Policy, practice, and prediction: model-based approaches to evaluating N. gonorrhoeae antibiotic susceptibility test uptake in Australia.

BACKGROUND: Antimicrobial resistance (AMR) represents a significant threat to global health with Neisseria gonorrhoea emerging as a key pathogen of concern. In Australia, the Australian Gonococcal Surveillance Program (AGSP) plays a critical role in monitoring resistance patterns. However, antibiotic susceptibility test (AST) uptake - a crucial component for effective resistance surveillance - remains to be a limiting factor. The study aims to model the processes involved in generating AST tests for N. gonorrhoea isolates within the Australian healthcare system and assess the potential impact of systematic and policy-level changes. METHODS: Two models were developed. The first model was a mathematical stochastic health systems model (SHSM) and a Bayesian Belief Network (BBN) to simulate the clinician-patient dynamics influencing AST initiation. Key variables were identified through systematic literature review to inform the construction of both models. Scenario analyses were conducted with the modification of model parameters. RESULTS: The SHSM and BBN highlighted clinician education and the use of clinical support tools as effective strategies to improve AST. Scenario analysis further identified adherence to guidelines and changes in patient-level factors, such as persistence of symptoms and high-risk behaviours, as significant determinants. Both models supported the notion of mandated testing to achieve higher AST initiation rates but with considerations necessary regarding practicality, laboratory constraints, and culture failure rate. CONCLUSION: The study fundamentally demonstrates a novel approach to conceptualising the patient-clinician dynamic within AMR testing utilising a model-based approach. It suggests targeted interventions to educational, support tools, and legislative framework as feasible strategies to improve AST initiation rates. However, the research fundamentally highlights substantial research gaps in the underlying understanding of AMR.

Strengthening antimicrobial resistance surveillance systems: a scoping review.

BACKGROUND: Antimicrobial resistance (AMR) is an emerging global public health crisis. Surveillance is a fundamental component in the monitoring and evaluation of AMR mitigation endeavours. The primary aim of the scoping review is to identify successes, barriers, and gaps in implementing AMR surveillance systems and utilising data from them. METHODS: PubMed, Web of Science, SCOPUS, and EMBASE databases were searched systematically to identify literature pertaining to implementation, monitoring, and evaluation of AMR surveillance systems. A thematic analysis was conducted where themes within the literature were inductively grouped based on the described content. RESULTS: The systematic search yielded 639 journal articles for screening. Following deduplication and screening, 46 articles were determined to be appropriate for inclusion. Generally, most studies focused on human AMR surveillance (n = 38, 82.6%). Regionally, there was equal focus on low- and middle-income countries (n = 7, 15.2%) and trans-national contexts (n = 7, 14.5%). All included articles (n = 46, 100.0%) discussed barriers to either implementing or utilising AMR surveillance systems. From the scoping review, 6 themes emerged: capacity for surveillance, data infrastructure, policy, representativeness, stakeholder engagement, and sustainability. Data infrastructure was most frequently discussed as problematic in evaluation of surveillance systems (n = 36, 75.0%). The most frequent success to surveillance system implementation was stakeholder engagement (n = 30, 65.2%). CONCLUSIONS: Experiences of AMR surveillance systems are diverse across contexts. There is a distinct separation of experiences between systems with emerging surveillance systems and those with established systems. Surveillance systems require extensive refinement to become representative and meet surveillance objectives.

Enhancing Insights into Australia's Gonococcal Surveillance Programme through Stochastic Modelling.

Continued surveillance of antimicrobial resistance is critical as a feedback mechanism for the generation of concerted public health action. A characteristic of importance in evaluating disease surveillance systems is representativeness. Scenario tree modelling offers an approach to quantify system representativeness. This paper utilises the modelling approach to assess the Australian Gonococcal Surveillance Programme's representativeness as a case study. The model was built by identifying the sequence of events necessary for surveillance output generation through expert consultation and literature review. A scenario tree model was developed encompassing 16 dichotomous branches representing individual system sub-components. Key classifications included biological sex, clinical symptom status, and location of healthcare service access. The expected sensitivities for gonococcal detection and antibiotic status ascertainment were 0.624 (95% CI; 0.524, 0.736) and 0.144 (95% CI; 0.106, 0.189), respectively. Detection capacity of the system was observed to be high overall. The stochastic modelling approach has highlighted the need to consider differential risk factors such as sex, health-seeking behaviours, and clinical behaviour in sample generation. Actionable points generated by this study include modification of clinician behaviour and supplementary systems to achieve a greater contextual understanding of the surveillance data generation process.

Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium vivax malaria in endemic countries: meta-analysis of randomized controlled studies.

BACKGROUND: This study aimed to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax malaria in people living in endemic countries. METHODOLOGY AND PRINCIPAL FINDINGS: This is a meta-analysis of randomized controlled trials (RCT). We searched relevant studies in electronic databases up to May 2013. RCTs comparing efficacy of (DHP) with other artemisinin-based combination therapy (ACT), non-ACT or placebo were selected. The primary endpoint was efficacy expressed as PCR-corrected parasitological failure. Efficacy was pooled by hazard ratio (HR) and 95% CI, if studies reported time-to-event outcomes by the Kaplan-Meier method or data available for calculation of HR Nine RCTs with 14 datasets were included in the quantitative analysis. Overall, most of the studies were of high quality. Only a few studies compared with the same antimalarial drugs and reported the outcomes of the same follow-up duration, which created some difficulties in pooling of outcome data. We found the superiority of DHP over chloroquine (CQ) (at day > 42-63, HR:2.33, 95% CI:1.86-2.93, I (2): 0%) or artemether-lumefentrine (AL) (at day 42, HR:2.07, 95% CI:1.38-3.09, I (2): 39%). On the basis of GRADE criteria, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. DISCUSSION/CONCLUSION: Findings document that DHP is more efficacious than CQ and AL in treating uncomplicated P. vivax malaria. The better safety profile of DHP and the once-daily dosage improves adherence, and its fixed co-formulation ensures that both drugs (dihydroartemisinin and piperaquine) are taken together. However, DHP is not active against the hypnozoite stage of P. vivax. DHP has the potential to become an alternative antimalarial drug for the treatment uncomplicated P. vivax malaria. This should be substantiated by future RCTs with other ACTs. Additional work is required to establish how best to combine this treatment with appropriate antirelapse therapy (primaquine or other drugs under development).

The economic impact of pig-associated parasitic zoonosis in Northern Lao PDR.

The parasitic zoonoses human cysticercosis (Taenia solium), taeniasis (other Taenia species) and trichinellosis (Trichinella species) are endemic in the Lao People's Democratic Republic (Lao PDR). This study was designed to quantify the economic burden pig-associated zoonotic disease pose in Lao PDR. In particular, the analysis included estimation of the losses in the pork industry as well as losses due to human illness and lost productivity. A Markov-probability based decision-tree model was chosen to form the basis of the calculations to estimate the economic and public health impacts of taeniasis, trichinellosis and cysticercosis. Two different decision trees were run simultaneously on the model's human cohort. A third decision tree simulated the potential impacts on pig production. The human capital method was used to estimate productivity loss. The results found varied significantly depending on the rate of hospitalisation due to neurocysticerosis. This study is the first systematic estimate of the economic impact of pig-associated zoonotic diseases in Lao PDR that demonstrates the significance of the diseases in that country.

A survey of Western Australian sheep, cattle and kangaroos to determine the prevalence of Coxiella burnetii.

The objective of this study was to investigate the prevalence of Coxiella burnetii in two domestic ruminant species (cattle and sheep) and the western grey kangaroo (Macropus fuliginosus) in Western Australia (WA). The IDEXX CHEKiT Q Fever ELISA and CFT were used to test sera from 50 sheep and 329 head of cattle for anti-C. burnetii antibodies and 343 kangaroo sera were tested using an indirect ELISA developed specifically for this study. Faecal or urine samples collected from the same animals were tested with two PCR assays to identify active shedding of C. burnetii in excreta. Only two of the 379 ruminant sera had detectable levels of anti-C. burnetii antibodies according to the ELISA while the CFT did not detect any positive samples. In contrast 115 of the 343 western grey kangaroo serum samples were positive when tested with the antibody-ELISA. The first qPCR assay, targeting the IS1111a element, identified 41 of 379 ruminant and 42 of 343 kangaroo DNA samples as positive for C. burnetii DNA. The second qPCR, targeting the JB153-3 gene, identified nine C. burnetii DNA-positive ruminant samples and six positive kangaroo samples. Sequence comparisons showed high degrees of identity with C. burnetii. Isolation of C. burnetii from faeces was also attempted but was not successful. From the results presented here it appears that domestic ruminants may not be the most significant reservoir of C. burnetii in WA and that kangaroos may pose a significant threat for zoonotic transfer of this pathogen.