Modeling infectious disease dynamics in the complex landscape of global health.

Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health

Exploring the integration of traditional and molecular epidemiological methods for infectious disease outbreaks

BACKGROUND: Understanding the transmission dynamics of infectious pathogens is critical to developing effective public health strategies. Traditionally, time consuming epidemiological methods were used, often limited by incomplete or inaccurate datasets. Novel phylogenetic techniques can determine transmission events, but have rarely been used in real-time outbreak settings to inform interventions and limit the impact of outbreaks. METHODS: I undertook a series of novel studies to explore the utility of combining phylogenetics with traditional epidemiological analysis to enhance the understanding of transmission dynamics. I investigated HIV in an endemic South African setting and Ebola in an acute outbreak in Sierra Leone. The strengths and limitations of this combined approach are explored, ethical issues investigated and recommendations made regarding the implications of this work for public health. RESULTS: Phylogenetics provides an exciting and synergistic tool to epidemiological analysis in outbreak investigation and control. These combined methods enable a more detailed understanding than is possible through either discipline alone. My key findings include: • Identification of infection source: Phylogenetics gives new insight into the role of external introductions (e.g. migrators) in driving and sustaining the high incidence of HIV. • Earlier identification of new emerging clusters: I identified a new cluster of HIV from around a mining community. This is one of the first examples of molecular methods detecting a previously unknown outbreak. • Identification of novel mechanisms of transmission: This work suggests that children may have been infected by playing in puddles contaminated with Ebola, a previously unrecognised route of transmission. CONCLUSION: The integration of these two methods facilitate sophisticated real-time techniques to maximise understanding of transmission dynamics, allowing faster and more effectively targeted interventions. Moving forwards, sequence data should be incorporated into standard outbreak investigation. This is critical at a time when infectious disease outbreaks have led to the some of the most significant global health threats of the recent past

Trends in Infectious Diseases

This book gives a comprehensive overview of recent trends in infectious diseases, as well as general concepts of infections, immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of infectious diseases, highlighting the ongoing issues, recent advances, with future directions in diagnostic approaches and therapeutic strategies. The book focuses on various aspects and properties of infectious diseases whose deep understanding is very important for safeguarding human race from more loss of resources and economies due to pathogens

Tracking Foodborne Pathogens from Farm to Table: Data Needs to Evaluate Control Options

Food safety policymakers and scientists came together at a conference in January 1995 to evaluate data available for analyzing control of foodborne microbial pathogens. This proceedings starts with data regarding human illnesses associated with foodborne pathogens and moves backwards in the food chain to examine pathogen data in the processing sector and at the farm level. Of special concern is the inability to link pathogen data throughout the food chain. Analytical tools to evaluate the impact of changing production and consumption practices on foodborne disease risks and their economic consequences are presented. The available data are examined to see how well they meet current analytical needs to support policy analysis. The policymaker roundtable highlights the tradeoffs involved in funding databases, the economic evaluation of USDA's Hazard Analysis Critical Control Point (HACCP) proposal and other food safety policy issues, and the necessity of a multidisciplinary approach toward improving food safety databases.food safety, cost benefit analysis, foodborne disease risk, foodborne pathogens, Hazard Analysis Critical Control Point (HACCP), probabilistic scenario analysis, fault-tree analysis, Food Consumption/Nutrition/Food Safety,

Development of a within-host mathematical model of urethral gonorrhoea infection and application to treatment

