Search Results (11)

Chagas disease is a neglected disease caused by the parasite Trypanosoma cruzi, a public health problem in both endemic and non-endemic countries. In Mexico, the southern region is considered endemic, and cases are frequently reported; however, in the northwestern region, only a few cases are confirmed annually. This study describes, for the first time, the Discrete Typing Unit (DTU) of Trypanosoma cruzi in a volunteer blood donor rejected for being reactive in the northwestern region of Mexico. Seroreactivity was confirmed using “in-house” ELISAs which employed three different antigens: total extract from Trypanosoma cruzi isolated from a vector (Triatoma rubida) from Sonora (strain T1), strain H1 and CL-Brener. The molecular characterization of Trypanosoma cruzi was conducted by amplifying satellite DNA by qPCR and posterior sequencing of the mini-exon gene, using Next Generation Sequencing (NGS) to enhance the accuracy of genetic characterization. The results show that the reactive status of this blood donor was confirmed using our in-house ELISAs, and the presence of Trypanosoma cruzi by detecting TcI DTU confirmed the infection status. Full article

Chagas disease, caused by the protozoan Trypanosoma cruzi (T. cruzi), is the most significant neglected tropical disease affecting individuals in the Americas. Currently, available drugs, such as nifurtimox and benznidazole (BZN), are both toxic and ineffective in the chronic phase of the disease. A promising alternative is the development of a Chagas disease vaccine, although this effort is hampered by the complexity of the parasite and HLA polymorphisms. In addition, the activation of epitope-specific CD8⁺ T cells is critical to conferring a robust cell-mediated immune response and protection by producing IFN-γ and perforin. Thus, the antigen (s) for the development of a Chagas vaccine or immunotherapy must include CD8⁺ T cell epitopes. In this study, we aimed to develop a multi-epitope recombinant protein as a novel human vaccine for Chagas disease. Sixteen database programs were used to predict de novo 40 potential epitopes for the HLA-A*02:01 allele. Nine out of the 40 predicted epitopes were able to elicit IFN-γ production in Peripheral Blood Mononuclear Cells (PBMCs) from Chagas patients. Molecular docking revealed a good binding affinity among the epitopes with diverse HLA molecules. Therefore, a recombinant multi-epitope protein including these nine T. cruzi CD8⁺ epitopes was expressed and demonstrated to recall an antigen-specific immune response in ex-vivo assays using PBMCs from Chagas patients with the HLA-A*02 allele. These findings support the development of this multi-epitope protein as a promising candidate human vaccine against Chagas disease. Full article

Chagas disease is a public health problem in the Americas, from the southern United States (USA) to Argentina. In the USA, less than 1% of domestic cases have been identified and less than 0.3% of total cases have received treatment. Little is known about affected immigrant Latin American communities. A prospective study was conducted to assess knowledge about Chagas disease among the Latin American community living in the Greater New Orleans area. Participants answered a baseline questionnaire, viewed a short educational video presentation, completed a post-presentation questionnaire, and were screened with an FDA-approved blood rapid diagnostic test (RDT). A total of 154 participants from 18 Latin American countries (n = 138) and the USA (n = 16) were enrolled and screened for Trypanosoma cruzi infection. At baseline, 57% of the participants knew that Chagas disease is transmitted through an insect vector, and 26% recognized images of the vector. Following the administration of an educational intervention, the participants’ knowledge regarding vector transmission increased to 91% and 35% of participants were able to successfully identify images of the vector. Five participants screened positive for T. cruzi infection, indicating a 3.24% [95%CI: 1.1–7.5%] prevalence of Trypanosoma cruzi infection within the Latin American community of the New Orleans area. Results highlight the urgent need for improving access to education and diagnostics of Chagas disease. Full article

Chagas disease, caused by the protozoa parasite Trypanosoma cruzi, is an anthropozoonosis that represents a major public health problem in the Americas, affecting 7 million people with at least 65 million at risk. We sought to assess the intensity of disease surveillance based on diagnostic test requests from hospitals in New Orleans, Louisiana. We extracted information from send-out labs at two major tertiary academic hospitals in New Orleans, Louisiana, USA, from 1 January 2018 to 1 December 2020. We found that in these three years there were 27 patients for whom Chagas disease testing was ordered. Most of these patients were male (70%), with a median age of 40 years old, and their most common ethnical background was Hispanic (74%). These findings demonstrate undertesting of this neglected disease in our region. Given the low Chagas disease surveillance, we need to increase awareness, health promotion, and education among healthcare workers. Full article

