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The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

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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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BACKGROUND: Neglected tropical diseases (NTDs) are parasitic and bacterial diseases that affect approximately 149 countries, mainly the poor population without basic sanitation. Among these, African Human Trypanosomiasis (HAT), known as sleeping sickness, shows alarming data, with treatment based on suramin and pentamidine in the initial phase and melarsoprol and eflornithine in the chronic phase. Thus, to discover new drugs, several studies point to rhodesain as a promising drug target due to the function of protein degradation and intracellular transport of proteins between the insect and host cells and is present in all cycle phases of the parasite. METHODOLOGY: Here, based on the previous studies by Nascimento et al. (2021) that show the main rhodesain inhibitors development in the last decade, molecular docking and dynamics were applied in these inhibitors datasets to reveal crucial information that can be into drug design. Thus, conventional and covalent docking was employed and highlighted the presence of Michael acceptors in the ligands in a peptidomimetics scaffold, and interaction with Gly19, Gly23, Gly65, Asp161, and Trp184 is essential to the inhibiting activity. RESULTS: Also, our findings using MD simulations and MM-PBSA calculations confirmed Gly19, Gly23, Gly65, Asp161, and Trp184, showing high binding energy (ΔGbind between -72.782 to -124.477 kJ.mol-1). In addition, Van der Waals interactions have a better contribution (-140,930 to -96,988 kJ.mol-1) than electrostatic forces (-43,270 to -6,854 kJ.mol-1), indicating Van der Waals interactions are the leading forces in forming and maintaining ligand-rhodesain complexes. CONCLUSION: Furthermore, the Dynamic Cross-Correlation Maps (DCCM) show more correlated movements for all complexes than the free rhodesain and strong interactions in the regions of the aforementioned residues. Principal Component Analysis (PCA) demonstrates complex stability corroborating with RMSF and RMSD. This study can provide valuable insights that can guide researchers worldwide to discover a new promising drug against HAT.

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Chagas disease (CD) is a typical tropical illness caused by Trypanosoma cruzi. The objective of this study was to assess the prevalence of Chagas disease in communities in two states of the Brazilian Amazon. Data collection occurred in July in the Alto Juruá region of Acre and in December in the communities of Humaitá, Amazonas, in 2019. A total of 477 participants were included in the study. In the communities of Alto Juruá, triatomine collections and analyses of T. cruzi infection were also carried out. All confirmed cases were found in the state of Acre, resulting in a total prevalence of 1.67. Of these eight cases, seven underwent ECG, all of which were concluded as normal by the physician team's cardiologists. Seventeen triatomine bugs, all belonging to the Rhodnius genus, were captured. The natural infection rate by T. cruzi was 25% in the Nova Cintra community and 66.67% in the Boca do Moa community (Alto Juruá). This research found that more than 1% of the studied population exhibited positive serological results for Chagas disease in the riverine communities during the study period, representing a small portion of cases among those who have not yet been diagnosed.

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ABSTRACT Background: Chagas disease, a zoonosis transmitted mainly by hematophagous insects of the subfamily Triatominae, is caused by Trypanosoma cruzi, classified into six discrete typing units (DTUs: TcI-TcVI and Tcbat). Methods: Insect vectors were collected from 84 human dwellings in the municipality of Santo Domingo Tehuantepec, Oaxaca, Mexico; 4.76% were infested. DTUs were determined using conventional and nested PCR. Results: The infection rate was 43.6%. All insects were infected with TcI while one specimen showed mixed infection with TcII. Conclusions: This is the first report of T. cruzi mixed infection in Triatoma phyllosoma, its main vector in the study region.

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There are few reports of Trypanosoma in snakes, as well as little information about its pathogenicity in these animals. Thus, the present study aimed to characterize Trypanosoma found in Boa constrictor snakes, to verify the influence of the parasitism on hematological and clinical biochemistry parameters, and to perform a phylogenetic study of the isolates. Blood samples from sixty-one boas were analyzed for the presence of trypanosomatids and by hematological and clinical biochemistry assays. The flagellates that were found in this analysis were used for cell culture, morphometry, and molecular analysis. Later, molecular typing phylogenetic studies were performed. Nine positive animals (14.75%) were identified by microscopy analysis. The hematological results showed that parasitized animals presented significantly lower levels of packed cell volume, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. In the leukogram, eosinophils and heterophils counts were higher in parasitized animals. Considering the molecular analyses, the isolates presented a higher identity of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the 18S small subunit ribosomal RNA (SSU rRNA) gene fragments with Trypanosoma serpentis. The phylogenetic tree, using the GAPDH, clustered all isolates with T. serpentis and Trypanosoma cascavelli. This is the first description of T. serpentis parasitizing boas and of the clinical changes caused by trypanosomatid infection in snakes.

