Abstract Chagas Disease (CD) is endemic in Ecuador, with a notable prevalence in the province of Manabí. Specifically, the Olmedo canton stands out as one of the most affected by this disease. The objective of the present study is to clinically and epidemiologically characterize the cases of CD, diagnosed from January 2019 to December 2022 in the Olmedo Canton, Manabí, Ecuador. An observational, descriptive study was carried out, registering 14 confirmed cases of Trypanosoma cruzi infection. The variables studied were the number of cases presented per year, sex, age groups, laboratory diagnosis, type of surveillance. A total of 14 reactive cases were identified; mostly represented by the male sex; with a predominance of people over 65 years of age. Active surveillance contributed to the highest number of notifications. The total number of cases corresponded to chronic Chagas disease. The communities of San Roque and the Divino Niño neighborhood presented the highest number of notifications of confirmed cases. In conclusion, it is proposed that Chagas Disease represents a silent health problem in the Olmedo Canton. Active surveillance through case search, as well as antibody tests, are key in diagnosis.

Resumen La Enfermedad de Chagas (EC) es endémica en el Ecuador, con una notable prevalencia en la provincia de Manabí. Específicamente, el cantón Olmedo destaca como uno de los más afectados por esta enfermedad. El objetivo del presente estudio es caracterizar clínica y epidemiológicamente los casos de EC, diagnosticados desde enero 2019 a diciembre 2022 en el Cantón Olmedo, Manabí, Ecuador. Se realizó un estudio observacional, descriptivo, de registro de 14 casos confirmados por infección de Trypanosoma cruzi. Las variables estudiadas fueron, el número de casos presentados por año, sexo, grupos de edades, diagnóstico de laboratorio, tipo de vigilancia. Se identificaron un total 14 casos reactivo; mayormente representada por el sexo masculino; con predominio de personas mayores de 65 años. La vigilancia activa contribuyó al mayor número de notificaciones. El total de casos correspondieron a Chagas crónicos. Las comunidades San Roque y el barrio Divino Niño, presentaron el mayor número de notificaciones de casos confirmados. En conclusión, se plantea que la Enfermedad de Chagas representa un problema de salud silente en el Cantón Olmedo. La vigilancia activa a través de búsqueda de casos, así como los test de anticuerpos son claves en el diagnóstico.

Resumo A reativação da doença de Chagas crônica é condição rara e ocorre apenas em pacientes imunossuprimidos. O envolvimento da pele foi reportado em pacientes com doença de Chagas crônica e transplante hepático e cardíaco com reativação da tripanossomíase. Em todos os casos cutâneos foi detectada a forma amastigota do Trypanosoma cruzi. Nosso caso traz paciente feminina de 51 anos com história de transplante cardíaco devido à doença de Chagas e imunodepressão. A equipe dermatológica foi chamada devido ao aparecimento de nódulos eritematosos dolorosos, após 30 dias de hospitalização. Primeiramente, a biópsia de pele foi compatível com hipótese de leishmaniose cutânea. Depois da imuno-histoquímica, confirmou-se a presença de T. cruzi, sendo decidido tratar reativação da doença de Chagas. O desenvolvimento de paniculite não é usualmente associado à doença de Chagas. Assim, ressalta-se a importância de não excluir tal diagnóstico e refere a necessidade da análise anatomopatológica e imuno-histoquímica para complementação diagnóstica.

Abstract Reactivation of chronic Chagas disease is a rare condition, occurring solely in immunosuppressed patients. Skin involvement has been reported in patients with chronic Chagas disease and heart or kidney transplantation who reactivated the trypanosomiasis. In all cases involving the skin, amastigote forms of Trypanosoma cruzi are detected. Our case focuses on a 51-year-old female with a history of cardiac transplantation due to Chagas disease and immunodepression. The dermatology team was consulted due to the presence of painful erythematous nodules, after 30 days of hospitalization. Initially, a skin biopsy suggested cutaneous leishmaniasis as a hypothesis. However, subsequent immunohistochemistry confirmed the presence of T. cruzi, leading to the decision to treat for Chagas disease reactivation. The development of panniculitis is not commonly associated with Chagas disease. This case underscores the importance of not disregarding such possibilities and highlights the necessity for histopathological and immunohistochemical analyses to complement the diagnostic process.

