• View in gallery

    Cumulative proportion of individuals with right bundle branch block by age and sex in persons seropositive and seronegative for Trypanosoma cruzi. The difference in prevalence between sero-positive and seronegative persons was highly significant (P = 6 × 10 −20). Age at electrocardiographic (ECG) testing is in years.

  • View in gallery

    Cumulative proportion of persons with any electrocardiographic (ECG) abnormality by age (years) and sex in persons seropositive and seronegative for Typanosoma cruzi. The difference in prevalence of an ECG abnormality between seropositive and seronegative persons was highly significant (P = 1.2 × 10−9).

  • 1

    Dias JC, Silveira AC, Schofield CJ, 2002. Impact of Chagas disease control in Latin America: a review. Mem Inst Oswaldo Cruz 97 :603–612.

    • Search Google Scholar
    • Export Citation
  • 2

    World Health Organization, 2002. Control of Chagas disease. World Health Organ Tech Rep Ser 905 :1–109.

  • 3

    Moncayo A, 2003. Chagas disease: current epidemiological trends after the interruption of vectoral and transfusional transmission in the Southern Cone countries. Mem Inst Oswaldo Cruz 98 :577–591.

    • Search Google Scholar
    • Export Citation
  • 4

    Dutra WO, Rocha MO, Teixeira MM, 2005. The clinical immunology of human Chagas disease. Trends Parasitol 21 :581–587.

  • 5

    Kirchhoff LV, 1999. American trypanosomiasis (Chagas disease). Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. New York: Churchill Livingstone, 785–796.

  • 6

    Coll-Cardenas R, Espinoza-Gomez F, Maldonado-Rodriguez A, Reyes-Lopez PA, Huerta-Viera M, Rojas-Larios F, 2004. Active transmission of human Chagas disease in Colima, Mexico. Mem Inst Oswaldo Cruz 99 :363–368.

    • Search Google Scholar
    • Export Citation
  • 7

    Rizzo NR, Arana BA, Diaz A, Cordon-Rosales C, Klein RE, Powell MR, 2003. Seroprevalence of Trypanosoma cruzi infection among school-age children in the endemic area of Guatemala. Am J Trop Med Hyg 68 :678–682.

    • Search Google Scholar
    • Export Citation
  • 8

    Grijalva MJ, Escalante L, Paarades RA, Costales JA, Padilla A, Rowland EC, Aguilar JM, Racines J, 2003. Seroprevalence and risk factors for Trypanosoma cruzi infection in the Amazon region of Ecuador. Am J Trop Med Hyg 69 :380–385.

    • Search Google Scholar
    • Export Citation
  • 9

    Pinto AY, Valente SA, Valente VC, 2004. Emerging acute Chagas disease in Amazonian Brazil: case reports with serious cardiac involvement. Braz J Infect Dis 8 :454–460.

    • Search Google Scholar
    • Export Citation
  • 10

    Gurtler RE, Cecere MC, Lauricella MA, Petersen RM, Chuit R, Segura EL, Cohen JE, 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.

    • Search Google Scholar
    • Export Citation
  • 11

    Borges JS, Machada de Assis GF, Gomes LV, Dias JC, Pinto ID, Martins-Filho OA, Torres RM, Vinas PA, Bahia MT, Machado-Coelho GL, Lana M, 2006. Seroprevalence of Chagas disease in school children from two municipalities of Jequitinhonha Valley, Minas Gerais, Brazil: six years following the onset of epidemiological surveillance. Rev Inst Med Trop Sao Paulo 48 :81–86.

    • Search Google Scholar
    • Export Citation
  • 12

    Garg N, Bhatia V, 2005. Current status and future prospects for a vaccine against American trypanosomiasis. Expert Rev Vaccines 4 :867–880.

    • Search Google Scholar
    • Export Citation
  • 13

    Urbino JA, Docompo R, 2004. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 19 :495–501.

  • 14

    Kirchhoff LV, 2003. Changing epidemiology and approaches to therapy for Chagas disease. Curr Infect Dis Rep 5 :59–65.

  • 15

    McCarthy M, 2003. American Red Cross to screen blood for Chagas disease. Lancet 362 :1988.

  • 16

    Busch MP, Kleinman SH, Nemo GJ, 2003. Current and emerging infectious risks of blood transfusions. JAMA 289 :959–961.

