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1.
N Engl J Med ; 382(21): 2023-2032, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32433838
2.
J Clin Microbiol ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32461283

RESUMO

Objectives: Streptococcal serology is a cornerstone in the diagnosis of acute rheumatic fever (ARF), a post-infectious sequalae associated with Group A Streptococcus infection. Current tests that measure anti-streptolysin-O (ASO) and anti-DNaseB (ADB) titres require parallel processing, with predictive value limited by the slow rate of decay in antibody response. Accordingly, our objective was to develop and assess the diagnostic potential of a triplex bead-based assay, which simultaneously quantifies ASO and ADB together with titres for a third antigen, SpnA.Methods: Our previous cytometric bead assay was transferred to the clinically appropriate Luminex platform by coupling streptolysin-O, DNaseB and SpnA to spectrally unique magnetic beads. Sera from over 350 subjects, including 97 ARF patients, were used to validate the assay and explore immunokinetics.Results: Operating parameters demonstrate the triplex assay produces accurate and reproducible antibody titres which, for ASO and ADB, are highly correlative with existing assay methodology. When ARF patients were stratified by time (days following hospital admission) there was no difference in ASO and ADB between <28 and 28+ days groups. However, for anti-SpnA there was a significant decrease (P<0.05) in the 28+ day group, indicative of faster anti-SpnA antibody decay.Conclusions: Anti-SpnA immunokinetics support very recent Group A Streptococcus infection, and may assist in diagnostic classification of ARF. Further, bead-based assays enable streptococcal serology to be performed efficiently in a high-throughput manner.

3.
Emerg Infect Dis ; 26(6): 1113-1121, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32441618

RESUMO

Group A Streptococcus (GAS) pharyngitis is a key initiator of acute rheumatic fever (ARF). In New Zealand, ARF cases occur more frequently among persons of certain ethnic and socioeconomic groups. We compared GAS pharyngitis estimates (1,257,058 throat swab samples) with ARF incidence (792 hospitalizations) in Auckland during 2010-2016. Among children 5-14 years of age in primary healthcare clinics, GAS pharyngitis was detected in similar proportions across ethnic groups (≈19%). Relative risk for GAS pharyngitis was moderately elevated among children of Pacific Islander and Maori ethnicities compared with those of European/other ethnicities, but risk for ARF was highly elevated for children of Pacific Islander and Maori ethnicity compared with those of European/other ethnicity. That ethnic disparities are much higher among children with ARF than among those with GAS pharyngitis implies that ARF is driven by factors other than rate of GAS pharyngitis alone.

5.
Emerg Infect Dis ; 26(5): 841-848, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32308193

RESUMO

A 3-month outbreak of invasive group A Streptococcus disease at an eldercare facility, in which 5 persons died, was biphasic. Although targeted chemoprophylaxis contained the initial outbreak, a second phase of the outbreak occurred after infection control processes ended. To retrospectively investigate the genomic epidemiology of the biphasic outbreak, we used whole-genome sequencing and multiple bioinformatics approaches. Analysis of isolates from the outbreak and isolates prospectively collected during the outbreak response indicated a single S. pyogenes emm81 clone among residents and staff members. Outbreak isolates differed from nonoutbreak emm81 isolates by harboring an integrative conjugative genomic element that contained the macrolide resistance determinant erm(TR). This study shows how retrospective high-resolution genomic investigations identified rapid spread of a closed-facilty clonal outbreak that was controlled, but not readily cleared, by infection control management procedures.

6.
J Clin Microbiol ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317257

RESUMO

Diagnostic testing for COVID-19 is central to controlling the global pandemic. ….

