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Soil-transmitted helminths (STH) are a significant public health problem in impoverished communities of tropical and subtropical areas. Improved diagnostic methods are crucial for Neglected Tropical Diseases programs, particularly for S. stercoralis, as traditional methods are inadequate. Thus, it is important to identify the most accurate and efficient methods for the diagnosis of STH. We performed a retrospective study analyzing laboratory data at the Instituto de Investigaciones de Enfermedades Tropicales from 2010 to 2019. The study included data from outpatients referred for stool analysis and public health interventions from urban and rural communities in northern Salta province, Argentina. Samples were included in this analysis if processed through sedimentation/concentration, Baermann, Harada-Mori and McMaster's, with a subgroup that also included Agar plate culture method (APC). Sensitivity was calculated against a composite reference standard. Of the 5625 samples collected, 944 qualified for this analysis, with a prevalence of 11.14% for A. lumbricoides, 8.16% for hookworm, 1.38% for T. trichiura, and 6.36% for S. stercoralis. The sedimentation/concentration method was the most sensitive for A. lumbricoides (96%), compared to the McMaster method, with a sensitivity of 62%. Similarly, for hookworms, sedimentation/concentration was more sensitive than McMaster's, Harada-Mori, and Baermann with sensitivities of 87%, 70%, 43%, and 13%, respectively. Most of these infections were of light intensity. For S. stercoralis, Baermann and sedimentation/concentration methods were the most sensitive, with 70% and 62% respectively, while Harada-Mori was the least sensitive. In a subset of 389 samples also analyzed by the APC, Baermann was more sensitive than APC for detecting S. stercoralis, and both methods were superior to Harada-Mori. Parasitological methods, mostly when used combined, offer adequate opportunities for the diagnosis of STH in clinical and public health laboratories. The incorporation of S. stercoralis into the control strategies of the World Health Organization requires rethinking the current diagnostic approach used for surveys. With sedimentation/concentration and Baermann appearing as the most sensitive methods for this species. Further studies, including implementation assessments, should help in identifying the most adequate and feasible all-STH diagnostic approach.

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Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.

A esquistossomose humana é uma doença parasitária causada por uma infecçâo por vermes sanguíneos do gènero Schistosoma. A doença afeta principalmente populaçoes empobrecidas. Cerca de 800 milhoes de pessoas estâo expostas à infecçâo, sendo um problema de saúde pública nas regioes tropicais e subtropicais de África, Ásia, Caribe e América do Sul. No Brasil, o Schistosoma mansoni é a única espécie causadora da esquistossomose e a doença é amplamente distribuida. O diagnóstico convencional da doença é realizado pela detecçâo dos ovos através de métodos parasitológicos, como o teste de Kato-Katz. A esquistossomose foi notificada em todas as regioes do Brasil, e é caracterizada como endèmica em sete estados da Regiâo Nordeste e dois estados da Regiâo Sudeste. Em 2015, 78,7% de todos os casos notificados no Brasil ocorreram na Regiâo Nordeste. Estima-se que 1,5 milhâo de pessoas estejam infectadas com esta doença no Brasil e mais de 25 milhoes vivam em áreas com alto risco de transmissâo. Apesar da reduçâo da mortalidade e morbidade, a esquistossomose foi relatada em 8.756 mortes entre 2000 e 2011 e em 2.517 mortes entre 2015 e 2019 no Brasil e continua sendo um importante problema de saúde pública. No Estado do Rio de Janeiro, algumas áreas apresentam baixa endemicidade ou focos isolados de Schistosoma mansoni e a maioria dos individuos infectados apresenta infecçoes leves. O último levantamento da doença no Estado do Rio de Janeiro foi realizado entre 2010 e 2015 em estudantes de 7 a 17 anos. A esquistossomose foi relatada em 10 dos 21 municipios estudados. Das 5.111 crianças escolares triadas para infecçâo por S. mansoni, 46 (1,65%) testaram positivo. Estudos realizados em áreas de baixa endemicidade no Rio de Janeiro mostraram que dentre os 205 pacientes infectados por S. mansoni em Sumidouro, cerca de 84% tinham 14 anos ou mais e todos, exceto um individuo, tinham a forma intestinal (91,2%) ou hepato-intestinal (8,3%) da esquistossomose. Outro estudo realizado em Sumidouro, mostrou que testes baseados em infecçâo patente de ovo de Schistosoma determinada pelo teste de Kato-Katz, infecçoes ativas foram diagnosticadas em oito (8/108) individuos. A intensidade de infecçâo expressa pelas cargas parasitárias variou de 6 a 72 ovos por grama de fezes/individuo. Os resultados mostraram amplificaçâo do DNA em 32 dos 100 individuos testados por PCR em tempo real. Todos os indivíduos com infecçâo ovo-patente apresentaram amplificaçâo de DNA positiva. Tais estudos mostraram que se analisarmos apenas crianças em idade escolar pelo teste de Kato-Katz, a maioria da populaçâo infectada nunca seria diagnosticada com infecçâo pelo S. mansoni. Em situaçoes de baixa endemicidade, com baixas intensidades de infecçâo, com baixa gravidade na populaçâo e nas faixas etárias mais afetadas, a esquistossomose requer uma abordagem diagnóstica mais sensivel (por exemplo, triagem por PCR em vez do teste de Kato), caso contràrio, muitos individuos infectados permanecerâo invisiveis para o sistema de saúde.