  • 17

    Beard CB, Pye G, Steurer FJ, Rodrigues R, Campman R, Peterson AT, Ramsey J, Wirtz RA, Robinson LE, 2003. Chagas disease in a domestic transmission cycle, southern Texas, USA. Emerg Infect Dis 9 :103–105.

    • Search Google Scholar
    • Export Citation
  • 18

    DiPentima MC, Hwang LY, Skeeter CM, Edwards MS, 1999. Prevalence of antibody to Trypanosoma cruzi in pregnant Hispanic women in Houston. Clin Infect Dis 28 :1281–1285.

    • Search Google Scholar
    • Export Citation
  • 19

    Leiby DA, Herron RM, Read EJ, Lenes BA, Stumpf RJ, 2002. Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion 42 :549–555.

    • Search Google Scholar
    • Export Citation
  • 20

    Centers for Disease Control and Prevention, 2002. Chagas disease after organ transplantation—United States, 2001. MMWR Morb Mortal Wkly Rep 51 :210–212.

    • Search Google Scholar
    • Export Citation
  • 21

    Kirchhoff LV, Weiss LM, Wittner M, Tanowitz HB, 2004. Parasitic diseases of the heart. Front Biosci 9 :706–723.

  • 22

    Prata A, 2001. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis 1 :92–100.

  • 23

    Goldbaum M, Ajimura FY, Litvoc J, Alves de Carvalho S, Eluf-Neto J, 2004. American trypansomiasis and electrocardiographic alterations among industrial workers in Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo 46 :299–302.

    • Search Google Scholar
    • Export Citation
  • 24

    Yacoub S, Birks EJ, Slavik Z, Henein M, 2003. Early detection of myocardial dysfunction in Chagas disease using novel echocardiographic indices. Trans R Soc Trop Med Hyg 97 :528–534.

    • Search Google Scholar
    • Export Citation
  • 25

    Sosa-Hurado F, Mazariego-Aranda M, Hernandez-Becerril N, Garza-Murillo V, Cardenas M, Reyes PA, Hirayama K, Monteon VM, 2003. Electrocardiographic findings in Mexican Chagasic subjects living in high and low endemic regions of Trypansoma cruzi infection. Mem Inst Oswaldo Cruz 98 :605–610.

    • Search Google Scholar
    • Export Citation
  • 26

    Rangel-Flores H, Sánchez B, Mendoza-Duarte J, Barbnabe C, Breniere FS, Ramos C, Espinoza B, 2001. Serologic and parasitologic demonstration of Trypansoma cruzi infections in an urban area of central Mexico: correlation with electrocardiographic alterations. Am J Trop Med Hyg 65 :887–895.

    • Search Google Scholar
    • Export Citation
  • 27

    Jorge MT, Macedo TA, Janones RS, Carizzi DP, Heredia RA, Acha RE, 2003. Types of arrhythmia among cases of American trypanosomiasis compared with those in other cardiology patients. Ann Trop Med Parasitol 97 :139–148.

    • Search Google Scholar
    • Export Citation
  • 28

    Maguire JH, Hoff R, Sherlock I, Guimaraes AC, Sleigh AC, Ramos NB, Mott KE, Weller TH, 1987. Cardiac morbidity and mortality due to Chagas disease: prospective electrocardiographic study of a Brazilian community. Circulation 75 :1140–1145.

    • Search Google Scholar
    • Export Citation
  • 29

    Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardosa C, 2003. Prognostic value of QT interval parameters for mortality risk stratification in Chagas disease: results of a long-term follow-up study. Circulation 108 :305–312.

    • Search Google Scholar
    • Export Citation
  • 30

    Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardosa C, 2004. T-wave axis deviation as an independent predictor of mortality in chronic Chagas disease. Am J Cardiol 93 :1136–1140.

    • Search Google Scholar
    • Export Citation
  • 31

    Almasy L, Blangero J, 1998. Multipoint quantitative trait linkage analysis in general pedigrees. Am J Hum Genet 62 :1198–1211.

  • 32

    Brutus L, Schneider D, Postigo J, Delgado W, Mollinedo S, Chippaux JP, 2007. Evidence of congenital transmission of Trypanosoma cruzi in a vector-free area of Bolivia. Trans R Soc Trop Med Hyg: (Epub ahead of print).

