International Society for Disease Surveillance Conference 2011: Building the Future of Public Health Surveillance: Building the Future of Public Health Surveillance

Daniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-04204pubpub1117

Efficient Decision Support Systems

This series is directed to diverse managerial professionals who are leading the transformation of individual domains by using expert information and domain knowledge to drive decision support systems (DSSs). The series offers a broad range of subjects addressed in specific areas such as health care, business management, banking, agriculture, environmental improvement, natural resource and spatial management, aviation administration, and hybrid applications of information technology aimed to interdisciplinary issues. This book series is composed of three volumes: Volume 1 consists of general concepts and methodology of DSSs; Volume 2 consists of applications of DSSs in the biomedical domain; Volume 3 consists of hybrid applications of DSSs in multidisciplinary domains. The book is shaped decision support strategies in the new infrastructure that assists the readers in full use of the creative technology to manipulate input data and to transform information into useful decisions for decision makers

Point-of-care diagnostics of childhood central nervous system infections, with a focus on usability in low-resource settings

Background: The inaccessibility of laboratory services sustains the high burden of paediatric infectious diseases, such as central nervous system (CNS) infections, in low-resource settings. New contextually fit and well-implemented point-of-care tests (POCTs) could relieve such a burden and narrow the diagnostic divide between rich and poor. Yet, current disengagement between product developers, end-users, and implementors of POCTs impedes their clinical use and utility in low-resource settings. Also, the lack of evidence gathered through field evaluations of many diagnostic instruments in low-resource settings raises questions of their clinical utility there. Objectives: The main aim of this thesis was to provide clinical and contextual guidance for developers of new POCTs for CNS infection diagnosis with high utility, especially in low-resource settings; and to implementors of POCT services towards their optimized clinical benefit. This was addressed through a multidisciplinary combination of qualitative, laboratory, and clinical studies. Methods: Qualitative focus group discussions were conducted with health care workers (HCW) in Mbarara, Uganda (Paper I), and in Stockholm, Sweden (Paper III). Discussions were audio recorded and transcribed verbatim. Qualitative content analysis with an inductive approach was pursued in for data analysis. Comparisons between the two settings were discussed. In Paper II, a vertical flow DNA microarray printed on paper was developed for the detection of Neisseria meningitidis – a major aetiology of paediatric bacterial CNS infection worldwide. The analytical performance of the microarray was laboratory evaluated on DNA extracted from the bacteria, through the detection of the ctrA gene sequence specific to N. meningitidis. In Paper IV, a commercially available polymerase chain reaction (PCR) instrument with the capability of multiplex single-sample cerebrospinal fluid (CSF) microbiology was prospectively field-evaluated for the diagnosis of paediatric CNS infection in Mbarara, Uganda. Clinical turnaround time (cTAT) was defined as time spent from lumbar puncture until reporting of microbiology analyses to clinicians. The PCR instrument’s influence on clinical and patient-centered outcomes (yield, cTAT, duration of hospitalization and antibiotic exposure, patient outcome) was compared to that of bacterial culture. Results: Fifty and 24 HCWs of different professions participated in the qualitative studies in Mbarara and Stockholm, respectively, expressing greater similarities than differences in perspectives of POCT use. POCTs were routinely used at both sites and credited for facilitating differential diagnostics and clinical decision-making. While the Ugandan setting with low laboratory accessibility was highly dependent on POCTs for sample analyses, the Swedish setting credited their use for having clinical and social value. Contrary to the described beneficial aspects, current POCTs were deemed contextually unfit in Mbarara, and their use to cause clinical distraction in Stockholm. Deficient implementation of POCT services was exposed in both places. Requests for ideal POCTs were aligned with those stipulated by the ‘ASSURED’ criteria of the World Health Organization. Specific POCTs for infectious diseases, including CNS infections, were requested. The laboratory study demonstrated an analytical sensitivity of 38 copies of ctrA per assay, with high specificity. The clinical study enrolled 212 children aged 0-12 years who were suspected of having CNS infection, with 193 of them being evaluated using the commercially available PCR instrument. A vast majority of children had been pre-administered antibiotics prior to lumbar puncture. Bacterial yield for the instrument was 12 % vs. 1.5 % for culture, with the addition of the instrument’s detection of viruses in 23 samples. Median cTAT for the instrument was 4.2 hours vs. 2 days for culture. Use of the instrument was associated with a statistically significant shorter antibiotic exposure of bacteria-negative vs. positive patients of five days, measured as from the time of reporting of laboratory results to the responsible clinicians. Similarly, its use was associated with a significantly shorter hospitalization for all-negative patients (five days) compared to those with any microorganism detected by it. No statistically significant differences in patient outcome were found due to its use, nor by its detection of any microorganisms. Conclusion: Point-of-care tests provide laboratory means to settings without laboratory capacity and to situations in need of timely results, and we could show how rapid molecular methods for CSF analysis could benefit paediatric children with suspected CNS infection. Yet, without any observed benefits in patient outcome, and at a cost not financially bearable in most lowresource settings. Contextually fit POCTs for paediatric CNS infections are needed in lowresource settings. Yet, there are design flaws in current POCTs and in implementations for their use, limiting their clinical benefits. Collaborative engagement of product developers, clinicians, laboratory professionals, and health policymakers would better serve low-resource settings with contextually fit POCTs and allow for their optimized implementation. The ‘POCTEST' framework for such an engagement is proposed in this thesis. Finally, as we provided proof of concept for a newly developed paper-printed molecular method, we will pursue its development towards contextual clinical utility in low-resource settings. Should we succeed, we hope to contribute to a decrease in preventable childhood mortality in such settings

