"Hospitals respond to demand. Public health needs to respond to risk": health system lessons from a case study of northern Queensland's COVID-19 surveillance and response.

BACKGROUND: The vast region of northern Queensland (NQ) in Australia experiences poorer health outcomes and a disproportionate burden of communicable diseases compared with urban populations in Australia. This study examined the governance of COVID-19 surveillance and response in NQ to identify strengths and opportunities for improvement. METHODS: The manuscript presents an analysis of one case-unit within a broader case study project examining systems for surveillance and response for COVID-19 in NQ. Data were collected between October 2020-December 2021 comprising 47 interviews with clinical and public health staff, document review, and observation in organisational settings. Thematic analysis produced five key themes. RESULTS: Study findings highlight key strengths of the COVID-19 response, including rapid implementation of response measures, and the relative autonomy of NQ's Public Health Units to lead logistical decision-making. However, findings also highlight limitations and fragility of the public health system more generally, including unclear accountabilities, constraints on local community engagement, and workforce and other resourcing shortfalls. These were framed by state-wide regulatory and organisational incentives that prioritise clinical health care rather than disease prevention, health protection, and health promotion. Although NQ mobilised an effective COVID-19 response, findings suggest that NQ public health systems are marked by fragility, calling into question the region's preparedness for future pandemic events and other public health crises. CONCLUSIONS: Study findings highlight an urgent need to improve governance, resourcing, and political priority of public health in NQ to address unmet needs and ongoing threats.

Reproducibility of COVID-era infectious disease models.

Infectious disease modelling has been prominent throughout the COVID-19 pandemic, helping to understand the virus' transmission dynamics and inform response policies. Given their potential importance and translational impact, we evaluated the computational reproducibility of infectious disease modelling articles from the COVID era. We found that four out of 100 randomly sampled studies released between January 2020 and August 2022 could be completely computationally reproduced using the resources provided (e.g., code, data, instructions) whilst a further eight were partially reproducible. For the 100 most highly cited articles from the same period we found that 11 were completely reproducible with a further 22 partially reproducible. Reflecting on our experience, we discuss common issues affecting computational reproducibility and how these might be addressed.

Critical Review of Tuberculosis Diagnosis in Children from Papua New Guinea Presenting to Health Facilities in the Torres Strait Islands, Australia.

Paediatric tuberculosis can be challenging to diagnose, and various approaches are used in different settings. A retrospective review was conducted on Papua New Guinea (PNG) children with presumptive TB who presented for health care in the Torres Strait Islands, Australia, between 2016 and 2019. We compared diagnostic algorithms including the modified Keith Edwards TB Score, The Union Desk Guide, and the new World Health Organization (WHO) algorithm, with diagnostic practices used in the remote Torres Strait Islands. Of the 66 children with presumptive TB, 7 had bacteriologically confirmed TB. The majority (52%) were under 5 years (median age 61 months), and 45% were malnourished. There was moderate agreement across the diagnostic methods (K = 0.34; 95% CI 0.23-0.46), with the highest concordance observed between The Union Desk Guide and the WHO's algorithm (K = 0.61). Local TB physicians might have over-diagnosed presumed lymph node TB while under-diagnosing TB overall. Enhancing the precision and promptness of paediatric TB diagnosis using practical tools is pivotal to decrease TB-related child mortality, notably in isolated regions like the Torres Strait and the Western Province of PNG.

Replicating superspreader dynamics with compartmental models.

Infectious disease outbreaks often exhibit superspreader dynamics, where most infected people generate no, or few secondary cases, and only a small fraction of individuals are responsible for a large proportion of transmission. Although capturing this heterogeneity is critical for estimating outbreak risk and the effectiveness of group-specific interventions, it is typically neglected in compartmental models of infectious disease transmission-which constitute the most common transmission dynamic modeling framework. In this study we propose different classes of compartmental epidemic models that incorporate transmission heterogeneity, fit them to a number of real outbreak datasets, and benchmark their performance against the canonical superspreader model (i.e., the negative binomial branching process model). We find that properly constructed compartmental models can capably reproduce observed superspreader dynamics and we provide the pathogen-specific parameter settings required to do so. As a consequence, we also show that compartmental models parameterized according to a binary clinical classification have limited support.

Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia.