  • 33

    Corbucci HA, Haber DM, Bestetti RB, Cordeiro JA, Fioroni ML, 2006. QT interval dispersion in patients with chronic heart failure secondary to Chagas cardiomyopathy: correlation with clinical variables of prognostic significance. Cardiovasc Pathol 15 :18–23.

    • Search Google Scholar
    • Export Citation
  • 34

    Soto-Rojas G, Cortes JM, Medrano GA, 1984. Electrocardiographic changes in 29 apparently healthy subjects with positive serological tests for Chagas disease. Arch Inst Cardiol Mex 54 :579–583.

    • Search Google Scholar
    • Export Citation
  • 35

    Pimenta J, Miranda M, Pereira CB, 1983. Electrophysiologic findings in long-term asymptomatic chagasic individuals. Am Heart J 106 :374–380.

    • Search Google Scholar
    • Export Citation
  • 36

    DeBacquer D, DeBacker G, Kornitzer M, 2000. Prevalences of ECG findings in large population based samples of men and women. Heart 84 :625–633.

    • Search Google Scholar
    • Export Citation
 
 

 

 

 

 

 

 

Electrocardiographic Characteristics in a Population with High Rates of Seropositivity for Trypanosoma cruzi Infection

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  • 1 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas; Centro de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil; Southwest National Primate Research Center, San Antonio, Texas

This study was conducted in Posse, a rural community in Goiàs, Brazil. Persons were recruited into the study through house-to-house sampling of all houses in the sampled area. Blood samples were collected for seropositivity assessments for Trypanosoma cruzi and an electrocardiogram was assessed using a portable system. The results demonstrate significant differences between seropositive and seronegative persons for electrocardiographic (ECG)–derived traits. Seropositive persons had substantially longer QRS and QT intervals than seronegative persons. The PR interval was significantly different between seropositive and seronegative persons. Conduction abnormalities were observed more frequently in seropositive than seronegative persons. Right bundle branch block, an ECG abnormality typical of Chagas disease, was observed in 15% of seropositive persons compared with less than 1% of seronegative persons. Results indicate that T. cruzi infection and subsequent Chagas disease will continue to be major health problems for the foreseeable future in this typical rural area of Brazil.

INTRODUCTION

Chagas disease is the leading cause of heart disease in Latin America, affecting approximately 17 million people.14 Trypanosoma cruzi, the parasitic cause of Chagas disease, is transmitted to the human host by reduiivid bugs that live in the walls and roofs of houses in many rural areas of Latin America.5 There are no effective therapies for the chronic long-term phase of the disease and there are no vaccines or drugs to prevent infection with T. cruzi.

Substantial resources have been dedicated to eliminating the vector from household structures in Latin America. However, active transmission occurs in many areas,611 and between 100 and 120 million persons are considered to be at risk for infection with T. cruzi.2 Approximately 300,000 persons are newly infected each year2 and approximately 60% of those infected with T. cruzi will experience a long-term chronic disease characterized by highly variable cardiac outcomes, and less frequently by mega-colon and/or megaesophagus.5

The presence of active transmission combined with the current lack of vaccines or effective prophylactic drugs5,1214 means that Chagas disease will remain a significant health burden and major economic drain in South America for the foreseeable future. In addition, Chagas disease is an emerging health threat in the United States and Canada, particularly in regions with large South and Central American immigrant populations.1521

The cardiac form of Chagas disease is evidenced in electrocardiographic (ECG) data by conduction abnormalities that include bradyarrythmias, premature ventricular contractions, and bundle branch blocks, particularly right bundle branch blocks.5,22 Case-control studies have found that right bundle branch block, left anterior hemiblock, and atrio-ventricular blocks occur at a much higher frequency in seropositive persons than in seronegative persons.2328 An elevated Q-T interval and T-wave axis deviation have both been implicated as predictive of mortality in patients with Chagas disease.29,30 Statistics indicate that more than half of those infected with T. cruzi can expect to progress to chronic Chagas disease and most will experience the cardiac form of the disease.5

There are few large-scale studies that have assessed ECG-related variables in populations in areas endemic for Chagas disease (however, see the study by Maguire and others28). The purpose of the current study was to assess the epidemiology of cardiac disease as shown by ECG characteristics in a population with high rates of infection with T. cruzi.

