Testing the intrinsic mechanisms driving the dynamics of Ross River Virus across Australia.

The mechanisms driving dynamics of many epidemiologically important mosquito-borne pathogens are complex, involving combinations of vector and host factors (e.g., species composition and life-history traits), and factors associated with transmission and reporting. Understanding which intrinsic mechanisms contribute most to observed disease dynamics is important, yet often poorly understood. Ross River virus (RRV) is Australia's most important mosquito-borne disease, with variable transmission dynamics across geographic regions. We used deterministic ordinary differential equation models to test mechanisms driving RRV dynamics across major epidemic centers in Brisbane, Darwin, Mandurah, Mildura, Gippsland, Renmark, Murray Bridge, and Coorong. We considered models with up to two vector species (Aedes vigilax, Culex annulirostris, Aedes camptorhynchus, Culex globocoxitus), two reservoir hosts (macropods, possums), seasonal transmission effects, and transmission parameters. We fit models against long-term RRV surveillance data (1991-2017) and used Akaike Information Criterion to select important mechanisms. The combination of two vector species, two reservoir hosts, and seasonal transmission effects explained RRV dynamics best across sites. Estimated vector-human transmission rate (average ß = 8.04x10-4per vector per day) was similar despite different dynamics. Models estimate 43% underreporting of RRV infections. Findings enhance understanding of RRV transmission mechanisms, provide disease parameter estimates which can be used to guide future research into public health improvements and offer a basis to evaluate mitigation practices.

Anaphylaxis in Victoria: presentations to emergency departments, with a focus on drug- and antimicrobial-related cases.

OBJECTIVE: To investigate the causes, characteristics, and outcomes of anaphylaxis, particularly drug-related anaphylaxis, in Victoria during the first two years of mandatory notification. DESIGN: Review of all anaphylaxis cases reported by emergency departments to the Victorian Department of Health and Human Services. SETTING, PARTICIPANTS: People presenting to all public and private hospital emergency departments in Victoria, 1 November 2018 - 31 December 2020. MAIN OUTCOME MEASURES: Rates of drug- and food-related anaphylaxis, by age group; characteristics of cases of drug-related anaphylaxis. RESULTS: A total of 4273 anaphylaxis episodes were reported (females: 2292 cases, 54%); the overall anaphylaxis rate was 31.9 episodes per 100 000 person-years. The most frequently reported causes were foods (2659 cases, 62%); drugs were implicated in 533 cases (12%), insect venoms in 342 (8%), and other causes in 144 (4%). No deaths were recorded. The median age in cases of food-related anaphylaxis was 17 years (IQR, 6-29 years), and 45 years (IQR, 30-60 years) in cases of drug-related anaphylaxis. Hospitalisation was required by 1538 patients (36%) and intensive care by 111 (2.6%; 7% of people admitted to hospital). Antimicrobial drugs were implicated in 258 cases of drug-related anaphylaxis (48%) and non-steroidal anti-inflammatory drugs in 85 cases (16%). Penicillin-class agents were implicated in 143 cases of antimicrobial-related anaphylaxis (56%), cephalosporins in 80 cases (31%). CONCLUSION: Our review of notified cases of anaphylaxis in Victoria over two years provides insights into drug- and antimicrobial-related anaphylaxis in non-hospitalised people presenting to emergency departments.

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.

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.

A Registry for Patients With Asplenia/Hyposplenism Reduces the Risk of Infections With Encapsulated Organisms.

