Evaluación del disbalance autonómico en el paciente con serología positiva para enfermedad de Chagas: Score de diagnóstico y tratamiento

La enfermedad de Chagas es una enfermedad parasitaria (Trypanosoma cruzi), endémica en 21 países de América y que las migraciones la han dispersado en distintos continentes. Una de las manifestaciones más precoces de esta enfermedad son las alteraciones disautonómicas o disfunción autonómica. La severidad de este inadecuado funcionamiento del sistema nervioso autónomo resulta mensurable, de modo que la evolución y/o progresión de la enfermedad puede constatarse mediante la alteración de estudios clínicos y detección de anticuerpos antimuscarínicos. Estos anticuerpos están presentes en un 30% de los infectados y aparecen muy precozmente una vez instalada la parasitosis; además otros estudios, como la dispersión del QT (>65 mseg) y la variabilidad de la frecuencia cardíaca (<100 mseg) presentan valores anormales. La utilización de nuevos paradigmas de atención, diagnóstico y tratamientos adecuados son imprescindibles para prevenir el desarrollo de esta cardiopatía.

Chagas disease is a parasitic disease (Trypanosoma cruzi), endemic in 21 countries of America and that migrations have dispersed it in different continents. One of the earliest manifestations of this disease is dysautonomic alterations or autonomic dysfunction. The severity of this inadequate functioning of the autonomic nervous system is measurable, so that the evolution and/or progression of the disease can be verified by altering clinical studies and detecting antimuscarinic antibodies. These antibodies are present in 30% of those infected and appear very early once the parasitosis is installed; In addition, other studies, such as QT dispersion (> 65 ms) and heart rate variability (<100 ms) show abnormal values. The use of new paradigms of care, diagnosis and appropriate treatments are essential to prevent the development of this heart disease.

A doença de Chagas é uma doença parasitária (Trypanosoma cruzi), endêmica em 21 países da América e que as migrações a dispersaram em diferentes continentes. Uma das primeiras manifestações desta doença são as alterações disautonômicas ou disfunção autonômica. A gravidade desse funcionamento inadequado do sistema nervoso autônomo é mensurável, de modo que a evolução e/ou progressão da doença pode ser verificada alterando os estudos clínicos e detectando anticorpos antimuscarínicos. Esses anticorpos estão presentes em 30% dos infectados e aparecem muito cedo, uma vez instalada a parasitose; Além disso, outros estudos, como a dispersão do QT (> 65 mseg) e a variabilidade da freqüência cardíaca (<100 mseg), mostram valores anormais. A utilização de novos paradigmas de atendimento, diagnóstico e tratamentos adequados são essenciais para prevenir o desenvolvimento desta doença cardíaca.

Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects.

Cardiovascular diseases (CVD) are group of complex and multifactorial pathologies, in which interleukin-6 (IL-6) gene polymorphisms have been associated with several components of the CVD. Thus, in this study, we thoroughly reviewed and meta-analyzed evidence on the association between the IL-6 (rs1800795) gene polymorphism and CVD. We systematically searched in the PubMed, Web of Sciences, and Scopus databases. The analyses were performed using five study groups based on (1) a combined pool of the overall populations, (2) the country of birth, (3) the continent of birth, (4) the diagnosis and (5) both location (country or continent) and diagnosis. The analysis included the allelic, homozygote, heterozygote, dominant and recessive models. The meta-analysis showed that -174G>C (rs1800795) is a risk factor for CVD (allelic: OR=1.06, CI 95%=1.02-1.10. Z p value <0.0001; homozygous: OR=1.11, CI 95%=1.03-1.19, Z p value= 0.002; heterozygous: OR=1.08, CI 95%=1.03-1.21, Z p value= 0.003; dominant: OR= 1.12, CI 95%= 1.07-1.18, Z p value= 0.001) and that this risk increases in the Chinese population. Additionally, we found that carriers of the C allele of 174G>C (rs1800795) polymorphism have an increase in the risk of coronary artery disease under the hereditary models assessed in the study. Using robust data, we found that IL-6 (rs1800795) -174G>C gene polymorphism is associated with CVD risk.

Association of vitamin D receptor polymorphisms and nephrolithiasis: A meta-analysis.

Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were "vitamin D receptor or VDR" and "polymorphisms or SNPs" combined with "urolithiasis or nephrolithiasis". A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73-0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54-0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48-0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66-0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63-0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.

