Oseltamivir-resistant influenza A(H1N1)pdm2009 strains found in Brazil are endowed with permissive mutations, which compensate the loss of fitness imposed by antiviral resistance

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future

Inframalleolar Bypass Grafts for Limb Salvage

AbstractObjectiveTo report our experience of long-term results of inframalleolar bypass.DesignRetrospective analysis.Materials and methodsWe analysed 122 inframalleolar bypasses performed between January 1991 and June 2005 in 116 patients. Most patients were treated for critical ischaemia (97%). The indication for the use of podalic arteries was a lack of tibial arteries with run-off to the foot. The dorsalis pedis was predominantly used for distal anastomoses (62.3%) and the greater saphenous vein (84.4%) as the conduit. The follow-up periods ranged from 1 to 60 months. The endpoints analysed were graft patency, limb salvage, preservation of deambulation and survival rate.ResultsThe cumulative patency was 58.2% at 3 years and 53.4% at 5 years. The best results were achieved with the devalvulated greater saphenous veins. Limb salvage was 70.0% at 3 years and 50.4% at 5 years, with preserved deambulation rates of 57.3% and 47.1%, respectively. There were 36 major and 45 minor amputations. At 3 years, the survival rate was 50.2% and the surgical mortality 13%. Female sex was associated with worse results for cumulative patency and limb salvage (P<0.01).ConclusionsIn the long term, inframalleolar bypass is a satisfactory option for limb salvage

Pathology and one health implications of fatal Leptospira interrogansinfection in an urbanized, free-ranging, black-tufted marmoset (Callithrix penicillata) in Brazil

Leptospirosis is a zoonotic neglected disease of worldwide public health concern. Lep tospira species can infect a wide range of wild and domestic mammals and lead to a spectrum of disease, including severe and fatal forms. Herein, we report for the first time a fatal Leptospira interrogansinfection in a free-ranging nonhuman primate (NHP), a black-tufted marmoset. Icterus, pulmonary haemorrhage, interstitial nephritis, and hepatocellular dissociation were the main findings raising the suspicion of leptospiro sis. Diagnostic confirmation was based on specific immunohistochemical and PCR assays for Leptospira species. Immunolocalization of leptospiral antigens and identifi cation of pathogenic species (L. interrogans species) were important for better under standing the pathogenesis of the disease. One Health–related implications of free ranging NHPs in anthropized areas and transmission dynamics of human and animal leptospirosis are discussed.Faculdade de Agronomia e Medicina Veterinária (FAV)Programa de Pós-Graduação em Ciências Animai

Cancer inpatients with COVID-19: A report from the Brazilian National Cancer Institute.

ObjectiveThis study aimed to describe the demographic and clinical characteristics of cancer inpatients with COVID-19 exploring clinical outcomes.MethodsA retrospective search in the electronic medical records of cancer inpatients admitted to the Brazilian National Cancer Institute from April 30, 2020 to May 26, 2020 granted identification of 181 patients with COVID-19 confirmed by RT-PCR.ResultsThe mean age was 55.3 years (SD ± 21.1). Comorbidities were present in 110 (60.8%) cases. The most prevalent solid tumors were breast (40 [22.1%]), gastrointestinal (24 [13.3%]), and gynecological (22 [12.2%]). Among hematological malignancies, lymphoma (20 [11%]) and leukemia (10 [5.5%]) predominated. Metastatic disease accounted for 90 (49.7%) cases. In total, 63 (34.8%) had recently received cytotoxic chemotherapy. The most common complications were respiratory failure (70 [38.7%]), septic shock (40 [22.1%]) and acute kidney injury (33 [18.2%]). A total of 60 (33.1%) patients died due to COVID-19 complications. For solid tumors, the COVID-19-specific mortality rate was 37.7% (52 out of 138 patients) and for hematological malignancies, 23.5% (8 out of 34). According to the univariate analysis COVID-19-specific mortality was significantly associated with age over 75 years (P = .002), metastatic cancer (p ConclusionThis is the first Brazilian cohort of cancer patients with COVID-19. The rates of complications and COVID-19-specific death were significantly high

International forum on management of blood donors with culture-positive platelet donations : summary

Bacterial contamination of platelets (Plts) stored at room temperature represents the highest risk for infection and fatality of any transfusable blood component. Contamination mitigation procedures include optimization of arm disinfection, sample diversion of initially collected blood, shorter dating or pathogen inactivation to avoid or prevent log-phase bacterial growth as well as detection of bacteria through immunoassay for bacterial antigens, assays for bacterial metabolic activity or bacterial culture. Point-of-care assays are operationally challenging for transfusion services, which often prefer that the blood collection establishments (BCEs) employ enhanced culture strategies or provide pathogen-reduced Plt products. The aim of this International Forum was to understand not only how Plt bacterial culture strategies are being employed by blood collectors internationally but, more specifically, how culture results impact donor management and ongoing donation eligibility. Using a proposed consensus definition of bottle and unit culture results following an automated sample incubator alarm, we desired to catalogue BCE procedures and donor work-ups as well as evaluation strategies for various scenarios, ranging from machine false-positive alarms to potentially bacteremic blood donors

Case report : urbanized non-human primates as sentinels for human zoonotic diseases : a case of acute fatal toxoplasmosis in a free-ranging marmoset in coinfection with yellow fever virus

Free-ranging non-human primates (NHP) can live in anthropized areas or urban environments in close contact with human populations. This condition can enable the emergence and transmission of high-impact zoonotic pathogens. For the first time, we detected a coinfection of the yellow fever (YF) virus with Toxoplasma gondii in a free-ranging NHP in a highly urbanized area of a metropolis in Brazil. Specifically, we observed this coinfection in a black-tufted marmoset found dead and taken for a necropsy by the local health surveillance service. After conducting an epidemiological investigation, characterizing the pathological features, and performing molecular assays, we confirmed that the marmoset developed an acute fatal infection caused by T. gondii in coinfection with a new YF virus South American-1 sub-lineage. As a result, we have raised concerns about the public health implications of these findings and discussed the importance of diagnosis and surveillance of zoonotic agents in urbanized NHPs. As competent hosts of zoonotic diseases such as YF and environmental sentinels for toxoplasmosis, NHPs play a crucial role in the One Health framework to predict and prevent the emergence of dangerous human pathogens.Faculdade de Agronomia e Medicina Veterinária (FAV)Programa de Pós-Graduação em Ciências Animai

West Nile virus in Brazil

Background: West Nile virus (WNV) was first sequenced in Brazil in 2019, when it was isolated from a horse in the Espírito Santo state. Despite multiple studies reporting serological evidence suggestive of past circulation since 2004, WNV remains a low priority for surveillance and public health, such that much is still unknown about its genomic diversity, evolution, and transmission in the country. Methods: A combination of diagnostic assays, nanopore sequencing, phylogenetic inference, and epidemiological modeling are here used to provide a holistic overview of what is known about WNV in Brazil. Results: We report new genetic evidence of WNV circulation in southern (Minas Gerais, São Paulo) and northeastern (Piauí) states isolated from equine red blood cells. A novel, climate-informed theoretical perspective of the potential transmission of WNV across the country highlights the state of Piauí as particularly relevant for WNV epidemiology in Brazil, although it does not reject possible circulation in other states. Conclusion: Our output demonstrates the scarceness of existing data, and that although there is sufficient evidence for the circulation and persistence of the virus, much is still unknown on its local evolution, epidemiology, and activity. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics with spill-over potential to humans