Chagas disease is a relevant public health threat that affects over 6 million people worldwide, resulting in devastating social and economic consequences. Moreover, the therapeutic options are limited, highlighting the urgency in searching for novel active antitrypanosomal molecules. Compounds with either thiazole or biaryl units have been described as possessing anti Trypanosoma cruzi activities. Therefore, here, we describe the synthesis of nine arylated and diarylated thiazole derivatives and the evaluation of their in vitro toxicity on mammalian cells as well as their anti T. cruzi activity. The compounds were prepared in straightforward synthetic routes, using Hantzsch thiazole synthesis and cross-coupling reactions as key steps. A pyridyl-phenyl-thiazole (PPT) derivative (4c) presented 76% of T. cruzi growth inhibition in preliminary tests using a fixed concentration of 20 µM. This compound was used as a scaffold for the synthesis of two novel PPT analogs (4g and 4h). Dose-response assays on intracellular forms of T. cruzi demonstrated that these three compounds presented high antiparasitic potency (half maximal effective concentration (EC50) values ranging from 1.15 to 2.38 μM) and low toxic profile against L929 cell lines. Hence, these findings highlight the pyridyl-phenyl-thiazole backbone as a novel privileged scaffold in the search for active molecules against T. cruzi.

RESUMEN Trypanosoma cruzi es el agente causal de la enfermedad de Chagas. En Paraguay se estima que existen 165.000 personas infectadas y actualmente la principal vía de transmisión es la congénita, con una prevalencia del 5% y con alrededor de 400 niños infectados nacidos por año. El departamento de Cordillera es área endémica de la Región Oriental del país, donde se implementó el Programa de Control Prenatal de Chagas en el año 1995. El objetivo de este estudio fue inferir sobre la potencial transmisión congénita de la enfermedad de Chagas en jóvenes embarazadas de segunda generación de Cordillera que asistieron a su control prenatal en el período 2010-2012, 15 años después de la implementación del Programa de Control Prenatal. De 9.588 embarazadas; 482 fueron seropositivas (5%); 2,74% en el grupo de 12 a 19 años, 4,93% de 20 a 30 años, 8,03% de 31 a 40 años y 16,11% de 41 a 48 años. Para estimar el origen de la transmisión congénita de segunda generación se tuvo en cuenta a las 72 seropositivas de 12 a 19 años y según la base de datos de las respectivas madres 61 eran seropositivas. Con esta información se estima que la transmisión a embarazadas de segunda generación de 12 a 19 años fue congénita en un 85% indicando una transmisión congénita muy significativa en la población de estudio. Esta información ayudaría al Programa Nacional de Chagas en el fortalecimiento del control de la transmisión congénita de la enfermedad de Chagas en el país.

ABSTRACT Trypanosoma cruzi is the causative agent of Chagas disease. In Paraguay, it is estimated that 165,000 people are infected and currently the main route of transmission is the congenital one, with a prevalence of 5% and about 400 infected children are born per year. The Department of Cordillera is an endemic area of the Eastern Region of the country, where the Chagas Prenatal Control Program was implemented in 1995. The aim of this study was to infer the potential congenital transmission of Chagas disease towards second generation pregnant women from the Department of Cordillera who attended their prenatal control in the period 2010-2012, 15 years after the implementation of the Prenatal Control Program. Of 9,588 pregnant women; 482 were seropositive (5%); 2.74% in the group aged 12 to 19 years, 4.93% aged 20 to 30 years, 8.03% aged 31 to 40 years, and 16.11% aged 41 to 48 years. To estimate the origin of second generation congenital transmission, the 72 seropositive women aged 12 to 19 years were taken into account and according to the database of their respective mothers, 61 mothers of the 72 were seropositive. With this información, it can be estimated that 85% of the transmission to second generation pregnant women aged 12 to 19 years was congenital showing a very significant congenital transmission in the study population. This information could help the National Chagas Program in strengthening the control of congenital transmission of Chagas disease in the country.

