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BACKGROUND AND AIMS: The natural history of untreated patients with type 1 Gaucher disease (GD1) is not well documented, and there is controversy over when and how to treat such patients, especially if they are only mildly symptomatic. Treatment of GD1 is inconvenient, very costly, and may result in undesirable side effects. We documented the clinical history of 31 untreated patients with GD1 followed in our clinic for 4-26 (median 15) years. METHODS: This was a retrospective, observational study of the progress of untreated adult patients with GD1 followed by blood tests (haemoglobin, platelet counts, ferritin and chitotriosidase), organ volumes (spleen and liver), bone manifestations (through magnetic resonance imaging and dual X-ray absorptiometry scans) and neurological and quality of life issues. Statistical analyses were performed with the use of the Student paired t test and the modified Wald test for 95% confidence intervals. RESULTS: We found that the above parameters remained stable in most patients over a period of 4-26 (median 15) years. Five patients progressed from normal bone density to osteopenia and two from osteopenia to osteofibrosis; six were peri- or post-menopausal females. The DS-3 was stable over time. Only four of the 31 patients were started on enzyme or substrate reduction therapy. CONCLUSIONS: Our results demonstrate that many patients with GD1, provided with close follow-up by a specialist centre, can be followed for many years without requiring treatment and with no or minimal worsening of their GD1 manifestations.
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Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder (NDD). Individuals shared a mild phenotype comprising motor delay and relative macrocephaly associated with ventriculomegaly. Populational data and bioinformatic analysis underscored the pathogenicity of all de novo missense variants. The eEF2 yeast model strains demonstrated that patient-derived variants affect cellular growth, sensitivity to translation inhibitors and translational fidelity. Consequently, we propose that pathogenic variants in the EEF2 gene, so far exclusively associated with late-onset SCA26, can cause a broader spectrum of neurologic disorders, including childhood-onset NDDs and benign external hydrocephalus.
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Quinasa del Factor 2 de Elongación/genética , Exoma , Heterocigoto , Hidrocefalia/patología , Mutación , Trastornos del Neurodesarrollo/patología , Niño , Preescolar , Humanos , Hidrocefalia/etiología , Hidrocefalia/metabolismo , Masculino , Trastornos del Neurodesarrollo/etiología , Trastornos del Neurodesarrollo/metabolismo , Fenotipo , Secuenciación del ExomaRESUMEN
OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.
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Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Linfoma , Masculino , Adulto , Humanos , Femenino , Anciano , Leucemia-Linfoma de Células T del Adulto/epidemiología , Estudios Transversales , Queensland/epidemiología , Estudios Retrospectivos , Australia/epidemiología , Transmisión Vertical de Enfermedad Infecciosa , Infecciones por HTLV-I/epidemiologíaRESUMEN
Genetics are fundamental to understanding the pathophysiology of neurological disease, including movement disorders. Genetic testing in clinical practice has changed dramatically over the last few decades. While the likelihood of establishing an etiological diagnosis is greater now with increased access to testing and more advanced technologies, clinicians face challenges when deciding whether to test, then selecting the appropriate test, and ultimately interpreting and sharing the results with patients and families. In this review, we use a case-based approach to cover core aspects of genetic testing for the neurologist, namely, genetic testing in Parkinson's disease, interpretation of inconclusive genetic test reports, and genetic testing for repeat expansion disorders using Huntington disease as a prototype.
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Trastornos del Movimiento , Enfermedad de Parkinson , Humanos , Pruebas Genéticas/métodos , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/genética , Enfermedad de Parkinson/genéticaRESUMEN
Non-syndromic retinitis pigmentosa (NSRP) is a clinically and genetically heterogeneous group of disorders characterized by progressive degeneration of the rod and cone photoreceptors, often leading to blindness. The evolving association of syndromic genes to cause NSRP and the increasing role of intronic variants in explaining missing heritability in genetic disorders present challenges in establishing conclusive clinical and genetic diagnoses. This study sought to identify and validate the causative genetic variant(s) in a 13-year-old male initially diagnosed with NSRP. Genome sequencing identified a pathogenic missense variant in MVK [NM_000431.3:c.803T>C (p.Ile268Thr)], in trans with a novel intronic variant predicted to create a new donor splice site (c.768+71C>A). Proband cDNA analysis confirmed the inclusion of the first 68 base pairs of intron 8 that resulted in a frameshift in MVK (r.768_769ins[768+1_768+68]) and significantly reduced the expression of reference transcript (17.6%). Patient re-phenotyping revealed ataxia, cerebellar atrophy, elevated urinary mevalonate and LTE4 , in keeping with mild mevalonic aciduria and associated syndromic retinitis pigmentosa. Leakage of reference transcript likely explains the milder phenotype observed in our patient. This is the first association of a deep intronic splice variant to cause MVK-related disorder. This report highlights the importance of variant validation and patient re-phenotyping in establishing accurate diagnosis in the era of genome sequencing.