Background: Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia. Clinical guidelines recommend numerous measures to reduce the risk of OPSI, but awareness and adherence to preventative measures are generally poor. We aimed to determine whether a registry for asplenic/hyposplenic patients was associated with a reduction in the incidence of infection with encapsulated bacteria. Methods: We performed a retrospective cohort study of asplenic/hyposplenic patients in the state of Victoria, Australia, who registered with Spleen Australia from 2003 through 2014. Spleen Australia provides education, clinical guidance, and annual vaccination reminders to registrants and their healthcare providers. We compared the incidence of infection with Streptococcus pneumoniae, Haemophilus influenzae type B (Hib), and Neisseria meningitidis before and after registration. Registry data were linked with Victorian notifiable disease data on invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD), and Hib between 2000 and 2014. Results: Twenty-seven cases of IPD and 1 of IMD occurred among 3221 registrants. No cases of Hib were reported. The rate of IPD/IMD was 150 per 100000 patient-years prior to registration and 36 per 100000 patient-years after registration; registration was associated with a 69% reduction in the risk of infection (incidence rate ratio, 0.31; 95% confidence interval, 0.12 to 0.83; P = .019). Based on the absolute reduction in incidence, we estimate that Spleen Australia prevents 5-6 invasive infections with encapsulated organisms annually among registrants. Conclusions: Systematic, long-term approaches to post-splenectomy care can significantly reduce the risk of infection with encapsulated organisms among individuals with asplenia/hyposplenism.

A Supervised Statistical Learning Approach for Accurate Legionella pneumophila Source Attribution during Outbreaks.

Public health agencies are increasingly relying on genomics during Legionnaires' disease investigations. However, the causative bacterium (Legionella pneumophila) has an unusual population structure, with extreme temporal and spatial genome sequence conservation. Furthermore, Legionnaires' disease outbreaks can be caused by multiple L. pneumophila genotypes in a single source. These factors can confound cluster identification using standard phylogenomic methods. Here, we show that a statistical learning approach based on L. pneumophila core genome single nucleotide polymorphism (SNP) comparisons eliminates ambiguity for defining outbreak clusters and accurately predicts exposure sources for clinical cases. We illustrate the performance of our method by genome comparisons of 234 L. pneumophila isolates obtained from patients and cooling towers in Melbourne, Australia, between 1994 and 2014. This collection included one of the largest reported Legionnaires' disease outbreaks, which involved 125 cases at an aquarium. Using only sequence data from L. pneumophila cooling tower isolates and including all core genome variation, we built a multivariate model using discriminant analysis of principal components (DAPC) to find cooling tower-specific genomic signatures and then used it to predict the origin of clinical isolates. Model assignments were 93% congruent with epidemiological data, including the aquarium Legionnaires' disease outbreak and three other unrelated outbreak investigations. We applied the same approach to a recently described investigation of Legionnaires' disease within a UK hospital and observed a model predictive ability of 86%. We have developed a promising means to breach L. pneumophila genetic diversity extremes and provide objective source attribution data for outbreak investigations.IMPORTANCE Microbial outbreak investigations are moving to a paradigm where whole-genome sequencing and phylogenetic trees are used to support epidemiological investigations. It is critical that outbreak source predictions are accurate, particularly for pathogens, like Legionella pneumophila, which can spread widely and rapidly via cooling system aerosols, causing Legionnaires' disease. Here, by studying hundreds of Legionella pneumophila genomes collected over 21 years around a major Australian city, we uncovered limitations with the phylogenetic approach that could lead to a misidentification of outbreak sources. We implement instead a statistical learning technique that eliminates the ambiguity of inferring disease transmission from phylogenies. Our approach takes geolocation information and core genome variation from environmental L. pneumophila isolates to build statistical models that predict with high confidence the environmental source of clinical L. pneumophila during disease outbreaks. We show the versatility of the technique by applying it to unrelated Legionnaires' disease outbreaks in Australia and the UK.

Increase in Meningococcal Serogroup W Disease, Victoria, Australia, 2013-2015.

In Victoria, Australia, invasive meningococcal disease caused by Neisseria meningitidis serogroup W increased from 4% of all cases in 2013 to 30% in 2015. This increase resulted largely from strains similar to those in the serogroup W sequence type 11 clonal complex, previously described in the United Kingdom and South America.

Infectious diseases notification practices, Victoria 2013.