The Type of Trypanosoma Cruzi Strain (Native or Non-Native) Used as Substrate for Immunoassays Influences the Ability of Screening Asymptomatic Blood Donors.

BACKGROUND: The origin (native or non-native) of Trypanosoma cruzi strains used as substrate for immunoassays may influence their performance. OBJECTIVE: To assess the performance of an immunoassay based on a native T. cruzi strain compared to another based on non-native T. cruzi strains, in asymptomatic blood donors from Mexico. METHODS: Serum samples from a tertiary referral center were tested by both ELISA-INC9 (native) and Chagatest (non-native) assays. All reactive serum samples were further analyzed by indirect immunofluorescence. RESULTS: Sera from 1,098 asymptomatic blood donors were tested. A 4.3 and 0.7% serum reactivity prevalence was observed using ELISA-INC9 and Chagatest, respectively (kappa = 0.13; -0.11 to 0.38). Subsequently, indirect immunofluorescence analyses showed higher positivity in serum samples reactive by ELISA-INC9 compared to those reactive by Chagatest (79 vs. 62.5%; p < 0.001). Furthermore, out of the 47 positive samples by both ELISA-INC9 and indirect immunofluorescence, only four (8.5%) were reactive in Chagatest assay. Meanwhile, four (80%) out of the five positive samples by both Chagatest and indirect immunofluorescence were reactive using ELISA-INC9. CONCLUSION: Immunoassays based on a native T. cruzi strain perform better than those based on non-native strains, highlighting the need to develop and validate screening assays in accordance to endemic T. cruzi strains.

Seroprevalence and major antigens recognized by sera from Trypanosoma cruzi-infected dogs from Jalisco, México.

Chagas disease is a major endemic disease caused by the protozoan parasite Trypanosoma cruzi. This parasitic disease is widely distributed throughout Latin America, affecting 10 million people. There are also reports of canine infection in the southern part of the United States. Dogs are considered the predominant domestic reservoir for T. cruzi in many areas of endemicity. In México, dog infection by this parasite has been poorly studied. In this work 209 dogs from six villages in Jalisco, México, were assessed to detect anti-T. cruzi antibodies by ELISA and Western blot. Seventeen (17) seropositive dogs (8.1 %) were detected by both tests, representing a seropositive value similar to that found in some southern states of México where the infection is present. No statistical differences were observed concerning the age and sex of infected and non-infected dogs. The major antigens recognized by positive sera were 26, 32, 66 and 80kDa. These proteins are candidates to develop a specific diagnostic method for canine Chagas. No antibodies against HSP16 protein were found in T. cruzi seropositive sera. This is the first report of canine serology of Chagas disease in this central part of México. This report will contribute to the knowledge of the infection status of domestic reservoirs in the state of Jalisco, México.

Seroprevalence and major antigens recognized by sera from Trypanosoma cruzi-infected dogs from Jalisco, México / Seroprevalencia y principales antígenos reconocidos por sueros de perros infectados con Trypanosoma cruzi en el estado de Jalisco, México

Chagas disease is a major endemic disease caused by the protozoan parasite Trypanosoma cruzi. This parasitic disease is widely distributed throughout Latin America, affecting 10 million people. There are also reports of canine infection in the southern part of the United States. Dogs are considered the predominant domestic reservoir for T. cruzi in many areas of endemicity. In México, dog infection by this parasite has been poorly studied. In this work 209 dogs from six villages in Jalisco, México, were assessed to detect anti-T. cruzi antibodies by ELISA and Western blot. Seventeen (17) seropositive dogs (8.1 %) were detected by both tests, representing a seropositive value similar to that found in some southern states of México where the infection is present. No statistical differences were observed concerning the age and sex of infected and non-infected dogs. The major antigens recognized by positive sera were 26, 32, 66 and 80 kDa. These proteins are candidates to develop a specific diagnostic method for canine Chagas. No antibodies against HSP16 protein were found in T. cruzi seropositive sera. This is the first report of canine serology of Chagas disease in this central part of México. This report will contribute to the knowledge of the infection status of domestic reservoirs in the state of Jalisco, México.