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Deficiencia de Mevalonato Quinasa , Retinitis Pigmentosa , Masculino , Humanos , Deficiencia de Mevalonato Quinasa/genética , Linaje , Retinitis Pigmentosa/genética , Mutación , IntronesRESUMEN
BACKGROUND: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, ß-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other ß-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. METHODS: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of ß-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. RESULTS: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC]â ≥â 256 µg/ml), ß-lactam/ß-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MICâ ≥â 256 µg/mL; ceftriaxone MICâ ≥â 8 µg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. CONCLUSIONS: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure.
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Corynebacterium diphtheriae , Difteria , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Corynebacterium diphtheriae/genética , Difteria/tratamiento farmacológico , Humanos , Lactamas/uso terapéutico , Pruebas de Sensibilidad Microbiana , Penicilinas/uso terapéuticoRESUMEN
LonP1 is crucial for maintaining mitochondrial proteostasis and mitigating cell stress. We identified a novel homozygous missense LONP1 variant, c.2282 C > T, (p.Pro761Leu), by whole-exome and Sanger sequencing in two siblings born to healthy consanguineous parents. Both siblings presented with stepwise regression during infancy, profound hypotonia and muscle weakness, severe intellectual disability and progressive cerebellar atrophy on brain imaging. Muscle biopsy revealed the absence of ragged-red fibers, however, scattered cytochrome c oxidase-negative staining and electron dense mitochondrial inclusions were observed. Primary cultured fibroblasts from the siblings showed normal levels of mtDNA and mitochondrial transcripts, and normal activities of oxidative phosphorylation complexes I through V. Interestingly, fibroblasts of both siblings showed glucose-repressed oxygen consumption compared to their mother, whereas galactose and palmitic acid utilization were similar. Notably, the siblings' fibroblasts had reduced pyruvate dehydrogenase (PDH) activity and elevated intracellular lactate:pyruvate ratios, whereas plasma ratios were normal. We demonstrated that in the siblings' fibroblasts, PDH dysfunction was caused by increased levels of the phosphorylated E1α subunit of PDH, which inhibits enzyme activity. Blocking E1α phosphorylation activated PDH and reduced intracellular lactate concentrations. In addition, overexpressing wild-type LonP1 in the siblings' fibroblasts down-regulated phosphoE1α. Furthermore, in vitro studies demonstrated that purified LonP1-P761L failed to degrade phosphorylated E1α, in contrast to wild-type LonP1. We propose a novel mechanism whereby homozygous expression of the LonP1-P761L variant leads to PDH deficiency and energy metabolism dysfunction, which promotes severe neurologic impairment and neurodegeneration.
