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1.
J Knee Surg ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38830606

RESUMO

Periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) is a severe complication causing a significant burden. The study aims were to establish the epidemiology of microorganisms in TKA PJI, the rate of persistent infection requiring further surgery, and the risk factors for this. Microbiological specimens between June 2002 and March 2017 at five regional hospital sites were identified with revision TKA procedures in the National Joint Replacement Registry. The time between procedures, type of revision strategy, and any subsequent further revision operations were collected. At minimum 2-year follow-up, 174 revision TKA were identified, with a mean patient age of 69 ± 11 years. A broad range of pathogens were identified. Fifty cases (29%) had persistent infection requiring at least one further operative procedure, 13 cases required 3 or more. Coagulase-negative Staphylococcus species (CNS) was seen most with failed surgery, polymicrobial infections also posing a significant risk factor. The best chance of a successful PJI surgical strategy was < 12 months from primary TKA, with the greatest risk between 3 and 5 years (p < 0.05). Younger age significantly increased the risk of further surgery (p < 0.05). Management varied; 103 (59%) debridement, antibiotic therapy and implant retention, with further surgery in 29%; 45 (17%) single-stage revision, with further surgery in 13%; and 26 (15%) two-stage revision, with further surgery in 12%. This study presents the most common causative pathogens for PJI in TKA, and the high rate of persistent infection after initial revision surgery. Risk factors for persistent infection and further revision surgery were polymicrobial and CNS infections, patients who presented between 3 and 5 years following primary TKA, and younger age. This study therefore raises important risk factors and areas for future research to reduce the burden of multiple operations after PJI.

2.
Am J Trop Med Hyg ; 110(1): 87-89, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37983904

RESUMO

We describe the successful management of Ancaliia Algerae microsporidial keratitis in an immunosuppressed 54-year-old woman with refractory linear IgA disease. The case highlights the challenges in diagnosis and management of this infection in immunocompromised individuals and emphasizes the usefulness of in vivo confocal microscopy as a novel, noninvasive tool to aid in the diagnosis and monitoring of microsporidial keratitis. We also discuss the possible mode of acquisition of this rare infection.


Assuntos
Infecções Oculares Fúngicas , Ceratite , Feminino , Humanos , Pessoa de Meia-Idade , New South Wales , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Austrália , Microscopia Confocal , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico
3.
Microorganisms ; 11(8)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37630545

RESUMO

Serological diagnostic assays are essential tools for determining an individual's protection against viruses like SARS-CoV-2, tracking the spread of the virus in the community, and evaluating population immunity. To assess the diversity and quality of the anti-SARS-CoV-2 antibody response, we have compared the antibody profiles of people with mild, moderate, and severe COVID-19 using a dot blot assay. The test targeted the four major structural proteins of SARS-CoV-2, namely the nucleocapsid (N), spike (S) protein domains S1 and S2, and receptor-binding domain (RBD). Serum samples were collected from 63 participants at various time points for up to 300 days after disease onset. The dot blot assay revealed patient-specific differences in the anti-SARS-CoV-2 antibody profiles. Out of the 63 participants with confirmed SARS-CoV-2 infections and clinical COVID-19, 35/63 participants exhibited diverse and robust responses against the tested antigens, while 14/63 participants displayed either limited responses to a subset of antigens or no detectable antibody response to any of the antigens. Anti-N-specific antibody levels decreased within 300 days after disease onset, whereas anti-S-specific antibodies persisted. The dynamics of the antibody response did not change during the test period, indicating stable antibody profiles. Among the participants, 28/63 patients with restricted anti-S antibody profiles or undetectable anti-S antibody levels in the dot blot assay also exhibited weak neutralization activity, as measured by a surrogate virus neutralization test (sVNT) and a microneutralization test. These results indicate that in some cases, natural infections do not lead to the production of neutralizing antibodies. Furthermore, the study revealed significant serological variability among patients, regardless of the severity of their COVID-19 illness. These differences need to be carefully considered when evaluating the protective antibody status of individuals who have experienced primary SARS-CoV-2 infections.