Analysis of Heterogeneous Data Sources for Veterinary Syndromic Surveillance to Improve Public Health Response and Aid Decision Making

The standard technique of implementing veterinary syndromic surveillance (VSyS) is the detection of temporal or spatial anomalies in the occurrence of health incidents above a set threshold in an observed population using the Frequentist modelling approach. Most implementation of this technique also requires the removal of historical outbreaks from the datasets to construct baselines. Unfortunately, some challenges exist, such as data scarcity, delayed reporting of health incidents, and variable data availability from sources, which make the VSyS implementation and alarm interpretation difficult, particularly when quantifying surveillance risk with associated uncertainties. This problem indicates that alternate or improved techniques are required to interpret alarms when incorporating uncertainties and previous knowledge of health incidents into the model to inform decision-making. Such methods must be capable of retaining historical outbreaks to assess surveillance risk. In this research work, the Stochastic Quantitative Risk Assessment (SQRA) model was proposed and developed for detecting and quantifying the risk of disease outbreaks with associated uncertainties using the Bayesian probabilistic approach in PyMC3. A systematic and comparative evaluation of the available techniques was used to select the most appropriate method and software packages based on flexibility, efficiency, usability, ability to retain historical outbreaks, and the ease of developing a model in Python. The social media datasets (Twitter) were first applied to infer a possible disease outbreak incident with associated uncertainties. Then, the inferences were subsequently updated using datasets from the clinical and other healthcare sources to reduce uncertainties in the model and validate the outbreak. Therefore, the proposed SQRA model demonstrates an approach that uses the successive refinement of analysis of different data streams to define a changepoint signalling a disease outbreak. The SQRA model was tested and validated to show the method's effectiveness and reliability for differentiating and identifying risk regions with corresponding changepoints to interpret an ongoing disease outbreak incident. This demonstrates that a technique such as the SQRA method obtained through this research may aid in overcoming some of the difficulties identified in VSyS, such as data scarcity, delayed reporting, and variable availability of data from sources, ultimately contributing to science and practice

Enhancing outbreak early warning surveillance in resource-limited Pacific island countries and territories

Comprehensive, timely, and accurate health data are essential for the detection of outbreak-prone diseases. If these go unnoticed or are identified late, they pose significant risks to the health of a population. In the Pacific islands, a syndrome-based surveillance strategy, known as the Pacific Syndromic Surveillance System (PSSS), is employed for the early detection of outbreaks. The PSSS, implemented in 2010, has provided a mechanism by which resource-limited Pacific island governments have been able to perform routine surveillance activities and address many of their national and international health protection needs and obligations. Despite being a cornerstone of health protection for many Pacific islands, the surveillance system had not been comprehensively evaluated. Nor had behavioural, technical, or upstream health system factors that influence its performance been investigated. This thesis assesses whether the PSSS is meeting its stated objectives and produces evidence to augment technical and operational elements of the system. The thesis answers the following questions: (i) is the PSSS meeting its stated objectives? (ii) are algorithm-based approaches to outbreak detection appropriate in the Pacific island systems and context?; (iii) how can the PSSS be enhanced to meet information needs during public health emergencies?; and (iv) what factors enable and constrain surveillance nurses’data collection and reporting practice? The thesis found that the surveillance system is simple, well regarded, trusted, and context-relevant mechanism that Pacific island governments from across the development spectrum have been able to adopt and maintain with minimal external technical or financial support. Despite these positive findings, the research identified several statistical, procedural, and broader systems barriers to optimal performance, including chronic staffing and other resource constraints, insufficient data on which to base outbreak detection analysis, and poor integration of health information systems. Looking ahead, the thesis identifies practical opportunities for system improvement and highlights areas for further research