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Proteasas ATP-Dependientes/genética , Enfermedades Cerebelosas/genética , Proteínas Mitocondriales/genética , Mutación , Enfermedades Neurodegenerativas/genética , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/genética , Alelos , Enfermedades Cerebelosas/enzimología , ADN Mitocondrial/metabolismo , Homocigoto , Humanos , Recién Nacido , Lactatos/metabolismo , Masculino , Enfermedades Neurodegenerativas/enzimología , Linaje , Fosforilación , Subunidades de Proteína/metabolismo , Proteolisis , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/patologíaRESUMEN
BACKGROUND: Mycoplasma genitalium was recently added to the CDC's antimicrobial resistance threats 'watch list', as it has rapidly become resistant to mainstay treatments. In Australia, treatment failure with fluoroquinolones remain commonplace, even when Sanger sequencing fails to identify evidence of resistance mutations. METHODS: Suspecting that Sanger sequencing may miss low-load mixed infections, we applied three additional PCR-based approaches (allele-specific primer-based PCR, probe-based PCR and amplicon deep sequencing) to detect mutations associated with fluoroquinolone susceptibility/resistance. We focused on resistance mutations at amino acid positions 83 and 87 of parC, as these were previously shown to be common in Australia. RESULTS: Our results showed evidence of mixtures of fluoroquinolone-susceptible and -resistant strains in up to 27/423 samples (6.4%). These included 1 sample that was indicated to be mixed by Sanger sequencing and all three additional PCR methods, 6 samples detected by two or more of the additional PCRs but not by Sanger sequencing and finally 20 samples that were detected by only one of the additional PCR methods. A key question was whether Sanger sequencing failed to detect fluoroquinolone resistance in any samples; overall, we observed that Sanger sequencing failed to detect fluoroquinolone resistance in up to 3.8% (16/423) of samples. CONCLUSIONS: The presence of mixed susceptibility infections may have important implications for clinical patient management and stresses the need for appropriate detection of resistance and selection of antimicrobials to ensure appropriate treatment of M. genitalium infections.
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Infecciones por Mycoplasma , Mycoplasma genitalium , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Australia , Farmacorresistencia Bacteriana , Fluoroquinolonas/farmacología , Humanos , Macrólidos , Mutación , Infecciones por Mycoplasma/tratamiento farmacológico , Mycoplasma genitalium/genética , ARN Ribosómico 23SRESUMEN
BACKGROUND: Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is nationwide longitudinal surveillance of C. difficile infection (CDI) in Australia. OBJECTIVES: To determine the antimicrobial susceptibility of C. difficile isolated in Australia between 2015 and 2018. METHODS: A total of 1091 strains of C. difficile were collected over a 3 year period by a network of 10 diagnostic microbiology laboratories in five Australian states. These strains were tested for their susceptibility to nine antimicrobials using the CLSI agar incorporation method. RESULTS: All strains were susceptible to metronidazole, fidaxomicin, rifaximin and amoxicillin/clavulanate and low numbers of resistant strains were observed for meropenem (0.1%; 1/1091), moxifloxacin (3.5%; 38/1091) and vancomycin (5.7%; 62/1091). Resistance to clindamycin was common (85.2%; 929/1091), followed by resistance to ceftriaxone (18.8%; 205/1091). The in vitro activity of fidaxomicin [geometric mean MIC (GM)â=â0.101 mg/L] was superior to that of vancomycin (1.700 mg/L) and metronidazole (0.229 mg/L). The prevalence of MDR C. difficile, as defined by resistance to ≥3 antimicrobial classes, was low (1.7%; 19/1091). CONCLUSIONS: The majority of C. difficile isolated in Australia did not show reduced susceptibility to antimicrobials recommended for treatment of CDI (vancomycin, metronidazole and fidaxomicin). Resistance to carbapenems and fluoroquinolones was low and MDR was uncommon; however, clindamycin resistance was frequent. One fluoroquinolone-resistant ribotype 027 strain was detected.
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Antiinfecciosos , Clostridioides difficile , Infecciones por Clostridium , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Australia/epidemiología , Clostridioides , Infecciones por Clostridium/epidemiología , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana , RibotipificaciónRESUMEN
BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Neurodegeneración Asociada a Pantotenato Quinasa , Actividades Cotidianas , Método Doble Ciego , Humanos , Neurodegeneración Asociada a Pantotenato Quinasa/tratamiento farmacológico , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Ácido Pantoténico/análogos & derivadosRESUMEN
BACKGROUND: Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood-brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. We report on the phenotypic spectrum of patients with pediatric GLUT1DS as well as their diagnostic methods from a single center in Canada. METHODS: We reviewed patient charts for clinical features, biochemical and molecular genetic investigations, neuroimaging, treatment modalities, and outcomes of patients with GLUT1DS at our institution. RESULTS: There were 13 patients. The most common initial symptom was seizures, with the most common seizure type being absence seizures (85%). Seventy-seven percent of the patients had movement disorders, and dystonia and ataxia were the most common movement disorders. Fifty-four percent of the patients did not have a history of developmental delay during their initial presentation, whereas all patients had developmental delay, intellectual disability, or cognitive dysfunction during their follow-up. All patients had a pathogenic or likely pathogenic variant in SLC2A1 and missense variants were the most common variant type. CONCLUSION: We present 13 patients with GLUT1DS in the pediatric patient population. Atypical clinical features such as hemiplegia and hemiplegic migraine were present in an infant; there was a high prevalence of absence seizures and movement disorders in our patient population. We report an increased number of patients with GLUT1DS since the introduction of next-generation sequencing in the clinical settings. We believe that GLUT1DS should be included in the differential diagnosis of seizures, movement disorders, and hemiplegic migraine.