7.
Pediatr Infect Dis J ; 39(5): 397-405, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32301919

RESUMO

BACKGROUND: In addition to health care settings, antibiotic resistance has also been increasing in the community. Healthy children represent an important potential reservoir of antibiotic-resistant (AR) bacteria. However, strategies to reduce the spread of AR bacteria often fail to specifically address the factors that promote the carriage of AR bacteria in this population.The objective of this review was to Identify risk factors for carriage of AR bacteria by healthy children. METHODS: We did a systematic search of MEDLINE, Embase and PubMed for studies in developed (OECD) countries that assessed risk factors for carriage of AR bacteria in healthy children in the community. We excluded studies done before 1998 and studies of AR Streptococcus pneumoniae carriage in the absence of pneumococcal conjugate vaccination. RESULTS: Of 1234 studies identified, 30 were eligible for inclusion. These studies assessed the impact of 49 risk factors on AR strains of S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes and Escherichia coli. The majority of these risk factors were assessed in 2 or fewer studies per bacteria. Recent antibiotic consumption was associated with carriage of resistant respiratory bacteria (S. pneumoniae, H. influenzae); however, it was not consistently associated with carriage of AR bacteria in skin or stool (S. aureus and E. coli). For AR S. aureus, transmission within households appeared to have a greater impact than individual antibiotic use. CONCLUSIONS: The factors that promote carriage of AR bacteria by healthy children differed between bacterial species. To reduce reservoirs of AR bacteria in the community, it is essential for intervention strategies to target the specific risk factors for different bacteria.

8.
Med J Aust ; 212(10): 459-462, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32237278

RESUMO

OBJECTIVES: To describe the first isolation and sequencing of SARS-CoV-2 in Australia and rapid sharing of the isolate. SETTING: SARS-CoV-2 was isolated from a 58-year-old man from Wuhan, China who arrived in Melbourne on 19 January 2020 and was admitted to the Monash Medical Centre, Melbourne from the emergency department on 24 January 2020 with fever, cough, and progressive dyspnoea. MAJOR OUTCOMES: Clinical course and laboratory features of the first reported case of COVID-19 (the illness caused by SARS-CoV-2) in Australia; isolation, whole genome sequencing, imaging, and rapid sharing of virus from the patient. RESULTS: A nasopharyngeal swab and sputum collected when the patient presented to hospital were each positive for SARS-CoV-2 (reverse transcription polymerase chain reaction). Inoculation of Vero/hSLAM cells with material from the nasopharyngeal swab led to the isolation of SARS-CoV-2 virus in culture. Electron microscopy of the supernatant confirmed the presence of virus particles with morphology characteristic of viruses of the family Coronaviridae. Whole genome sequencing of the viral isolate and phylogenetic analysis indicated the isolate exhibited greater than 99.99% sequence identity with other publicly available SARS-CoV-2 genomes. Within 24 hours of isolation, the first Australian SARS-CoV-2 isolate was shared with local and overseas reference laboratories and major North American and European culture collections. CONCLUSIONS: The ability to rapidly identify, propagate, and internationally share our SARS-CoV-2 isolate is an important step in collaborative scientific efforts to deal effectively with this international public health emergency by developing better diagnostic procedures, vaccine candidates, and antiviral agents.

9.
J Clin Microbiol ; 58(5)2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32132192

RESUMO

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae at the pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Combining the three individual-site samples into a single pooled sample could result in significant cost savings, provided there is no significant sensitivity reduction. The aim of this study was to examine the sensitivity of pooled samples for detecting chlamydia and gonorrhea in asymptomatic MSM using a nucleic acid amplification test. Asymptomatic MSM who tested positive for chlamydia or gonorrhoea were invited to participate. Paired samples were obtained from participants prior to administration of treatment. To form the pooled sample, the anorectal swab was agitated in the urine specimen transport tube and then discarded. The pharyngeal swab and 2 ml of urine sample were then added to the tube. The difference in sensitivity between testing of pooled samples and individual-site testing was calculated against an expanded gold standard, where an individual is considered positive if either pooled-sample or individual-site testing returns a positive result. All samples were tested using the Aptima Combo 2 assay. A total of 162 MSM were enrolled in the study. Sensitivities of pooled-sample testing were 86% (94/109; 95% confidence interval [CI], 79 to 92%]) for chlamydia and 91% (73/80; 95% CI, 83 to 96%) for gonorrhea. The sensitivity reduction was significant for chlamydia (P = 0.02) but not for gonorrhea (P = 0.34). Pooling caused 22 infections (15 chlamydia and 7 gonorrhoea) to be missed, and the majority were single-site infections (19/22). Pooling urogenital and extragenital samples from asymptomatic MSM reduced the sensitivity of detection by approximately 10% for chlamydia but not for gonorrhea.