Resumen La tripanosomiasis Americana es una de las enfermedades tropicales desatendidas a nivel mundial, y es causada por el protozoario hemoflagelado Trypanosoma cruzi (Tc). Actualmente, los fármacos anti-Tc son limitados y no hay vacuna disponible. El objetivo de esta investigación fue evaluar el efecto de las nanopartículas de plata (AgNPs) contra los tripomastigotes de las cepas Sylvio X10/4 (TcI) y Esmeraldo (TcII). Las AgNPs se obtuvieron por el método de reducción y se les realizó una caracterización estructural. La actividad citotóxica de las AgNPs (actividad anti-Tc) se determinó mediante el cálculo de los valores de la mitad de la concentración inhibitoria máxima (IC50) en las células HaCaT y en los parásitos. Las AgNPs no mostraron citotoxicidad contra las células HaCaT en los valores de IC50 probadas en los parásitos, y la IC50 calculada en los tripomastigotes fue de 4.05 µg/ml y de 6.16 µg/ml en las cepas TcI y TcII respectivamente. Las AgNPs fueron más activas contra las dos cepas de Trypanosoma cruzi, que el nifurtimox (400 µg/ml) in vitro. Estos resultados sientan las bases para la evaluación mayor de las AgNPs, por investigar su potencial quimioterapéutico para combatir la infección por T. cruzi en modelos animales.

Abstract American trypanosomiasis is one the globally neglected tropical disease, and is cause by the protozoan haemoflagellate Trypanosoma cruzi (Tc). Currently, the anti-Tc drugs are limited and no vaccine is available. The objective of the study was to determine the effects of silver nanoparticles (AgNPs) against trypomastigotes of the Sylvio X10/4 (TcI) and Esmeraldo (TcII) strains. The AgNPs were obtained by the reduction method and a structural characterization was carried out. The cytotoxic activity of the AgNPs (antiTc activity) was determined by calculating the values of half the maximum inhibitory concentration (IC50) in HaCaT cells and parasites. AgNPs showed no-cytotoxicity against HaCaT cells at the IC50 values assayed in parasites, and the calculated IC50 trypomastigotes was 4.05 µg/ml and 6.16 µg/ml for TcI and TcII strains, respectively. AgNPs were more active against both Trypanosoma cruzi strains than nifurtimox (400 µg/ml) in vitro assays. These results lay the groundwork for further evaluation of AgNPs, to investigate its chemotherapeutic value to figh T. cruzi infection in animal models.

ABSTRACT Microalgae have proven to have multiple applications in the biotechnology industry. Porphyridium cruentum is a microalgae that exhibits a wide content of polysaccharides and proteins with potential pharmacological activity. This work evaluates the antimicrobial activity of the P. cruentum biomass against the parasites Leishmania infantum, Trypanosoma rhodesiense, Trypanosoma cruzi, and Trypanosoma brucei through the microdilution method in plates, as well as the cytotoxicity in leukocyte cell lines, using as a drug reference Tamoxifen. The biomass showed inhibitory activity against the parasites T. brucei, T. rhodesiensis, and T. cruzi. The study also demonstrated that the biomass does not exert cytotoxic activity on THP-1 human monocytes and RAW 264.7 murine macrophages. The results obtained indicate that the active compounds present in Porphyridium cruentum could be considered as possible antimicrobial candidates.

