Hospitalizations and emergency attendance averted by influenza vaccination in Victoria, Australia, 2017 - 2019.

Seasonal influenza epidemics result in high levels of healthcare utilization. Vaccination is an effective strategy to reduce the influenza-related burden of disease. However, reporting vaccine effectiveness does not convey the population impacts of influenza vaccination. We aimed to calculate the burden of influenza-related hospitalizations and emergency department (ED) attendance averted by influenza vaccination in Victoria, Australia, from 2017 to 2019, and associated economic savings. We applied a compartmental model to hospitalizations and ED attendances with influenza-specific, and pneumonia and influenza (P&I) with the International Classification of Diseases, 10th Revision, Australian Modification (ICD-10-AM) diagnostic codes of J09-J11 and J09-J18, respectively. We estimated an annual average of 7657 (120 per 100000 population) hospitalizations and 20560 (322 per 100000 population) ED attendances over the study period, associated with A$85 million hospital expenditure. We estimated that influenza vaccination averted an annual average of 1182 [range: 556 - 2277] hospitalizations and 3286 [range: 1554 - 6257] ED attendances and reduced the demand for healthcare services at the influenza season peak. This equated to approximately A13 [range: A6 - A25] million of savings over the study period. Calculating the burden averted is feasible in Australia and auseful approach to demonstrate the health and economic benefits of influenza vaccination.

Comparison of contemporary invasive and non-invasive Streptococcus pneumoniae isolates reveals new insights into circulating anti-microbial resistance determinants.

Streptococcus pneumoniae is a major human pathogen with a high burden of disease. Non-invasive isolates (those found in non-sterile sites) are thought to be a key source of invasive isolates (those found in sterile sites) and a reservoir of anti-microbial resistance (AMR) determinants. Despite this, pneumococcal surveillance has almost exclusively focused on invasive isolates. We aimed to compare contemporaneous invasive and non-invasive isolate populations to understand how they interact and identify differences in AMR gene distribution. We used a combination of whole-genome sequencing and phenotypic anti-microbial susceptibility testing and a data set of invasive (n = 1,288) and non-invasive (n = 186) pneumococcal isolates, collected in Victoria, Australia, between 2018 and 2022. The non-invasive population had increased levels of antibiotic resistance to multiple classes of antibiotics including beta-lactam antibiotics penicillin and ceftriaxone. We identified genomic intersections between the invasive and non-invasive populations and no distinct phylogenetic clustering of the two populations. However, this analysis revealed sub-populations overrepresented in each population. The sub-populations that had high levels of AMR were overrepresented in the non-invasive population. We determined that WamR-Pneumo was the most accurate in silico tool for predicting resistance to the antibiotics tested. This tool was then used to assess the allelic diversity of the penicillin-binding protein genes, which acquire mutations leading to beta-lactam antibiotic resistance, and found that they were highly conserved (≥80% shared) between the two populations. These findings show the potential of non-invasive isolates to serve as reservoirs of AMR determinants.

The impact of the National Shingles Vaccination Program on the epidemiology of herpes zoster among adults ≥ 60 years in Victoria, Australia.

Introduction: In November 2016, Australia recommended herpes zoster (HZ) vaccination for adults aged ≥ 60 years and implemented a National Shingles Vaccination Program (NSVP) offering free HZ vaccination to adults aged 70-79 years. This study investigated trends in HZ epidemiology among Victorian adults aged ≥ 60 years and the impact of the NSVP in this population. Methods: We conducted epidemiological analyses of routinely collected HZ surveillance data for Victorian adults aged ≥ 60 years who were notified as having a HZ illness or vaccination between 2012 and 2021. Annual incidence rates are presented for vaccinations, case notifications, emergency department presentations, hospitalisations and deaths by five-year age groups. Age-specific incidence rate ratios are calculated comparing the period prior to (1 January 2012 to 31 October 2016) and following (1 November 2016 to 31 December 2021) NSVP implementation. Results: HZ vaccination rates were highest among those eligible to receive free vaccination (70-79 years), but appear to have plateaued across all age groups and remained below full coverage. Incidence rate ratios showed a statistically significant increase (p < 0.01) in HZ notifications across all age-groups. Emergency presentations and hospitalisations showed a statistically significant decline (p < 0.05) among the 70-79 year old age groups; however, these rates remained consistent or increased among other age groups for whom vaccination is recommended. Mortality rates declined, particularly among those aged 85+ years. Discussion: HZ continues to cause significant disease among the older adult population in Victoria. The findings of this study suggest the NSVP has led to some changes in the epidemiology of HZ among the 70-79 years old age group in Victoria; however, there is less evidence that it has influenced other age groups for whom vaccination is recommended. An evaluation of the NSVP and epidemiology of HZ at a national level is required to identify strategies to improve vaccination coverage among the target populations.