11.
Emerg Infect Dis ; 26(6): 1326-1328, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32213261

RESUMO

Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization. Phylogenetic analysis revealed putative transmission between 2 patients and suspected overseas acquisition in the others. Vigilant screening of at-risk patients is required.

12.
Sex Transm Infect ; 96(4): 265-270, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32169881

RESUMO

BACKGROUND: Outbreaks of hepatitis A are being reported more commonly among men who have sex with men (MSM) globally. Australia has also reported a sharp increase in the number of cases of hepatitis A in 2017. This study aimed to determine the level of immunity to hepatitis A among MSM attending a large urban sexual health clinic in Victoria in the lead up to recent outbreak. METHODS: This was a retrospective audit of serological testing data from first-time MSM attendees at Melbourne Sexual Health Centre (MSHC) in Australia from 1 January 2012 to 31 December 2018. We determined the proportion of MSM who were tested and who had serological detection of hepatitis A IgG, stratified by age and calendar year. We used univariable and multivariable logistic regression to investigate factors associated with testing for and detection of hepatitis A IgG. RESULTS: There were 16 609 first-time MSM attendees at MSHC over the 7-year period, of which 9718 (59%, 95% CI 58% to 60%) were tested for hepatitis A IgG. There was a 2% annual increase in the proportion of men tested (from 60% in 2012 to 69% in 2018; OR=1.02, 95% CI 1.00 to 1.03, p=0.025). Men born outside of Australia/New Zealand, and younger men <30 years had higher odds of being tested. Of those tested, 44% (n=4304, 95% CI 43% to 45%) had hepatitis A IgG detected at their first visit, with no change over time (OR=1.01, 95% CI 0.99 to 1.03, p=0.210). Detection of hepatitis A IgG was associated with being aged 30 years or older (adjusted OR=2.06, 95% CI 1.89 to 2.24, p<0.001) or being born overseas versus Australia/New Zealand (AOR=1.21, 95% CI 1.11 to 1.31, p<0.001). CONCLUSION: Hepatitis A immunity among MSM remains below the estimated 70% required to prevent outbreaks. Measures including increased testing and higher vaccination coverage are needed to prevent outbreaks and to limit the number of cases and deaths.

13.
J Infect Dis ; 221(6): 1017-1024, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32031634

RESUMO

BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.

14.
Microb Genom ; 6(1)2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31913111

RESUMO

Resistance to meticillin and vancomycin in Staphylococcus aureus significantly complicates the management of severe infections like bacteraemia, endocarditis or osteomyelitis. Here, we review the molecular mechanisms and genomic epidemiology of resistance to these agents, with a focus on how genomics has provided insights into the emergence and evolution of major meticillin-resistant S. aureus clones. We also provide insights on the use of bacterial whole-genome sequencing to inform management of S. aureus infections and for control of transmission at the hospital and in the community.

15.
J Med Microbiol ; 69(2): 244-248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958047

RESUMO

Introduction. Mycoplasma genitalium is a sexually transmitted organism with high levels of resistance to the recommended first-line therapy, azithromycin. The ResistancePlus MG test concurrently detects M. genitalium, and the presence of macrolide-resistance mutations (MRM). European, UK and Australian guidelines recommend a diagnostic test that reports MRM to optimize treatment through resistance-guided therapy. Hence, for samples collected for use on other platforms, reflex testing using the ResistancePlus MG test would be beneficial.Aim. To validate the ResistancePlus MG assay using samples collected in Aptima buffer for testing on the Hologic Panther.Methodology. Positive (n=99) and negative (n=229) clinical samples collected in Aptima buffer were extracted on the MagNA Pure 96 (Roche Diagnostics), and tested with the ResistancePlus MG test on the LightCycler 480 II (Roche Diagnostics). Results were compared to matched samples collected using standard sample collection (urine or swab resuspended in PBS), with positive percent agreement (PPA), negative percent agreement (NPA) and Cohen's Kappa statistic.Results. The ResistancePlus MG test had high performance with a 200 µl input volume (PPA/NPA for M. genitalium detection, 92.9 % [95 % confidence interval (CI): 85.5-96.9]/100 % [95 % CI: 97.9-100], MRM detection, 96.9 % [95 % CI: 88.2-99.5]/85.7 % [95 % CI: 66.4-95.3]) and for 1 ml input volume (PPA/NPA for M. genitalium detection, 95.9%/96.6%, MRM detection, 98.4%/90.3%). Samples remained positive after storage at room temperature beyond the manufacturer-recommended storage of <60 days (mean storage time for 1 ml extraction: 129 days).Conclusion. Samples collected using Aptima collection kits are suitable for reflex testing using the ResistancePlus MG test, allowing detection of macrolide resistance.