RESUMEN Actualmente, existe una creciente preocupación por el aumento de la resistencia microbiana de numerosos agentes patógenos. Las microalgas han demostrado tener múltiples aplicaciones en la industria biotecnológica. Porphyridium cruentum es una microalga que exhibe un amplio contenido de polisacáridos y proteínas con potencial actividad farmacológica. Este trabajo evalúa la actividad antimicrobiana de la biomasa P. cruentum frente a los parásitos Leishmania infantum, Trypanosoma rhodesiense, Trypanosoma cruzi, y Trypanosoma brucei a través del método de microdilución en placas, así como la citotoxicidad en líneas celulares de leucocitos, utilizando como fármaco de referencia el Tamoxifeno. La biomasa mostró actividad inhibitoria frente a los parásitos T. brucei, T. rhodesiensis, y T. cruzi. El estudio demostró, además, que la biomasa no ejerce actividad citotóxica sobre monocitos humanos THP-1 y macrófagos murinos RAW 264.7. Los resultados obtenidos apuntan que los compuestos activos presentes en Porphyridium cruentum podrían ser considerados como posibles candidatos antimicrobianos.

Resumen Chagas es una endemia que afecta a Latinoamérica con alto impacto biomédico y social. Es un caso único en la historia médica donde primero se descubre un microorganismo y luego la enfermedad que produce. El “redescubrimiento” de su importancia se origina en la Argentina, con los estudios de Salvador Mazza y colaboradores de diferentes provincias en la Misión de Estudios de Patología Regional Argentina (MEPRA). A pesar de su magnitud, es objeto de adjetivaciones como “endemia olvidada”, “enfermedad silenciosa”, “mal escondido” y está incluida entre las “enfermedades desatendidas”. Originalmente era una endemia rural, actualmente se ha urbanizado y globalizado por migraciones y propagación interhumana, principalmente por la transmisión madre-hijo. Además, la vía oral hace años adquirió importancia epidemiológica. El diagnóstico de laboratorio está protocolizado y es posible realizarlo incluso en laboratorios de baja complejidad. Para la prevención, interferir en la cadena epidemiológica que incluye reservorios domésticos es una estrategia que puede contribuir a disminuir la infección en zonas con transmisión vectorial. La vacunación con Trypanosoma rangeli, parásito inmunológicamente similar a Trypanosoma cruzi pero no patógeno, ha demostrado su eficacia para proteger perros y cobayos contra la infección por T. cruzi. Basso et al. han estudiado además mecanismos protectores, demostrando la importancia de la inmunidad innata, además de la clásica inmunidad adaptativa. Por último, este artículo aborda aspectos académicos, sociales y bioéticos, enfatizando la importancia de la enseñanza de Chagas en ciencias de la salud y la necesidad de garantizar los principios y valores bioéticos aplicables a poblaciones vulnerables.

Resumo Chagas é uma doença endêmica que afeta à América Latina com alto impacto biomédico e social. É um caso único na história da Medicina, onde primeiro se descobre um microrganismo e depois a doença que ele produz. A “redescoberta” de sua importância tem origem na Argentina, com os estudos de Salvador Mazza e colaboradores de diferentes províncias na Missão de Estudos de Patologia Regional Argentina (MEPRA). Apesar de sua importância, é objeto de adjetivos como “endemia esquecida”, “doença silenciosa”, “mal escondido” e está incluída entre as “doenças negligenciadas”. Originalmente endemia rural, agora é urbanizada e globalizada por migrações e disseminação inter-humana, principalmente a transmissão mãe-filho. Por outro lado, a transmissão oral faz anos adquiriu importância epidemiológica. O diagnóstico laboratorial é protocolizado e é possível realizá-lo mesmo em laboratórios de baixa complexidade. Quanto à prevenção, a interrupção da cadeia epidemiológica que inclui reservatórios domésticos, é uma estratégia que pode contribuir a reduzir a infecção em áreas com transmissão vetorial. A vacinação com Trypanosoma rangeli, parasita imunologicamente semelhante ao Trypanosoma cruzi, mas não patogênico, tem se mostrado eficaz na proteção de cães e cobaias contra a infecção por T. cruzi. Basso et al. estudaram os mecanismos protetores, demonstrando a importância da imunidade inata, além da imunidade adaptativa clássica. Finalmente, o artigo aborda aspectos acadêmicos, sociais e bioéticos, enfatizando a importância do ensino de Chagas em Ciências da Saúde, e a necessidade de garantir os princípios e valores bioéticos aplicáveis às populações vulneráveis.