4.
Nat Commun ; 14(1): 687, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755042

RESUMO

Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Animais , Camundongos , Anticorpos Amplamente Neutralizantes , Leucócitos Mononucleares , Anticorpos Antivirais , Anticorpos Monoclonais , Anticorpos Neutralizantes , Epitopos , Glicoproteína da Espícula de Coronavírus/genética , Testes de Neutralização
5.
Immunol Cell Biol ; 101(2): 142-155, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36353774

RESUMO

The long-term health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still being understood. The molecular and phenotypic properties of SARS-CoV-2 antigen-specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen-specific memory B-cell (MBC) population has not yet been analyzed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe coronavirus disease 2019 (COVID-19). Here, we performed single-cell molecular analysis of the SARS-CoV-2 receptor-binding domain (RBD)-specific MBC population in three patients after severe COVID-19 and four patients after mild/moderate COVID-19. We analyzed the transcriptomic and B-cell receptor repertoire profiles at ~2 months and ~4 months after symptom onset. Transcriptomic analysis revealed a higher level of tumor necrosis factor-alpha (TNF-α) signaling via nuclear factor-kappa B in the severe group, involving CD80, FOS, CD83 and TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80hi TNFAIP3hi and CD11chi CD95hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long-term RBD-specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID-19 severity.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Células B de Memória , Convalescença , Anticorpos Antivirais
6.
NEJM Evid ; 2(2): EVIDoa2200293, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38320033

RESUMO

BACKGROUND: Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS: In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS: Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n=1273; Australia and New Zealand, n=138; and Nepal, n=115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio<1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS: In hospitalized non­critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions. (Funded by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants and others; ClinicalTrials.gov number, NCT04483960.)


Assuntos
COVID-19 , Humanos , Anticoagulantes/farmacologia , Coagulação Sanguínea , Aspirina/farmacologia
7.
NEJM Evid ; 2(11): EVIDoa2300132, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38320527

RESUMO

BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Guanidinas/farmacologia , Benzamidinas
8.
J Immunol ; 209(8): 1499-1512, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36165172

RESUMO

Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and role remain to be fully elucidated. In this study of 62 acute and convalescent patients, we found that patients with acute coronavirus disease 2019 can mount a phagocytic response to autologous plasma-opsonized Spike protein-coated microbeads as early as 10 d after symptom onset, while heat inactivation of this plasma caused 77-95% abrogation of the phagocytic response and preblocking of Fc receptors showed variable 18-60% inhibition. In convalescent patients, phagocytic response significantly correlated with anti-Spike IgG titers and older patients, while patients with severe disease had significantly higher phagocytosis and neutralization functions compared with patients with asymptomatic, mild, or moderate disease. A longitudinal subset of the convalescent patients over 12 mo showed an increase in plasma Ab affinity toward Spike Ag and preservation of phagocytic and neutralization functions, despite a decline in the anti-Spike IgG titers by >90%. Our data suggest that early phagocytosis is primarily driven by heat-liable components of the plasma, such as activated complements, while anti-Spike IgG titers account for the majority of observed phagocytosis at convalescence. Longitudinally, a significant increase in the affinity of the anti-Spike Abs was observed that correlated with the maintenance of both the phagocytic and neutralization functions, suggesting an improvement in the quality of the Abs.


Assuntos
COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , Antivirais , Humanos , Imunoglobulina G , Receptores Fc , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
10.
Cell Rep ; 38(6): 110345, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35090598

RESUMO

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%-76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection.