Assuntos
Antibacterianos/farmacologia , Testes Diagnósticos de Rotina/métodos , Farmacorresistência Bacteriana , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/efeitos dos fármacos , Mycoplasma genitalium/isolamento & purificação , Austrália , Testes Diagnósticos de Rotina/instrumentação , Humanos , Macrolídeos/farmacologia , Infecções por Mycoplasma/diagnóstico , Mycoplasma genitalium/genética , Kit de Reagentes para Diagnóstico , Manejo de Espécimes
16.
Immunol Cell Biol ; 98(1): 12-21, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742781

RESUMO

Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF. Patients were stratified by C-reactive protein (CRP) concentration into high (≥10 µg mL-1 ) and low (<10 µg mL-1 ) groups to distinguish those with clinically significant inflammatory processes from those with abating inflammation. The circulating concentrations of 17 complement factors and six immunoglobulin isotypes and subclasses were measured in ARF patients and highly matched healthy controls using multiplex bead-based immunoassays. An integrative statistical approach combining feature selection and principal component analysis revealed a linked IgG3-C4 response in ARF patients with high CRP that was absent in controls. Strikingly, both IgG3 and C4 were elevated above clinical reference ranges, suggesting these features are a marker of ARF-associated inflammation. Humoral immunity in response to M protein, an antigen implicated in ARF pathogenesis, was completely polarized to IgG3 in the patient group. Furthermore, the anti-M-protein IgG3 response was correlated with circulating IgG3 concentration, highlighting a potential role for this potent immunoglobulin subclass in disease. In conclusion, a linked IgG3-C4 response appears important in the initial, inflammatory stage of ARF and may have immediate utility as a clinical biomarker given the lack of specific diagnostic tests currently available.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31731673

RESUMO

Acute rheumatic fever (ARF) and its sequela, rheumatic heart disease (RHD), have largely disappeared from high-income countries. However, in New Zealand (NZ), rates remain unacceptably high in indigenous Maori and Pacific populations. The goal of this study is to identify potentially modifiable risk factors for ARF to support effective disease prevention policies and programmes. A case-control design is used. Cases are those meeting the standard NZ case-definition for ARF, recruited within four weeks of hospitalisation for a first episode of ARF, aged less than 20 years, and residing in the North Island of NZ. This study aims to recruit at least 120 cases and 360 controls matched by age, ethnicity, gender, deprivation, district, and time period. For data collection, a comprehensive pre-tested questionnaire focussed on exposures during the four weeks prior to illness or interview will be used. Linked data include previous hospitalisations, dental records, and school characteristics. Specimen collection includes a throat swab (Group A Streptococcus), a nasal swab (Staphylococcus aureus), blood (vitamin D, ferritin, DNA for genetic testing, immune-profiling), and head hair (nicotine). A major strength of this study is its comprehensive focus covering organism, host and environmental factors. Having closely matched controls enables the examination of a wide range of specific environmental risk factors.

18.
Emerg Infect Dis ; 25(12): 2226-2234, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31742539

RESUMO

In 2014, antimicrobial drug-resistant Campylobacter jejuni sequence type 6964 emerged contemporaneously in poultry from 3 supply companies in the North Island of New Zealand and as a major cause of campylobacteriosis in humans in New Zealand. This lineage, not previously identified in New Zealand, was resistant to tetracycline and fluoroquinolones. Genomic analysis revealed divergence into 2 major clades; both clades were associated with human infection, 1 with poultry companies A and B and the other with company C. Accessory genome evolution was associated with a plasmid, phage insertions, and natural transformation. We hypothesize that the tetO gene and a phage were inserted into the chromosome after conjugation, leaving a remnant plasmid that was lost from isolates from company C. The emergence and rapid spread of a resistant clone of C. jejuni in New Zealand, coupled with evolutionary change in the accessory genome, demonstrate the need for ongoing Campylobacter surveillance among poultry and humans.

