Veterinary Chagas Disease (American Trypanosomiasis) in the United States.

Veterinary Chagas disease is a persistent threat to humans, dogs, and other wild or domestic mammals that live where infected triatomine "kissing bug" insect vectors occur across the Americas, including 28 states in the Southern United States. Animals infected with the Trypanosoma cruzi parasite may be asymptomatic or may develop myocarditis, heart failure, and sudden death. It is difficult to prevent animal contact with vectors because they are endemic in sylvatic environments and often disperse to domestic habitats. Challenges for disease management include imperfect diagnostic tests and limited antiparasitic treatment options.

Verificación del desempeño general del método Elecsys® Chagas en la detección de anticuerpos específicos contra Trypanosoma cruzi / Verification of the general performance of the Elecsys® Chagas method in the detection of specific antibodies against Trypanosoma cruzi

Resumen La enfermedad de Chagas es una parasitosis producida por Trypanosoma cruzi, prevalente principalmente en el continente americano, y observada en regiones no endémicas, producto de viajes y migraciones. El objetivo de este estudio fue comparar el desempeño del ensayo Elecsys® Chagas (Roche Diagnostics Alemania) (ECLIA) para el diagnóstico de la infección chagásica crónica con el método estándar y evaluar su posible empleo en reemplazo del método automatizado existente. Se estudiaron 77 muestras de sueros pertenecientes a pacientes con diagnóstico presuntivo de enfermedad de Chagas, procesadas por los distintos métodos disponibles en la Sección Parasitología del Hospital Muñiz: inmunoensayo quimioluminiscente de micropartículas (CMIA) (Abbott), enzimoinmunoanálisis de adsorción (ELISA) (Wiener) y hemaglutinación indirecta (HAI) (Lab. Lemos S.R.L.). Los resultados de los métodos ELISA y HAI fueron comparados con los obtenidos en la prueba ECLIA, y estos a su vez con el método automatizado disponible. De las muestras analizadas, 22 (28,57%) presentaron IgG anti-T. cruzi y 55 (71,43%) resultaron negativas. Con el método ECLIA se logró un 100% en los parámetros de desempeño, con diferencias en los intervalos de confianza. La razón de verosimilitud positiva y la razón de verosimilitud negativa clasificaron al ensayo como excelente y la potencia global del test apoyó esa afirmación. Los métodos inmunológicos automatizados ayudan a la performance diagnóstica en la etapa crónica de la enfermedad de Chagas, permiten minimizar errores, favorecen la velocidad de emisión de los resultados y, debido a su alta sensibilidad y especificidad, en ciertos escenarios podrían proponerse para usar como única técnica.

Abstract Chagas disease is a parasitosis caused by Trypanosoma cruzi, prevalent mainly in the American continent, and observed in non-endemic regions as a result of travel and migration. The objective of this study was to compare the performance of the Elecsys® Chagas (Roche Diagnostics Alemania) (ECLIA) assay for the diagnosis of chronic Chagas infection with the diagnostic standard, and to evaluate its possible use as a replacement for the existing automated method. A total of 77 serum samples belonging to patients with a presumptive diagnosis of Chagas disease were evaluated, processed by the different methods available in the Parasitology Section of Hospital Muñiz: microparticle chemiluminescent immunoassay (CMIA) (Abbott), enzyme-linked immunosorbent assay (ELISA) (Wiener) and indirect hemagglutination (HAI) (Lab. Lemos S.R.L). The results of the ELISA and HAI methods were compared with those obtained in the ECLIA test, and these in turn with the available automated method. Of the samples analysed, 22 (28.57%) presented IgG anti-T. cruzi and 55 (71.43%) were negative. With the ECLIA method, 100% was achieved in the performance parameters, with differences in the confidence intervals. The positive likelihood ratio and the negative likelihood ratio classify the essay as excellent, and the overall power of the test supports this statement. Automated immunological methods help diagnostic performance in the chronic stage of Chagas disease, allow minimising errors, favour the speed of issuance of results, and due to the high sensitivity and specificity, in certain scenarios, they could be proposed for use as single technique.