El mal de Chagas es una enfermedad endémica causada por el parásito protozoario Trypanosoma cruzi. Este padecimiento está ampliamente distribuido en América, donde afecta a alrededor de 10 millones de personas. También existen comunicaciones de la infección canina desde el sur de los Estados Unidos hasta países de Sudamérica. Los perros son considerados los principales reservorios domésticos de T. cruzi en muchas áreas endémicas. En México, la infección canina ha sido estudiada escasamente. En el presente trabajo se evaluó mediante ELISA y Western blot la presencia de anticuerpos anti-T. cruzi en el suero de 209 perros de seis localidades del estado de Jalisco, México. Se encontraron 17 perros seropositivos (8,1 %) a ambas pruebas. No se observaron diferencias de significación estadística en la edad o el sexo de los perros infectados comparados con los no infectados. Los principales antígenos reconocidos por los sueros positivos fueron de 26, 32, 66 y 80 kDa. Estas proteínas son candidatos para desarrollar un método de diagnóstico específico para Chagas canino. No se encontraron anticuerpos contra la proteína HSP16 en los sueros positivos anti-T. cruzi. Este es el primer informe de serología canina en la región central de México y contribuirá al conocimiento de la infección en reservorios domésticos de Jalisco, México.

Seroprevalence and major antigens recognized by sera from Trypanosoma cruzi-infected dogs from Jalisco, México / Seroprevalencia y principales antígenos reconocidos por sueros de perros infectados con Trypanosoma cruzi en el estado de Jalisco, México

Chagas disease is a major endemic disease caused by the protozoan parasite Trypanosoma cruzi. This parasitic disease is widely distributed throughout Latin America, affecting 10 million people. There are also reports of canine infection in the southern part of the United States. Dogs are considered the predominant domestic reservoir for T. cruzi in many areas of endemicity. In México, dog infection by this parasite has been poorly studied. In this work 209 dogs from six villages in Jalisco, México, were assessed to detect anti-T. cruzi antibodies by ELISA and Western blot. Seventeen (17) seropositive dogs (8.1 %) were detected by both tests, representing a seropositive value similar to that found in some southern states of México where the infection is present. No statistical differences were observed concerning the age and sex of infected and non-infected dogs. The major antigens recognized by positive sera were 26, 32, 66 and 80 kDa. These proteins are candidates to develop a specific diagnostic method for canine Chagas. No antibodies against HSP16 protein were found in T. cruzi seropositive sera. This is the first report of canine serology of Chagas disease in this central part of México. This report will contribute to the knowledge of the infection status of domestic reservoirs in the state of Jalisco, México.(AU)

El mal de Chagas es una enfermedad endémica causada por el parásito protozoario Trypanosoma cruzi. Este padecimiento está ampliamente distribuido en América, donde afecta a alrededor de 10 millones de personas. También existen comunicaciones de la infección canina desde el sur de los Estados Unidos hasta países de Sudamérica. Los perros son considerados los principales reservorios domésticos de T. cruzi en muchas áreas endémicas. En México, la infección canina ha sido estudiada escasamente. En el presente trabajo se evaluó mediante ELISA y Western blot la presencia de anticuerpos anti-T. cruzi en el suero de 209 perros de seis localidades del estado de Jalisco, México. Se encontraron 17 perros seropositivos (8,1 %) a ambas pruebas. No se observaron diferencias de significación estadística en la edad o el sexo de los perros infectados comparados con los no infectados. Los principales antígenos reconocidos por los sueros positivos fueron de 26, 32, 66 y 80 kDa. Estas proteínas son candidatos para desarrollar un método de diagnóstico específico para Chagas canino. No se encontraron anticuerpos contra la proteína HSP16 en los sueros positivos anti-T. cruzi. Este es el primer informe de serología canina en la región central de México y contribuirá al conocimiento de la infección en reservorios domésticos de Jalisco, México.(AU)

Seroprevalence and major antigens recognized by sera from Trypanosoma cruzi-infected dogs from Jalisco, México. / Seroprevalence and major antigens recognized by sera from Trypanosoma cruzi-infected dogs from Jalisco, México.

Chagas disease is a major endemic disease caused by the protozoan parasite Trypanosoma cruzi. This parasitic disease is widely distributed throughout Latin America, affecting 10 million people. There are also reports of canine infection in the southern part of the United States. Dogs are considered the predominant domestic reservoir for T. cruzi in many areas of endemicity. In México, dog infection by this parasite has been poorly studied. In this work 209 dogs from six villages in Jalisco, México, were assessed to detect anti-T. cruzi antibodies by ELISA and Western blot. Seventeen (17) seropositive dogs (8.1

) were detected by both tests, representing a seropositive value similar to that found in some southern states of México where the infection is present. No statistical differences were observed concerning the age and sex of infected and non-infected dogs. The major antigens recognized by positive sera were 26, 32, 66 and 80kDa. These proteins are candidates to develop a specific diagnostic method for canine Chagas. No antibodies against HSP16 protein were found in T. cruzi seropositive sera. This is the first report of canine serology of Chagas disease in this central part of México. This report will contribute to the knowledge of the infection status of domestic reservoirs in the state of Jalisco, México.

cDNA cloning and partial characterization of amastigote specific surface protein from Trypanosoma cruzi.