19.
Euro Surveill ; 24(44)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31690365

RESUMO

BackgroundInternational travel is considered a risk factor for acquiring Chlamydia trachomatis; however, there are little empirical data to support this.AimTo examine the prevalence and risk factors for Chlamydia trachomatis infections among heterosexual international travellers (n = 28,786) attending the Melbourne Sexual Health Centre (MSHC), Australia, compared to Australian residents (n = 20,614).MethodsWe conducted a repeated cross-sectional study and analysed sexual behaviours and chlamydia positivity among heterosexual males and females aged ≤ 30 attending MSHC for the first time between January 2007 and February 2017. 'Travellers' were defined as individuals born outside of Australia who had resided in the country < 2 years. Associations between patient characteristics and chlamydia positivity were examined.ResultsChlamydia positivity was higher among travellers (11.2%) compared with Australian residents (8.5%; p < 0.001). Male travellers had higher chlamydia positivity (12.1%) than Australian males (9.3%; p < 0.001), as did female travellers (10.4%) compared with Australian females (7.7%; p < 0.001). Travellers had a higher mean number of sexual partners than Australian residents among males (5.7 vs 4.7; p < 0.001) and females (3.6 vs 3.2; p < 0.001). Travellers from the United Kingdom, Europe, Ireland and New Zealand accounted for 29.6%, 21%, 8.5% and 5.8% of C. trachomatis infections, respectively. Chlamydia in males and females was associated with younger age (≤ 25), inconsistent condom use, a higher number of sexual partners (≥ 4 partners) and being a traveller (p < 0.001).ConclusionsWe found that international travel is an independent risk factor for chlamydia among young heterosexual travellers in Australia, who should therefore be a target group for chlamydia prevention.

20.
J Clin Microbiol ; 58(1)2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31694973

RESUMO

The aim of this study was to determine whether Chlamydia trachomatis could be detected in saliva and if infection is specific to an anatomical site in the oropharynx. Men who have sex with men (MSM) who were diagnosed with oropharyngeal chlamydia at the Melbourne Sexual Health Centre in 2017-2018 were invited to participate upon returning for treatment. Swabs at the tonsillar fossae and posterior oropharynx and a saliva sample were collected. Throat samples were tested for C. trachomatis by the Aptima Combo 2 assay. The bacterial loads of C. trachomatis in all samples were assessed by quantitative PCR (qPCR) detecting the ompA gene. We calculated the positivity and bacterial load of C. trachomatis for all samples. Forty-two MSM were included. The median age was 28 years (interquartile range [IQR], 24 to 33 years). Thirty-two participants (76.2%; 95% confidence interval [CI], 60.5% to 87.9%) had C. trachomatis detected by qPCR at both the tonsillar fossae and the posterior oropharynx, followed by 9.5% (n = 4; 95% CI, 2.7% to 22.6%) positive at the posterior oropharynx only and 4.8% (n = 2; 95% CI, 0.58% to 16.2%) positive at the tonsillar fossae only. Twenty-nine MSM had C. trachomatis detected in saliva (69.0%; 95% CI, 52.9% to 82.3%). The median C. trachomatis load in saliva was 446 copies/ml (IQR, 204 to 1,390 copies/ml), that in the tonsillar fossae was 893 copies/swab (IQR, 390 to 13,224 copies/ml), and that in the posterior oropharynx was 1,204 copies/swab (IQR, 330 to 16,211). There was no significant difference in C. trachomatis load between the tonsillar fossae and the posterior oropharynx (P = 0.119). Among MSM with oropharyngeal chlamydia, nearly three-quarters had chlamydia DNA detected in saliva, although the viability and implications for transmission are unknown.

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