Resumo A doença de Chagas é uma parasitose causada pelo Trypanosoma cruzi, prevalente principalmente no continente americano, e observada em regiões não endêmicas em decorrência de viagens e migrações. O objetivo deste estudo foi comparar o desempenho do ensaio Elecsys® Chagas (Roche Diagnostics Alemanha) (ECLIA) para o diagnóstico da infecção crônica de Chagas com o método padrão e avaliar seu possível uso em substituição do método automatizado existente. Foram avaliadas 77 amostras de soro pertencentes a pacientes com diagnóstico presuntivo de doença de Chagas, processadas pelos diferentes métodos disponíveis na Seção de Parasitologia do Hospital Muñiz: imunoensaio quimioluminescente de micropartículas (CMIA) (Abbott), ensaio imunoenzimático de adsorção (ELISA) (Wiener) e hemaglutinação indireta (HAI) (Lab. Lemos S.R.L). Os resultados dos métodos ELISA e HAI foram comparados com os obtidos no teste ECLIA, e estes por sua vez com o método automatizado disponível. Das amostras analisadas, 22 (28,57%) apresentaram IgG anti-T. cruzi e 55 (71,43%) foram negativos. Com o método ECLIA, foram obtidos 100% nos parâmetros de desempenho, com diferenças nos intervalos de confiança. A razão de verossimilhança positiva e a razão de verossimilhança negativa classificam o ensaio como excelente, e a potencia geral do teste conformou essa afirmação. Os métodos imunológicos automatizados auxiliam no desempenho diagnóstico na fase crônica da doença de Chagas, permitem minimizar erros, favorecem a rapidez na emissão dos resultados e, devido à alta sensibilidade e especificidade, em determinados cenários, poderiam ser propostos para uso como técnica única.

Is Antibody-Dependent Enhancement of Trypanosoma cruzi Infection Contributing to Congenital/Neonatal Chagas Disease?

The newborns of women infected with the parasite Trypanosoma cruzi (the agent of Chagas disease) can be infected either before birth (congenitally), or after birth (as e.g., by vector route). Congenital Chagas disease can induce high levels of neonatal morbidity and mortality. Parasite-infected pregnant women transmit antibodies to their fetus. Antibodies, by opsonizing parasites, can promote phagocytosis and killing of T. cruzi by cells expressing FcγR, on the mandatory condition that such cells are sufficiently activated in an inflammatory context. Antibody-dependent enhancement (ADE) is a mechanism well described in viral infections, by which antibodies enhance entry of infectious agents into host cells by exploiting the phagocytic FcγR pathway. Previously reported Chagas disease studies highlighted a severe reduction of the maternal-fetal/neonatal inflammatory context in parasite-transmitting pregnant women and their congenitally infected newborns. Otherwise, experimental observations brought to light ADE of T. cruzi infection (involving FcγR) in mouse pups displaying maternally transferred antibodies, out of an inflammatory context. Herein, based on such data, we discuss the previously unconsidered possibility of a role of ADE in the trans-placental parasite transmission, and/or the development of severe and mortal clinical forms of congenital/neonatal Chagas disease in newborns of T. cruzi-infected mothers.

Risk factors for infestation by Triatoma dimidiata in a rural locality of Veracruz, Mexico, with active transmission of Trypanosoma cruzi: weather and rain as factors.

OBJECTIVE: To analyse the ecological and social factors involved in infestation of houses by Triatoma dimidiata in a rural locality of Veracruz, Mexico, where active transmission of the parasite is occurring. METHODS: A survey was applied to the households of the locality to obtain sociodemographic data. In parallel, T. dimidiata insects were collected during one year through community participation. Using PCR, the insects were genotyped, their infection status was assessed, and parasite genotypes infecting the insects were identified. The vector's blood meal sources were identified using a polymerase-heteroduplex chain reaction assay. RESULTS: Seasonal variations in the patterns of infestation by T. dimidiata were observed. An overall infestation rate of 19.46%, a colonisation index of 9.09%, a dispersion rate of 22.15% and a synanthropy index of 80.6% were found. The collected insects were identified as ITS-2 group 2 insects, and a natural infection with T. cruzi of 54.35% was found. TcI and no-TcI genotypes of T. cruzi were found in infected insects. Factors such as rain (P = 0.0006) and temperature (P < 0.0001) were associated with infestation. Analysis of the blood meal sources indicated frequent feeding upon humans and mice. Furthermore, house materials and peridomiciles were found to play an important role in the dynamics of infestation. CONCLUSIONS: The contribution of this study is important for understanding the epidemiology of Chagas disease in rural areas of the state of Veracruz and will help to the establishment of an entomological surveillance system and implementation of prevention and control measures in accordance with the reality of the area.