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Introduction: Leishmaniasis, a neglected tropical parasitic disease, is regarded as a major public health problem worldwide. The first-line drugs for leishmaniasis suffer from limitations related to toxicity and the development of resistance in certain parasitic strains. Therefore, the discovery of alternative treatments for leishmaniasis is imperative, and natural products represent a valuable source of potential therapeutic agents. Methods: The present study aimed at finding new potential antileishmanial agents from the aerial parts of the medicinal plant Momordica charantia. This study was based on bioassay-guided fractionation of the M. charantia extract against promastigotes and amastigotes of Leishmania (Leishmania) amazonensis. The cytotoxicity of the extract, fractions, and isolated compounds were evaluated against peritoneal murine macrophages by employing the MTT assay for assessing cell metabolic activity. Results: Antileishmanial assay-guided fractionation of the M. charantia extract led to the bioactive cucurbitacin-enriched fraction and the isolation of four bioactive cucurbitacin-type triterpenoids, which exhibited significant antileishmanial activity, with IC50 values between 2.11 and 3.25 µg.mL-1 against promastigote and amastigote forms, low toxicity and selectivity indexes ranging from 8.5 to 17.2. Conclusion: Our findings demonstrate that the fractions and cucurbitacin-type triterpenoids obtained from the aerial parts of M. charantia are promising natural leishmanicidal candidates.

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Introduction: This paper explores the role of Brazilian research institutions in the global and national context of study of medicinal plants. Most of these plants have ethnopharmacological use and herbal medicines related to the Amazon. It highlights Brazil's position in scientific production and the importance of Amazonian resources in developing phytomedicines. The study aims to provide an overview of the technical-scientific production of medicinal plants and herbal medicines related to the Amazon, focusing on scientific impact, collaboration, Technology Readiness Level (TRL) of scientific production, and innovation system maturity. Methods: The study employs a comprehensive methodological approach, including data collection from Scopus covering the period from 2002 to 2022. The data was cleaned and analyzed using bibliometric and network analysis techniques. Advanced natural language processing techniques, such as Latent Dirichlet Allocation and Jaccard distance measure, were used for TRL classification. Results: The findings reveal a predominant contribution from Brazilian institutions and authors, with 1,850 publications analyzed. Key areas identified include Pharmacology, Toxicology, Pharmaceuticals, Medicine, and Biochemistry. The study also uncovers various collaborative networks and technological maturity levels, with a significant focus on early-stage development phases. Discussion: The research concludes that Brazilian institutions, particularly those in the Amazon region, play a significant role in the scientific exploration and development of medicinal plants and herbal medicines. Despite this, countries like the USA were proportionally more productive in clinical trial research. The study underscores the potential of Brazil's rich biodiversity and traditional knowledge in the pharmaceutical industry, particularly for neglected diseases. It suggests the need for stronger research systems and international collaboration to leverage these resources for global health benefits.