INTRODUCTION: Infectious disease notification practices in Victoria were reviewed to identify areas for potential improvement. METHODS: Confirmed or probable cases of certain infectious diseases required to be notified to the Department of Health and Human Services (DHHS) Victoria in 2013, excluding elevated blood lead, foodborne or water-borne illness with 2 or more related cases and chlamydial infection, were analysed according to: notification source of doctor ± laboratory vs. laboratory-only; routine follow-up by public health staff for selected conditions vs. not routine; priority for Indigenous status reporting for 18 priority conditions with a target of ≥ 95% completeness vs. other conditions with a target of ≥ 80% completeness; and urgency of notification (conditions requiring immediate [same day] notification vs. conditions requiring notification within 5 days). RESULTS: Almost half (49%) the 34,893 confirmed and probable cases were notified by laboratory report alone. Indigenous status was complete for 48% of cases. Indigenous status was more likely to be completed for conditions with active vs. no active follow-up (RR 1.88 (95% CI 1.84-1.92)) and priority conditions for Indigenous status reporting vs. other conditions (RR 1.62 (95% CI 1.59-1.66)). Among conditions without active follow-up, doctor-notified cases had more complete Indigenous status reporting than laboratory-only notified cases (86% vs. 6%, RR 15.06 (95% CI 14.15-16.03)). Fewer notifications requiring same day notification were received within the legislated time frame (59%) than notifications required to be notified within 5 days (90%). DISCUSSION: DHHS Victoria handles a large volume of infectious disease notifications. Incomplete Indigenous status reporting, particularly for conditions without active follow-up, and delayed notification of conditions requiring immediate attention warrant attention. These findings will be used to improve notification practices in Victoria. Commun Dis Intell 2016;40(3):E317-E325.

A cross sectional survey of attitudes, awareness and uptake of the parental pertussis booster vaccine as part of a cocooning strategy, Victoria, Australia.

BACKGROUND: The Victorian Government Department of Health funded a diphtheria, tetanus and acellular pertussis vaccine for parents of infants from June 2009 to June 2012 as part of a cocooning strategy for the control of pertussis. The aim of this study was to assess parents' attitudes and awareness of the vaccination program, and to estimate vaccine uptake. METHODS: A cross-sectional survey of 253 families with a child born in the first quarter of 2010 residing within five metropolitan and four rural local government areas in Victoria was conducted. Univariate analyses were performed to describe the relationship between demographic variables, knowledge and awareness of the disease, the vaccine program and vaccine uptake. Multivariate analyses examining predictors for awareness of the vaccine program and for the uptake of vaccination were also conducted. RESULTS: One hundred and five families were surveyed (response rate 43%). Of these, 93% indicated that they had heard of 'pertussis' or 'whooping cough' and 75% of mothers and 69% of fathers were aware the pertussis vaccine was available and funded for new parents. Overall, 70% of mothers and 53% of fathers were vaccinated following their child's birth, with metropolitan fathers less likely to be vaccinated as rural fathers (RR=0.6, p=0.002). Being a younger mother (p=0.02) or father (p=0.047), and being an Australian-born father (RR=1.9, p=0.03) were found to predict uptake of the vaccine in parents. CONCLUSION: Parents indicated a reasonable level of knowledge of pertussis and a willingness to be vaccinated to protect their child. However, vaccine uptake estimates indicated further opportunity for program improvement. Future cocooning strategies would benefit from specifically targeting fathers and metropolitan maternity hospitals to increase vaccine uptake. Wider promotion of the availability of vaccine providers may increase uptake to maximise the success of cocooning programs. Further investigation of the effectiveness of the cocooning strategy in decreasing infant morbidity and mortality is required.

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.

Syndromic surveillance for influenza in two hospital emergency departments. Relationships between ICD-10 codes and notified cases, before and during a pandemic.