Avaliação externa da qualidade da identificação entomológica de triatomíneos realizada na Rede de Laboratórios Públicos em Pernambuco, 2017 / Evaluación externa de la calidad en la identificación entomológica de triatominos realizada en la red de laboratorios públicos en Pernambuco, Brasil, 2017 / External quality assessment of entomological identification of triatomines carried out in the Pernambuco Public Health Laboratory network, Brazil, 2017

Objetivo: Avaliar a qualidade da identificação de triatomíneos na rede de laboratórios do estado de Pernambuco, Brasil. Métodos: Os nove laboratórios participantes receberam material de apoio com as chaves dicotômicas e um painel composto por sete insetos triatomíneos conhecidos no estado, para identificação da situação do espécime no recebimento (estrutura completa ou danificada), espécie e sexo. Resultados: Nove laboratórios de 12 aderiram ao estudo. A proporção de acerto para identificação do sexo foi de 56/63, e para espécie, 45/63, não apresentando relação direta com a ocorrência de danos nas estruturas morfológicas durante o transporte dos insetos. Para Panstrongylus megistus, houve acerto em todos os espécimes (9/9), enquanto para espécies do gênero Rhodnius a proporção foi menor (3/9). Conclusão: Apesar do bom desempenho na identificação entomológica, as fragilidades observadas poderão orientar ações para melhoria na rede de laboratórios e serão essenciais para os programas de controle vetorial da doença de Chagas.

Objetivo: Evaluar la calidad de la identificación de triatominos en la red de laboratorios del estado de Pernambuco, Brasil. Métodos: Los nueve laboratorios participantes recibieron material de apoyo con claves dicotómicas y un panel conformado por siete insectos triatominos conocidas en el estado, para identificar la situación del espécimen al recibirlo (estructura completa o dañada), especie y sexo. Resultados: La adherencia al laboratorio fue del 9/12. La proporción de aciertos para la identificación del sexo fue del 56/63, y para las especies 45/63, no mostraron relación directa con la ocurrencia de daños en las estructuras morfológicas durante el transporte de insectos. Solo Panstrongylus megistus logró el 9/9 de precisión, mientras que para las especies del género Rhodnius fue el más pequeño (3/9). Conclusión: A pesar del buen desempeño en identificación entomológica, la evaluación indicó debilidades que permitirán implementar acciones correctivas para mejorar la red de laboratorios, esenciales para los programas de control vectorial de la enfermedad de Chagas.

Objective: To assess the quality of triatomine identification in the laboratory network of the state of Pernambuco, Brazil. Methods: The participating laboratories received support material with dichotomous keys and a panel made up of seven triatomine insects known in the Pernambuco, in order to identify specimen status on receipt (intact or damaged structure), as well as species and sex. Results: Nine out of 12 laboratories took part of the study. The proportion of correct answers was 56/63 for sex identification, and 45/63, for species. The answers did not present a direct relationship with occurrence of damage to morphological structures during insect transportation. Panstrongylus megistus identification was correct for all specimens (9/9 laboratories), while correct identification of species of the Rhodnius genus was the lowest (3/9 laboratories). Conclusion: Despite the good performance in entomological identification, the weaknesses observed may guide improvements in the laboratory network and will be essential for Chagas disease vector control programs.

Chagas bugs and trypanosoma cruzi: Puppets and puppeteer?

A widely accepted idea in parasite-host relationships is that the former manipulates the latter so that it increases its own success. In the case of complex life cycles, this means that the parasite is able to manipulate the first host which allows its transmission to the second host. In this paper, I formalize the idea that this may be the case for the Trypanosoma cruzi parasite and its vectors, bugs of the subfamily Triatominae. I discuss the sources of existing evidence and propose some types of manipulation. This manipulation could also occur in the second host, that is, a vertebrate. Here, I emphasize humans and domesticated animals. I also discuss how global change and insecticide resistance may drive the arms race between both, triatomines and T. cruzi, and host manipulation.