Assuntos
Anticorpos Amplamente Neutralizantes/metabolismo , Células B de Memória/metabolismo , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Austrália , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , COVID-19/imunologia , Estudos de Coortes , Feminino , Humanos , Imunidade/imunologia , Imunidade Humoral/imunologia , Masculino , Células B de Memória/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Open Heart ; 8(2)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34876491

RESUMO

OBJECTIVE: To assess whether hypertension is an independent risk factor for mortality among patients hospitalised with COVID-19, and to evaluate the impact of ACE inhibitor and angiotensin receptor blocker (ARB) use on mortality in patients with a background of hypertension. METHOD: This observational cohort study included all index hospitalisations with laboratory-proven COVID-19 aged ≥18 years across 21 Australian hospitals. Patients with suspected, but not laboratory-proven COVID-19, were excluded. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs. RESULTS: 546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (adjusted OR (aOR) 1.09, 95% CI 1.07 to 1.12, p<0.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13 to 6.53, p=0.026), chronic kidney disease (aOR 2.33, 95% CI 1.02 to 5.32, p=0.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06 to 4.85, p=0.035). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48 to 1.77, p=0.81). Among patients with hypertension, ACE inhibitor (aOR 1.37, 95% CI 0.61 to 3.08, p=0.61) and ARB (aOR 0.64, 95% CI 0.27 to 1.49, p=0.30) use was not associated with mortality. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.


Assuntos
COVID-19/mortalidade , Mortalidade Hospitalar , Hospitalização , Hipertensão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Austrália/epidemiologia , COVID-19/diagnóstico , COVID-19/terapia , Comorbidade , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo
12.
Heart Lung Circ ; 30(12): 1834-1840, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34481762

RESUMO

OBJECTIVES: Describe the incidence of cardiac complications in patients admitted to hospital with COVID-19 in Australia. DESIGN: Observational cohort study. SETTING: Twenty-one (21) Australian hospitals. PARTICIPANTS: Consecutive patients aged ≥18 years admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MAIN OUTCOME MEASURES: Incidence of cardiac complications. RESULTS: Six-hundred-and-forty-four (644) hospitalised patients (62.5±20.1 yo, 51.1% male) with COVID-19 were enrolled in the study. Overall in-hospital mortality was 14.3%. Twenty (20) (3.6%) patients developed new atrial fibrillation or flutter during admission and 9 (1.6%) patients were diagnosed with new heart failure or cardiomyopathy. Three (3) (0.5%) patients developed high grade atrioventricular (AV) block. Two (2) (0.3%) patients were clinically diagnosed with pericarditis or myopericarditis. Among the 295 (45.8%) patients with at least one troponin measurement, 99 (33.6%) had a peak troponin above the upper limit of normal (ULN). In-hospital mortality was higher in patients with raised troponin (32.3% vs 6.1%, p<0.001). New onset atrial fibrillation or flutter (6.4% vs 1.0%, p=0.001) and troponin elevation above the ULN (50.3% vs 16.4%, p<0.001) were more common in patients 65 years and older. There was no significant difference in the rate of cardiac complications between males and females. CONCLUSIONS: Among patients with COVID-19 requiring hospitalisation in Australia, troponin elevation was common but clinical cardiac sequelae were uncommon. The incidence of atrial arrhythmias and troponin elevation was greatest in patients 65 years and older.


Assuntos
Fibrilação Atrial , COVID-19 , Pericardite , Adolescente , Adulto , Fibrilação Atrial/epidemiologia , Austrália/epidemiologia , Feminino , Humanos , Masculino , SARS-CoV-2
13.
Cell Rep Med ; 2(4): 100228, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33748788

RESUMO

Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort's neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire.


Assuntos
Anticorpos Neutralizantes/sangue , COVID-19/patologia , Células B de Memória/metabolismo , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Doenças Assintomáticas , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Domínios Proteicos/imunologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Fatores de Tempo , Adulto Jovem
14.
Open Forum Infect Dis ; 7(5): ofaa158, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32500091

RESUMO

Whole-genome sequencing clustered Australian Candida auris isolates from sporadic cases within clade III. Case isolates were genomically distinct; however, unexpectedly, those from 1 case comprised 2 groups separated by >60 single nucleotide polymorphisms (SNPs) with no isolate being identical, in contrast to outbreaks where isolates from any 1 individual have differed by <3 SNPs. Multidrug resistance was absent. High within-host genetic heterogeneity should be considered when investigating C. auris infections.

