Chagas disease vectors. Medicina (B Aires) 59 (2), 41–46.