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Scabies is a neglected tropical disease and has been highlighted as a target for control. Sarcoptic mange affects animals, but mange is also considered a zoonosis. We present rapid assessment data on scabies and sarcoptic mange collected from key informants via a web-based questionnaire in Ceará State (1265 data entries). A total of 181/184 (98.3%) municipalities reported the occurrence of human scabies; 149 (80.9%) current occurrence; 168 (91.3%) severe cases; and 113 (61.4%) severe cases currently. Sarcoptic mange was reported from 149/184 (80.9%) municipalities, and severe mange from 128 (69.9%), most commonly in dogs (117 municipalities), cats (79), pigs (17), cattle (15), horses (15), and goats (2). Respondents from 171 (92.9%) municipalities observed seasonality of occurrence. Scabies and sarcoptic mange are important public health issues in a northeast Brazilian state. The wide distribution of severe cases requires an integrated One Health approach effectively and sustainably to reduce the disease burden.

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BACKGROUND: Schistosomiasis continues to represent a serious public health problem in Brazil. With the coronavirus disease 2019 (COVID-19) pandemic, several control strategies were suspended, probably compromising the goals of eradicating the disease in the country. We aimed to assess the impact of the COVID-19 pandemic on Schistosomiasis Control Program (PCE) actions in all endemic states of Brazil. METHODS: We performed an ecological study using spatial analysis techniques. The PCE variables assessed were the population surveyed, the number of Kato-Katz tests, positive cases of schistosomiasis and the percentage of cases treated between 2015 and 2021. The percent change was calculated to verify if there was an increase or decrease in 2020 and 2021, along with time trend analyses provided by the Joinpoint model. Spatial distribution maps were elaborated considering the percent change. RESULTS: The surveyed population decreased in 2020 (-65.38%) and 2021 (-37.94%) across Brazil. There was a proportional reduction in the number of Kato-Katz tests (2020, -67.48%; 2021, -40.52%), a decrease in the percentage of positive cases (2020, -71.16%; 2021, -40.5%) and a reduction in the percentage of treated cases (2020, -72.09%; 2021, -41.67%). Time trend analyses showed a decreasing trend in most PCE variables. CONCLUSIONS: The PCE activities were impacted by the COVID-19 pandemic in Brazil and PCE strategies must be urgently reviewed, focusing on investments in all endemic areas.

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Over a hundred years ago after the discovery of Chagas disease (CD) in Brazil, the World Health Organization estimates a number of 6 to 7 million people infected by Trypanosoma cruzi worldwide. Therefore, the goal of this work was to identify variables related to the spread of infection by T. cruzi in humans living in rural areas, seeking predictor variables. A systematic review of the literature has been conducted, with a search in the Scopus platform, using the search string "Chagas disease" and "rural", resulting in 85 valid and analyzed scientific studies (1977 and 2022). Twenty-seven predictor variables have been acquired, and 19 of them have been grouped, such as: socioeconomic and educational, housing, environmental, sanitary, and cultural; and 8 variables related to T. cruzi seropositive individuals. The predictor variables yielded significant results (p-value < 0.05) in 59.5% of the cases (195/328), with a median of 66.7%. In other words, studies relating to 50% of the 27 variables showed significance equal to or greater than 66.7% of the time. The independent variables with the highest proportion of significant data (p-value < 0.05) were Education (87.6%), Intradomicile building (70%), Domestic animals (69.6%), and Triatomines (69.2%) in the households. Some variables reached 100%; however, few articles were found, indicating the need for further research, especially for Sanitation and Culture. It has been concluded that, in the several contexts found, the social vulnerability and lack of information led the individual to living in environments where inhabitability is inadequate, to perform limited work activity and develop habits and behaviors which impair them in an environmental insalubrity situation, favorable to the access of vectors and pathogens of anthropozoonoses such as CD.