BACKGROUND: Interest in the use of emergency department (ED) data by syndromic surveillance systems to detect influenza outbreaks has been growing. Evaluations of these systems generally focus on events during influenza seasons. The aims of this study were to identify which emergency department disease codes best correlated with confirmed influenza cases and to determine if these same codes would be useful in the non-influenza season. The 2009 influenza pandemic in Victoria, Australia, provided further opportunity to examine the performance of the syndromic surveillance system during this event. METHODS: We undertook a retrospective analysis of data from the Victorian Department of Health's pilot syndromic surveillance programme, 'SynSurv'. SynSurv automatically captures patient information as it is entered by ED staff. This information includes patient demographics, their presenting symptoms and a preliminary diagnosis using ICD-10 coding. To determine which codes were best correlated with influenza notifications, weekly counts for each of the ICD-10 diagnosis codes ever used in the dataset were calculated and compared with the corresponding weekly count of confirmed influenza cases. Correlations between these codes and confirmed influenza cases in the non-influenza season were then undertaken. The data covered the period from July 2001 until August 2009 and included the 2009 influenza pandemic. RESULTS: There was a marked increase in weekly counts of both laboratory-confirmed influenza cases and relevant ICD-10 codes during the influenza pandemic period. The increase in laboratory confirmed cases was more than four times greater than the previous highest number reported, in 2007, even though the influenza-like-illness activity in the community was considered comparable to 2003 and 2007. We found five ICD-10 codes to be moderately and significantly correlated with influenza cases. None of these codes was correlated with laboratory confirmed influenza notifications outside the influenza season, at least in part because of the small number of influenza cases notified during that period. CONCLUSIONS: This study suggests that the choice of codes made by ED staff to record a case of influenza-like illness is influenced by their perceptions of how much influenza is circulating at the time. The ability of syndromic surveillance to detect outbreaks early may be impeded because case diagnosis is influenced by what ED staff believes to be occurring in the community.

Infectious Disease Notification Practices in Victoria, 2016-17.

INTRODUCTION: Infectious disease surveillance in Victoria, Australia is based upon a legislated requirement for doctors and laboratories to notify suspected or diagnosed cases of specific conditions to the Department of Health and Human Services (DHHS). The department undertakes regular audits of notification practices in Victoria typically every two years. The objective of this particular audit was to describe notification practices in 2016 and 2017, assess the effect of enhanced surveillance programs (ESPs) on Indigenous status data completeness and provide a baseline assessment that can be used to monitor the impact of a recent legislative change to notification requirements for several of the notifiable diseases which came into effect on 1 September 2018. METHODS: Notified cases reported to DHHS between 1 January 2016 and 31 December 2017 which met the confirmed and probable national case definitions were analysed by year, notifier type (doctor-only, laboratory-only, or both) and condition category (urgent versus routine). For three notifiable conditions (gonococcal infection and hepatitis B and hepatitis C of unspecified duration) Indigenous status completeness was compared pre- and post ESP commencement. RESULTS: The number of notified cases in Victoria increased 50% from 76,904 in 2016 to 115,318 in 2017 with a 277% increase in notified influenza alone. Almost half of cases were notified by both laboratory and doctor. Indigenous status was more likely to be complete following the introduction of ESPs (relative risk, RR 1.36 (95%CI: 1.33 - 1.40) p>0 .001). DISCUSSION: DHHS Victoria experienced a 1.5-fold increase in notified cases in 2017 compared with 2016, which was almost entirely attributable to influenza. For three notifiable conditions which had ESPs introduced during this period, Indigenous status reporting significantly improved. Indigenous identifiers on pathology request forms and data linkage are both interventions which are being considered to improve Indigenous status reporting in Victoria.

Anatomy of a seasonal influenza epidemic forecast

Bayesian methods have been used to predict the timing of infectious disease epidemics in various settings and for many infectious diseases, including seasonal influenza. But integrating these techniques into public health practice remains an ongoing challenge, and requires close collaboration between modellers, epidemiologists, and public health staff. During the 2016 and 2017 Australian influenza seasons, weekly seasonal influenza forecasts were produced for cities in the three states with the largest populations: Victoria, New South Wales, and Queensland. Forecast results were presented to Health Department disease surveillance units in these jurisdictions, who provided feedback about the plausibility and public health utility of these predictions. In earlier studies we found that delays in reporting and processing of surveillance data substantially limited forecast performance, and that incorporating climatic effects on transmission improved forecast performance. In this study of the 2016 and 2017 seasons, we sought to refine the forecasting method to account for delays in receiving the data, and used meteorological data from past years to modulate the force of infection. We demonstrate how these refinements improved the forecast's predictive capacity, and use the 2017 influenza season to highlight challenges in accounting for population and clinician behaviour changes in response to a severe season.