MATERIALS AND METHODS

The study was conducted in Posse, a rural community in the state of Goiás, Brazil located approximately 350 km northeast of Brasilia, the capital of Brazil. The population consists primarily of subsistence farmers, most of whom were born in the municipality. The population is highly admixed and derived from European, African, and Amerindian ancestry.

Persons were recruited into the study through house-to-house sampling using a protocol that was reviewed and approved by the Institutional Review Boards of the University of Texas Health Science Center in San Antonio and the Rene Rachou Research Center of the Oswaldo Cruz Foundation in Belo Horizonte, Minas Gerais, Brazil. The sample is population based and includes all eligible adults in the sampling area who were willing to participate. The study was explained at each household and persons who elected to participate provided a consent form that was either signed or fingerprinted. A total of 1,389 persons were successfully recruited.

A 10-mL blood sample was collected into a red-top tube for assessment of seropositivity status. Samples were allowed to clot, and then were kept on wet ice until they were separated into serum and clot no more than eight hours after collection. Serum samples were then aliquotted and frozen in liquid nitrogen until transfer to the laboratories in Belo Horizonte and San Antonio on dry ice.

Serum samples from all persons were assessed by three standardized tests (enzyme-linked immunosorbent assay [ELISA], hemagglutination, and immunofluorescence) by the Laboratory of Cellular and Molecular Immunology at the Rene Rachou Research Center, FIOCRUZ. Persons were considered seropositive if two or more of these standardized tests indicated seropositivity for T. cruzi infection. A total of 1,190 persons (86%) were typed with all three tests, and were determined to be positive if two or more tests showed positive results. The remaining persons were scored based on the results of two tests: 121 persons were scored as negative based on results of the hemagglutination and immunofluoresence tests, 3 persons were scored as positive on the basis of positive ELISA and immunofluorescence test results, and 75 persons were scored as positive on the basis of positive hemagglutination and immunofluorescence test results.

The ECGs were collected from all participants using the portable Marquette MAC5000 System (GE Medical Systems Information Technologies, Milwaukee, WI). In addition to the automated quantitative data output by the machine, qualitative ECG variables were verified by a clinical cardiologist experienced in the treatment of Chagas disease.

For the quantitative ECG traits, statistical analysis using a linear model was performed to test for differences between seropositive and seronegative persons. All analyses were performed simultaneously adjusting for the effects of several covariates including sex, age, age2, sex × age, and sex × age2. Results are provided both as the covariate-adjusted means for seropositive and seronegative persons and as standardized differences measured in standard deviation units. The latter index allows for easier comparison across variables and provides a measure of the biologic importance of a given statistical difference. Because the data set consists of large numbers of related persons, we explicitly allowed for kinship-based non-independence by performing all analyses conditional upon the known pedigree structure. Non-independence was modeled through a familiality parameter that was treated as a nuisance parameter given that the focus of the current report is on the changes in mean effects induced by T. cruzi infection. Dichotomous discrete ECG variables such as bundle branch abnormalities were similarly analyzed using a probit regression model allowing for non-independence due to kinship. The program SOLAR,31 which enables arbitrary modeling of mean effects in the presence of structured non-independence, was used for all statistical analyses.

RESULTS

Seropositivity and ECG measures were available for 1,389 persons. There were 690 males and 699 females. These persons were members of 110 families although almost all (1,193) can be placed into a single, large, extended family. The average age of the persons was 41.9 years. The rate of T. cruzi seropositivity observed was high in this population. There were 722 seropositive persons and 667 seronegative persons; 52% of the sampled persons were seropositive for T. cruzi infection.

A number of traits were determined from the ECG readings. Quantitative intervals were determined directly from the ECG. The quantitative intervals evaluated included the QRS interval, the QT interval, and the PR interval. The mean values for each interval in seropositive and seronegative persons are shown in Table 1. Also shown is the difference in standard deviation units between seropositive and seronegative persons.