Linear mixed model for weight analysis in mice infected by Trypanosoma cruzi

The use of linear mixed models for nested structure longitudinal data is called hierarchical linear modeling. Thismodeling takes into account the dependence of existing data within each level and between hierarchical levels. The process of modeling, estimating and analyzing diagnoses was illustrated through data on the weights of mice experimentally infected by Trypanosoma cruzi, divided into different treatment groups, with the purpose of verifying the evolution of their body weight as a result of usingdifferent types of biotherapeutics produced from Gallus gallus domesticus(chicken) serum to treat Trypanosoma cruzi. Through the model selection criteria AIC and BIC and the likelihood ratio test, a model was chosen to describe the data correctly. Model diagnoses were then performed by means of residual analysis for both levels and an analysis of influential observations to verify if any observations were signaled as influencing the fixed effects, the components of variance and the adjusted values. After the analysis, it was possible to notice that the observations that were signaled as influential had little impact on the Model chosen initially, so it was maintained, with no differences being evidenced between the treatments with the biotherapeutics tested; only the Time variable and the Random intercept were necessary to describe the weight of the mice.

Analyzing weight evolution in mice infected by Trypanosoma cruzi

Concerning the specificities of a longitudinal study, the trajectories of a subject's mean responses not always present a linear behavior, which calls for tools that take into account the non-linearity of individual trajectories and that describe them towards associating possible random effects with each individual. Generalized additive mixed models (GAMMs) have come to solve this problem, since, in this class of models, it is possible to assign specific random effects to individuals, in addition to rewriting the linear term by summing unknown smooth functions, not parametrically specified, then using the P-splines smoothing technique. Thus, this article aims to introduce this methodology applied to a dataset referring to an experiment involving 57 Swiss mice infected by Trypanosoma cruzi, which had their weights monitored for 12 weeks. The analyses showed significant differences in the weight trajectory of the individuals by treatment group; besides, the assumptions required to validate the model were met. Therefore, it is possible to conclude that this methodology is satisfactory in modeling data of longitudinal sort, because, with this approach, in addition to the possibility of including fixed and random effects, these models allow adding complex correlation structures to residuals.

Poblaciones silvestres y domiciliadas de Triatoma Infestans en comunidades del municipio de Mecapaca próximas a la ciudad de La Paz / Wild and domiciled populations of Triatoma Infestans in communities of the municipality of Mecapaca next to the city of La Paz

OBJETIVO: determinar la presencia de Triatoma infestans y las características de sus poblaciones en algunas comunidades del Municipio de Mecapaca cercanas a la cuidad de La Paz. MÉTODOS: la búsqueda entomológica de Triatoma infestans con trampas cebo ratón en sitios silvestres y peridomiciliares o manuales dentro de domicilios, fue realizada en 11 zonas de 8 comunidades del Municipio de Mecapaca, determinando la altura sobre el nivel del mar y la ubicación geográfica de las mismas. Mediante claves dicotómicas según Lent y Wygodzinski se ha realizado la identificación morfológica de los especímenes capturados. Con la observación directa en microscopio óptico de las deyecciones de los especímenes y análisis molecular por PCR Multiplex se ha determinado la infección por Trypanosoma cruzi y las DTUs (Unidades Discretas de Tipificación). RESULTADOS: se encontraron sitios positivos para la presencia de T. infestan, siendo el Indice de Dispersión Entomológica de 50%. Del total de los especímenes capturados (N=103), 91 especímenes (88%) fueron individuos en fase ninfal y 12 individuos (12%) fueron adultos. Se caracterizó T. cruzi TcI y el índice tripano triatominico fue de 50% en individuos capturados en zona silvestre de Huayhuasi y de 16% en individuos capturados en zona peridomiciliar de Huajchilla distante solo a 20 km desde la ciudad de La Paz. CONCLUSIONES: los resultados han constatado presencia de poblaciones silvestres y domiciliadas de T. infestans en sitios silvestres y domiciliares de comunidades del Municipio de Mecapaca cercanas a la ciudad de La Paz. El hallazgo determinaría nuevos esquemas de distribución geográfica de poblaciones de T. infestans e infestación de hábitat humano.