Background To understand the emergence and spread of drug resistance in the context of Neisseria gonorrhoeae (NG) it is first important to characterise the within-host dynamics that influence these events. However, in the context of NG, the within-host infection process is not well understood, with little investigation into the role of intracellular NG on the progression of natural infection and the dynamics of infection under treatment. This thesis aims to address this gap through the use of novel within-host mathematical models to describe symptomatic male urethral NG infection. Methods Initially, we developed a model to describe the progression of natural infection by considering the interaction between extracellular and intracellular NG with immune response through PMN. This initial model was then adopted to incorporate treatment of NG infection through pharmacokinetic (PK) and pharmacodynamic (PD) approaches for several antibiotics, examining both extracellular and intracellular dynamics after treatment. While this relatively simple treatment model with conventional approaches was successful in explaining the infection dynamics for the non-β-lactam drugs we test, using β-lactams the model struggled to describe infection dynamics consistent with the literature, leading to a revised approach applied to cefixime and ceftriaxone. This new approach incorporated a transition between bacteriostatic and bactericidal effects determined through threshold effects applied to the fraction of drug bound penicillin-binding-proteins. Parameter values were estimated by fitting to existing empirical data where sub-models to reflect different in vitro experimental conditions were adopted. Results Using the natural infection model, we successfully reproduced known phenomena on bacterial load and infection duration and found that the simulated natural infection was mainly driven by intracellular NG with ~80% of the total NG population internalised from day 5 on. In addition, we achieved realistic infection clearance times for each drug considered and simulations showed treatment failure to be largely driven by unsuccessful clearance of intracellular NG. We also identified relevant PK indices at the intracellular level that differentiated treatment success and failure. Although we investigated multiple dose strategies for orally administered drugs (gepotidacin, azithromycin and cefixime), we found little difference in treatment success for a fixed total dose. Discussion In this study we contribute new theoretical results tied to available observations in an area that has had limited experimental attention. In particular, this has involved development of a new mechanistic model of NG infection within-host and incorporation of realistic features of treatment. The study findings mainly emphasise the importance of the role of intracellular NG in prolonging natural infection and determining treatment success. The treatment model facilitates exploration of differing treatment regimens, the link between PK/PD indices and treatment success and where relevant incorporates mechanistic effects of drug-target binding. This work suggests the importance of intracellular infection in both persistence of infection and drug clearance, and presents and opportunity to investigate these predictions in future experiments. The approach taken here is flexible and has the potential to be expanded in various ways, including to other anatomical sites, consider the role of vaccines in clearance and to address the motivating questions around the emergence of drug resistance within-host

Optimal Control Problem for Cholera Disease and Cost-Effectiveness Analysis

Cholera is a disease that continues to be a threat to public health globally and is an indicator of inequity and lack of social development in countries. For this reason, strategies for its control need to be investigated. In this work, an optimal control problem related to cholera disease was formulated by introducing personal protection, drug treatment and water sanitation as control strategies. First, the existence and characterization of controls to minimize the performance index or cost function was proved by using classic control theory. Then, the theoretical results were validated with numerical experiments by using data reported in the literature. Finally, the effectiveness and efficiency of the proposed controls were determined through a cost-effectiveness analysis. The results showed that the use of the three controls simultaneously is the cheapest and most effective strategy to control the disease

VI Workshop on Computational Data Analysis and Numerical Methods: Book of Abstracts

The VI Workshop on Computational Data Analysis and Numerical Methods (WCDANM) is going to be held on June 27-29, 2019, in the Department of Mathematics of the University of Beira Interior (UBI), Covilhã, Portugal and it is a unique opportunity to disseminate scientific research related to the areas of Mathematics in general, with particular relevance to the areas of Computational Data Analysis and Numerical Methods in theoretical and/or practical field, using new techniques, giving especial emphasis to applications in Medicine, Biology, Biotechnology, Engineering, Industry, Environmental Sciences, Finance, Insurance, Management and Administration. The meeting will provide a forum for discussion and debate of ideas with interest to the scientific community in general. With this meeting new scientific collaborations among colleagues, namely new collaborations in Masters and PhD projects are expected. The event is open to the entire scientific community (with or without communication/poster)

Identifying and characterising sexual transmission of enteric pathogens in men who have sex with men using classical and molecular epidemiological methods