These results show that there were significant differences between seropositive and seronegative persons for most of the quantitative ECG variables that were assessed in the population. All quantitative ECG-derived variables showed significant differences between seropostive and seronegative persons. Seropositive persons had substantially longer QRS and QT intervals than seronegative persons. The observed highly significant differences are of a magnitude approximately 0.4 of a standard deviation for these traits. Such a large standardized difference is quite striking. The PR interval was also significantly different in length between seropositive and seronegative persons. However, this increase is rather modest and represents a displacement of approximately 0.14 of a standard deviation unit. Seropositive persons also had significantly lower ventricular rates than persons seronegative for T. cruzi infection. This highly significant difference in ventricular rate represents a displacement of the seropositive mean approaching nearly a 0.75 of a standard deviation unit. Taken together, these results on a large population show dramatic differences in cardiovascular-related parameters between seropositive and seronegative persons.

We also assessed the frequency of a variety of qualitative Chagas disease–related traits in seropositive and seronegative persons. These traits are shown in Table 2. As is the case with the quantitative ECG measures, there were significant differences between persons who were seropositive for T. cruzi infection and uninfected persons.

Conduction abnormalities were more frequently observed in infected than uninfected persons. For example, right bundle branch block is an ECG characteristic that is typical of Chagas disease.5 As expected, right bundle branch block is much more frequent in seropositive persons than in seronegative persons, with less than 1% of seronegative persons having a right bundle branch block compared with 15% of seropositive persons having this branch block. This difference was highly significant (P = 6 × 10−20). Thus, right bundle branch block appears to be closely related to infection in this population.

Figure 1 shows the cumulative proportion of persons with right bundle branch block by age in males and females. There was no significant difference in the frequency of right bundle branch block between males and females in seronegative persons. However, in seropositive persons, right bundle branch block increases significantly with age, and also shows a substantial difference between males and females. Among seropositive persons, males are more likely to develop a right bundle branch block than females.

Other conduction abnormalities are altered by T. cruzi infection. As shown in Table 1, bifascicular block, left anterior fascicular block, and left axis deviation are present in seropositive persons at significantly higher frequencies than in seronegative persons. Significant differences in the frequencies of marked sinus bradycardia, left ventricular hypertrophy, and atrial fibrillation were not observed. However, for each of these abnormalities, infected persons showed nominally higher frequencies than uninfected persons. There was a substantial difference in the frequency of ECG abnormalities, with seropositive persons having a prevalence of approximately 43% versus only 18% in seronegative persons (P = 1 × 10−9). These results clearly demonstrate the effect of T. cruzi infection on sub-clinical heart abnormalities.

Figure 2 shows the plot of presence of any type of conduction block by age in seropositive and seronegative persons from the Posse population. Seropositive persons had much higher rates of conduction blocks at all ages. Although some conduction blocks are expected in uninfected persons, seropositive persons have higher prevalences of conduction blocks at all ages.

DISCUSSION

The study region in Posse is typical of many rural areas in central Brazil. This large-scale study of the local population provides insights into the implications of Chagas disease for local health services that surveys of cases and controls conducted in hospital settings cannot. The high rates of seropositivity in this rural area indicate that Chagas disease will be a continuing public health problem in the region for the foreseeable future. Despite intensive vector control efforts, Chagas disease will persist as a major consumer of health care resources because of the large population of persons who are already infected. Congenital transmission can result in new infections in regions with no vector-transmitted disease.32 Active transmission still occurs in many areas and congenital transmission also can cause infections. With the decreased emphasis on vector control in Brazil, it is possible that active transmission will recur in areas that were previously considered to be controlled.

The population variation in QT and QRS intervals may be informative in predicting the future health care needs in the region. Several investigators have noted the potential value of QT interval parameters for predicting outcome in Chagas disease.29,33 The QT and QRS intervals were significantly increased in seropositive persons in the Posse population. As previously reported,3436 persons with ECG abnormalities predictive of a negative outcome in Chagas disease may be apparently healthy. Population level surveys conducted through general health clinics may be an excellent mechanism for identifying asymptomatic seropositive persons whose cardiac health should be monitored on a regular basis.

Epidemiologic studies of European populations that were not exposed to T. cruzi infection showed that ECG abnormalities are more common in males than in females.36 That pattern was seen in the Posse population in seronegative persons. Interestingly, the divergence in prevalence of abnormalities between males and females was greater in seropositive persons. This finding may be reflective of increased physical labor by males in this agricultural population, which can put additional strain on the cardiovascular system. In particular, right bundle branch blocks are more frequent in seropositive persons than seronegative persons. The difference in ECG abnormalities between seropositive males and females reflects the general trend for increased rates of abnormalities in men.