From October 2014 to February 2019, local authorities in Townsville, North Queensland, Australia continually introduced Wolbachia-infected mosquitoes to control seasonal outbreaks of dengue infection. In this study, we develop a mathematical modelling framework to estimate the effectiveness of this intervention as well as the relative dengue transmission rates of Wolbachia-infected and wild-type mosquitoes. We find that the transmission rate of Wolbachia-infected mosquitoes is reduced approximately by a factor of 20 relative to the uninfected wild-type population. In addition, the Townsville Wolbachia release program led to a 65% reduction in predicted dengue incidence during the release period and over 95% reduction in the 24 months that followed. Finally, to investigate the potential impact of other Wolbachia release programs, we use our estimates of relative transmissibility to calculate the relationship between the reproductive number of dengue and the proportion of Wolbachia-infected mosquitoes in the vector population.

Time to commencement of effective treatment in patients with drug-resistant tuberculosis diagnosed in the Torres Strait-Papua New Guinea cross-border region.

INTRODUCTION: Delays between self-reported symptom onset and commencement of effective treatment contribute to ongoing tuberculosis (TB) transmission, which is a particular concern in patients with drug-resistant (DR)-TB. The study authors assessed improvements in time to commencement of effective treatment in patients diagnosed with DR-TB in the Torres Strait-Papua New Guinea cross-border region. METHODS: All laboratory-confirmed DR-TB cases diagnosed in the Torres Strait between 1 March 2000 and 31 March 2020 were reviewed. Total time from self-reported onset of symptoms to effective treatment commencement in different programmatic time periods was assessed. Pairwise analyses and time to event proportional hazard calculations were used to explore the association between delays in median time to effective treatment, and selected variables. Data were further analysed to examine predictors of excessive treatment delay. RESULTS: The median number of days from self-reported onset of symptoms to effective treatment commencement was 124 days (interquartile range 51-214) over two decades. Between 2006 and 2012, most (57%) cases exceeded this 'grand median' while the median 'time to treat' in the most recent time period (2016-2020) was significantly reduced to 29 days (p<0.001). Although there was a reduction in the median 'time to treat' with the introduction of Xpert MTB/RIF (135 days pre-Xpert v 67 days post-Xpert) this was not statistically significant (p=0.07). Establishment of the Torres and Cape TB Control Unit on Thursday Island (2016-2020) was significantly associated with reduced treatment delay, compared to the previous TB program period (2000-2005, p<0.04; 2006-2012, p<0.001). CONCLUSION: Minimising TB treatment delay in remote settings like the Torres Strait-Papua New Guinea cross-border region requires effective decentralised diagnosis and management structures. The results of this study suggest that the establishment of the Torres and Cape TB Control Unit on Thursday Island significantly improved time to commencement of effective TB treatment. Possible contributing factors include better TB education, cross-border communication and patient-centred care.

A Systematic Review of Mathematical Models of Dengue Transmission and Vector Control: 2010-2020.

Vector control methods are considered effective in averting dengue transmission. However, several factors may modify their impact. Of these controls, chemical methods, in the long run, may increase mosquitoes' resistance to chemicides, thereby decreasing control efficacy. The biological methods, which may be self-sustaining and very effective, could be hampered by seasonality or heatwaves (resulting in, e.g., loss of Wolbachia infection). The environmental methods that could be more effective than the chemical methods are under-investigated. In this study, a systematic review is conducted to explore the present understanding of the effectiveness of vector control approaches via dengue transmission models.

Predictors of unfavourable treatment outcome in patients diagnosed with drug-resistant tuberculosis in the Torres Strait / Papua New Guinea border region.

Drug-resistant tuberculosis (DR-TB) is an ongoing challenge in the Torres Strait Islands (TSI) / Papua New Guinea (PNG) border region. Treatment success rates have historically been poor for patients diagnosed with DR-TB, leading to increased transmission. This study aimed to identify variables associated with unfavourable outcome in patients diagnosed with DR-TB to inform programmatic improvements. A retrospective study of all DR-TB cases who presented to Australian health facilities in the Torres Strait between 1 March 2000 and 31 March 2020 was performed. This time period covers four distinct TB programmatic approaches which reflect Australian and Queensland Government decisions on TB management in this remote region. Univariate and multivariate predictors of unfavourable outcome were analysed. Unfavourable outcome was defined as lost to follow up, treatment failure and death. Successful outcome was defined as cure and treatment completion. In total, 133 patients with resistance to at least one TB drug were identified. The vast majority (123/133; 92%) of DR-TB patients had pulmonary involvement; and of these, 41% (50/123) had both pulmonary and extrapulmonary TB. Unfavourable outcomes were observed in 29% (39/133) of patients. Patients living with human immunodeficiency virus, renal disease or diabetes (4/133; 4/133; 3/133) had an increased frequency of unfavourable outcome (p <0.05), but the numbers were small. Among all 133 DR-TB patients, 41% had a low lymphocyte count, which was significantly associated with unfavourable outcome (p <0.05). We noted a 50% increase in successful outcomes achieved in the 2016-2020 programmatic period, compared to earlier periods (OR 5.3, 95% Confidence Interval [1.3, 20.4]). Being a close contact of a known TB case was associated with improved outcome. While DR-TB treatment outcomes have improved over time, enhanced surveillance for DR-TB, better cross border collaboration and consistent diagnosis and management of comorbidities and other risk factors should further improve patient care and outcomes.