Enteric pathogens are transmitted via the faecal-oral route and commonly cause diarrhoea and/or vomiting. In recent years, there have been numerous outbreaks in men who have sex with men (MSM), primarily Shigella spp., often associated with antimicrobial resistance. My research aimed to investigate the characteristics, risk factors and burden of bacterial enteric pathogens (BEPs) in MSM that could inform control. I conducted a cross-sectional study at a London sexual health clinic (SHC) to estimate the prevalence of BEPs in MSM and associated risk factors. I linked whole genome sequencing (WGS) data with clinical and behavioural data on reported cases of Shigella flexneri to i) characterise transmission within sexual networks of MSM and ii) validate a public health tool for identifying MSM clusters in near real-time. One in 10 predominantly asymptomatic MSM attending the SHC had a BEP detected, which was associated with higher-risk sexual behaviours. Among MSM with a BEP, presence of a genotypic marker of azithromycin resistance was associated with a history of bacterial sexually transmitted infections (STIs). In the WGS study, S. flexneri isolates from MSM largely belonged to two clades associated with genotypic markers of azithromycin resistance, with evidence of sustained transmission through sex between men. Over one third of isolates within MSM clades were from people living with HIV. The public health tool distinguished MSM from non-sexual transmission clusters. My research provides strong evidence that BEPs are transmitted sexually in MSM and asymptomatic carriage may be sustaining transmission. The findings suggest that antimicrobial treatment for STIs selected for resistance in gut organisms, emphasising the need for better antimicrobial stewardship. Phylogenetic analyses provided novel insights about S. flexneri transmission in sexual networks of MSM that could inform clinical care and public health management. Real-time identification of MSM clusters might inform the delivery of rapid and appropriate responses

Conditioners of the infectious diseases dynamics

The natural history of diseases is a concept in epidemiology that describes at the individual level the interaction of an individual with a disease stimulus, its clinical horizons, and transmission routes, which enable the identification of critical points for the prevention and control of infectious diseases. However, although this concept implies a dynamic process of exposure, contraction of disease, and cure or death, it does not provide an understanding of the dynamics of transmission of infectious agents at the population level in different scenarios, where anthropological, biological, clinical and social factors can act as conditioners for infectious diseases, that can manifest and transform in a variety of ways in different human populations. In this context, the objective of this work was to review the literature according to the Cooper (1988) methodology, to generate perspectives on the dynamics of infectious diseases, their conditioners and their interrelationship. It is demonstrated that environmental changes, pathogens evolution and host co-evolution, as well as behavioral and social set,  influence significantly the epidemic events, and mathematical modeling represents an important tool to analyze this influence

Leveraging and adapting global health systems and programs during the COVID-19 pandemic