In conclusion, population level surveys of seropositivity for T. cruzi infection and ECG variables are useful in predicting the future health care needs of local populations in Brazil. The epidemiologic data on seropositivity and ECG variables in the Posse population clearly indicate that Chagas disease will persist for a long time as a major public health burden. Despite the successes of the vector control programs in diminishing active transmission of T. cruzi when assessed at the national level, local populations in areas that are endemic for Chagas disease are still struggling with this devastating disease and will continue to do so for the foreseeable future.

Table 1

Mean electrocardiographic (ECG) parameters in Trypanosoma cruzi–seropositive and -seronegative persons adjusted for age and sex*

ECG traitMean value in seronegative personsMean value in seropositive personsDifference in SDUsP
* SDUs = standard deviation units.
QRS91.08 ms98.55 ms0.44239.3 × 10−12
QT382.49 ms396.97 ms0.39405.1 × 10−10
PR152.15 ms155.73 ms0.13760.0275
Ventricular rate70.21 bpm67.04 bpm−0.24600.00004
Table 2

Frequency of qualitative electrocardiographic (ECG) traits in seropositive and seronegative persons adjusted for age and sex

ECG traitFrequency in seronegative personsFrequency in seropositive personsP
Right bundle branch block0.00900.15246.0 × 10−20
Bifascicular block0.00000.05262.8 × 10−9
Left anterior fascicular block0.00450.07898.6 × 10−7
Marked sinus bradycardia0.01500.02490.3874
Left axis deviation0.01500.05400.0060
Left ventricular hypertrophy0.05250.08450.7128
Atrial fibrillation0.00150.00690.2248
Abnormal ECG0.18290.43491.2 × 10−9
Figure 1.
Figure 1.

Cumulative proportion of individuals with right bundle branch block by age and sex in persons seropositive and seronegative for Trypanosoma cruzi. The difference in prevalence between sero-positive and seronegative persons was highly significant (P = 6 × 10 −20). Age at electrocardiographic (ECG) testing is in years.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 77, 3; 10.4269/ajtmh.2007.77.495

Figure 2.
Figure 2.

Cumulative proportion of persons with any electrocardiographic (ECG) abnormality by age (years) and sex in persons seropositive and seronegative for Typanosoma cruzi. The difference in prevalence of an ECG abnormality between seropositive and seronegative persons was highly significant (P = 1.2 × 10−9).

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 77, 3; 10.4269/ajtmh.2007.77.495

*

Address correspondence to S. Williams-Blangero, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549. E-mail: sarah@darwin.sfbr.org

Authors’ addresses: S. Williams-Blangero, E. Rainwater, and J. Blangero, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549. T. Magalhaes and R. Corrêa-Oliveira, Centro de Pesquisas Rene Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil. J. L. VandeBerg, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549 and Southwest National Primate Research Center, PO Box 760549, San Antonio, TX 78245-0549.

Acknowledgments: We thank Antonio R.L. Teixeira for his contributions to initiating this project, FIOCRUZ and the Brazilian Ministry of Health for logistical assistance, and the people of Posse for their generous cooperation with this long-term study.

Financial support: This research was supported by grants HL66480 to S. Williams-Blangero and MH59490 to J. Blangero from the National Institutes of Health. This work was conducted in part in facilities constructed with support from the Research Facilities Improvement Program under grant C06 RR017515 from the National Center for Research Resources of the National Institutes of Health.

REFERENCES

  • 1

    Dias JC, Silveira AC, Schofield CJ, 2002. Impact of Chagas disease control in Latin America: a review. Mem Inst Oswaldo Cruz 97 :603–612.

    • Search Google Scholar
    • Export Citation
  • 2

    World Health Organization, 2002. Control of Chagas disease. World Health Organ Tech Rep Ser 905 :1–109.

  • 3

    Moncayo A, 2003. Chagas disease: current epidemiological trends after the interruption of vectoral and transfusional transmission in the Southern Cone countries. Mem Inst Oswaldo Cruz 98 :577–591.

    • Search Google Scholar
    • Export Citation
  • 4

    Dutra WO, Rocha MO, Teixeira MM, 2005. The clinical immunology of human Chagas disease. Trends Parasitol 21 :581–587.