The operation of many nuclear pressurized water reactors is being extended beyond their design lifetime limit. From the perspective of possible further lifetime extension, safety requirements are a priority. Therefore, the quantification of the neutron irradiation embrittlement of the reactor pressure vessel (RPV) is an important issue, as this is a guiding parameter that influences the reactor lifetime. In this context, the Institut de Radioprotection et de Sûreté Nucléaire developed a calculation scheme for the analysis of RPV aging under neutron irradiation, named VACS (vessel aging calculation scheme). VACS couples a deterministic approach (CASMO5 and SIMULATE5) to evaluate the full-core fission neutron source term and a Monte Carlo modeling (MCNP6) approach to model the neutron attenuation from the core to sites of interest (RPV, surveillance capsules, etc.). To ensure the reliability of aging predictions, this paper describes a detailed analysis of the neutron H.B. Robinson-2 reactor pressure vessel dosimetry benchmark. The results indicate that VACS shows satisfactory accuracy when the ENDF-B/VII.1 or JEFF-3.3 nuclear data libraries are used in the attenuation calculation. However, the use of ENDF-B/VIII.0 leads to significantly worse results. Full article

Fluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p < 0.001) and DC (19.4% vs. 5.8%, p < 0.001) than CAPCT and reduced the time for diagnosis in patients (3.8 vs. 17.6 months, p = 0.02). Arthralgia (OR 4.90, p = 0.0012), DO of PET/CT (OR 4.09, p = 0.016), CRP > 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis. Full article

While the diagnosis of adult-onset Still’s disease (AOSD) involves the exclusion of differential diagnoses, the characteristics and value of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography coupled with CT (PET/CT) in the management of AOSD remain poorly known. Our retrospective study included patients from four centers, fulfilling Yamaguchi or Fautrel criteria, who underwent a PET/CT during an active AOSD. Thirty-five patients were included. At the time of PET/CT, the Yamaguchi criteria were met in 23 of 29 evaluable cases. PET/CT showed bone marrow (74.3%), lymph node (74.3%), and splenic (48.6%) FDG uptake. Despite arthralgia or arthritis in most patients, joints were rarely the sites of 18F-FDG accumulation. The spatial distribution of 18F-FDG uptake was nonspecific, and its intensity could be similar to malignant disease. Lymph node or bone marrow biopsy was performed after PET/CT in 20 patients (57.1%). The intensity of bone marrow; splenic and lymph node hypermetabolism appeared to be correlated with disease activity. Abnormal PET/CT in the cervical lymph nodes and age ≥ 60 years seemed to be predictive factors for monocyclic evolution. The clinical value of PET/CT is not in direct diagnosis; but as an aid in excluding differential diagnoses by searching for their scintigraphic features and guiding biopsy. Full article

Chagas disease is an important vector-borne neglected tropical disease that causes great health and economic losses. The etiological agent, Trypanosoma cruzi, is a protozoan parasite endemic to the Americas, comprised by important diversity, which has been suggested to contribute to poor serological diagnostic performance. Current nomenclature describes seven discrete typing units (DTUs), or lineages. We performed the first large scale analysis of T. cruzi diversity among 52 previously published genomes from strains covering multiple countries and parasite DTUs and assessed how different markers summarize this genetic diversity. We also examined how seven antigens currently used in commercial serologic tests are conserved across this diversity of strains. DTU structuration was confirmed at the whole-genome level, with evidence of sub-DTU diversity, associated in part to geographic structuring. We observed very comparable phylogenetic tree topographies for most of the 32 markers investigated, with clear clustering of sequences by DTU, and a few of these markers suggested some degree of intra-lineage diversity. At least three of the currently used antigens represent poorly conserved sequences, with sequences used in tests quite divergent from sequences in many strains. Most markers are well suited for estimating parasite diversity to DTU level, and a few are particularly well-suited to assess intra-DTU diversity. Analysis of antigen sequences across all strains indicates that antigenic diversity is a likely explanation for limited diagnostic performance in Central and North America. Full article

Infections with SARS-CoV-2 can progress toward multiple clinical outcomes, and the identification of factors associated with disease severity would represent a major advance to guide care and improve prognosis. We tested for associations between SARS-CoV-2 genomic variants from an international cohort of 2508 patients and mortality rates. Findings were validated in a second cohort. Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality. Three SNPs remained associated with mortality in a generalized linear model (GLM) that also included patient age, sex, geographic region, and month of sample collection. Multiple SNPs were confirmed in the validation cohort. These SNPs represent targets to assess the mechanisms underlying COVID-19 disease severity and warrant straightforward validation in functional studies. Full article

Chagas disease is a major neglected tropical disease, transmitted predominantly by triatomine insect vectors, but also through congenital and oral routes. While endemic in the Americas, it has turned into a global disease. Because of the current drug treatment limitations, a vaccine would represent a major advancement for better control of the disease. Here, we review some of the rationale, advances, and challenges for the ongoing development of a vaccine against Chagas disease. Recent pre-clinical studies in murine models have further expanded (i) the range of vaccine platforms and formulations tested; (ii) our understanding of the immune correlates for protection; and (iii) the extent of vaccine effects on cardiac function, beyond survival and parasite burden. We further discuss outstanding issues and opportunities to move Chagas disease development forward in the near future. Full article

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations. Full article