OBJECTIVE: to determine the presence of Triatoma infestans and the characteristics of their populations in some communities of the Municipality of Mecapaca next to the city of La Paz. METHODS: The entomological search of Triatoma infestans with mouse bait traps in wild and peridomiciliary or manual sites within homes, was carried out in 11 areas of 8 communities of the Municipality of Mecapaca, determining the altitude above sea level and their geographical location. By means of dichotomous keys according to Lent and Wygodzinski, the morphological identification of the captured specimens has been carried out. With direct microscopic observation of specimen dejections and molecular analysis by Multiplex PCR, Trypanosoma cruzi infection and DTUs (Discrete Typification Units) have been determined. RESULTS: positive sites were found for the presence of T. infestan, with the Entomological Dispersion Index being 50%. Of the total of the specimens captured (N = 103), 91 specimens (88%) were individuals in the nymphal phase and 12 individuals (12%) were adults. T. cruzi TcI was characterized and the triatominic trypan index was 50% in individuals captured in the wild zone of Huayhuasi and 16% in individuals captured in the peridomiciliary area of Huajchilla, only 20 km away from the city of La Paz. CONCLUSIONS: the results have confirmed the presence of wild and domiciled populations of T. infestans in wild and domiciliary sites of communities of the Municipality of Mecapaca near the city of La Paz. The finding would determine new geographical distribution schemes of T. infestans populations and human habitat infestation.

Zombie bugs? Manipulation of kissing bug behavior by the parasite Trypanosoma cruzi.

The parasite manipulation hypothesis states that the parasite modifies host's behavior thereby increasing the probability that the parasite will pass from an intermediate host to its final host. We used the kissing bugs Triatoma pallidipennis and T. longipennis and two isolates of the Trypanosoma cruzi parasite (Chilpancingo and Morelos) to test these ideas. These insects are intermediate hosts of this parasite, which is the causal agent of Chagas disease. The Chilpancingo isolate is more pathogenic than the Morelos isolate, in the bugs. We expected that infected bugs would be more active and likely at detecting human-like odors. Given the differences in pathogenicity between isolates, we expected the Chilpancingo isolate to induce these effects more strongly and lead to higher parasite number than the Morelos isolate. Finally, infected bugs would gain less mass (a mechanism thought to increase bite rate, and thus transmission) than non-infected bugs. Having determined that both isolate haplotypes belong to the Tc1a group, we found that: (a) young instars of both species were more active and likely to detect human odor when they were infected, regardless of the isolate; (b) there was no difference in parasite abundance depending on isolate; and, (c) infected bugs did not end up with less weight than uninfected bugs. These results suggest that T. cruzi can manipulate the bugs, which implies a higher risk to contract Chagas disease than previously thought.

Enfermedad de chagas congénito: presentación de caso clínico / Congenital chagas disease: case report

El agente etiológico de la enfermedad de Chagas es un protozoario parásito (Tripano-soma Cruzi) que causa una infección aguda y crónica, en humanos. La extensión del daño varía de acuerdo a las cepas parasita-rias y características individuales del hués-ped; puede causar incapacidad y muerte. Han sido descritas diferentes vías de infec-ción: vectorial, transfusional, accidental, digestiva y congénita. Esta última vía de la infección depende de dos indicadores bási-cos, la prevalencia de gestantes chagásicas e incidencia de la transmisión vertical. El diagnóstico presenta un desafío en aquellos lugares del país en donde, si bien la enfer-medad es considerada endémica, no se realiza actualmente el screening obligatorio en la embarazada. Es importante saber que el tratamiento antes del primer año de vida tiene una excelente respuesta y evita secue-las crónicas que pueden ser invalidantes en etapa adulta...(AU)

Caracterización de donadores seropositivos por trypanosoma cruzi y su manejo, banco de sangre, Hospital Escuela, Tegucigalpa, 2016 / Characterization and management of Trypanosoma cruzi seropositive donors, Blood Bank, Hospital Escuela, Tegucigalpa, 2016