  • 5

    Kirchhoff LV, 1999. American trypanosomiasis (Chagas disease). Guerrant RL, Walker DH, Weller PF, eds. Tropical Infectious Diseases: Principles, Pathogens, and Practice. New York: Churchill Livingstone, 785–796.

  • 6

    Coll-Cardenas R, Espinoza-Gomez F, Maldonado-Rodriguez A, Reyes-Lopez PA, Huerta-Viera M, Rojas-Larios F, 2004. Active transmission of human Chagas disease in Colima, Mexico. Mem Inst Oswaldo Cruz 99 :363–368.

    • Search Google Scholar
    • Export Citation
  • 7

    Rizzo NR, Arana BA, Diaz A, Cordon-Rosales C, Klein RE, Powell MR, 2003. Seroprevalence of Trypanosoma cruzi infection among school-age children in the endemic area of Guatemala. Am J Trop Med Hyg 68 :678–682.

    • Search Google Scholar
    • Export Citation
  • 8

    Grijalva MJ, Escalante L, Paarades RA, Costales JA, Padilla A, Rowland EC, Aguilar JM, Racines J, 2003. Seroprevalence and risk factors for Trypanosoma cruzi infection in the Amazon region of Ecuador. Am J Trop Med Hyg 69 :380–385.

    • Search Google Scholar
    • Export Citation
  • 9

    Pinto AY, Valente SA, Valente VC, 2004. Emerging acute Chagas disease in Amazonian Brazil: case reports with serious cardiac involvement. Braz J Infect Dis 8 :454–460.

    • Search Google Scholar
    • Export Citation
  • 10

    Gurtler RE, Cecere MC, Lauricella MA, Petersen RM, Chuit R, Segura EL, Cohen JE, 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.

    • Search Google Scholar
    • Export Citation
  • 11

    Borges JS, Machada de Assis GF, Gomes LV, Dias JC, Pinto ID, Martins-Filho OA, Torres RM, Vinas PA, Bahia MT, Machado-Coelho GL, Lana M, 2006. Seroprevalence of Chagas disease in school children from two municipalities of Jequitinhonha Valley, Minas Gerais, Brazil: six years following the onset of epidemiological surveillance. Rev Inst Med Trop Sao Paulo 48 :81–86.

    • Search Google Scholar
    • Export Citation
  • 12

    Garg N, Bhatia V, 2005. Current status and future prospects for a vaccine against American trypanosomiasis. Expert Rev Vaccines 4 :867–880.

    • Search Google Scholar
    • Export Citation
  • 13

    Urbino JA, Docompo R, 2004. Specific chemotherapy of Chagas disease: controversies and advances. Trends Parasitol 19 :495–501.

  • 14

    Kirchhoff LV, 2003. Changing epidemiology and approaches to therapy for Chagas disease. Curr Infect Dis Rep 5 :59–65.

  • 15

    McCarthy M, 2003. American Red Cross to screen blood for Chagas disease. Lancet 362 :1988.

  • 16

    Busch MP, Kleinman SH, Nemo GJ, 2003. Current and emerging infectious risks of blood transfusions. JAMA 289 :959–961.

  • 17

    Beard CB, Pye G, Steurer FJ, Rodrigues R, Campman R, Peterson AT, Ramsey J, Wirtz RA, Robinson LE, 2003. Chagas disease in a domestic transmission cycle, southern Texas, USA. Emerg Infect Dis 9 :103–105.

    • Search Google Scholar
    • Export Citation
  • 18

    DiPentima MC, Hwang LY, Skeeter CM, Edwards MS, 1999. Prevalence of antibody to Trypanosoma cruzi in pregnant Hispanic women in Houston. Clin Infect Dis 28 :1281–1285.

    • Search Google Scholar
    • Export Citation
  • 19

    Leiby DA, Herron RM, Read EJ, Lenes BA, Stumpf RJ, 2002. Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion 42 :549–555.

    • Search Google Scholar
    • Export Citation
  • 20

    Centers for Disease Control and Prevention, 2002. Chagas disease after organ transplantation—United States, 2001. MMWR Morb Mortal Wkly Rep 51 :210–212.

    • Search Google Scholar
    • Export Citation
  • 21

    Kirchhoff LV, Weiss LM, Wittner M, Tanowitz HB, 2004. Parasitic diseases of the heart. Front Biosci 9 :706–723.