Trypanosoma cruzi amastigote surface proteins are the target of both humoral and cell-mediated immune responses; however, few such molecules have been thoroughly studied. In order to study a T. cruzi amastigote-specific protein (SSP4), we used antibodies against the deglycosylated form of this molecule to clone cDNA. The selected cDNA clone (2070 bp) encodes for a 64 kDa protein product whose sequence analysis revealed no N-glycosylation signal. The DNA sequence showed high homology with a member of a previously reported dispersed repetitive gene family of T. cruzi. Antibodies against the recombinant protein reacted strongly with a 66 kDa protein and weakly with an 84 kDa protein in amastigote extracts. Immunoelectron microscopy studies showed that intracellular amastigotes express the native protein on their surfaces and flagellar pockets. The antibody label was also associated with an amorphous material present in the parasitic cavity and in direct contact with the parasite surface, which suggest that amastigotes are releasing this material. On cell-free amastigotes, the antibody showed strong decoration of the cell surface and labeling of intracellular vesicles. Immunofluorescence analysis showed that the superficial protein is expressed shortly after trypomastigotes begin to transform into amastigotes. Anti-recombinant protein antibodies recognized proteins of 100 kDa and 50-60 kDa in protein extracts of rat heart and skeletal muscle, respectively.

[Heterogeneous distribution of the prevalence of anti-Trypanosoma cruzi antibodies among blood donors in the State of Puebla, Mexico]. / Distribución heterogénea de la prevalencia de anticuerpos contra Trypanosoma cruzi en donadores de sangre en Puebla, México.

OBJECTIVE: To determine the seroprevalence and associated factors, of antibodies against Trypanosoma cruzi (T. cruzi Ab) among blood donors living in rural and suburban areas and risk regions. MATERIAL AND METHODS: A cross-sectional study was conducted from January to December 2003, in 2489 blood donors of seven regions of Puebla, who were evaluated for mandatory viral and T. cruzi serological tests using validated procedures. RESULTS: The seroprevalence for T. cruzi Ab was 1.24% (31/2489), similar to hepatitis C (HVC) (1.5%) and higher than human immunodeficiency virus (HIV) (0.4%) and hepatitis B (HVB) (0.3%). The highest seroprevalences were observed in the regions of Tehuacan-Sierra Negra and Mixteca, up to 2.6%, while in Sierra nororiental and Angelopolis no positive blood donors were identified. A positive association was observed between seropositivity and being older than forty years and being born and raised in Tehuacan-Sierra Negra and Mixteca. CONCLUSIONS: T. cruzi seroprevalence distribution is heterogeneous, from 0% to 2.6%, with higher seroprevalences in the regions of Tehuacan-Sierra Negra and Mixteca.

Distribución heterogénea de la prevalencia de anticuerpos contra Trypanosoma cruzi en donadores de sangre en Puebla, México / Heterogeneous distribution of the prevalence of anti-Trypanosoma cruzi antibodies among blood donors in the State of Puebla, Mexico