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Background: Triatomine bugs are natural vectors of Trypanosoma cruzi, which causes Chagas disease or American trypanosomiasis. The role of sylvatic triatomine species as vectors of T. cruzi in Mexico remains to be fully understood. Our research on the epidemiology of Chagas disease in Southeastern Mexico involved sampling triatomines in rural settings. Materials and Methods: A triatomine was collected in a peridomestic environment of a rural dwelling in the state of Chiapas. The triatomine was identified morphologically as an adult female Eratyrus cuspidatus Stal. Results: Microscopic analysis revealed flagellate forms of T. cruzi in the feces of the E. cuspidatus collected. This was confirmed by quantitative polymerase chain reaction. Amplification of the mini-exon gene showed that the T. cruzi infecting E. cuspidatus corresponded to lineage I. Conclusions: This is the first report from Mexico of E. cuspidatus found infected in a human dwelling, which represents an important adaptation process to inhabit human environments.

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Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.

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BACKGROUND: Human African trypanosomiasis (HAT) is a parasitic infection that may lead to death if left untreated. This disease is caused by a protozoan parasite of the genus Trypanosoma and is transmitted to humans through tsetse fly bites. The disease is widespread across Sub-Saharan Africa, with 70% of cases in recent reports in the Democratic Republic of the Congo and an average of less than 1000 cases are declared annually. Since there is no appropriate treatment for HAT, steroidal and triterpenoid saponins have been reported to be effective in in vitro studies and might serve as scaffolds for the discovery of new treatments against this disease. AIM OF THE STUDY: The present study aimed to summarize up-to-date information on the anti-Trypanosoma brucei activity of steroidal and triterpenoid saponins. The mechanisms of action of in vitro bioactive compounds were also discussed. METHODS: Information on the anti-Trypanosoma brucei activity of plant saponins was obtained from published articles, dissertations, theses, and textbooks through a variety of libraries and electronic databases. RESULTS: There has been incredible progress in the identification of steroidal and triterpenoid saponins with pronounced in vitro activity against Trypanosoma brucei. Indeed, more than forty saponins were identified as having anti-T. brucei effect with activity ranging from moderate to highly active. The mechanisms of action of most of these saponins included DNA damage, cell cycle arrest, induction of apoptosis through downregulation of bcl-2 and MDM2, and upregulation of Bax and Bak, among others. CONCLUSION: Referring to in vitro studies, plant saponins have shown anti-Trypanosoma brucei activity; however, more cytotoxic and in vivo studies and detailed mechanisms of action of the bioactive saponins should be further considered.

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BACKGROUND: Parasitic infections are a public health problem since they have high morbidity and mortality worldwide. In parasitosis such as malaria, leishmaniasis and trypanosomiasis it is necessary to develop new compounds for their treatment since an increase in drug resistance and toxic effects have been observed. Therefore, the use of different compounds that couple vanadium in their structure and that have a broad spectrum against different parasites have been proposed experimentally. OBJECTIVE: Report the mechanisms of action exerted by vanadium in different parasites. CONCLUSION: In this review, some of the targets that vanadium compounds have were identified and it was observed that they have a broad spectrum against different parasites, which represents an advance to continue investigating therapeutic options.

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Cattle trypanosomiasis negatively impacts animal husbandry due to high morbidity, productivity losses, and mortality rates. Knowledge regarding Trypanosoma evansi infections in locally adapted breeds remains limited. Some cattle breeds exhibit trypanotolerance, requiring the determination of prevalence, as well as related tolerance and resistance characteristics, for disease control programs. This study aimed to determine T. evansi prevalence in Crioula Lageana cattle and associate clinical, hematological, and biochemical aspects with the infection to further research on tolerance in this population. Blood samples from 310 Crioula Lageana cattle were tested using Polymerase Chain Reaction (PCR) and Indirect Immunofluorescence Reaction (IIFR). T. evansi prevalence was 8% (24/310) using PCR and 4% (11/310) using IIFR. Positive animals showed increased ruminal movements, elevated eosinophil counts, and reduced monocyte numbers, but both latter within the reference range for the species. Albumin concentrations were low in positive cases and remained below the reference range limit for both groups. However, triglycerides exceeded the physiological range for the species in both positive and negative groups. Increased gamma-glutamyltransferase (GGT) activity was observed in positive animals. In conclusion, Crioula Lageana cattle exhibited enzootic instability with a low T. evansi infection prevalence when assessed using PCR and IIFR techniques. Furthermore, the animals did not display clinical, hematological, or biochemical alterations attributable to the presence of hemoparasites.

