Abstract INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.

Abstract Chagas disease is a chronic parasitological disease, which could cause cardiac manifestations in approximately one-third of affected individuals. Benznidazole and nifurtimox are used to treat this parasitological infection caused by Trypanosoma cruzi. Conventionally, the criterion for cure is consistently negative serological tests after treatment. We report a case of a patient who was treated when she was 13 years old and achieved T. cruzi negative seroconversion but developed Chagas disease cardiomyopathy as an adult.

Pharmacological treatment of Chagas disease with benznidazole (BNZ) is effective in children in all stages, but it is controversial in chronically infected adults. We report the pharmacokinetics and pharmacodynamics in six adult patients with Chagas disease treated with the new BNZ formulation (ABARAX®) in doses between 2.5-5.5 mg/Kg/day. All but one patient had plasmatic BNZ concentrations within the expected range. All patients finalised treatment with nondetectable Trypanosoma cruziquantitative polymerase chain reaction, which remained nondetectable at the six month follow-up. Our data suggests parasitological responses with the new BNZ and supports the hypothesis that treatment protocols with lower BNZ doses may be effective.

Urban visceral leishmaniasis is an emerging zoonosis in Argentina. In the Americas the disease is produced by Leishmania infantum, with dogs as the primary reservoir and phlebotomine sandflies as the vectors. This article presents the experience acquired by professionals from the National Leishmaniasis Program in Argentina as visceral leishmaniasis has emerged and spread, especially in clinical and laboratory diagnosis, disease treatment, vector biology, reservoir management, and conflicts regarding recommendations for infected dogs. Early detection and treatment, along with decentralized and horizontal strategies, will contribute to the decrease in morbidity and mortality associated with visceral leishmaniasis. Control over the transmission and spread of the disease requires integral environmental management and responsible dog ownership. The interests and discourses put into conflict by visceral leishmaniasis are discussed in the framework of the human-dog relationship, and the search for a consensus-based risk discourse is proposed.

La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con las acciones recomendadas en relación con los perros infectados. La detección temprana y el tratamiento precoz, con estrategias descentralizadas y horizontales, contribuirán a disminuir la morbimortalidad asociada a la leishmaniasis visceral. El control de su transmisión y dispersión requiere de un manejo ambiental integral y la tenencia responsable de perros. Se discuten los intereses y discursos en conflicto generados por la leishmaniasis visceral en el marco de la relación humano-perro, proponiendo la búsqueda de un discurso consensuado de riesgo.

Urban visceral leishmaniasis is an emerging zoonosis in Argentina. In the Americas the disease is produced by Leishmania infantum, with dogs as the primary reservoir and phlebotomine sandflies as the vectors. This article presents the experience acquired by professionals from the National Leishmaniasis Program in Argentina as visceral leishmaniasis has emerged and spread, especially in clinical and laboratory diagnosis, disease treatment, vector biology, reservoir management, and conflicts regarding recommendations for infected dogs. Early detection and treatment, along with decentralized and horizontal strategies, will contribute to the decrease in morbidity and mortality associated with visceral leishmaniasis. Control over the transmission and spread of the disease requires integral environmental management and responsible dog ownership. The interests and discourses put into conflict by visceral leishmaniasis are discussed in the framework of the human-dog relationship, and the search for a consensus-based risk discourse is proposed.

La leishmaniasis visceral urbana es una zoonosis emergente en Argentina. En América es producida por Leishmania infantum, con el perro como reservorio principal e insectos flebotomíneos como vectores. En este artículo se presenta el conocimiento acumulado a partir de su emergencia y dispersión en el país, por los referentes del Programa Nacional de Leishmaniasis, en el diagnóstico clínico y de laboratorio, tratamiento, biología de vectores, manejo de reservorio, y el conflicto generado con las acciones recomendadas en relación con los perros infectados. La detección temprana y el tratamiento precoz, con estrategias descentralizadas y horizontales, contribuirán a disminuir la morbimortalidad asociada a la leishmaniasis visceral. El control de su transmisión y dispersión requiere de un manejo ambiental integral y la tenencia responsable de perros. Se discuten los intereses y discursos en conflicto generados por la leishmaniasis visceral en el marco de la relación humano-perro, proponiendo la búsqueda de un discurso consensuado de riesgo.