OBJETIVO: Identificar la seroprevalencia de anticuerpos anti Trypanosoma cruzi (Ac anti-T. cruzi) en donadores de sangre que habitan en ámbito rural y suburbano, así como las regiones del estado de mayor riesgo y factores asociados. MATERIAL Y MÉTODOS: Estudio transversal realizado de enero a diciembre de 2003. Se analizaron 2 489 donadores de sangre reclutados en 10 puestos de sangrado del Instituto Mexicano del Seguro Social (IMSS) distribuidos en las siete regiones económicas del estado de Puebla, México. Se determinó la seroprevalencia mediante las pruebas serológicas obligatorias del panel viral y, además, para T. cruzi, región de reclutamiento y de origen de los donadores. RESULTADOS: La seroprevalencia de Ac anti-T. cruzi fue de 1.24 por ciento (31/2 489) comparable con la obtenida para el virus de la hepatitis C (1.5 por ciento) y por arriba de la del virus de la inmunodeficiencia humana (0.4 por ciento) y del antígeno de superficie del virus de la hepatitis B (0.3 por ciento). Las regiones de Tehuacán-Sierra Negra y Mixteca fueron las de mayor riesgo con seroprevalencias, por el origen del donador, de 2.6 por ciento para T. cruzi, mientras que en los originarios de las regiones Sierra nororiental y Angelópolis no se detectaron casos positivos. Se observó asociación entre ser seropositivo y mayor de 40 años y ser originario de las regiones de Tehuacán-Sierra Negra y Mixteca. CONCLUSIONES: La distribución de seroprevalencia a T. cruzi es heterogénea, oscila desde 0 por ciento hasta 2.6 por ciento, y se reconoce a Tehuacán-Sierra Negra y Mixteca como las regiones de mayor riesgo.

Active transmission of human chagas disease in Colima Mexico.

Despite efforts to eradicate American trypanosomiasis (AT) and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4% positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.

Active transmission of human chagas disease in Colima Mexico

Despite efforts to eradicate American trypanosomiasis (AT) and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4 percent positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.

Cardiopatía chagásica en Tehuantepec. Informe preliminar / Chagasic cardiopathy in Tehuantepec

La tripanosomosis americana (TA) fue descrita en México en el estado de Oaxaca, probablemente es endémica en zonas rurales. Antes de este informe no se conocían casos de cardiopatía chagásica crónica en el Istmo de Tehuantepec. Objetivo: Identificar pacientes con TA entre los que acuden a consulta de cardiología y establecer diagnóstico de miocardiopatía dilatada (MD). Material y métodos: Pacientes consecutivos que en el período de enero de 1995 a septiembre de 1997 fueron clasificados como MD. Se realizó historia clínica con anamnesis epidemiológica, serie cardíaca, ECG y ecocardiograma, además se estudió el suero en busca de anticuerpos IgG anti T. cruzi (inmunofluorescencia, ELISA y elec-troinmunotransferencia). Resultados: En 540 consultas se encontraron 16 (2.4 por ciento) casos de MD, 13 de éstos (81 por ciento) tienen anticuerpos anti T. cruzi. Todos vienen de medio rural pobre, tienen insuficiencia cardíaca global y/o trastornos del ritmo o conducción e hipocinesia. El diagnóstico de cardiopatía chagásica crónica (CCC) se estableció sin dificultad. Conclusiones: La TA y su consecuencia de la CCC se encontraron con frecuencia en una población seleccionada en la consulta de cardiología de 2 Hospitales Generales en Salina Cruz, Oaxaca. Es necesario estudiar adecuadamente la situación epidemiológica en el Istmo de Tehuantepec en relación a TA.

American trypanosomiasis (Chagas'Disease) and blood banking in Mexico City: seroprevalance and its potential transfusional transmission risk

Background. American trypanosomiasis (Chagas' disease), an anthropozoonosis fairly common in rural Latin American, has become an urban disease due to continuous migration, intra- and internationally. Blood transfusion, the second important pathway for transmission, increases its impact. Recognition of seropositive subjects among blood donors is now recommended, and clinical and serological screening enforced. Maneuvers to inactivate or remove Trypanosoma cruzi present in collected blood are recommended. Methods. We surveyed voluntary donors at the National Institute of Cardiology in Mexico City in of anti-T. cruzi by indirect immunofluorescence, ELISA, and Western blot analysis. Seropositive donors were identified and tested for immunoglobulin. We used types and fractions of donated blood to extract DNA and perform the PCR technique using kinetoplast primers seeking parasite DNA in blood. Results. After 3,300 donors were screened, we identified 10 seropositive subjects (0.3 percent). These subjects were considered as indeterminate chagasic patients, came mainly from rural areas, and had IgG (100 percent) and IgA (30 percent) antibodies aginst a crude extract as well as a recombinant T. cruzi antigen. Identification of parasite DNA in red cell and platelet fraction was achieved from eight blood units. Conclusions. The present data provide evidence that blood donors at an urban hospital are seropositive for T. cruzi and at least 50 percent of donors carry the parasite potentially able to transmit T. cruzi in their cellular blood products. Serological screening should be included in routine blood-banking. It is also necessary to adopt measures to inactivate or eliminate organisms in donated blood