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PURPOSE: Chagas disease (CD) a Neglected Tropical Diseases is an important public health issue in countries where is still endemic, included in the Sustainable Development Goals (SDG). Traditionally restricted to rural areas with diverse routes of transmissions from vectorial to oral with acute manifestations but being more common diagnosed in chronic stages. The aim of this investigation was to characterize the Knowledge, Attitudes and Practices (KAP) related to Chagas disease (CD) in two rural settlements of the Colombian Caribbean with previous records of the disease and/or the parasite. METHODS: A cross-sectional descriptive study was made in two rural settlements in Colombia and surveillance instrument was developed to measure Knowledge, Attitudes and Practices (KAP) related to Chagas disease (CD). RESULTS: In a population with > 60% women and access to social security around 66.5%; 81,6% were homeowners with access to water and electricity > 90% but only 9% of sewerage. The level of knowledge about CD was around 62% but lack of specificity about comprehension of transmission routes (74,6%), and symptoms (85,3%) were found; concluding that 86% of the surveyed sample had very poor level of knowledge about the disease despite preventive campaigns carried out in the two communities studied. CONCLUSIONS: Despite of a low frequency of CD in this Caribbean areas, the presence of vector, risk factors plus poor level of knowledge about the disease justify that public health intervention strategies should be implemented and monitored over time to maintain uninterrupted surveillance of Chagas Disease.

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To present the current epidemiological scenario of schistosomiasis related to urban transmission through an epidemiological risk assessment in Porto de Galinhas, a coastal area of Pernambuco, Brazil. Malacological and parasitological surveys were performed between the years 2018 and 2020. Snails were identified taxonomically and examined to confirm infection by Schistosoma mansoni, and so to identify Schistosomiasis Transmission Foci (STF) by the artificial light exposure technique. Stool samples were examined using the Kato-Katz method to identify schistosomiasis cases. Socioeconomic, environmental, behavioural and health data were collected by a questionnaire applied to participates in the survey and used to predict the schistosomiasis risk occurrence by multivariate logistic regression. In all, a total of 6466 snails of Biomphalaria glabrata were collected and 36 breeding sites were identified, of which 25 % were STF. A total of 2236 individuals took part of the survey which identified 187 cases of schistosomiasis, registering a positivity percentage of 8.36 %. The surveys identified the neighbourhoods with the highest risk for transmission while the socioenvironmental analysis identifies other risk factors for disease occurrence, such as gender, age range, level of education and absence of water drainage. We found that areas with poor sanitation, flooding during winter periods and dwellings located near mangroves should be treated by health authorities as priority areas for health interventions to minimize disease transmission. In addition, efforts to improve the population's educational level could certainly contribute to the adoption of measures to prevent and control this neglected tropical disease.

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Cutaneous leishmaniasis is a neglected disease prevalent in tropical countries, and conventional treatment can cause several serious side effects. Photodynamic therapy (PDT) can be considered a promising treatment alternative, as it is non-invasive therapy that has no side effects and uses accessible and low-cost substances, such as curcumin. This study evaluated the PDT response with cationic and anionic BSA nanoparticles encapsulated with curcumin in macrophages infected with L. braziliensis, L. major, and L. amazonensis. The nanoparticle system was characterized using a steady-state technique, scanning electron microscopy (SEM) study, and its biological activity was evaluated using macrophage cell lines infected with different Leishmania species. All spectroscopy measurements demonstrated that BSA curcumin (BSACur) has good photophysical properties, and confocal microscopy shows that macrophages and protozoa internalized the nanoparticles. The viability test demonstrated that at low concentrations, such as 0.1, 0.7, and 1.0 µmol. L-1, there was a decrease in cell viability after PDT application. Furthermore, a decrease in the number of parasites recovered was observed in the PDT groups. The results allowed us to conclude that curcumin loaded into BSA nanoparticles may have potential application in drug delivery systems for PDT protocols, demonstrating reduced cell viability at lower concentrations than free curcumin.