An eight-year old boy from Posadas (27º 23'S, 55º 54'W) was diagnosed with visceral leishmaniasis (VL) during 2006. Lutzomyia longipalpis was discovered in the backyard of his house, while the spread of canine visceral leishmaniasis was confirmed in Posadas. This is the southernmost report of a VL transmission focus and the first in Argentina.

Novas alternativas terapêuticas contra a leishmaniose são ainda uma prioridade. A atividade da azitromicina contra a Leishmania (Leishmania) major foi anteriormente demonstrada. Diferentes respostas entre as espécies de Leishmania fazem com que um screening de drogas específicas para espécies seja necessário. A atividade da azitromicina contra a Leishmania (Viannia) braziliensis e a Leishmania (Leishmania) amazonensis foi avaliada em Golden hamsters infectados a través de injeções de promastigotas metacíclicas e comparando com controles sem tratamento e animais tratados com antimoniato de N-metil-glucamina. Foram analisadas a espessura da pata, a cultura das lesões e disseminação para órgãos internos. A azitromicina oral em dose de 450mg/kg não teve atividade contra a infecção por Leishmania ( Leishmania) amazonensis. Para infecções devidas à Leishmania (Viannia) braziliensis, a azitromicina teve uma atividade significativa em relação aos controles sem tratamento, mas foi inferior ao antimoniato de N-metil-glucamina quanto ao controle do tamanho das lesões. Nenhuma das drogas conseguiu eliminar totalmente os parasitos das lesões. Foi concluído que a azitromicina tem atividade contra Leishmania (Viannia) braziliensis, mas não tem atividade contra Leishmania (Leishmania) amazonensis neste modelo.

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensis but not against Leishmania (Leishmania) amazonensis in this model.

Objective The present clinical study is aimed at assessing the safety and feasibility of cardio implantation of mononuclear bone marrow cells, as well as analyzing the clinical and ventricular function changes in patients with cardiac failure secondary to dilated myocardial disease of chagasic origin that underwent this procedure. Material and Methods The sample included 5 consecutive patients (3 male), mean age 55, 8 ± 8, 1 years that showed cardiac failure secondary to chagasic myocardial disease. Average pre-surgery data in these patients were 2, 6 ± 0, 5 functional class (NYHA), whereas the left ventricle fraction corresponded to 27, 6% ± 5, 9%, the left ventricle diastolic diameter was 49, 7 ± 7, 6 mm. The cellular suspension obtained from mononuclear bone marrow cells contained 10, 6 ± 7 ml with 1, 43 ± 0, 6 (E+08) cell counting with a viability higher than 95%. Corresponding to CD34+, 5, 07 ± 9, 51 (E+06) fraction and CD133+, 5, 11 ± 4, 3 (E+06). Suspension was intracoronary injected in pulses to four patients and transepicardially to the fifth during the course of a surgery (mitral valve replacement, revascularization and degradable bioartificial matrix). Results At 17,2 ± 8,8 average months follow up, 4 patients were alive and with functional class I (p < 0,005). One patient died of sudden death after 17 months of follow up. During this evolution time period no adverse events were observed in none of the patients referred for cellular implantation. In regards to the ejection fraction, a 36,6% ± 2,3% (p < 0,05) increase was observed. Data obtained from the assessment of the left ventricle systolic and diastolic diameters did not show significant statistical changes. Conclusions This study represents the second world communication on the use of stem cells in Chagas-Mazza heart disease. The procedure resulted feasible and safe and was associated to improvement of the functional capacity and ventricular function during follow up. These conditional results should be corroborated by broader controlled clinical trials.