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Campeiro horse is a breed locally adapted to the Santa Catarina plateau region and its main characteristic is the gait, it is known as "Marchador das Araucárias." It is a breed considered in danger of extinction, being fundamental the search for the preservation of this important genetic resource. Surra, caused by the protozoan Trypanosoma evansi, is among the diseases that affect horses. However, there are no data on the prevalence of infection in Campeiro horses. This study aimed to determine the prevalence of T. evansi in Campeiro horses, correlate hematology and serum biochemistry, and identify possible risk factors. Blood samples were collected by venipuncture of 214 Campeiro horses, 50 males and 164 females, aged between 3 months and 27 years, from 16 properties located in the States of Santa Catarina, Rio Grande do Sul, and Paraná. An epidemiological questionnaire was carried out with the owners to analyze the associated risk factors. The blood samples were submitted to polymerase chain reaction, immunofluorescence antibody test, complete blood count, and serum biochemistry. The prevalence was 14% of positive animals by polymerase chain reaction and 59% by immunofluorescence antibody test . There was an increase in hematocrit, and in the number of basophils, a decrease in plasmatic fibrinogen, and in the enzymatic activity of alanine aminotransferase, aspartate aminotransferase, and urea, and an increase in creatine phosphokinase and creatinine in positive animals, which is possibly unrelated to the infection. The data obtained through the epidemiological questionnaires showed no difference. Therefore, T. evansi is present in the South of Brazil, with a high prevalence in Campeiro horses.

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Trypanosoma cruzi, the etiologic agent of American trypanosomiasis, is a vector-borne zoonotic parasite which has been little studied regarding its infection in domestic animals. In this study, we evaluated the occurrence of natural infection by T. cruzi in farm animals using molecular markers and phylogenetic analysis in blood clot samples of 60 sheep (Ovis aires), 22 goats (Capra hircus), and 14 horses (Equus caballus) in eight municipalities located in an infection risk area in the state of Rio Grande do Norte (RN), Northeast Region of Brazil. Trypanosoma spp. infection was identified by amplifying the rRNA 18S SSU gene in 48.9% of the samples. The SH022 sample showed 99.8% similarity with the Y strain of T. cruzi in phylogeny, grouped in the DTU II clade. Blood clots of sheep, goats, and horses detected T. cruzi kDNA in 28.3% (17/60), 22.7% (5/22), and 15.4% (2/14) of the samples, respectively. These animals were distributed in the three studied mesoregions throughout the state of RN. The identification of natural infection in domestic animals contributes to expand the epidemiological transmission scenario in an area where T. brasiliensis is the main vector.

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Infections provoked by parasites are among the most prevalent diseases worldwide and generate important health and socioeconomic problems. Despite the enormous amount of work done, the chemotherapy for most of them remains unsolved. Usually, treatments are based on no specific drugs associated, in several cases, with long-term treatments and severe side effects. In addition, drug resistance and different strains' susceptibility are further drawbacks of the existing chemotherapy. Considering that 1,4-dihydropyridines derivatives constitute an important class of compounds for new drug development, we present in this review an in-depth overview of the work done so far on 1,4-dihydropyridines and their antiparasitic activities. The development of new derivatives or the application of known drugs used for other diseases is described in terms of their potential usefulness for drug design.

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Purpose of Review: Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne parasitic neglected tropical disease (NTD) endemic in sub-Saharan Africa. This review aims to enhance our understanding of HAT and provide valuable insights to combat this significant public health issue by synthesizing the latest research and evidence. Recent Findings: HAT has reached a historical < 1000 cases in 2018. In patients without neurologic symptoms and signs, the likelihood of a severe meningoencephalitic stage is deemed low, obviating the need for a lumbar puncture to guide treatment decisions using fexinidazole. Summary: Both forms of the disease, gambiense HAT (gHAT) and rhodesiense HAT (rHAT), have specific epidemiology, risk factors, diagnosis, and treatment. Disease management still requires a high index of suspicion, infectious disease expertise, and specialized medical care. Essential stakeholders in health policy are critical to accomplishing the elimination goals of the NTD roadmap for 2021-2030.