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Errores Innatos del Metabolismo de los Carbohidratos , Dieta Cetogénica , Transportador de Glucosa de Tipo 1/metabolismo , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/genética , Niño , Dieta Cetogénica/métodos , Proteínas Facilitadoras del Transporte de la Glucosa , Transportador de Glucosa de Tipo 1/genética , Humanos , Lactante , Proteínas de Transporte de Monosacáridos/genética , Convulsiones/genéticaRESUMEN
An accurate rotavirus diagnosis is important for clinical management and monitoring active disease and vaccine effectiveness. Between 2016-2018, rotavirus-positive results in our laboratory were from vaccine virus shedding in 71/152 (46.7%) infants with a request for rotavirus testing. Routine infant diagnostic testing should ideally distinguish vaccine from wild-type viruses.
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Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Virus de la Viruela Vacuna , Heces , Humanos , Lactante , Uso Excesivo de los Servicios de Salud , Rotavirus/genética , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/prevención & control , Vacunas AtenuadasRESUMEN
In the early 2000s, a binary toxin (CDT)-producing strain of Clostridium difficile, ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The C. difficile Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of C. difficile infection (CDI) in Australia. Here, we describe the molecular epidemiology of CDI in Australian health care and community settings over the first 5 years of the study, 2013 to 2018. Between 2013 and 2018, 10 diagnostic microbiology laboratories from five states in Australia participated in the CDARS study. From each of five states, one private (representing community) and one public (representing hospitals) laboratory submitted isolates of C. difficile or PCR-positive stool samples during two collection periods per year, February-March (summer/autumn) and August-September (winter/spring). C. difficile was characterized by toxin gene profiling and ribotyping. A total of 1,523 isolates of C. difficile were studied. PCR ribotyping yielded 203 different RTs, the most prevalent being RT014/020 (n = 449; 29.5%). The epidemic CDT+ RT027 (n = 2) and RT078 (n = 6), and the recently described RT251 (n = 10) and RT244 (n = 6) were not common, while RT126 (n = 17) was the most prevalent CDT+ type. A heterogeneous C. difficile population was identified. C. difficile RT014/020 was the most prevalent type found in humans with CDI. Continued surveillance of CDI in Australia remains critical for the detection of emerging strain lineages.
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Clostridioides difficile , Infecciones por Clostridium , Australia/epidemiología , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Atención a la Salud , Europa (Continente) , Humanos , Laboratorios , América del Norte , RibotipificaciónRESUMEN
We report 3 cases of koala bite wound infection with Lonepinella koalarum-like bacteria requiring antimicrobial and surgical management. The pathogens could not be identified by standard tests. Phylogenetic analysis of 16S rRNA and housekeeping genes identified the genus. Clinicians should isolate bacteria and determine antimicrobial susceptibilities when managing these infections.