Objetivo La presente investigación clínica persigue evaluar la seguridad y la factibilidad del cardioimplante de células mononucleares de médula ósea, así como analizar los cambios clínicos y de la función ventricular, en pacientes portadores de insuficiencia cardíaca secundaria a miocardiopatía dilatada de origen chagásico sometidos a este procedimiento. Material y métodos La muestra comprende 5 pacientes consecutivos (3 masculinos) con una edad promedio de 55,8 ± 8,1 años, que presentaban insuficiencia cardíaca secundaria a miocardiopatía chagásica. Los datos preoperatorios promedio de estos pacientes indicaban una clase funcional (NYHA) de 2,6 ± 0,5, mientras que la fracción del ventrículo izquierdo correspondía al 27,6% ± 5,9%, el diámetro diastólico ventricular izquierdo era de 62,9 ± 6,2 mm y el diámetro sistólico del ventrículo izquierdo era de 49,7 ± 7,6 mm. La suspensión celular obtenida de células mononucleares de la médula ósea contenía 10,6 ± 7 ml con un conteo de 1,43 ± 0,6 (E+08) células con una viabilidad mayor del 95%. Correspondían a la fracción CD34+, 5,07 ± 9,51 (E+06) y a la CD133+, 5,11 ± 4,3 (E+06). La suspensión se inyectó por pulsos en cuatro pacientes por vía intracoronaria y en el quinto por vía transepicárdica en el transcurso de una cirugía (reemplazo valvular mitral, revascularización y colocación de matriz bioartificial degradable). Resultados A los 17,2 ± 8,8 meses de seguimiento promedio, 4 enfermos se hallaban vivos y en clase funcional I (p < 0,005). Un paciente falleció de muerte súbita a los 17 meses de seguimiento. En este tiempo de evolución no se observaron efectos adversos en ninguno de los pacientes referidos al implante celular. En relación con la fracción de eyección, se notó un incremento a 36,6% ± 2,3% (p < 0,05). Los datos obtenidos en la medición de los diámetros sistólico y diastólico del ventrículo izquierdo no mostraron cambios estadísticos significativos. Conclusiones Este trabajo representa la segunda comunicación mundial sobre el uso de stem cells en cardiopatía de Chagas-Mazza. El procedimiento resultó factible y seguro y se asoció con mejoría de la capacidad funcional y de la función ventricular en el seguimiento. Estos hallazgos provisorios deberán ser corroborados por estudios clínicos controlados más amplios.

We assessed the distribution of Trypanosoma cruzi infection in peridomestic triatomines collected manually at a district-wide scale in rural villages around Olta, Western Argentina, and typed the isolated strains according to their pathogenicity to laboratory mice. Of 1623 triatomines examined, only 14 (0.9%) were infected with T. cruzi based on microscopical examination of feces. The prevalence of T. cruzi infection was 0.8% in Triatoma infestans, 2.3% in T. guasayana, and nil in T. garciabesi, T. platensis, and T. eratyrusiformis. Local transmission occurred in kitchens, store-rooms and goat corrals or nearby, though at very low levels. T. cruzi was detected by at least one parasitological method in 11 (79%) of 14 microscope-positive bugs. Hemoculture was the most sensitive method (67%) followed by culture of organ homogenates, histopathology or xenodiagnosis of inoculated suckling mice (55-58%), and culture of microscope-positive bug feces (46%). The evidence suggests that most of the isolated T. cruzi strains would be myotropic type III. Our study establishes for the first time that peridomestic, microscope-positive T. guasayana nymphs were actually infected with T. cruzi, and may be implicated as a putative secondary vector of T. cruzi in domestic or peridomestic sites.

To identify wild hosts of Trypanosoma cruzi, surveys were conducted in the subandean valleys of Jujuy Province, Argentina, between June 1986 and March 1987. Seventy two mammals from 13 different species were examined by xenodiagnosis. Fifty two of them were mostly roedents trapped at the localities of Maimará, León and Tilcara, and the remainder had been kept in captivity at the Estación Biológica Experimental, in Jujuy. Trypanosoma cruzi infection was detected only in 2 Octodontomys gliroides (2 pos./8 exam. 25%) from all 72 examined mammals. Isolates were called Octodontomys Argentina 1 and 2 (OA1 and OA2). Both infected animals were caught at the archaelogical ruin of Pucará, at Tilcara. Repeated searches for triatomines in the ruin itself and in neighbour houses rendered negative results. Groups of mice inoculated with either OA1 or OA2 isolates became infected between 7 (OA1) to 12 days (OA2) postinoculation PI. Parasitemia peaks were observed between day 12th - 14th PI. Scarce amastigote nests were found in myocardium and skeletal muscle. Mortality was observed only for mice inoculated with OA1. Isoenzyme patterns of OA1 and OA2 were identical to one found in dogs and slightly different from that of human parasites in Argentina. Bones from Octodontomys sp., were recently found in a cave, dated 10200-8600 BC, in Pumamarca, near Tilcara, Jujuy. There are evidences that O. gliroides cohabited with man in ancient times and was associated to the domestic cycle of T. cruzi transmission, playing a role like that of domestic cavies. in Bolivia.