Lessons from the re-emergence of imported measles cases following the COVID-19 pandemic in Victoria, Australia.

Introduction: Australia was declared to have eliminated endemic measles in 2014; however, imported cases continue to pose a threat of outbreaks. International travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic led to a rapid decline in measles cases. The re-opening of the Australian international border to measles endemic regions returns the threat of outbreaks, which may be further compounded by disruptions in routine vaccinations during the COVID-19 pandemic. We consider lessons learned from the public health response to recent measles cases. Methods: This case series includes all confirmed measles cases meeting the national case definition reported to the Victorian Government Department of Health (the Department) between 1 January and 31 December 2022. The Department conducted active case finding and contact tracing of all cases in line with national guidelines. Cases were descriptively analysed. Results: In 2022, six of the seven measles cases reported in Australia occurred in Victoria, all of whom resided in Australia and acquired their infection overseas. Three cases were unlinked, and three formed an epidemiologically-linked household cluster. One case was partially vaccinated, one was not eligible for vaccination, one had unknown vaccination status, and three were unvaccinated, one of whom was under 12 months old but would have been eligible for vaccination prior to travel to endemic regions. None of the cases led to secondary transmission within Australia. Discussion: Following the COVID-19 pandemic, measles importations have re-commenced in Victoria. Although few measles cases occurred in 2022 and none resulted in onwards transmission, imported measles cases remain complex and require substantial public health follow-up. Delays in case diagnosis and flight contact tracing pose a significant risk for outbreaks of measles. Public health interventions are needed to maintain high vaccination rates, improve contact tracing, and ensure public health authorities and healthcare providers can rapidly identify and respond to imported measles cases.

The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia, 2021 to 2022.

BackgroundCOVID-19 pandemic mitigation measures, including travel restrictions, limited global circulation of influenza viruses. In Australia, travel bans for non-residents and quarantine requirements for returned travellers were eased in November 2021, providing pathways for influenza viruses to be re-introduced.AimWe aimed to describe the epidemiological and virological characteristics of the re-emergence of influenza in Victoria, Australia to inform public health interventions.MethodsFrom 1 November 2021 to 30 April 2022, we conducted an epidemiological study analysing case notification data from the Victorian Department of Health to describe case demographics, interviewed the first 200 cases to establish probable routes of virus reintroduction and examined phylogenetic and antigenic data to understand virus diversity and susceptibility to current vaccines.ResultsOverall, 1,598 notifications and 1,064 positive specimens were analysed. The majority of cases (61.4%) occurred in the 15-34 years age group. Interviews revealed a higher incidence of international travel exposure during the first month of case detections, and high levels of transmission in university residential colleges were associated with return to campus. Influenza A(H3N2) was the predominant subtype, with a single lineage predominating despite multiple importations.ConclusionEnhanced testing for respiratory viruses during the COVID-19 pandemic provided a more complete picture of influenza virus transmission compared with previous seasons. Returned international travellers were important drivers of influenza reemergence, as were young adults, a group whose role has previously been under-recognised in the establishment of seasonal influenza epidemics. Targeting interventions, including vaccination, to these groups could reduce future influenza transmission.

Population structure, serotype distribution and antibiotic resistance of Streptococcus pneumoniae causing invasive disease in Victoria, Australia.

Streptococcus pneumoniae is a major human pathogen and can cause a range of conditions from asymptomatic colonization to invasive pneumococcal disease (IPD). The epidemiology and distribution of IPD-causing serotypes in Australia has undergone large changes following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV) in 2005 and the 13-valent PCV in 2011. In this study, to provide a contemporary understanding of the IPD causing population in Victoria, Australia, we aimed to examine the population structure and prevalence of antimicrobial resistance using whole-genome sequencing and comprehensive antimicrobial susceptibility data of 1288 isolates collected between 2018 and 2022. We observed high diversity among the isolates with 52 serotypes, 203 sequence types (STs) and 70 Global Pneumococcal Sequencing Project Clusters (GPSCs) identified. Serotypes contained in the 13v-PCV represented 35.3 % (n=405) of isolates. Antimicrobial resistance (AMR) to at least one antibiotic was identified in 23.8 % (n=358) of isolates with penicillin resistance the most prevalent (20.3 %, n=261 using meningitis breakpoints and 5.1 % n=65 using oral breakpoints). Of the AMR isolates, 28 % (n=101) were multidrug resistant (MDR) (resistant to three or more drug classes). Vaccination status of cases was determined for a subset of isolates with 34 cases classified as vaccine failure events (fully vaccinated IPD cases of vaccine serotype). However, no phylogenetic association with failure events was observed. Within the highly diverse IPD population, we identified six high-risk sub-populations of public health concern characterized by high prevalence, high rates of AMR and MDR, or serotype inclusion in vaccines. High-risk serotypes included serotypes 3, 19F, 19A, 14, 11A, 15A and serofamily 23. In addition, we present our data validating seroBA for in silico serotyping to facilitate ISO-accreditation of this test in routine use in a public health reference laboratory and have made this data set available. This study provides insights into the population dynamics, highlights non-vaccine serotypes of concern that are highly resistant, and provides a genomic framework for the ongoing surveillance of IPD in Australia which can inform next-generation IPD prevention strategies.

Effect of COVID-19 restrictions and border closures on vaccine preventable diseases in Victoria, Australia, 2020-2021.

Background: In 2020, Victoria introduced multiple interventions aimed at containing the spread of coronavirus disease 2019 (COVID-19). We examine the effect of these restrictions on other vaccine preventable diseases (VPDs). Methods: We analysed the mandatory reporting data, notified to the Victorian Department of Health, for VPDs from January 2015 to December 2021. Results: Reductions in notifications were seen for most notifiable VPDs. A precipitous decline in influenza and measles notifications was recorded in April 2020, which was sustained for both diseases throughout 2020-2021. Notifications for chickenpox, invasive meningococcal disease, invasive pneumococcal disease, and pertussis were reduced by greater than 50% from the 2015-2019 average. No notified cases of diphtheria, poliomyelitis, or rubella were reported in 2020-2021. Conclusion: Restrictions placed to mitigate the effects of the COVID-19 pandemic were associated with significant reductions in other VPDs, which were sustained into 2021. Nevertheless, it is important that high levels of population vaccine coverage continue, to prevent a rebound increase in VPDs as restrictions are eased, and to maximise protection against VPDs for all Australians.

Clinical manifestations of invasive meningococcal disease in Victoria with the emergence of serogroup W and serogroup Y Neisseria meningitidis.

BACKGROUND: Historically, Australian cases of invasive meningococcal disease (IMD) have been most frequently caused by Neisseria meningitidis serogroup B, but recently an increase in cases due to serogroup W (MenW) and serogroup Y (MenY) has occurred. AIM: To determine whether clinical manifestations of IMD have changed due to increased incidence of MenW and MenY. METHODS: We performed a retrospective review of IMD cases notified to the Department of Health and Human Services in Victoria, Australia. We compared the period between January 2013 and June 2015 (defined as P1) immediately before the increase in MenW and MenY was noted, with the equal time period of July 2015 to December 2017 (P2), when this increase was observed. RESULTS: IMD was notified more frequently in P2 than P1 (1.24 vs 0.53 per 100 000 person-years, P < 0.001). IMD cases in P2 were older (46 vs 19 years, P < 0.001), and more likely due to MenW (92/187, 49.2% vs 11/80, 13.8%, P < 0.001) or MenY (31/187, 16.6% vs 4/80, 5.0%, P = 0.01). IMD cases from P2 were more likely bacteraemic (151/187, 80.7% vs 55/80, 68.8%, P = 0.04), while meningitis (68/187, 36.4% vs 41/80, 51.3%, P = 0.03) and rash (65/181, 35.9% vs 45/78, 57.7%, P = 0.002) were less frequent. Intensive care unit admission rates and in-hospital mortality were unchanged. CONCLUSION: Alongside an increase in IMD in Victoria, the proliferation of cases of MenW and MenY occurred in older patients, and were more often identified through bacteraemia rather than meningitis or purpura fulminans. Clinicians should be aware of these changes to facilitate earlier identification and treatment of IMD.

Incidence of Invasive Pneumococcal Disease Higher Among People Notified With Markers of Hepatitis C Virus Infection: Population-based Surveillance in Victoria, Australia, 2001-2017.

BACKGROUND: Worse outcomes from invasive pneumococcal disease (IPD) have been reported among those coinfected with hepatitis C. We aimed to establish if IPD notification rates are higher among people notified with markers of hepatitis C virus infection than the general population. METHODS: IPD cases notified in Victoria, Australia, from July 2001-December 2017 were linked with hepatitis C cases (diagnosed by serology or PCR testing) notified from January 1991-December 2017. IPD incidence was calculated using population data and the estimated number of Victorians with hepatitis C. RESULTS: From July 2001-December 2017, 6407 IPD cases were notified. Hepatitis C infection was notified in 342 (5.3%) of IPD cases overall, and 24.4% among IPD cases aged 45-49 years. Among IPD cases also notified with hepatitis C, 55.3% were infected with 13-valent pneumococcal conjugate vaccine serotypes and 82.8% with 23-valent pneumococcal polysaccharide vaccine serotypes. Compared with IPD cases without hepatitis C, IPD cases also notified with hepatitis C were younger (mean age, 45.7 vs 49.4 years; P = .011) and more often male (65.5% vs 55.5%, P < .001). Annual IPD notification incidence was 6.8/100 000 among people without hepatitis C and 39.4/100 000 among people with hepatitis C (IRR, 5.8; 95% CI, 5.2-6.4; P < .001). CONCLUSIONS: IPD notification incidence was 5 times higher among people notified with markers of hepatitis C than the general population. Pneumococcal vaccination should be offered to people with markers of hepatitis C virus infection. To facilitate appropriate treatment, young and middle-aged adults with IPD should be tested for hepatitis C.

Measles immunisation status of healthcare workers in smaller Victorian hospitals: can we do better?

OBJECTIVE: To determine the proportion of healthcare workers (HCWs) in smaller Victorian public healthcare facilities with documented evidence of measles immunity. METHODS: A cross-sectional survey, developed by the Victorian Healthcare Associated Surveillance System Coordinating Centre, was completed by all eligible facilities. HCWs were reported as having evidence or no evidence of measles immunity. Those without evidence of immunity were sub-classified as incomplete, declined or unknown status. RESULTS: Seventy-five facilities reported measles immunity status of 17,522 employed HCWs. Of these, 11,751 (67.1%) had documented evidence of immunity. The proportion with evidence of immunity was lowest (45.6%) in facilities with ≤50 HCWs. The majority of HCWs without evidence of immunity (88.2%) had 'unknown' status. Declination or incomplete status comprised very low overall proportions (0.3% and 3.6%, respectively). CONCLUSIONS: Reported evidence of HCW measles immunity was moderate in surveyed facilities, with a large proportion having unknown status. HCW immunisation programs in some facilities require refinement to appropriately support public health responses to measles cases and prevention of occupational acquisition of measles. Implications for public health: Non-immune HCWs are at increased risk for acquiring and transmitting measles. Timely access to accurate HCW immunisation records is required to ensure that public health responses are effective.

Long-term Impact of Pneumococcal Conjugate Vaccines on Invasive Disease and Pneumonia Hospitalizations in Indigenous and Non-Indigenous Australians.

BACKGROUND: Universal pneumococcal conjugate vaccine (PCV) programs began in Indigenous Australian children in 2001 and all children in 2005, changing to 13-valent PCV (PCV13) in 2011. We used laboratory data for invasive pneumococcal disease (IPD) and coded hospitalizations for noninvasive pneumococcal community-acquired pneumonia (PnCAP) to evaluate long-term impact. METHODS: Annual incidence (per 100 000 population) was calculated for age-specific total IPD, PCV13 non-7-valent PCV (PCV7) serotypes, and PnCAP by Indigenous status. Incidence in the pre-universal PCV7 (2002-2004), early PCV7 (2005-2007), pre-PCV13 (2008 to mid-2011), and post-PCV13 (mid-2011 to 2016) periods was used to calculate incidence rate ratios (IRRs). RESULTS: In the total population, all-age incidence of IPD declined from 11.8 pre-PCV7 to 7.1 post-PCV13 (IRR, 0.61 [95% confidence interval {CI}, .59-.63]) but for PnCAP declined among ages <1 year (IRR, 0.34 [95% CI, .25-.45]) and 1-4 years (IRR, 0.50 [95% CI, .43-.57]) but increased significantly among age ≥5 years (IRRs, 1.08-1.14). In Indigenous people, baseline PCV13 non-PCV7 IPD incidence was 3-fold higher, amplified by a serotype 1 epidemic in 2011. By 2015-2016, although incidence of IPD and PnCAP in children aged <5 years decreased by 38%, neither decreased in people aged ≥5 years. CONCLUSIONS: Fifteen years post-PCV and 5 years post-PCV13, direct and indirect impact on IPD and PnCAP differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.Fifteen years after pneumococcal conjugate vaccine (PCV) introduction and 5 years post-PCV13, direct and indirect impact on invasive pneumococcal disease and pneumococcal community-acquired pneumonia differed by age and between Indigenous and non-Indigenous people, with potential implications for long-term PCV impact in comparable settings.

Emergence of Attenuated Measles Illness Among IgG-positive/IgM-negative Measles Cases: Victoria, Australia, 2008-2017.

BACKGROUND: Waning measles immunity among vaccinated individuals may result in an attenuated illness. This study compares the epidemiological, clinical, and laboratory profile of measles cases with waning immunity with other measles cases. METHODS: Polymerase chain reaction-positive (+) measles cases notified to Victoria's Department of Health and Human Services from 2008 to 2017 with immunoglobulin (Ig) M and IgG tested at diagnosis were classified according to serology at diagnosis: IgG negative (-) (nonimmune), IgM+/IgG+ (indeterminate), or IgM-/IgG+ (waning immunity). RESULTS: Between 2008 and 2017, 297 measles cases were notified, of whom 190 (64%) were included; 151 of 190 (79%) were nonimmune at diagnosis, 26 (14%) were indeterminate, and 13 (7%) had waning immunity. Between 2008-2013 and 2014-2017, the proportion of cases with waning immunity increased from 0 of 87 (0%) to 13 of 103 (13%) (P < .001) and the diagnostic sensitivity of initial IgM fell from 93% to 81% (P = .012), respectively. Seven (54%) waning immunity cases reported receiving measles-containing vaccines; 1 case had 2 documented doses. Compared with nonimmune and indeterminate cases, waning immunity cases were more likely to be male; less likely to report fever, coryza, and cough; and had lower burden of virus (higher cycle threshold values). Waning immunity cases had higher IgG titers than indeterminate cases (mean optical density values, 1.96 vs 0.71; P = .004). Onward transmission from 1 waning immunity case was documented. CONCLUSIONS: Waning immunity among measles cases, associated with secondary vaccine failure and modified clinical illness, is emerging in Victoria with transmission potential.

Recent trends in invasive group A Streptococcus disease in Victoria

Background: Invasive Group A Streptococcus (iGAS) disease can cause permanent disability and death. The incidence of iGAS has increased in many developed countries since the 1980s. iGAS disease is not nationally notifiable in Australia or at the state level in Victoria. The Victorian Hospital Pathogen Surveillance Scheme (VHPSS) is a voluntary laboratory-based surveillance system established in 1988. We assessed the trends and molecular epidemiology of iGAS disease in Victoria from 2007-2017. Methods: A case of iGAS was defined as an individual for whom Group A Streptococcus (GAS) was isolated from a normally sterile body site. Data on all iGAS cases, as reported to the VHPSS, between 1 January 2007 and 31 December 2017 were examined. Results: A total of 1,311 iGAS cases had associated isolates, and M Protein Gene (emm) typing was performed for 91.6%. The mean annual incidence was 2.1 (95% CI: 1.8-2.5) per 100,000 population per year, increasing 2.7-fold over the study period. In total, 140 different iGAS emm-types were observed, with the ten most prevalent types comprising 63.1% of the sample. Conclusions: Despite limitations in this surveillance data, we observed increasing rates of iGAS disease in Victoria. iGAS incidence exceeded the mean annual incidence for invasive meningococcal disease, calculated using Victorian data from the National Notifiable Diseases Surveillance System (2.1 vs. 0.6 cases per 100,000 population per year, respectively). Mandatory case notification could enhance disease control and prevention. Further, the diversity in emm-types emphasises the importance of effective secondary chemoprophylaxis in prevention, alongside GAS vaccine development.

The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: a population-level genomic study.

Background: Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm. Methods: A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid. Results: vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission. Conclusions: Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad.

Increasing Antimicrobial Resistance in Nontyphoidal Salmonella Isolates in Australia from 1979 to 2015.

Australia has high and increasing rates of salmonellosis. To date, the serovar distribution and associated antimicrobial resistance (AMR) patterns of nontyphoidal Salmonella enterica (NTS) in Australia have not been assessed. Such information provides critical knowledge about AMR in the food chain and informs decisions about public health. We reviewed longitudinal data on NTS in two Australian states over a 37-year period, between 1979 and 2015, and antimicrobial resistance since 1984. Overall, 17% of isolates were nonsusceptible to at least one antimicrobial, 4.9% were nonsusceptible to ciprofloxacin, and 0.6% were nonsusceptible to cefotaxime. In total, 2.5% of isolates were from invasive infections, with no significant difference in AMR profiles between invasive and noninvasive isolates. Most isolates with clinically relevant AMR profiles were associated with travel, particularly to Southeast Asia, with multiple "incursions" of virulent and resistant clones into Australia. Our findings represent the largest longitudinal surveillance system for NTS in Australia and provide valuable public health knowledge on the trends and distribution of AMR in NTS. Ongoing surveillance is critical to identify local emergence of resistant isolates.

Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji.

As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most common pathogen detected (n = 17) followed by N. meningitidis (n = 13). The use of qPCR significantly increased detection of IB-VPD pathogens (P = 0.0001): of 35 samples that were qPCR positive for S. pneumoniae, N. meningitidis, and H. influenzae, only 10 were culture positive. This was particularly relevant for N. meningitidis, as only 1/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of S. pneumoniae, N. meningitidis, and H. influenzae in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD.

Emergence of endemic MLST non-typeable vancomycin-resistant Enterococcus faecium.

BACKGROUND: Enterococcus faecium is a major nosocomial pathogen causing significant morbidity and mortality worldwide. Assessment of E. faecium using MLST to understand the spread of this organism is an important component of hospital infection control measures. Recent studies, however, suggest that MLST might be inadequate for E. faecium surveillance. OBJECTIVES: To use WGS to characterize recently identified vancomycin-resistant E. faecium (VREfm) isolates non-typeable by MLST that appear to be causing a multi-jurisdictional outbreak in Australia. METHODS: Illumina NextSeq and Pacific Biosciences SMRT sequencing platforms were used to determine the genome sequences of 66 non-typeable E. faecium (NTEfm) isolates. Phylogenetic and bioinformatics analyses were subsequently performed using a number of in silico tools. RESULTS: Sixty-six E. faecium isolates were identified by WGS from multiple health jurisdictions in Australia that could not be typed by MLST due to a missing pstS allele. SMRT sequencing and complete genome assembly revealed a large chromosomal rearrangement in representative strain DMG1500801, which likely facilitated the deletion of the pstS region. Phylogenomic analysis of this population suggests that deletion of pstS within E. faecium has arisen independently on at least three occasions. Importantly, the majority of these isolates displayed a vancomycin-resistant genotype. CONCLUSIONS: We have identified NTEfm isolates that appear to be causing a multi-jurisdictional outbreak in Australia. Identification of these isolates has important implications for MLST-based typing activities designed to monitor the spread of VREfm and provides further evidence supporting the use of WGS for hospital surveillance of E. faecium.