Abstract Chagas disease is an endemic disease that affects Latin America with high biomedical and social impact. This work addresses aspects and particularities that characterise this disease. It is a unique case in medicine as the microorganism was discovered before the disease it causes. The re-discovery of its relevance had its origin in Argentina, due to studies conducted by Salvador Mazza and collaborators from various provinces, within the Mission of Regional Pathology Studies from Argentina (MEPRA). Notwithstanding its importance, it is often described as “forgotten endemic disease”, “silent disease”, “hidden illness”, and it is included among the “neglected diseases”. Originally considered as rural endemic, nowadays it is urbanised and globalised, due to migrations and inter-human propagation, mainly by mother-child transmission. On the other hand, oral transmission is considered now of epidemiological relevance. Laboratory diagnosis is protocolised and it is possible to carry it out even in low complexity laboratories. Concerning disease prevention, interrupting the epidemiological chain that includes domestic reservoirs is a strategy that can contribute to reducing the infection in areas where it is vector-borne. Vaccination with Trypanosoma rangeli, a parasite immunologically similar to Trypanosoma cruzi but which is nonpathogenic, has demonstrated its efficacy in protecting dogs and guinea pigs against T. cruzi infection. Basso et al. have studied the importance of innate immunity, in addition to the classic adaptive immunity. Finally, this article addresses academic, social and bioethical aspects, emphasizing the importance of an adequate education in the health science field, as well as the need to guarantee bioethical principles and values regarding vulnerable populations.

Chagas disease, caused by the parasite Trypanosoma cruzi, occurs most commonly in Latin America. As the treatment is highly toxic and ineffective in the chronic phase of the disease, alternative treatments are needed. Through quantitative structure-activity relationship modeling (QSAR) analysis using ligand-based and structure-based virtual screening methods, we predicted the trypanocidal potential of 47 neolignans against three targets, the enzymes cruzain, trypanothione reductase, and sterol 14-alpha demethylase. A combined analysis allowed for the selection of potent inhibitors against Trypanosoma cruzi. Of these compounds, two were isolated and shown to inhibit the growth of epimastigotes at concentrations of 9.64 and 8.72 µM, and trypomastigote forms at 4.88 and 2.73 µM. Therefore, the compounds (2R, 3R)-2,3-dihydro-2 (4 methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (46) and ottomentosa (47) may be a good option of growth inhibitors for the parasite stages and warrant additional study.

Resumo O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T.cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.

Abstract Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

RESUMEN El diagnóstico serológico de la enfermedad de Chagas, causada por Trypanosoma cruzi, carece de “gold standard”, siendo considerada la inmunofluorescencia indirecta (IFI) como prueba de referencia para la detección de anticuerpos. Actualmente en Paraguay, el diagnóstico se basa en combinar dos pruebas serológicas. El objetivo del estudio fue evaluar la concordancia entre una prueba in-house de IFI y un test comercial de hemoaglutinación indirecta (HAI), para la detección de anticuerpos IgG anti-T. cruzi. Se evaluaron 54 muestras de pacientes que acudieron al Instituto de Investigaciones en Ciencias de la Salud (IICS) con solicitud médica de serología para Chagas. Los sueros fueron primeramente analizados por IFI (29 positivos y 25 negativos) y almacenados en una seroteca, posteriormente, se descongelaron para su análisis por HAI. Se determinó la concordancia entre IFI y HAI utilizando el índice Kappa. La concordancia observada entre ambos métodos fue muy buena (Índice Kappa=0,96; p(0,0001). No se observaron diferencias significativas en las frecuencias de muestras que presentaron IgG anti-T.cruzi en los niveles bajo (p=0,759), intermedio (p=1,000) y alto (p=0,592). Los anticuerpos medidos por ambos métodos mostraron buena correlación (Rho de Spearman= 0,715; p<0,01). La sensibilidad y especificidad de HAI frente a IFI fue 96,6% y 100%, respectivamente. Los hallazgos sugieren que la combinación de ambas pruebas evaluadas, o bien HAI con otras pruebas serológicas, sería una buena elección diagnóstica en la enfermedad de Chagas en nuestro medio.