This study reports the embryogenesis of T. infestans (Hemiptera, Reduviidae). Morphological parameters of growth sequences from oviposition until hatching (12-14 d 28ºC) were established. Five periods, as percent of time of development (TD), were characterized from oviposition until hatching. The most important morphological features were: 1) formation of blastoderm within 7% of TD; 2) germ band and gastrulation within 30% of TD; 3) nerve cord, limb budding, thoracic and abdominal segmentation and formation of body cavity within 50% of TD; 4) nervous system and blastokinesis end, and development of embryonic cuticle within 65% of TD; 5) differentiation of the mouth parts, fat body, and Malphigian tubules during final stage and completion of embryo at day 12 to day 14 around hatching. These signals were chosen as appropriate morphological parameters which should enable the evaluation of embryologic modifications due to the action/s of different insecticides

En este estudio se caracterizó el desarrollo embrionario del T. infestans (Hemiptera Reduviidae). Se establecieron parámetros morfológicos secuenciales de crecimiento desde la oviposición hasta la eclosión, (12-14 d 28ºC). Cinco períodos de crecimiento fueron determinados y expresados como fracciones porcentuales del tiempo total del desarrollo (TD) hasta la eclosión. Los eventos morfológicos mas importantes fueron: 1) La formación del blastodermo hasta el 7% del TD; 2) La aparición de la banda germinativa y su gastrulación transcurridos un 30% del TD; 3) El comienzo de la formación del cordón nervioso, de las extremidades, la segmentación torácica y abdominal y la formación del mixocele cuando la embriogénesis alcanzó el 50% del TD; 4) La terminación de la blastoquinesis, el desarrollo completo del sistema nervioso y la aparición de la cutícula embrionaria hasta el 65% del TD; 5) En la etapa final de la embriogenesis se observó la diferenciación del aparato mandibular, el cuerpo graso, los tubos de Malpighy. El embrión completa su organogénesis entre los 12 y 14 días. Estos parámetros morfológicos fueron seleccionados para evidenciar potenciales modificaciones embriológicas debidas a la acción ovicidas de diferentes insecticidas

Estudou-se a dinâmica populacional e a prevalência de infecção chagásica de 352 cães vivendo em 108 moradias rurais infestadas por triato-míneos. A área foi dividida em três setores de acordo com suas crescentes distâncias em relação a um povoado urbano. Cada animal foi identificado mediante suas características particulares, e seus donos deram informações a respeito de seus hábitos. As prevalências de infecção foram determinadas por sorologia, correlação parasitológica-sorológica, percentual de traçados eletrocardiográficos alterados e o percentual de moradias com cães parasitados. A área rural mostrou um padrão característico de infecção por T. cruzi e observaram-se diferenças nos parâmetros de população canina em relação às restantes áreas: maior proporção de filhotes, maior população humana e canina sedentárias, maiores prevalências de infecção por xenodiagnóstico em cães e maior proporção de barbeiros infectados com T. cruzi nos cômodos da casa. Supõe-se que as características sedentárias da população humana desta área rural é fundamental para a oferta de sangue para as populações triatomíneas, e a elevada porcentagem de cães parasitêmicos dessa área contribui para o aumento de barbeiros infectados com T. cruzi encontrados nos quartos de dormir.

The population dynamics and the prevalence of chagasic infection of 352 dogs living in 108 rural houses infested by triatomines were studied. The region was divided into three sections according to increasing distances to an urban area. Each animal was identified by means of its particular characteristics and built, and its owners gave information about its habits. By means of xenodiagnosis, serology and ECG studies, prevalences of infection, parasitological-serological correlation, percentage of altered electrocardiographic outlines and percentage of houses with parasitemic dogs, were determined. The rural area showed a characteristic T. cruzi infection pattern and differences in the canine population parameters with respect to the other areas were observed: a higher proportion of puppies than adult dogs, a more sedentary population, higher prevalences of infection, as measured by xenodiagnosis, in dogs, and the highest proportion of bedroom insects infected with T. cruzi. It is assumed that the sedentary characteristics of the human population in that rural area impinge in the blood offer to the triatomine population, and the high percentage of parasitemic dogs of the area, contribute to the rise of "kissing ougs" infected with T. cruzi found in bedrooms.