15.
Case Rep Vet Med ; 2020: 9785861, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015929

RESUMO

We describe three cases of osteoarticular infection (OAI) in young thoroughbred horses in which the causative organism was identified by MALDI-TOF as Kingella species. The pattern of OAI resembled that reported with Kingella infection in humans. Analysis by 16S rRNA PCR enabled construction of a phylogenetic tree that placed the isolates closer to Simonsiella and Alysiella species, rather than Kingella species. Average nucleotide identity (ANI) comparison between the new isolate and Kingella kingae and Alysiella crassa however revealed low probability that the new isolate belonged to either of these species. This preliminary analysis suggests the organism isolated is a previously unrecognised species.

16.
J Antimicrob Chemother ; 75(5): 1112-1116, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32016400

RESUMO

BACKGROUND: Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45. OBJECTIVES: To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia. METHODS: WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed. RESULTS: Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this 'spa-deletion' MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations. CONCLUSIONS: This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new 'spa-deletion' MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time.


Assuntos
Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Austrália/epidemiologia , Surtos de Doenças , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , New South Wales/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus
17.
Viruses ; 11(8)2019 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-31382657

RESUMO

Papillomaviruses (PVs) have been identified in a wide range of animal species and are associated with a variety of disease syndromes including classical papillomatosis, aural plaques, and genital papillomas. In horses, 13 PVs have been described to date, falling into six genera. Using total RNA sequencing (meta-transcriptomics) we identified a novel equine papillomavirus in semen taken from a thoroughbred stallion suffering a genital lesion, which was confirmed by nested RT-PCR. We designate this novel virus Equus caballus papillomavirus 9 (EcPV9). The complete 7656 bp genome of EcPV9 exhibited similar characteristics to those of other horse papillomaviruses. Phylogenetic analysis based on concatenated E1-E2-L2-L1 amino acid sequences revealed that EcPV9 clustered with EcPV2, EcPV4, and EcPV5, although was distinct enough to represent a new viral species within the genus Dyoiotapapillomavirus (69.35%, 59.25%, and 58.00% nucleotide similarity to EcPV2, EcPV4, and EcPV5, respectively). In sum, we demonstrate the presence of a novel equine papillomavirus for which more detailed studies of disease association are merited.


Assuntos
Doenças dos Cavalos/virologia , Papillomaviridae/classificação , Infecções por Papillomavirus/veterinária , Pênis/virologia , Sêmen/virologia , Animais , Cruzamento , DNA Viral/genética , Evolução Molecular , Genoma Viral/genética , Cavalos/virologia , Masculino , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Pênis/patologia , Filogenia , Especificidade da Espécie , Proteínas Virais/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-30746341

RESUMO

There are 17 human-biting ticks known in Australia. The bites of Ixodes holocyclus, Ornithodoros capensis, and Ornithodoros gurneyi can cause paralysis, inflammation, and severe local and systemic reactions in humans, respectively. Six ticks, including Amblyomma triguttatum, Bothriocroton hydrosauri, Haemaphysalis novaeguineae, Ixodes cornuatus, Ixodes holocyclus, and Ixodes tasmani may transmit Coxiella burnetii, Rickettsia australis, Rickettsia honei, or Rickettsia honei subsp. marmionii. These bacterial pathogens cause Q fever, Queensland tick typhus (QTT), Flinders Island spotted fever (FISF), and Australian spotted fever (ASF). It is also believed that babesiosis can be transmitted by ticks to humans in Australia. In addition, Argas robertsi, Haemaphysalis bancrofti, Haemaphysalis longicornis, Ixodes hirsti, Rhipicephalus australis, and Rhipicephalus sanguineus ticks may play active roles in transmission of other pathogens that already exist or could potentially be introduced into Australia. These pathogens include Anaplasma spp., Bartonella spp., Burkholderia spp., Francisella spp., Dera Ghazi Khan virus (DGKV), tick-borne encephalitis virus (TBEV), Lake Clarendon virus (LCV), Saumarez Reef virus (SREV), Upolu virus (UPOV), or Vinegar Hill virus (VINHV). It is important to regularly update clinicians' knowledge about tick-borne infections because these bacteria and arboviruses are pathogens of humans that may cause fatal illness. An increase in the incidence of tick-borne infections of human may be observed in the future due to changes in demography, climate change, and increase in travel and shipments and even migratory patterns of birds or other animals. Moreover, the geographical conditions of Australia are favorable for many exotic ticks, which may become endemic to Australia given an opportunity. There are some human pathogens, such as Rickettsia conorii and Rickettsia rickettsii that are not currently present in Australia, but can be transmitted by some human-biting ticks found in Australia, such as Rhipicephalus sanguineus, if they enter and establish in this country. Despite these threats, our knowledge of Australian ticks and tick-borne diseases is in its infancy.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Protozoários/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Viroses/epidemiologia , Zoonoses/epidemiologia , Animais , Austrália/epidemiologia , Infecções Bacterianas/patologia , Humanos , Incidência , Infecções por Protozoários/patologia , Doenças Transmitidas por Carrapatos/patologia , Viroses/patologia , Zoonoses/patologia
19.
Autoimmun Rev ; 16(3): 213-222, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28137477