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Infecciones por Pasteurellaceae/diagnóstico , Pasteurellaceae/aislamiento & purificación , Phascolarctidae/microbiología , Infección de Heridas/diagnóstico , Anciano , Animales , Mordeduras y Picaduras , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Pasteurellaceae/microbiología , Queensland , Infección de Heridas/microbiologíaRESUMEN
BACKGROUND: Carbapenemase-producing organisms (CPOs) have emerged as antibiotic-resistant bacteria of global concern. Here we assessed the performance of the Carba (beta) assay, a multiplex real-time PCR assay developed by SpeeDx for the detection of key carbapenemase-encoding genes: KPC, NDM, OXA-48-like, IMP-4-like, and VIM. METHODS: DNA extracts of 180 isolates were tested with the Carba (beta) assay, using previously validated in-house TaqMan probe assays for the relevant carbapenemase genes as the reference standard. The Carba (beta) assay was then directly used to screen 460 DNA extracts of faecal specimens, with positive results subjected to the aforementioned in-house assays plus Sanger sequencing. RESULTS: The Carba (beta) assay correctly identified the presence of the respective carbapenemase genes in 154 of 156 isolates and provided negative results for all 24 non-CPO isolates. Two isolates provided positive results for OXA-48-like carbapenemase by the Carba (beta) assay only. The Carba (beta) assay had sensitivities of 100% for all targets, and specificities of 100% for KPC, NDM, IMP-4-like, and VIM targets, and 98.5% for OXA-48-like targets. When applied directly to faecal specimens, eight samples were positive by the Carba (beta) assay, two of which were confirmed by in-house TaqMan probe PCR or DNA sequencing. CONCLUSIONS: The Carba (beta) assay is highly sensitive and specific for detecting key carbapenemase genes in isolates. Further testing is required to assess this assay's suitability for direct screening of clinical specimens.
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Bacterias/genética , Proteínas Bacterianas/genética , Reacción en Cadena de la Polimerasa Multiplex/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , beta-Lactamasas/genética , Antibacterianos , Bacterias/efectos de los fármacos , Técnicas Bacteriológicas/métodos , Proteínas de Escherichia coli/genética , Heces/microbiología , Humanos , Sensibilidad y EspecificidadRESUMEN
The ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone was first observed in Japan in 2015, and in 2017, it was documented in Denmark, Canada, and Australia. Here, we describe a PCR for direct detection of the penA gene associated with this strain that can be used to enhance surveillance activities.
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Antibacterianos/farmacología , Proteínas Portadoras/genética , Ceftriaxona/farmacología , Gonorrea/epidemiología , Neisseria gonorrhoeae/genética , Resistencia betalactámica/genética , Alelos , Australia/epidemiología , Secuencia de Bases , Células Clonales , Cartilla de ADN/química , Cartilla de ADN/metabolismo , Expresión Génica , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Humanos , Mosaicismo , Neisseria gonorrhoeae/clasificación , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Alineación de Secuencia , D-Ala-D-Ala Carboxipeptidasa de Tipo SerinaRESUMEN
Background: Healthcare adapted meticillin-resistant Staphylococcus aureus (MRSA) has spread to hospitals around the world over 50 years. More recently, other strains of MRSA have emerged with the ability to spread in the community and infect otherwise healthy individuals. Morbidity and mortality associated with MRSA remains high and its control in both the healthcare and community setting has proven challenging. Sources of data: Pubmed (Medline). Areas of agreement: The use of targeted screening and decolonization, hand hygiene and antimicrobial stewardship is supported by the most robust studies, though many studies have implemented bundles for effective healthcare-associated (HA)-MRSA control. Areas of contention: Universal screening, universal decolonization and contact precautions for HA-MRSA control are supported by less evidence. Some interventions may not be cost-effective. Contact precautions may be associated with potential for patient harm. Evidence for effective control community acquired (CA)-MRSA is largely lacking. Growing points: Programmes that focus on implementing bundles of interventions aimed at targeting HA-MRSA are more likely to be effective, with an emphasis on hand hygiene as a key component. Control of CA-MRSA is likely to be more difficult to achieve and relies on prevalence, risk factors and community healthcare interactions on a broader scale. Areas timely for developing research: Further research in the area of CA-MRSA in particular is required. Antimicrobial stewardship for both CA and HA-MRSA is promising, as is the role of whole genome sequencing in characterizing transmission. However, further work is required to assess their long-term roles in controlling MRSA. With many institutions applying widespread use of chlorhexidine washes, monitoring for chlorhexidine resistance is paramount to sustaining efforts at controlling MRSA.