Antecedentes: La eliminación de la transmisión no-vectorial de Trypanosoma cruzi es objetivo nacional de salud pública. La seroprevalencia en donadores de sangre es blanco de estrategias de eliminación de la Enfermedad de Chagas. Objetivo: Caracterizar donadores seropositivos por T. cruzi y su manejo en el Banco de Sangre, Hospital Escuela, Tegucigalpa, 2016. Metodología: Estudio descriptivo transversal sobre muestra aleatoria de 150 donadores de sangre, mayores de 18 años de edad, seleccionados a partir de un sub-grupo de 726 casos seropositivos por enfermedades de notificación obligatoria. Los donadores seropositivos por T. cruzi fueron invitados a participar mediante seguimiento telefónico. Se registró información sobre diagnóstico, características sociodemográficas, notificación, referencia y seguimiento. El protocolo fue aprobado por comité de ética institucional, Facultad de Ciencias Médicas UNAH. Resultados: Se identificaron 30 casos seropositivos por T. cruzi (20.0%, IC95% 13.3-26.7), edad media 39.1 años, sexo masculino 66.7% (20), procedentes de regiones centro-sur-oriente y de bajo nivel socioeconómico. De estos 30 casos, 15 respondieron y aceptaron participar; de estos, 6 informaron que se les notificó el resultado serológico y 5 fueron referidos para evaluación y tratamiento. Entre estos 5, en un caso se realizó una segunda prueba diagnóstica. Ninguno fue notificado sobre su aptitud para donar sangre. Conclusión: Los casos identificados son adultos jóvenes, con relación hombre a mujer 2:1. Es necesario implementar un sistema de registro nacional de notificación y seguimiento de casos identificados en los bancos de sangre. Este sistema debe estar integrado al sistema de vigilancia de la Secretaría de Salud de Honduras...(AU)

Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico.

Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans. Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control. We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses. Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection. The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years. In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico. This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities. Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.

Trypanosoma cruzi Transmission Among Captive Nonhuman Primates, Wildlife, and Vectors.

Natural infection of captive nonhuman primates (NHPs) with Trypanosoma cruzi (agent of Chagas disease) is an increasingly recognized problem in facilities across the southern USA, with negative consequences for NHP health and biomedical research. We explored a central Texas NHP facility as a nidus of transmission by characterizing parasite discrete typing units (DTU) in seropositive rhesus macaques (Macaca mulatta), identifying the wildlife reservoirs, and characterizing vector infection. In seropositive NHPs, we documented low and intermittent concentrations of circulating T. cruzi DNA, with two DTUs in equal proportions, TcI and TcIV. In contrast, consistently high concentrations of T. cruzi DNA were found in wild mesomammals at the facility, yet rodents were PCR-negative. Strong wildlife host associations were found in which raccoons (Procyon lotor) harbored TcIV and opossums (Didelphis virginiana) harbored TcI, while skunks (Mephitis mephitis) were infected with both DTUs. Active and passive vector surveillance yielded three species of triatomines from the facility and in proximity to the NHP enclosures, with 17% T. cruzi infection prevalence. Interventions to protect NHP and human health must focus on interrupting spillover from the robust sylvatic transmission in the surrounding environment.

Cardiomiopatia da Doença de Chagas / Chagas disease cardiomyopathy

A cardiomiopatia crônica da doença de Chagas (CCDC) é resultante de miocardite fibrosante focal de baixa intensidade, mas incessante, causada pela infecção persistente do T cruzi, associada à inflamação mediada por mecanismos imunes adversos. Cerca de 30% dos infectados desenvolvem, ao longo da vida, a forma crônica cardíaca da doença de Chagas com manifestação clínica proteiforme, que pode incluir morte súbita, sintomas e sinais de insuficiência cardíaca, eventos cardioembólicos, arritmia e sintomas anginoides. A morte súbita e a progressão da insuficiência cardíaca (IC) são os mecanismos mais comuns de óbito nesta condição. Os aspectos prognósticos mais relevantes são sintomas de IC avançada (CF III/IV da NYHA), cardiomegalia, disfunção sistólica do VE e taquicardia ventricular não sustentada. A prevenção dos eventos cardioembólicos é aspecto importante no manejo dos pacientes com CCDC. Agentes anticoagulantes orais devem ser indicados para pacientes com risco elevado, conforme a presença de um conjunto de fatores de risco: disfunção sistólica do VE, aneurisma apical, alteração da repolarização ventricular ao ECG e idade avançada. O tratamento da IC na CCDC segue os mesmos princípios aplicados à IC secundária à cardiomiopatia dilatada de outras etiologias

Behavior of alfa-tomatine and tomatidine against several genera of trypanosomatids from insects and plants and Trypanosoma cruzi / Comportamento de alfa-tomatina e tomatidina contra vários gêneros de tripanossomatídeos de insetos e plantas e Trypanosoma cruzi