Modelling the ecological dynamics of mosquito populations with multiple co-circulating Wolbachia strains.

Wolbachia intracellular bacteria successfully reduce the transmissibility of arthropod-borne viruses (arboviruses) when introduced into virus-carrying vectors such as mosquitoes. Despite the progress made by introducing Wolbachia bacteria into the Aedes aegypti wild-type population to control arboviral infections, reports suggest that heat-induced loss-of-Wolbachia-infection as a result of climate change may reverse these gains. Novel, supplemental Wolbachia strains that are more resilient to increased temperatures may circumvent these concerns, and could potentially act synergistically with existing variants. In this article, we model the ecological dynamics among three distinct mosquito (sub)populations: a wild-type population free of any Wolbachia infection; an invading population infected with a particular Wolbachia strain; and a second invading population infected with a distinct Wolbachia strain from that of the first invader. We explore how the range of possible characteristics of each Wolbachia strain impacts mosquito prevalence. Further, we analyse the differential system governing the mosquito populations and the Wolbachia infection dynamics by computing the full set of basic and invasive reproduction numbers and use these to establish stability of identified equilibria. Our results show that releasing mosquitoes with two different strains of Wolbachia did not increase their prevalence, compared with a single-strain Wolbachia-infected mosquito introduction and only delayed Wolbachia dominance.

Phylodynamic signatures in the emergence of community-associated MRSA.

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.

Diversity of Leptospira spp. in bats and rodents from Papua New Guinea.

Leptospirosis is the most common bacterial zoonosis globally. The pathogen, Leptospira spp., is primarily associated with rodent reservoirs. However, a wide range of other species has been implicated as reservoirs or dead-end hosts. We conducted a survey for Leptospira spp. in bats and rodents from Papua New Guinea. Kidney samples were collected from 97 pteropodid bats (five species), 37 insectivorous bats from four different families (six species) and 188 rodents (two species). Leptospires were detected in a high proportion of pteropodid bats, including Nyctimene cf. albiventer (35%), Macroglossus minimus (34%) and Rousettus amplexicaudatus (36%). Partial sequencing of the secY gene from rodent and bat leptospires showed host species clustering, with Leptospira interrogans and L. weilii detected in rodents and L. kirschneri and a potential novel species of Leptospira detected in bats. Further research is needed in Papua New Guinea and other locales in the Pacific region to gain a better understanding of the circulation dynamics of leptospires in reservoir species and the risks to public and veterinary health.

Critical Consideration of Tuberculosis Management of Papua New Guinea Nationals and Cross-Border Health Issues in the Remote Torres Strait Islands, Australia.

The international border between Australia and Papua New Guinea (PNG) serves as a gateway for the delivery of primary and tertiary healthcare for PNG patients presenting to Australian health facilities with presumptive tuberculosis (TB). An audit of all PNG nationals with presumptive TB who presented to clinics in the Torres Strait between 2016 and 2019 was conducted to evaluate outcomes for PNG patients and to consider the consistency and equity of decision-making regarding aeromedical evacuation. We also reviewed the current aeromedical retrieval policy and the outcomes of patients referred back to Daru General Hospital in PNG. During the study period, 213 PNG nationals presented with presumptive TB to primary health centres (PHC) in the Torres Strait. In total, 44 (21%) patients were medically evacuated to Australian hospitals; 26 met the evacuation criteria of whom 3 died, and 18 did not meet the criteria of whom 1 died. A further 22 patients who met the medical evacuation criteria into Australia were referred to Daru General Hospital of whom 2 died and 10 were lost to follow-up. The cross-border movement of people from PNG into Australia is associated with an emergent duty of care. Ongoing monitoring and evaluation of patient outcomes are necessary for transparency and justice.

Mathematical analysis of a two-strain tuberculosis model in Bangladesh.