Overview -- Surveillance, Information, and Laboratory Systems -- Workforce, Institutional, and Public Health Capacity Development -- Clinical and Health Services Delivery and Impact -- Commentaries -- About the Cover.Overview: Partnerships, Collaborations, and Investments Integral to CDC\u2019s International Response to COVID-19 / R. P. Walensky -- Global Responses to the COVID-19 Pandemic / C. H. Cassell et al. -- Surveillance, Information, and Laboratory Systems: Lessons Learned from CDC\u2019s Global COVID-19 Early Warning and Response Surveillance System / P. M. Ricks et al. -- Enhancing Respiratory Disease Surveillance to Detect COVID-19 in Shelters for Displaced Persons, Thailand\u2013Myanmar Border, 2020\u20132021 / B. Knust et al. -- Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic / P. Marcenac et al. -- Incorporating COVID-19 into Acute Febrile Illness Surveillance Systems, Belize, Kenya, Ethiopia, Peru, and Liberia, 2020\u20132021 / D. C. Shih et al. -- Extending and Strengthening Routine DHIS2 Surveillance Systems for COVID-19 Responses in Sierra Leone, Sri Lanka, and Uganda / C. Kinkade et al. -- Leveraging PEPFAR-Supported Health Information Systems for COVID-19 Pandemic Response / M. Mirza et al. -- Contribution of PEPFAR-Supported HIV and TB Molecular Diagnostic Networks to COVID-19 Testing Preparedness in 16 Countries / E. Rottinghaus Romano et al. -- A Nationally Representative Survey of COVID-19 in Pakistan, 2021\u20132022 / S. Aheron et al. -- SARS-CoV-2 Prevalence in Malawi Based on Data from Survey of Communities and Health Workers in 5 High-Burden Districts, October 2020 / J. Theu et al. -- Determining Gaps in Publicly Shared SARS-CoV-2 Genomic Surveillance Data by Analysis of Global Submissions / E. C. Ohlsen et al. -- Comparison of COVID-19 Pandemic Waves in 10 Countries in Southern Africa, 2020\u20132021 / J. Smith-Sreen et al. -- Using Population Mobility Patterns to Adapt COVID-19 Response Strategies in 3 East Africa Countries / R. D. Merrill et al. -- Community-Based Surveillance and Geographic Information System\u2012Linked Contact Tracing in COVID-19 Case Identification, Ghana, March\u2012June 2020 / E. Kenu et al. -- The Future of Infodemic Surveillance as Public Health Surveillance / H. Chiou et al. -- Workforce, Institutional, and Public Health Capacity Development: Continuing Contributions of Field Epidemiology Training Programs to Global COVID-19 Response / E. Bell et al. -- India Field Epidemiology Training Program Response to COVID-19 Pandemic, 2020\u20132021 / S. Singh et al. -- COVID-19 Response Roles among CDC International Public Health Emergency Management Fellowship Graduates / S. Krishnan et al. -- Exploratory Literature Review of the Role of National Public Health Institutes in COVID-19 Response / A. Zuber et al. -- Adapting Longstanding Public Health Collaborations between Government of Kenya and CDC Kenya in Response to the COVID-19 Pandemic, 2020\u20132021 / A. Herman-Roloff et al. -- Effect of Nigeria Presidential Task Force on COVID-19 Pandemic, Nigeria / O. Bolu et al. -- Use of Epidemiology Surge Support to Enhance Robustness and Expand Capacity of SARS-CoV-2 Pandemic Response, South Africa / R. Taback-Esra et al. -- Building on Capacity Established through US Centers for Disease Control and Prevention Global Health Programs to Respond to COVID-19, Cameroon / E. Dokubo et al. -- Use of Project ECHO in Response to COVID-19 in Countries Supported by US President\u2019s Emergency Plan for AIDS Relief / J. Wright et al. -- Faith Community Engagement to Mitigate COVID-19 Transmission Associated with Mass Gathering, Uman, Ukraine, September 2021 / L. Erickson-Mamane et al. -- Clinical and Health Services Delivery and Impact: Effects of COVID-19 on Vaccine-Preventable Disease Surveillance Systems in the World Health Organization African Region, 2020 / J. Bigouette et al. -- CDC\u2019s COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions / H. M. Soeters et al. -- Effects of Decreased Immunization Coverage for Hepatitis B Virus Caused by COVID-19 in World Health Organization Western Pacific and African Regions, 2020 / H. J. Kabore et al. -- Past as Prologue\u2014Use of Rubella Vaccination Program Lessons to Inform COVID-19 Vaccination / M. G. Dixon et al. -- Leveraging Lessons Learned from Yellow Fever and Polio Immunization Campaigns during COVID-19 Pandemic, Ghana, 2021 / K. Amponsa-Achiano et al. -- Effectiveness of Whole-Virus COVID-19 Vaccine among Healthcare Personnel, Lima, Peru / C. S. Arriola et al. -- Leveraging HIV Program and Civil Society to Accelerate COVID-19 Vaccine Uptake, Zambia / P. Bobo et al. -- Adopting World Health Organization Multimodal Infection Prevention and Control Strategies to Respond to COVID-19, Kenya / D. Kimani et al. -- Infection Prevention and Control Initiatives to Prevent Healthcare-Associated Transmission of SARS-CoV-2, East Africa / D. J. Gomes et al. -- Effects of COVID-19 Pandemic on Voluntary Medical Male Circumcision Services for HIV Prevention, Sub-Saharan Africa, 2020 / M. E. Peck et al. -- Sexual Violence Trends before and after Rollout of COVID-19 Mitigation Measures, Kenya / W. Ochieng et al. -- Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala / D. Olson et al. -- Outcomes after Acute Malnutrition Program Adaptations to COVID-19, Uganda, Ethiopia, and Somalia / T. Shragai et al. -- Commentaries: Lessons from Nigeria\u2019s Adaptation of Global Health Initiatives during the COVID-19 Pandemic / C. Ihekweazu -- About the Cover: A United Response to COVID-19\u2014an Artist\u2019s Perspective / B. Breedlove et al