Epidemic forecasts as a tool for public health: interpretation and (re)calibration.

OBJECTIVE: Recent studies have used Bayesian methods to predict timing of influenza epidemics many weeks in advance, but there is no documented evaluation of how such forecasts might support the day-to-day operations of public health staff. METHODS: During the 2015 influenza season in Melbourne, Australia, weekly forecasts were presented at Health Department surveillance unit meetings, where they were evaluated and updated in light of expert opinion to improve their accuracy and usefulness. RESULTS: Predictive capacity of the model was substantially limited by delays in reporting and processing arising from an unprecedented number of notifications, disproportionate to seasonal intensity. Adjustment of the predictive algorithm to account for these delays and increased reporting propensity improved both current situational awareness and forecasting accuracy. CONCLUSIONS: Collaborative engagement with public health practitioners in model development improved understanding of the context and limitations of emerging surveillance data. Incorporation of these insights in a quantitative model resulted in more robust estimates of disease activity for public health use. Implications for public health: In addition to predicting future disease trends, forecasting methods can quantify the impact of delays in data availability and variable reporting practice on the accuracy of current epidemic assessment. Such evidence supports investment in systems capacity.

Effectiveness of parental cocooning as a vaccination strategy to prevent pertussis infection in infants: A case-control study.

BACKGROUND: During a pertussis epidemic in 2009, the Department of Health, Victoria, Australia, implemented a cocoon program offering parents of new babies a funded-dose of pertussis-containing vaccine. We assessed vaccine effectiveness (VE) of the program in reducing pertussis infection in infants. METHODS: Using a matched case-control design, infants aged <12 months that were notified with pertussis between 1 January 2010 and 31 December 2011, and born during the time that the cocoon program was in place, were identified. Controls were matched by area of residence and date of birth. Telephone interviews we conducted to ascertain parents' vaccination status, and if vaccinated, timing of vaccination receipt relative to the birth of their baby. Odds ratios (ORs) were calculated for the association between vaccination and pertussis infection, with VE calculated as (1 - OR) × 100%. RESULTS: The study recruited 215 cases and 240 controls (response rates 67% and 25% of eligible participants, respectively). Vaccination of both parents after delivery of the infant and ≥28 days prior to illness onset reduced pertussis infection by 77% (Vaccine Effectiveness [VE] = 77% (confidence interval [95% CI], 18-93%). After adjusting for maternal education, presence of a sibling within the household, and the infants' primary course vaccination status, the adjusted VE was 64% (95% CI, -58-92%). CONCLUSIONS: Although not reaching statistical significance, our results demonstrated that cocoon immunisation - where both parents are vaccinated in the post-partum period - may offer some protection again infant pertussis infection. Cocoon immunisation could be considered in circumstances where antenatal vaccination of the mother has not occurred.

Q-Vax Q fever vaccine failures, Victoria, Australia 1994-2013.

Q-Vax®, a whole cell formalin inactivated vaccine, is currently the only licensed Q fever vaccine for humans world-wide. Efficacy is high, although vaccine failures have been described for those vaccinated within the incubation of a naturally acquired infection. In Australia, it is widely used to prevent occupational acquisition of Q fever and is the mainstay for outbreak control. A retrospective review of all notified cases of acute Q fever to the Victorian department of health, 1993-2013, revealed 34 of 659 cases were previously vaccinated and 10 cases were positive on pre-vaccination screening, precluding vaccination. Twenty-one cases described high-risk exposures for C. burnetii prior to and within 15 days post vaccination and are likely to have been vaccinated within the incubation period of a natural infection. Thirteen cases described symptom onset more than 15 days post vaccination and thus may represent the first described series of Q-Vax vaccine failures following appropriate vaccination.