  • 22

    Prata A, 2001. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis 1 :92–100.

  • 23

    Goldbaum M, Ajimura FY, Litvoc J, Alves de Carvalho S, Eluf-Neto J, 2004. American trypansomiasis and electrocardiographic alterations among industrial workers in Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo 46 :299–302.

    • Search Google Scholar
    • Export Citation
  • 24

    Yacoub S, Birks EJ, Slavik Z, Henein M, 2003. Early detection of myocardial dysfunction in Chagas disease using novel echocardiographic indices. Trans R Soc Trop Med Hyg 97 :528–534.

    • Search Google Scholar
    • Export Citation
  • 25

    Sosa-Hurado F, Mazariego-Aranda M, Hernandez-Becerril N, Garza-Murillo V, Cardenas M, Reyes PA, Hirayama K, Monteon VM, 2003. Electrocardiographic findings in Mexican Chagasic subjects living in high and low endemic regions of Trypansoma cruzi infection. Mem Inst Oswaldo Cruz 98 :605–610.

    • Search Google Scholar
    • Export Citation
  • 26

    Rangel-Flores H, Sánchez B, Mendoza-Duarte J, Barbnabe C, Breniere FS, Ramos C, Espinoza B, 2001. Serologic and parasitologic demonstration of Trypansoma cruzi infections in an urban area of central Mexico: correlation with electrocardiographic alterations. Am J Trop Med Hyg 65 :887–895.

    • Search Google Scholar
    • Export Citation
  • 27

    Jorge MT, Macedo TA, Janones RS, Carizzi DP, Heredia RA, Acha RE, 2003. Types of arrhythmia among cases of American trypanosomiasis compared with those in other cardiology patients. Ann Trop Med Parasitol 97 :139–148.

    • Search Google Scholar
    • Export Citation
  • 28

    Maguire JH, Hoff R, Sherlock I, Guimaraes AC, Sleigh AC, Ramos NB, Mott KE, Weller TH, 1987. Cardiac morbidity and mortality due to Chagas disease: prospective electrocardiographic study of a Brazilian community. Circulation 75 :1140–1145.

    • Search Google Scholar
    • Export Citation
  • 29

    Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardosa C, 2003. Prognostic value of QT interval parameters for mortality risk stratification in Chagas disease: results of a long-term follow-up study. Circulation 108 :305–312.

    • Search Google Scholar
    • Export Citation
  • 30

    Salles G, Xavier S, Sousa A, Hasslocher-Moreno A, Cardosa C, 2004. T-wave axis deviation as an independent predictor of mortality in chronic Chagas disease. Am J Cardiol 93 :1136–1140.

    • Search Google Scholar
    • Export Citation
  • 31

    Almasy L, Blangero J, 1998. Multipoint quantitative trait linkage analysis in general pedigrees. Am J Hum Genet 62 :1198–1211.

  • 32

    Brutus L, Schneider D, Postigo J, Delgado W, Mollinedo S, Chippaux JP, 2007. Evidence of congenital transmission of Trypanosoma cruzi in a vector-free area of Bolivia. Trans R Soc Trop Med Hyg: (Epub ahead of print).

  • 33

    Corbucci HA, Haber DM, Bestetti RB, Cordeiro JA, Fioroni ML, 2006. QT interval dispersion in patients with chronic heart failure secondary to Chagas cardiomyopathy: correlation with clinical variables of prognostic significance. Cardiovasc Pathol 15 :18–23.

    • Search Google Scholar
    • Export Citation
  • 34

    Soto-Rojas G, Cortes JM, Medrano GA, 1984. Electrocardiographic changes in 29 apparently healthy subjects with positive serological tests for Chagas disease. Arch Inst Cardiol Mex 54 :579–583.

    • Search Google Scholar
    • Export Citation
  • 35

    Pimenta J, Miranda M, Pereira CB, 1983. Electrophysiologic findings in long-term asymptomatic chagasic individuals. Am Heart J 106 :374–380.

    • Search Google Scholar
    • Export Citation
  • 36

    DeBacquer D, DeBacker G, Kornitzer M, 2000. Prevalences of ECG findings in large population based samples of men and women. Heart 84 :625–633.

    • Search Google Scholar
    • Export Citation
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