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Control de Enfermedades Transmisibles/organización & administración , Infección Hospitalaria , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Servicios Preventivos de Salud , Infecciones Estafilocócicas , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Humanos , Evaluación de Necesidades , Servicios Preventivos de Salud/métodos , Servicios Preventivos de Salud/organización & administración , Salud Pública/métodos , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/prevención & controlRESUMEN
Biallelic likely pathogenic variants in SLC52A2 and SLC52A3 cause riboflavin transporter deficiency. It is characterized by muscle weakness, ataxia, progressive ponto-bulbar palsy, amyotrophy, and sensorineural hearing loss. Oral riboflavin halts disease progression and may reverse symptoms. We report two new patients whose clinical and biochemical features were mimicking mitochondrial myopathy. Patient 1 is an 8-year-old male with global developmental delay, axial and appendicular hypotonia, ataxia, and sensorineural hearing loss. His muscle biopsy showed complex II deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing revealed a homozygous likely pathogenic variant in SLC52A2 (c.917G>A; p.Gly306Glu). Patient 2 is a 14-month-old boy with global developmental delay, respiratory insufficiency requiring ventilator support within the first year of life. His muscle biopsy revealed combined complex II + III deficiency and ragged red fibers consistent with mitochondrial myopathy. Whole exome sequencing identified a homozygous likely pathogenic variant in SCL52A3 (c.1223G>A; p.Gly408Asp). We report two new patients with riboflavin transporter deficiency, caused by mutations in two different riboflavin transporter genes. Both patients presented with complex II deficiency. This treatable neurometabolic disorder can mimic mitochondrial myopathy. In patients with complex II deficiency, riboflavin transporter deficiency should be included in the differential diagnosis to allow early treatment and improve neurodevelopmental outcome.
Asunto(s)
Complejo III de Transporte de Electrones/deficiencia , Complejo II de Transporte de Electrones/deficiencia , Proteínas de Transporte de Membrana/genética , Miopatías Mitocondriales/genética , Receptores Acoplados a Proteínas G/genética , Biopsia , Niño , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/fisiopatología , Progresión de la Enfermedad , Complejo II de Transporte de Electrones/genética , Complejo III de Transporte de Electrones/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Lactante , Masculino , Errores Innatos del Metabolismo , Enfermedades Mitocondriales , Miopatías Mitocondriales/fisiopatología , Riboflavina/genética , Riboflavina/metabolismo , Deficiencia de Riboflavina/genética , Deficiencia de Riboflavina/fisiopatologíaRESUMEN
Objectives: To investigate the genetic context associated with the emergence of vanA VRE in Australia. Methods: The whole genomes of 18 randomly selected vanA -positive Enterococcus faecium patient isolates, collected between 2011 and 2013 from hospitals in four Australian capitals, were sequenced and analysed. Results: In silico typing and transposon/plasmid assembly revealed that the sequenced isolates represented (in most cases) different hospital-adapted STs and were associated with a variety of different Tn 1546 variants and plasmid backbone structures. Conclusions: The recent emergence of vanA VRE in Australia was polyclonal and not associated with the dissemination of a single 'dominant' ST or vanA -encoding plasmid. Interestingly, the factors contributing to this epidemiological change are not known and future studies may need to consider investigation of potential community sources.
Asunto(s)
Proteínas Bacterianas/genética , Ligasas de Carbono-Oxígeno/genética , Enterococcus faecium/clasificación , Enterococcus faecium/aislamiento & purificación , Variación Genética , Infecciones por Bacterias Grampositivas/microbiología , Enterococos Resistentes a la Vancomicina/clasificación , Enterococos Resistentes a la Vancomicina/genética , Australia/epidemiología , Elementos Transponibles de ADN , Enterococcus faecium/efectos de los fármacos , Enterococcus faecium/genética , Genoma Bacteriano , Infecciones por Bacterias Grampositivas/epidemiología , Hospitales , Humanos , Tipificación Molecular , Plásmidos/análisis , Análisis de Secuencia de ADNRESUMEN
Toscana virus (TOSV) is identified in sandflies, animals, and humans around the Mediterranean Sea. TOSV has not been reported in Australia. During investigations of cerebrospinal fluid samples from patients with encephalitis, TOSV genetic sequences were identified in a traveler returning to Australia from Europe. TOSV should be considered, especially during May to October, in travelers to Australia who embarked in countries in and around the Mediterranean Sea and who subsequently present for medical care because of neurological symptoms.