Glycoalkaloids are important secondary metabolites accumulated by plants as protection against pathogens. One of them, α-tomatine, is found in high concentrations in green tomato fruits, while in the ripe fruits, its aglycone form, tomatidine, does not present a protective effect, and it is usual to find parasites of tomatoes like Phytomonas serpens in these ripe fruits. To investigate the sensitivity of trypanosomatids to the action of α-tomatine, we used logarithmic growth phase culture of 20 trypanosomatids from insects and plants and Trypanosoma cruzi. The lethal dose 50% (LD50) was determined by mixing 107 cells of the different isolates with α-tomatine at concentrations ranging from 10-3 to 10-8 M for 30 min at room temperature. The same tests performed with the tomatidine as a control showed no detectable toxicity against the same trypanosomatid cultures. The tests involved determination of the percentage (%) survival of the protozoan cultures in a Neubauer chamber using optical microscopy. The LD50 values varied from 10-4 to 10-6 M α-tomatine. Slight differences were detected among the LD50 values of the analyzed samples, and none of them showed evidence of resistance to the action of tomatinase, as shown by some pathogenic fungi.

Os glicoalcaloides são metabólitos secundários importantes produzidos pelas plantas e estão envolvidos em sua proteção contra agentes patogênicos. Um deles, α-tomatina, é encontrado em altas concentrações em frutos de tomate verde, enquanto que, nos frutos maduros, sua forma aglicona, tomatidina, não apresenta um efeito protetor, sendo comum encontrar parasitas de tomates como Phytomonas serpens nesses frutos maduros. Para investigar a sensibilidade dos tripanossomatídeos à ação da α-tomatina, utilizamos formas de cultura em fase logarítmica de 20 tripanossomatídeos de plantas e insetos e Trypanosoma cruzi. A dose letal 50% (DL50) foi determinada, misturando 107 células das formas de cultura com concentrações de 10-3 a 10-8 M de α-tomatina durante trinta minutos a temperatura ambiente. Testes realizados com a tomatidina como controle não mostraram toxicidade detectável contra os mesmos tripanossomatídeos. Os testes foram avaliados pela porcentagem (%) de sobrevivência das formas de cultura dos protozoários observados por microscopia óptica em câmara de Neubauer. Os resultados da determinação de DL50 mostraram que esta variou entre 10-4 a 10-6 M de α-tomatina. Pequenas diferenças foram observadas entre os valores de DL50 das amostras analisadas, e nenhuma delas mostrou evidência de resistência pela ação da tomatinidase, como demonstrado em alguns fungos patogênicos.

Can sexual transmission support the enzootic cycle of Trypanosoma cruzi?

BACKGROUND Trypanosoma cruzi circulates in sylvatic habitats, mainly through blood-feeding triatomines, although other routes also contribute to its dispersion. Sexual transmission of T. cruzi is an understudied topic, especially among wild mammals. Because of the difficulties inherent to field work, experimentally infected mice are frequently used to evaluate the transmission of T. cruzi. OBJECTIVE This study aimed to evaluate the sexual transmission of T. cruzi in acutely infected mice. METHODS Male and female mice in the acute phase of Chagas disease were mated with naïve partners. Then, parasitological tests, immunohistochemistry, serological assays, and polymerase chain reaction (PCR) assays were used to detect infection. FINDINGS Parasitological analysis showed trypomastigotes in the blood of 20% of the naïve mice after mating with infected partners. Serological assays detected anti-T. cruzi antibodies in all naïve females mated with infected males and in 60% of naïve males mated with infected females. PCR showed T. cruzi nDNA bands for all naïve mice mated with infected partners. The possibility of sexual transmission was also confirmed by visualisation of amastigotes in the testes. MAIN CONCLUSIONS Our results demonstrate that sexual transmission of T. cruzi is an ordinary event that may contribute to maintenance of the parasite's enzootic cycle.

