Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Biodemes of Trypanosoma cruzi strains isolated from humans from three endemic areas in Minas Gerais State

Submitted by Sandra Infurna ([email protected]) on 2019-07-11T16:38:43Z No. of bitstreams: 1 XimenaIlarremendi_OctavioFernandes_etal_IOC_2002.pdf: 82679 bytes, checksum: 1b4cacc244096703581e44ae7ec27622 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-07-11T16:50:17Z (GMT) No. of bitstreams: 1 XimenaIlarremendi_OctavioFernandes_etal_IOC_2002.pdf: 82679 bytes, checksum: 1b4cacc244096703581e44ae7ec27622 (MD5)Made available in DSpace on 2019-07-11T16:50:17Z (GMT). No. of bitstreams: 1 XimenaIlarremendi_OctavioFernandes_etal_IOC_2002.pdf: 82679 bytes, checksum: 1b4cacc244096703581e44ae7ec27622 (MD5) Previous issue date: 2002Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Rio de Janeiro, RJ. Brasil / Universidad de Oriente. Escuela de Medicina. Departamento de Parasitología y Microbiología. Ciudad Bolivar, Venezuela.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Bioquímica e Biologia Molecular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Rio de Janeiro, RJ. Brasil / Universidade do Estado do Rio de Janeiro. Departamento de Patologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Medicina Tropical. Rio de Janeiro, RJ. Brasil.Com o objetivo de estudar o comportamento biológico de cepas do T. cruzi e determinar a possível relação entre o biodema da cepa e as formas clínicas da doença de Chagas, 14 cepas do protozoário isoladas de humanos, procedentes de Pains, Iguatama e Berilo, foram avaliadas. Para estudar o comportamento biológico das cepas, grupos de camundongos albinos suíços, machos, pesando entre 10-15 gramas foram infectados com 1x104 tripomastigotas sangüíneos para avaliação da infectividade, parasitemia, morfologia dos tripomastigotas sangüíneos, virulência e distribuição do protozoário nos tecidos. Nove cepas apresentaram comportamento similar ao da cepa São Felipe do biodema II e cinco se caracterizaram como pertencentes ao biodema III. Não foi possível estabelecer uma relação entre o biodema da cepa e gravidade da doença nos pacientes.In order to study the biological behavior of T. cruzi strains and to determine a putative association between their biodeme and the clinical forms of Chagas disease, 14 strains isolated from humans were evaluated. The individuals were from the municipalities of Pains, Iguatama and Berilo (Minas Gerais State). The biological behavior was evaluated in albino swiss mice, weighing 10 to 15 grams, which were infected with 1x104 blood tripomastigotes. The infectivity, parasitemia, tripomastigote morphology, virulence and the tissue distribution of the protozoan were analyzed. A behavior similar to biodeme II (São Felipe strain) was observed in 9 strains, while 5 stocks were characterized as belonging to biodeme III. It was not possible to establish a relationship between the biodeme strain and the severity of the disease in the patients

Epidemiology and control of malaria in Colombia

Malaria is currently one of the most serious public health problems in Colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. Plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to Plasmodium falciparum. A limited number of severe and complicated cases have resulted in mortality, which is a downward trend that has been maintained over the last few years. More than 90% of the malaria cases in Colombia are confined to 70 municipalities (about 7% of the total municipalities of Colombia), with high predominance (85%) in rural areas. The purpose of this paper is to review the progress of malaria-eradication activities and control measures over the past century within the eco-epidemiologic context of malaria transmission together with official consolidated morbidity and mortality reports. This review may contribute to the formulation of new antimalarial strategies and policies intended to achieve malaria elimination/eradication in Colombia and in the region

A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention

The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, primarily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease