Multilevel genome typing: genomics-guided scalable resolution typing of microbial pathogens.

BackgroundBoth long- and short-term epidemiology are fundamental to disease control and require accurate bacterial typing. Genomic data resulting from implementation of whole genome sequencing in many public health laboratories can potentially provide highly sensitive and accurate descriptions of strain relatedness. Previous typing efforts using these data have mainly focussed on outbreak detection.AimWe aimed to develop multilevel genome typing (MGT), using consecutive multilocus sequence typing (MLST) schemes of increasing sizes, stepping up from seven-gene MLST to core genome MLST, to allow examination of genetic relatedness at multiple resolution levels.MethodsThe system was applied to Salmonellaenterica serovar Typhimurium. The MLST scheme used at each step (MGT level), defined a given MGT-level specific sequence type (ST). The list of STs generated from all of these increasing MGT levels, was named a genome type (GT). Using MGT, we typed 9,096 previously characterised isolates with publicly available data.ResultsOur approach could identify previously described S. Typhimurium populations, such as the DT104 multidrug resistance lineage (GT 19-2-11) and two invasive lineages of African isolates (GT 313-2-3 and 313-2-752). Further, we showed that MGT-derived clusters can accurately distinguish five outbreaks from each other and five background isolates.ConclusionMGT provides a universal and stable nomenclature at multiple resolutions for S. Typhimurium strains and could be implemented as an internationally standardised strain identification system. While established so far only for S. Typhimurium, the results here suggest that MGT could form the basis for typing systems in other similar microorganisms.

Population vulnerability to heat: A case-crossover analysis of heat health alerts and hospital morbidity data in Victoria, Australia.

OBJECTIVE: From 2010 to 2022, the Victorian Department of Health operated a heat health alert system. We explored whether changes to morbidity occurred during or directly after these alerts, and how this differed for certain population groups. METHODS: We used a space-time-stratified case-crossover design and conditional logistic regression to examine the associations between heat health alerts and heat-related and all-cause emergency department (ED) presentations and hospital admissions at the state-wide level, with models created for the whole population and subgroups. Data were included for the warm season (November-March) from 2014 to 2021. RESULTS: Increases occurred in heat-related ED presentations (OR 1.73, 95% CI: 1.53-1.96) and heat-related hospital admissions (OR 1.23, 95% CI: 1.16-1.30) on days on or after heat health alerts. Effect sizes were largest for those 65 years and older, Aboriginal and Torres Strait Islander people, and those living in the most disadvantaged areas. CONCLUSIONS: We confirm that increases in morbidity occurred in Victoria during heat health alerts and describe which population groups are more likely to require healthcare in a hospital. IMPLICATIONS FOR PUBLIC HEALTH: These findings can inform responses before and during periods of extreme heat, data-driven adaptation strategies, and the development of heat health surveillance systems.

Alternatives to low birthweight as a population-level indicator of infant and child health.

BACKGROUND: Low birthweight (<2500 g) is often used as a population-level indicator of maternal-child health, as it is easy to measure and correlates with poorer infant health outcomes. However, it conflates preterm birth and intrauterine growth restriction, which have different causal pathways and require different approaches to prevention. Small for gestational age (SGA) (a proxy for growth restriction) and preterm birth may be more informative measures. We evaluated low birthweight as a population-level indicator. METHODS: We conducted a population-based cohort study of singleton live births in New South Wales (NSW), Australia, using linked data from 1994-2006 birth, hospital, death and educational records, with follow-up until 2014. Outcomes of babies born of low birthweight, preterm and SGA were compared with well-grown term infants (i.e. not low birthweight or SGA). Overlap between groups and temporal trends were also examined. RESULTS: Of 1 093 765 singleton live births, 47 946 (4.4%) infants were low birthweight and had poorer outcomes than well-grown term infants (2.7% vs. 0.1% infant mortality; 13% vs. 6% below national minimum numeracy standard). SGA and preterm infants also had poorer outcomes (0.5%, 2.3% infant mortality respectively; 10%, 11% below numeracy standard) but 80% of SGA and 47% of preterm infants were not low birthweight. For all outcomes, low birthweight identified a smaller proportion of infants with poor outcomes than preterm birth and than either SGA or low birthweight at term. The proportion of low-birthweight births remained constant over time, while the proportion of births that were preterm increased and proportion of SGA decreased. CONCLUSIONS: Low birthweight, SGA and preterm infants are all at higher risk of poorer outcomes but low birthweight inadequately captures, and masks trends in, both preterm births and births that are SGA. Reporting preterm births and an indicator of growth restriction at term will identify vulnerable groups better than using the measure of low birthweight.

Examining the use of antiviral prophylaxis for influenza outbreaks in residential aged care facilities in NSW, Australia.

BACKGROUND: Influenza attack rates in closed population settings, such as residential aged care facilities (RACFs), can be more than 50% during annual epidemics. Uncertainty about the effectiveness of neuraminidase inhibitors (NAIs) as prophylaxis for influenza outbreaks has led to variations in their use in RACFs in New South Wales (NSW), Australia. OBJECTIVES: To examine the use of prophylactic NAIs by NSW RACFs for residents during influenza outbreaks in the 2015 influenza season. METHODS: A prospective cohort study of influenza outbreaks reported to NSW Public Health Units from 1 June 2015 - 31 October 2015. RESULTS: Eighty-eight RACFs reported influenza outbreaks; 86 were included in the study. Fifty-two RACFs used prophylactic NAIs; 34 did not. The median time to start NAI prophylaxis from the onset date of the first case was 8.5 days (range 2-23). The average proportion of residents within a facility that received prophylaxis was 51%percnt; (range 0.7-95). CONCLUSION: Variations in the use of prophylactic NAIs exist across RACFs. Earlier initiation of NAI prophylaxis, improved resident coverage where appropriate and other practice changes are recommended for the management of influenza outbreaks in RACFs.

An evaluation of enhanced surveillance of hospitalised COVID-19 patients to inform the public health response in Victoria.

BACKGROUND: Public health surveillance is crucial for supporting a rapid and effective response to public health emergencies. In response to the coronavirus disease (COVID-19) pandemic, an enhanced surveillance system of hospitalised COVID-19 patients was established by the Victorian Department of Health and Human Services (DHHS) and the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. The system aimed to reduce workforce capacity constraints and increase situational awareness on the status of hospitalised patients. METHODS: The system was evaluated, using guidelines from the United States Centers for Disease Control and Prevention, against eight attributes: acceptability; data quality; flexibility; representativeness; simplicity; stability; timeliness; and usefulness. Evidence was generated from stakeholder consultation, participant observation, document review, systems review, issues log review and audits. Data were collected and analysed over a period of up to three months, covering pre- and post-implementation from March to June 2020. RESULTS: This system was rapidly established by leveraging established relationships and infrastructure. Stakeholders agreed that the system was important but was limited by a reliance on daily manual labour (including weekends), which impeded scalability. The ability of the system to perform well in each attribute was expected to shift with the severity of the pandemic; however, at the time of this evaluation, when there were an average 23 new cases per day (0.3 cases per 100,000 population per day), the system performed well. CONCLUSION: This enhanced surveillance system was useful and achieved its key DHHS objectives during the COVID-19 public health emergency in Victoria. Recommendations for improvement were made to the current and future systems, including the need to plan alternatives to improve the system's scalability and to maintain stakeholder acceptability.

Investigation and response to an outbreak of leptospirosis among raspberry workers in Australia, 2018.

BACKGROUND: In 2018, an outbreak of leptospirosis was identified among raspberry workers from a mixed-berry farm in New South Wales, Australia. Initial testing had not revealed a cause, but eventually leptospirosis was detected via polymerase chain reaction (PCR). Further serological testing detected Leptospira borgpetersenii serovar Arborea, of which rodents are the predominant reservoir. Leptospirosis is rare in Australia, with outbreaks usually related to flooding. We conducted an investigation to identify risk factors for infection, to inform control measures. METHODS: Cases were detected through laboratory notifications, hospital-based syndromic surveillance, awareness-raising among farm employees and clinician alerts. Confirmed cases had a four-fold rise in antibody titre or single titre ≥400 on microscopic agglutination test, and a positive IgM. Probable cases had a positive Leptospira PCR or IgM, and possible cases had a clinically compatible illness. We conducted a case-control study among raspberry workers on the farm and compared reported exposures between cases and seronegative controls. We assessed environmental risks on-site and tested rodents for leptospirosis. RESULTS: We identified 84 cases over a 5-month period (50 confirmed, 19 probable and 15 possible). Compared with controls, cases were less likely to wear gloves and more recently employed. Cases also more commonly reported always having scratched hands, likely from the thorns on raspberry plants. We observed evidence of rodent activity around raspberry plants and three of thirteen trapped mice tested positive for Leptospira Arborea. Control measures included enhanced glove use, doxycycline prophylaxis and rodent control. CONCLUSIONS: This is the largest known outbreak of leptospirosis in Australia. Workers were likely exposed through scratches inflicted during harvesting, which became contaminated with environmental leptospires from mice. Leptospirosis should be considered an occupational risk for raspberry workers, requiring protective measures. Chemoprophylaxis may assist in controlling outbreaks. PCR assists in the early diagnosis and detection of leptospirosis and should be included in surveillance case definitions.

Mutations associated with in vitro resistance to bedaquiline in Mycobacterium tuberculosis isolates in Australia.

Genome-wide analysis of 517 Mycobacterium tuberculosis isolates from New South Wales, Australia, have identified previously reported and 8 new mutations in Rv0678 and atpE genes linked to in vitro resistance to bedaquiline, a new class of antimycobacterial drugs. These mutations were present in 2.9% of prospectively sequenced genomes but in 10.6% of strains that were phenotypically multidrug-resistant. However only 14% of isolates with these mutations demonstrated elevated minimum inhibitory concentrations to bedaquiline.

Revised approach for identification of isolates within the Burkholderia cepacia complex and description of clinical isolates not assigned to any of the known genomovars.

One hundred thirty-eight clinical isolates of the Burkholderia cepacia complex (Bcc) were identified using a modified strategy that involved PCR detection of the cblA gene for the ET12 lineage simultaneously with detection of the Bcc recA PCR product; recA sequence cluster analysis also was part of the strategy. Four strains could not be assigned to any of the known genomovars.