Tuberculosis (TB) is an airborne infectious disease that causes millions of deaths worldwide each year (1.2 million people died in 2019). Alarmingly, several strains of the causative agent, Mycobacterium tuberculosis (MTB)-including drug-susceptible (DS) and drug-resistant (DR) variants-already circulate throughout most developing and developed countries, particularly in Bangladesh, with totally drug-resistant strains starting to emerge. In this study we develop a two-strain DS and DR TB transmission model and perform an analysis of the system properties and solutions. Both analytical and numerical results show that the prevalence of drug-resistant infection increases with an increasing drug use through amplification. Both analytic results and numerical simulations suggest that if the basic reproduction numbers of both DS ([Formula: see text]) and DR ([Formula: see text]) TB are less than one, i.e. [Formula: see text] the disease-free equilibrium is asymptotically stable, meaning that the disease naturally dies out. Furthermore, if [Formula: see text], then DS TB dies out but DR TB persists in the population, and if [Formula: see text] both DS TB and DR TB persist in the population. Further, sensitivity analysis of the model parameters found that the transmission rate of both strains had the greatest influence on DS and DR TB prevalence. We also investigated the effect of treatment rates and amplification on both DS and DR TB prevalence; results indicate that inadequate or inappropriate treatment makes co-existence more likely and increases the relative abundance of DR TB infections.

Estimating the long-term effects of mass screening for latent and active tuberculosis in the Marshall Islands.

BACKGROUND: Ambitious population-based screening programmes for latent and active tuberculosis (TB) were implemented in the Republic of the Marshall Islands in 2017 and 2018. METHODS: We used a transmission dynamic model of TB informed by local data to capture the Marshall Islands epidemic's historical dynamics. We then used the model to project the future epidemic trajectory following the active screening interventions, as well as considering a counterfactual scenario with no intervention. We also simulated future scenarios including periodic interventions similar to those previously implemented, to assess their ability to reach the End TB Strategy targets and TB pre-elimination in the Marshall Islands. RESULTS: The screening activities conducted in 2017 and 2018 were estimated to have reduced TB incidence and mortality by around one-third in 2020, and are predicted to achieve the End TB Strategy milestone of 50% incidence reduction by 2025 compared with 2015. Screening interventions had a considerably greater impact when latent TB screening and treatment were included, compared with active case finding alone. Such combined programmes implemented at the national level could achieve TB pre-elimination around 2040 if repeated every 2 years. CONCLUSIONS: Our model suggests that it would be possible to achieve TB pre-elimination by 2040 in the Marshall Islands through frequent repetition of the same interventions as those already implemented in the country. It also highlights the importance of including latent infection testing in active screening activities.

Phylodynamic Inference of Bacterial Outbreak Parameters Using Nanopore Sequencing.

Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354-1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth-death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG.

Modeling the Cost-Effectiveness of Latent Tuberculosis Screening and Treatment Strategies in Recent Migrants to a Low-Incidence Setting.

Many tuberculosis (TB) cases in low-incidence settings are attributed to reactivation of latent TB infection (LTBI) acquired overseas. We assessed the cost-effectiveness of community-based LTBI screening and treatment strategies in recent migrants to a low-incidence setting (Australia). A decision-analytical Markov model was developed that cycled 1 migrant cohort (≥11-year-olds) annually over a lifetime from 2020. Postmigration/onshore and offshore (screening during visa application) strategies were compared with existing policy (chest x-ray during visa application). Outcomes included TB cases averted and discounted cost per quality-adjusted life-year (QALY) gained from a health-sector perspective. Most recent migrants are young adults and cost-effectiveness is limited by their relatively low LTBI prevalence, low TB mortality risks, and high emigration probability. Onshore strategies cost at least $203,188 (Australian) per QALY gained, preventing approximately 2.3%-7.0% of TB cases in the cohort. Offshore strategies (screening costs incurred by migrants) cost at least $13,907 per QALY gained, preventing 5.5%-16.9% of cases. Findings were most sensitive to the LTBI treatment quality-of-life decrement (further to severe adverse events); with a minimal decrement, all strategies caused more ill health than they prevented. Additional LTBI strategies in recent migrants could only marginally contribute to TB elimination and are unlikely to be cost-effective unless screening costs are borne by migrants and potential LTBI treatment quality-of-life decrements are ignored.

Understanding how Victoria, Australia gained control of its second COVID-19 wave.

During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria's second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2-56.4%) and of face coverings of 45.9% (95%CrI 32.9-55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important.