ABSTRACT The serological diagnosis of Chagas disease, caused by Trypanosoma cruzi, lacks a "gold standard", being indirect immunofluorescence (IFI) considered the reference test for the detection of antibodies. Currently in Paraguay, the diagnosis is based on combining two serological tests. The objective of the study was to evaluate the agreement between an IFI in-house assay and a commercial indirect haemagglutination test (HAI) for the detection of IgG anti-T. cruzi. A total of 54 samples were evaluated, all from patients who attended the Instituto de Investigaciones en Ciencias de la Salud (IICS) with a medical request for Chagas serology. The specimens were first analyzed by IFI (29 positive and 25 negative) and stored in a serum bank, later they were thawed for analysis by HAI. Agreement between IFI and HAI was determined using the Kappa index. The agreement observed between both methods was very good (Kappa Index=0.96; p<0.0001). No significant differences were observed in the frequencies of samples that presented anti-T. cruzi IgG at low (p=0.759), intermediate (p=1,000) and high (p=0.592) levels. The antibodies measured by both methods showed a good correlation (Spearman's Rho= 0.715; p<0.01). The sensitivity and specificity of HAI versus IFI was 96.6% and 100%, respectively. The findings suggest that the combination of both tests, or HAI with other serological tests, would be a good diagnostic choice in Chagas disease at local level.

ABSTRACT Chagas disease (CD) is a neglected tropical disease caused by Trypanosoma cruzi and is genetically classified in six discrete typing units (DTUs). The isolates reported in Mexico are generally associated with DTU I. We presented a case of a prolonged cutaneous lesion in a Mexican man, caused by DTU II in coinfection with Bacillus velezensis and Corynebacterium sp. The patient assessment included a complete clinical history, physical exam, laboratory tests, and a skin biopsy. In the facial tissues, intracellular parasites were revealed. The PCR tests were positive for T. cruzi in tissue and blood samples. DNA satellite sequencing was correlated with the DTU II. The initial serological tests reported negative results. However, four months later, two serological tests reported positive results. These exams were performed in different health centers. Mexico is considered an endemic area for CD; nevertheless, this is just the second cutaneous case associated with a DTU different from DTU-I noted in this country. From an ecological point of view, this fact suggests a geographical expansion of DTU II and an association with atypical skin manifestations. Further studies should be conducted to understand this exciting association between DTU-II and prolonged cutaneous expression in humans.

Mental disorders such as anxiety, depression, and memory loss have been described in patients with chronic Chagas disease (CD), a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. Social, psychological, and biological stressors may take part in these processes. There is a consensus on the recognition of an acute nervous form of CD. In chronic CD patients, a neurological form is associated with immunosuppression and neurobehavioural changes as sequelae of stroke. The chronic nervous form of CD has been refuted, based on the absence of histopathological lesions and neuroinflammation; however, computed tomography shows brain atrophy. Overall, in preclinical models of chronic T. cruzi infection in the absence of neuroinflammation, behavioural disorders such as anxiety and depression, and memory loss are related to brain atrophy, parasite persistence, oxidative stress, and cytokine production in the central nervous system. Interferon-gamma (IFNγ)-bearing microglial cells are colocalised with astrocytes carrying T. cruzi amastigote forms. In vitro studies suggest that IFNγ fuels astrocyte infection by T. cruzi and implicate IFNγ-stimulated infected astrocytes as sources of TNF and nitric oxide, which may also contribute to parasite persistence in the brain tissue and promote behavioural and neurocognitive changes. Preclinical trials in chronically infected mice targeting the TNF pathway or the parasite opened paths for therapeutic approaches with a beneficial impact on depression and memory loss. Despite the path taken, replicating aspects of the chronic CD and testing therapeutic schemes in preclinical models, these findings may get lost in translation as the chronic nervous form of CD does not fulfil biomedical model requirements, as the presence of neuroinflammation, to be recognised. It is hoped that brain atrophy and behavioural and neurocognitive changes are sufficient traits to bring the attention of researchers to study the biological and molecular basis of the central nervous system commitment in chronic CD.