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ABSTRACT Background: We report the presence of Triatoma longipennis for the first time in two localities in Hidalgo, Mexico. Methods: This study was conducted at Tecozautla municipality, Hidalgo. Collection was performed in April 2022. Results: We collected eight triatomines from Guadalupe: two fourth-instar nymphs, three fifth-instar nymphs, one female, and two males. In San Miguel Caltepantla, a female was collected inside a dwelling. One sample tested positive for Trypanosoma cruzi. Conclusions: These findings suggest the need to investigate the dynamics of this species with respect to the inhabitants of the study area.

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A tripanossomíase bovina é causada pelo protozoário Trypanosoma vivax. A transmissão biológica ocorre apenas no continente africano pela mosca Tsé-tsé, de forma mecânica por dípteros hematófagos em todos os continentes, ou pelo compartilhamento de agulhas e por práticas associadas. O estudo teve como objetivo relatar o primeiro diagnóstico parasitológico, sorológico e molecular de T. vivax em bovinos leiteiros provenientes de cinco propriedades do município de Unai, Minas Gerais, Brasil. Cento e quinze animais selecionados por conveniência apresentavam sinais clínicos ou pertenciam a lotes de animais suspeitos. Foram detectados positivos pelos testes parasitológico (técnica de Woo), sorológico (ELISA) e molecular (LAMP). A maior prevalência global para T. vivax foi de 11,11% na propriedade A. O único sinal clínico dos animais positivos estudados foi baixa taxa de concepção. O primeiro diagnóstico de tripanossomíase no noroeste mineiro é extremamente importante, haja vista o tamanho do rebanho leiteiro da região e as possíveis perdas econômicas provocadas pela enfermidade. Ademais, faz-se necessário maior controle sanitário na região, uma vez que a transmissão no Brasil é intimamente ligada às práticas de compartilhamento de agulhas no manejo dos animais e ao parasitismo de moscas hematófagas.

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Chagas disease (CD) is a parasitic zoonosis endemic in Central and South America affecting nearly 10 million people, with 100 million people at high risk of contracting the disease. Treatment is only effective when received at the early stages of the disease and it involved two drugs (nifurtimox (NFX) and benznidazole (BNZ)). Both treatments require multiple daily administrations of high doses, suffer from variable efficacy and insufficient efficacy in chronic CD, many side effects, and a very long duration of treatment that results in poor compliance, while combined available therapies that lead to reduced duration of treatment are not available and polypharmacy reduces compliance and increases the cost further. Here we present self-nanoemulsified drug delivery systems (SNEDDS) able to produce easily scalable combined formulations of NFX and BNZ that can allow for tailoring of the dose and can be easily converted to oral solid dosage form by impregnation on mesoporous silica particles. SNEDDS demonstrated an enhanced solubilisation capacity for both drugs as demonstrated by flow-through studies and in vitro lipolysis studies. High loading of SNEDDS to Syloid 244 and 3050 silicas (2:1 w/w) allowed clinically translatable amounts of both NFX and BNZ to be loaded. Tablets prepared from NFX-BNZ combined SNEDDS loaded on Syloid 3050 silicas demonstration near complete dissolution in the flow through cell apparatus compared to NFX and BNZ commercial tablets respectively (Lampit® and Rochagan®). NFX-BNZ-SNEDDS demonstrated nanomolar efficacy in epimastigotes and amastigotes of T. cruzi with acceptable selectivity indexes and demonstrated enhanced survival and reduced parasitaemia in acute murine experimental models of CD. Thus, the results presented here illustrate the ability for an easily scalable and personalised combination oral therapy prepared from GRAS excipients, enabling treatment access worldwide for the treatment of CD.

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We analyzed epidemiologic characteristics and distribution of 492 deaths related to Chagas disease and coronavirus disease (COVID-19) co-infection in Brazil during March‒December 2020. Cumulative co-infected death rates were highest among advanced age groups, persons of Afro-Brazilian ethnicity and with low education levels, and geographically distributed mainly in major Chagas disease‒endemic areas.

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The main effects of trypanosomosis in Brazil are related to reproductive alterations. In this context, the present study aimed to report the occurrence of abortions in goats and sheeps in the semiarid region of Northeastern Brazil, associated with Trypanosoma vivax. Trypomastigotes forms visualized by Buffy coat technique (BCT) method in 68.7% of the goats and 50.0% of the ewes that aborted. PCR identified that 100% of the goats and ewes that aborted were infected with T. vivax. The goats and ewes that aborted showed high parasitemia and developed clinical signs of trypanosomosis. The presence of T. vivax DNA was identified in the blood of fetuses by the PCR technique, proving infection by T. vivax in aborted fetuses, as well as confirming the congenital transmission of the parasite.

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