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BACKGROUND: Schistosoma mansoni is a parasitic disease of great magnitude for Brazilian public health. We aimed to analyse the temporal trend and spatial and spatiotemporal distribution of positivity rates for schistosomiasis mansoni in northeast Brazil. METHODS: This is a descriptive study with an ecological approach, carried out between 2005 and 2016. We calculated the positivity rate for the disease and then performed a segmented trend analysis (Joinpoint). For spatial analysis, we smoothed the positivity rates using the local empirical Bayesian method. We checked for spatial autocorrelation using Moran's global and local. Subsequently, we performed Kulldorff's space time sweep analysis. RESULTS: In the period under review, 7 745 650 tests were performed in the northeast, of which 577 793 were positive for Schistosoma mansoni. In the historical series of positivities, it is noted that the highest rates were in Sergipe, Alagoas and Pernambuco. The states of Alagoas and Sergipe showed higher positivity in relation to the average positivity of the northeast and of Brazil. The spatial analysis maps identify clusters of high risk of schistosomiasis cases, mainly in coastal municipalities. There was also stability in positivity rates in some states and the maintenance of endemic areas. CONCLUSIONS: Thus effective public health policies are needed in health education in order to reduce schistosomiasis positivity and improve the health conditions of the northeastern population.

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BACKGROUND: Previous studies on the distribution of mycetoma globally have failed to identify Ecuador as an endemic country. METHODS: We present data on 35 cases of mycetoma in Ecuador between 1955 and 2021: 5 cases from our experience and 30 cases from the literature. RESULTS: Eight cases of eumycetoma (23%) and 27 cases of actinomycetoma (77%) were diagnosed. Most cases originated from the coastal region of Ecuador. CONCLUSIONS: For the first time in an English-language publication, this communication confirms the presence of mycetoma in Ecuador, securing Ecuador's position on the global mycetoma map.

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Visceral leishmaniasis and Chagas disease are neglected tropical diseases (NTDs) that severely impact the developing world. With current therapies suffering from poor efficacy and safety profiles as well as emerging resistance, new drug leads are direly needed. In this work, 26 alkaloids (9 natural and 17 synthetic) belonging to the benzyltetrahydroisoquinoline (BI) family were evaluated against both the pro/trypomastigote and amastigote forms of the parasites Leishmania infantum and Trypanosoma cruzi, the causative agents of these diseases. These alkaloids were synthesized via an efficient and modular enantioselective approach based on Bischler-Napieralski cyclization/Noyori asymmetric transfer hydrogenation to build the tetrahydroisoquinoline core. The bis-benzyltetrahydroisoquinoline (BBI) alkaloids were prepared using an Ullmann coupling of two BI units to form the biaryl ether linkage, which enabled a comprehensive survey of the influence of BI stereochemistry on bioactivity. Preliminary studies into the mechanism of action against Leishmania mexicana demonstrate that these compounds interfere with the cell cycle, potentially through inhibition of kinetoplast division, which may offer opportunities to identify a new target/mechanism of action. Three of the synthesized alkaloids showed promising druglike potential, meeting the Drugs for Neglected Disease initiative (DNDi) criteria for a hit against Chagas disease.

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BACKGROUND: Lobomycosis is a rare cutaneous tropical neglected disease caused by the fungal agent Lacazia loboi, recently renamed Paracoccidioides lobogeorgii. Our objectives were to present all cases of lobomycosis diagnosed in French Guiana, to offer a precise description of their histopathological features and to propose a new clinico-histological prognostic classification. METHODS: All cases of lobomycosis diagnosed in French Guiana between 1959 and 2022 were included. We looked for associations between the occurrence of relapses and the clinic-histological form. RESULTS: 31 patients diagnosed with lobomycosis were included. An epidemiological shift was observed in the 2000s as Brazilian patients became the most important ethnic group. Gold mining, forestry and fishing/sailing were reported as professional exposures. New histological features, such as inflammatory "rosettes" formations were described. We describe two clinic-histological patterns: a major form (high fungal density and/or multifocal lesions) and a minor form (low fungal density, unifocal lesions, association with fewer relapses). CONCLUSIONS: The changing epidemiology of lobomycosis in French Guiana is characterized by a shift towards Brazilian patients, mostly gold miners. Minor forms should be treated with surgery, major forms with a combination of surgery followed by nultiple drug therapy (MDT) or posaconazole.

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(1) Background: Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods: Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300-350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania (Leishmania) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da. deleoni and Pa. undulata by L. (L.) Mexicana. In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species.