ABSTRACT Rhodnius prolixus is the most important vector of Trypanosoma cruzi in the northern part of South America. The compound eyes in adults of R. prolixus are involved in the nocturnal flight dispersion from sylvatic environments into human dwellings. During this behavior, the artificial lights play an important role in attracting R. prolixus; however, it is still not clear whether the compound eyes of this species use different visible wavelengths as a cue during active dispersion. We applied electrophysiological (electroretinography or ERG) and behavioral (take-off) experiments in a controlled laboratory setting to determine the spectral sensitivity of the compound eyes and the attraction of R. prolixus adults to discrete visible wavelengths. For the ERG experiments, flashes of 300 ms at wavelengths ranging between 350 and 700 nm at a constant intensity of 3.4 µW/cm2 were tested after adaptation to darkness and to blue and yellow lights. For the behavioral experiments, the adults were exposed to nine visible wavelengths at three different intensities, and their direction of take-off in an experimental arena was established with circular statistics. The ERG results showed peaks of spectral sensitivity at 470–490 nm and 520–550 nm in adults, while behavioral experiments showed attractions to blue, green and red lights, depending on the intensity of the light stimuli. The electrophysiological and behavioral results confirm that R. prolixus adults can detect certain wavelengths in the visible spectrum of light and be attracted to them during take-off.

ABSTRACT This study describes the laboratory investigation of two acute Chagas disease outbreaks that occurred in the riverside communities of Marimarituba and Cachoeira do Arua, in the Santarem municipality, Para State, located in the Northern region of Brazil, and occurred in March 2016 and August 2017, respectively. The generation of data regarding the diversity of Trypanosoma cruzi parasites circulating in the Amazon region is key for understanding the emergence and expansion of Chagas disease. This study aimed to identify T. cruzi Discrete Typing Units (DTUs) involved in two outbreaks of acute Chagas disease (ACD) directly from the patient’s biological sample. Nested and multiplex PCR targeting the 24Sα (rRNA) and mini-exon genes, respectively, were used to identify T. cruzi DTU in blood samples from patients diagnosed with ACD. The samples with positive cPCR were submitted for analysis for T. cruzi DTUs, which included 13 samples from the patients with ACD by oral transmission and two samples collected from two newborns of two women with ACD, from Marimarituba and Cachoeira do Arua. The samples were classified as T. cruzi TcIV, from Marimarituba’s outbreak, and T. cruzi TcI, from Cachoeira do Arua’s outbreak. The molecular identification of T. cruzi may increase understanding of the role of this parasite in Chagas disease’s emergence within the Amazon region, contributing to the improvement of the management of this important, but also neglected, disease.

ABSTRACT Background: Chagas disease (CD) is caused by Trypanosoma cruzi and transmitted by triatomines. Historical information from the 20th century demonstrates T. cruzi records in the metropolitan region of Salvador (MRS), the third largest urban agglomeration in the Brazilian Northeast and the eighth largest in Brazil, an area with intense migratory activity from CD-endemic regions. Therefore, this study aimed to evaluate CD indicators (prevalence and mortality) in the MRS. Methods: A mixed ecological and descriptive study was conducted using secondary data. We analyzed data from 2008 to 2015: deaths due to CD, self-reported cases of CD, and blood donors that were non-negative for T. cruzi infection. Results: São Francisco do Conde was one of the municipalities with the highest mortality rates due to CD. The seroprevalence rates varied by year and municipality; those with the highest values were 2008: Vera Cruz, 2009: Mata de São João, 2010: Dias D'Ávila, 2011 and 2015: São Francisco do Conde, 2012: São Sebastião do Passé, and 2013 and 2014: Pojuca. Spatial correlations between the municipalities were not detected. Conclusions: We conclude that CD is present in the MRS. The indicators analyzed in the MRS are below-state-level data. Given the importance of indicator analysis for the surveillance and control of CD at the state and national levels, it is important to strengthen the surveillance program at the municipal level, including the regions classified as low risk for T. cruzi vector transmission.