RESUMO

AIM: To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy. METHOD: The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease. CONCLUSION: We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects.


Assuntos
Terapia Biológica/métodos , Imunossupressores/uso terapêutico , Uveíte/tratamento farmacológico , Humanos
20.
J Bone Joint Surg Am ; 98(20): 1722-1728, 2016 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-27869623

RESUMO

BACKGROUND: Propionibacterium acnes is a common pathogen identified in postoperative shoulder infection. It has been shown to be present in culture specimens during primary shoulder arthroplasty; however, recent work has suggested that it is most likely to be a contaminant. Our aim was to identify the potential sources of contamination in shoulder arthroplasty. METHODS: Tissue swabs were obtained for microbiological analysis from consecutive patients undergoing primary shoulder arthroplasty. Routine surgical technique was maintained, and 5 specimens were taken from different sites: (1) the subdermal layer, (2) the tip of the surgeon's glove, (3) the inside scalpel blade (used for deeper incision), (4) the forceps, and (5) the outside scalpel blade (used for the skin incision). RESULTS: Forty patients (25 female patients and 15 male patients) were included. Thirteen (33%) of the 40 patients had at least 1 culture specimen positive for P. acnes. Two (8%) of the 25 female patients and 11 (73%) of the 15 male patients had ≥1 culture specimen positive for P. acnes. The most common site of growth of P. acnes was the subdermal layer (12 positive samples), followed by the forceps (7 positive samples), the tip of the surgeon's glove (7 positive samples), the outside scalpel blade (4 positive samples), and the inside scalpel blade (1 positive sample). There were 27 of 75 swabs that were positive on culture for P. acnes in male patients compared with 4 of 125 swabs in female patients. Male patients had 66 times (95% confidence interval, 6 to 680 times) higher odds of having a positive culture indicating subdermal colonization compared with female patients (p < 0.001). CONCLUSIONS: P. acnes is a common contaminant of the surgical field in primary shoulder arthroplasty. The subdermal layer may be the source of this contamination, and the prevalence of P. acnes in the surgical wound may be due to the surgeon's manipulation with gloves and instruments. Our findings are consistent with those regarding the increased rates of P. acnes bacterial load and intraoperative growth in male patients compared with female patients. CLINICAL RELEVANCE: P. acnes is likely to be spread throughout the surgical field from the subdermal layer via soft-tissue handling by the surgeon and instruments. Strategies need to be utilized to minimize this contact and to reduce the chance of colonization.


Assuntos
Artroplastia do Ombro/efeitos adversos , Infecções por Bactérias Gram-Positivas/etiologia , Propionibacterium acnes/isolamento & purificação , Articulação do Ombro/cirurgia , Pele/microbiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/microbiologia , Articulação do Ombro/microbiologia
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