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Community engagement strategies provide tools for sustainable vector-borne disease control. A previous cluster randomized control trial engaged nine intervention communities in seven participatory activities to promote management of the domestic and peri-domestic environment to reduce risk factors for vector-borne Chagas disease. This study aims to assess the adoption of this innovative community-based strategy, which included chickens' management, indoor cleaning practices, and domestic rodent infestation control, using concepts from the Diffusion of Innovations Theory. We used questionnaires and semi-structured interviews to understand perceptions of knowledge gained, intervention adoption level, innovation attributes, and limiting or facilitating factors for adoption. The analysis process focused on five innovation attributes proposed by the Diffusion of Innovations Theory: relative advantage, compatibility, complexity, trialability, and observability. Rodent management was highly adopted by participants, as it had a relative advantage regarding the use of poison and was compatible with local practices. The higher complexity was reduced by offering several types of trapping systems and having practical workshops allowed trialability. Observability was limited because the traps were indoors, but information and traps were shared with neighbors. Chicken management was not as widely adopted due to the higher complexity of the method, and lower compatibility with local practices. Using the concepts proposed by the Diffusion of Innovations Theory helped us to identify the enablers and constraints in the implementation of the Chagas vector control strategy. Based on this experience, community engagement and intersectoral collaboration improve the acceptance and adoption of novel and integrated strategies to improve the prevention and control of neglected diseases.

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Some diseases caused by trypanosomatid parasites, like Leishmaniasis, Chagas Disease, and Human African Trypanosomiasis (HTA), are challenging to manage, mainly concerning pharmacological therapy because they are associated with vulnerable populations. Unfortunately, there is a lack of significant investments in the search for new drugs. Therefore, one of the strategies to aid the discovery of new drugs is to identify and inhibit molecular targets essential to the parasite's survival, such as the proteasome, which degrades most proteins in the parasite cells. Our study has presented several proteasome inhibitors with various pharmacophoric cores, and two of them, 5, and 13, have stood out in the clinical phase of treatment for leishmaniasis.

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Schistosoma mansoni is a parasitic flatworm that causes a human disease called schistosomiasis, or bilharzia. At the genomic level, S. mansoni is AT-rich, but has some compositional heterogeneity. Indeed, some regions of its genome are GC-rich, mainly in the regions located near the extreme ends of the chromosomes. Recently, we showed that, despite the strong bias towards A/T ending codons, highly expressed genes tend to use GC-rich codons. Here, we address the following question: are highly expressed sequences biased in their amino acid frequencies? Our analyses show that these sequences in S. mansoni, as in species ranging from bacteria to human, are strongly biased in nucleotide composition. Highly expressed genes tend to use GC-rich codons (in the first and second codon positions), which code the energetically cheapest amino acids. Therefore, we conclude that amino acid usage, at least in highly expressed genes, is strongly shaped by natural selection to avoid energetically expensive residues. Whether this is an adaptation to the parasitic way of life of S. mansoni, is unclear since the same pattern occurs in free-living species.

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An early hit-to-lead optimization of a novel pyrazinylpiperazine series against L. infantum and L. braziliensis has been performed after an extensive SAR focusing on the benzoyl fragment of hit (4). Deletion of the meta-Cl of (4) led to the obtention of the para-hydroxyl derivative (12), on which the design of most monosubstituted derivatives of the SAR was based. Further optimization of the series, involving disubstituted benzoyl fragments and the hydroxyl substituent of (12), allowed the obtention of a total of 15 compounds with increased antileishmanial potency (IC50 < 10 µM), nine of which displayed activity in the low micromolar range (IC50 < 5 µM). This optimization ultimately identified the ortho, meta-dihydroxyl derivative (46) as an early lead for this series (IC50 (L. infantum) = 2.8 µM, IC50 (L. braziliensis) = 0.2 µM). Additional assessment of some selected compounds against other trypanosomatid parasites revealed that this series is selective towards Leishmania parasites, and in silico ADMET predictions revealed satisfactory profiles for these compounds, allowing further lead optimization of the pyrazinylpiperazine class against Leishmania.

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