Estudos farmacológicos de novos compostos semissintéticos com potencial terapêutico na doença de chagas / Pharmacological studies of new semi-synthetic compounds with therapeutic potential in Chagas disease

A doença de Chagas afeta mais de 8 milhões de pessoas nos países em desenvolvimento, e dispõe de uma terapia ultrapassada e altamente tóxica. Considerando o Brasil uma das maiores biodiversidades do mundo, compostos de sua flora podem contribuir como novos protótipos farmacêuticos. Neolignanas, isoladas da planta Nectandra leucantha, apresentaram previamente atividade anti-Trypanosoma cruzi e neste trabalho, serviram como base para a semissíntese de uma série de 24 análogos. Estudos in vitro demonstratram que 19 compostos não apresentaram citotoxicidade em células de mamífero até 200 µM. Seis compostos apresentaram atividade contra as formas tripomastigotas (CE50 8 a 76 µM) e 8 compostos contra os amastigotas intracelulares (CE50 7 a 16 µM). Estudos da relação estrutura-atividade biológica (SAR), demonstraram que a presença de pelo menos uma cadeia lateral alílica era importante para a atividade anti-T. cruzi e que o grupo fenol não era essencial. O composto 8 foi eficaz contra as duas formas do parasita e eliminou 100% das formas amastigotas no interior dos macrófagos, sendo escolhido para estudos de mecanismo de ação. O composto 8 afetou rapidamente a mitocôndria do T. cruzi,...(AU)

Chagas disease affects more than 8 million people in developing countries and the available therapy is old and highly toxic. Considering Brazil one of the biggest biodiversity in the world, compounds from the flora can contribute as new pharmaceutical prototypes. Neolignans, isolated from the plant Nectandra leucantha, previously showed anti-Trypanosoma cruzi activity and served as the basis for the semi-synthesis of a series of 24 analogues. In vitro studies demonstrated that 19 compounds caused no cytotoxicity in mammalian cells up to 200 µM. Six compounds showed activity against trypomastigote forms (IC50 8 to 76 µM) and 8 compounds against intracellular amastigotes (IC50 7 to 16 µM). Studies of the structure activity relationships (SAR) showed that the presence of at least one allylic side chain was important for anti-T. cruzi activity and that the phenol group was not essential. Compound 8 was chosen for mechanism of action studies as it was effective against both forms of the parasite and eliminated 100% of the intracellular amastigotes. Compound 8 rapidly affected the mitochondria of T. cruzi, causing an intense depolarization of the mitochondrial membrane potential, with decreasing levels of reactive oxygen species...(AU)

Triatoma dimidiata en Colombia; distribución, ecología e importancia epidemiológica / Triatoma dimidiata in Colombia: Distribution, ecology and epidemiological importance

RESUMEN Triatoma dimidiata es un importante vector de la enfermedad de Chagas en Centroamérica y en los países del norte de Suramérica. En Colombia, tiene una amplia distribución y su presencia se ha reportado en 14 departamentos de las regiones Andina, Caribe, de los Llanos Orientales y del Alto Magdalena, en las cuales ocupa diferentes ecótopos naturales y artificiales. La especie está clasificada como secundaria para la transmisión de Trypanosoma cruzi; sin embargo, su presencia en el ambiente silvestre, peridoméstico y doméstico en la región Andina, y su capacidad de movilizarse entre ellos, le han permitido escapar al control basado en la aspersión con piretroides y ello resalta su importancia en el mantenimiento de la transmisión del parásito debido a la potencial reinfestación de las viviendas. La comprensión de las relaciones de T. dimidiata con su hábitat, así como el empoderamiento de la comunidad, contribuyen al desarrollo de sistemas de control efectivos y perdurables. El propósito de esta revisión fue describir la distribución, los factores de riesgo, la ecología, las características entomológicas y los hábitats de las poblaciones de T. dimidiata en Colombia, y proponer alternativas de intervención acordes con las características particulares de esta especie.

ABSTRACT Triatoma dimidiata is an important vector of Chagas disease in Central America and countries of northern South America. In Colombia, it has a wide geographical distribution with reported presence in 14 departments in the Andean, Caribbean, Eastern plains and Upper Magdalena regions, where it occupies different natural and artificial ecotopes. The species is considered a secondary vector in the transmission of Trypanosoma cruzi. Its presence in wild, peridomestic and intradomiciliary habitats in the Andean region, coupled with its ability to move between them, has allowed it to escape the control based on pyrethroids spraying, highlighting its importance in maintaining transmission of the parasite through the potential reinfestation of homes. Understanding the relation of T. dimidiata and its habitats, as well as the empowerment of communities, will contribute to the development of effective and lasting control systems. The purpose of this review was to describe the distribution, risk factors, ecology, entomological features and habitats of T. dimidiata populations in Colombia, and to propose alternative interventions in agreement with the specific characteristics of the species.