Low Annexin A1 level in HTLV-1 infected patients is a potential biomarker for the clinical progression and diagnosis of HAM/TSP.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients. METHODS: This study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: ANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000). CONCLUSIONS: Our results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.

Andexanet Alfa versus Four-Factor Prothrombin Complex Concentrate for the Reversal of Factor Xa (FXa) Inhibitor-Associated Intracranial Hemorrhage: A Systematic Review of Retrospective Studies.

Background/Objectives: There are limited data on the risks and benefits of using Andexanet alfa (AA) compared with four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitor-associated intracranial hemorrhage (ICH). Our aim was to describe a compilation of the information available in the literature to date. Methods: PubMed, Embase, Web of Science (Clarivate Analytics) and the Cochrane Central Register of Controlled Trials were searched until December 2023. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review included studies that were retrospective in design and evaluated both drugs to control bleeding and complications (death and thromboembolic events). Two researchers re-examined the studies for relevance, extracted the data and assessed the risk of bias. No meta-analyses were performed for the results. Results: In this limited patient sample, we found no differences between published articles in terms of neuroimaging stability or thrombotic events. However, some studies show significant differences in mortality, suggesting that one of the AAs may be superior to 4F-PCC. Conclusions: Our qualitative analysis shows that AA has a better efficacy profile compared with 4F-PCC. However, further studies monitoring these patients and a multicenter collaborative network dedicated to this topic are needed.

A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses.

A third vaccine dose is often required to achieve potent, long-lasting immune responses. We investigated the effect of three 8-µg doses of CVnCoV, CureVac's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate containing sequence-optimized unmodified mRNA encoding the spike (S) glycoprotein, administered at 0, 4, and 28 weeks, on immune responses in rhesus macaques. After the third dose, S-specific binding and neutralizing antibodies increased 50-fold compared with post-dose 2 levels, with increased responses also evident in the lower airways and against the SARS-CoV-2 B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) variants. Enhanced binding affinity of serum antibodies after the third dose correlated with higher somatic hypermutation in S-specific B cells, corresponding with improved binding properties of monoclonal antibodies expressed from isolated B cells. Administration of low-dose mRNA led to fewer cells expressing antigen in vivo at the injection site and in the draining lymph nodes compared with a 10-fold higher dose, possibly reducing engagement of precursor cells with the antigen and resulting in the suboptimal response observed after two-dose vaccination schedules in phase IIb/III clinical trials of CVnCoV. However, when immune memory is established, a third dose efficiently boosts the immunological responses and improves antibody affinity and breadth.

Spatio-temporal analysis of leptospirosis in Eastern Amazon, State of Pará, Brazil.

INTRODUCTION: Brazil has registered more than 62,000 confirmed cases of leptospirosis between 2001 and 2017, with more than 2,000 cases confirmed in the State of Pará. Despite a large number of cases, no study has been conducted to trace the spatio-temporal profile of the disease. METHODOLOGY: Confirmed cases of leptospirosis from 2001 to 2017 from the state of Pará were the basis for this space-time study. The database of the Department of Informatics of the Ministry of Health was used to access data on leptospirosis. The spatio-temporal analysis was performed in the SaTScan software for the detection of clusters, and maps were generated in the QGIS software. RESULTS: The municipalities of Belém and Santarém were among the ones with the highest incidence rates of leptospirosis for the whole study period. Increased number of cases in Soure, Inhangapi, São João da Ponta and Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal, and São Domingos do Capim were identified in different time periods. Santarém and Belém are the main foci of leptospirosis because they are the most urbanized and densely populated municipalities in the State. The cases found in smaller municipalities may be associated with periods of more frequent rainfall and circulation of Leptospira sp. in marsupials and cattle, in the northeastern part of the State. CONCLUSION: Further studies are needed to help identify the risk factors that contribute to the occurrence of leptospirosis in the State of Pará, particularly in areas with lower population density.

Spatio-temporal analysis of leptospirosis in Eastern Amazon, State of Pará, Brazil / Análise espaço-temporal da leptospirose na Amazônia Oriental, Estado do Pará, Brasil

ABSTRACT: Introduction: Brazil has registered more than 62,000 confirmed cases of leptospirosis between 2001 and 2017, with more than 2,000 cases confirmed in the State of Pará. Despite a large number of cases, no study has been conducted to trace the spatio-temporal profile of the disease. Methodology: Confirmed cases of leptospirosis from 2001 to 2017 from the state of Pará were the basis for this space-time study. The database of the Department of Informatics of the Ministry of Health was used to access data on leptospirosis. The spatio-temporal analysis was performed in the SaTScan software for the detection of clusters, and maps were generated in the QGIS software. Results: The municipalities of Belém and Santarém were among the ones with the highest incidence rates of leptospirosis for the whole study period. Increased number of cases in Soure, Inhangapi, São João da Ponta and Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal, and São Domingos do Capim were identified in different time periods. Santarém and Belém are the main foci of leptospirosis because they are the most urbanized and densely populated municipalities in the State. The cases found in smaller municipalities may be associated with periods of more frequent rainfall and circulation of Leptospira sp. in marsupials and cattle, in the northeastern part of the State. Conclusion: Further studies are needed to help identify the risk factors that contribute to the occurrence of leptospirosis in the State of Pará, particularly in areas with lower population density.

RESUMO: Introdução: O Brasil registrou mais de 62 mil casos de leptospirose confirmados entre 2001 e 2017, com mais de 2.000 casos confirmados no estado do Pará. Apesar da grande quantidade de casos, nenhum estudo até este momento traçou o perfil espaço-temporal da doença. Metodologia: Este é um estudo espaço-temporal com base nos casos confirmados de leptospirose entre 2001 a 2017 no estado do Pará. O banco de dados do Departamento de Informática do Ministério da Saúde foi utilizado para acessar os dados de leptospirose. A análise espaço-temporal foi realizada no software SaTScan para detecção de clusters e os mapas foram gerados no software QGIS. Resultados: O município de Belém e Santarém se mantiveram entre as maiores taxas de incidência de leptospirose durante todo o período estudado. O aumento no número de casos em Soure, Inhangapi, São João da Ponta e Magalhães Barata, Ponta de Pedras, Breves, Bragança, Castanhal e São Domingos do Capim foram identificados em diferentes períodos. Santarém e Belém são os principais focos de leptospirose por serem os municípios mais urbanizados e com maior densidade populacional do estado. Os casos observados em municípios menores podem estar associados a períodos de maior pluviosidade e circulação de Leptospira sp. em marsupiais e em gado no nordeste do estado. Conclusão: Com o exposto, torna-se necessário mais estudos visando o conhecimento dos fatores que contribuem com a ocorrência da leptospirose no estado do Pará, particularmente em áreas com menor adensamento populacional.